Researchers have found that having a transient ischemic attack (TIA) can reduce a person’s life expectancy up to 20%, according to a study published online November 10 in Stroke. “There is a lack of modern-day data quantifying the effect of TIA on survival, and recent data do not take into account expected survival,” the researchers commented. To investigate the impact of a TIA on survival, the investigators analyzed data from 22,157 patients hospitalized with a TIA, then estimated survival relative to the age- and sex-matched general population up to nine years after hospitalization. At one-year follow-up, 91.5% of TIA patients survived, compared with 95.0% expected survival in the general population; by nine-years follow-up, observed survival was 20% lower than expected. Older age, prior hospitalization for stroke (but not TIA), atrial fibrillation, and congestive heart failure significantly increased the risk of excess death in these patients.
Higher levels of urinary sodium excretion were associated with an increased risk of cardiovascular events, while lower levels were associated with cardiovascular death and hospitalization for congestive heart failure, according to a study published in the November 23 JAMA. “[Our objective was] to determine the association between estimated urinary sodium and potassium excretion (surrogates for intake) and cardiovascular events in patients with established cardiovascular disease or diabetes mellitus,” stated the researchers. The results of their observational analyses revealed that “compared with baseline sodium excretion of 4 to 5.99 g per day, sodium excretion of greater than 7 g per day was associated with an increased risk of all cardiovascular events.” In addition, a sodium excretion of less than 3 g per day was associated with increased risk of cardiovascular mortality and hospitalization for congestive heart failure, and a higher estimated potassium excretion was associated with a reduced risk of stroke.
Serum vitamin D levels are significantly lower in patients with recurrent inflammatory spinal cord disease, according to the results of a study published online November 14 in Archives of Neurology. The study authors performed a retrospective analysis evaluating vitamin D levels of 77 patients with monophasic and recurrent inflammatory spinal cord diseases. “Vitamin D levels are significantly lower in patients who developed recurrent spinal cord disease, adjusting for season, age, sex, and race,” the investigators concluded. “This study provides a basis for a prospective trial of measuring 25-hydroxyvitamin D levels in these patient populations and assessing the influence of vitamin D supplementation on the frequency of relapses in those with recurrent inflammatory spinal cord disease.”
The FDA has approved AdaptiveStim with RestoreSensor neurostimulation system for the management of chronic pain. Unlike other implantable neurostimulation devices that require frequent manual adjustments with changes in body positions, the AdaptiveStim system (Medtronic, Inc; Minneapolis) automatically adapts stimulation levels to the needs of people with chronic back and/or leg pain by recognizing and remembering the correlation between a change in body position and the level of stimulation needed. The FDA’s approval was based on data from a clinical trial in which 86.5% of study participants with chronic pain experienced better pain relief and convenience when the system was turned on, compared with a control period when the participants manually adjusted neurostimulation settings; 80.3% of study participants also reported functional improvements, including improved comfort during position changes. The AdaptiveStim system was also approved for use in MRI head scans if recommended by a physician.
