Case Reports

Background

Oropharyngeal squamous cell carcinoma (OPSCC) arises in the middle pharynx, including the tonsils, base of the tongue, and surrounding tissues. While OPSCC commonly metastasizes to regional lymph nodes, distant metastases to sites like the liver are rare, occurring in about 1-4% of cases with advanced disease.

Case Presentation

A 66-year-old male presented to the emergency department with recurrent right-sided facial swelling and a two-week history of sore throat. CT imaging revealed a large right tonsillar mass extending to the base of the tongue. Further evaluation with PET scan showed hypermetabolic activity in the right tonsil, multiple hypermetabolic lymph nodes in the right neck (stations 1B, 2, 3, 4, 5), right supraclavicular fossa, and small retropharyngeal nodes. Additionally, PET scan detected a hypermetabolic lesion in the liver and focal activity at T10 suggestive of bone metastasis. Fine needle aspiration (FNA) confirmed squamous cell carcinoma. Biopsy of the liver lesion revealed metastatic squamous cell carcinoma with basaloid differentiation, positive for p40 and p63 stains. Clinical staging was T2b cN2 cM1. The patient’s case was discussed in tumor boards, leading to a treatment plan of palliative radiotherapy with radiosensitizer (weekly carboplatin/paclitaxel) due to recent myocardial infarction, precluding cisplatin or 5FU use. Post-radiotherapy, Pembrolizumab was planned based on 60% PD-L1 expression. The patient opted to forego additional systemic chemotherapy and currently receives Keytruda every three weeks.

Discussion

Liver metastases from head and neck SCC are rare, highlighting the complexity of treatment decisions in such cases. Effective management requires a multidisciplinary approach to optimize therapeutic outcomes while considering patient-specific factors and comorbidities.

Conclusions

This case underscores the challenges and poor prognosis associated with tonsillar SCC with liver metastases. It underscores the need for personalized treatment strategies tailored to the unique characteristics of each patient’s disease.

Background

Oropharyngeal squamous cell carcinoma (OPSCC) arises in the middle pharynx, including the tonsils, base of the tongue, and surrounding tissues. While OPSCC commonly metastasizes to regional lymph nodes, distant metastases to sites like the liver are rare, occurring in about 1-4% of cases with advanced disease.

Case Presentation

A 66-year-old male presented to the emergency department with recurrent right-sided facial swelling and a two-week history of sore throat. CT imaging revealed a large right tonsillar mass extending to the base of the tongue. Further evaluation with PET scan showed hypermetabolic activity in the right tonsil, multiple hypermetabolic lymph nodes in the right neck (stations 1B, 2, 3, 4, 5), right supraclavicular fossa, and small retropharyngeal nodes. Additionally, PET scan detected a hypermetabolic lesion in the liver and focal activity at T10 suggestive of bone metastasis. Fine needle aspiration (FNA) confirmed squamous cell carcinoma. Biopsy of the liver lesion revealed metastatic squamous cell carcinoma with basaloid differentiation, positive for p40 and p63 stains. Clinical staging was T2b cN2 cM1. The patient’s case was discussed in tumor boards, leading to a treatment plan of palliative radiotherapy with radiosensitizer (weekly carboplatin/paclitaxel) due to recent myocardial infarction, precluding cisplatin or 5FU use. Post-radiotherapy, Pembrolizumab was planned based on 60% PD-L1 expression. The patient opted to forego additional systemic chemotherapy and currently receives Keytruda every three weeks.

Discussion

Liver metastases from head and neck SCC are rare, highlighting the complexity of treatment decisions in such cases. Effective management requires a multidisciplinary approach to optimize therapeutic outcomes while considering patient-specific factors and comorbidities.

Conclusions

This case underscores the challenges and poor prognosis associated with tonsillar SCC with liver metastases. It underscores the need for personalized treatment strategies tailored to the unique characteristics of each patient’s disease.

Background

Oropharyngeal squamous cell carcinoma (OPSCC) arises in the middle pharynx, including the tonsils, base of the tongue, and surrounding tissues. While OPSCC commonly metastasizes to regional lymph nodes, distant metastases to sites like the liver are rare, occurring in about 1-4% of cases with advanced disease.

Case Presentation

A 66-year-old male presented to the emergency department with recurrent right-sided facial swelling and a two-week history of sore throat. CT imaging revealed a large right tonsillar mass extending to the base of the tongue. Further evaluation with PET scan showed hypermetabolic activity in the right tonsil, multiple hypermetabolic lymph nodes in the right neck (stations 1B, 2, 3, 4, 5), right supraclavicular fossa, and small retropharyngeal nodes. Additionally, PET scan detected a hypermetabolic lesion in the liver and focal activity at T10 suggestive of bone metastasis. Fine needle aspiration (FNA) confirmed squamous cell carcinoma. Biopsy of the liver lesion revealed metastatic squamous cell carcinoma with basaloid differentiation, positive for p40 and p63 stains. Clinical staging was T2b cN2 cM1. The patient’s case was discussed in tumor boards, leading to a treatment plan of palliative radiotherapy with radiosensitizer (weekly carboplatin/paclitaxel) due to recent myocardial infarction, precluding cisplatin or 5FU use. Post-radiotherapy, Pembrolizumab was planned based on 60% PD-L1 expression. The patient opted to forego additional systemic chemotherapy and currently receives Keytruda every three weeks.

Discussion

Liver metastases from head and neck SCC are rare, highlighting the complexity of treatment decisions in such cases. Effective management requires a multidisciplinary approach to optimize therapeutic outcomes while considering patient-specific factors and comorbidities.

Conclusions

This case underscores the challenges and poor prognosis associated with tonsillar SCC with liver metastases. It underscores the need for personalized treatment strategies tailored to the unique characteristics of each patient’s disease.

Background

The Jesse Brown Veterans Affairs Medical Center (JBVAMC) serves predominantly Black American veterans, many with significant psychosocial needs, who live in Chicago’s South and West sides and Northwest Indiana. The JBVAMC hematology/oncology clinic is adopting the 4R Oncology Model (Right Info/ Care/Patient/Time) for patient-facing care planning and self-management, to enhance supportive and health maintenance care delivery. In order to guide the integration of the 4R model, baseline data were collected regarding patients’ understanding of their disease, social determinants of health, and use of services offered by JBVAMC.

Methods

Patients at JBVAMC were surveyed from February 2023 to September 2023. As a small incentive, these veterans received a $25 gift card for their participation. Analysis was conducted using descriptive statistics.

Results

Survey response rate was 67% (30/45). Median age was 66 (range 38-80). The population was 93% male, 83% black, 57% with highest level of education being high school or less, 59% with annual income less than $30k, and 47% living alone. Less than half (43%) of respondents knew their stage of cancer at diagnosis, and only 63% were aware of their treatment goals. Furthermore, only 17% remember receiving recommendations for support services that may be available through JBVAMC such as transportation assistance and home care. Information regarding “emotional distress or worry support recommendations” was acquired by 24% of veteran respondents. More than half, 57%, of veterans were encouraged to talk to their primary care provider about routine health maintenance during cancer treatment. Just over a quarter, 27%, were referred to a dietician.

Conclusions

This survey uncovered gaps in care planning, supportive services, and health maintenance care. These data will serve as a baseline to assess the effectiveness of the 4R care plan model. The implementation of the 4R Oncology Model is designed to address these gaps by providing a personalized care sequence that establishes a clear roadmap through the patient’s care trajectory, ultimately enhancing patient-centered care. Post-intervention survey results will be shared when available.

Background

The Jesse Brown Veterans Affairs Medical Center (JBVAMC) serves predominantly Black American veterans, many with significant psychosocial needs, who live in Chicago’s South and West sides and Northwest Indiana. The JBVAMC hematology/oncology clinic is adopting the 4R Oncology Model (Right Info/ Care/Patient/Time) for patient-facing care planning and self-management, to enhance supportive and health maintenance care delivery. In order to guide the integration of the 4R model, baseline data were collected regarding patients’ understanding of their disease, social determinants of health, and use of services offered by JBVAMC.

Methods

Patients at JBVAMC were surveyed from February 2023 to September 2023. As a small incentive, these veterans received a $25 gift card for their participation. Analysis was conducted using descriptive statistics.

Results

Survey response rate was 67% (30/45). Median age was 66 (range 38-80). The population was 93% male, 83% black, 57% with highest level of education being high school or less, 59% with annual income less than $30k, and 47% living alone. Less than half (43%) of respondents knew their stage of cancer at diagnosis, and only 63% were aware of their treatment goals. Furthermore, only 17% remember receiving recommendations for support services that may be available through JBVAMC such as transportation assistance and home care. Information regarding “emotional distress or worry support recommendations” was acquired by 24% of veteran respondents. More than half, 57%, of veterans were encouraged to talk to their primary care provider about routine health maintenance during cancer treatment. Just over a quarter, 27%, were referred to a dietician.

Conclusions

This survey uncovered gaps in care planning, supportive services, and health maintenance care. These data will serve as a baseline to assess the effectiveness of the 4R care plan model. The implementation of the 4R Oncology Model is designed to address these gaps by providing a personalized care sequence that establishes a clear roadmap through the patient’s care trajectory, ultimately enhancing patient-centered care. Post-intervention survey results will be shared when available.

Background

The Jesse Brown Veterans Affairs Medical Center (JBVAMC) serves predominantly Black American veterans, many with significant psychosocial needs, who live in Chicago’s South and West sides and Northwest Indiana. The JBVAMC hematology/oncology clinic is adopting the 4R Oncology Model (Right Info/ Care/Patient/Time) for patient-facing care planning and self-management, to enhance supportive and health maintenance care delivery. In order to guide the integration of the 4R model, baseline data were collected regarding patients’ understanding of their disease, social determinants of health, and use of services offered by JBVAMC.

Methods

Patients at JBVAMC were surveyed from February 2023 to September 2023. As a small incentive, these veterans received a $25 gift card for their participation. Analysis was conducted using descriptive statistics.

Results

Survey response rate was 67% (30/45). Median age was 66 (range 38-80). The population was 93% male, 83% black, 57% with highest level of education being high school or less, 59% with annual income less than $30k, and 47% living alone. Less than half (43%) of respondents knew their stage of cancer at diagnosis, and only 63% were aware of their treatment goals. Furthermore, only 17% remember receiving recommendations for support services that may be available through JBVAMC such as transportation assistance and home care. Information regarding “emotional distress or worry support recommendations” was acquired by 24% of veteran respondents. More than half, 57%, of veterans were encouraged to talk to their primary care provider about routine health maintenance during cancer treatment. Just over a quarter, 27%, were referred to a dietician.

Conclusions

This survey uncovered gaps in care planning, supportive services, and health maintenance care. These data will serve as a baseline to assess the effectiveness of the 4R care plan model. The implementation of the 4R Oncology Model is designed to address these gaps by providing a personalized care sequence that establishes a clear roadmap through the patient’s care trajectory, ultimately enhancing patient-centered care. Post-intervention survey results will be shared when available.

Introduction

Signet ring cell carcinoma (SRCC) of the small intestine is very rare. It is characterized by the presence of malignant cells that contain mucin that push nuclei to the periphery. It is more aggressive compared to other adenocarcinomas due to early metastasis and poorer prognosis.

Case Presentation

A 59-year-old male with a history of HIV/AIDS, presented with complaints of anorexia, vomiting and weight loss. Initial abdominal CT showed a retroperitoneal mass causing gastric outlet obstruction. The patient elected to go home after supportive treatment and follow up as an outpatient, however, he presented 10 days later with worsening symptoms. Evaluation with CT abdomen and pelvis showed enlarging soft tissue density in the retrocrural space extending into the retroperitoneum around the aorta, as well as a 1.5 cm intraluminal cystic lesion in the duodenum. Endoscopic ultrasound revealed lymphadenopathy of celiac and porta hepatis regions, along with duodenal stenosis, stent placement for decompression was not feasible and biopsies were inconclusive. The decision was made to proceed with laparotomy for decompression and additional biopsies from the retroperitoneal mass and omental lymph nodes, which confirmed poorly differentiated adenocarcinoma with signet ring cells. The presence of a mass in the duodenum strongly suggested adenocarcinoma of small intestine origin. As the patient’s symptoms worsened, imaging revealed progression with lung metastases. The patient continued to deteriorate rapidly requiring dialysis and gangrenous cholecystitis. Given his complex medical history, patient decided to transition to comfort care.

Discussion

SRCC can present with any GI symptoms. Most important step in diagnosing SRCC is biopsy. Current treatment options for small intestinal malignancies include wide resection that includes the mesentery and corresponding lymph nodes. The use of adjuvant chemotherapy has been described only in small retrospective studies. Due to its scarcity, there isn’t sufficient data for optimal treatment strategies compared to gastric SRCC.

Conclusions

This case report highlights the importance of how rare and aggressive signet ring cell adenocarcinoma of the small intestine. There are only a few cases documented in the literature, which is why we lack data on how to manage the disease. 

Introduction

Signet ring cell carcinoma (SRCC) of the small intestine is very rare. It is characterized by the presence of malignant cells that contain mucin that push nuclei to the periphery. It is more aggressive compared to other adenocarcinomas due to early metastasis and poorer prognosis.

Case Presentation

A 59-year-old male with a history of HIV/AIDS, presented with complaints of anorexia, vomiting and weight loss. Initial abdominal CT showed a retroperitoneal mass causing gastric outlet obstruction. The patient elected to go home after supportive treatment and follow up as an outpatient, however, he presented 10 days later with worsening symptoms. Evaluation with CT abdomen and pelvis showed enlarging soft tissue density in the retrocrural space extending into the retroperitoneum around the aorta, as well as a 1.5 cm intraluminal cystic lesion in the duodenum. Endoscopic ultrasound revealed lymphadenopathy of celiac and porta hepatis regions, along with duodenal stenosis, stent placement for decompression was not feasible and biopsies were inconclusive. The decision was made to proceed with laparotomy for decompression and additional biopsies from the retroperitoneal mass and omental lymph nodes, which confirmed poorly differentiated adenocarcinoma with signet ring cells. The presence of a mass in the duodenum strongly suggested adenocarcinoma of small intestine origin. As the patient’s symptoms worsened, imaging revealed progression with lung metastases. The patient continued to deteriorate rapidly requiring dialysis and gangrenous cholecystitis. Given his complex medical history, patient decided to transition to comfort care.

Discussion

SRCC can present with any GI symptoms. Most important step in diagnosing SRCC is biopsy. Current treatment options for small intestinal malignancies include wide resection that includes the mesentery and corresponding lymph nodes. The use of adjuvant chemotherapy has been described only in small retrospective studies. Due to its scarcity, there isn’t sufficient data for optimal treatment strategies compared to gastric SRCC.

Conclusions

This case report highlights the importance of how rare and aggressive signet ring cell adenocarcinoma of the small intestine. There are only a few cases documented in the literature, which is why we lack data on how to manage the disease. 

Introduction

Signet ring cell carcinoma (SRCC) of the small intestine is very rare. It is characterized by the presence of malignant cells that contain mucin that push nuclei to the periphery. It is more aggressive compared to other adenocarcinomas due to early metastasis and poorer prognosis.

Case Presentation

A 59-year-old male with a history of HIV/AIDS, presented with complaints of anorexia, vomiting and weight loss. Initial abdominal CT showed a retroperitoneal mass causing gastric outlet obstruction. The patient elected to go home after supportive treatment and follow up as an outpatient, however, he presented 10 days later with worsening symptoms. Evaluation with CT abdomen and pelvis showed enlarging soft tissue density in the retrocrural space extending into the retroperitoneum around the aorta, as well as a 1.5 cm intraluminal cystic lesion in the duodenum. Endoscopic ultrasound revealed lymphadenopathy of celiac and porta hepatis regions, along with duodenal stenosis, stent placement for decompression was not feasible and biopsies were inconclusive. The decision was made to proceed with laparotomy for decompression and additional biopsies from the retroperitoneal mass and omental lymph nodes, which confirmed poorly differentiated adenocarcinoma with signet ring cells. The presence of a mass in the duodenum strongly suggested adenocarcinoma of small intestine origin. As the patient’s symptoms worsened, imaging revealed progression with lung metastases. The patient continued to deteriorate rapidly requiring dialysis and gangrenous cholecystitis. Given his complex medical history, patient decided to transition to comfort care.

