Case Reports

Angiolipomas are benign subcutaneous tumors that usually present on the arms, legs, and trunk in young men. Angiolipomas typically range in size from 1 to 4 cm in diameter, and multiple lesions often are present. Tenderness or mild pain may be elicited with palpation, particularly during the initial growth period. Grossly they appear as yellow, firm, circumscribed tumors. Histologic examination generally is characterized by mature adipose tissue with an admixture of capillaries that often contain fibrin thrombi.

Angiolipomas most often occur sporadically, but in a minority of cases a family history can be identified. Although the exact incidence of familial cases has not been identified in the literature, it is estimated to be 5% to 10%.¹ This rare condition has been classified as familial angiolipomatosis, which may be inherited in either an autosomal-recessive or autosomal-dominant fashion, the former being far more prevalent.² We report the case of a 31-year-old man with multiple angiolipomas who served as a proband for an evaluation of familial angiolipomatosis transmitted in an autosomal-dominant fashion among several male family members.

Case Report

A 31-year-old man presented with a history of fatty tumors on the bilateral upper extremities. The patient’s medical history was remarkable for allergy to dogs and cats, as confirmed by positive skin testing, which was treated with hydroxyzine and albuterol. Physical examination was unremarkable, except for the subcutaneous nodules on both arms and forearms. Laboratory results from a complete blood cell count and a comprehensive metabolic panel including total cholesterol, triglycerides, and high-density lipoproteins were all within reference range. A family history revealed that the patient’s brother, father, and 3 paternal uncles had a history of similar fatty tumors, as well as 2 of his paternal grandmother’s brothers (Figure 1). At the time of presentation, clinical examination revealed multiple tumors distributed on the upper and lower left arm as well as on the posterior and anterior aspect of the right forearm and upper arm. The patient did not report antecedent trauma to these areas.

 

Figure 1. An autosomal-dominant inheritance pattern of familial angiolipomatosis with 8 affected individuals. Arrow indicates the proband.

During surgical evaluation several months later, the subcutaneous nodules were preliminarily diagnosed by the surgeon as lipomas. Following surgical excision of all 5 lesions, gross examination revealed tan-yellow, circumscribed, soft-tissue nodules measuring 0.6 to 2.1 cm. Histologic examination revealed circumscribed nodules surrounded by a thin fibrous capsule. The lesions were composed of mature fat cells and benign vessels arranged in lobules of various sizes divided by fibrous septa. The vascular component ranged from 10% to approximately 50% of the lesion and was predominantly composed of capillary-sized vessels with scattered intraluminal fibrin thrombi (Figure 2). The histologic findings were considered a classic presentation of angiolipoma. Unfortunately, the patient was not able to provide pathology results pertaining to the lesions of his relatives, which he referred to as fatty tumors. At follow-up 13 months after excision, the patient developed new lesions and was planning to return for further excisions.

Comment

 

Figure 2. Histologic examination showed an encapsulated tumor composed of adipose tissue and a vascular component more prominent in the subcapsular areas (A)(H&E, original magnification ×20). Histopathology of the lesion also showed mature fat cells admixed with a vascular component (B)(H&E original magnification ×100) and scattered fibrin thrombi (C)(H&E, original magnification ×200).

Angiolipomas are benign mesenchymal neoplasms composed of adipose tissue and blood vessels. They usually present subcutaneously but have been documented in other areas including the spinal region in rare instances.³ The most common locations include the forearms, upper arms, and trunk.⁴ Our case demonstrates a classic presentation of angiolipomatosis manifesting as multiple subcutaneous nodules on the upper arms of a young man. Although lipomas were clinically suspected, histologic examination revealed that the lesions were in fact angiolipomas.

Angiolipomas account for approximately 17% of all fatty tumors and are characterized by mature adipose tissue with an admixture of capillaries that often contain fibrin thrombi.⁴ Histologic variants of angiolipomas including cellular angiolipomas and angiomyxolipomas rarely are encountered.^5-7 Cellular angiolipomas are composed almost entirely of small vessels (>95% of the lesion).^5,6 In addition to the classic presentation, cellular angiolipomas also have been documented in unusual locations. Kahng et al⁸ reported a 73-year-old woman with abnormal mammographic findings who was found to have a cellular angiolipoma of the breast. Cellular angiolipoma with lymph node involvement was reported in a 67-year-old man with adenocarcinoma of the prostate who underwent a radical retropubic prostatectomy.⁹ Due to their prominent vascular component, cellular angiolipomas must be differentiated from spindle cell lipomas, Kaposi sarcoma, and other vascular tumors. Kaposi sarcomas usually have slitlike vascular spaces, contain globules in the cytoplasm of some cells that are positive on periodic acid–Schiff staining, display immunoreactivity for human herpesvirus 8, and lack microthrombi. Angiomyxolipomas also are rare. This variant of angiolipomas contains mature adipose tissue, extensive myxoid stroma, and numerous blood vessels.⁷ The differential diagnosis for angiomyxolipomas includes myxoid liposarcomas and other adipocytic lesions (eg, myxolipomas, myxoid spindle cell lipomas).

 

Angiolipomas most often occur sporadically; however, family history has been identified in a minority of cases. This rare finding has been classified as familial angiolipomatosis (Online Mendelian Inheritance in Man [OMIM] 206550), which can be inherited in either anautosomal-recessive or very rarely in an autosomal-dominant fashion.² Our patient had numerous relatives with a history of similar lesions, which supported the diagnosis of familial angiolipomatosis in an autosomal-dominant inheritance pattern (Figure 1). Patients with autosomal-dominant familial angiolipomatosis also have been described to have other coincidental medical conditions, such as polycystic kidney disease.¹⁰

The clinical presentation of familial angiolipomatosis includes multiple subcutaneous tumors and a family history of similar lesions that are not associated with malignant transformation. Subcutaneous tumors and a family history with autosomal-dominant inheritance also can be seen in neurofibromatosis type I, which is associated with various benign and malignant neoplasms (eg, meningiomas, gliomas, pheochromocytomas). Therefore, in familial cases of multiple subcutaneous tumors transmitted in an autosomal-dominant pattern, histologic examination is essential to establish the correct diagnosis. Goodman and Baskin¹¹ reported a patient with familial angiolipomatosis who initially was suspected to have neurofibromatosis. The patient also had a granular cell tumor, which occasionally can be seen in neurofibromatosis.¹¹ Another diagnostic problem between familial angiolipomatosis and neurofibromatosis was described by Cina et al² who documented a case of familial angiolipomatosis with Lisch nodules, which are common in neurofibromatosis but rarely are seen in patients without this condition.¹² These reported parallels have prompted some investigators to suggest that similar pathogenetic mechanisms might be involved in both familial angiolipomatosis with an autosomal-dominant inheritance and neurofibromatosis type I.¹¹ Karyotyping performed on angiolipomas has failed to reveal reproducible cytogenetic abnormalities,¹³ with the exception of 1 report that documented a patient in which 1 of 5 angiolipomas had a t(X;2) abnormality.¹⁴ Conversely, ordinary lipomas are associated with numerous karyotypic abnormalities.¹⁴

Angiolipomas are benign tumors, but patients with large or disfiguring angiolipomas may choose to undergo surgical excision. For neoplasms that deeply extend between muscles, tendons, and joint capsules, subtotal excision may be required to restore regular function; however, local recurrence with muscular hypotrophy and deformation of the bones near the affected joints may occur.¹⁵

Conclusion

We present the case of a 31-year-old man with a rare form of familial angiolipomatosis characterized by an autosomal-dominant inheritance pattern. Our case emphasizes the need to obtain a detailed family history to determine the inheritance pattern in patients with multiple lesions of angiolipoma. Pathology review is essential to differentiate other diseases such as neurofibromatosis, which may present in a similar fashion. We encourage reports of further cases of familial angiolipomatosis to document the inheritance patterns.

Angiolipomas are benign subcutaneous tumors that usually present on the arms, legs, and trunk in young men. Angiolipomas typically range in size from 1 to 4 cm in diameter, and multiple lesions often are present. Tenderness or mild pain may be elicited with palpation, particularly during the initial growth period. Grossly they appear as yellow, firm, circumscribed tumors. Histologic examination generally is characterized by mature adipose tissue with an admixture of capillaries that often contain fibrin thrombi.

Angiolipomas most often occur sporadically, but in a minority of cases a family history can be identified. Although the exact incidence of familial cases has not been identified in the literature, it is estimated to be 5% to 10%.¹ This rare condition has been classified as familial angiolipomatosis, which may be inherited in either an autosomal-recessive or autosomal-dominant fashion, the former being far more prevalent.² We report the case of a 31-year-old man with multiple angiolipomas who served as a proband for an evaluation of familial angiolipomatosis transmitted in an autosomal-dominant fashion among several male family members.

Case Report

A 31-year-old man presented with a history of fatty tumors on the bilateral upper extremities. The patient’s medical history was remarkable for allergy to dogs and cats, as confirmed by positive skin testing, which was treated with hydroxyzine and albuterol. Physical examination was unremarkable, except for the subcutaneous nodules on both arms and forearms. Laboratory results from a complete blood cell count and a comprehensive metabolic panel including total cholesterol, triglycerides, and high-density lipoproteins were all within reference range. A family history revealed that the patient’s brother, father, and 3 paternal uncles had a history of similar fatty tumors, as well as 2 of his paternal grandmother’s brothers (Figure 1). At the time of presentation, clinical examination revealed multiple tumors distributed on the upper and lower left arm as well as on the posterior and anterior aspect of the right forearm and upper arm. The patient did not report antecedent trauma to these areas.

 

Figure 1. An autosomal-dominant inheritance pattern of familial angiolipomatosis with 8 affected individuals. Arrow indicates the proband.

During surgical evaluation several months later, the subcutaneous nodules were preliminarily diagnosed by the surgeon as lipomas. Following surgical excision of all 5 lesions, gross examination revealed tan-yellow, circumscribed, soft-tissue nodules measuring 0.6 to 2.1 cm. Histologic examination revealed circumscribed nodules surrounded by a thin fibrous capsule. The lesions were composed of mature fat cells and benign vessels arranged in lobules of various sizes divided by fibrous septa. The vascular component ranged from 10% to approximately 50% of the lesion and was predominantly composed of capillary-sized vessels with scattered intraluminal fibrin thrombi (Figure 2). The histologic findings were considered a classic presentation of angiolipoma. Unfortunately, the patient was not able to provide pathology results pertaining to the lesions of his relatives, which he referred to as fatty tumors. At follow-up 13 months after excision, the patient developed new lesions and was planning to return for further excisions.

Comment

 

Figure 2. Histologic examination showed an encapsulated tumor composed of adipose tissue and a vascular component more prominent in the subcapsular areas (A)(H&E, original magnification ×20). Histopathology of the lesion also showed mature fat cells admixed with a vascular component (B)(H&E original magnification ×100) and scattered fibrin thrombi (C)(H&E, original magnification ×200).

Angiolipomas are benign mesenchymal neoplasms composed of adipose tissue and blood vessels. They usually present subcutaneously but have been documented in other areas including the spinal region in rare instances.³ The most common locations include the forearms, upper arms, and trunk.⁴ Our case demonstrates a classic presentation of angiolipomatosis manifesting as multiple subcutaneous nodules on the upper arms of a young man. Although lipomas were clinically suspected, histologic examination revealed that the lesions were in fact angiolipomas.

Angiolipomas account for approximately 17% of all fatty tumors and are characterized by mature adipose tissue with an admixture of capillaries that often contain fibrin thrombi.⁴ Histologic variants of angiolipomas including cellular angiolipomas and angiomyxolipomas rarely are encountered.^5-7 Cellular angiolipomas are composed almost entirely of small vessels (>95% of the lesion).^5,6 In addition to the classic presentation, cellular angiolipomas also have been documented in unusual locations. Kahng et al⁸ reported a 73-year-old woman with abnormal mammographic findings who was found to have a cellular angiolipoma of the breast. Cellular angiolipoma with lymph node involvement was reported in a 67-year-old man with adenocarcinoma of the prostate who underwent a radical retropubic prostatectomy.⁹ Due to their prominent vascular component, cellular angiolipomas must be differentiated from spindle cell lipomas, Kaposi sarcoma, and other vascular tumors. Kaposi sarcomas usually have slitlike vascular spaces, contain globules in the cytoplasm of some cells that are positive on periodic acid–Schiff staining, display immunoreactivity for human herpesvirus 8, and lack microthrombi. Angiomyxolipomas also are rare. This variant of angiolipomas contains mature adipose tissue, extensive myxoid stroma, and numerous blood vessels.⁷ The differential diagnosis for angiomyxolipomas includes myxoid liposarcomas and other adipocytic lesions (eg, myxolipomas, myxoid spindle cell lipomas).

 

Angiolipomas most often occur sporadically; however, family history has been identified in a minority of cases. This rare finding has been classified as familial angiolipomatosis (Online Mendelian Inheritance in Man [OMIM] 206550), which can be inherited in either anautosomal-recessive or very rarely in an autosomal-dominant fashion.² Our patient had numerous relatives with a history of similar lesions, which supported the diagnosis of familial angiolipomatosis in an autosomal-dominant inheritance pattern (Figure 1). Patients with autosomal-dominant familial angiolipomatosis also have been described to have other coincidental medical conditions, such as polycystic kidney disease.¹⁰

The clinical presentation of familial angiolipomatosis includes multiple subcutaneous tumors and a family history of similar lesions that are not associated with malignant transformation. Subcutaneous tumors and a family history with autosomal-dominant inheritance also can be seen in neurofibromatosis type I, which is associated with various benign and malignant neoplasms (eg, meningiomas, gliomas, pheochromocytomas). Therefore, in familial cases of multiple subcutaneous tumors transmitted in an autosomal-dominant pattern, histologic examination is essential to establish the correct diagnosis. Goodman and Baskin¹¹ reported a patient with familial angiolipomatosis who initially was suspected to have neurofibromatosis. The patient also had a granular cell tumor, which occasionally can be seen in neurofibromatosis.¹¹ Another diagnostic problem between familial angiolipomatosis and neurofibromatosis was described by Cina et al² who documented a case of familial angiolipomatosis with Lisch nodules, which are common in neurofibromatosis but rarely are seen in patients without this condition.¹² These reported parallels have prompted some investigators to suggest that similar pathogenetic mechanisms might be involved in both familial angiolipomatosis with an autosomal-dominant inheritance and neurofibromatosis type I.¹¹ Karyotyping performed on angiolipomas has failed to reveal reproducible cytogenetic abnormalities,¹³ with the exception of 1 report that documented a patient in which 1 of 5 angiolipomas had a t(X;2) abnormality.¹⁴ Conversely, ordinary lipomas are associated with numerous karyotypic abnormalities.¹⁴

Angiolipomas are benign tumors, but patients with large or disfiguring angiolipomas may choose to undergo surgical excision. For neoplasms that deeply extend between muscles, tendons, and joint capsules, subtotal excision may be required to restore regular function; however, local recurrence with muscular hypotrophy and deformation of the bones near the affected joints may occur.¹⁵

Conclusion

We present the case of a 31-year-old man with a rare form of familial angiolipomatosis characterized by an autosomal-dominant inheritance pattern. Our case emphasizes the need to obtain a detailed family history to determine the inheritance pattern in patients with multiple lesions of angiolipoma. Pathology review is essential to differentiate other diseases such as neurofibromatosis, which may present in a similar fashion. We encourage reports of further cases of familial angiolipomatosis to document the inheritance patterns.

Angiolipomas are benign subcutaneous tumors that usually present on the arms, legs, and trunk in young men. Angiolipomas typically range in size from 1 to 4 cm in diameter, and multiple lesions often are present. Tenderness or mild pain may be elicited with palpation, particularly during the initial growth period. Grossly they appear as yellow, firm, circumscribed tumors. Histologic examination generally is characterized by mature adipose tissue with an admixture of capillaries that often contain fibrin thrombi.

Angiolipomas most often occur sporadically, but in a minority of cases a family history can be identified. Although the exact incidence of familial cases has not been identified in the literature, it is estimated to be 5% to 10%.¹ This rare condition has been classified as familial angiolipomatosis, which may be inherited in either an autosomal-recessive or autosomal-dominant fashion, the former being far more prevalent.² We report the case of a 31-year-old man with multiple angiolipomas who served as a proband for an evaluation of familial angiolipomatosis transmitted in an autosomal-dominant fashion among several male family members.

Case Report

A 31-year-old man presented with a history of fatty tumors on the bilateral upper extremities. The patient’s medical history was remarkable for allergy to dogs and cats, as confirmed by positive skin testing, which was treated with hydroxyzine and albuterol. Physical examination was unremarkable, except for the subcutaneous nodules on both arms and forearms. Laboratory results from a complete blood cell count and a comprehensive metabolic panel including total cholesterol, triglycerides, and high-density lipoproteins were all within reference range. A family history revealed that the patient’s brother, father, and 3 paternal uncles had a history of similar fatty tumors, as well as 2 of his paternal grandmother’s brothers (Figure 1). At the time of presentation, clinical examination revealed multiple tumors distributed on the upper and lower left arm as well as on the posterior and anterior aspect of the right forearm and upper arm. The patient did not report antecedent trauma to these areas.

 

Figure 1. An autosomal-dominant inheritance pattern of familial angiolipomatosis with 8 affected individuals. Arrow indicates the proband.

During surgical evaluation several months later, the subcutaneous nodules were preliminarily diagnosed by the surgeon as lipomas. Following surgical excision of all 5 lesions, gross examination revealed tan-yellow, circumscribed, soft-tissue nodules measuring 0.6 to 2.1 cm. Histologic examination revealed circumscribed nodules surrounded by a thin fibrous capsule. The lesions were composed of mature fat cells and benign vessels arranged in lobules of various sizes divided by fibrous septa. The vascular component ranged from 10% to approximately 50% of the lesion and was predominantly composed of capillary-sized vessels with scattered intraluminal fibrin thrombi (Figure 2). The histologic findings were considered a classic presentation of angiolipoma. Unfortunately, the patient was not able to provide pathology results pertaining to the lesions of his relatives, which he referred to as fatty tumors. At follow-up 13 months after excision, the patient developed new lesions and was planning to return for further excisions.

Comment

 

Figure 2. Histologic examination showed an encapsulated tumor composed of adipose tissue and a vascular component more prominent in the subcapsular areas (A)(H&E, original magnification ×20). Histopathology of the lesion also showed mature fat cells admixed with a vascular component (B)(H&E original magnification ×100) and scattered fibrin thrombi (C)(H&E, original magnification ×200).

Angiolipomas are benign mesenchymal neoplasms composed of adipose tissue and blood vessels. They usually present subcutaneously but have been documented in other areas including the spinal region in rare instances.³ The most common locations include the forearms, upper arms, and trunk.⁴ Our case demonstrates a classic presentation of angiolipomatosis manifesting as multiple subcutaneous nodules on the upper arms of a young man. Although lipomas were clinically suspected, histologic examination revealed that the lesions were in fact angiolipomas.