Brain overgrowth in boys with autism involves an abnormal excess number of neurons, according to the results of a small preliminary study published in the November 9 JAMA. “Autism often involves early brain overgrowth, including the prefrontal cortex,” the investigators stated. “Although prefrontal abnormality has been theorized to underlie some autistic symptoms, the cellular defects that cause abnormal overgrowth remain unknown.” To investigate whether this overgrowth in children with autism involves excess neuron numbers, the researchers compared postmortem tissue from the prefrontal cortex of seven boys (age range, 2 to 16) who had autism with postmortem tissue of six typically developing boys. They found that children with autism had 67% more neurons in the prefrontal cortex. “Brain weight in the autistic case differed from normative mean weight for age by a mean of 17.6%, while brains in controls differed by a mean of 0.2%,” the researchers reported.
A person’s stroke risk profile may also be helpful in predicting whether a person will develop memory problems and cognitive impairment later in life, according to a study published in the November 8 Neurology. “Participants included subjects without stroke at baseline … with at least two cognitive function assessments during the follow-up,” the researchers explained. “During a mean follow-up of 4.1 years, 1,907 participants met criteria for incident cognitive impairment.” The researchers determined that male sex, black race, less education, older age, and presence of left ventricular hypertrophy were related to the development of cognitive impairment. “Total Framingham Stroke Risk Profile score, elevated blood pressure, and left ventricular hypertrophy predict development of clinically significant cognitive dysfunction,” the investigators concluded. “Prevention and treatment of high blood pressure may be effective in preserving cognitive health.”
The FDA has approved Xarelto (rivaroxaban) to reduce the risk of stroke in people who have nonvalvular atrial fibrillation. Xarelto (Janssen Pharmaceuticals Inc; Titusville, New Jersey) is an oral anti-clotting drug that has also been approved to reduce the risk of blood clots, deep vein thrombosis, and pulmonary embolism following knee or hip replacement surgery. The FDA’s approval was based on the results of a clinical trial with more than 14,000 patients that compared Xarelto with the anti-clotting drug warfarin; Xarelto proved similar to warfarin in its ability to prevent stroke. Bleeding was the most common adverse event reported by patients treated with Xarelto in this clinical trial, and the risk of bleeding was similar to the risk of bleeding associated with warfarin.
Patients with dementia who have a stroke have a higher likelihood of becoming disabled and being institutionalized, compared with patients who did not have dementia at the time of their stroke, according to a report in the November 1 Neurology. Investigators conducted a retrospective cohort study that included 9,304 patients with an acute ischemic stroke, 702 of whom had a history of dementia. “Patients with dementia were older (mean age, 81 vs 70), had more severe strokes, and were more likely to have atrial fibrillation than those without dementia,” the investigators determined. They also found that patients with dementia were slightly less likely to be admitted to a stroke unit, had a higher disability at discharge, and were less likely to be discharged to their prestroke place of residence. “In patients with stroke, preexisting dementia is associated with high rates of disability and institutionalization, representing an increasing challenge for the health care system,” the researchers concluded.