Discussion

SRCC can present with any GI symptoms. Most important step in diagnosing SRCC is biopsy. Current treatment options for small intestinal malignancies include wide resection that includes the mesentery and corresponding lymph nodes. The use of adjuvant chemotherapy has been described only in small retrospective studies. Due to its scarcity, there isn’t sufficient data for optimal treatment strategies compared to gastric SRCC.

Conclusions

This case report highlights the importance of how rare and aggressive signet ring cell adenocarcinoma of the small intestine. There are only a few cases documented in the literature, which is why we lack data on how to manage the disease. 

Compartment syndrome occurs when the interstitial tissue pressures within a confined space are elevated to a level at which the arterial perfusion is diminished. Multiple etiologies exist and can be extrinsic (a cast that is too tight or prolonged compression on a limb), iatrogenic (aggressive resuscitation, drug infiltration, arterial puncture, or a spontaneous bleed from anticoagulation), and traumatic (fracture, snake envenomation, circumferential burn, or electrocution). If the compartments are not released, irreversible changes happen to the cells, including nerve and muscle death.¹ Definitive management of this emergency requires prompt fasciotomy to decompress the compartment(s).^1-3

Case Presentation

A 76-year-old right-handed woman with a history of chronic obstructive pulmonary disease, hypertension, and hyperlipidemia presented to the emergency department with 2 days of extensive right upper extremity ecchymosis and severe pain that was localized to her forearm (Figure 1). She was taking low-dose aspirin (81 mg/d) for left subclavian stenosis and over-the-counter ginkgo biloba. Leading up to the presentation, the patient was able to perform routine household chores, including yard work, cleaning, and taking care of her cats. Wrist and elbow X-rays were negative for a fracture. An upper extremity ultrasound found no venous occlusion. A computed tomography (CT) angiogram of her arm and chest found diffuse edema around the right elbow and forearm without pulmonary or right upper extremity emboli, fractures, hematoma, abscess, or air in the tissues.

The plastic surgery service was consulted. The patient was found to have a very tense forearm and pain to passive digital extension. The 2-point discrimination and pulses were intact. The patient was diagnosed with compartment syndrome based on the examination alone and gave consent for an emergent forearm and hand fasciotomy. A carpal tunnel release and a standard S-shaped volar forearm fasciotomy release were performed, which provided immediate decompression (Figure 2). The rest of the hand and extremity were soft. Edematous, healthy flexor muscle belly was identified without a hematoma. Most of the forearm wound was left open because the skin could not be reapproximated. Oxidized regenerated cellulose (Surgicel) was placed around the wound edges and the muscle was covered with a nonadherent dressing. Hemoglobin on admission was 12.9 g/dL(reference range, 12 to 16 g/dL). Kidney function was within normal limits. The rest of the complete blood count was unremarkable. Postoperative hemoglobin was 8.6 g/dL. Over the next several days, the patient's skin edges and muscle bellies continued to slowly bleed, and her hemoglobin fell to 5.6 g/dL by postoperative Day 2. The bleeding was managed with topical oxidized regenerated cellulose, thrombin spray, a hemostatic dressing made with kaolin (QuikClot), and a transfusion of 2 units of packed red blood cells.

A hematology consultation was requested. The patient was noted to have an elevated partial thromboplastin time (PTT) since admission measuring between 39.9 to 61.7 seconds (reference range, 26.2 to 37.2 seconds) and a normal prothrombin time test with an international normalized ratio. A PTT measured 17 months prior to admission was within the normal range. She reported no personal or family history of bleeding disorders. Until recently, she had never had easy bruisability. She reported no history of heavy menses or epistaxis. The patient had no children and had never been pregnant. She had tolerated an exploratory laparotomy 40 years prior to admission without bleeding complications and had never required blood transfusions before. A PTT 1:1 mixing study revealed incomplete correction. Subsequent workup included factor VIII (FVIII) activity, factor IX activity, factor XI activity, von Willebrand factor antigen, ristocetin cofactor assay, and von Willebrand factor multimers. FVIII activity was severely reduced at 7.8% (reference, > 54%) with a positive Bethesda assay of 300 to 400 Bodansky units (BU), indicating a strong FVIII inhibitor was present and establishing a diagnosis of acquired hemophilia A. Further workup for secondary causes of acquired hemophilia A including abdominal and pelvic CT, serum protein electrophoresis, and serum free light chains, were negative. She was started on prednisone 1 mg/kg daily and rituximab 375 mg/m². Her hemoglobin stabilized, and she required no further blood transfusions.

The patient underwent wound closure on postoperative Day 11. At the time of the second surgery, there was still no improvement in her FVIII levels or PTT; therefore, 70 mcg/kg of recombinant coagulation-activated FVII was given just before surgery with no bleeding complications. The skin was closed primarily except for the most distal 3 cm (Figure 3). Due to concerns regarding further bleeding with skin graft, the remaining wound was allowed to close by secondary intention. As a precaution, the wound was covered with oxidized regenerated cellulose and thrombin spray. The patient continued to progress postoperatively without bleeding complications or a need for additional transfusions. She was seen by the hand therapist before and after the second surgery to help with edema management and joint mobility. She completed 4 weekly doses of 375 mg/m² rituximab and prednisone was tapered by 10 mg weekly.

Three weeks after starting treatment, her PTT normalized, and her FVIII increased to 33.7%. The Bethesda assay remained high at 198 BU, although it was lower than at admission. She was discharged home with dressing changes and monthly follow-up appointments. The wounds were fully closed at her 3-month appointment when she proudly demonstrated full digital extension and flexion into her palm.

Discussion

Forearm compartment syndrome is most often caused by fractures—distal radius in adults and supracondylar in children.² This case initially presented as a diagnostic puzzle to the emergency department due to the patient’s lucid review of several days of nontraumatic injury.

The clinical hallmarks of compartment syndrome are the 5 Ps: pain, pallor, paresthesia, paralysis, and pulselessness. Patients will describe the pain as out of proportion to the nature of the injury; the compartments will be tense and swollen, they will have pain to passive muscle stretch, and sensation will progressively diminish. Distal pulses are the last to go, and permanent tissue damage can still occur when pulses are present.¹

Compartment Syndrome

Compartment syndrome is generally a clinical diagnosis; however, in patients who are sedated or uncooperative, or if the clinical findings are equivocal, the examination can be supplemented with intercompartmental pressures using an arterial line transducer system.² In general, a tissue pressure of 30 mm Hg or a 20- to 30-mm Hg difference between the diastolic and compartment pressures are indications for fasciotomy.¹ The hand is treated with an open carpal tunnel release, interosseous muscle release through 2 dorsal hand incisions, and thenar and hypothenar muscle release. The forearm is treated through a curved volar incision that usually decompresses the dorsal compartment, as it did in our patient. If pressures are still high in the forearm, a longitudinal dorsal incision over the mobile wad is necessary. Wounds can be closed primarily days later, left open to close by secondary intention, or reconstructed with skin grafts.² In our patient, compartment syndrome was isolated to her forearm and the carpal tunnel release was performed prophylactically since it did not add significant time or morbidity to the surgery.

Nontraumatic upper extremity compartment syndrome is rare. A 2021 review of acute nontraumatic upper extremity compartment syndrome found a bleeding disorder as the etiology in 3 cases published in the literature between 1993 and 2016.⁴ One of these cases was secondary to a known diagnosis of hemophilia A in a teenager.⁵ Ogrodnik and colleagues described a spontaneous hand hematoma secondary to previously undiagnosed acquired hemophilia A and Waldenström macroglobulinemia.⁴ Ilyas and colleagues described a spontaneous hematoma in the forearm dorsal compartment in a 67-year-old woman, which presented as compartment syndrome and elevated PTT and led to a diagnosis of acquired FVIII inhibitor. The authors recommended prompt hematology consultation to coordinate treatment once this diagnosis issuspected.⁶ Compartment syndrome also has been found to develop slowly over weeks in patients with acquired FVIII deficiency, suggesting a high index of suspicion and frequent examinations are needed when patients with known acquired hemophilia A present with a painful extremity.⁷

Nontraumatic compartment syndrome in the lower extremity in patients with previously undiagnosed acquired hemophilia A has also been described in the literature.^8-11 Case reports describe the delay in diagnosis as the patients were originally seen by clinicians for lower extremity pain and swelling within days of presenting to the emergency room with compartment syndrome. Persistent bleeding and abnormal laboratory results prompted further tests and examinations.^8,9,11 This underscores the need to be suspicious of this unusual pathology without a history of trauma.

Acquired Hemophilia A

Acquired hemophilia A is an autoimmune disease most often found in older individuals, with a mean age of approximately 70 years.¹² It is caused by the spontaneous production of neutralizing immunoglobin autoantibodies that target endogenous FVIII. Many cases are idiopathic; however, up to 50% of cases are associated with underlying autoimmunity, malignancy (especially lymphoproliferative disorders), or pregnancy. It often presents as bleeding that is subcutaneous or in the gastrointestinal system, muscle, retroperitoneal space, or genitourinary system. Unlike congenital hemophilia A, joint bleeding is rare.¹³

The diagnosis is suspected with an isolated elevated PTT in the absence of other coagulation abnormalities. A 1:1 mixing study will typically show incomplete correction, which suggests the presence of an inhibitor. FVIII activity is reduced, and the FVIII inhibitor is confirmed with the Bethesda assay. Clinically active bleeding is treated with bypassing agents such as recombinant coagulation-activated FVII, activated prothrombin complex concentrates such as anti-inhibitor coagulant complex (FEIBA), or recombinant porcine FVIII.^12,14 Not all patients require hemostatic treatment, but close monitoring, education, recognition, and immediate treatment, if needed, are indicated.¹³ Immunosuppressive therapy (corticosteroids, rituximab, and/or cyclophosphamide) is prescribed to eradicate the antibodies and induce remission.¹²

Conclusions

An older woman without a preceding trauma was diagnosed with an unusual case of acute compartment syndrome in the forearm. No hematoma was found, but muscle and skin bleeding plus an elevated PTT prompted a hematology workup, and, ultimately, the diagnosis of FVIII inhibitor secondary to acquired hemophilia A.

While a nontraumatic cause of compartment syndrome is rare, it should be considered in differential diagnosis for clinicians who see hand and upper extremity emergencies. An isolated elevated PTT in a patient with a bleed should raise suspicions and trigger immediate further evaluation. Once suspected, multidisciplinary treatment is indicated for immediate and long-term successful outcomes.

Acknowledgments

This manuscript is the result of work supported withresources and the use of facilities at the North Florida/South Georgia Veterans Health System, Gainesville, Florida.

Compartment syndrome occurs when the interstitial tissue pressures within a confined space are elevated to a level at which the arterial perfusion is diminished. Multiple etiologies exist and can be extrinsic (a cast that is too tight or prolonged compression on a limb), iatrogenic (aggressive resuscitation, drug infiltration, arterial puncture, or a spontaneous bleed from anticoagulation), and traumatic (fracture, snake envenomation, circumferential burn, or electrocution). If the compartments are not released, irreversible changes happen to the cells, including nerve and muscle death.¹ Definitive management of this emergency requires prompt fasciotomy to decompress the compartment(s).^1-3

Case Presentation

A 76-year-old right-handed woman with a history of chronic obstructive pulmonary disease, hypertension, and hyperlipidemia presented to the emergency department with 2 days of extensive right upper extremity ecchymosis and severe pain that was localized to her forearm (Figure 1). She was taking low-dose aspirin (81 mg/d) for left subclavian stenosis and over-the-counter ginkgo biloba. Leading up to the presentation, the patient was able to perform routine household chores, including yard work, cleaning, and taking care of her cats. Wrist and elbow X-rays were negative for a fracture. An upper extremity ultrasound found no venous occlusion. A computed tomography (CT) angiogram of her arm and chest found diffuse edema around the right elbow and forearm without pulmonary or right upper extremity emboli, fractures, hematoma, abscess, or air in the tissues.

The plastic surgery service was consulted. The patient was found to have a very tense forearm and pain to passive digital extension. The 2-point discrimination and pulses were intact. The patient was diagnosed with compartment syndrome based on the examination alone and gave consent for an emergent forearm and hand fasciotomy. A carpal tunnel release and a standard S-shaped volar forearm fasciotomy release were performed, which provided immediate decompression (Figure 2). The rest of the hand and extremity were soft. Edematous, healthy flexor muscle belly was identified without a hematoma. Most of the forearm wound was left open because the skin could not be reapproximated. Oxidized regenerated cellulose (Surgicel) was placed around the wound edges and the muscle was covered with a nonadherent dressing. Hemoglobin on admission was 12.9 g/dL(reference range, 12 to 16 g/dL). Kidney function was within normal limits. The rest of the complete blood count was unremarkable. Postoperative hemoglobin was 8.6 g/dL. Over the next several days, the patient's skin edges and muscle bellies continued to slowly bleed, and her hemoglobin fell to 5.6 g/dL by postoperative Day 2. The bleeding was managed with topical oxidized regenerated cellulose, thrombin spray, a hemostatic dressing made with kaolin (QuikClot), and a transfusion of 2 units of packed red blood cells.

A hematology consultation was requested. The patient was noted to have an elevated partial thromboplastin time (PTT) since admission measuring between 39.9 to 61.7 seconds (reference range, 26.2 to 37.2 seconds) and a normal prothrombin time test with an international normalized ratio. A PTT measured 17 months prior to admission was within the normal range. She reported no personal or family history of bleeding disorders. Until recently, she had never had easy bruisability. She reported no history of heavy menses or epistaxis. The patient had no children and had never been pregnant. She had tolerated an exploratory laparotomy 40 years prior to admission without bleeding complications and had never required blood transfusions before. A PTT 1:1 mixing study revealed incomplete correction. Subsequent workup included factor VIII (FVIII) activity, factor IX activity, factor XI activity, von Willebrand factor antigen, ristocetin cofactor assay, and von Willebrand factor multimers. FVIII activity was severely reduced at 7.8% (reference, > 54%) with a positive Bethesda assay of 300 to 400 Bodansky units (BU), indicating a strong FVIII inhibitor was present and establishing a diagnosis of acquired hemophilia A. Further workup for secondary causes of acquired hemophilia A including abdominal and pelvic CT, serum protein electrophoresis, and serum free light chains, were negative. She was started on prednisone 1 mg/kg daily and rituximab 375 mg/m². Her hemoglobin stabilized, and she required no further blood transfusions.

The patient underwent wound closure on postoperative Day 11. At the time of the second surgery, there was still no improvement in her FVIII levels or PTT; therefore, 70 mcg/kg of recombinant coagulation-activated FVII was given just before surgery with no bleeding complications. The skin was closed primarily except for the most distal 3 cm (Figure 3). Due to concerns regarding further bleeding with skin graft, the remaining wound was allowed to close by secondary intention. As a precaution, the wound was covered with oxidized regenerated cellulose and thrombin spray. The patient continued to progress postoperatively without bleeding complications or a need for additional transfusions. She was seen by the hand therapist before and after the second surgery to help with edema management and joint mobility. She completed 4 weekly doses of 375 mg/m² rituximab and prednisone was tapered by 10 mg weekly.

Three weeks after starting treatment, her PTT normalized, and her FVIII increased to 33.7%. The Bethesda assay remained high at 198 BU, although it was lower than at admission. She was discharged home with dressing changes and monthly follow-up appointments. The wounds were fully closed at her 3-month appointment when she proudly demonstrated full digital extension and flexion into her palm.

Discussion

Forearm compartment syndrome is most often caused by fractures—distal radius in adults and supracondylar in children.² This case initially presented as a diagnostic puzzle to the emergency department due to the patient’s lucid review of several days of nontraumatic injury.

The clinical hallmarks of compartment syndrome are the 5 Ps: pain, pallor, paresthesia, paralysis, and pulselessness. Patients will describe the pain as out of proportion to the nature of the injury; the compartments will be tense and swollen, they will have pain to passive muscle stretch, and sensation will progressively diminish. Distal pulses are the last to go, and permanent tissue damage can still occur when pulses are present.¹

Compartment Syndrome

Compartment syndrome is generally a clinical diagnosis; however, in patients who are sedated or uncooperative, or if the clinical findings are equivocal, the examination can be supplemented with intercompartmental pressures using an arterial line transducer system.² In general, a tissue pressure of 30 mm Hg or a 20- to 30-mm Hg difference between the diastolic and compartment pressures are indications for fasciotomy.¹ The hand is treated with an open carpal tunnel release, interosseous muscle release through 2 dorsal hand incisions, and thenar and hypothenar muscle release. The forearm is treated through a curved volar incision that usually decompresses the dorsal compartment, as it did in our patient. If pressures are still high in the forearm, a longitudinal dorsal incision over the mobile wad is necessary. Wounds can be closed primarily days later, left open to close by secondary intention, or reconstructed with skin grafts.² In our patient, compartment syndrome was isolated to her forearm and the carpal tunnel release was performed prophylactically since it did not add significant time or morbidity to the surgery.