Angiolipomas account for approximately 17% of all fatty tumors and are characterized by mature adipose tissue with an admixture of capillaries that often contain fibrin thrombi.⁴ Histologic variants of angiolipomas including cellular angiolipomas and angiomyxolipomas rarely are encountered.^5-7 Cellular angiolipomas are composed almost entirely of small vessels (>95% of the lesion).^5,6 In addition to the classic presentation, cellular angiolipomas also have been documented in unusual locations. Kahng et al⁸ reported a 73-year-old woman with abnormal mammographic findings who was found to have a cellular angiolipoma of the breast. Cellular angiolipoma with lymph node involvement was reported in a 67-year-old man with adenocarcinoma of the prostate who underwent a radical retropubic prostatectomy.⁹ Due to their prominent vascular component, cellular angiolipomas must be differentiated from spindle cell lipomas, Kaposi sarcoma, and other vascular tumors. Kaposi sarcomas usually have slitlike vascular spaces, contain globules in the cytoplasm of some cells that are positive on periodic acid–Schiff staining, display immunoreactivity for human herpesvirus 8, and lack microthrombi. Angiomyxolipomas also are rare. This variant of angiolipomas contains mature adipose tissue, extensive myxoid stroma, and numerous blood vessels.⁷ The differential diagnosis for angiomyxolipomas includes myxoid liposarcomas and other adipocytic lesions (eg, myxolipomas, myxoid spindle cell lipomas).

 

Angiolipomas most often occur sporadically; however, family history has been identified in a minority of cases. This rare finding has been classified as familial angiolipomatosis (Online Mendelian Inheritance in Man [OMIM] 206550), which can be inherited in either anautosomal-recessive or very rarely in an autosomal-dominant fashion.² Our patient had numerous relatives with a history of similar lesions, which supported the diagnosis of familial angiolipomatosis in an autosomal-dominant inheritance pattern (Figure 1). Patients with autosomal-dominant familial angiolipomatosis also have been described to have other coincidental medical conditions, such as polycystic kidney disease.¹⁰

The clinical presentation of familial angiolipomatosis includes multiple subcutaneous tumors and a family history of similar lesions that are not associated with malignant transformation. Subcutaneous tumors and a family history with autosomal-dominant inheritance also can be seen in neurofibromatosis type I, which is associated with various benign and malignant neoplasms (eg, meningiomas, gliomas, pheochromocytomas). Therefore, in familial cases of multiple subcutaneous tumors transmitted in an autosomal-dominant pattern, histologic examination is essential to establish the correct diagnosis. Goodman and Baskin¹¹ reported a patient with familial angiolipomatosis who initially was suspected to have neurofibromatosis. The patient also had a granular cell tumor, which occasionally can be seen in neurofibromatosis.¹¹ Another diagnostic problem between familial angiolipomatosis and neurofibromatosis was described by Cina et al² who documented a case of familial angiolipomatosis with Lisch nodules, which are common in neurofibromatosis but rarely are seen in patients without this condition.¹² These reported parallels have prompted some investigators to suggest that similar pathogenetic mechanisms might be involved in both familial angiolipomatosis with an autosomal-dominant inheritance and neurofibromatosis type I.¹¹ Karyotyping performed on angiolipomas has failed to reveal reproducible cytogenetic abnormalities,¹³ with the exception of 1 report that documented a patient in which 1 of 5 angiolipomas had a t(X;2) abnormality.¹⁴ Conversely, ordinary lipomas are associated with numerous karyotypic abnormalities.¹⁴

Angiolipomas are benign tumors, but patients with large or disfiguring angiolipomas may choose to undergo surgical excision. For neoplasms that deeply extend between muscles, tendons, and joint capsules, subtotal excision may be required to restore regular function; however, local recurrence with muscular hypotrophy and deformation of the bones near the affected joints may occur.¹⁵

Conclusion

We present the case of a 31-year-old man with a rare form of familial angiolipomatosis characterized by an autosomal-dominant inheritance pattern. Our case emphasizes the need to obtain a detailed family history to determine the inheritance pattern in patients with multiple lesions of angiolipoma. Pathology review is essential to differentiate other diseases such as neurofibromatosis, which may present in a similar fashion. We encourage reports of further cases of familial angiolipomatosis to document the inheritance patterns.

Case

A 46-year-old white woman with sudden onset of numbness in her lower extremities and inability to ambulate was transported to the ED via emergency medical services. At the onset of symptoms, the patient reported a feeling of “heaviness” in her lower extremities, which was greater on the left side than the right. After an unsuccessful attempt at ambulation, she subsequently presented to a community hospital where she could no longer move her left lower extremity. Upon evaluation, the patient was found to have progressive neurological deficits and was transferred by ambulance to the authors’ tertiary medical center for definitive management. 

A review of the patient’s recent symptoms indicated that she had also experienced lower abdominal paresthesias of 5 days’ duration. She described this sensation as sharp, numb, and constant since its onset and unrelieved with the use of a muscle relaxant at home. She further noted that the pain became worse with movement, having no palliative modifying factors. Upon further questioning, the patient acknowledged recent urinary incontinence of unknown duration, nausea, and current menstruation. She denied any recent injury or illness.

Her past medical history was unknown, and she stated that she had not seen a physician in several years. The patient’s surgical history included a tonsillectomy and an appendectomy at a young age. She had no known drug allergies. Although she denied the use of medications, electronic medical records show that the patient had been prescribed baclofen, hydrochlorothiazide, metoprolol, and tramadol. She was unaware of her family’s medical history and denied use of tobacco, alcohol, or illicit drugs.

Upon physical examination, the patient’s vital signs were: blood pressure, 161/99 mm Hg; heart rate, 103 beats/minute; respiratory rate, 16 breaths/minute; oxygen saturation, 97% on room air; and temperature, 97.0°F. She appeared to be a middle-aged obese woman in no apparent distress and was alert with normal mentation, lying comfortably on the gurney.

The head and neck examinations were normal. Lung auscultation demonstrated equal and unlabored breath sounds bilaterally with no adventitious sounds. Incidentally, it was noted at this time that the left breast had a significantly large fungating mass about the areola and within the deep tissue that was visually evidenced by prominent erythema and classic peau d’orange skin. The right breast had minimal skin involvement with a smaller palpable mass below the dermal surface. Both breast masses and enlarged axillary lymph nodes on the left were nontender. The cardiovascular examination demonstrated mild tachycardia with normal heart sounds, no extremity edema, and normal pulses throughout. The gastrointestinal examination had normal borborygmus with mild infraabdominal tenderness to palpation superficially over a nondistended abdomen. Neither organomegaly, hernia, nor masses were appreciated. In addition to urinary incontinence, the patient also had fecal incontinence, which correlated with diminished tone on digital rectal examination.

 Neurological sensation was intact in all extremities and no deficits were noted in the cranial nerves. Patellar and ankle tendon-testing demonstrated left-sided hyperreflexia with ipsilateral Babinski reflex exhibiting up-going toes. Musculoskeletal weakness was grossly noted in the left lower extremity to be +2/5, whereas the right lower limb had +4/5 strength. Palpation of the thoracic and lumbar spines did not elicit tenderness. Aside from the aforementioned observations, no additional integumentary findings were noted. 

The patient was given oxygen by nasal cannula, connected to cardiac monitoring and pulse oximetry. A urinary catheter was inserted, and she was given parenteral dexamethasone,³ morphine sulfate, ondansetron, and normal saline. An electrocardiogram showed a normal sinus rhythm. A chest X-ray and basic blood analysis were ordered in preparation for the likelihood of surgical management. Neurosurgery and radiology were consulted. Emergent magnetic resonance imaging (MRI) of the cervical, thoracic, and lumbar spine with and without contrast was obtained to rule out SCC.

The MRI of the spine revealed pathologic fractures leading to cord compression at T9 and spinal stenosis at the L2 segment (Figure 1); diffuse bone metastasis of the spine was also observed. Subsequent surgical decompressive laminectomy from T7 to L3 was performed without complication. Despite the reportedly poor outcome in CMS,^2,4-6 the patient demonstrated a moderate return of strength, sensation, and function within the first month of postoperative follow-up. At 3 months, she had minimal subjective and objective deficits and was ambulating without difficulty. She denied urinary and fecal incontinence during these periods. The biopsied breast mass was determined to be stage IV infiltrating ductal carcinoma mucinous type, for which she was followed by an oncologist and received radiation and chemotherapy.

 

Discussion

The patient’s chief complaint of lower extremity muscle weakness was a clinical emergency that merited thorough investigation in a timely manner to preserve limb function. Since her medical history did not provide pathologic insight concerning her condition, physical examination by emergency personnel served as the founding evidence for this patient’s diagnosis. Decreased muscle tone of the lower extremities and rectal sphincter raised suspicion for a neurological etiology. These symptoms, along with hyperreflexia, the presence of a Babinski sign, and dual-system incontinence, were suggestive of an underlying central nervous system lesion. Of note, urinary complaints commonly result from retention leading to overflow incontinence, a time-dependent symptom that may not be experienced before presentation to medical personnel. Urinary retention is one of the most consistent findings in patients with CMS and SCC, with a relative prevalence of 90%.^4,7,8

For providers not familiar with CMS presentation, preserved tactile sensation, normoreflexia, and lack of a Babinski sign and/or incontinence are not sufficient indicators to discontinue the consideration of spinal cord lesions in the differential diagnosis and may in fact be misleading.^6,9,10 Although the patient’s deficits were not symmetrical as is commonly reported, this did not rule out the diagnosis. 

Appropriate diagnosis and treatment of such a rare entity in the emergency setting consists of a high clinical suspicion, MRI of the spine, urgent consultations, and early treatment with parenteral corticosteroids.^3,4 The patient did not have a previous diagnosis of breast carcinoma; however, once discovered on examination, the condition became suspect as approximately 80% of patients with SCC have a preexisting cancer. The peak incidence of SCC is in the sixth and seventh decades of life. The most common primary cancers metastasizing to bone are breast, prostate, and lung. When found to affect the spine, roughly 60% will be located in the thoracic spine, 30% at the lumbosacral level, and 10% in the cervical spine.

As demonstrated in this case presentation, a thorough examination cannot be stressed enough in emergent situations. The patient’s dermatological findings and nontender lymphadenopathy were adequately significant to consider the possibility of a metastatic process as the underlying etiology. Although discouraged due to the fast-paced environment of the ED, patients are frequently assessed and examined in street clothing, which in this case, may have masked the underlying cause of the patient’s neurological deficits. As a result, imaging studies, corticosteroid treatment, consultations, and surgical management may have been delayed, leading to a nonreversible outcome for the patient.

Central and Peripheral Nervous System Structures and Deficits

Central and peripheral nervous system structures animate the body through coordinated signaling of upper and lower motor neurons respectively. In most adults, the distal spinal cord terminates at the level of the first or second lumbar vertebrae where the conus medullaris is found, giving rise to S2, S3 and S4 functionality. Lesions at this level exhibit lower motor neuron deficits of the bladder and rectum resulting in incontinence and sexual dysfunction. Deficits of sensorium such as saddle anesthesia or upper motor neuron lesions as evidenced by increased motor tone and abnormal reflexes are not uncommon.¹ Branches of the cauda equina extend caudally from the epiconus, a structure proximal to the conus medullaris, as peripheral nervous system branches that innervate spinal cord segments L4 through S1 (Figure 2). Lesions of the epiconus are clinically distinguished by lower motor neuron deficits wherein muscles of the lower extremities are often weakened with potential sparing of the bulbocavernosus and micturition reflexes.²

Among the many etiologies of CMS, the most common are due to compressive lesions. These include spinal trauma, neoplasm, nucleus pulposus herniation, and spinal infection. When the spinal foramen becomes either stenotic or space-occupying lesions compress, neurological function at the affected level may be compromised. In the case of CMS, neurological deficits may present as lower extremity weakness, perineal pain, or altered deep tendon reflexes (hyperreflexia or areflexia). Tactile sensation is usually spared and incontinence is frequently present. Pure lesions of the conus medullaris are uncommon and are often combined with cauda equina symptoms¹ (Table).

Conclusion

While many EPs are cognizant of cauda equina syndrome and its presentation, CMS is less well known and not commonly documented. Due to symptomatic overlap and epidemiological rarity of these conditions, most of the literature describing these entities combines their discussion. This case contributes to the growing body of literature to assist clinicians in the evaluation and management of CMS.

Dr Batt is an emergency medicine resident, Arrowhead Regional Medical Center, Colton, California. Dr Stone is the emergency medical services director, Travis Air Force Base, Fairfield, California.

Case

A 46-year-old white woman with sudden onset of numbness in her lower extremities and inability to ambulate was transported to the ED via emergency medical services. At the onset of symptoms, the patient reported a feeling of “heaviness” in her lower extremities, which was greater on the left side than the right. After an unsuccessful attempt at ambulation, she subsequently presented to a community hospital where she could no longer move her left lower extremity. Upon evaluation, the patient was found to have progressive neurological deficits and was transferred by ambulance to the authors’ tertiary medical center for definitive management. 

A review of the patient’s recent symptoms indicated that she had also experienced lower abdominal paresthesias of 5 days’ duration. She described this sensation as sharp, numb, and constant since its onset and unrelieved with the use of a muscle relaxant at home. She further noted that the pain became worse with movement, having no palliative modifying factors. Upon further questioning, the patient acknowledged recent urinary incontinence of unknown duration, nausea, and current menstruation. She denied any recent injury or illness.

Her past medical history was unknown, and she stated that she had not seen a physician in several years. The patient’s surgical history included a tonsillectomy and an appendectomy at a young age. She had no known drug allergies. Although she denied the use of medications, electronic medical records show that the patient had been prescribed baclofen, hydrochlorothiazide, metoprolol, and tramadol. She was unaware of her family’s medical history and denied use of tobacco, alcohol, or illicit drugs.

Upon physical examination, the patient’s vital signs were: blood pressure, 161/99 mm Hg; heart rate, 103 beats/minute; respiratory rate, 16 breaths/minute; oxygen saturation, 97% on room air; and temperature, 97.0°F. She appeared to be a middle-aged obese woman in no apparent distress and was alert with normal mentation, lying comfortably on the gurney.

The head and neck examinations were normal. Lung auscultation demonstrated equal and unlabored breath sounds bilaterally with no adventitious sounds. Incidentally, it was noted at this time that the left breast had a significantly large fungating mass about the areola and within the deep tissue that was visually evidenced by prominent erythema and classic peau d’orange skin. The right breast had minimal skin involvement with a smaller palpable mass below the dermal surface. Both breast masses and enlarged axillary lymph nodes on the left were nontender. The cardiovascular examination demonstrated mild tachycardia with normal heart sounds, no extremity edema, and normal pulses throughout. The gastrointestinal examination had normal borborygmus with mild infraabdominal tenderness to palpation superficially over a nondistended abdomen. Neither organomegaly, hernia, nor masses were appreciated. In addition to urinary incontinence, the patient also had fecal incontinence, which correlated with diminished tone on digital rectal examination.

 Neurological sensation was intact in all extremities and no deficits were noted in the cranial nerves. Patellar and ankle tendon-testing demonstrated left-sided hyperreflexia with ipsilateral Babinski reflex exhibiting up-going toes. Musculoskeletal weakness was grossly noted in the left lower extremity to be +2/5, whereas the right lower limb had +4/5 strength. Palpation of the thoracic and lumbar spines did not elicit tenderness. Aside from the aforementioned observations, no additional integumentary findings were noted. 

The patient was given oxygen by nasal cannula, connected to cardiac monitoring and pulse oximetry. A urinary catheter was inserted, and she was given parenteral dexamethasone,³ morphine sulfate, ondansetron, and normal saline. An electrocardiogram showed a normal sinus rhythm. A chest X-ray and basic blood analysis were ordered in preparation for the likelihood of surgical management. Neurosurgery and radiology were consulted. Emergent magnetic resonance imaging (MRI) of the cervical, thoracic, and lumbar spine with and without contrast was obtained to rule out SCC.

The MRI of the spine revealed pathologic fractures leading to cord compression at T9 and spinal stenosis at the L2 segment (Figure 1); diffuse bone metastasis of the spine was also observed. Subsequent surgical decompressive laminectomy from T7 to L3 was performed without complication. Despite the reportedly poor outcome in CMS,^2,4-6 the patient demonstrated a moderate return of strength, sensation, and function within the first month of postoperative follow-up. At 3 months, she had minimal subjective and objective deficits and was ambulating without difficulty. She denied urinary and fecal incontinence during these periods. The biopsied breast mass was determined to be stage IV infiltrating ductal carcinoma mucinous type, for which she was followed by an oncologist and received radiation and chemotherapy.

 

Discussion

The patient’s chief complaint of lower extremity muscle weakness was a clinical emergency that merited thorough investigation in a timely manner to preserve limb function. Since her medical history did not provide pathologic insight concerning her condition, physical examination by emergency personnel served as the founding evidence for this patient’s diagnosis. Decreased muscle tone of the lower extremities and rectal sphincter raised suspicion for a neurological etiology. These symptoms, along with hyperreflexia, the presence of a Babinski sign, and dual-system incontinence, were suggestive of an underlying central nervous system lesion. Of note, urinary complaints commonly result from retention leading to overflow incontinence, a time-dependent symptom that may not be experienced before presentation to medical personnel. Urinary retention is one of the most consistent findings in patients with CMS and SCC, with a relative prevalence of 90%.^4,7,8

For providers not familiar with CMS presentation, preserved tactile sensation, normoreflexia, and lack of a Babinski sign and/or incontinence are not sufficient indicators to discontinue the consideration of spinal cord lesions in the differential diagnosis and may in fact be misleading.^6,9,10 Although the patient’s deficits were not symmetrical as is commonly reported, this did not rule out the diagnosis. 

Appropriate diagnosis and treatment of such a rare entity in the emergency setting consists of a high clinical suspicion, MRI of the spine, urgent consultations, and early treatment with parenteral corticosteroids.^3,4 The patient did not have a previous diagnosis of breast carcinoma; however, once discovered on examination, the condition became suspect as approximately 80% of patients with SCC have a preexisting cancer. The peak incidence of SCC is in the sixth and seventh decades of life. The most common primary cancers metastasizing to bone are breast, prostate, and lung. When found to affect the spine, roughly 60% will be located in the thoracic spine, 30% at the lumbosacral level, and 10% in the cervical spine.

As demonstrated in this case presentation, a thorough examination cannot be stressed enough in emergent situations. The patient’s dermatological findings and nontender lymphadenopathy were adequately significant to consider the possibility of a metastatic process as the underlying etiology. Although discouraged due to the fast-paced environment of the ED, patients are frequently assessed and examined in street clothing, which in this case, may have masked the underlying cause of the patient’s neurological deficits. As a result, imaging studies, corticosteroid treatment, consultations, and surgical management may have been delayed, leading to a nonreversible outcome for the patient.

Central and Peripheral Nervous System Structures and Deficits

Central and peripheral nervous system structures animate the body through coordinated signaling of upper and lower motor neurons respectively. In most adults, the distal spinal cord terminates at the level of the first or second lumbar vertebrae where the conus medullaris is found, giving rise to S2, S3 and S4 functionality. Lesions at this level exhibit lower motor neuron deficits of the bladder and rectum resulting in incontinence and sexual dysfunction. Deficits of sensorium such as saddle anesthesia or upper motor neuron lesions as evidenced by increased motor tone and abnormal reflexes are not uncommon.¹ Branches of the cauda equina extend caudally from the epiconus, a structure proximal to the conus medullaris, as peripheral nervous system branches that innervate spinal cord segments L4 through S1 (Figure 2). Lesions of the epiconus are clinically distinguished by lower motor neuron deficits wherein muscles of the lower extremities are often weakened with potential sparing of the bulbocavernosus and micturition reflexes.²

Among the many etiologies of CMS, the most common are due to compressive lesions. These include spinal trauma, neoplasm, nucleus pulposus herniation, and spinal infection. When the spinal foramen becomes either stenotic or space-occupying lesions compress, neurological function at the affected level may be compromised. In the case of CMS, neurological deficits may present as lower extremity weakness, perineal pain, or altered deep tendon reflexes (hyperreflexia or areflexia). Tactile sensation is usually spared and incontinence is frequently present. Pure lesions of the conus medullaris are uncommon and are often combined with cauda equina symptoms¹ (Table).