Researchers have found that having a transient ischemic attack (TIA) can reduce a person’s life expectancy up to 20%, according to a study published online November 10 in Stroke. “There is a lack of modern-day data quantifying the effect of TIA on survival, and recent data do not take into account expected survival,” the researchers commented. To investigate the impact of a TIA on survival, the investigators analyzed data from 22,157 patients hospitalized with a TIA, then estimated survival relative to the age- and sex-matched general population up to nine years after hospitalization. At one-year follow-up, 91.5% of TIA patients survived, compared with 95.0% expected survival in the general population; by nine-years follow-up, observed survival was 20% lower than expected. Older age, prior hospitalization for stroke (but not TIA), atrial fibrillation, and congestive heart failure significantly increased the risk of excess death in these patients.
Higher levels of urinary sodium excretion were associated with an increased risk of cardiovascular events, while lower levels were associated with cardiovascular death and hospitalization for congestive heart failure, according to a study published in the November 23 JAMA. “[Our objective was] to determine the association between estimated urinary sodium and potassium excretion (surrogates for intake) and cardiovascular events in patients with established cardiovascular disease or diabetes mellitus,” stated the researchers. The results of their observational analyses revealed that “compared with baseline sodium excretion of 4 to 5.99 g per day, sodium excretion of greater than 7 g per day was associated with an increased risk of all cardiovascular events.” In addition, a sodium excretion of less than 3 g per day was associated with increased risk of cardiovascular mortality and hospitalization for congestive heart failure, and a higher estimated potassium excretion was associated with a reduced risk of stroke.
Serum vitamin D levels are significantly lower in patients with recurrent inflammatory spinal cord disease, according to the results of a study published online November 14 in Archives of Neurology. The study authors performed a retrospective analysis evaluating vitamin D levels of 77 patients with monophasic and recurrent inflammatory spinal cord diseases. “Vitamin D levels are significantly lower in patients who developed recurrent spinal cord disease, adjusting for season, age, sex, and race,” the investigators concluded. “This study provides a basis for a prospective trial of measuring 25-hydroxyvitamin D levels in these patient populations and assessing the influence of vitamin D supplementation on the frequency of relapses in those with recurrent inflammatory spinal cord disease.”
The FDA has approved AdaptiveStim with RestoreSensor neurostimulation system for the management of chronic pain. Unlike other implantable neurostimulation devices that require frequent manual adjustments with changes in body positions, the AdaptiveStim system (Medtronic, Inc; Minneapolis) automatically adapts stimulation levels to the needs of people with chronic back and/or leg pain by recognizing and remembering the correlation between a change in body position and the level of stimulation needed. The FDA’s approval was based on data from a clinical trial in which 86.5% of study participants with chronic pain experienced better pain relief and convenience when the system was turned on, compared with a control period when the participants manually adjusted neurostimulation settings; 80.3% of study participants also reported functional improvements, including improved comfort during position changes. The AdaptiveStim system was also approved for use in MRI head scans if recommended by a physician.
Brain overgrowth in boys with autism involves an abnormal excess number of neurons, according to the results of a small preliminary study published in the November 9 JAMA. “Autism often involves early brain overgrowth, including the prefrontal cortex,” the investigators stated. “Although prefrontal abnormality has been theorized to underlie some autistic symptoms, the cellular defects that cause abnormal overgrowth remain unknown.” To investigate whether this overgrowth in children with autism involves excess neuron numbers, the researchers compared postmortem tissue from the prefrontal cortex of seven boys (age range, 2 to 16) who had autism with postmortem tissue of six typically developing boys. They found that children with autism had 67% more neurons in the prefrontal cortex. “Brain weight in the autistic case differed from normative mean weight for age by a mean of 17.6%, while brains in controls differed by a mean of 0.2%,” the researchers reported.
A person’s stroke risk profile may also be helpful in predicting whether a person will develop memory problems and cognitive impairment later in life, according to a study published in the November 8 Neurology. “Participants included subjects without stroke at baseline … with at least two cognitive function assessments during the follow-up,” the researchers explained. “During a mean follow-up of 4.1 years, 1,907 participants met criteria for incident cognitive impairment.” The researchers determined that male sex, black race, less education, older age, and presence of left ventricular hypertrophy were related to the development of cognitive impairment. “Total Framingham Stroke Risk Profile score, elevated blood pressure, and left ventricular hypertrophy predict development of clinically significant cognitive dysfunction,” the investigators concluded. “Prevention and treatment of high blood pressure may be effective in preserving cognitive health.”
The FDA has approved Xarelto (rivaroxaban) to reduce the risk of stroke in people who have nonvalvular atrial fibrillation. Xarelto (Janssen Pharmaceuticals Inc; Titusville, New Jersey) is an oral anti-clotting drug that has also been approved to reduce the risk of blood clots, deep vein thrombosis, and pulmonary embolism following knee or hip replacement surgery. The FDA’s approval was based on the results of a clinical trial with more than 14,000 patients that compared Xarelto with the anti-clotting drug warfarin; Xarelto proved similar to warfarin in its ability to prevent stroke. Bleeding was the most common adverse event reported by patients treated with Xarelto in this clinical trial, and the risk of bleeding was similar to the risk of bleeding associated with warfarin.
Patients with dementia who have a stroke have a higher likelihood of becoming disabled and being institutionalized, compared with patients who did not have dementia at the time of their stroke, according to a report in the November 1 Neurology. Investigators conducted a retrospective cohort study that included 9,304 patients with an acute ischemic stroke, 702 of whom had a history of dementia. “Patients with dementia were older (mean age, 81 vs 70), had more severe strokes, and were more likely to have atrial fibrillation than those without dementia,” the investigators determined. They also found that patients with dementia were slightly less likely to be admitted to a stroke unit, had a higher disability at discharge, and were less likely to be discharged to their prestroke place of residence. “In patients with stroke, preexisting dementia is associated with high rates of disability and institutionalization, representing an increasing challenge for the health care system,” the researchers concluded.