Nontraumatic upper extremity compartment syndrome is rare. A 2021 review of acute nontraumatic upper extremity compartment syndrome found a bleeding disorder as the etiology in 3 cases published in the literature between 1993 and 2016.⁴ One of these cases was secondary to a known diagnosis of hemophilia A in a teenager.⁵ Ogrodnik and colleagues described a spontaneous hand hematoma secondary to previously undiagnosed acquired hemophilia A and Waldenström macroglobulinemia.⁴ Ilyas and colleagues described a spontaneous hematoma in the forearm dorsal compartment in a 67-year-old woman, which presented as compartment syndrome and elevated PTT and led to a diagnosis of acquired FVIII inhibitor. The authors recommended prompt hematology consultation to coordinate treatment once this diagnosis issuspected.⁶ Compartment syndrome also has been found to develop slowly over weeks in patients with acquired FVIII deficiency, suggesting a high index of suspicion and frequent examinations are needed when patients with known acquired hemophilia A present with a painful extremity.⁷

Nontraumatic compartment syndrome in the lower extremity in patients with previously undiagnosed acquired hemophilia A has also been described in the literature.^8-11 Case reports describe the delay in diagnosis as the patients were originally seen by clinicians for lower extremity pain and swelling within days of presenting to the emergency room with compartment syndrome. Persistent bleeding and abnormal laboratory results prompted further tests and examinations.^8,9,11 This underscores the need to be suspicious of this unusual pathology without a history of trauma.

Acquired Hemophilia A

Acquired hemophilia A is an autoimmune disease most often found in older individuals, with a mean age of approximately 70 years.¹² It is caused by the spontaneous production of neutralizing immunoglobin autoantibodies that target endogenous FVIII. Many cases are idiopathic; however, up to 50% of cases are associated with underlying autoimmunity, malignancy (especially lymphoproliferative disorders), or pregnancy. It often presents as bleeding that is subcutaneous or in the gastrointestinal system, muscle, retroperitoneal space, or genitourinary system. Unlike congenital hemophilia A, joint bleeding is rare.¹³

The diagnosis is suspected with an isolated elevated PTT in the absence of other coagulation abnormalities. A 1:1 mixing study will typically show incomplete correction, which suggests the presence of an inhibitor. FVIII activity is reduced, and the FVIII inhibitor is confirmed with the Bethesda assay. Clinically active bleeding is treated with bypassing agents such as recombinant coagulation-activated FVII, activated prothrombin complex concentrates such as anti-inhibitor coagulant complex (FEIBA), or recombinant porcine FVIII.^12,14 Not all patients require hemostatic treatment, but close monitoring, education, recognition, and immediate treatment, if needed, are indicated.¹³ Immunosuppressive therapy (corticosteroids, rituximab, and/or cyclophosphamide) is prescribed to eradicate the antibodies and induce remission.¹²

Conclusions

An older woman without a preceding trauma was diagnosed with an unusual case of acute compartment syndrome in the forearm. No hematoma was found, but muscle and skin bleeding plus an elevated PTT prompted a hematology workup, and, ultimately, the diagnosis of FVIII inhibitor secondary to acquired hemophilia A.

While a nontraumatic cause of compartment syndrome is rare, it should be considered in differential diagnosis for clinicians who see hand and upper extremity emergencies. An isolated elevated PTT in a patient with a bleed should raise suspicions and trigger immediate further evaluation. Once suspected, multidisciplinary treatment is indicated for immediate and long-term successful outcomes.

Acknowledgments

This manuscript is the result of work supported withresources and the use of facilities at the North Florida/South Georgia Veterans Health System, Gainesville, Florida.

Compartment syndrome occurs when the interstitial tissue pressures within a confined space are elevated to a level at which the arterial perfusion is diminished. Multiple etiologies exist and can be extrinsic (a cast that is too tight or prolonged compression on a limb), iatrogenic (aggressive resuscitation, drug infiltration, arterial puncture, or a spontaneous bleed from anticoagulation), and traumatic (fracture, snake envenomation, circumferential burn, or electrocution). If the compartments are not released, irreversible changes happen to the cells, including nerve and muscle death.¹ Definitive management of this emergency requires prompt fasciotomy to decompress the compartment(s).^1-3

Case Presentation

A 76-year-old right-handed woman with a history of chronic obstructive pulmonary disease, hypertension, and hyperlipidemia presented to the emergency department with 2 days of extensive right upper extremity ecchymosis and severe pain that was localized to her forearm (Figure 1). She was taking low-dose aspirin (81 mg/d) for left subclavian stenosis and over-the-counter ginkgo biloba. Leading up to the presentation, the patient was able to perform routine household chores, including yard work, cleaning, and taking care of her cats. Wrist and elbow X-rays were negative for a fracture. An upper extremity ultrasound found no venous occlusion. A computed tomography (CT) angiogram of her arm and chest found diffuse edema around the right elbow and forearm without pulmonary or right upper extremity emboli, fractures, hematoma, abscess, or air in the tissues.

The plastic surgery service was consulted. The patient was found to have a very tense forearm and pain to passive digital extension. The 2-point discrimination and pulses were intact. The patient was diagnosed with compartment syndrome based on the examination alone and gave consent for an emergent forearm and hand fasciotomy. A carpal tunnel release and a standard S-shaped volar forearm fasciotomy release were performed, which provided immediate decompression (Figure 2). The rest of the hand and extremity were soft. Edematous, healthy flexor muscle belly was identified without a hematoma. Most of the forearm wound was left open because the skin could not be reapproximated. Oxidized regenerated cellulose (Surgicel) was placed around the wound edges and the muscle was covered with a nonadherent dressing. Hemoglobin on admission was 12.9 g/dL(reference range, 12 to 16 g/dL). Kidney function was within normal limits. The rest of the complete blood count was unremarkable. Postoperative hemoglobin was 8.6 g/dL. Over the next several days, the patient's skin edges and muscle bellies continued to slowly bleed, and her hemoglobin fell to 5.6 g/dL by postoperative Day 2. The bleeding was managed with topical oxidized regenerated cellulose, thrombin spray, a hemostatic dressing made with kaolin (QuikClot), and a transfusion of 2 units of packed red blood cells.

A hematology consultation was requested. The patient was noted to have an elevated partial thromboplastin time (PTT) since admission measuring between 39.9 to 61.7 seconds (reference range, 26.2 to 37.2 seconds) and a normal prothrombin time test with an international normalized ratio. A PTT measured 17 months prior to admission was within the normal range. She reported no personal or family history of bleeding disorders. Until recently, she had never had easy bruisability. She reported no history of heavy menses or epistaxis. The patient had no children and had never been pregnant. She had tolerated an exploratory laparotomy 40 years prior to admission without bleeding complications and had never required blood transfusions before. A PTT 1:1 mixing study revealed incomplete correction. Subsequent workup included factor VIII (FVIII) activity, factor IX activity, factor XI activity, von Willebrand factor antigen, ristocetin cofactor assay, and von Willebrand factor multimers. FVIII activity was severely reduced at 7.8% (reference, > 54%) with a positive Bethesda assay of 300 to 400 Bodansky units (BU), indicating a strong FVIII inhibitor was present and establishing a diagnosis of acquired hemophilia A. Further workup for secondary causes of acquired hemophilia A including abdominal and pelvic CT, serum protein electrophoresis, and serum free light chains, were negative. She was started on prednisone 1 mg/kg daily and rituximab 375 mg/m². Her hemoglobin stabilized, and she required no further blood transfusions.

The patient underwent wound closure on postoperative Day 11. At the time of the second surgery, there was still no improvement in her FVIII levels or PTT; therefore, 70 mcg/kg of recombinant coagulation-activated FVII was given just before surgery with no bleeding complications. The skin was closed primarily except for the most distal 3 cm (Figure 3). Due to concerns regarding further bleeding with skin graft, the remaining wound was allowed to close by secondary intention. As a precaution, the wound was covered with oxidized regenerated cellulose and thrombin spray. The patient continued to progress postoperatively without bleeding complications or a need for additional transfusions. She was seen by the hand therapist before and after the second surgery to help with edema management and joint mobility. She completed 4 weekly doses of 375 mg/m² rituximab and prednisone was tapered by 10 mg weekly.

Three weeks after starting treatment, her PTT normalized, and her FVIII increased to 33.7%. The Bethesda assay remained high at 198 BU, although it was lower than at admission. She was discharged home with dressing changes and monthly follow-up appointments. The wounds were fully closed at her 3-month appointment when she proudly demonstrated full digital extension and flexion into her palm.

Discussion

Forearm compartment syndrome is most often caused by fractures—distal radius in adults and supracondylar in children.² This case initially presented as a diagnostic puzzle to the emergency department due to the patient’s lucid review of several days of nontraumatic injury.

The clinical hallmarks of compartment syndrome are the 5 Ps: pain, pallor, paresthesia, paralysis, and pulselessness. Patients will describe the pain as out of proportion to the nature of the injury; the compartments will be tense and swollen, they will have pain to passive muscle stretch, and sensation will progressively diminish. Distal pulses are the last to go, and permanent tissue damage can still occur when pulses are present.¹

Compartment Syndrome

Compartment syndrome is generally a clinical diagnosis; however, in patients who are sedated or uncooperative, or if the clinical findings are equivocal, the examination can be supplemented with intercompartmental pressures using an arterial line transducer system.² In general, a tissue pressure of 30 mm Hg or a 20- to 30-mm Hg difference between the diastolic and compartment pressures are indications for fasciotomy.¹ The hand is treated with an open carpal tunnel release, interosseous muscle release through 2 dorsal hand incisions, and thenar and hypothenar muscle release. The forearm is treated through a curved volar incision that usually decompresses the dorsal compartment, as it did in our patient. If pressures are still high in the forearm, a longitudinal dorsal incision over the mobile wad is necessary. Wounds can be closed primarily days later, left open to close by secondary intention, or reconstructed with skin grafts.² In our patient, compartment syndrome was isolated to her forearm and the carpal tunnel release was performed prophylactically since it did not add significant time or morbidity to the surgery.

Nontraumatic upper extremity compartment syndrome is rare. A 2021 review of acute nontraumatic upper extremity compartment syndrome found a bleeding disorder as the etiology in 3 cases published in the literature between 1993 and 2016.⁴ One of these cases was secondary to a known diagnosis of hemophilia A in a teenager.⁵ Ogrodnik and colleagues described a spontaneous hand hematoma secondary to previously undiagnosed acquired hemophilia A and Waldenström macroglobulinemia.⁴ Ilyas and colleagues described a spontaneous hematoma in the forearm dorsal compartment in a 67-year-old woman, which presented as compartment syndrome and elevated PTT and led to a diagnosis of acquired FVIII inhibitor. The authors recommended prompt hematology consultation to coordinate treatment once this diagnosis issuspected.⁶ Compartment syndrome also has been found to develop slowly over weeks in patients with acquired FVIII deficiency, suggesting a high index of suspicion and frequent examinations are needed when patients with known acquired hemophilia A present with a painful extremity.⁷

Nontraumatic compartment syndrome in the lower extremity in patients with previously undiagnosed acquired hemophilia A has also been described in the literature.^8-11 Case reports describe the delay in diagnosis as the patients were originally seen by clinicians for lower extremity pain and swelling within days of presenting to the emergency room with compartment syndrome. Persistent bleeding and abnormal laboratory results prompted further tests and examinations.^8,9,11 This underscores the need to be suspicious of this unusual pathology without a history of trauma.

Acquired Hemophilia A

Acquired hemophilia A is an autoimmune disease most often found in older individuals, with a mean age of approximately 70 years.¹² It is caused by the spontaneous production of neutralizing immunoglobin autoantibodies that target endogenous FVIII. Many cases are idiopathic; however, up to 50% of cases are associated with underlying autoimmunity, malignancy (especially lymphoproliferative disorders), or pregnancy. It often presents as bleeding that is subcutaneous or in the gastrointestinal system, muscle, retroperitoneal space, or genitourinary system. Unlike congenital hemophilia A, joint bleeding is rare.¹³

The diagnosis is suspected with an isolated elevated PTT in the absence of other coagulation abnormalities. A 1:1 mixing study will typically show incomplete correction, which suggests the presence of an inhibitor. FVIII activity is reduced, and the FVIII inhibitor is confirmed with the Bethesda assay. Clinically active bleeding is treated with bypassing agents such as recombinant coagulation-activated FVII, activated prothrombin complex concentrates such as anti-inhibitor coagulant complex (FEIBA), or recombinant porcine FVIII.^12,14 Not all patients require hemostatic treatment, but close monitoring, education, recognition, and immediate treatment, if needed, are indicated.¹³ Immunosuppressive therapy (corticosteroids, rituximab, and/or cyclophosphamide) is prescribed to eradicate the antibodies and induce remission.¹²

Conclusions

An older woman without a preceding trauma was diagnosed with an unusual case of acute compartment syndrome in the forearm. No hematoma was found, but muscle and skin bleeding plus an elevated PTT prompted a hematology workup, and, ultimately, the diagnosis of FVIII inhibitor secondary to acquired hemophilia A.

While a nontraumatic cause of compartment syndrome is rare, it should be considered in differential diagnosis for clinicians who see hand and upper extremity emergencies. An isolated elevated PTT in a patient with a bleed should raise suspicions and trigger immediate further evaluation. Once suspected, multidisciplinary treatment is indicated for immediate and long-term successful outcomes.

Acknowledgments

This manuscript is the result of work supported withresources and the use of facilities at the North Florida/South Georgia Veterans Health System, Gainesville, Florida.

Predicting life expectancy and providing an end-of-life diagnosis in hospice and palliative care is a challenge for most clinicians. Lack of training, limited communication skills, and relationships with patients are all contributing factors. These skills can improve with the use of functional scoring tools in conjunction with the patient’s comorbidities and physical/psychological symptoms. The Palliative Performance Scale (PPS), Karnofsky Performance Scale (KPS), and Eastern Cooperative Oncology Group Performance Status Scale (ECOG) are commonly used functional scoring tools.

The PPS measures 5 functional dimensions including ambulation, activity level, ability to administer self-care, oral intake, and level of consciousness.¹ It has been shown to be valid for a broad range of palliative care patients, including those with advanced cancer or life-threatening noncancer diagnoses in hospitals or hospice care.² The scale, measured in 10% increments, runs from 100% (completely functional) to 0% (dead). A PPS ≤ 70% helps meet hospice eligibility criteria.

The KPS evaluates functional impairment and helps with prognostication. Developed in 1948, it evaluates a patient’s functional ability to tolerate chemotherapy, specifically in lung cancer,and has since been validated to predict mortality across older adults and in chronic disease populations.^3,4 The KPS is also measured in 10% increments ranging from 100% (completely functional without assistance) to 0% (dead). A KPS ≤ 70% assists with hospice eligibility criteria (Table 1).⁵

Developed in 1974, the ECOG has been identified as one of the most important functional status tools in adult cancer care.⁶ It describes a cancer patient’s functional ability, evaluating their ability to care for oneself and participate in daily activities.⁷ The ECOG is a 6-point scale; patients can receive scores ranging from 0 (fully active) to 5 (dead). An ECOG score of 4 (sometimes 3) is generally supportive of meeting hospice eligibility (Table 2).⁶

CASE Presentation

An 80-year-old patient was admitted to the hospice service at the Veterans Affairs Puget Sound Health Care System (VAPSHCS) community living center (CLC) in Tacoma, Washington, from a community-based acute care hospital. His medical history included prostate cancer with metastasis to his pelvis and type 2 diabetes mellitus, which was stable with treatment with oral medication. Six weeks earlier the patient reported a severe frontal headache that was not responding to over-the-counter analgesics. After 2 days with these symptoms, including a ground-level fall without injuries, he presented to the VAPSHCS emergency department (ED) where a complete neurological examination, including magnetic resonance imaging, revealed a left frontoparietal brain lesion that was 4.2 cm × 3.4 cm × 4.2 cm.