Conclusion

While many EPs are cognizant of cauda equina syndrome and its presentation, CMS is less well known and not commonly documented. Due to symptomatic overlap and epidemiological rarity of these conditions, most of the literature describing these entities combines their discussion. This case contributes to the growing body of literature to assist clinicians in the evaluation and management of CMS.

Dr Batt is an emergency medicine resident, Arrowhead Regional Medical Center, Colton, California. Dr Stone is the emergency medical services director, Travis Air Force Base, Fairfield, California.

Case

A 46-year-old white woman with sudden onset of numbness in her lower extremities and inability to ambulate was transported to the ED via emergency medical services. At the onset of symptoms, the patient reported a feeling of “heaviness” in her lower extremities, which was greater on the left side than the right. After an unsuccessful attempt at ambulation, she subsequently presented to a community hospital where she could no longer move her left lower extremity. Upon evaluation, the patient was found to have progressive neurological deficits and was transferred by ambulance to the authors’ tertiary medical center for definitive management. 

A review of the patient’s recent symptoms indicated that she had also experienced lower abdominal paresthesias of 5 days’ duration. She described this sensation as sharp, numb, and constant since its onset and unrelieved with the use of a muscle relaxant at home. She further noted that the pain became worse with movement, having no palliative modifying factors. Upon further questioning, the patient acknowledged recent urinary incontinence of unknown duration, nausea, and current menstruation. She denied any recent injury or illness.

Her past medical history was unknown, and she stated that she had not seen a physician in several years. The patient’s surgical history included a tonsillectomy and an appendectomy at a young age. She had no known drug allergies. Although she denied the use of medications, electronic medical records show that the patient had been prescribed baclofen, hydrochlorothiazide, metoprolol, and tramadol. She was unaware of her family’s medical history and denied use of tobacco, alcohol, or illicit drugs.

Upon physical examination, the patient’s vital signs were: blood pressure, 161/99 mm Hg; heart rate, 103 beats/minute; respiratory rate, 16 breaths/minute; oxygen saturation, 97% on room air; and temperature, 97.0°F. She appeared to be a middle-aged obese woman in no apparent distress and was alert with normal mentation, lying comfortably on the gurney.

The head and neck examinations were normal. Lung auscultation demonstrated equal and unlabored breath sounds bilaterally with no adventitious sounds. Incidentally, it was noted at this time that the left breast had a significantly large fungating mass about the areola and within the deep tissue that was visually evidenced by prominent erythema and classic peau d’orange skin. The right breast had minimal skin involvement with a smaller palpable mass below the dermal surface. Both breast masses and enlarged axillary lymph nodes on the left were nontender. The cardiovascular examination demonstrated mild tachycardia with normal heart sounds, no extremity edema, and normal pulses throughout. The gastrointestinal examination had normal borborygmus with mild infraabdominal tenderness to palpation superficially over a nondistended abdomen. Neither organomegaly, hernia, nor masses were appreciated. In addition to urinary incontinence, the patient also had fecal incontinence, which correlated with diminished tone on digital rectal examination.

 Neurological sensation was intact in all extremities and no deficits were noted in the cranial nerves. Patellar and ankle tendon-testing demonstrated left-sided hyperreflexia with ipsilateral Babinski reflex exhibiting up-going toes. Musculoskeletal weakness was grossly noted in the left lower extremity to be +2/5, whereas the right lower limb had +4/5 strength. Palpation of the thoracic and lumbar spines did not elicit tenderness. Aside from the aforementioned observations, no additional integumentary findings were noted. 

The patient was given oxygen by nasal cannula, connected to cardiac monitoring and pulse oximetry. A urinary catheter was inserted, and she was given parenteral dexamethasone,³ morphine sulfate, ondansetron, and normal saline. An electrocardiogram showed a normal sinus rhythm. A chest X-ray and basic blood analysis were ordered in preparation for the likelihood of surgical management. Neurosurgery and radiology were consulted. Emergent magnetic resonance imaging (MRI) of the cervical, thoracic, and lumbar spine with and without contrast was obtained to rule out SCC.

The MRI of the spine revealed pathologic fractures leading to cord compression at T9 and spinal stenosis at the L2 segment (Figure 1); diffuse bone metastasis of the spine was also observed. Subsequent surgical decompressive laminectomy from T7 to L3 was performed without complication. Despite the reportedly poor outcome in CMS,^2,4-6 the patient demonstrated a moderate return of strength, sensation, and function within the first month of postoperative follow-up. At 3 months, she had minimal subjective and objective deficits and was ambulating without difficulty. She denied urinary and fecal incontinence during these periods. The biopsied breast mass was determined to be stage IV infiltrating ductal carcinoma mucinous type, for which she was followed by an oncologist and received radiation and chemotherapy.

 

Discussion

The patient’s chief complaint of lower extremity muscle weakness was a clinical emergency that merited thorough investigation in a timely manner to preserve limb function. Since her medical history did not provide pathologic insight concerning her condition, physical examination by emergency personnel served as the founding evidence for this patient’s diagnosis. Decreased muscle tone of the lower extremities and rectal sphincter raised suspicion for a neurological etiology. These symptoms, along with hyperreflexia, the presence of a Babinski sign, and dual-system incontinence, were suggestive of an underlying central nervous system lesion. Of note, urinary complaints commonly result from retention leading to overflow incontinence, a time-dependent symptom that may not be experienced before presentation to medical personnel. Urinary retention is one of the most consistent findings in patients with CMS and SCC, with a relative prevalence of 90%.^4,7,8

For providers not familiar with CMS presentation, preserved tactile sensation, normoreflexia, and lack of a Babinski sign and/or incontinence are not sufficient indicators to discontinue the consideration of spinal cord lesions in the differential diagnosis and may in fact be misleading.^6,9,10 Although the patient’s deficits were not symmetrical as is commonly reported, this did not rule out the diagnosis. 

Appropriate diagnosis and treatment of such a rare entity in the emergency setting consists of a high clinical suspicion, MRI of the spine, urgent consultations, and early treatment with parenteral corticosteroids.^3,4 The patient did not have a previous diagnosis of breast carcinoma; however, once discovered on examination, the condition became suspect as approximately 80% of patients with SCC have a preexisting cancer. The peak incidence of SCC is in the sixth and seventh decades of life. The most common primary cancers metastasizing to bone are breast, prostate, and lung. When found to affect the spine, roughly 60% will be located in the thoracic spine, 30% at the lumbosacral level, and 10% in the cervical spine.

As demonstrated in this case presentation, a thorough examination cannot be stressed enough in emergent situations. The patient’s dermatological findings and nontender lymphadenopathy were adequately significant to consider the possibility of a metastatic process as the underlying etiology. Although discouraged due to the fast-paced environment of the ED, patients are frequently assessed and examined in street clothing, which in this case, may have masked the underlying cause of the patient’s neurological deficits. As a result, imaging studies, corticosteroid treatment, consultations, and surgical management may have been delayed, leading to a nonreversible outcome for the patient.

Central and Peripheral Nervous System Structures and Deficits

Central and peripheral nervous system structures animate the body through coordinated signaling of upper and lower motor neurons respectively. In most adults, the distal spinal cord terminates at the level of the first or second lumbar vertebrae where the conus medullaris is found, giving rise to S2, S3 and S4 functionality. Lesions at this level exhibit lower motor neuron deficits of the bladder and rectum resulting in incontinence and sexual dysfunction. Deficits of sensorium such as saddle anesthesia or upper motor neuron lesions as evidenced by increased motor tone and abnormal reflexes are not uncommon.¹ Branches of the cauda equina extend caudally from the epiconus, a structure proximal to the conus medullaris, as peripheral nervous system branches that innervate spinal cord segments L4 through S1 (Figure 2). Lesions of the epiconus are clinically distinguished by lower motor neuron deficits wherein muscles of the lower extremities are often weakened with potential sparing of the bulbocavernosus and micturition reflexes.²

Among the many etiologies of CMS, the most common are due to compressive lesions. These include spinal trauma, neoplasm, nucleus pulposus herniation, and spinal infection. When the spinal foramen becomes either stenotic or space-occupying lesions compress, neurological function at the affected level may be compromised. In the case of CMS, neurological deficits may present as lower extremity weakness, perineal pain, or altered deep tendon reflexes (hyperreflexia or areflexia). Tactile sensation is usually spared and incontinence is frequently present. Pure lesions of the conus medullaris are uncommon and are often combined with cauda equina symptoms¹ (Table).

Conclusion

While many EPs are cognizant of cauda equina syndrome and its presentation, CMS is less well known and not commonly documented. Due to symptomatic overlap and epidemiological rarity of these conditions, most of the literature describing these entities combines their discussion. This case contributes to the growing body of literature to assist clinicians in the evaluation and management of CMS.

Dr Batt is an emergency medicine resident, Arrowhead Regional Medical Center, Colton, California. Dr Stone is the emergency medical services director, Travis Air Force Base, Fairfield, California.

Case

A 22-year-old white man presented to the ED after waking from sleep and experiencing painless bilateral lower extremity weakness that ascended to the right upper extremity. This weakness left the patient unable to walk. He denied incontinence and was otherwise healthy with no prior history of similar symptoms. A family history of the presenting symptomatology was denied, and there was no family history of diabetes or kidney disease. The patient did state he had upper respiratory symptoms with a sore throat and runny nose 2 weeks earlier. He denied use of tobacco, alcohol, and illicit drugs.

Physical examination revealed abnormal deep tendon reflexes, absent patellar and achilles reflexes on the right side, reduced patellar and achilles reflexes of the left side, and diminished bilateral brachioradialis reflexes. Examination of the lower extremities revealed motor strength at 2/5 on the left and 1/5 on the right. His upper extremities demonstrated bilateral 4/5 motor strength. No ptosis was observed. All pulses of the extremities were normal with good capillary refill. His vital signs were: blood pressure, 131/75 mm Hg; pulse, 75 beats/minute; respiratory rate, 18 breaths/minute; and temperature, 97.2°F

Brain and cervical spine magnetic resonance imaging, computed tomography of the head, and blood cultures were ordered; the results of each were unremarkable. A lumbar puncture (LP) was attempted in the ED, but was unsuccessful due to difficulty in patient positioning secondary to profound weakness. An LP was later succesfully performed under fluoroscopy and revealed no abnormal findings. An electrocardiogram (ECG) demonstrated normal sinus rhythm with ST-segment flattening. The differential diagnosis for rapidly ascending weakness included Guillain-Barré syndrome, transverse myelitis, toxic metabolic syndromes, and myelopathies.

A basic metabolic panel showed that the patient was profoundly hypokalemic, with a potassium level of 1.9 mEq/L. After further blood analysis, mild hypomagnesemia was observed, with a level of 1.4 mEq/L. Whle in the ED, he was given 40 mEq potassium chloride intravenously (IV) and orally, and 2 g IV magnesium sulfate in the ED. The patient was evaluated by a neurologist in the ED. No respiratory compromise was present and the patient was admitted to neurology service with consultations from both nephrology and endocrinology.

Within 12 hours of starting potassium and magnesium supplementation, the patient’s potassium and magnesium levels returned to normal and his weakness concurrently subsided. The final diagnosis of the patient was hypokalemic periodic paralysis.

Discussion

Hypokalemic periodic paralysis (HPP), a rare autosomal dominant disorder with a prevalence of one in 100,000, is characterized by muscle weakness with accompanying hypokalemia. The first onset of symptoms is usually in the first or second decade of life, with a quarter of cases presenting before the age 10 years, and half before age 16 years. Being a typically-inherited autosomal dominant disorder, approximately two-thirds of cases present with a family history—unlike this patient case in which there was no family history of the disease. It is three to four times more common in men than women.

Hypokalemic periodic paralysis typically occurs upon waking from sleep or during rest following exercise. It may also be triggered by high-carbohydrate or high-salt meals, or from alcohol consumption. The muscles of the extremeties are usually affected, while those of the eyes, face, and sphincters are typically spared. If untreated, an attack can last from several hours to several days. Tendon and cutaneous reflexes can also be reduced or absent.¹ The manifestation of HPP can, at first impression, lead the differential diagnosis in the direction of the many other conditions that cause weakness of the extremities. Guillain-Barré syndrome and transverse myelitis are the more common diagnoses for which HPP can be mistaken. It is therefore important that the EP consider HPP in the differential so that an unusual presentation such as the one in this case may be diagnosed.

When presented with extraneous complications (eg, when the condition is encountered perioperatively or suffered comorbidly with similar conditions such as Guillain-Barré syndrome), HPP can be especially difficult to recognize.^2,3 Although a relatively uncommon condition, it can be potentially life-threatening if not recognized and treated appropriately. Severe hypokalemia may cause sequela such as respiratory failure and cardiac arhythmia. Thus, ECG and cardiorespiratory monitoring are essential in patients with HPP and hypokalemia as very severe hypokalemia may also cause paralysis of bulbar and cranial nerve musculature. Electocardiographic changes are common, and may include ST-segment sagging and flattening, U waves, and T-wave inversion. Other causes in patients presenting with HPP must also be considered, as hypokalemic paralysis of a sporadic nature may be associated with conditions including barium poisoning, hyperthyroidism, renal disorders, certain endocrinopathies, and gastrointestinal potassium losses.⁴

 

The pathogenesis of HPP is not completely understood; however, alteration in potassium regulation are well documented. Treatment of HPP includes both oral and IV potassium supplementation. Prophylaxis against recurrent attacks has been successful with various modalities including spiranolactone daily and acetazolamide.⁴ Care must be taken to consider thyrotoxic periodic paralysis, which most commonly presents in Asian men, as hyperthyroid symptoms may be subtle. Treatment focuses on reversal of the thyrotoxic state. β-Adrenergic blocking agents reduce the frequency and severity of attacks and should be started while measures to control thyrotoxicosis are being instituted.⁴

Before a diagnosis of HPP is made, other causes of hypokalemic paralysis must first be excluded.

Conclusion

This case is important because it demonstrates an unusual presentation of HPP in an emergency setting. This perspective of HPP can help the EP in recognizing and differentiating the condsition from similar disorders. 

Dr Orlik is a resident, department of emergency medicine, Akron General Medical Center, Ohio. Mr Kovacs is a student and summer research fellow, department of emergency medicine, Akron General Medical Center, Ohio. Dr Simon is the emergency medicine research director, department of emergency medicine, Akron General Medical Center, Northeast Ohio Medical University.

Case

A 22-year-old white man presented to the ED after waking from sleep and experiencing painless bilateral lower extremity weakness that ascended to the right upper extremity. This weakness left the patient unable to walk. He denied incontinence and was otherwise healthy with no prior history of similar symptoms. A family history of the presenting symptomatology was denied, and there was no family history of diabetes or kidney disease. The patient did state he had upper respiratory symptoms with a sore throat and runny nose 2 weeks earlier. He denied use of tobacco, alcohol, and illicit drugs.

Physical examination revealed abnormal deep tendon reflexes, absent patellar and achilles reflexes on the right side, reduced patellar and achilles reflexes of the left side, and diminished bilateral brachioradialis reflexes. Examination of the lower extremities revealed motor strength at 2/5 on the left and 1/5 on the right. His upper extremities demonstrated bilateral 4/5 motor strength. No ptosis was observed. All pulses of the extremities were normal with good capillary refill. His vital signs were: blood pressure, 131/75 mm Hg; pulse, 75 beats/minute; respiratory rate, 18 breaths/minute; and temperature, 97.2°F

Brain and cervical spine magnetic resonance imaging, computed tomography of the head, and blood cultures were ordered; the results of each were unremarkable. A lumbar puncture (LP) was attempted in the ED, but was unsuccessful due to difficulty in patient positioning secondary to profound weakness. An LP was later succesfully performed under fluoroscopy and revealed no abnormal findings. An electrocardiogram (ECG) demonstrated normal sinus rhythm with ST-segment flattening. The differential diagnosis for rapidly ascending weakness included Guillain-Barré syndrome, transverse myelitis, toxic metabolic syndromes, and myelopathies.

A basic metabolic panel showed that the patient was profoundly hypokalemic, with a potassium level of 1.9 mEq/L. After further blood analysis, mild hypomagnesemia was observed, with a level of 1.4 mEq/L. Whle in the ED, he was given 40 mEq potassium chloride intravenously (IV) and orally, and 2 g IV magnesium sulfate in the ED. The patient was evaluated by a neurologist in the ED. No respiratory compromise was present and the patient was admitted to neurology service with consultations from both nephrology and endocrinology.

Within 12 hours of starting potassium and magnesium supplementation, the patient’s potassium and magnesium levels returned to normal and his weakness concurrently subsided. The final diagnosis of the patient was hypokalemic periodic paralysis.

Discussion

Hypokalemic periodic paralysis (HPP), a rare autosomal dominant disorder with a prevalence of one in 100,000, is characterized by muscle weakness with accompanying hypokalemia. The first onset of symptoms is usually in the first or second decade of life, with a quarter of cases presenting before the age 10 years, and half before age 16 years. Being a typically-inherited autosomal dominant disorder, approximately two-thirds of cases present with a family history—unlike this patient case in which there was no family history of the disease. It is three to four times more common in men than women.

Hypokalemic periodic paralysis typically occurs upon waking from sleep or during rest following exercise. It may also be triggered by high-carbohydrate or high-salt meals, or from alcohol consumption. The muscles of the extremeties are usually affected, while those of the eyes, face, and sphincters are typically spared. If untreated, an attack can last from several hours to several days. Tendon and cutaneous reflexes can also be reduced or absent.¹ The manifestation of HPP can, at first impression, lead the differential diagnosis in the direction of the many other conditions that cause weakness of the extremities. Guillain-Barré syndrome and transverse myelitis are the more common diagnoses for which HPP can be mistaken. It is therefore important that the EP consider HPP in the differential so that an unusual presentation such as the one in this case may be diagnosed.

When presented with extraneous complications (eg, when the condition is encountered perioperatively or suffered comorbidly with similar conditions such as Guillain-Barré syndrome), HPP can be especially difficult to recognize.^2,3 Although a relatively uncommon condition, it can be potentially life-threatening if not recognized and treated appropriately. Severe hypokalemia may cause sequela such as respiratory failure and cardiac arhythmia. Thus, ECG and cardiorespiratory monitoring are essential in patients with HPP and hypokalemia as very severe hypokalemia may also cause paralysis of bulbar and cranial nerve musculature. Electocardiographic changes are common, and may include ST-segment sagging and flattening, U waves, and T-wave inversion. Other causes in patients presenting with HPP must also be considered, as hypokalemic paralysis of a sporadic nature may be associated with conditions including barium poisoning, hyperthyroidism, renal disorders, certain endocrinopathies, and gastrointestinal potassium losses.⁴

 

The pathogenesis of HPP is not completely understood; however, alteration in potassium regulation are well documented. Treatment of HPP includes both oral and IV potassium supplementation. Prophylaxis against recurrent attacks has been successful with various modalities including spiranolactone daily and acetazolamide.⁴ Care must be taken to consider thyrotoxic periodic paralysis, which most commonly presents in Asian men, as hyperthyroid symptoms may be subtle. Treatment focuses on reversal of the thyrotoxic state. β-Adrenergic blocking agents reduce the frequency and severity of attacks and should be started while measures to control thyrotoxicosis are being instituted.⁴

Before a diagnosis of HPP is made, other causes of hypokalemic paralysis must first be excluded.