Researchers have found that having a transient ischemic attack (TIA) can reduce a person’s life expectancy up to 20%, according to a study published online November 10 in Stroke. “There is a lack of modern-day data quantifying the effect of TIA on survival, and recent data do not take into account expected survival,” the researchers commented. To investigate the impact of a TIA on survival, the investigators analyzed data from 22,157 patients hospitalized with a TIA, then estimated survival relative to the age- and sex-matched general population up to nine years after hospitalization. At one-year follow-up, 91.5% of TIA patients survived, compared with 95.0% expected survival in the general population; by nine-years follow-up, observed survival was 20% lower than expected. Older age, prior hospitalization for stroke (but not TIA), atrial fibrillation, and congestive heart failure significantly increased the risk of excess death in these patients.
Higher levels of urinary sodium excretion were associated with an increased risk of cardiovascular events, while lower levels were associated with cardiovascular death and hospitalization for congestive heart failure, according to a study published in the November 23 JAMA. “[Our objective was] to determine the association between estimated urinary sodium and potassium excretion (surrogates for intake) and cardiovascular events in patients with established cardiovascular disease or diabetes mellitus,” stated the researchers. The results of their observational analyses revealed that “compared with baseline sodium excretion of 4 to 5.99 g per day, sodium excretion of greater than 7 g per day was associated with an increased risk of all cardiovascular events.” In addition, a sodium excretion of less than 3 g per day was associated with increased risk of cardiovascular mortality and hospitalization for congestive heart failure, and a higher estimated potassium excretion was associated with a reduced risk of stroke.
Serum vitamin D levels are significantly lower in patients with recurrent inflammatory spinal cord disease, according to the results of a study published online November 14 in Archives of Neurology. The study authors performed a retrospective analysis evaluating vitamin D levels of 77 patients with monophasic and recurrent inflammatory spinal cord diseases. “Vitamin D levels are significantly lower in patients who developed recurrent spinal cord disease, adjusting for season, age, sex, and race,” the investigators concluded. “This study provides a basis for a prospective trial of measuring 25-hydroxyvitamin D levels in these patient populations and assessing the influence of vitamin D supplementation on the frequency of relapses in those with recurrent inflammatory spinal cord disease.”
The FDA has approved AdaptiveStim with RestoreSensor neurostimulation system for the management of chronic pain. Unlike other implantable neurostimulation devices that require frequent manual adjustments with changes in body positions, the AdaptiveStim system (Medtronic, Inc; Minneapolis) automatically adapts stimulation levels to the needs of people with chronic back and/or leg pain by recognizing and remembering the correlation between a change in body position and the level of stimulation needed. The FDA’s approval was based on data from a clinical trial in which 86.5% of study participants with chronic pain experienced better pain relief and convenience when the system was turned on, compared with a control period when the participants manually adjusted neurostimulation settings; 80.3% of study participants also reported functional improvements, including improved comfort during position changes. The AdaptiveStim system was also approved for use in MRI head scans if recommended by a physician.
Brain overgrowth in boys with autism involves an abnormal excess number of neurons, according to the results of a small preliminary study published in the November 9 JAMA. “Autism often involves early brain overgrowth, including the prefrontal cortex,” the investigators stated. “Although prefrontal abnormality has been theorized to underlie some autistic symptoms, the cellular defects that cause abnormal overgrowth remain unknown.” To investigate whether this overgrowth in children with autism involves excess neuron numbers, the researchers compared postmortem tissue from the prefrontal cortex of seven boys (age range, 2 to 16) who had autism with postmortem tissue of six typically developing boys. They found that children with autism had 67% more neurons in the prefrontal cortex. “Brain weight in the autistic case differed from normative mean weight for age by a mean of 17.6%, while brains in controls differed by a mean of 0.2%,” the researchers reported.
A person’s stroke risk profile may also be helpful in predicting whether a person will develop memory problems and cognitive impairment later in life, according to a study published in the November 8 Neurology. “Participants included subjects without stroke at baseline … with at least two cognitive function assessments during the follow-up,” the researchers explained. “During a mean follow-up of 4.1 years, 1,907 participants met criteria for incident cognitive impairment.” The researchers determined that male sex, black race, less education, older age, and presence of left ventricular hypertrophy were related to the development of cognitive impairment. “Total Framingham Stroke Risk Profile score, elevated blood pressure, and left ventricular hypertrophy predict development of clinically significant cognitive dysfunction,” the investigators concluded. “Prevention and treatment of high blood pressure may be effective in preserving cognitive health.”
The FDA has approved Xarelto (rivaroxaban) to reduce the risk of stroke in people who have nonvalvular atrial fibrillation. Xarelto (Janssen Pharmaceuticals Inc; Titusville, New Jersey) is an oral anti-clotting drug that has also been approved to reduce the risk of blood clots, deep vein thrombosis, and pulmonary embolism following knee or hip replacement surgery. The FDA’s approval was based on the results of a clinical trial with more than 14,000 patients that compared Xarelto with the anti-clotting drug warfarin; Xarelto proved similar to warfarin in its ability to prevent stroke. Bleeding was the most common adverse event reported by patients treated with Xarelto in this clinical trial, and the risk of bleeding was similar to the risk of bleeding associated with warfarin.
Patients with dementia who have a stroke have a higher likelihood of becoming disabled and being institutionalized, compared with patients who did not have dementia at the time of their stroke, according to a report in the November 1 Neurology. Investigators conducted a retrospective cohort study that included 9,304 patients with an acute ischemic stroke, 702 of whom had a history of dementia. “Patients with dementia were older (mean age, 81 vs 70), had more severe strokes, and were more likely to have atrial fibrillation than those without dementia,” the investigators determined. They also found that patients with dementia were slightly less likely to be admitted to a stroke unit, had a higher disability at discharge, and were less likely to be discharged to their prestroke place of residence. “In patients with stroke, preexisting dementia is associated with high rates of disability and institutionalization, representing an increasing challenge for the health care system,” the researchers concluded.