The patient experienced a seizure during his ED evaluation and was admitted for treatment. He underwent a craniotomy where most, but not all the lesions were successfully removed. Postoperatively, the patient exhibited right-sided neglect, gait instability, emotional lability, and cognitive communication disorder. The patient completed 15 of 20 planned radiation treatments but declined further radiation or chemotherapy. The patient decided to halt radiation treatments after being informed by the oncology service that the treatments would likely only add 1 to 2 months to his overall survival, which was < 6 months. The patient elected to focus his goals of care on comfort, dignity, and respect at the end of life and accepted recommendations to be placed into end-of-life hospice care. He was then transferred to the VAPSHCS CLC in Tacoma, Washington, for hospice care.

Upon admission, the patient weighed 94 kg, his vital signs were within reference range, and he reported no pain or headaches. His initial laboratory results revealed a 13.2 g/dL hemoglobin, 3.6 g/dL serum albumin, and a 5.5% hemoglobin A_1c, all of which fall into a normal reference range. He had a reported ECOG score of 3 and a KPS score of 50% by the transferring medical team. The patient’s medications included scheduled dexamethasone, metformin, senna, levetiracetam, and as-needed midazolam nasal spray for breakthrough seizures. He also had as-needed acetaminophen for pain. He was alert, oriented ×3, and fully ambulatory but continuously used a 4-wheeled walker for safety and gait instability.

After the patient’s first night, the hospice team met with him to discuss his understanding of his health issues. The patient appeared to have low health literacy but told the team, “I know I am dying.” He had completed written advance directives and a Portable Order for Life-Sustaining Treatment indicating that life-sustaining treatments, including cardiopulmonary resuscitation, supplemental mechanical feeding, or intubation, were not to be used to keep him alive.

At his first 90-day recertification, the patient had gained 8 kg and laboratory results revealed a 14.6 g/dL hemoglobin, 3.8 g/dL serum albumin, and a 6.1% hemoglobin A_1c. His ECOG score remained at 3, but his KPS score had increased to 60%. The patient exhibited no new neurologic symptoms or seizures and reported no headaches but had 2 ground-level falls without injury. On both occasions the patient chose not to use his walker to go to the bathroom because it was “too far from my bed.” Per VA policy, after discussions with the hospice team, he was recertified for 90 more days of hospice care. At the end of 6 months in CLC, the patient’s weight remained stable, as did his complete blood count and comprehensive medical panel. He had 1 additional noninjurious ground-level fall and again reported no pain and no use of as-needed acetaminophen. His only medical complication was testing positive for COVID-19, but he remained asymptomatic. The patient was graduated from hospice care and referred to a nearby non-VA adult family home in the community after 180 days. At that time his ECOG score was 2 and his KPS score had increased to 70%.

DISCUSSION

Primary brain tumors account for about 2% of all malignant neoplasms in adults. About half of them represent gliomas. Glioblastoma multiforme derived from neuroepithelial cells is the most frequent and deadly primary malignant central nervous system tumor in adults.⁸ About 50% of patients with glioblastomas are aged ≥ 65 years at diagnosis.⁹ A retrospective study of Centers for Medicare and Medicaid Services claims data paired with the Surveillance, Epidemiology, and End Results database indicated a median survival of 4 months for patients with glioblastoma multiforme aged > 65 years, including all treatment modalities.¹⁰ Surgical resection combined with radiation and chemotherapy offers the best prognosis for the preservation of neurologic function.¹¹ However, comorbidities, adverse drug effects, and the potential for postoperative complications pose significant risks, especially for older patients. Ultimately, goals of care conversations and advance directives play a very important role in evaluating benefits vs risks with this malignancy.

Our patient was aged 80 years and had previously been diagnosed with metastatic prostate malignancy. His goals of care focused on spending time with his friends, leaving his room to eat in the facility dining area, and continuing his daily walks. He remained clear that he did not want his care team to institute life-sustaining treatments to be kept alive and felt the information regarding the risks vs benefits of accepting chemotherapy was not aligned with his goals of care. Over the 6 months that he received hospice care, he gained weight, improved his hemoglobin and serum albumin levels, and ambulated with the use of a 4-wheeled walker. As the patient exhibited no functional decline or new comorbidities and his functional status improved, the clinical staff felt he no longer needed hospice services. The patient had an ECOG score of 2 and a KPS score of 70% at his hospice graduation.

Medical prognostication is one of the biggest challenges clinicians face. Clinicians are generally “over prognosticators,” and their thoughts tend to be based on the patient relationship, overall experiences in health care, and desire to treat and cure patients.¹² In hospice we are asked to define the usual, normal, or expected course of a disease, but what does that mean? Although metastatic malignancies usually have a predictable course in comparison to diagnoses such as dementia, chronic obstructive pulmonary disease, or congestive heart failure, the challenges to improve prognostic ability andpredict disease course continue.^13-15 Focusing on functional status, goals of care, and comorbidities are keys to helping with prognosis. Given the challenge, we find the PPS, KPS, and ECOG scales important tools.

When prognosticating, we attempt to define quantity and quality of life (which our patients must define independently or from the voice of their surrogate) and their ability to perform daily activities. Quality of life in patients with glioblastoma is progressively and significantly impacted due to the emergence of debilitating neurologic symptoms arising from infiltrative tumor growth into functionally intact brain tissue that restricts and disrupts normal day-to-day activities. However, functional status plays a significant role in helping the hospice team improve its overall prognosis.

Conclusions

This case study illustrates the difficulty that comes with prognostication(s) despite a patient's severely morbid disease, history of metastatic prostate cancer, and advanced age. Although a diagnosis may be concerning, documenting a patient’s status using functional scales prior to hospice admission and during the recertification process is helpful in prognostication. Doing so will allow health care professionals to have an accepted medical standard to use regardless how distinct the patient's diagnosis. The expression, “as the disease does not read the textbook,” may serve as a helpful reminder in talking with patients and their families. This is important as most patient’s clinical disease courses are different and having the opportunity to use performance status scales may help improve prognostic skills.

Predicting life expectancy and providing an end-of-life diagnosis in hospice and palliative care is a challenge for most clinicians. Lack of training, limited communication skills, and relationships with patients are all contributing factors. These skills can improve with the use of functional scoring tools in conjunction with the patient’s comorbidities and physical/psychological symptoms. The Palliative Performance Scale (PPS), Karnofsky Performance Scale (KPS), and Eastern Cooperative Oncology Group Performance Status Scale (ECOG) are commonly used functional scoring tools.

The PPS measures 5 functional dimensions including ambulation, activity level, ability to administer self-care, oral intake, and level of consciousness.¹ It has been shown to be valid for a broad range of palliative care patients, including those with advanced cancer or life-threatening noncancer diagnoses in hospitals or hospice care.² The scale, measured in 10% increments, runs from 100% (completely functional) to 0% (dead). A PPS ≤ 70% helps meet hospice eligibility criteria.

The KPS evaluates functional impairment and helps with prognostication. Developed in 1948, it evaluates a patient’s functional ability to tolerate chemotherapy, specifically in lung cancer,and has since been validated to predict mortality across older adults and in chronic disease populations.^3,4 The KPS is also measured in 10% increments ranging from 100% (completely functional without assistance) to 0% (dead). A KPS ≤ 70% assists with hospice eligibility criteria (Table 1).⁵

Developed in 1974, the ECOG has been identified as one of the most important functional status tools in adult cancer care.⁶ It describes a cancer patient’s functional ability, evaluating their ability to care for oneself and participate in daily activities.⁷ The ECOG is a 6-point scale; patients can receive scores ranging from 0 (fully active) to 5 (dead). An ECOG score of 4 (sometimes 3) is generally supportive of meeting hospice eligibility (Table 2).⁶

CASE Presentation

An 80-year-old patient was admitted to the hospice service at the Veterans Affairs Puget Sound Health Care System (VAPSHCS) community living center (CLC) in Tacoma, Washington, from a community-based acute care hospital. His medical history included prostate cancer with metastasis to his pelvis and type 2 diabetes mellitus, which was stable with treatment with oral medication. Six weeks earlier the patient reported a severe frontal headache that was not responding to over-the-counter analgesics. After 2 days with these symptoms, including a ground-level fall without injuries, he presented to the VAPSHCS emergency department (ED) where a complete neurological examination, including magnetic resonance imaging, revealed a left frontoparietal brain lesion that was 4.2 cm × 3.4 cm × 4.2 cm.

The patient experienced a seizure during his ED evaluation and was admitted for treatment. He underwent a craniotomy where most, but not all the lesions were successfully removed. Postoperatively, the patient exhibited right-sided neglect, gait instability, emotional lability, and cognitive communication disorder. The patient completed 15 of 20 planned radiation treatments but declined further radiation or chemotherapy. The patient decided to halt radiation treatments after being informed by the oncology service that the treatments would likely only add 1 to 2 months to his overall survival, which was < 6 months. The patient elected to focus his goals of care on comfort, dignity, and respect at the end of life and accepted recommendations to be placed into end-of-life hospice care. He was then transferred to the VAPSHCS CLC in Tacoma, Washington, for hospice care.

Upon admission, the patient weighed 94 kg, his vital signs were within reference range, and he reported no pain or headaches. His initial laboratory results revealed a 13.2 g/dL hemoglobin, 3.6 g/dL serum albumin, and a 5.5% hemoglobin A_1c, all of which fall into a normal reference range. He had a reported ECOG score of 3 and a KPS score of 50% by the transferring medical team. The patient’s medications included scheduled dexamethasone, metformin, senna, levetiracetam, and as-needed midazolam nasal spray for breakthrough seizures. He also had as-needed acetaminophen for pain. He was alert, oriented ×3, and fully ambulatory but continuously used a 4-wheeled walker for safety and gait instability.

After the patient’s first night, the hospice team met with him to discuss his understanding of his health issues. The patient appeared to have low health literacy but told the team, “I know I am dying.” He had completed written advance directives and a Portable Order for Life-Sustaining Treatment indicating that life-sustaining treatments, including cardiopulmonary resuscitation, supplemental mechanical feeding, or intubation, were not to be used to keep him alive.

At his first 90-day recertification, the patient had gained 8 kg and laboratory results revealed a 14.6 g/dL hemoglobin, 3.8 g/dL serum albumin, and a 6.1% hemoglobin A_1c. His ECOG score remained at 3, but his KPS score had increased to 60%. The patient exhibited no new neurologic symptoms or seizures and reported no headaches but had 2 ground-level falls without injury. On both occasions the patient chose not to use his walker to go to the bathroom because it was “too far from my bed.” Per VA policy, after discussions with the hospice team, he was recertified for 90 more days of hospice care. At the end of 6 months in CLC, the patient’s weight remained stable, as did his complete blood count and comprehensive medical panel. He had 1 additional noninjurious ground-level fall and again reported no pain and no use of as-needed acetaminophen. His only medical complication was testing positive for COVID-19, but he remained asymptomatic. The patient was graduated from hospice care and referred to a nearby non-VA adult family home in the community after 180 days. At that time his ECOG score was 2 and his KPS score had increased to 70%.

DISCUSSION

Primary brain tumors account for about 2% of all malignant neoplasms in adults. About half of them represent gliomas. Glioblastoma multiforme derived from neuroepithelial cells is the most frequent and deadly primary malignant central nervous system tumor in adults.⁸ About 50% of patients with glioblastomas are aged ≥ 65 years at diagnosis.⁹ A retrospective study of Centers for Medicare and Medicaid Services claims data paired with the Surveillance, Epidemiology, and End Results database indicated a median survival of 4 months for patients with glioblastoma multiforme aged > 65 years, including all treatment modalities.¹⁰ Surgical resection combined with radiation and chemotherapy offers the best prognosis for the preservation of neurologic function.¹¹ However, comorbidities, adverse drug effects, and the potential for postoperative complications pose significant risks, especially for older patients. Ultimately, goals of care conversations and advance directives play a very important role in evaluating benefits vs risks with this malignancy.

Our patient was aged 80 years and had previously been diagnosed with metastatic prostate malignancy. His goals of care focused on spending time with his friends, leaving his room to eat in the facility dining area, and continuing his daily walks. He remained clear that he did not want his care team to institute life-sustaining treatments to be kept alive and felt the information regarding the risks vs benefits of accepting chemotherapy was not aligned with his goals of care. Over the 6 months that he received hospice care, he gained weight, improved his hemoglobin and serum albumin levels, and ambulated with the use of a 4-wheeled walker. As the patient exhibited no functional decline or new comorbidities and his functional status improved, the clinical staff felt he no longer needed hospice services. The patient had an ECOG score of 2 and a KPS score of 70% at his hospice graduation.

Medical prognostication is one of the biggest challenges clinicians face. Clinicians are generally “over prognosticators,” and their thoughts tend to be based on the patient relationship, overall experiences in health care, and desire to treat and cure patients.¹² In hospice we are asked to define the usual, normal, or expected course of a disease, but what does that mean? Although metastatic malignancies usually have a predictable course in comparison to diagnoses such as dementia, chronic obstructive pulmonary disease, or congestive heart failure, the challenges to improve prognostic ability andpredict disease course continue.^13-15 Focusing on functional status, goals of care, and comorbidities are keys to helping with prognosis. Given the challenge, we find the PPS, KPS, and ECOG scales important tools.

When prognosticating, we attempt to define quantity and quality of life (which our patients must define independently or from the voice of their surrogate) and their ability to perform daily activities. Quality of life in patients with glioblastoma is progressively and significantly impacted due to the emergence of debilitating neurologic symptoms arising from infiltrative tumor growth into functionally intact brain tissue that restricts and disrupts normal day-to-day activities. However, functional status plays a significant role in helping the hospice team improve its overall prognosis.

Conclusions

This case study illustrates the difficulty that comes with prognostication(s) despite a patient's severely morbid disease, history of metastatic prostate cancer, and advanced age. Although a diagnosis may be concerning, documenting a patient’s status using functional scales prior to hospice admission and during the recertification process is helpful in prognostication. Doing so will allow health care professionals to have an accepted medical standard to use regardless how distinct the patient's diagnosis. The expression, “as the disease does not read the textbook,” may serve as a helpful reminder in talking with patients and their families. This is important as most patient’s clinical disease courses are different and having the opportunity to use performance status scales may help improve prognostic skills.

Predicting life expectancy and providing an end-of-life diagnosis in hospice and palliative care is a challenge for most clinicians. Lack of training, limited communication skills, and relationships with patients are all contributing factors. These skills can improve with the use of functional scoring tools in conjunction with the patient’s comorbidities and physical/psychological symptoms. The Palliative Performance Scale (PPS), Karnofsky Performance Scale (KPS), and Eastern Cooperative Oncology Group Performance Status Scale (ECOG) are commonly used functional scoring tools.

The PPS measures 5 functional dimensions including ambulation, activity level, ability to administer self-care, oral intake, and level of consciousness.¹ It has been shown to be valid for a broad range of palliative care patients, including those with advanced cancer or life-threatening noncancer diagnoses in hospitals or hospice care.² The scale, measured in 10% increments, runs from 100% (completely functional) to 0% (dead). A PPS ≤ 70% helps meet hospice eligibility criteria.

The KPS evaluates functional impairment and helps with prognostication. Developed in 1948, it evaluates a patient’s functional ability to tolerate chemotherapy, specifically in lung cancer,and has since been validated to predict mortality across older adults and in chronic disease populations.^3,4 The KPS is also measured in 10% increments ranging from 100% (completely functional without assistance) to 0% (dead). A KPS ≤ 70% assists with hospice eligibility criteria (Table 1).⁵

Developed in 1974, the ECOG has been identified as one of the most important functional status tools in adult cancer care.⁶ It describes a cancer patient’s functional ability, evaluating their ability to care for oneself and participate in daily activities.⁷ The ECOG is a 6-point scale; patients can receive scores ranging from 0 (fully active) to 5 (dead). An ECOG score of 4 (sometimes 3) is generally supportive of meeting hospice eligibility (Table 2).⁶

CASE Presentation

An 80-year-old patient was admitted to the hospice service at the Veterans Affairs Puget Sound Health Care System (VAPSHCS) community living center (CLC) in Tacoma, Washington, from a community-based acute care hospital. His medical history included prostate cancer with metastasis to his pelvis and type 2 diabetes mellitus, which was stable with treatment with oral medication. Six weeks earlier the patient reported a severe frontal headache that was not responding to over-the-counter analgesics. After 2 days with these symptoms, including a ground-level fall without injuries, he presented to the VAPSHCS emergency department (ED) where a complete neurological examination, including magnetic resonance imaging, revealed a left frontoparietal brain lesion that was 4.2 cm × 3.4 cm × 4.2 cm.