Conclusion

This case is important because it demonstrates an unusual presentation of HPP in an emergency setting. This perspective of HPP can help the EP in recognizing and differentiating the condsition from similar disorders. 

Dr Orlik is a resident, department of emergency medicine, Akron General Medical Center, Ohio. Mr Kovacs is a student and summer research fellow, department of emergency medicine, Akron General Medical Center, Ohio. Dr Simon is the emergency medicine research director, department of emergency medicine, Akron General Medical Center, Northeast Ohio Medical University.

Case

A 22-year-old white man presented to the ED after waking from sleep and experiencing painless bilateral lower extremity weakness that ascended to the right upper extremity. This weakness left the patient unable to walk. He denied incontinence and was otherwise healthy with no prior history of similar symptoms. A family history of the presenting symptomatology was denied, and there was no family history of diabetes or kidney disease. The patient did state he had upper respiratory symptoms with a sore throat and runny nose 2 weeks earlier. He denied use of tobacco, alcohol, and illicit drugs.

Physical examination revealed abnormal deep tendon reflexes, absent patellar and achilles reflexes on the right side, reduced patellar and achilles reflexes of the left side, and diminished bilateral brachioradialis reflexes. Examination of the lower extremities revealed motor strength at 2/5 on the left and 1/5 on the right. His upper extremities demonstrated bilateral 4/5 motor strength. No ptosis was observed. All pulses of the extremities were normal with good capillary refill. His vital signs were: blood pressure, 131/75 mm Hg; pulse, 75 beats/minute; respiratory rate, 18 breaths/minute; and temperature, 97.2°F

Brain and cervical spine magnetic resonance imaging, computed tomography of the head, and blood cultures were ordered; the results of each were unremarkable. A lumbar puncture (LP) was attempted in the ED, but was unsuccessful due to difficulty in patient positioning secondary to profound weakness. An LP was later succesfully performed under fluoroscopy and revealed no abnormal findings. An electrocardiogram (ECG) demonstrated normal sinus rhythm with ST-segment flattening. The differential diagnosis for rapidly ascending weakness included Guillain-Barré syndrome, transverse myelitis, toxic metabolic syndromes, and myelopathies.

A basic metabolic panel showed that the patient was profoundly hypokalemic, with a potassium level of 1.9 mEq/L. After further blood analysis, mild hypomagnesemia was observed, with a level of 1.4 mEq/L. Whle in the ED, he was given 40 mEq potassium chloride intravenously (IV) and orally, and 2 g IV magnesium sulfate in the ED. The patient was evaluated by a neurologist in the ED. No respiratory compromise was present and the patient was admitted to neurology service with consultations from both nephrology and endocrinology.

Within 12 hours of starting potassium and magnesium supplementation, the patient’s potassium and magnesium levels returned to normal and his weakness concurrently subsided. The final diagnosis of the patient was hypokalemic periodic paralysis.

Discussion

Hypokalemic periodic paralysis (HPP), a rare autosomal dominant disorder with a prevalence of one in 100,000, is characterized by muscle weakness with accompanying hypokalemia. The first onset of symptoms is usually in the first or second decade of life, with a quarter of cases presenting before the age 10 years, and half before age 16 years. Being a typically-inherited autosomal dominant disorder, approximately two-thirds of cases present with a family history—unlike this patient case in which there was no family history of the disease. It is three to four times more common in men than women.

Hypokalemic periodic paralysis typically occurs upon waking from sleep or during rest following exercise. It may also be triggered by high-carbohydrate or high-salt meals, or from alcohol consumption. The muscles of the extremeties are usually affected, while those of the eyes, face, and sphincters are typically spared. If untreated, an attack can last from several hours to several days. Tendon and cutaneous reflexes can also be reduced or absent.¹ The manifestation of HPP can, at first impression, lead the differential diagnosis in the direction of the many other conditions that cause weakness of the extremities. Guillain-Barré syndrome and transverse myelitis are the more common diagnoses for which HPP can be mistaken. It is therefore important that the EP consider HPP in the differential so that an unusual presentation such as the one in this case may be diagnosed.

When presented with extraneous complications (eg, when the condition is encountered perioperatively or suffered comorbidly with similar conditions such as Guillain-Barré syndrome), HPP can be especially difficult to recognize.^2,3 Although a relatively uncommon condition, it can be potentially life-threatening if not recognized and treated appropriately. Severe hypokalemia may cause sequela such as respiratory failure and cardiac arhythmia. Thus, ECG and cardiorespiratory monitoring are essential in patients with HPP and hypokalemia as very severe hypokalemia may also cause paralysis of bulbar and cranial nerve musculature. Electocardiographic changes are common, and may include ST-segment sagging and flattening, U waves, and T-wave inversion. Other causes in patients presenting with HPP must also be considered, as hypokalemic paralysis of a sporadic nature may be associated with conditions including barium poisoning, hyperthyroidism, renal disorders, certain endocrinopathies, and gastrointestinal potassium losses.⁴

 

The pathogenesis of HPP is not completely understood; however, alteration in potassium regulation are well documented. Treatment of HPP includes both oral and IV potassium supplementation. Prophylaxis against recurrent attacks has been successful with various modalities including spiranolactone daily and acetazolamide.⁴ Care must be taken to consider thyrotoxic periodic paralysis, which most commonly presents in Asian men, as hyperthyroid symptoms may be subtle. Treatment focuses on reversal of the thyrotoxic state. β-Adrenergic blocking agents reduce the frequency and severity of attacks and should be started while measures to control thyrotoxicosis are being instituted.⁴

Before a diagnosis of HPP is made, other causes of hypokalemic paralysis must first be excluded.

Conclusion

This case is important because it demonstrates an unusual presentation of HPP in an emergency setting. This perspective of HPP can help the EP in recognizing and differentiating the condsition from similar disorders. 

Dr Orlik is a resident, department of emergency medicine, Akron General Medical Center, Ohio. Mr Kovacs is a student and summer research fellow, department of emergency medicine, Akron General Medical Center, Ohio. Dr Simon is the emergency medicine research director, department of emergency medicine, Akron General Medical Center, Northeast Ohio Medical University.

Case

A 24-year-old man was brought to the ED by emergency medical services (EMS) for altered mental status. The EMS crew reported they had picked up the patient at a nearby arts festival and concert series. A bystander at the event reported that the patient had taken something called “dragonfly.”

Initial assessment revealed the patient to be disoriented, with nonlinear thought patterns and an inability to follow commands. His vital signs were: blood pressure, 160/100 mm Hg; heart rate, 120 beats/minute; respiratory rate, 24 breaths/minute; and temperature, 102.2˚F. Oxygen saturation was 99% on room air. He was diaphoretic and agitated, and the nursing staff was concerned he would become aggressive and potentially violent. A quick Web search revealed that the agent the bystander mentioned was most likely Bromo-DragonFLY (BDF).

What is Bromo-DragonFLY?

In the 1960s, an American chemist named Alexander Shulgin ushered in a new era of psychedelic drug use by establishing a simple synthesis of 3,4-methylenedioxy-methamphetamine (MDMA). Following this discovery, he suggested a therapist friend use the drug therapeutically.¹ Shulgin then began a process of homologation (ie, creating novel compounds by slightly altering existing ones in an organized fashion) and developed systems for rating the drug experiences and naming the drugs in shorthand, both of which are still in use. The chemical structure common to nearly all of the drugs he studied is phenylethylamine. The Figure shows the structures of several phenylethylamine derivatives that were created by adding functional groups to the phenylethylamine backbone. Although the popularity of psychedelic drugs surged during this time period, 2,5-dimethoxy-N-(2-methoxybenzyl)phenylethylamine) (NBOMe), one of a number of newly popular psychedelics, only became available in 2003.

What is known about the pharmacology of Bromo-DragonFLY and NBOMe?

The major target of psychedelic drugs is the serotonin (5-HT₂) receptor, specifically the central 5-HT_2A subtype. Bromo-DragonFLY is a classic example of designer pharmacology in that the it was intended to potently exert its effect at this specific receptor site.

As its name suggests,  BDF adds the “wings of the fly” to the phenylethylamine backbone furanyl rings at positions 2 and 5, and a halogen (bromine) at position 4. The furanyl ring impairs enzymatic clearance of the drug,² resulting in a duration of action of up to 3 days.³ The addition of halogens increases drug potency, but the mechanism is not clear. The psychedelic agent NBOMe results from chemical additions of methoxy groups at position 2 and 5, and the halogen moiety (iodine in this case) at position 4 of the phenyl ring of the phenylethylamine structure.⁴

Through the work of Shulgin, some of his colleagues, and many disparate street chemists, a vast family of substituted phenylethylamines have been synthesized and used. Shulgin’s semiautobiographical book PiHKAL: A Chemical Love Story includes his laboratory notes for the synthesis and initial test-dose experience of 179 compounds¹; this does not include research done by others or any work since its publication in 1995.          

Notable popular drugs chemically similar to NBOMe and BDF are mescaline (found in peyote), cathinones (“bath salts”), and MDMA (found in ecstasy) (Figure). Naturally occurring (and more complex) compounds with similar effects include ayahuasca, a plant-derived beverage consisting of Banisteriopsis caapi and either Psychotria viridis or Diplopterys cabrerana from the Brazilian rainforest (see Emerg Med. 2014;46[12]:553-556); psilocybin (“magic mushrooms”); and lysergic acid diethylamide. 

How are these drugs used and what are their clinical effects?

Most phenylethylamine compounds are well absorbed across the buccal mucosa, which is why BDF and NBOMe are commonly used in liquid form or on blotter paper. Dosing guides also exist for insufflation and claim equipotent dosing for this route.⁵ Regardless of delivery route, given the high potency, inadvertent exposures to these drugs should be expected.

Users simply seeking to hallucinate may not be aware of the significant risks associated with these potent serotonergic agents, which include both life- and limb-threatening effects.⁶ The high 5-HT_2A potency results both in vasoconstriction and promotion of clot formation due to the presence of 5HT_2A receptors on small blood vessels and platelets, respectively. Ergotism, historically called Saint Anthony’s fire, is an example of serotonergic vasoconstriction and hallucination.⁷ Chronic users of substituted amphetamines can develop necrotic ulcers in distal vascular beds such as the hands and feet; these ulcers may progress to amputation despite treatment attempts with vasodilators.

In addition to the vasoconstrictive properties, there are multiple reports of serotonin toxicity (serotonin syndrome) associated with use of these designer serotonergic amphetamines. This syndrome includes severe psychomotor agitation that can lead to personal injury, along with muscle rigidity, tremor, hyperthermia, rhabdomyolysis, and seizures.⁸

 

 How are patients with phenylethylamine exposures managed?

 Management of a patient with a substituted phenylethylamine exposure is similar to management of those with cocaine overdose. Attention to the life-threatening clinical effects of psychomotor agitation, hyperthermia, and seizures is paramount. Appropriate supportive care includes intravenous (IV) benzodiazepines to control agitation and muscle rigidity, replacement of lost volume with crystalloids, and active cooling measures. Failure of benzodiazepines (preferably in conjunction with continuous electroencephalogram monitoring) to control rigidity may lead to the need for propofol and/or result in paralysis. Similar to patients with cocaine intoxication, some may experience ischemic chest pain, and the usual protocol of sedation, nitroglycerin, morphine, and an antiplatelet drug is appropriate.

Identification of phenylethylamines typically requires specialized laboratory testing since most will not trigger a positive result on a standard urine immunoassay. Many specialized laboratories have test catalogs on their Web sites listing under the “stimulants panel” which drugs can be identified. However, none of these assays is likely truly comprehensive, and minor alterations or substitutions to the compounds result in new analogs that may not be in the reference laboratory’s identification library.

 

Case

A 24-year-old man was brought to the ED by emergency medical services (EMS) for altered mental status. The EMS crew reported they had picked up the patient at a nearby arts festival and concert series. A bystander at the event reported that the patient had taken something called “dragonfly.”

Initial assessment revealed the patient to be disoriented, with nonlinear thought patterns and an inability to follow commands. His vital signs were: blood pressure, 160/100 mm Hg; heart rate, 120 beats/minute; respiratory rate, 24 breaths/minute; and temperature, 102.2˚F. Oxygen saturation was 99% on room air. He was diaphoretic and agitated, and the nursing staff was concerned he would become aggressive and potentially violent. A quick Web search revealed that the agent the bystander mentioned was most likely Bromo-DragonFLY (BDF).

What is Bromo-DragonFLY?

In the 1960s, an American chemist named Alexander Shulgin ushered in a new era of psychedelic drug use by establishing a simple synthesis of 3,4-methylenedioxy-methamphetamine (MDMA). Following this discovery, he suggested a therapist friend use the drug therapeutically.¹ Shulgin then began a process of homologation (ie, creating novel compounds by slightly altering existing ones in an organized fashion) and developed systems for rating the drug experiences and naming the drugs in shorthand, both of which are still in use. The chemical structure common to nearly all of the drugs he studied is phenylethylamine. The Figure shows the structures of several phenylethylamine derivatives that were created by adding functional groups to the phenylethylamine backbone. Although the popularity of psychedelic drugs surged during this time period, 2,5-dimethoxy-N-(2-methoxybenzyl)phenylethylamine) (NBOMe), one of a number of newly popular psychedelics, only became available in 2003.

What is known about the pharmacology of Bromo-DragonFLY and NBOMe?

The major target of psychedelic drugs is the serotonin (5-HT₂) receptor, specifically the central 5-HT_2A subtype. Bromo-DragonFLY is a classic example of designer pharmacology in that the it was intended to potently exert its effect at this specific receptor site.

As its name suggests,  BDF adds the “wings of the fly” to the phenylethylamine backbone furanyl rings at positions 2 and 5, and a halogen (bromine) at position 4. The furanyl ring impairs enzymatic clearance of the drug,² resulting in a duration of action of up to 3 days.³ The addition of halogens increases drug potency, but the mechanism is not clear. The psychedelic agent NBOMe results from chemical additions of methoxy groups at position 2 and 5, and the halogen moiety (iodine in this case) at position 4 of the phenyl ring of the phenylethylamine structure.⁴

Through the work of Shulgin, some of his colleagues, and many disparate street chemists, a vast family of substituted phenylethylamines have been synthesized and used. Shulgin’s semiautobiographical book PiHKAL: A Chemical Love Story includes his laboratory notes for the synthesis and initial test-dose experience of 179 compounds¹; this does not include research done by others or any work since its publication in 1995.          

Notable popular drugs chemically similar to NBOMe and BDF are mescaline (found in peyote), cathinones (“bath salts”), and MDMA (found in ecstasy) (Figure). Naturally occurring (and more complex) compounds with similar effects include ayahuasca, a plant-derived beverage consisting of Banisteriopsis caapi and either Psychotria viridis or Diplopterys cabrerana from the Brazilian rainforest (see Emerg Med. 2014;46[12]:553-556); psilocybin (“magic mushrooms”); and lysergic acid diethylamide. 

How are these drugs used and what are their clinical effects?

Most phenylethylamine compounds are well absorbed across the buccal mucosa, which is why BDF and NBOMe are commonly used in liquid form or on blotter paper. Dosing guides also exist for insufflation and claim equipotent dosing for this route.⁵ Regardless of delivery route, given the high potency, inadvertent exposures to these drugs should be expected.

Users simply seeking to hallucinate may not be aware of the significant risks associated with these potent serotonergic agents, which include both life- and limb-threatening effects.⁶ The high 5-HT_2A potency results both in vasoconstriction and promotion of clot formation due to the presence of 5HT_2A receptors on small blood vessels and platelets, respectively. Ergotism, historically called Saint Anthony’s fire, is an example of serotonergic vasoconstriction and hallucination.⁷ Chronic users of substituted amphetamines can develop necrotic ulcers in distal vascular beds such as the hands and feet; these ulcers may progress to amputation despite treatment attempts with vasodilators.

In addition to the vasoconstrictive properties, there are multiple reports of serotonin toxicity (serotonin syndrome) associated with use of these designer serotonergic amphetamines. This syndrome includes severe psychomotor agitation that can lead to personal injury, along with muscle rigidity, tremor, hyperthermia, rhabdomyolysis, and seizures.⁸

 

 How are patients with phenylethylamine exposures managed?

 Management of a patient with a substituted phenylethylamine exposure is similar to management of those with cocaine overdose. Attention to the life-threatening clinical effects of psychomotor agitation, hyperthermia, and seizures is paramount. Appropriate supportive care includes intravenous (IV) benzodiazepines to control agitation and muscle rigidity, replacement of lost volume with crystalloids, and active cooling measures. Failure of benzodiazepines (preferably in conjunction with continuous electroencephalogram monitoring) to control rigidity may lead to the need for propofol and/or result in paralysis. Similar to patients with cocaine intoxication, some may experience ischemic chest pain, and the usual protocol of sedation, nitroglycerin, morphine, and an antiplatelet drug is appropriate.

Identification of phenylethylamines typically requires specialized laboratory testing since most will not trigger a positive result on a standard urine immunoassay. Many specialized laboratories have test catalogs on their Web sites listing under the “stimulants panel” which drugs can be identified. However, none of these assays is likely truly comprehensive, and minor alterations or substitutions to the compounds result in new analogs that may not be in the reference laboratory’s identification library.

 

Case

A 24-year-old man was brought to the ED by emergency medical services (EMS) for altered mental status. The EMS crew reported they had picked up the patient at a nearby arts festival and concert series. A bystander at the event reported that the patient had taken something called “dragonfly.”

Initial assessment revealed the patient to be disoriented, with nonlinear thought patterns and an inability to follow commands. His vital signs were: blood pressure, 160/100 mm Hg; heart rate, 120 beats/minute; respiratory rate, 24 breaths/minute; and temperature, 102.2˚F. Oxygen saturation was 99% on room air. He was diaphoretic and agitated, and the nursing staff was concerned he would become aggressive and potentially violent. A quick Web search revealed that the agent the bystander mentioned was most likely Bromo-DragonFLY (BDF).

What is Bromo-DragonFLY?

In the 1960s, an American chemist named Alexander Shulgin ushered in a new era of psychedelic drug use by establishing a simple synthesis of 3,4-methylenedioxy-methamphetamine (MDMA). Following this discovery, he suggested a therapist friend use the drug therapeutically.¹ Shulgin then began a process of homologation (ie, creating novel compounds by slightly altering existing ones in an organized fashion) and developed systems for rating the drug experiences and naming the drugs in shorthand, both of which are still in use. The chemical structure common to nearly all of the drugs he studied is phenylethylamine. The Figure shows the structures of several phenylethylamine derivatives that were created by adding functional groups to the phenylethylamine backbone. Although the popularity of psychedelic drugs surged during this time period, 2,5-dimethoxy-N-(2-methoxybenzyl)phenylethylamine) (NBOMe), one of a number of newly popular psychedelics, only became available in 2003.

What is known about the pharmacology of Bromo-DragonFLY and NBOMe?

The major target of psychedelic drugs is the serotonin (5-HT₂) receptor, specifically the central 5-HT_2A subtype. Bromo-DragonFLY is a classic example of designer pharmacology in that the it was intended to potently exert its effect at this specific receptor site.