A 33-year-old woman in her 32nd week of pregnancy (gravida 3, para 2) presented to the emergency department (ED) with a five-day history of weakness and ascending numbness below the right knee. She related a two-week history of right-sided low back pain that radiated to the right buttock and was associated with severe right lower extremity (RLE) pain, most prominent in the posterolateral aspect of the right calf. She denied perianal numbness, incontinence, or other changes in bowel or bladder function. She also denied left lower extremity involvement or trauma.

The patient had had one uneventful pregnancy to date. Her medical history included hypothyroidism, treated with levothyroxine; and anxiety, for which she was taking sertraline. She denied any history of allergies, alcohol consumption, smoking, or illicit drug use. She had been evaluated twice and received reassurance in the two weeks before her presentation to the ED. She was admitted to the obstetric service secondary to pain, and a stat MRI rather than x-ray was ordered by obstetrics. An orthopedic consult was ordered. A spine surgeon happened to be on call.

Examination revealed that the patient walked plantigrade, with her right foot slightly externally rotated. She was unable to dorsiflex or plantarflex her right foot. She was unable to heel- or toe-walk on the right side, possessed 0 out of 5 strength at the right extensor hallucis longus and 2 to 3 out of 5 at the right tibialis anterior and gastroc soleus complex. She complained of pain with right leg elevation exceeding 30° and had very limited sensation to light touch in the right L5 and S1 dermatomes. Deep tendon reflex was absent at the right ankle. The patient refused a rectal exam or post-void evaluation. 

The initial diagnosis considered by the ED clinician was sciatica, with a differential diagnosis that included pelvic pain of pregnancy, lumbar sprain strain, sciatica, lumbar disk, herniated nucleus pulposus with radiculopathy, and cauda equina syndrome. Trauma was considered and ruled out, as were malignancies; inflammatory, infectious, or degenerative conditions; or other compressive processes.¹

Lumbar MRI demonstrated a very large, right-sided disk herniation at L5-S1 with an extruded fragment that was severely compressing the thecal sac and the right S1 nerve root, causing severe right foraminal stenosis at the level of L5-S1. Degenerative changes were noted at L4-5 with disk dessication and no lesions seen.

The patient was diagnosed with cauda equina syndrome, which was felt to be causing severe RLE weakness and ascending numbness. The options of observation, analgesia, physical therapy, and epidural injections were discussed with the patient; however, surgery was strongly recommended due to her profound weakness and the severity of pain she was experiencing, in addition to the size of the disk herniation. She opted for surgery.

The patient was given epidural anesthesia at the L3-4 level, with a catheter left in place during the procedure. A test dose of lidocaine (1.5 cc) with epinephrine was injected to ensure proper placement, and bupivacaine 0.5% was given in increments of 5.0 cc three times during the case. Propofol was administered for sedation, and a 2.0-mg dose of a long-acting morphine was given to the patient before removal of the epidural catheter. Fetal monitoring was performed by obstetrics throughout the procedure.

A laminotomy, partial facetectomy, and diskectomy were performed at L5-S1 with excision of a free fragment. Surgical pathology described the disk as fibrocartilaginous tissue measuring 3.5 cm x 1.4 cm x 0.6 cm.

DISCUSSION
Although nearly half of pregnant women experience low back pain, cauda equina syndrome (CES), a complication of lumbar disk herniation, is extremely rare in the gravid patient.² In a decade-long review of 48,760 consecutive deliveries, LaBan et al³ identified symptomatic lumbar herniated nucleus pulposus in only five patients (approximately one in 10,000 pregnancies). In pregnant women who do experience CES, symptoms most commonly develop between the fifth and seventh month of pregnancy.⁴ According to Small et al,⁵ “The major pitfall in diagnosis is not including CES in the back pain differential.”

True CES presents as a triad of symptoms: lower extremity weakness, altered sensation in the skin of the buttocks and upper posterior thighs (saddle anesthesia), and dysfunction or paralysis of the bowel and bladder. However, few patients present with all of the classic symptoms,⁶ and patients with CES are often dismissed by several clinicians in their search for relief before presenting to a subspecialist. Kostuik et al⁷ consider “unilateral sciatica with motor and sensory disturbance” a more common presentation of CES; also indicative of this condition, they report, is “urinary dysfunction combined with motor and sensory loss in the presence of a disc lesion.”

The polypeptide relaxin, which is secreted by the corpus luteum to promote joint laxity in late pregnancy, has been associated with low back pain and pelvic pain of pregnancy; it has also been suggested as a possible contributing cause of CES during pregnancy.^8,9 Additionally, increased lumbar lordosis with positional and postural stress may cause direct pressure by the gravid uterus on nerve roots. The great vessels may also be compressed by the uterus, resulting in ischemia of the neural element and back pain that radiates to the legs.¹⁰ Many cases of lumbar disk prolapse occur during the first and second trimesters. The most clinically incapacitated patients have been found to have the highest levels of relaxin.⁹

The Diagnosis
Early diagnosis of CES, through proper physical examination and radiologic studies, is paramount. A rectal examination should be performed to assess for sphincter tone (which may be diminished in 80% of patients) and to assess for perineal sensation.⁵ Catheterization yielding a postvoid residual urine greater than 100/200 cc is reported to have a specificity and sensitivity of 90% or greater for CES. Small et al⁵ recommend a straight leg raise maneuver to assess for radiculopathy.