The patient experienced a seizure during his ED evaluation and was admitted for treatment. He underwent a craniotomy where most, but not all the lesions were successfully removed. Postoperatively, the patient exhibited right-sided neglect, gait instability, emotional lability, and cognitive communication disorder. The patient completed 15 of 20 planned radiation treatments but declined further radiation or chemotherapy. The patient decided to halt radiation treatments after being informed by the oncology service that the treatments would likely only add 1 to 2 months to his overall survival, which was < 6 months. The patient elected to focus his goals of care on comfort, dignity, and respect at the end of life and accepted recommendations to be placed into end-of-life hospice care. He was then transferred to the VAPSHCS CLC in Tacoma, Washington, for hospice care.

Upon admission, the patient weighed 94 kg, his vital signs were within reference range, and he reported no pain or headaches. His initial laboratory results revealed a 13.2 g/dL hemoglobin, 3.6 g/dL serum albumin, and a 5.5% hemoglobin A_1c, all of which fall into a normal reference range. He had a reported ECOG score of 3 and a KPS score of 50% by the transferring medical team. The patient’s medications included scheduled dexamethasone, metformin, senna, levetiracetam, and as-needed midazolam nasal spray for breakthrough seizures. He also had as-needed acetaminophen for pain. He was alert, oriented ×3, and fully ambulatory but continuously used a 4-wheeled walker for safety and gait instability.

After the patient’s first night, the hospice team met with him to discuss his understanding of his health issues. The patient appeared to have low health literacy but told the team, “I know I am dying.” He had completed written advance directives and a Portable Order for Life-Sustaining Treatment indicating that life-sustaining treatments, including cardiopulmonary resuscitation, supplemental mechanical feeding, or intubation, were not to be used to keep him alive.

At his first 90-day recertification, the patient had gained 8 kg and laboratory results revealed a 14.6 g/dL hemoglobin, 3.8 g/dL serum albumin, and a 6.1% hemoglobin A_1c. His ECOG score remained at 3, but his KPS score had increased to 60%. The patient exhibited no new neurologic symptoms or seizures and reported no headaches but had 2 ground-level falls without injury. On both occasions the patient chose not to use his walker to go to the bathroom because it was “too far from my bed.” Per VA policy, after discussions with the hospice team, he was recertified for 90 more days of hospice care. At the end of 6 months in CLC, the patient’s weight remained stable, as did his complete blood count and comprehensive medical panel. He had 1 additional noninjurious ground-level fall and again reported no pain and no use of as-needed acetaminophen. His only medical complication was testing positive for COVID-19, but he remained asymptomatic. The patient was graduated from hospice care and referred to a nearby non-VA adult family home in the community after 180 days. At that time his ECOG score was 2 and his KPS score had increased to 70%.

DISCUSSION

Primary brain tumors account for about 2% of all malignant neoplasms in adults. About half of them represent gliomas. Glioblastoma multiforme derived from neuroepithelial cells is the most frequent and deadly primary malignant central nervous system tumor in adults.⁸ About 50% of patients with glioblastomas are aged ≥ 65 years at diagnosis.⁹ A retrospective study of Centers for Medicare and Medicaid Services claims data paired with the Surveillance, Epidemiology, and End Results database indicated a median survival of 4 months for patients with glioblastoma multiforme aged > 65 years, including all treatment modalities.¹⁰ Surgical resection combined with radiation and chemotherapy offers the best prognosis for the preservation of neurologic function.¹¹ However, comorbidities, adverse drug effects, and the potential for postoperative complications pose significant risks, especially for older patients. Ultimately, goals of care conversations and advance directives play a very important role in evaluating benefits vs risks with this malignancy.

Our patient was aged 80 years and had previously been diagnosed with metastatic prostate malignancy. His goals of care focused on spending time with his friends, leaving his room to eat in the facility dining area, and continuing his daily walks. He remained clear that he did not want his care team to institute life-sustaining treatments to be kept alive and felt the information regarding the risks vs benefits of accepting chemotherapy was not aligned with his goals of care. Over the 6 months that he received hospice care, he gained weight, improved his hemoglobin and serum albumin levels, and ambulated with the use of a 4-wheeled walker. As the patient exhibited no functional decline or new comorbidities and his functional status improved, the clinical staff felt he no longer needed hospice services. The patient had an ECOG score of 2 and a KPS score of 70% at his hospice graduation.

Medical prognostication is one of the biggest challenges clinicians face. Clinicians are generally “over prognosticators,” and their thoughts tend to be based on the patient relationship, overall experiences in health care, and desire to treat and cure patients.¹² In hospice we are asked to define the usual, normal, or expected course of a disease, but what does that mean? Although metastatic malignancies usually have a predictable course in comparison to diagnoses such as dementia, chronic obstructive pulmonary disease, or congestive heart failure, the challenges to improve prognostic ability andpredict disease course continue.^13-15 Focusing on functional status, goals of care, and comorbidities are keys to helping with prognosis. Given the challenge, we find the PPS, KPS, and ECOG scales important tools.

When prognosticating, we attempt to define quantity and quality of life (which our patients must define independently or from the voice of their surrogate) and their ability to perform daily activities. Quality of life in patients with glioblastoma is progressively and significantly impacted due to the emergence of debilitating neurologic symptoms arising from infiltrative tumor growth into functionally intact brain tissue that restricts and disrupts normal day-to-day activities. However, functional status plays a significant role in helping the hospice team improve its overall prognosis.

Conclusions

This case study illustrates the difficulty that comes with prognostication(s) despite a patient's severely morbid disease, history of metastatic prostate cancer, and advanced age. Although a diagnosis may be concerning, documenting a patient’s status using functional scales prior to hospice admission and during the recertification process is helpful in prognostication. Doing so will allow health care professionals to have an accepted medical standard to use regardless how distinct the patient's diagnosis. The expression, “as the disease does not read the textbook,” may serve as a helpful reminder in talking with patients and their families. This is important as most patient’s clinical disease courses are different and having the opportunity to use performance status scales may help improve prognostic skills.

Perioperative visual loss (POVL) is a well-documented yet uncommon complication of nonocular surgery. Patients undergoing cardiac and spinal surgery are at the greatest risk, though POVL may occur during other neurosurgical and vascular procedures as well. The most common causes of POVL are central retinal artery occlusion (CRAO) and ischemic optic neuropathy (ION),^1-3 though cases of orbital compartment syndrome (OCS) have also been reported.^4-7

We describe a case of POVL during a temporal meningioma excision using the pterional approach. Though the etiology is not fully understood, the patient’s clinical course was complicated by a third cranial nerve (CN III) palsy and CRAO, which, together with the patient’s presentation, were consistent with previously documented cases of OCS. The goals of this case report are to increase awareness of this surgical outcome, identify practices that may have contributed to its development, and delineate methods to minimize its occurrence.

Informed consent regarding this research was obtained from the patient and an institutional Health Insurance Portability and Accountability Act authorization form was completed. This manuscript adheres to the applicable Enhancing the Quality and Transparency of Health Research guideline.⁸

Case Presentation

A 47-year-old woman underwent a left temporal craniotomy for resection of a sphenoid wing meningioma discovered during a workup for persistent headaches. She had no medical history of diabetes, hypertension, coronary artery disease, or ophthalmic disease. Two months before her scheduled surgery, the patient reported bilateral blurry vision and underwent ophthalmologic evaluation. Her intraocular pressure (IOP) was normal, and she had no pupillary or retinal disease. She showed evidence of decreased vision in her left eye, suggesting a possible mass effect from her meningioma. Subsequent imaging of the optic nerve and retina had unremarkable physiology (Figure 1). Preoperative magnetic resonance imaging (MRI) demonstrated a stable enhancing mass involving the left great sphenoid wing and left cavernous sinus(Figure 2). There was a superior mass effect on the left middle cerebral artery, but all vessels were patent without evidence of thrombosis.

The patient underwent general anesthesia with invasive hemodynamic monitoring used throughout the procedure. She was induced with fentanyl, propofol, and rocuronium; anesthesia was maintained with isoflurane and a remifentanil infusion. Hypotension was treated with phenylephrine and intravenous fluids. Intraoperative neuromonitoring with electroencephalogram (EEG) and somatosensory evoked potentials was performed. During the surgery, the patient was positioned supine in a Mayfield 3-point head fixation system. All pressure points were padded appropriately and continually checked. A standard left pterional craniotomy was performed, and the scalp was reflected anteriorly and secured using fish hooks with rubber bands. The operation did not violate the cavernous sinus or orbital compartment. There was no evidence of active bleeding upon inspection nor with the Valsalva maneuver. No changes were noted in EEG or somatosensory evoked potentials; blood pressure remained within 20 mm Hg of the patient’s baseline. She was extubated at the end of the 10-hour case and was hemodynamically stable upon transport to the surgical intensive care unit. Postoperative imaging confirmed the successful removal of the left sphenoid wing meningioma.

The patient’s postoperative examination demonstrated a 5 mm dilated, nonresponsive left pupil, though the patient did not report visual loss at that time. Defects were noted in the inferior oblique, superior, inferior, and medial rectus muscles, consistent with CN III palsy. The surgery included manipulation of CN III, which made this a possible outcome, but an alternate causative pathology like OCS was not immediately suspected. Postoperative computed tomography (CT) showed an expected pneumocephalus and left scalp swelling without evidence of mass effect or midline shift.

Repeat MRI showed denervation of the left medial rectus and minimal left-sided proptosis. A 3-month ophthalmologic follow-up revealed a persistent CN III palsy, including an afferent pupillary defect, absence of light perception in her left eye, and continued ophthalmoplegia. Repeat examination showed a left-sided 4+ afferent pupillary defect unreactive to light, 4+ pallor surrounding the optic nerve, macular atrophy, sclerotic vessels, and 17 mm Hg intraocular pressure bilaterally. The eye had diffuse atrophy of the inner retina and significant patchy atrophy of the outer retinal components without neovascularization of the iris. Postoperative retinal imaging can be seen in Figure 3. Her vision loss persisted at this encounter and has continued through subsequent follow-up examinations.

Discussion

Perioperative visual loss is a rare surgical complication, with an estimated incidence of once in every 60,000 to 125,000 cases.⁹ The mechanism of injury is variable and dependent upon the type of surgical intervention, with cardiac and spine surgeries carrying the greatest risk.^10,11 The injury often results in either CRAO or ION, which may result in visual loss.^1-3 POVL can also occur in the aftermath of rapid changes in intracranial pressure during decompressive craniotomies, though the pathophysiology in such cases is not well understood.⁵

Among the myriad ways in which POVL can occur, neurosurgical cases carry the unique risk of direct cranial nerve injury. Such an insult can lead to vision loss via optic nerve damage or ophthalmoplegia if damage occurs to CN III, IV, or VI. This can occur during manipulation or resection, especially if the surgical approach involves the orbital cavity or the cavernous sinus. Though neither space was entered in this patient, direct injury cannot be ruled out as the etiology for either her vision loss or persistent ophthalmoplegia. An alternate causative scenario for both symptoms involve an impaired blood supply, with the vision loss potentially occurring secondary to CRAO and the ophthalmoplegia to an alternate cause of decreased blood flow. It is unclear which of these 2 conditions occurred first or if they occurred due to the same insult, but OCS could lead to both. Though it is a less common etiology for POVL, this patient’s presentation was similar to those in previously reported cases, and OCS was identified as the likely diagnosis.

OCS is precipitated by an elevated orbital pressure, which leads to ischemia of the retina and damage to orbital contents. Though associated with retrobulbar hemorrhage and orbital trauma, another proposed mechanism for OCS is extrinsic orbital compression, resulting in increased IOP and subsequent CRAO.¹⁰ A cherry red spot is visible on fundoscopy, as only the macula with its thin retinal layer will permit the choroidal vessels to be visualized. In a separate process, the relative increase in orbital pressure may lead to impaired perfusion or damage of CN III. However, a causative relationship between the 2 may be difficult to establish. Such an injury to the oculomotor nerve is demonstrated by impaired function of the inferior oblique, superior rectus, inferior rectus, and medial rectus muscles, which may persist even after the compressive symptoms of OCS have resolved.¹² Other reported symptoms of OCS include erythema, ophthalmoplegia, conjunctival chemosis, ptosis, corneal abrasion, and eyelid edema.^12-15

Alternate Diagnoses

OCS is a diagnosis of exclusion, and several alternate mechanisms were considered before identifying it as the likely etiology. The patient’s preoperative imaging demonstrated a stable enhancing mass involving the left great sphenoid wing and left cavernous sinus, with displacement of the left middle cerebral artery, left cavernous internal carotid artery, and left optic canal. Dissection and removal of this tumor could have compromised the arterial or venous blood supply to the orbit, thus causing ischemia to the retina and other ocular structures. CN III was manipulated during surgery, and it may have been inadvertently damaged during exposure or resection of the tumor.

The patient’s Valsalva-dependent patent foramen ovale put her at risk of a paroxysmal embolus as an alternate explanation, particularly as a Valsalva maneuver was utilized to confirm hemostasis. The patient did not, however, demonstrate any evidence of venous thromboembolism (VTE) on ultrasound, nor did she have the common risk factors of hypertension, diabetes, or smoking history that would increase VTE risk.¹⁶Her cancer diagnosis and surgical status may have put her at risk of VTE, but she did not have any clinical or laboratory values suggestive of hypercoagulability. Had an embolism occurred, it may have compromised the orbital blood supply and led to the CRAO. A similar scenario may have occurred from an atherosclerotic plaque in either of her carotid arteries, as she did have evidence of atherosclerosis on postoperative CT angiography. However, atherosclerosis as a risk factor for POVL appears to be related more to its impact upon impaired blood supply rather than as an embolic source. The patient did not have any significant intraoperative hypotensive episodes, making ION in the setting of atherosclerosis and hypotension a less likely etiology.¹⁷

This patient differed from other reported OCS cases. She was never placed in a prone or jackknife position, nor was she agitated or straining for a sustained period. These factors, along with the fact that the orbital compartment was not entered, decreased the likelihood of intraorbital hemorrhage and other intrinsic causes of elevated IOP.¹² Additionally, the presentation of our patient’s vision loss was delayed compared with other cases, despite clinicians observing a dilated left pupil and CN III palsy on examination immediately after surgery.¹⁴ It is significant to note that OCS may not demonstrate a significant increase in IOP once the source of compression is removed, which may explain the absence of proptosis on her postoperative examination.

The diagnosis of OCS was primarily implicated by the positioning of the myocutaneous flap during the pterional approach to craniotomy. It was retracted anteriorly and superiorly, ultimately resting over her left orbit for most of the 10-hour surgery. Kim and colleagues found that myocutaneous flaps may increase IOP as much as 17.5 mm Hg if improperly positioned, providing an unrecognized source of compression and increasing the risk of damage to orbital contents. According to their review, elevated IOP > 40 mm Hg, particularly over several hours, can compromise blood flow to the optic nerve and increase the risk for POVL.¹⁸ The flap was secured using fish hooks and rubber bands. However, it is suspected that the orbital rim did not fully support its pressure, thereby resting to some degree directly on the globe for an extended period and compromising the orbital blood supply. There are no current methods for measuring intraoperative IOP, though surrogate markers are under investigation and may yield clinical utility.¹⁸ The myocutaneous flap was created and positioned by the surgeons, but it may be that increased vigilance and communication from the anesthesia and nursing teams could have prevented it from remaining in an improper position.

Conclusions

Despite having few reported cases, OCS must be considered in neurosurgical patients with ophthalmoplegia and CRAO on postoperative examinations. Myocutaneous flaps that are retracted across the orbit can lead to significant elevations in IOP, leading to vision loss, which likely occurred with the patient in this case. Though protecting neurovascular structures is within the purview of the surgeon, all members of the intraoperative team should assist with ensuring proper flap positioning. These measures can help ensure adequate blood flow to the ophthalmic artery, decrease the likelihood of elevated IOP due to extrinsic compression, and help prevent the development of POVL and OCS in these patients.