As its name suggests,  BDF adds the “wings of the fly” to the phenylethylamine backbone furanyl rings at positions 2 and 5, and a halogen (bromine) at position 4. The furanyl ring impairs enzymatic clearance of the drug,² resulting in a duration of action of up to 3 days.³ The addition of halogens increases drug potency, but the mechanism is not clear. The psychedelic agent NBOMe results from chemical additions of methoxy groups at position 2 and 5, and the halogen moiety (iodine in this case) at position 4 of the phenyl ring of the phenylethylamine structure.⁴

Through the work of Shulgin, some of his colleagues, and many disparate street chemists, a vast family of substituted phenylethylamines have been synthesized and used. Shulgin’s semiautobiographical book PiHKAL: A Chemical Love Story includes his laboratory notes for the synthesis and initial test-dose experience of 179 compounds¹; this does not include research done by others or any work since its publication in 1995.          

Notable popular drugs chemically similar to NBOMe and BDF are mescaline (found in peyote), cathinones (“bath salts”), and MDMA (found in ecstasy) (Figure). Naturally occurring (and more complex) compounds with similar effects include ayahuasca, a plant-derived beverage consisting of Banisteriopsis caapi and either Psychotria viridis or Diplopterys cabrerana from the Brazilian rainforest (see Emerg Med. 2014;46[12]:553-556); psilocybin (“magic mushrooms”); and lysergic acid diethylamide. 

How are these drugs used and what are their clinical effects?

Most phenylethylamine compounds are well absorbed across the buccal mucosa, which is why BDF and NBOMe are commonly used in liquid form or on blotter paper. Dosing guides also exist for insufflation and claim equipotent dosing for this route.⁵ Regardless of delivery route, given the high potency, inadvertent exposures to these drugs should be expected.

Users simply seeking to hallucinate may not be aware of the significant risks associated with these potent serotonergic agents, which include both life- and limb-threatening effects.⁶ The high 5-HT_2A potency results both in vasoconstriction and promotion of clot formation due to the presence of 5HT_2A receptors on small blood vessels and platelets, respectively. Ergotism, historically called Saint Anthony’s fire, is an example of serotonergic vasoconstriction and hallucination.⁷ Chronic users of substituted amphetamines can develop necrotic ulcers in distal vascular beds such as the hands and feet; these ulcers may progress to amputation despite treatment attempts with vasodilators.

In addition to the vasoconstrictive properties, there are multiple reports of serotonin toxicity (serotonin syndrome) associated with use of these designer serotonergic amphetamines. This syndrome includes severe psychomotor agitation that can lead to personal injury, along with muscle rigidity, tremor, hyperthermia, rhabdomyolysis, and seizures.⁸

 

 How are patients with phenylethylamine exposures managed?

 Management of a patient with a substituted phenylethylamine exposure is similar to management of those with cocaine overdose. Attention to the life-threatening clinical effects of psychomotor agitation, hyperthermia, and seizures is paramount. Appropriate supportive care includes intravenous (IV) benzodiazepines to control agitation and muscle rigidity, replacement of lost volume with crystalloids, and active cooling measures. Failure of benzodiazepines (preferably in conjunction with continuous electroencephalogram monitoring) to control rigidity may lead to the need for propofol and/or result in paralysis. Similar to patients with cocaine intoxication, some may experience ischemic chest pain, and the usual protocol of sedation, nitroglycerin, morphine, and an antiplatelet drug is appropriate.

Identification of phenylethylamines typically requires specialized laboratory testing since most will not trigger a positive result on a standard urine immunoassay. Many specialized laboratories have test catalogs on their Web sites listing under the “stimulants panel” which drugs can be identified. However, none of these assays is likely truly comprehensive, and minor alterations or substitutions to the compounds result in new analogs that may not be in the reference laboratory’s identification library.

 

Soft-tissue sarcomas are quite rare, with an annual incidence of 20 to 30 per 1,000,000 persons in the United States.¹ Because of their heterogeneous presentation, they remain a diagnostic challenge and are often initially confused for more common, benign disorders.² Chronic expanding hematoma, first described by Friedlander and colleagues³ in 1968, is a rare entity that is particularly difficult to distinguish from soft-tissue malignancy.^3-5 Chronic expanding hematoma is defined as a hematoma that gradually expands over 1 month or longer, is absent of neoplastic change on histologic sections, and does not occur in the setting of coagulopathy.⁶

Typically associated with remote trauma, these lesions often present as a slowly growing mass on the anterior or lateral thigh, calf, or buttock.^3-4,7-9 They have been reported to persist as long as 46 years, with sizes ranging from 3 to 55 cm in maximum diameter.⁷ On imaging, they have a cystic appearance with a dense fibrous capsule.^7-8 Most cases resolve uneventfully after drainage or marginal excision, although some cases require repeated intervention.⁷ This case report describes a morbidly obese patient with a chronic expanding hematoma in the distal posterior thigh whose definitive treatment was delayed 6 months because of her pregnancy status and inability to lie prone for open biopsy. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 27-year-old morbidly obese woman, who was pregnant at 12 weeks gestation, was seen in an orthopedic oncology clinic with a 1-month history of a slowly growing, painful posterior thigh mass. She had no history of cancer or bleeding disorder, and denied a history of trauma or constitutional symptoms consistent with malignancy. Coagulation studies were normal. Magnetic resonance imaging (MRI) obtained 2 weeks prior in the emergency room showed a cystic lesion with mass-like components in the posterior compartment of the distal right thigh, measuring 17 cm longitudinally. The lesion was located adjacent to, but not involving, the sciatic nerve and femoral vasculature. On initial examination, the large soft-tissue mass was evident and moderately painful to palpation; no skin changes were noted, and the patient had a normal sensorimotor examination. Fine-needle aspiration was performed, which resulted in amorphous debris consistent with hematoma.

Repeat MRI 2 months later showed increased size of the lesion (9.5×10.5 cm axial, 22.0 cm craniocaudal). Although most findings of a more extensive imaging protocol, including precontrast and postcontrast sequences, were consistent with hematoma, the lesion also had several characteristics that indicated soft-tissue sarcoma. Specifically, findings suggestive of chronic hematoma included the hyperintense short tau inversion recovery (STIR) T1/T2 signal of the cystic component consistent with proteinaceous fluid and the low STIR TI/T2 signal of the periphery consistent with a rim of hemosiderin (Figure 1). Additionally, the cystic component of the lesion had multiple fine septations that are atypical for a hematoma (Figure 1), and several lymph nodes greater than 1.7 cm in short axis were noted in the anterior thigh and hemipelvis that were suspicious of metastatic lymphadenopathy. The encapsulated appearance of the lesion with a sharply defined margin and short transition zone were also reassuring findings for a benign lesion (Figures 1, 2A, 2B). However, several findings were identified that suggested soft-tissue sarcoma, including a nodular soft-tissue component on the medial wall of the lesion that had heterogeneous enhancement with contrast (Figure 2B). We, therefore, proceeded with ultrasound-guided core needle biopsy of the mass and cytologic sampling of the fluid components, which were again consistent with hematoma; no evidence of internal vascular flow was noted on Doppler ultrasound. Ultrasound-guided right inguinal lymph node biopsy was also performed and was negative for malignancy. Because of her large body habitus and pregnancy status, it was agreed that open biopsy should be delayed until after delivery to avoid placing the patient in a prone position.

The patient visited the emergency room several times during the following months because of intermittent exacerbations of her lower extremity pain, swelling, and occasional paresthesias. About 6 months after initial presentation, repeat MRI again showed increased size of the mass (13.5×13.5 cm axial, 28 cm craniocaudal). There was also increased displacement of the adjacent neurovascular structures but no evidence of deep vein thrombosis. Because of concerns about the increased symptomatology of her thigh mass and possible sampling error of the previous biopsies, an elective cesarean section was performed at 35 weeks gestation. One week later, after clearance by her obstetrician, we proceeded with open biopsy of the mass in prone position. Initial sampling was negative for malignancy on frozen section; then, we expressed 1.75 L of brown fluid and solidified blood products, irrigated copiously, and placed a surgical drain. The permanent histologic specimens were again consistent with hematoma, and microbial cultures were negative. A week later, the patient accidentally removed her drain, and she presented with a fever (101°F) on postoperative day (POD) 15. Computed tomography showed reaccumulation of fluid; duplex ultrasound was negative. She was placed on cephalexin and underwent ultrasound-guided replacement of the drain with removal of an additional 750 mL fluid on POD 20. She drained an additional 150 to 200 mL/d for 1 month, with marked improvement in her leg swelling and knee range of motion. The drainage decreased during the next 3 weeks, and the drain was removed on POD 75.

 

Discussion

The presence of a hematoma in the extremities is usually a straightforward diagnosis. However, the unusual circumstances of this case highlight all the indications for investigation for possible soft-tissue sarcoma when a patient presents with what appears to be a benign condition.

Hematomas are rare in the absence of trauma or coagulopathy, with chronic expansion of hematomas rarer still.^4,7,10-11 The patient had no evidence of coagulopathy because of her ability to have an uncomplicated pregnancy and elective cesarean section. She denied a history of trauma, and the location of her hematoma at the posterior distal thigh is an uncommon site of injury. In this setting, fine-needle aspiration and serial imaging to assess for progressive increase in lesion size were indicated to rule out malignancy.²

MRI is the gold-standard imaging modality for distinguishing soft-tissue masses from hematomas.^5,12-14 Unlike the typical appearance of a hematoma, sarcomas of the soft-tissue extremities are often complex cystic lesions with multiple septations, internal soft-tissue components, and relatively ill-defined margins.^15-17 However, as a hematoma becomes chronic, it can develop a fibrinous capsule, and the contents can manifest an atypical, heterogeneous appearance from scattered, progressive accumulation of blood products that is essentially indistinguishable from sarcomas on imaging.⁵

Because of the expansion of the hematoma and the atypical appearance of the mass on imaging, repeated core biopsy and, eventually, open biopsy were indicated, despite a preliminary negative diagnosis based on fine-needle aspiration. This resulted from the possibility of sampling error that is particularly relevant to cystic sarcomas, because only portions of the mass may be composed of malignant cells.² An unusual aspect of this case is the regional lymphadenopathy noted on MRI, because regional lymphatic spread is a known mechanism of metastasis in soft-tissue sarcomas.¹⁸ However, the inguinal biopsies showed a chronic inflammatory infiltrate and were negative for malignancy, and enlarged nodes were not seen on imaging several months later. It is possible that the lymphadenopathy resulted from an unrelated process; alternatively, it may have been secondary to impaired lymphatic drainage because of mass effect from the hematoma, which also caused temporary lower extremity swelling.

The distal posterior thigh is an unreported location for a chronic expanding hematoma. Our patient developed slowly progressive lower-limb swelling and, eventually, paresthesias because of displacement of the neurovasculature, an unusual sequela that was recently reported in a similar case of an acute spontaneous hematoma in a patient on warfarin.¹⁹ Rupture of a Baker cyst is a possible inciting factor in our patient, although the proximal location of the lesion and the clearly defined tissue plane on MRI between the hematoma and the popliteal region make this unlikely. Finally, the patient’s lesion showed no evidence of vascular flow on Doppler ultrasonography, although giant hematomas secondary to popliteal aneurysm rupture have been reported.^20-22

Conclusion

This case highlights the features of a chronic expanding hematoma that can suggest soft-tissue sarcoma and shows the recommended diagnostic steps to differentiate the 2 conditions. This case also describes an unreported location for a chronic expanding hematoma with resulting progressive neurovascular displacement caused by mass effect. We recommend careful monitoring of patients with similarly expansile lesions in this region for signs of neurovascular compromise.

Soft-tissue sarcomas are quite rare, with an annual incidence of 20 to 30 per 1,000,000 persons in the United States.¹ Because of their heterogeneous presentation, they remain a diagnostic challenge and are often initially confused for more common, benign disorders.² Chronic expanding hematoma, first described by Friedlander and colleagues³ in 1968, is a rare entity that is particularly difficult to distinguish from soft-tissue malignancy.^3-5 Chronic expanding hematoma is defined as a hematoma that gradually expands over 1 month or longer, is absent of neoplastic change on histologic sections, and does not occur in the setting of coagulopathy.⁶

Typically associated with remote trauma, these lesions often present as a slowly growing mass on the anterior or lateral thigh, calf, or buttock.^3-4,7-9 They have been reported to persist as long as 46 years, with sizes ranging from 3 to 55 cm in maximum diameter.⁷ On imaging, they have a cystic appearance with a dense fibrous capsule.^7-8 Most cases resolve uneventfully after drainage or marginal excision, although some cases require repeated intervention.⁷ This case report describes a morbidly obese patient with a chronic expanding hematoma in the distal posterior thigh whose definitive treatment was delayed 6 months because of her pregnancy status and inability to lie prone for open biopsy. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 27-year-old morbidly obese woman, who was pregnant at 12 weeks gestation, was seen in an orthopedic oncology clinic with a 1-month history of a slowly growing, painful posterior thigh mass. She had no history of cancer or bleeding disorder, and denied a history of trauma or constitutional symptoms consistent with malignancy. Coagulation studies were normal. Magnetic resonance imaging (MRI) obtained 2 weeks prior in the emergency room showed a cystic lesion with mass-like components in the posterior compartment of the distal right thigh, measuring 17 cm longitudinally. The lesion was located adjacent to, but not involving, the sciatic nerve and femoral vasculature. On initial examination, the large soft-tissue mass was evident and moderately painful to palpation; no skin changes were noted, and the patient had a normal sensorimotor examination. Fine-needle aspiration was performed, which resulted in amorphous debris consistent with hematoma.

Repeat MRI 2 months later showed increased size of the lesion (9.5×10.5 cm axial, 22.0 cm craniocaudal). Although most findings of a more extensive imaging protocol, including precontrast and postcontrast sequences, were consistent with hematoma, the lesion also had several characteristics that indicated soft-tissue sarcoma. Specifically, findings suggestive of chronic hematoma included the hyperintense short tau inversion recovery (STIR) T1/T2 signal of the cystic component consistent with proteinaceous fluid and the low STIR TI/T2 signal of the periphery consistent with a rim of hemosiderin (Figure 1). Additionally, the cystic component of the lesion had multiple fine septations that are atypical for a hematoma (Figure 1), and several lymph nodes greater than 1.7 cm in short axis were noted in the anterior thigh and hemipelvis that were suspicious of metastatic lymphadenopathy. The encapsulated appearance of the lesion with a sharply defined margin and short transition zone were also reassuring findings for a benign lesion (Figures 1, 2A, 2B). However, several findings were identified that suggested soft-tissue sarcoma, including a nodular soft-tissue component on the medial wall of the lesion that had heterogeneous enhancement with contrast (Figure 2B). We, therefore, proceeded with ultrasound-guided core needle biopsy of the mass and cytologic sampling of the fluid components, which were again consistent with hematoma; no evidence of internal vascular flow was noted on Doppler ultrasound. Ultrasound-guided right inguinal lymph node biopsy was also performed and was negative for malignancy. Because of her large body habitus and pregnancy status, it was agreed that open biopsy should be delayed until after delivery to avoid placing the patient in a prone position.

The patient visited the emergency room several times during the following months because of intermittent exacerbations of her lower extremity pain, swelling, and occasional paresthesias. About 6 months after initial presentation, repeat MRI again showed increased size of the mass (13.5×13.5 cm axial, 28 cm craniocaudal). There was also increased displacement of the adjacent neurovascular structures but no evidence of deep vein thrombosis. Because of concerns about the increased symptomatology of her thigh mass and possible sampling error of the previous biopsies, an elective cesarean section was performed at 35 weeks gestation. One week later, after clearance by her obstetrician, we proceeded with open biopsy of the mass in prone position. Initial sampling was negative for malignancy on frozen section; then, we expressed 1.75 L of brown fluid and solidified blood products, irrigated copiously, and placed a surgical drain. The permanent histologic specimens were again consistent with hematoma, and microbial cultures were negative. A week later, the patient accidentally removed her drain, and she presented with a fever (101°F) on postoperative day (POD) 15. Computed tomography showed reaccumulation of fluid; duplex ultrasound was negative. She was placed on cephalexin and underwent ultrasound-guided replacement of the drain with removal of an additional 750 mL fluid on POD 20. She drained an additional 150 to 200 mL/d for 1 month, with marked improvement in her leg swelling and knee range of motion. The drainage decreased during the next 3 weeks, and the drain was removed on POD 75.

 

Discussion

The presence of a hematoma in the extremities is usually a straightforward diagnosis. However, the unusual circumstances of this case highlight all the indications for investigation for possible soft-tissue sarcoma when a patient presents with what appears to be a benign condition.

Hematomas are rare in the absence of trauma or coagulopathy, with chronic expansion of hematomas rarer still.^4,7,10-11 The patient had no evidence of coagulopathy because of her ability to have an uncomplicated pregnancy and elective cesarean section. She denied a history of trauma, and the location of her hematoma at the posterior distal thigh is an uncommon site of injury. In this setting, fine-needle aspiration and serial imaging to assess for progressive increase in lesion size were indicated to rule out malignancy.²

MRI is the gold-standard imaging modality for distinguishing soft-tissue masses from hematomas.^5,12-14 Unlike the typical appearance of a hematoma, sarcomas of the soft-tissue extremities are often complex cystic lesions with multiple septations, internal soft-tissue components, and relatively ill-defined margins.^15-17 However, as a hematoma becomes chronic, it can develop a fibrinous capsule, and the contents can manifest an atypical, heterogeneous appearance from scattered, progressive accumulation of blood products that is essentially indistinguishable from sarcomas on imaging.⁵

Because of the expansion of the hematoma and the atypical appearance of the mass on imaging, repeated core biopsy and, eventually, open biopsy were indicated, despite a preliminary negative diagnosis based on fine-needle aspiration. This resulted from the possibility of sampling error that is particularly relevant to cystic sarcomas, because only portions of the mass may be composed of malignant cells.² An unusual aspect of this case is the regional lymphadenopathy noted on MRI, because regional lymphatic spread is a known mechanism of metastasis in soft-tissue sarcomas.¹⁸ However, the inguinal biopsies showed a chronic inflammatory infiltrate and were negative for malignancy, and enlarged nodes were not seen on imaging several months later. It is possible that the lymphadenopathy resulted from an unrelated process; alternatively, it may have been secondary to impaired lymphatic drainage because of mass effect from the hematoma, which also caused temporary lower extremity swelling.

The distal posterior thigh is an unreported location for a chronic expanding hematoma. Our patient developed slowly progressive lower-limb swelling and, eventually, paresthesias because of displacement of the neurovasculature, an unusual sequela that was recently reported in a similar case of an acute spontaneous hematoma in a patient on warfarin.¹⁹ Rupture of a Baker cyst is a possible inciting factor in our patient, although the proximal location of the lesion and the clearly defined tissue plane on MRI between the hematoma and the popliteal region make this unlikely. Finally, the patient’s lesion showed no evidence of vascular flow on Doppler ultrasonography, although giant hematomas secondary to popliteal aneurysm rupture have been reported.^20-22

Conclusion

This case highlights the features of a chronic expanding hematoma that can suggest soft-tissue sarcoma and shows the recommended diagnostic steps to differentiate the 2 conditions. This case also describes an unreported location for a chronic expanding hematoma with resulting progressive neurovascular displacement caused by mass effect. We recommend careful monitoring of patients with similarly expansile lesions in this region for signs of neurovascular compromise.