Various studies in the literature support the use of MRI in the gravid patient to confirm the diagnosis of CES and to identify the degree and level of disk ­protrusion.^2-4,11

Treatment
CES requires urgent surgical decompression.¹¹ Early recognition of CES attributable to lumbar disk prolapse, report O’Laoire et al,¹² is essential to prevent irreversible sphincter paralysis. They liken the condition’s urgency to that of extradural hematoma in a head injury.

Disk surgery during pregnancy—preferably a team effort, with obstetrics performing perioperative fetal monitoring—has been deemed a safe management method.^2,4 Spinal or general anesthesia during nonobstetric surgery is generally considered safe for both mother and fetus.^13,14 Adequate oxygenation without risk for hyperventilation is considered essential.¹⁵

PATIENT OUTCOME
In the immediate postoperative period, the patient continued to complain of RLE pain, which abated significantly by the time she was discharged. When she was seen in follow-up four days later, she was able to heel- and toe-walk on the right side, and her strength had improved to 3 or 4 out of 5 at the RLE. She continued to experience diminished sensation to the plantar aspect of the right foot, which persisted at the one-month follow up. At that visit, the patient also reported occasional pain in the right buttock. Physical therapy was started to strengthen the RLE. 

By three months postsurgery, the patient had undergone uneventful vaginal delivery. She had an entirely benign exam with 5 out of 5 strength at the RLE and no neurologic deficits. She was cleared to return to light weightlifting with good technique and lumbar support but was told to refrain from running until the sixth month postsurgery.

CONCLUSION
Although the case patient did not have a “true” (ie, typical) presentation of CES, her symptoms warranted a full workup and treatment to prevent possible long-term sequelae. Medical practitioners should be familiar with the triad presentation of CES. They must differentiate lower back pain of muscular origin from lumbar disk herniation and be able to appreciate the degree of symptom severity reported by the gravid patient. A thorough history and physical assessment must be performed in every such case. When in doubt, the clinician must err on the side of caution, referring the patient for MRI and consulting with a specialist.

REFERENCES
1. Johnston RA. The management of acute spinal cord compression. J Neurol Neurosurg Psychiatr. 1993;56(10):1046-1054.

2. Brown MD, Levi AD. Surgery for lumbar disc herniation during pregnancy. Spine (Phila PA 1976). 2001;26(5):440-443.

3. LaBan MM, Perrin JCS, Latimer FR. Pregnancy and the herniated lumbar disc. Arch Phys Med Rehabil. 1983;64(7):319-321.

4. LaBan MM, Rapp NS, Van Oeyen P, Meerschaert JR. The lumbar herniated disk of pregnancy: a report of six cases identified by magnetic resonance imaging. Arch Phys Med Rehabil. 1995;76(5):476-479.

5. Small SA, Perron AD, Brady WJ. Orthopedic pitfalls: cauda equina syndrome. Am J Emerg Med. 2005;23(2):159-163.

6. Tay EC, Chacha PB. Midline prolapse of a lumbar intervertebral disc with compression of the cauda equina. J Bone Joint Surg. 1979;61(1):43-46.

7. Kostuik JP, Harrington I, Alexander D, et al. Cauda equina syndrome and lumbar disc herniation. J Bone Joint Surg Am. 1986;68(3):386-391.

8. Russell R, Reynolds F. Back pain, pregnancy, and childbirth. BMJ. 1997;314(7087):1062-1063.

9. MacLennan AH, Nicholson R, Green RC, Bath M. Serum relaxin and pelvic pain of pregnancy. Lancet. 1986;2(8501):243-245.

10. Ashkan K, Casey AT, Powell M, Crockard HA. Back pain during pregnancy and after childbirth: an unusual cause not to miss. J R Soc Med. 1998;91(2):88-90.

11. Busse JW, Bhandari M, Schnittker JB, et al. Delayed presentation of cauda equina syndrome secondary to lumbar disc herniation: functional outcomes and health-related quality of life. CJEM. 2001;3(4):285-291.

12. O’Laoire SA, Crockard HA, Thomas DG. Prognosis for sphincter recovery after operation for cauda equina compression owing to lumbar disc prolapse. Br Med J (Clin Res Ed). 1981;282(6279):1852-1854.

13. Kuczkowski KM. The safety of anaesthetics in pregnant women. Expert Opin Drug Saf. 2006; 5(2):251-264.

14. Kuczkowski KM. Nonobstetric surgery during pregnancy: what are the risks of anesthesia? Obstet Gynecol Surv. 2004;59(1):52-56.

15. Birnbach DJ, Browne IM. Anesthesia for obstetrics. In: Miller RD, Eriksson LI, Fleisher LA, et al. Miller’s Anesthesia. Philadelphia, PA: Churchill Livingston, Elsevier Health Science; 2010: 2203-2240.