Perioperative visual loss (POVL) is a well-documented yet uncommon complication of nonocular surgery. Patients undergoing cardiac and spinal surgery are at the greatest risk, though POVL may occur during other neurosurgical and vascular procedures as well. The most common causes of POVL are central retinal artery occlusion (CRAO) and ischemic optic neuropathy (ION),^1-3 though cases of orbital compartment syndrome (OCS) have also been reported.^4-7

We describe a case of POVL during a temporal meningioma excision using the pterional approach. Though the etiology is not fully understood, the patient’s clinical course was complicated by a third cranial nerve (CN III) palsy and CRAO, which, together with the patient’s presentation, were consistent with previously documented cases of OCS. The goals of this case report are to increase awareness of this surgical outcome, identify practices that may have contributed to its development, and delineate methods to minimize its occurrence.

Informed consent regarding this research was obtained from the patient and an institutional Health Insurance Portability and Accountability Act authorization form was completed. This manuscript adheres to the applicable Enhancing the Quality and Transparency of Health Research guideline.⁸

Case Presentation

A 47-year-old woman underwent a left temporal craniotomy for resection of a sphenoid wing meningioma discovered during a workup for persistent headaches. She had no medical history of diabetes, hypertension, coronary artery disease, or ophthalmic disease. Two months before her scheduled surgery, the patient reported bilateral blurry vision and underwent ophthalmologic evaluation. Her intraocular pressure (IOP) was normal, and she had no pupillary or retinal disease. She showed evidence of decreased vision in her left eye, suggesting a possible mass effect from her meningioma. Subsequent imaging of the optic nerve and retina had unremarkable physiology (Figure 1). Preoperative magnetic resonance imaging (MRI) demonstrated a stable enhancing mass involving the left great sphenoid wing and left cavernous sinus(Figure 2). There was a superior mass effect on the left middle cerebral artery, but all vessels were patent without evidence of thrombosis.

The patient underwent general anesthesia with invasive hemodynamic monitoring used throughout the procedure. She was induced with fentanyl, propofol, and rocuronium; anesthesia was maintained with isoflurane and a remifentanil infusion. Hypotension was treated with phenylephrine and intravenous fluids. Intraoperative neuromonitoring with electroencephalogram (EEG) and somatosensory evoked potentials was performed. During the surgery, the patient was positioned supine in a Mayfield 3-point head fixation system. All pressure points were padded appropriately and continually checked. A standard left pterional craniotomy was performed, and the scalp was reflected anteriorly and secured using fish hooks with rubber bands. The operation did not violate the cavernous sinus or orbital compartment. There was no evidence of active bleeding upon inspection nor with the Valsalva maneuver. No changes were noted in EEG or somatosensory evoked potentials; blood pressure remained within 20 mm Hg of the patient’s baseline. She was extubated at the end of the 10-hour case and was hemodynamically stable upon transport to the surgical intensive care unit. Postoperative imaging confirmed the successful removal of the left sphenoid wing meningioma.

The patient’s postoperative examination demonstrated a 5 mm dilated, nonresponsive left pupil, though the patient did not report visual loss at that time. Defects were noted in the inferior oblique, superior, inferior, and medial rectus muscles, consistent with CN III palsy. The surgery included manipulation of CN III, which made this a possible outcome, but an alternate causative pathology like OCS was not immediately suspected. Postoperative computed tomography (CT) showed an expected pneumocephalus and left scalp swelling without evidence of mass effect or midline shift.

Repeat MRI showed denervation of the left medial rectus and minimal left-sided proptosis. A 3-month ophthalmologic follow-up revealed a persistent CN III palsy, including an afferent pupillary defect, absence of light perception in her left eye, and continued ophthalmoplegia. Repeat examination showed a left-sided 4+ afferent pupillary defect unreactive to light, 4+ pallor surrounding the optic nerve, macular atrophy, sclerotic vessels, and 17 mm Hg intraocular pressure bilaterally. The eye had diffuse atrophy of the inner retina and significant patchy atrophy of the outer retinal components without neovascularization of the iris. Postoperative retinal imaging can be seen in Figure 3. Her vision loss persisted at this encounter and has continued through subsequent follow-up examinations.

Discussion

Perioperative visual loss is a rare surgical complication, with an estimated incidence of once in every 60,000 to 125,000 cases.⁹ The mechanism of injury is variable and dependent upon the type of surgical intervention, with cardiac and spine surgeries carrying the greatest risk.^10,11 The injury often results in either CRAO or ION, which may result in visual loss.^1-3 POVL can also occur in the aftermath of rapid changes in intracranial pressure during decompressive craniotomies, though the pathophysiology in such cases is not well understood.⁵

Among the myriad ways in which POVL can occur, neurosurgical cases carry the unique risk of direct cranial nerve injury. Such an insult can lead to vision loss via optic nerve damage or ophthalmoplegia if damage occurs to CN III, IV, or VI. This can occur during manipulation or resection, especially if the surgical approach involves the orbital cavity or the cavernous sinus. Though neither space was entered in this patient, direct injury cannot be ruled out as the etiology for either her vision loss or persistent ophthalmoplegia. An alternate causative scenario for both symptoms involve an impaired blood supply, with the vision loss potentially occurring secondary to CRAO and the ophthalmoplegia to an alternate cause of decreased blood flow. It is unclear which of these 2 conditions occurred first or if they occurred due to the same insult, but OCS could lead to both. Though it is a less common etiology for POVL, this patient’s presentation was similar to those in previously reported cases, and OCS was identified as the likely diagnosis.

OCS is precipitated by an elevated orbital pressure, which leads to ischemia of the retina and damage to orbital contents. Though associated with retrobulbar hemorrhage and orbital trauma, another proposed mechanism for OCS is extrinsic orbital compression, resulting in increased IOP and subsequent CRAO.¹⁰ A cherry red spot is visible on fundoscopy, as only the macula with its thin retinal layer will permit the choroidal vessels to be visualized. In a separate process, the relative increase in orbital pressure may lead to impaired perfusion or damage of CN III. However, a causative relationship between the 2 may be difficult to establish. Such an injury to the oculomotor nerve is demonstrated by impaired function of the inferior oblique, superior rectus, inferior rectus, and medial rectus muscles, which may persist even after the compressive symptoms of OCS have resolved.¹² Other reported symptoms of OCS include erythema, ophthalmoplegia, conjunctival chemosis, ptosis, corneal abrasion, and eyelid edema.^12-15

Alternate Diagnoses

OCS is a diagnosis of exclusion, and several alternate mechanisms were considered before identifying it as the likely etiology. The patient’s preoperative imaging demonstrated a stable enhancing mass involving the left great sphenoid wing and left cavernous sinus, with displacement of the left middle cerebral artery, left cavernous internal carotid artery, and left optic canal. Dissection and removal of this tumor could have compromised the arterial or venous blood supply to the orbit, thus causing ischemia to the retina and other ocular structures. CN III was manipulated during surgery, and it may have been inadvertently damaged during exposure or resection of the tumor.

The patient’s Valsalva-dependent patent foramen ovale put her at risk of a paroxysmal embolus as an alternate explanation, particularly as a Valsalva maneuver was utilized to confirm hemostasis. The patient did not, however, demonstrate any evidence of venous thromboembolism (VTE) on ultrasound, nor did she have the common risk factors of hypertension, diabetes, or smoking history that would increase VTE risk.¹⁶Her cancer diagnosis and surgical status may have put her at risk of VTE, but she did not have any clinical or laboratory values suggestive of hypercoagulability. Had an embolism occurred, it may have compromised the orbital blood supply and led to the CRAO. A similar scenario may have occurred from an atherosclerotic plaque in either of her carotid arteries, as she did have evidence of atherosclerosis on postoperative CT angiography. However, atherosclerosis as a risk factor for POVL appears to be related more to its impact upon impaired blood supply rather than as an embolic source. The patient did not have any significant intraoperative hypotensive episodes, making ION in the setting of atherosclerosis and hypotension a less likely etiology.¹⁷

This patient differed from other reported OCS cases. She was never placed in a prone or jackknife position, nor was she agitated or straining for a sustained period. These factors, along with the fact that the orbital compartment was not entered, decreased the likelihood of intraorbital hemorrhage and other intrinsic causes of elevated IOP.¹² Additionally, the presentation of our patient’s vision loss was delayed compared with other cases, despite clinicians observing a dilated left pupil and CN III palsy on examination immediately after surgery.¹⁴ It is significant to note that OCS may not demonstrate a significant increase in IOP once the source of compression is removed, which may explain the absence of proptosis on her postoperative examination.

The diagnosis of OCS was primarily implicated by the positioning of the myocutaneous flap during the pterional approach to craniotomy. It was retracted anteriorly and superiorly, ultimately resting over her left orbit for most of the 10-hour surgery. Kim and colleagues found that myocutaneous flaps may increase IOP as much as 17.5 mm Hg if improperly positioned, providing an unrecognized source of compression and increasing the risk of damage to orbital contents. According to their review, elevated IOP > 40 mm Hg, particularly over several hours, can compromise blood flow to the optic nerve and increase the risk for POVL.¹⁸ The flap was secured using fish hooks and rubber bands. However, it is suspected that the orbital rim did not fully support its pressure, thereby resting to some degree directly on the globe for an extended period and compromising the orbital blood supply. There are no current methods for measuring intraoperative IOP, though surrogate markers are under investigation and may yield clinical utility.¹⁸ The myocutaneous flap was created and positioned by the surgeons, but it may be that increased vigilance and communication from the anesthesia and nursing teams could have prevented it from remaining in an improper position.

Conclusions

Despite having few reported cases, OCS must be considered in neurosurgical patients with ophthalmoplegia and CRAO on postoperative examinations. Myocutaneous flaps that are retracted across the orbit can lead to significant elevations in IOP, leading to vision loss, which likely occurred with the patient in this case. Though protecting neurovascular structures is within the purview of the surgeon, all members of the intraoperative team should assist with ensuring proper flap positioning. These measures can help ensure adequate blood flow to the ophthalmic artery, decrease the likelihood of elevated IOP due to extrinsic compression, and help prevent the development of POVL and OCS in these patients.

Perioperative visual loss (POVL) is a well-documented yet uncommon complication of nonocular surgery. Patients undergoing cardiac and spinal surgery are at the greatest risk, though POVL may occur during other neurosurgical and vascular procedures as well. The most common causes of POVL are central retinal artery occlusion (CRAO) and ischemic optic neuropathy (ION),^1-3 though cases of orbital compartment syndrome (OCS) have also been reported.^4-7

We describe a case of POVL during a temporal meningioma excision using the pterional approach. Though the etiology is not fully understood, the patient’s clinical course was complicated by a third cranial nerve (CN III) palsy and CRAO, which, together with the patient’s presentation, were consistent with previously documented cases of OCS. The goals of this case report are to increase awareness of this surgical outcome, identify practices that may have contributed to its development, and delineate methods to minimize its occurrence.

Informed consent regarding this research was obtained from the patient and an institutional Health Insurance Portability and Accountability Act authorization form was completed. This manuscript adheres to the applicable Enhancing the Quality and Transparency of Health Research guideline.⁸

Case Presentation

A 47-year-old woman underwent a left temporal craniotomy for resection of a sphenoid wing meningioma discovered during a workup for persistent headaches. She had no medical history of diabetes, hypertension, coronary artery disease, or ophthalmic disease. Two months before her scheduled surgery, the patient reported bilateral blurry vision and underwent ophthalmologic evaluation. Her intraocular pressure (IOP) was normal, and she had no pupillary or retinal disease. She showed evidence of decreased vision in her left eye, suggesting a possible mass effect from her meningioma. Subsequent imaging of the optic nerve and retina had unremarkable physiology (Figure 1). Preoperative magnetic resonance imaging (MRI) demonstrated a stable enhancing mass involving the left great sphenoid wing and left cavernous sinus(Figure 2). There was a superior mass effect on the left middle cerebral artery, but all vessels were patent without evidence of thrombosis.

The patient underwent general anesthesia with invasive hemodynamic monitoring used throughout the procedure. She was induced with fentanyl, propofol, and rocuronium; anesthesia was maintained with isoflurane and a remifentanil infusion. Hypotension was treated with phenylephrine and intravenous fluids. Intraoperative neuromonitoring with electroencephalogram (EEG) and somatosensory evoked potentials was performed. During the surgery, the patient was positioned supine in a Mayfield 3-point head fixation system. All pressure points were padded appropriately and continually checked. A standard left pterional craniotomy was performed, and the scalp was reflected anteriorly and secured using fish hooks with rubber bands. The operation did not violate the cavernous sinus or orbital compartment. There was no evidence of active bleeding upon inspection nor with the Valsalva maneuver. No changes were noted in EEG or somatosensory evoked potentials; blood pressure remained within 20 mm Hg of the patient’s baseline. She was extubated at the end of the 10-hour case and was hemodynamically stable upon transport to the surgical intensive care unit. Postoperative imaging confirmed the successful removal of the left sphenoid wing meningioma.

The patient’s postoperative examination demonstrated a 5 mm dilated, nonresponsive left pupil, though the patient did not report visual loss at that time. Defects were noted in the inferior oblique, superior, inferior, and medial rectus muscles, consistent with CN III palsy. The surgery included manipulation of CN III, which made this a possible outcome, but an alternate causative pathology like OCS was not immediately suspected. Postoperative computed tomography (CT) showed an expected pneumocephalus and left scalp swelling without evidence of mass effect or midline shift.

Repeat MRI showed denervation of the left medial rectus and minimal left-sided proptosis. A 3-month ophthalmologic follow-up revealed a persistent CN III palsy, including an afferent pupillary defect, absence of light perception in her left eye, and continued ophthalmoplegia. Repeat examination showed a left-sided 4+ afferent pupillary defect unreactive to light, 4+ pallor surrounding the optic nerve, macular atrophy, sclerotic vessels, and 17 mm Hg intraocular pressure bilaterally. The eye had diffuse atrophy of the inner retina and significant patchy atrophy of the outer retinal components without neovascularization of the iris. Postoperative retinal imaging can be seen in Figure 3. Her vision loss persisted at this encounter and has continued through subsequent follow-up examinations.

Discussion

Perioperative visual loss is a rare surgical complication, with an estimated incidence of once in every 60,000 to 125,000 cases.⁹ The mechanism of injury is variable and dependent upon the type of surgical intervention, with cardiac and spine surgeries carrying the greatest risk.^10,11 The injury often results in either CRAO or ION, which may result in visual loss.^1-3 POVL can also occur in the aftermath of rapid changes in intracranial pressure during decompressive craniotomies, though the pathophysiology in such cases is not well understood.⁵

Among the myriad ways in which POVL can occur, neurosurgical cases carry the unique risk of direct cranial nerve injury. Such an insult can lead to vision loss via optic nerve damage or ophthalmoplegia if damage occurs to CN III, IV, or VI. This can occur during manipulation or resection, especially if the surgical approach involves the orbital cavity or the cavernous sinus. Though neither space was entered in this patient, direct injury cannot be ruled out as the etiology for either her vision loss or persistent ophthalmoplegia. An alternate causative scenario for both symptoms involve an impaired blood supply, with the vision loss potentially occurring secondary to CRAO and the ophthalmoplegia to an alternate cause of decreased blood flow. It is unclear which of these 2 conditions occurred first or if they occurred due to the same insult, but OCS could lead to both. Though it is a less common etiology for POVL, this patient’s presentation was similar to those in previously reported cases, and OCS was identified as the likely diagnosis.

OCS is precipitated by an elevated orbital pressure, which leads to ischemia of the retina and damage to orbital contents. Though associated with retrobulbar hemorrhage and orbital trauma, another proposed mechanism for OCS is extrinsic orbital compression, resulting in increased IOP and subsequent CRAO.¹⁰ A cherry red spot is visible on fundoscopy, as only the macula with its thin retinal layer will permit the choroidal vessels to be visualized. In a separate process, the relative increase in orbital pressure may lead to impaired perfusion or damage of CN III. However, a causative relationship between the 2 may be difficult to establish. Such an injury to the oculomotor nerve is demonstrated by impaired function of the inferior oblique, superior rectus, inferior rectus, and medial rectus muscles, which may persist even after the compressive symptoms of OCS have resolved.¹² Other reported symptoms of OCS include erythema, ophthalmoplegia, conjunctival chemosis, ptosis, corneal abrasion, and eyelid edema.^12-15

Alternate Diagnoses

OCS is a diagnosis of exclusion, and several alternate mechanisms were considered before identifying it as the likely etiology. The patient’s preoperative imaging demonstrated a stable enhancing mass involving the left great sphenoid wing and left cavernous sinus, with displacement of the left middle cerebral artery, left cavernous internal carotid artery, and left optic canal. Dissection and removal of this tumor could have compromised the arterial or venous blood supply to the orbit, thus causing ischemia to the retina and other ocular structures. CN III was manipulated during surgery, and it may have been inadvertently damaged during exposure or resection of the tumor.