Soft-tissue sarcomas are quite rare, with an annual incidence of 20 to 30 per 1,000,000 persons in the United States.¹ Because of their heterogeneous presentation, they remain a diagnostic challenge and are often initially confused for more common, benign disorders.² Chronic expanding hematoma, first described by Friedlander and colleagues³ in 1968, is a rare entity that is particularly difficult to distinguish from soft-tissue malignancy.^3-5 Chronic expanding hematoma is defined as a hematoma that gradually expands over 1 month or longer, is absent of neoplastic change on histologic sections, and does not occur in the setting of coagulopathy.⁶

Typically associated with remote trauma, these lesions often present as a slowly growing mass on the anterior or lateral thigh, calf, or buttock.^3-4,7-9 They have been reported to persist as long as 46 years, with sizes ranging from 3 to 55 cm in maximum diameter.⁷ On imaging, they have a cystic appearance with a dense fibrous capsule.^7-8 Most cases resolve uneventfully after drainage or marginal excision, although some cases require repeated intervention.⁷ This case report describes a morbidly obese patient with a chronic expanding hematoma in the distal posterior thigh whose definitive treatment was delayed 6 months because of her pregnancy status and inability to lie prone for open biopsy. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 27-year-old morbidly obese woman, who was pregnant at 12 weeks gestation, was seen in an orthopedic oncology clinic with a 1-month history of a slowly growing, painful posterior thigh mass. She had no history of cancer or bleeding disorder, and denied a history of trauma or constitutional symptoms consistent with malignancy. Coagulation studies were normal. Magnetic resonance imaging (MRI) obtained 2 weeks prior in the emergency room showed a cystic lesion with mass-like components in the posterior compartment of the distal right thigh, measuring 17 cm longitudinally. The lesion was located adjacent to, but not involving, the sciatic nerve and femoral vasculature. On initial examination, the large soft-tissue mass was evident and moderately painful to palpation; no skin changes were noted, and the patient had a normal sensorimotor examination. Fine-needle aspiration was performed, which resulted in amorphous debris consistent with hematoma.

Repeat MRI 2 months later showed increased size of the lesion (9.5×10.5 cm axial, 22.0 cm craniocaudal). Although most findings of a more extensive imaging protocol, including precontrast and postcontrast sequences, were consistent with hematoma, the lesion also had several characteristics that indicated soft-tissue sarcoma. Specifically, findings suggestive of chronic hematoma included the hyperintense short tau inversion recovery (STIR) T1/T2 signal of the cystic component consistent with proteinaceous fluid and the low STIR TI/T2 signal of the periphery consistent with a rim of hemosiderin (Figure 1). Additionally, the cystic component of the lesion had multiple fine septations that are atypical for a hematoma (Figure 1), and several lymph nodes greater than 1.7 cm in short axis were noted in the anterior thigh and hemipelvis that were suspicious of metastatic lymphadenopathy. The encapsulated appearance of the lesion with a sharply defined margin and short transition zone were also reassuring findings for a benign lesion (Figures 1, 2A, 2B). However, several findings were identified that suggested soft-tissue sarcoma, including a nodular soft-tissue component on the medial wall of the lesion that had heterogeneous enhancement with contrast (Figure 2B). We, therefore, proceeded with ultrasound-guided core needle biopsy of the mass and cytologic sampling of the fluid components, which were again consistent with hematoma; no evidence of internal vascular flow was noted on Doppler ultrasound. Ultrasound-guided right inguinal lymph node biopsy was also performed and was negative for malignancy. Because of her large body habitus and pregnancy status, it was agreed that open biopsy should be delayed until after delivery to avoid placing the patient in a prone position.

The patient visited the emergency room several times during the following months because of intermittent exacerbations of her lower extremity pain, swelling, and occasional paresthesias. About 6 months after initial presentation, repeat MRI again showed increased size of the mass (13.5×13.5 cm axial, 28 cm craniocaudal). There was also increased displacement of the adjacent neurovascular structures but no evidence of deep vein thrombosis. Because of concerns about the increased symptomatology of her thigh mass and possible sampling error of the previous biopsies, an elective cesarean section was performed at 35 weeks gestation. One week later, after clearance by her obstetrician, we proceeded with open biopsy of the mass in prone position. Initial sampling was negative for malignancy on frozen section; then, we expressed 1.75 L of brown fluid and solidified blood products, irrigated copiously, and placed a surgical drain. The permanent histologic specimens were again consistent with hematoma, and microbial cultures were negative. A week later, the patient accidentally removed her drain, and she presented with a fever (101°F) on postoperative day (POD) 15. Computed tomography showed reaccumulation of fluid; duplex ultrasound was negative. She was placed on cephalexin and underwent ultrasound-guided replacement of the drain with removal of an additional 750 mL fluid on POD 20. She drained an additional 150 to 200 mL/d for 1 month, with marked improvement in her leg swelling and knee range of motion. The drainage decreased during the next 3 weeks, and the drain was removed on POD 75.

 

Discussion

The presence of a hematoma in the extremities is usually a straightforward diagnosis. However, the unusual circumstances of this case highlight all the indications for investigation for possible soft-tissue sarcoma when a patient presents with what appears to be a benign condition.

Hematomas are rare in the absence of trauma or coagulopathy, with chronic expansion of hematomas rarer still.^4,7,10-11 The patient had no evidence of coagulopathy because of her ability to have an uncomplicated pregnancy and elective cesarean section. She denied a history of trauma, and the location of her hematoma at the posterior distal thigh is an uncommon site of injury. In this setting, fine-needle aspiration and serial imaging to assess for progressive increase in lesion size were indicated to rule out malignancy.²

MRI is the gold-standard imaging modality for distinguishing soft-tissue masses from hematomas.^5,12-14 Unlike the typical appearance of a hematoma, sarcomas of the soft-tissue extremities are often complex cystic lesions with multiple septations, internal soft-tissue components, and relatively ill-defined margins.^15-17 However, as a hematoma becomes chronic, it can develop a fibrinous capsule, and the contents can manifest an atypical, heterogeneous appearance from scattered, progressive accumulation of blood products that is essentially indistinguishable from sarcomas on imaging.⁵

Because of the expansion of the hematoma and the atypical appearance of the mass on imaging, repeated core biopsy and, eventually, open biopsy were indicated, despite a preliminary negative diagnosis based on fine-needle aspiration. This resulted from the possibility of sampling error that is particularly relevant to cystic sarcomas, because only portions of the mass may be composed of malignant cells.² An unusual aspect of this case is the regional lymphadenopathy noted on MRI, because regional lymphatic spread is a known mechanism of metastasis in soft-tissue sarcomas.¹⁸ However, the inguinal biopsies showed a chronic inflammatory infiltrate and were negative for malignancy, and enlarged nodes were not seen on imaging several months later. It is possible that the lymphadenopathy resulted from an unrelated process; alternatively, it may have been secondary to impaired lymphatic drainage because of mass effect from the hematoma, which also caused temporary lower extremity swelling.

The distal posterior thigh is an unreported location for a chronic expanding hematoma. Our patient developed slowly progressive lower-limb swelling and, eventually, paresthesias because of displacement of the neurovasculature, an unusual sequela that was recently reported in a similar case of an acute spontaneous hematoma in a patient on warfarin.¹⁹ Rupture of a Baker cyst is a possible inciting factor in our patient, although the proximal location of the lesion and the clearly defined tissue plane on MRI between the hematoma and the popliteal region make this unlikely. Finally, the patient’s lesion showed no evidence of vascular flow on Doppler ultrasonography, although giant hematomas secondary to popliteal aneurysm rupture have been reported.^20-22

Conclusion

This case highlights the features of a chronic expanding hematoma that can suggest soft-tissue sarcoma and shows the recommended diagnostic steps to differentiate the 2 conditions. This case also describes an unreported location for a chronic expanding hematoma with resulting progressive neurovascular displacement caused by mass effect. We recommend careful monitoring of patients with similarly expansile lesions in this region for signs of neurovascular compromise.

Fat embolism syndrome (FES) was first described by Von Bergmann in 1873 in a patient with a fractured femur.¹ While fat within the circulation (fat embolism) is relatively common following long-bone fracture, the clinical pattern of symptoms that make up FES is less so, occurring in 1% to 3% of isolated long-bone fractures and 5% to 10% of patients with multiple skeletal trauma.¹ A variety of clinical, laboratory, and imaging criteria has been described, classically by Gurd in 1970 (Table).^1-6 Most commonly, however, it is a diagnosis of exclusion when the classic triad of respiratory difficulty, neurologic abnormalities, and a characteristic petechial rash are present in the appropriate clinical setting.⁶ 

The neurologic sequelae of this syndrome can range from headache, confusion, and agitation to stupor, focal neurologic signs, and, less commonly, coma.⁷ Onset of these symptoms usually occurs between 24 hours and 48 hours (mean, 40 hours) after trauma.¹ While these neurologic manifestations occur in up to 86% of patients with FES, it is rare for them to be present without the pulmonary symptoms of dyspnea, hypoxemia, and tachypnea, which are the most common presenting symptoms of the disease.^1-6 In this case report, we describe severe, rapid-onset neurologic manifestations, without the typical pulmonary involvement, as the primary clinical presentation of FES in a polytrauma patient. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A previously healthy 50-year-old man presented to the emergency room in transfer from an outside hospital after a rollover motor vehicle collision in which he was ejected approximately 50 feet. Injuries included a right proximal humerus fracture/dislocation (Figure 1), right ulnar styloid fracture, L1 compression fracture, and multiple rib fractures. On admission, the patient had an ethanol level of 969 mg/L (.097%) and a urine drug screen positive only for opioids, presumably because of pain medication given that day. He denied a history of alcohol abuse and reported consuming 2 to 3 beers per week. The patient was awake, alert, and oriented with a Glasgow Coma Scale (GCS) of 15. He was tachycardic (heart rate, 126), tachypneic (respiratory rate, 24), and febrile (temperature, 38.6°C [101.5°F]), and his white blood cell count was elevated at 29.5×10⁹/L. On examination, his right arm was found to be neurovascularly intact; it was placed in a sling with a forearm splint, and the patient was admitted to the intermediate special care unit on spine precautions with a plan for right shoulder hemiarthroplasty the following day.

Overnight the patient’s mental status began to deteriorate, and approximately 10 hours after initial assessment, he was not answering questions but was able to respond to some commands. On hospital day 2, approximately 20 hours after initial assessment, the patient had a GCS of 8, was not responding to commands, and moved only in response to painful stimuli. The patient had been prescribed morphine by patient-controlled analgesia and had received intravenous hydromorphone on the day of admission, although the amount of medication delivered was not thought adequate to explain this deterioration. On the morning of hospital day 2, noncontrast brain computed tomography (CT) was normal with no evidence of intracranial hemorrhage or infarct. This was followed by brain magnetic resonance imaging (MRI), with the T2-weighted images showing numerous, small hyperintense lesions in subcortical and periventricular white matter, corpus callosum, basal ganglia, brain stem, and cerebellar hemispheres (Figure 2). The lesions also showed hyperintensity on diffusion-weighted MRI and were interpreted to be consistent with multiple, tiny infarcts (Figure 3). In addition, susceptibility-weighted sequences showed low signal in the same areas, suggesting multiple microhemorrhages, a pattern consistent with FES. Oxygen saturations remained 95% to 99%, and chest radiograph revealed clear lung fields without infiltrate. On hospital day 2, the patient was transferred to the intensive care unit and intubated for airway protection owing to an inability to clear secretions, although arterial blood gas levels remained normal. An echocardiogram revealed no right-to-left shunt, such as a patent foramen ovale (PFO); an electroencephalogram showed no seizure-like activity. No petechial rash was noted on skin examination. The patient was treated with supportive care. Right shoulder hemiarthroplasty was performed on hospital day 7 without complications (Figure 1). On hospital day 13, the patient was following commands and on day 14 he was extubated. His mental status continued to improve, and he was discharged to a rehabilitation facility after 36 days. On last follow-up, 6 months after initial injury, the patient was recovering well with no residual neurologic deficits and only minor limitation in range of motion of the right shoulder.

 

Discussion

This case presented an interesting diagnostic challenge regarding the patient’s rapid decline in mental status, with a differential diagnosis including diffuse axonal injury (DAI), anoxic brain injury, posttraumatic seizure, other intracranial pathology, such as stroke or hemorrhage, and FES. FES was diagnosed, when other possibilities were ruled out, given the characteristic findings on brain MRI described above in the context of multiple fractures.

Pathophysiology

Despite its recognition in 1873, there is no consensus on the pathophysiological mechanism that causes the clinical symptoms of FES. In the setting of trauma, there are 2 predominant theories. The mechanical theory postulates that fat globules enter the circulation through disrupted venules after the fracture of marrow-containing bones, passing to the arterial circulation through pulmonary vasculature, or paradoxically, by way of a right-to-left shunt, such as a PFO.^1,3 The presence of fat in the heart, visualized as echogenic material in the right and left atria on transesophageal echocardiography, has been confirmed in multiple studies during orthopedic procedures, including total knee arthroplasty and femoral reaming.^8,9 These fat particles can lodge as microembolisms in target organs such as the skin and brain. However, autopsy studies have shown a lack of correlation of the severity of symptoms and the quantity of intravascular fat.¹ In addition, the typical 24- to 72-hour delay in the onset of symptoms after initial trauma would argue against a solely mechanical explanation.¹⁰

Alternatively or concomitantly, the biochemical theory proposes that embolized fat may be degraded to toxic intermediaries, such as free fatty acids and C-reactive protein, which cause end-organ damage.³ This has been shown in an animal model, in which intravascular injection of free fatty acids was associated with endothelial damage and increased capillary permeability in the lung, leading to acute respiratory distress syndrome (ARDS).¹¹ The same mechanism could explain injury to other end organs and is consistent with the delay in onset of symptoms after acute injury. In our patient’s case, the absence of pulmonary involvement, lack of a right-to-left vascular shunt such as a PFO, and presence of a systemic inflammatory response on admission may implicate the production of toxic intermediaries from the metabolism of embolized fat as the source of this patient’s FES.

Clinical Presentation

The initial presentation of FES usually manifests as respiratory distress and hypoxia.¹⁰ Chest radiographs are often normal, as in our patient, but can show bilateral diffuse interstitial or alveolar infiltrates.^2,6 CT more often has findings, including bilateral ground-glass opacities with interlobar septal thickening.¹² A petechial rash can be found on the head, neck, anterior thorax, axillae, subconjunctiva, and oral mucous membranes, although it occurs in only 20% to 50% of cases.^1,2,13 Neurologic sequelae are present in up to 80% of patients,⁷ with onset typically following pulmonary symptoms.^1,10 These sequelae can range from headache, confusion, and agitation to stupor, focal neurologic signs, and, less commonly, coma.⁷ Onset of symptoms generally occurs between 24 and 48 hours after trauma,¹ although they have been reported as early as 12 hours.¹⁰ This case is an example of an atypical course, with the initial presentation of neurologic symptoms at approximately 14 hours after trauma with rapid progression to coma without classic pulmonary symptoms.

Diagnosis

Owing to the nonspecific clinical features of FES, a variety of clinical, laboratory, and imaging criteria has been described. Of these criteria, the most frequently referenced is by Gurd in 1970,^4,5 who divided the features into major and minor, with 1 major and 4 minor features required to make the diagnosis (Table). In applying these criteria to our patient, we found that he exhibited the major criteria of cerebral involvement and minor criteria of tachycardia, fever, and thrombocytopenia. Respiratory insufficiency and petechial rash, as well as jaundice, renal changes, and anemia were negative features. Retinal changes, elevated erythrocyte sedimentation rate, and fat macroglobulinemia were not tested or examined. Although in our case the clinical and laboratory criteria for the diagnosis of FES as defined by Gurd were not met, the sensitivity of Gurd’s and other criteria is debated.¹⁰

Laboratory tests specific for the disease have not been developed. Although elevated serum levels of lipase, increased blood lipid levels, and fat globules in the urine, sputum, and blood have all been proposed, they are found in trauma patients with and without FES.^2,5,6

The nonspecific nature of the signs and symptoms of FES and the lack of reliable laboratory tests for diagnosis of the syndrome highlight the importance of radiographic evaluation in patients with neurologic symptoms. Brain CT scans are usually negative,¹⁴ although, in some cases, they may show diffuse edema with scattered low attenuating areas and hemorrhage.¹⁵ MRI is more sensitive, and T2-weighted images typically reveal multiple small, nonconfluent hyperintense lesions, usually in the periventricular, subcortical, and deep white matter, sometimes referred to as the “starfield” pattern.^14,16 The differential diagnosis for these findings is broad and, in addition to FES, includes DAI, vasogenic edema with microinfarcts, and demyelinating disease.¹⁴ Sensitivity and specificity may be increased with the addition of diffusion-weighted MRI, which shows scattered bright spots on a dark background in a similar “starfield” pattern as on T2-weighted images.¹⁵ Susceptibility-weighted MRI has recently been introduced as having utility in the diagnosis of FES, with areas of low-signal intensity indicating diffuse microhemorrhages.¹⁷ DAI can show a similar pattern; however, the autopsy-confirmed locations of the abnormalities are distinct, with those of FES being found in cerebral and cerebellar white matter and splenium of the corpus callosum and radiographic abnormalities of DAI being found in the gray-white matter junction, dorsolateral brainstem, and splenium of corpus callosum.¹⁷

 

Prevention and Treatment

Of primary importance in the prevention of FES is early stabilization of fractures. Several studies have shown a decreased incidence of FES when long-bone fractures are treated with immediate operative fixation.^18,19 However, in the setting of polytrauma, the desire for early definitive treatment must be balanced against the risks for the exaggerated immune response from prolonged surgery.²⁰ The timing of fracture fixation to prevent sequelae of the inflammatory response, such as ARDS and multiple organ dysfunction syndrome, is still debated. In a review article, Pape and colleagues²⁰ suggest classifying the multiply injured patient as stable, borderline, unstable, and in extremis based on clinical and laboratory criteria. They recommend early definitive fixation for stable patients and those patients who are borderline or unstable and responsive to resuscitation, whereas damage-control orthopedics and staged fracture fixation should be considered in the other groups.

Several pharmacologic interventions have been described, although their effects are highly variable and none have clear indications.^1-3,6 The most heavily researched is corticosteroids, with the proposed mechanisms of action including blunting of the inflammatory response, stabilizing the pulmonary capillary membrane to reduce interstitial edema, preventing activation of the complement system, and retarding platelet aggregation.²¹ A recent meta-analysis to assess this intervention examined 6 studies with a total of 386 patients with long-bone fractures who were randomized to treatment with corticosteroids or supportive care only.²² They found a reduced risk for FES in those patients who received corticosteroids, but there was no difference in mortality between groups. Given these results, the utility of corticosteroids is still debated.   

Once FES has occurred, treatment options usually focus on supportive care, with most patients having a full recovery.^1,3 No specific treatments are available, and symptomatic treatment is the suggested approach, including ensuring adequate oxygenation and ventilation and providing hemodynamic support and volume and blood-product resuscitation as needed.^1-3,6  

Conclusion

We have presented a case of FES unique in its rapid onset, an initial presentation with neurologic manifestations without typical pulmonary involvement, and the mechanism of end-organ damage without a right-to-left shunt. This case emphasizes the importance of considering FES in the patient with deteriorating mental status in the setting of multiple fractures, particularly in the absence of other characteristic clinical findings, such as pulmonary distress and the pathognomonic petechial rash. Brain MRI can play an important role in diagnosing those patients presenting with predominantly neurological symptoms. Early recognition of this condition allows for the anticipation of complications of the disease process, such as respiratory distress, and the potential need for mechanical ventilation and hemodynamic support.