A 33-year-old woman in her 32nd week of pregnancy (gravida 3, para 2) presented to the emergency department (ED) with a five-day history of weakness and ascending numbness below the right knee. She related a two-week history of right-sided low back pain that radiated to the right buttock and was associated with severe right lower extremity (RLE) pain, most prominent in the posterolateral aspect of the right calf. She denied perianal numbness, incontinence, or other changes in bowel or bladder function. She also denied left lower extremity involvement or trauma.

The patient had had one uneventful pregnancy to date. Her medical history included hypothyroidism, treated with levothyroxine; and anxiety, for which she was taking sertraline. She denied any history of allergies, alcohol consumption, smoking, or illicit drug use. She had been evaluated twice and received reassurance in the two weeks before her presentation to the ED. She was admitted to the obstetric service secondary to pain, and a stat MRI rather than x-ray was ordered by obstetrics. An orthopedic consult was ordered. A spine surgeon happened to be on call.

Examination revealed that the patient walked plantigrade, with her right foot slightly externally rotated. She was unable to dorsiflex or plantarflex her right foot. She was unable to heel- or toe-walk on the right side, possessed 0 out of 5 strength at the right extensor hallucis longus and 2 to 3 out of 5 at the right tibialis anterior and gastroc soleus complex. She complained of pain with right leg elevation exceeding 30° and had very limited sensation to light touch in the right L5 and S1 dermatomes. Deep tendon reflex was absent at the right ankle. The patient refused a rectal exam or post-void evaluation. 

The initial diagnosis considered by the ED clinician was sciatica, with a differential diagnosis that included pelvic pain of pregnancy, lumbar sprain strain, sciatica, lumbar disk, herniated nucleus pulposus with radiculopathy, and cauda equina syndrome. Trauma was considered and ruled out, as were malignancies; inflammatory, infectious, or degenerative conditions; or other compressive processes.¹

Lumbar MRI demonstrated a very large, right-sided disk herniation at L5-S1 with an extruded fragment that was severely compressing the thecal sac and the right S1 nerve root, causing severe right foraminal stenosis at the level of L5-S1. Degenerative changes were noted at L4-5 with disk dessication and no lesions seen.

The patient was diagnosed with cauda equina syndrome, which was felt to be causing severe RLE weakness and ascending numbness. The options of observation, analgesia, physical therapy, and epidural injections were discussed with the patient; however, surgery was strongly recommended due to her profound weakness and the severity of pain she was experiencing, in addition to the size of the disk herniation. She opted for surgery.

The patient was given epidural anesthesia at the L3-4 level, with a catheter left in place during the procedure. A test dose of lidocaine (1.5 cc) with epinephrine was injected to ensure proper placement, and bupivacaine 0.5% was given in increments of 5.0 cc three times during the case. Propofol was administered for sedation, and a 2.0-mg dose of a long-acting morphine was given to the patient before removal of the epidural catheter. Fetal monitoring was performed by obstetrics throughout the procedure.

A laminotomy, partial facetectomy, and diskectomy were performed at L5-S1 with excision of a free fragment. Surgical pathology described the disk as fibrocartilaginous tissue measuring 3.5 cm x 1.4 cm x 0.6 cm.

DISCUSSION
Although nearly half of pregnant women experience low back pain, cauda equina syndrome (CES), a complication of lumbar disk herniation, is extremely rare in the gravid patient.² In a decade-long review of 48,760 consecutive deliveries, LaBan et al³ identified symptomatic lumbar herniated nucleus pulposus in only five patients (approximately one in 10,000 pregnancies). In pregnant women who do experience CES, symptoms most commonly develop between the fifth and seventh month of pregnancy.⁴ According to Small et al,⁵ “The major pitfall in diagnosis is not including CES in the back pain differential.”

True CES presents as a triad of symptoms: lower extremity weakness, altered sensation in the skin of the buttocks and upper posterior thighs (saddle anesthesia), and dysfunction or paralysis of the bowel and bladder. However, few patients present with all of the classic symptoms,⁶ and patients with CES are often dismissed by several clinicians in their search for relief before presenting to a subspecialist. Kostuik et al⁷ consider “unilateral sciatica with motor and sensory disturbance” a more common presentation of CES; also indicative of this condition, they report, is “urinary dysfunction combined with motor and sensory loss in the presence of a disc lesion.”