The patient’s Valsalva-dependent patent foramen ovale put her at risk of a paroxysmal embolus as an alternate explanation, particularly as a Valsalva maneuver was utilized to confirm hemostasis. The patient did not, however, demonstrate any evidence of venous thromboembolism (VTE) on ultrasound, nor did she have the common risk factors of hypertension, diabetes, or smoking history that would increase VTE risk.¹⁶Her cancer diagnosis and surgical status may have put her at risk of VTE, but she did not have any clinical or laboratory values suggestive of hypercoagulability. Had an embolism occurred, it may have compromised the orbital blood supply and led to the CRAO. A similar scenario may have occurred from an atherosclerotic plaque in either of her carotid arteries, as she did have evidence of atherosclerosis on postoperative CT angiography. However, atherosclerosis as a risk factor for POVL appears to be related more to its impact upon impaired blood supply rather than as an embolic source. The patient did not have any significant intraoperative hypotensive episodes, making ION in the setting of atherosclerosis and hypotension a less likely etiology.¹⁷

This patient differed from other reported OCS cases. She was never placed in a prone or jackknife position, nor was she agitated or straining for a sustained period. These factors, along with the fact that the orbital compartment was not entered, decreased the likelihood of intraorbital hemorrhage and other intrinsic causes of elevated IOP.¹² Additionally, the presentation of our patient’s vision loss was delayed compared with other cases, despite clinicians observing a dilated left pupil and CN III palsy on examination immediately after surgery.¹⁴ It is significant to note that OCS may not demonstrate a significant increase in IOP once the source of compression is removed, which may explain the absence of proptosis on her postoperative examination.

The diagnosis of OCS was primarily implicated by the positioning of the myocutaneous flap during the pterional approach to craniotomy. It was retracted anteriorly and superiorly, ultimately resting over her left orbit for most of the 10-hour surgery. Kim and colleagues found that myocutaneous flaps may increase IOP as much as 17.5 mm Hg if improperly positioned, providing an unrecognized source of compression and increasing the risk of damage to orbital contents. According to their review, elevated IOP > 40 mm Hg, particularly over several hours, can compromise blood flow to the optic nerve and increase the risk for POVL.¹⁸ The flap was secured using fish hooks and rubber bands. However, it is suspected that the orbital rim did not fully support its pressure, thereby resting to some degree directly on the globe for an extended period and compromising the orbital blood supply. There are no current methods for measuring intraoperative IOP, though surrogate markers are under investigation and may yield clinical utility.¹⁸ The myocutaneous flap was created and positioned by the surgeons, but it may be that increased vigilance and communication from the anesthesia and nursing teams could have prevented it from remaining in an improper position.

Conclusions

Despite having few reported cases, OCS must be considered in neurosurgical patients with ophthalmoplegia and CRAO on postoperative examinations. Myocutaneous flaps that are retracted across the orbit can lead to significant elevations in IOP, leading to vision loss, which likely occurred with the patient in this case. Though protecting neurovascular structures is within the purview of the surgeon, all members of the intraoperative team should assist with ensuring proper flap positioning. These measures can help ensure adequate blood flow to the ophthalmic artery, decrease the likelihood of elevated IOP due to extrinsic compression, and help prevent the development of POVL and OCS in these patients.

The circulation of cerebrospinal fluid (CSF) is crucial for maintaining homeostasis for the optimal functioning of the multiple complex activities of the brain and spinal cord, including the disposal of metabolic waste products of brain and spinal cord activity into the cerebral venous drainage. Throughout the brain, the arachnoid mater forms small outpouchings or diverticula that penetrate the dura mater and communicate with the dural venous sinuses. These outpuchings are called arachnoid granulations or arachnoid villi, and most are found within the dural sinuses, primarily in the transverse sinuses and superior sagittal sinus, but can occasionally be seen extending into the inner table of the calvarium.^1,2

The amount of arachnoid granulations seen in bone, particularly around the superior sagittal sinus, may increase with age.² Arachnoid granulations are generally small but the largest ones can be seen on gross examination during intracranial procedures or autopsy.³ Magnetic resonance imaging (MRI) can detect arachnoid granulations, which are characterized as T1 hypointense and T2 hyperintense (CSF isointense), well-circumscribed, small, nonenhancing masses within the dural sinuses or in the diploic space (Figure 1). Even small arachnoid granulations < 1 mm in length can be detected.²

Smaller arachnoid granulations have been described histologically as entirely covered by a dural membrane, thus creating a subdural space that separates the body of the arachnoid granulation from the lumen of the accompanying venous sinus.⁴ However, larger arachnoid granulations may not be completely covered by a dural membrane, thus creating a point of contact between the arachnoid granulation and the venous sinus.⁴ Larger arachnoid granulations are normally filled with CSF, and their signal characteristics are similar to CSF on imaging.^5,6 Arachnoid granulations also often contain vessels draining into the adjacent venous sinus.^5,6

When larger arachnoid granulations are present, they may permit the protrusion of herniated brain tissue. There has been an increasing number of reports of these brain herniations into arachnoid granulations (BHAGs) in the literature.^7-10 While these herniations have been associated with nonspecific neurologic symptoms like tinnitus and idiopathic intracranial hypertension, their true clinical significance remains undetermined.^10,11 This article presents 5 cases of BHAG, discusses their clinical presentations and image findings, and reviews the current literature.

Case 1

A 30-year-old male with a history of multiple traumatic brain injuries presented for evaluation of seizures. The patient described the semiology of the seizures as a bright, colorful light in his right visual field, followed by loss of vision, then loss of awareness and full body convulsion. The semiology of this patient’s seizures was consistent with left temporo-occipital lobe seizure. The only abnormality seen in the brain MRI was the herniation of brain parenchyma originating from the occipital lobe into the transverse sinus, presumably through an arachnoid granulation (Figure 1). An electroencephalogram (EEG) was unremarkable, though the semiology of the seizure historically described by the patient was localized to the area of BHAG. The patient is currently taking antiseizure medications and has experienced no additional seizures.

Case 2

A male aged 53 years with a history of peripheral artery disease presented with a 6-month history of headaches and dizziness. The patient reported the onset of visual aura to his right visual field, starting as a fingernail-sized scintillating kaleidoscope light that would gradually increase in size to a round shape with fading kaleidoscope colors. This episode would last for a few minutes and was immediately followed by a headache. There was no alteration of consciousness during visual aura, although sometimes the patient would have right-sided scalp tingling. These episodes were often unprovoked, but occasionally triggered by bright lights. A single routine EEG was unremarkable. The patient reported headaches without aura, but not aura without headaches, which made occipital lobe seizure less likely. MRI demonstrated a small herniation of brain parenchyma into the inner table of the left occipital bone (Figure 2). The patient was diagnosed with migraine with aura, and the semiology of the visual aura corresponded to the location of the herniation in the left occipital region.

Case 3

A 77-year-old male with a history of left ear diving injury presented with left-sided asymmetric hearing loss and word recognition difficulty for several years. MRI obtained as part of his work-up to evaluate for possible schwannoma of the eighth left cranial nerve instead demonstrated an incidental right cerebellar herniation within an arachnoid granulation into the diploic space of the occipital bone (Figure 3). The BHAG for this patient appeared to be an incidental finding unrelated to his asymmetric hearing loss.

Case 4

A male aged 62 years with a history of metastatic esophageal cancer, substance abuse, and a prior presumed alcohol withdrawal seizure underwent an MRI for evaluation of brain metastasis after presenting to the hospital with confusion 1 day after starting chemotherapy (Figure 4). Nine years prior, the patient had an isolated generalized tonic-clonic seizure approximately 72 hours following a period of alcohol cessation. The MRI demonstrated an incidental left parasagittal herniation of left parietal lobe tissue through an arachnoid granulation into the superior sagittal sinus, in addition to metastatic brain lesions. An EEG showed mild encephalopathy without evidence of seizures. It was determined that the patient's confusion was most likely due to toxic-metabolic encephalopathy from chemotherapy.

Case 5

A 51-year-old male presented with worsening headache severity and frequency. He had a history of chronic headaches for about 20 years that occurred annually, but were now occurring twice weekly. The headaches often started with a left eye visual aura followed by pressure in the left eye, left frontal region, and left ear, with at times a cervicogenic component. No cervical spine imaging was available. An MRI revealed 2 small adjacent areas of cerebellar herniation into arachnoid granulations in the left occipital bone (Figure 5).

Arachnoid granulations appear very early in life, although they are uncommon before age 2 years.² Classically, they have been understood to act as 1-way valves permitting the outflow of CSF from the subarachnoid space to the dural venous sinuses. However, increasing evidence shows they may only play a minor role in that process.¹² The structure of arachnoid granulations is being reexamined. A recent microscopy study demonstrated structural heterogeneity with a fine, porous lining that permits flow.¹³ Additionally, associated immune components in the microenvironment suggests that arachnoid granulations may function similarly to lymph nodes as part of a central nervous system lymphatic network.¹³ Evidence is lacking for arachnoid granulations being the primary route of CSF outflow, and newer models include CSF exit pathways along the cranial nerves and drainage through lymphatics within the dura mater.¹²

New MRI systems have demonstrated that the prevalence of arachnoid granulations increases with age. One study found that all subjects in the aged 40 years cohort had detectable arachnoid granulations on images obtained with a 3T MRI system, with the main site being the superior sagittal sinus.² The prevalence increased until age 40 years and then noticeably decreased. Not only did the prevalence increase in this pattern, but the total number of detectable arachnoid granulations followed a similar pattern.² In addition, the detectable arachnoid granulations tend to be larger in older patients. Arachnoid granulations are very common in adults, but little is known about when and why brain tissue herniates through these structures.

This case series illustrates how a small amount of adult cerebral or cerebellar matter in large arachnoid granulations can herniate into the dural sinuses and diploic space. Although arachnoid granulations extending into the dural sinuses and diploic space are a relatively common finding on MRI,BHAGs are rare in these locations.^1,2,8 Improved spatial resolution afforded by newer high-field scanners with thinner sections, such as very thin (1 mm) T1- and heavily T2-weighted 3 dimensional sequences may lead to increased detection of BHAG. Some of these herniations are small and may be easily missed or confused for normal arachnoid granulations on 3 to 5 mm thickness MRIs.

Despite increased recognition, it is still uncertain to what degree these herniations contribute to the clinical presentations. Associated neurologic symptoms may include seizures, headaches, tinnitus, syncope, and increased intracranial pressure.^7-10

Three cases presented in this article demonstrated abnormal signals adjacent to the herniated brain, presumably due to dysplasia of gliotic tissue. In 1 study, parenchymal signal and structural changes occurred in about one-half of the reported BHAG, all of which were cerebellar herniations.⁷ In Case 1, the herniation and adjacent abnormal MRI signal corresponded to localization of the seizure semiology as obtained from patient history, strongly suggesting the BHAG played a role in the presentation. Signal abnormality accompanying an adjacent BHAG may suggest a higher likelihood that the BHAG has clinical relevance. However, the patient in Case 2 had a visual aura that corresponded to the BHAG location, so a signal abnormality may not be necessary for a patient to develop symptoms. Case 1 also included a history of documented traumatic brain injuries, suggesting that perhaps head trauma may facilitate BHAG development. Regardless, there is likely also a congenital component to their formation, as BHAG has been observed in the pediatric population.¹⁴

The patient's asymmetric left-sided hearing loss in Case 3 appeared unrelated to the BHAG as its location was in the contralateral cerebellar region and did not correspond to the patient’s clinical findings. The patient in Case 4 had a limited history regarding localization details of their prior presumed alcohol withdrawal seizure, such as head movements, eye deviation, or lateralized onset of convulsions. Given this limited data, it is unclear whether their prior seizure could have been related to BHAG or not. The patient in case 5 reported worsening headaches on the left side of his head, which corresponded to BHAG occurring on the left side. However, given that the increased T2 signal occurred in the left cerebellar hemisphere with BHAG in the left occipital bone, the occipital cortex was not involved. In this case, the BHAG would not explain the patient’s visual aura as such a lesion would have been expected in the right occipital cortex rather than its actual location in this patient’s left cerebellar hemisphere.

CONCLUSIONS

Understanding the clinical impact of brain herniations is important because they are probably more common than previously thought. Improved MRI capabilities suggest that more BHAG will be detected moving forward as radiologists interpret images with higher resolution and thinner slices. Until its significance is fully understood, BHAG will continue to complicate the diagnosis of patients with neurologic complaints whose brain MRIs and EEGs are otherwise unremarkable.

There have been no cases of surgical BHAG intervention and pathology analysis that would help determine their clinical significance. A related entity, temporal lobe encephalocele, has been linked to focal temporal lobe epilepsy, which has demonstrated significant symptom improvement following surgical correction.¹⁵ However, encephaloceles have been distinguished from BHAG in part because they do not necessarily herniate through an arachnoid granulation.⁸ BHAG has only begun to be characterized in detail over the last decade, so more research is needed to understand how it develops and what clinical significance it truly holds.

The circulation of cerebrospinal fluid (CSF) is crucial for maintaining homeostasis for the optimal functioning of the multiple complex activities of the brain and spinal cord, including the disposal of metabolic waste products of brain and spinal cord activity into the cerebral venous drainage. Throughout the brain, the arachnoid mater forms small outpouchings or diverticula that penetrate the dura mater and communicate with the dural venous sinuses. These outpuchings are called arachnoid granulations or arachnoid villi, and most are found within the dural sinuses, primarily in the transverse sinuses and superior sagittal sinus, but can occasionally be seen extending into the inner table of the calvarium.^1,2

The amount of arachnoid granulations seen in bone, particularly around the superior sagittal sinus, may increase with age.² Arachnoid granulations are generally small but the largest ones can be seen on gross examination during intracranial procedures or autopsy.³ Magnetic resonance imaging (MRI) can detect arachnoid granulations, which are characterized as T1 hypointense and T2 hyperintense (CSF isointense), well-circumscribed, small, nonenhancing masses within the dural sinuses or in the diploic space (Figure 1). Even small arachnoid granulations < 1 mm in length can be detected.²

Smaller arachnoid granulations have been described histologically as entirely covered by a dural membrane, thus creating a subdural space that separates the body of the arachnoid granulation from the lumen of the accompanying venous sinus.⁴ However, larger arachnoid granulations may not be completely covered by a dural membrane, thus creating a point of contact between the arachnoid granulation and the venous sinus.⁴ Larger arachnoid granulations are normally filled with CSF, and their signal characteristics are similar to CSF on imaging.^5,6 Arachnoid granulations also often contain vessels draining into the adjacent venous sinus.^5,6

When larger arachnoid granulations are present, they may permit the protrusion of herniated brain tissue. There has been an increasing number of reports of these brain herniations into arachnoid granulations (BHAGs) in the literature.^7-10 While these herniations have been associated with nonspecific neurologic symptoms like tinnitus and idiopathic intracranial hypertension, their true clinical significance remains undetermined.^10,11 This article presents 5 cases of BHAG, discusses their clinical presentations and image findings, and reviews the current literature.

Case 1

A 30-year-old male with a history of multiple traumatic brain injuries presented for evaluation of seizures. The patient described the semiology of the seizures as a bright, colorful light in his right visual field, followed by loss of vision, then loss of awareness and full body convulsion. The semiology of this patient’s seizures was consistent with left temporo-occipital lobe seizure. The only abnormality seen in the brain MRI was the herniation of brain parenchyma originating from the occipital lobe into the transverse sinus, presumably through an arachnoid granulation (Figure 1). An electroencephalogram (EEG) was unremarkable, though the semiology of the seizure historically described by the patient was localized to the area of BHAG. The patient is currently taking antiseizure medications and has experienced no additional seizures.