Fat embolism syndrome (FES) was first described by Von Bergmann in 1873 in a patient with a fractured femur.¹ While fat within the circulation (fat embolism) is relatively common following long-bone fracture, the clinical pattern of symptoms that make up FES is less so, occurring in 1% to 3% of isolated long-bone fractures and 5% to 10% of patients with multiple skeletal trauma.¹ A variety of clinical, laboratory, and imaging criteria has been described, classically by Gurd in 1970 (Table).^1-6 Most commonly, however, it is a diagnosis of exclusion when the classic triad of respiratory difficulty, neurologic abnormalities, and a characteristic petechial rash are present in the appropriate clinical setting.⁶ 

The neurologic sequelae of this syndrome can range from headache, confusion, and agitation to stupor, focal neurologic signs, and, less commonly, coma.⁷ Onset of these symptoms usually occurs between 24 hours and 48 hours (mean, 40 hours) after trauma.¹ While these neurologic manifestations occur in up to 86% of patients with FES, it is rare for them to be present without the pulmonary symptoms of dyspnea, hypoxemia, and tachypnea, which are the most common presenting symptoms of the disease.^1-6 In this case report, we describe severe, rapid-onset neurologic manifestations, without the typical pulmonary involvement, as the primary clinical presentation of FES in a polytrauma patient. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A previously healthy 50-year-old man presented to the emergency room in transfer from an outside hospital after a rollover motor vehicle collision in which he was ejected approximately 50 feet. Injuries included a right proximal humerus fracture/dislocation (Figure 1), right ulnar styloid fracture, L1 compression fracture, and multiple rib fractures. On admission, the patient had an ethanol level of 969 mg/L (.097%) and a urine drug screen positive only for opioids, presumably because of pain medication given that day. He denied a history of alcohol abuse and reported consuming 2 to 3 beers per week. The patient was awake, alert, and oriented with a Glasgow Coma Scale (GCS) of 15. He was tachycardic (heart rate, 126), tachypneic (respiratory rate, 24), and febrile (temperature, 38.6°C [101.5°F]), and his white blood cell count was elevated at 29.5×10⁹/L. On examination, his right arm was found to be neurovascularly intact; it was placed in a sling with a forearm splint, and the patient was admitted to the intermediate special care unit on spine precautions with a plan for right shoulder hemiarthroplasty the following day.

Overnight the patient’s mental status began to deteriorate, and approximately 10 hours after initial assessment, he was not answering questions but was able to respond to some commands. On hospital day 2, approximately 20 hours after initial assessment, the patient had a GCS of 8, was not responding to commands, and moved only in response to painful stimuli. The patient had been prescribed morphine by patient-controlled analgesia and had received intravenous hydromorphone on the day of admission, although the amount of medication delivered was not thought adequate to explain this deterioration. On the morning of hospital day 2, noncontrast brain computed tomography (CT) was normal with no evidence of intracranial hemorrhage or infarct. This was followed by brain magnetic resonance imaging (MRI), with the T2-weighted images showing numerous, small hyperintense lesions in subcortical and periventricular white matter, corpus callosum, basal ganglia, brain stem, and cerebellar hemispheres (Figure 2). The lesions also showed hyperintensity on diffusion-weighted MRI and were interpreted to be consistent with multiple, tiny infarcts (Figure 3). In addition, susceptibility-weighted sequences showed low signal in the same areas, suggesting multiple microhemorrhages, a pattern consistent with FES. Oxygen saturations remained 95% to 99%, and chest radiograph revealed clear lung fields without infiltrate. On hospital day 2, the patient was transferred to the intensive care unit and intubated for airway protection owing to an inability to clear secretions, although arterial blood gas levels remained normal. An echocardiogram revealed no right-to-left shunt, such as a patent foramen ovale (PFO); an electroencephalogram showed no seizure-like activity. No petechial rash was noted on skin examination. The patient was treated with supportive care. Right shoulder hemiarthroplasty was performed on hospital day 7 without complications (Figure 1). On hospital day 13, the patient was following commands and on day 14 he was extubated. His mental status continued to improve, and he was discharged to a rehabilitation facility after 36 days. On last follow-up, 6 months after initial injury, the patient was recovering well with no residual neurologic deficits and only minor limitation in range of motion of the right shoulder.

 

Discussion

This case presented an interesting diagnostic challenge regarding the patient’s rapid decline in mental status, with a differential diagnosis including diffuse axonal injury (DAI), anoxic brain injury, posttraumatic seizure, other intracranial pathology, such as stroke or hemorrhage, and FES. FES was diagnosed, when other possibilities were ruled out, given the characteristic findings on brain MRI described above in the context of multiple fractures.

Pathophysiology

Despite its recognition in 1873, there is no consensus on the pathophysiological mechanism that causes the clinical symptoms of FES. In the setting of trauma, there are 2 predominant theories. The mechanical theory postulates that fat globules enter the circulation through disrupted venules after the fracture of marrow-containing bones, passing to the arterial circulation through pulmonary vasculature, or paradoxically, by way of a right-to-left shunt, such as a PFO.^1,3 The presence of fat in the heart, visualized as echogenic material in the right and left atria on transesophageal echocardiography, has been confirmed in multiple studies during orthopedic procedures, including total knee arthroplasty and femoral reaming.^8,9 These fat particles can lodge as microembolisms in target organs such as the skin and brain. However, autopsy studies have shown a lack of correlation of the severity of symptoms and the quantity of intravascular fat.¹ In addition, the typical 24- to 72-hour delay in the onset of symptoms after initial trauma would argue against a solely mechanical explanation.¹⁰

Alternatively or concomitantly, the biochemical theory proposes that embolized fat may be degraded to toxic intermediaries, such as free fatty acids and C-reactive protein, which cause end-organ damage.³ This has been shown in an animal model, in which intravascular injection of free fatty acids was associated with endothelial damage and increased capillary permeability in the lung, leading to acute respiratory distress syndrome (ARDS).¹¹ The same mechanism could explain injury to other end organs and is consistent with the delay in onset of symptoms after acute injury. In our patient’s case, the absence of pulmonary involvement, lack of a right-to-left vascular shunt such as a PFO, and presence of a systemic inflammatory response on admission may implicate the production of toxic intermediaries from the metabolism of embolized fat as the source of this patient’s FES.

Clinical Presentation

The initial presentation of FES usually manifests as respiratory distress and hypoxia.¹⁰ Chest radiographs are often normal, as in our patient, but can show bilateral diffuse interstitial or alveolar infiltrates.^2,6 CT more often has findings, including bilateral ground-glass opacities with interlobar septal thickening.¹² A petechial rash can be found on the head, neck, anterior thorax, axillae, subconjunctiva, and oral mucous membranes, although it occurs in only 20% to 50% of cases.^1,2,13 Neurologic sequelae are present in up to 80% of patients,⁷ with onset typically following pulmonary symptoms.^1,10 These sequelae can range from headache, confusion, and agitation to stupor, focal neurologic signs, and, less commonly, coma.⁷ Onset of symptoms generally occurs between 24 and 48 hours after trauma,¹ although they have been reported as early as 12 hours.¹⁰ This case is an example of an atypical course, with the initial presentation of neurologic symptoms at approximately 14 hours after trauma with rapid progression to coma without classic pulmonary symptoms.

Diagnosis

Owing to the nonspecific clinical features of FES, a variety of clinical, laboratory, and imaging criteria has been described. Of these criteria, the most frequently referenced is by Gurd in 1970,^4,5 who divided the features into major and minor, with 1 major and 4 minor features required to make the diagnosis (Table). In applying these criteria to our patient, we found that he exhibited the major criteria of cerebral involvement and minor criteria of tachycardia, fever, and thrombocytopenia. Respiratory insufficiency and petechial rash, as well as jaundice, renal changes, and anemia were negative features. Retinal changes, elevated erythrocyte sedimentation rate, and fat macroglobulinemia were not tested or examined. Although in our case the clinical and laboratory criteria for the diagnosis of FES as defined by Gurd were not met, the sensitivity of Gurd’s and other criteria is debated.¹⁰

Laboratory tests specific for the disease have not been developed. Although elevated serum levels of lipase, increased blood lipid levels, and fat globules in the urine, sputum, and blood have all been proposed, they are found in trauma patients with and without FES.^2,5,6

The nonspecific nature of the signs and symptoms of FES and the lack of reliable laboratory tests for diagnosis of the syndrome highlight the importance of radiographic evaluation in patients with neurologic symptoms. Brain CT scans are usually negative,¹⁴ although, in some cases, they may show diffuse edema with scattered low attenuating areas and hemorrhage.¹⁵ MRI is more sensitive, and T2-weighted images typically reveal multiple small, nonconfluent hyperintense lesions, usually in the periventricular, subcortical, and deep white matter, sometimes referred to as the “starfield” pattern.^14,16 The differential diagnosis for these findings is broad and, in addition to FES, includes DAI, vasogenic edema with microinfarcts, and demyelinating disease.¹⁴ Sensitivity and specificity may be increased with the addition of diffusion-weighted MRI, which shows scattered bright spots on a dark background in a similar “starfield” pattern as on T2-weighted images.¹⁵ Susceptibility-weighted MRI has recently been introduced as having utility in the diagnosis of FES, with areas of low-signal intensity indicating diffuse microhemorrhages.¹⁷ DAI can show a similar pattern; however, the autopsy-confirmed locations of the abnormalities are distinct, with those of FES being found in cerebral and cerebellar white matter and splenium of the corpus callosum and radiographic abnormalities of DAI being found in the gray-white matter junction, dorsolateral brainstem, and splenium of corpus callosum.¹⁷

 

Prevention and Treatment

Of primary importance in the prevention of FES is early stabilization of fractures. Several studies have shown a decreased incidence of FES when long-bone fractures are treated with immediate operative fixation.^18,19 However, in the setting of polytrauma, the desire for early definitive treatment must be balanced against the risks for the exaggerated immune response from prolonged surgery.²⁰ The timing of fracture fixation to prevent sequelae of the inflammatory response, such as ARDS and multiple organ dysfunction syndrome, is still debated. In a review article, Pape and colleagues²⁰ suggest classifying the multiply injured patient as stable, borderline, unstable, and in extremis based on clinical and laboratory criteria. They recommend early definitive fixation for stable patients and those patients who are borderline or unstable and responsive to resuscitation, whereas damage-control orthopedics and staged fracture fixation should be considered in the other groups.

Several pharmacologic interventions have been described, although their effects are highly variable and none have clear indications.^1-3,6 The most heavily researched is corticosteroids, with the proposed mechanisms of action including blunting of the inflammatory response, stabilizing the pulmonary capillary membrane to reduce interstitial edema, preventing activation of the complement system, and retarding platelet aggregation.²¹ A recent meta-analysis to assess this intervention examined 6 studies with a total of 386 patients with long-bone fractures who were randomized to treatment with corticosteroids or supportive care only.²² They found a reduced risk for FES in those patients who received corticosteroids, but there was no difference in mortality between groups. Given these results, the utility of corticosteroids is still debated.   

Once FES has occurred, treatment options usually focus on supportive care, with most patients having a full recovery.^1,3 No specific treatments are available, and symptomatic treatment is the suggested approach, including ensuring adequate oxygenation and ventilation and providing hemodynamic support and volume and blood-product resuscitation as needed.^1-3,6  

Conclusion

We have presented a case of FES unique in its rapid onset, an initial presentation with neurologic manifestations without typical pulmonary involvement, and the mechanism of end-organ damage without a right-to-left shunt. This case emphasizes the importance of considering FES in the patient with deteriorating mental status in the setting of multiple fractures, particularly in the absence of other characteristic clinical findings, such as pulmonary distress and the pathognomonic petechial rash. Brain MRI can play an important role in diagnosing those patients presenting with predominantly neurological symptoms. Early recognition of this condition allows for the anticipation of complications of the disease process, such as respiratory distress, and the potential need for mechanical ventilation and hemodynamic support.

Fat embolism syndrome (FES) was first described by Von Bergmann in 1873 in a patient with a fractured femur.¹ While fat within the circulation (fat embolism) is relatively common following long-bone fracture, the clinical pattern of symptoms that make up FES is less so, occurring in 1% to 3% of isolated long-bone fractures and 5% to 10% of patients with multiple skeletal trauma.¹ A variety of clinical, laboratory, and imaging criteria has been described, classically by Gurd in 1970 (Table).^1-6 Most commonly, however, it is a diagnosis of exclusion when the classic triad of respiratory difficulty, neurologic abnormalities, and a characteristic petechial rash are present in the appropriate clinical setting.⁶ 

The neurologic sequelae of this syndrome can range from headache, confusion, and agitation to stupor, focal neurologic signs, and, less commonly, coma.⁷ Onset of these symptoms usually occurs between 24 hours and 48 hours (mean, 40 hours) after trauma.¹ While these neurologic manifestations occur in up to 86% of patients with FES, it is rare for them to be present without the pulmonary symptoms of dyspnea, hypoxemia, and tachypnea, which are the most common presenting symptoms of the disease.^1-6 In this case report, we describe severe, rapid-onset neurologic manifestations, without the typical pulmonary involvement, as the primary clinical presentation of FES in a polytrauma patient. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A previously healthy 50-year-old man presented to the emergency room in transfer from an outside hospital after a rollover motor vehicle collision in which he was ejected approximately 50 feet. Injuries included a right proximal humerus fracture/dislocation (Figure 1), right ulnar styloid fracture, L1 compression fracture, and multiple rib fractures. On admission, the patient had an ethanol level of 969 mg/L (.097%) and a urine drug screen positive only for opioids, presumably because of pain medication given that day. He denied a history of alcohol abuse and reported consuming 2 to 3 beers per week. The patient was awake, alert, and oriented with a Glasgow Coma Scale (GCS) of 15. He was tachycardic (heart rate, 126), tachypneic (respiratory rate, 24), and febrile (temperature, 38.6°C [101.5°F]), and his white blood cell count was elevated at 29.5×10⁹/L. On examination, his right arm was found to be neurovascularly intact; it was placed in a sling with a forearm splint, and the patient was admitted to the intermediate special care unit on spine precautions with a plan for right shoulder hemiarthroplasty the following day.

Overnight the patient’s mental status began to deteriorate, and approximately 10 hours after initial assessment, he was not answering questions but was able to respond to some commands. On hospital day 2, approximately 20 hours after initial assessment, the patient had a GCS of 8, was not responding to commands, and moved only in response to painful stimuli. The patient had been prescribed morphine by patient-controlled analgesia and had received intravenous hydromorphone on the day of admission, although the amount of medication delivered was not thought adequate to explain this deterioration. On the morning of hospital day 2, noncontrast brain computed tomography (CT) was normal with no evidence of intracranial hemorrhage or infarct. This was followed by brain magnetic resonance imaging (MRI), with the T2-weighted images showing numerous, small hyperintense lesions in subcortical and periventricular white matter, corpus callosum, basal ganglia, brain stem, and cerebellar hemispheres (Figure 2). The lesions also showed hyperintensity on diffusion-weighted MRI and were interpreted to be consistent with multiple, tiny infarcts (Figure 3). In addition, susceptibility-weighted sequences showed low signal in the same areas, suggesting multiple microhemorrhages, a pattern consistent with FES. Oxygen saturations remained 95% to 99%, and chest radiograph revealed clear lung fields without infiltrate. On hospital day 2, the patient was transferred to the intensive care unit and intubated for airway protection owing to an inability to clear secretions, although arterial blood gas levels remained normal. An echocardiogram revealed no right-to-left shunt, such as a patent foramen ovale (PFO); an electroencephalogram showed no seizure-like activity. No petechial rash was noted on skin examination. The patient was treated with supportive care. Right shoulder hemiarthroplasty was performed on hospital day 7 without complications (Figure 1). On hospital day 13, the patient was following commands and on day 14 he was extubated. His mental status continued to improve, and he was discharged to a rehabilitation facility after 36 days. On last follow-up, 6 months after initial injury, the patient was recovering well with no residual neurologic deficits and only minor limitation in range of motion of the right shoulder.

 

Discussion

This case presented an interesting diagnostic challenge regarding the patient’s rapid decline in mental status, with a differential diagnosis including diffuse axonal injury (DAI), anoxic brain injury, posttraumatic seizure, other intracranial pathology, such as stroke or hemorrhage, and FES. FES was diagnosed, when other possibilities were ruled out, given the characteristic findings on brain MRI described above in the context of multiple fractures.

Pathophysiology

Despite its recognition in 1873, there is no consensus on the pathophysiological mechanism that causes the clinical symptoms of FES. In the setting of trauma, there are 2 predominant theories. The mechanical theory postulates that fat globules enter the circulation through disrupted venules after the fracture of marrow-containing bones, passing to the arterial circulation through pulmonary vasculature, or paradoxically, by way of a right-to-left shunt, such as a PFO.^1,3 The presence of fat in the heart, visualized as echogenic material in the right and left atria on transesophageal echocardiography, has been confirmed in multiple studies during orthopedic procedures, including total knee arthroplasty and femoral reaming.^8,9 These fat particles can lodge as microembolisms in target organs such as the skin and brain. However, autopsy studies have shown a lack of correlation of the severity of symptoms and the quantity of intravascular fat.¹ In addition, the typical 24- to 72-hour delay in the onset of symptoms after initial trauma would argue against a solely mechanical explanation.¹⁰

Alternatively or concomitantly, the biochemical theory proposes that embolized fat may be degraded to toxic intermediaries, such as free fatty acids and C-reactive protein, which cause end-organ damage.³ This has been shown in an animal model, in which intravascular injection of free fatty acids was associated with endothelial damage and increased capillary permeability in the lung, leading to acute respiratory distress syndrome (ARDS).¹¹ The same mechanism could explain injury to other end organs and is consistent with the delay in onset of symptoms after acute injury. In our patient’s case, the absence of pulmonary involvement, lack of a right-to-left vascular shunt such as a PFO, and presence of a systemic inflammatory response on admission may implicate the production of toxic intermediaries from the metabolism of embolized fat as the source of this patient’s FES.

Clinical Presentation

The initial presentation of FES usually manifests as respiratory distress and hypoxia.¹⁰ Chest radiographs are often normal, as in our patient, but can show bilateral diffuse interstitial or alveolar infiltrates.^2,6 CT more often has findings, including bilateral ground-glass opacities with interlobar septal thickening.¹² A petechial rash can be found on the head, neck, anterior thorax, axillae, subconjunctiva, and oral mucous membranes, although it occurs in only 20% to 50% of cases.^1,2,13 Neurologic sequelae are present in up to 80% of patients,⁷ with onset typically following pulmonary symptoms.^1,10 These sequelae can range from headache, confusion, and agitation to stupor, focal neurologic signs, and, less commonly, coma.⁷ Onset of symptoms generally occurs between 24 and 48 hours after trauma,¹ although they have been reported as early as 12 hours.¹⁰ This case is an example of an atypical course, with the initial presentation of neurologic symptoms at approximately 14 hours after trauma with rapid progression to coma without classic pulmonary symptoms.

Diagnosis

Owing to the nonspecific clinical features of FES, a variety of clinical, laboratory, and imaging criteria has been described. Of these criteria, the most frequently referenced is by Gurd in 1970,^4,5 who divided the features into major and minor, with 1 major and 4 minor features required to make the diagnosis (Table). In applying these criteria to our patient, we found that he exhibited the major criteria of cerebral involvement and minor criteria of tachycardia, fever, and thrombocytopenia. Respiratory insufficiency and petechial rash, as well as jaundice, renal changes, and anemia were negative features. Retinal changes, elevated erythrocyte sedimentation rate, and fat macroglobulinemia were not tested or examined. Although in our case the clinical and laboratory criteria for the diagnosis of FES as defined by Gurd were not met, the sensitivity of Gurd’s and other criteria is debated.¹⁰

Laboratory tests specific for the disease have not been developed. Although elevated serum levels of lipase, increased blood lipid levels, and fat globules in the urine, sputum, and blood have all been proposed, they are found in trauma patients with and without FES.^2,5,6

The nonspecific nature of the signs and symptoms of FES and the lack of reliable laboratory tests for diagnosis of the syndrome highlight the importance of radiographic evaluation in patients with neurologic symptoms. Brain CT scans are usually negative,¹⁴ although, in some cases, they may show diffuse edema with scattered low attenuating areas and hemorrhage.¹⁵ MRI is more sensitive, and T2-weighted images typically reveal multiple small, nonconfluent hyperintense lesions, usually in the periventricular, subcortical, and deep white matter, sometimes referred to as the “starfield” pattern.^14,16 The differential diagnosis for these findings is broad and, in addition to FES, includes DAI, vasogenic edema with microinfarcts, and demyelinating disease.¹⁴ Sensitivity and specificity may be increased with the addition of diffusion-weighted MRI, which shows scattered bright spots on a dark background in a similar “starfield” pattern as on T2-weighted images.¹⁵ Susceptibility-weighted MRI has recently been introduced as having utility in the diagnosis of FES, with areas of low-signal intensity indicating diffuse microhemorrhages.¹⁷ DAI can show a similar pattern; however, the autopsy-confirmed locations of the abnormalities are distinct, with those of FES being found in cerebral and cerebellar white matter and splenium of the corpus callosum and radiographic abnormalities of DAI being found in the gray-white matter junction, dorsolateral brainstem, and splenium of corpus callosum.¹⁷

 

Prevention and Treatment

Of primary importance in the prevention of FES is early stabilization of fractures. Several studies have shown a decreased incidence of FES when long-bone fractures are treated with immediate operative fixation.^18,19 However, in the setting of polytrauma, the desire for early definitive treatment must be balanced against the risks for the exaggerated immune response from prolonged surgery.²⁰ The timing of fracture fixation to prevent sequelae of the inflammatory response, such as ARDS and multiple organ dysfunction syndrome, is still debated. In a review article, Pape and colleagues²⁰ suggest classifying the multiply injured patient as stable, borderline, unstable, and in extremis based on clinical and laboratory criteria. They recommend early definitive fixation for stable patients and those patients who are borderline or unstable and responsive to resuscitation, whereas damage-control orthopedics and staged fracture fixation should be considered in the other groups.

Several pharmacologic interventions have been described, although their effects are highly variable and none have clear indications.^1-3,6 The most heavily researched is corticosteroids, with the proposed mechanisms of action including blunting of the inflammatory response, stabilizing the pulmonary capillary membrane to reduce interstitial edema, preventing activation of the complement system, and retarding platelet aggregation.²¹ A recent meta-analysis to assess this intervention examined 6 studies with a total of 386 patients with long-bone fractures who were randomized to treatment with corticosteroids or supportive care only.²² They found a reduced risk for FES in those patients who received corticosteroids, but there was no difference in mortality between groups. Given these results, the utility of corticosteroids is still debated.   

Once FES has occurred, treatment options usually focus on supportive care, with most patients having a full recovery.^1,3 No specific treatments are available, and symptomatic treatment is the suggested approach, including ensuring adequate oxygenation and ventilation and providing hemodynamic support and volume and blood-product resuscitation as needed.^1-3,6  

Conclusion

We have presented a case of FES unique in its rapid onset, an initial presentation with neurologic manifestations without typical pulmonary involvement, and the mechanism of end-organ damage without a right-to-left shunt. This case emphasizes the importance of considering FES in the patient with deteriorating mental status in the setting of multiple fractures, particularly in the absence of other characteristic clinical findings, such as pulmonary distress and the pathognomonic petechial rash. Brain MRI can play an important role in diagnosing those patients presenting with predominantly neurological symptoms. Early recognition of this condition allows for the anticipation of complications of the disease process, such as respiratory distress, and the potential need for mechanical ventilation and hemodynamic support.

Subtrochanteric fractures and other complications related to hardware removal in children with slipped capital femoral epiphysis (SCFE) have been well documented.^1-3 Subtrochanteric fractures after cannulated screw fixation of femoral neck fractures in adults have also been well recognized,⁴ and there are several reports on the topic.^4,5 However, there are no reports on subtrochanteric fractures after removal of the screws for femoral neck fractures in children.

In this article, we report the case of a child who sustained a subtrochanteric fracture after the screw removal and healing that followed a femoral neck fracture. The patient’s parent provided written informed consent for print and electronic publication of this case report. In addition, our institutional review board approved this case report.

Case Report

A 10-year-old boy was brought to our emergency department with the chief complaint of left hip pain after a car accident. Anteroposterior and axial lateral radiographs showed a displaced cervicotrochanteric femoral neck fracture (Figures 1A, 1B). The patient was admitted to the hospital and underwent closed reduction and internal fixation with two 3.5-mm cannulated titanium screws within 12 hours of arrival. The screws did not cross the physis to avoid iatrogenic injury of the capital femoral epiphysis (Figures 2A, 2B). The entry point was located at the lower level of the lesser trochanter. The lateral cortex was penetrated only once by the guide wire for the placement of each screw.

The patient was discharged to home care with a crutch and an ischial weight-bearing long leg brace for protection from unexpected external force. Two months after surgery, we allowed the patient to walk with the brace and without the crutch. Full-weight-bearing ambulation was allowed 3 months after surgery.

About 9 months after initial surgery, we removed 2 titanium screws, which were completely covered with growing new bone. The lateral cortex surrounding the screw heads was chiseled from the lower level of the lesser trochanter to remove the completely immersed screw heads (Figures 3A, 3B).

After screw removal, we recommended non-weight-bearing crutch-walking for 2 weeks followed by partial weight-bearing with crutch for another month. However, the patient started full weight-bearing 2 weeks after screw removal. One month after screw removal, he was brought to the emergency department with severe left hip pain after missing a step on a path. Anteroposterior and lateral radiographs showed an oblique subtrochanteric fracture at the empty screw holes (Figures 4A, 4B). A plate and 4 screws were placed to stabilize the subtrochanteric fracture, and a hip spica cast was applied and was to be worn for 3 weeks (Figures 5A, 5B).

At final follow-up, 6 months after the second surgery, the fracture was healed, and there had been no complications, such as avascular necrosis of the femoral head and leg-length discrepancy (Figures 6A, 6B).

Discussion

Although in situ pinning of SCFE is a common procedure with good results, the rate of complications of hardware removal can be as high as 34%; these complications are well documented.⁵ Subtrochanteric fracture as a complication of proximal femoral neck pinning in adults is also well documented.^4,5 However, there are no reports on subtrochanteric fractures after screw removal in the treatment of femoral neck fractures in children.

Brooks and colleagues⁶ emphasized the point that multiple passes weakened the lateral cortex, decreased the energy-absorbing capacity by 55.2%, and increased local stress. Even if a screw is placed in a relatively safe zone above the lesser trochanter, pie-crusting of the cortex can weaken it enough to predispose it to failure under a relatively normal load.⁷ We inserted 2 cannulated titanium screws without repositioning or multiple drilling, and the femoral neck fracture was united.

The common denominator for subtrochanteric fractures after screw or pin fixation of femoral neck fractures in adults seemed to be the entry point of the lateral cortex below the level of the most inferior edge of the lesser trochanter.⁴ The pin should have its entry site proximal to the level of the lesser trochnater. Paloski and colleagues⁷ and Canale and colleagues⁸ hypothesized that this screw acted as a stress riser to the normal bone, which underwent abnormal loads caused by the patient’s habitus and later mechanism of injury. In our patient’s case, the appropriate starting point for perpendicular penetration of the femoral neck fracture line was on the lateral femoral cortex at the level of the lesser trochanter. We thought this entry on the lateral cortex might predispose the patient to a subtrochanteric fracture. The starting point of the screw is considered the most important factor in preventing fracture after screw removal.

 

As titanium pins cause very tight bone ingrowth,^9,10 the surface of titanium screws used for femoral neck fractures in children are smoothed to reduce turning force.¹ The hexagonal sockets wore off rapidly and proved to be too weak to overcome the necessary torque for loosening the pin from the bone.

Lee and colleagues¹⁰ found that significantly more operative time was needed to remove titanium pins (vs steel pins) after 12 months or longer. When Asnis III pins (Howmedica, Rutherford, New Jersey) were used in the treatment of femoral neck fractures in aged patients, similar problems did not occur. One possible explanation is that bone density is higher in adolescents than in adults. In addition, more bone ingrowth and higher bone compression might occur in adolescent bones.¹ Given the considerable disadvantages noted in their series, Ilchmann and Parsch¹ concluded that use of cannulated titanium screws should be suspended and that stainless steel pins are safe to use in SCFE.

In our patient’s case, we also struggled to remove titanium screws. Subtrochanteric fractures can be complications after removal of screws for femoral neck fractures in children. If there are no specific screw-related symptoms, one should consider leaving the screw in place and avoiding screw removal.

Subtrochanteric fractures and other complications related to hardware removal in children with slipped capital femoral epiphysis (SCFE) have been well documented.^1-3 Subtrochanteric fractures after cannulated screw fixation of femoral neck fractures in adults have also been well recognized,⁴ and there are several reports on the topic.^4,5 However, there are no reports on subtrochanteric fractures after removal of the screws for femoral neck fractures in children.

In this article, we report the case of a child who sustained a subtrochanteric fracture after the screw removal and healing that followed a femoral neck fracture. The patient’s parent provided written informed consent for print and electronic publication of this case report. In addition, our institutional review board approved this case report.

Case Report

A 10-year-old boy was brought to our emergency department with the chief complaint of left hip pain after a car accident. Anteroposterior and axial lateral radiographs showed a displaced cervicotrochanteric femoral neck fracture (Figures 1A, 1B). The patient was admitted to the hospital and underwent closed reduction and internal fixation with two 3.5-mm cannulated titanium screws within 12 hours of arrival. The screws did not cross the physis to avoid iatrogenic injury of the capital femoral epiphysis (Figures 2A, 2B). The entry point was located at the lower level of the lesser trochanter. The lateral cortex was penetrated only once by the guide wire for the placement of each screw.

The patient was discharged to home care with a crutch and an ischial weight-bearing long leg brace for protection from unexpected external force. Two months after surgery, we allowed the patient to walk with the brace and without the crutch. Full-weight-bearing ambulation was allowed 3 months after surgery.

About 9 months after initial surgery, we removed 2 titanium screws, which were completely covered with growing new bone. The lateral cortex surrounding the screw heads was chiseled from the lower level of the lesser trochanter to remove the completely immersed screw heads (Figures 3A, 3B).

After screw removal, we recommended non-weight-bearing crutch-walking for 2 weeks followed by partial weight-bearing with crutch for another month. However, the patient started full weight-bearing 2 weeks after screw removal. One month after screw removal, he was brought to the emergency department with severe left hip pain after missing a step on a path. Anteroposterior and lateral radiographs showed an oblique subtrochanteric fracture at the empty screw holes (Figures 4A, 4B). A plate and 4 screws were placed to stabilize the subtrochanteric fracture, and a hip spica cast was applied and was to be worn for 3 weeks (Figures 5A, 5B).

At final follow-up, 6 months after the second surgery, the fracture was healed, and there had been no complications, such as avascular necrosis of the femoral head and leg-length discrepancy (Figures 6A, 6B).

Discussion

Although in situ pinning of SCFE is a common procedure with good results, the rate of complications of hardware removal can be as high as 34%; these complications are well documented.⁵ Subtrochanteric fracture as a complication of proximal femoral neck pinning in adults is also well documented.^4,5 However, there are no reports on subtrochanteric fractures after screw removal in the treatment of femoral neck fractures in children.

Brooks and colleagues⁶ emphasized the point that multiple passes weakened the lateral cortex, decreased the energy-absorbing capacity by 55.2%, and increased local stress. Even if a screw is placed in a relatively safe zone above the lesser trochanter, pie-crusting of the cortex can weaken it enough to predispose it to failure under a relatively normal load.⁷ We inserted 2 cannulated titanium screws without repositioning or multiple drilling, and the femoral neck fracture was united.

The common denominator for subtrochanteric fractures after screw or pin fixation of femoral neck fractures in adults seemed to be the entry point of the lateral cortex below the level of the most inferior edge of the lesser trochanter.⁴ The pin should have its entry site proximal to the level of the lesser trochnater. Paloski and colleagues⁷ and Canale and colleagues⁸ hypothesized that this screw acted as a stress riser to the normal bone, which underwent abnormal loads caused by the patient’s habitus and later mechanism of injury. In our patient’s case, the appropriate starting point for perpendicular penetration of the femoral neck fracture line was on the lateral femoral cortex at the level of the lesser trochanter. We thought this entry on the lateral cortex might predispose the patient to a subtrochanteric fracture. The starting point of the screw is considered the most important factor in preventing fracture after screw removal.

 

As titanium pins cause very tight bone ingrowth,^9,10 the surface of titanium screws used for femoral neck fractures in children are smoothed to reduce turning force.¹ The hexagonal sockets wore off rapidly and proved to be too weak to overcome the necessary torque for loosening the pin from the bone.

Lee and colleagues¹⁰ found that significantly more operative time was needed to remove titanium pins (vs steel pins) after 12 months or longer. When Asnis III pins (Howmedica, Rutherford, New Jersey) were used in the treatment of femoral neck fractures in aged patients, similar problems did not occur. One possible explanation is that bone density is higher in adolescents than in adults. In addition, more bone ingrowth and higher bone compression might occur in adolescent bones.¹ Given the considerable disadvantages noted in their series, Ilchmann and Parsch¹ concluded that use of cannulated titanium screws should be suspended and that stainless steel pins are safe to use in SCFE.

In our patient’s case, we also struggled to remove titanium screws. Subtrochanteric fractures can be complications after removal of screws for femoral neck fractures in children. If there are no specific screw-related symptoms, one should consider leaving the screw in place and avoiding screw removal.

Subtrochanteric fractures and other complications related to hardware removal in children with slipped capital femoral epiphysis (SCFE) have been well documented.^1-3 Subtrochanteric fractures after cannulated screw fixation of femoral neck fractures in adults have also been well recognized,⁴ and there are several reports on the topic.^4,5 However, there are no reports on subtrochanteric fractures after removal of the screws for femoral neck fractures in children.

In this article, we report the case of a child who sustained a subtrochanteric fracture after the screw removal and healing that followed a femoral neck fracture. The patient’s parent provided written informed consent for print and electronic publication of this case report. In addition, our institutional review board approved this case report.

Case Report

A 10-year-old boy was brought to our emergency department with the chief complaint of left hip pain after a car accident. Anteroposterior and axial lateral radiographs showed a displaced cervicotrochanteric femoral neck fracture (Figures 1A, 1B). The patient was admitted to the hospital and underwent closed reduction and internal fixation with two 3.5-mm cannulated titanium screws within 12 hours of arrival. The screws did not cross the physis to avoid iatrogenic injury of the capital femoral epiphysis (Figures 2A, 2B). The entry point was located at the lower level of the lesser trochanter. The lateral cortex was penetrated only once by the guide wire for the placement of each screw.

The patient was discharged to home care with a crutch and an ischial weight-bearing long leg brace for protection from unexpected external force. Two months after surgery, we allowed the patient to walk with the brace and without the crutch. Full-weight-bearing ambulation was allowed 3 months after surgery.

About 9 months after initial surgery, we removed 2 titanium screws, which were completely covered with growing new bone. The lateral cortex surrounding the screw heads was chiseled from the lower level of the lesser trochanter to remove the completely immersed screw heads (Figures 3A, 3B).

After screw removal, we recommended non-weight-bearing crutch-walking for 2 weeks followed by partial weight-bearing with crutch for another month. However, the patient started full weight-bearing 2 weeks after screw removal. One month after screw removal, he was brought to the emergency department with severe left hip pain after missing a step on a path. Anteroposterior and lateral radiographs showed an oblique subtrochanteric fracture at the empty screw holes (Figures 4A, 4B). A plate and 4 screws were placed to stabilize the subtrochanteric fracture, and a hip spica cast was applied and was to be worn for 3 weeks (Figures 5A, 5B).

At final follow-up, 6 months after the second surgery, the fracture was healed, and there had been no complications, such as avascular necrosis of the femoral head and leg-length discrepancy (Figures 6A, 6B).

Discussion

Although in situ pinning of SCFE is a common procedure with good results, the rate of complications of hardware removal can be as high as 34%; these complications are well documented.⁵ Subtrochanteric fracture as a complication of proximal femoral neck pinning in adults is also well documented.^4,5 However, there are no reports on subtrochanteric fractures after screw removal in the treatment of femoral neck fractures in children.

Brooks and colleagues⁶ emphasized the point that multiple passes weakened the lateral cortex, decreased the energy-absorbing capacity by 55.2%, and increased local stress. Even if a screw is placed in a relatively safe zone above the lesser trochanter, pie-crusting of the cortex can weaken it enough to predispose it to failure under a relatively normal load.⁷ We inserted 2 cannulated titanium screws without repositioning or multiple drilling, and the femoral neck fracture was united.

The common denominator for subtrochanteric fractures after screw or pin fixation of femoral neck fractures in adults seemed to be the entry point of the lateral cortex below the level of the most inferior edge of the lesser trochanter.⁴ The pin should have its entry site proximal to the level of the lesser trochnater. Paloski and colleagues⁷ and Canale and colleagues⁸ hypothesized that this screw acted as a stress riser to the normal bone, which underwent abnormal loads caused by the patient’s habitus and later mechanism of injury. In our patient’s case, the appropriate starting point for perpendicular penetration of the femoral neck fracture line was on the lateral femoral cortex at the level of the lesser trochanter. We thought this entry on the lateral cortex might predispose the patient to a subtrochanteric fracture. The starting point of the screw is considered the most important factor in preventing fracture after screw removal.

 

As titanium pins cause very tight bone ingrowth,^9,10 the surface of titanium screws used for femoral neck fractures in children are smoothed to reduce turning force.¹ The hexagonal sockets wore off rapidly and proved to be too weak to overcome the necessary torque for loosening the pin from the bone.

Lee and colleagues¹⁰ found that significantly more operative time was needed to remove titanium pins (vs steel pins) after 12 months or longer. When Asnis III pins (Howmedica, Rutherford, New Jersey) were used in the treatment of femoral neck fractures in aged patients, similar problems did not occur. One possible explanation is that bone density is higher in adolescents than in adults. In addition, more bone ingrowth and higher bone compression might occur in adolescent bones.¹ Given the considerable disadvantages noted in their series, Ilchmann and Parsch¹ concluded that use of cannulated titanium screws should be suspended and that stainless steel pins are safe to use in SCFE.

In our patient’s case, we also struggled to remove titanium screws. Subtrochanteric fractures can be complications after removal of screws for femoral neck fractures in children. If there are no specific screw-related symptoms, one should consider leaving the screw in place and avoiding screw removal.