Case 2

A male aged 53 years with a history of peripheral artery disease presented with a 6-month history of headaches and dizziness. The patient reported the onset of visual aura to his right visual field, starting as a fingernail-sized scintillating kaleidoscope light that would gradually increase in size to a round shape with fading kaleidoscope colors. This episode would last for a few minutes and was immediately followed by a headache. There was no alteration of consciousness during visual aura, although sometimes the patient would have right-sided scalp tingling. These episodes were often unprovoked, but occasionally triggered by bright lights. A single routine EEG was unremarkable. The patient reported headaches without aura, but not aura without headaches, which made occipital lobe seizure less likely. MRI demonstrated a small herniation of brain parenchyma into the inner table of the left occipital bone (Figure 2). The patient was diagnosed with migraine with aura, and the semiology of the visual aura corresponded to the location of the herniation in the left occipital region.

Case 3

A 77-year-old male with a history of left ear diving injury presented with left-sided asymmetric hearing loss and word recognition difficulty for several years. MRI obtained as part of his work-up to evaluate for possible schwannoma of the eighth left cranial nerve instead demonstrated an incidental right cerebellar herniation within an arachnoid granulation into the diploic space of the occipital bone (Figure 3). The BHAG for this patient appeared to be an incidental finding unrelated to his asymmetric hearing loss.

Case 4

A male aged 62 years with a history of metastatic esophageal cancer, substance abuse, and a prior presumed alcohol withdrawal seizure underwent an MRI for evaluation of brain metastasis after presenting to the hospital with confusion 1 day after starting chemotherapy (Figure 4). Nine years prior, the patient had an isolated generalized tonic-clonic seizure approximately 72 hours following a period of alcohol cessation. The MRI demonstrated an incidental left parasagittal herniation of left parietal lobe tissue through an arachnoid granulation into the superior sagittal sinus, in addition to metastatic brain lesions. An EEG showed mild encephalopathy without evidence of seizures. It was determined that the patient's confusion was most likely due to toxic-metabolic encephalopathy from chemotherapy.

Case 5

A 51-year-old male presented with worsening headache severity and frequency. He had a history of chronic headaches for about 20 years that occurred annually, but were now occurring twice weekly. The headaches often started with a left eye visual aura followed by pressure in the left eye, left frontal region, and left ear, with at times a cervicogenic component. No cervical spine imaging was available. An MRI revealed 2 small adjacent areas of cerebellar herniation into arachnoid granulations in the left occipital bone (Figure 5).

Arachnoid granulations appear very early in life, although they are uncommon before age 2 years.² Classically, they have been understood to act as 1-way valves permitting the outflow of CSF from the subarachnoid space to the dural venous sinuses. However, increasing evidence shows they may only play a minor role in that process.¹² The structure of arachnoid granulations is being reexamined. A recent microscopy study demonstrated structural heterogeneity with a fine, porous lining that permits flow.¹³ Additionally, associated immune components in the microenvironment suggests that arachnoid granulations may function similarly to lymph nodes as part of a central nervous system lymphatic network.¹³ Evidence is lacking for arachnoid granulations being the primary route of CSF outflow, and newer models include CSF exit pathways along the cranial nerves and drainage through lymphatics within the dura mater.¹²

New MRI systems have demonstrated that the prevalence of arachnoid granulations increases with age. One study found that all subjects in the aged 40 years cohort had detectable arachnoid granulations on images obtained with a 3T MRI system, with the main site being the superior sagittal sinus.² The prevalence increased until age 40 years and then noticeably decreased. Not only did the prevalence increase in this pattern, but the total number of detectable arachnoid granulations followed a similar pattern.² In addition, the detectable arachnoid granulations tend to be larger in older patients. Arachnoid granulations are very common in adults, but little is known about when and why brain tissue herniates through these structures.

This case series illustrates how a small amount of adult cerebral or cerebellar matter in large arachnoid granulations can herniate into the dural sinuses and diploic space. Although arachnoid granulations extending into the dural sinuses and diploic space are a relatively common finding on MRI,BHAGs are rare in these locations.^1,2,8 Improved spatial resolution afforded by newer high-field scanners with thinner sections, such as very thin (1 mm) T1- and heavily T2-weighted 3 dimensional sequences may lead to increased detection of BHAG. Some of these herniations are small and may be easily missed or confused for normal arachnoid granulations on 3 to 5 mm thickness MRIs.

Despite increased recognition, it is still uncertain to what degree these herniations contribute to the clinical presentations. Associated neurologic symptoms may include seizures, headaches, tinnitus, syncope, and increased intracranial pressure.^7-10

Three cases presented in this article demonstrated abnormal signals adjacent to the herniated brain, presumably due to dysplasia of gliotic tissue. In 1 study, parenchymal signal and structural changes occurred in about one-half of the reported BHAG, all of which were cerebellar herniations.⁷ In Case 1, the herniation and adjacent abnormal MRI signal corresponded to localization of the seizure semiology as obtained from patient history, strongly suggesting the BHAG played a role in the presentation. Signal abnormality accompanying an adjacent BHAG may suggest a higher likelihood that the BHAG has clinical relevance. However, the patient in Case 2 had a visual aura that corresponded to the BHAG location, so a signal abnormality may not be necessary for a patient to develop symptoms. Case 1 also included a history of documented traumatic brain injuries, suggesting that perhaps head trauma may facilitate BHAG development. Regardless, there is likely also a congenital component to their formation, as BHAG has been observed in the pediatric population.¹⁴

The patient's asymmetric left-sided hearing loss in Case 3 appeared unrelated to the BHAG as its location was in the contralateral cerebellar region and did not correspond to the patient’s clinical findings. The patient in Case 4 had a limited history regarding localization details of their prior presumed alcohol withdrawal seizure, such as head movements, eye deviation, or lateralized onset of convulsions. Given this limited data, it is unclear whether their prior seizure could have been related to BHAG or not. The patient in case 5 reported worsening headaches on the left side of his head, which corresponded to BHAG occurring on the left side. However, given that the increased T2 signal occurred in the left cerebellar hemisphere with BHAG in the left occipital bone, the occipital cortex was not involved. In this case, the BHAG would not explain the patient’s visual aura as such a lesion would have been expected in the right occipital cortex rather than its actual location in this patient’s left cerebellar hemisphere.

CONCLUSIONS

Understanding the clinical impact of brain herniations is important because they are probably more common than previously thought. Improved MRI capabilities suggest that more BHAG will be detected moving forward as radiologists interpret images with higher resolution and thinner slices. Until its significance is fully understood, BHAG will continue to complicate the diagnosis of patients with neurologic complaints whose brain MRIs and EEGs are otherwise unremarkable.

There have been no cases of surgical BHAG intervention and pathology analysis that would help determine their clinical significance. A related entity, temporal lobe encephalocele, has been linked to focal temporal lobe epilepsy, which has demonstrated significant symptom improvement following surgical correction.¹⁵ However, encephaloceles have been distinguished from BHAG in part because they do not necessarily herniate through an arachnoid granulation.⁸ BHAG has only begun to be characterized in detail over the last decade, so more research is needed to understand how it develops and what clinical significance it truly holds.

The circulation of cerebrospinal fluid (CSF) is crucial for maintaining homeostasis for the optimal functioning of the multiple complex activities of the brain and spinal cord, including the disposal of metabolic waste products of brain and spinal cord activity into the cerebral venous drainage. Throughout the brain, the arachnoid mater forms small outpouchings or diverticula that penetrate the dura mater and communicate with the dural venous sinuses. These outpuchings are called arachnoid granulations or arachnoid villi, and most are found within the dural sinuses, primarily in the transverse sinuses and superior sagittal sinus, but can occasionally be seen extending into the inner table of the calvarium.^1,2

The amount of arachnoid granulations seen in bone, particularly around the superior sagittal sinus, may increase with age.² Arachnoid granulations are generally small but the largest ones can be seen on gross examination during intracranial procedures or autopsy.³ Magnetic resonance imaging (MRI) can detect arachnoid granulations, which are characterized as T1 hypointense and T2 hyperintense (CSF isointense), well-circumscribed, small, nonenhancing masses within the dural sinuses or in the diploic space (Figure 1). Even small arachnoid granulations < 1 mm in length can be detected.²

Smaller arachnoid granulations have been described histologically as entirely covered by a dural membrane, thus creating a subdural space that separates the body of the arachnoid granulation from the lumen of the accompanying venous sinus.⁴ However, larger arachnoid granulations may not be completely covered by a dural membrane, thus creating a point of contact between the arachnoid granulation and the venous sinus.⁴ Larger arachnoid granulations are normally filled with CSF, and their signal characteristics are similar to CSF on imaging.^5,6 Arachnoid granulations also often contain vessels draining into the adjacent venous sinus.^5,6

When larger arachnoid granulations are present, they may permit the protrusion of herniated brain tissue. There has been an increasing number of reports of these brain herniations into arachnoid granulations (BHAGs) in the literature.^7-10 While these herniations have been associated with nonspecific neurologic symptoms like tinnitus and idiopathic intracranial hypertension, their true clinical significance remains undetermined.^10,11 This article presents 5 cases of BHAG, discusses their clinical presentations and image findings, and reviews the current literature.

Case 1

A 30-year-old male with a history of multiple traumatic brain injuries presented for evaluation of seizures. The patient described the semiology of the seizures as a bright, colorful light in his right visual field, followed by loss of vision, then loss of awareness and full body convulsion. The semiology of this patient’s seizures was consistent with left temporo-occipital lobe seizure. The only abnormality seen in the brain MRI was the herniation of brain parenchyma originating from the occipital lobe into the transverse sinus, presumably through an arachnoid granulation (Figure 1). An electroencephalogram (EEG) was unremarkable, though the semiology of the seizure historically described by the patient was localized to the area of BHAG. The patient is currently taking antiseizure medications and has experienced no additional seizures.

Case 2

A male aged 53 years with a history of peripheral artery disease presented with a 6-month history of headaches and dizziness. The patient reported the onset of visual aura to his right visual field, starting as a fingernail-sized scintillating kaleidoscope light that would gradually increase in size to a round shape with fading kaleidoscope colors. This episode would last for a few minutes and was immediately followed by a headache. There was no alteration of consciousness during visual aura, although sometimes the patient would have right-sided scalp tingling. These episodes were often unprovoked, but occasionally triggered by bright lights. A single routine EEG was unremarkable. The patient reported headaches without aura, but not aura without headaches, which made occipital lobe seizure less likely. MRI demonstrated a small herniation of brain parenchyma into the inner table of the left occipital bone (Figure 2). The patient was diagnosed with migraine with aura, and the semiology of the visual aura corresponded to the location of the herniation in the left occipital region.

Case 3

A 77-year-old male with a history of left ear diving injury presented with left-sided asymmetric hearing loss and word recognition difficulty for several years. MRI obtained as part of his work-up to evaluate for possible schwannoma of the eighth left cranial nerve instead demonstrated an incidental right cerebellar herniation within an arachnoid granulation into the diploic space of the occipital bone (Figure 3). The BHAG for this patient appeared to be an incidental finding unrelated to his asymmetric hearing loss.

Case 4

A male aged 62 years with a history of metastatic esophageal cancer, substance abuse, and a prior presumed alcohol withdrawal seizure underwent an MRI for evaluation of brain metastasis after presenting to the hospital with confusion 1 day after starting chemotherapy (Figure 4). Nine years prior, the patient had an isolated generalized tonic-clonic seizure approximately 72 hours following a period of alcohol cessation. The MRI demonstrated an incidental left parasagittal herniation of left parietal lobe tissue through an arachnoid granulation into the superior sagittal sinus, in addition to metastatic brain lesions. An EEG showed mild encephalopathy without evidence of seizures. It was determined that the patient's confusion was most likely due to toxic-metabolic encephalopathy from chemotherapy.

Case 5

A 51-year-old male presented with worsening headache severity and frequency. He had a history of chronic headaches for about 20 years that occurred annually, but were now occurring twice weekly. The headaches often started with a left eye visual aura followed by pressure in the left eye, left frontal region, and left ear, with at times a cervicogenic component. No cervical spine imaging was available. An MRI revealed 2 small adjacent areas of cerebellar herniation into arachnoid granulations in the left occipital bone (Figure 5).

Arachnoid granulations appear very early in life, although they are uncommon before age 2 years.² Classically, they have been understood to act as 1-way valves permitting the outflow of CSF from the subarachnoid space to the dural venous sinuses. However, increasing evidence shows they may only play a minor role in that process.¹² The structure of arachnoid granulations is being reexamined. A recent microscopy study demonstrated structural heterogeneity with a fine, porous lining that permits flow.¹³ Additionally, associated immune components in the microenvironment suggests that arachnoid granulations may function similarly to lymph nodes as part of a central nervous system lymphatic network.¹³ Evidence is lacking for arachnoid granulations being the primary route of CSF outflow, and newer models include CSF exit pathways along the cranial nerves and drainage through lymphatics within the dura mater.¹²

New MRI systems have demonstrated that the prevalence of arachnoid granulations increases with age. One study found that all subjects in the aged 40 years cohort had detectable arachnoid granulations on images obtained with a 3T MRI system, with the main site being the superior sagittal sinus.² The prevalence increased until age 40 years and then noticeably decreased. Not only did the prevalence increase in this pattern, but the total number of detectable arachnoid granulations followed a similar pattern.² In addition, the detectable arachnoid granulations tend to be larger in older patients. Arachnoid granulations are very common in adults, but little is known about when and why brain tissue herniates through these structures.

This case series illustrates how a small amount of adult cerebral or cerebellar matter in large arachnoid granulations can herniate into the dural sinuses and diploic space. Although arachnoid granulations extending into the dural sinuses and diploic space are a relatively common finding on MRI,BHAGs are rare in these locations.^1,2,8 Improved spatial resolution afforded by newer high-field scanners with thinner sections, such as very thin (1 mm) T1- and heavily T2-weighted 3 dimensional sequences may lead to increased detection of BHAG. Some of these herniations are small and may be easily missed or confused for normal arachnoid granulations on 3 to 5 mm thickness MRIs.

Despite increased recognition, it is still uncertain to what degree these herniations contribute to the clinical presentations. Associated neurologic symptoms may include seizures, headaches, tinnitus, syncope, and increased intracranial pressure.^7-10

Three cases presented in this article demonstrated abnormal signals adjacent to the herniated brain, presumably due to dysplasia of gliotic tissue. In 1 study, parenchymal signal and structural changes occurred in about one-half of the reported BHAG, all of which were cerebellar herniations.⁷ In Case 1, the herniation and adjacent abnormal MRI signal corresponded to localization of the seizure semiology as obtained from patient history, strongly suggesting the BHAG played a role in the presentation. Signal abnormality accompanying an adjacent BHAG may suggest a higher likelihood that the BHAG has clinical relevance. However, the patient in Case 2 had a visual aura that corresponded to the BHAG location, so a signal abnormality may not be necessary for a patient to develop symptoms. Case 1 also included a history of documented traumatic brain injuries, suggesting that perhaps head trauma may facilitate BHAG development. Regardless, there is likely also a congenital component to their formation, as BHAG has been observed in the pediatric population.¹⁴

The patient's asymmetric left-sided hearing loss in Case 3 appeared unrelated to the BHAG as its location was in the contralateral cerebellar region and did not correspond to the patient’s clinical findings. The patient in Case 4 had a limited history regarding localization details of their prior presumed alcohol withdrawal seizure, such as head movements, eye deviation, or lateralized onset of convulsions. Given this limited data, it is unclear whether their prior seizure could have been related to BHAG or not. The patient in case 5 reported worsening headaches on the left side of his head, which corresponded to BHAG occurring on the left side. However, given that the increased T2 signal occurred in the left cerebellar hemisphere with BHAG in the left occipital bone, the occipital cortex was not involved. In this case, the BHAG would not explain the patient’s visual aura as such a lesion would have been expected in the right occipital cortex rather than its actual location in this patient’s left cerebellar hemisphere.

CONCLUSIONS

Understanding the clinical impact of brain herniations is important because they are probably more common than previously thought. Improved MRI capabilities suggest that more BHAG will be detected moving forward as radiologists interpret images with higher resolution and thinner slices. Until its significance is fully understood, BHAG will continue to complicate the diagnosis of patients with neurologic complaints whose brain MRIs and EEGs are otherwise unremarkable.

There have been no cases of surgical BHAG intervention and pathology analysis that would help determine their clinical significance. A related entity, temporal lobe encephalocele, has been linked to focal temporal lobe epilepsy, which has demonstrated significant symptom improvement following surgical correction.¹⁵ However, encephaloceles have been distinguished from BHAG in part because they do not necessarily herniate through an arachnoid granulation.⁸ BHAG has only begun to be characterized in detail over the last decade, so more research is needed to understand how it develops and what clinical significance it truly holds.