The polypeptide relaxin, which is secreted by the corpus luteum to promote joint laxity in late pregnancy, has been associated with low back pain and pelvic pain of pregnancy; it has also been suggested as a possible contributing cause of CES during pregnancy.^8,9 Additionally, increased lumbar lordosis with positional and postural stress may cause direct pressure by the gravid uterus on nerve roots. The great vessels may also be compressed by the uterus, resulting in ischemia of the neural element and back pain that radiates to the legs.¹⁰ Many cases of lumbar disk prolapse occur during the first and second trimesters. The most clinically incapacitated patients have been found to have the highest levels of relaxin.⁹

The Diagnosis
Early diagnosis of CES, through proper physical examination and radiologic studies, is paramount. A rectal examination should be performed to assess for sphincter tone (which may be diminished in 80% of patients) and to assess for perineal sensation.⁵ Catheterization yielding a postvoid residual urine greater than 100/200 cc is reported to have a specificity and sensitivity of 90% or greater for CES. Small et al⁵ recommend a straight leg raise maneuver to assess for radiculopathy.

Various studies in the literature support the use of MRI in the gravid patient to confirm the diagnosis of CES and to identify the degree and level of disk ­protrusion.^2-4,11

Treatment
CES requires urgent surgical decompression.¹¹ Early recognition of CES attributable to lumbar disk prolapse, report O’Laoire et al,¹² is essential to prevent irreversible sphincter paralysis. They liken the condition’s urgency to that of extradural hematoma in a head injury.

Disk surgery during pregnancy—preferably a team effort, with obstetrics performing perioperative fetal monitoring—has been deemed a safe management method.^2,4 Spinal or general anesthesia during nonobstetric surgery is generally considered safe for both mother and fetus.^13,14 Adequate oxygenation without risk for hyperventilation is considered essential.¹⁵

PATIENT OUTCOME
In the immediate postoperative period, the patient continued to complain of RLE pain, which abated significantly by the time she was discharged. When she was seen in follow-up four days later, she was able to heel- and toe-walk on the right side, and her strength had improved to 3 or 4 out of 5 at the RLE. She continued to experience diminished sensation to the plantar aspect of the right foot, which persisted at the one-month follow up. At that visit, the patient also reported occasional pain in the right buttock. Physical therapy was started to strengthen the RLE. 

By three months postsurgery, the patient had undergone uneventful vaginal delivery. She had an entirely benign exam with 5 out of 5 strength at the RLE and no neurologic deficits. She was cleared to return to light weightlifting with good technique and lumbar support but was told to refrain from running until the sixth month postsurgery.

CONCLUSION
Although the case patient did not have a “true” (ie, typical) presentation of CES, her symptoms warranted a full workup and treatment to prevent possible long-term sequelae. Medical practitioners should be familiar with the triad presentation of CES. They must differentiate lower back pain of muscular origin from lumbar disk herniation and be able to appreciate the degree of symptom severity reported by the gravid patient. A thorough history and physical assessment must be performed in every such case. When in doubt, the clinician must err on the side of caution, referring the patient for MRI and consulting with a specialist.

REFERENCES
1. Johnston RA. The management of acute spinal cord compression. J Neurol Neurosurg Psychiatr. 1993;56(10):1046-1054.

2. Brown MD, Levi AD. Surgery for lumbar disc herniation during pregnancy. Spine (Phila PA 1976). 2001;26(5):440-443.

3. LaBan MM, Perrin JCS, Latimer FR. Pregnancy and the herniated lumbar disc. Arch Phys Med Rehabil. 1983;64(7):319-321.

4. LaBan MM, Rapp NS, Van Oeyen P, Meerschaert JR. The lumbar herniated disk of pregnancy: a report of six cases identified by magnetic resonance imaging. Arch Phys Med Rehabil. 1995;76(5):476-479.

5. Small SA, Perron AD, Brady WJ. Orthopedic pitfalls: cauda equina syndrome. Am J Emerg Med. 2005;23(2):159-163.

6. Tay EC, Chacha PB. Midline prolapse of a lumbar intervertebral disc with compression of the cauda equina. J Bone Joint Surg. 1979;61(1):43-46.

7. Kostuik JP, Harrington I, Alexander D, et al. Cauda equina syndrome and lumbar disc herniation. J Bone Joint Surg Am. 1986;68(3):386-391.

8. Russell R, Reynolds F. Back pain, pregnancy, and childbirth. BMJ. 1997;314(7087):1062-1063.

9. MacLennan AH, Nicholson R, Green RC, Bath M. Serum relaxin and pelvic pain of pregnancy. Lancet. 1986;2(8501):243-245.

10. Ashkan K, Casey AT, Powell M, Crockard HA. Back pain during pregnancy and after childbirth: an unusual cause not to miss. J R Soc Med. 1998;91(2):88-90.

11. Busse JW, Bhandari M, Schnittker JB, et al. Delayed presentation of cauda equina syndrome secondary to lumbar disc herniation: functional outcomes and health-related quality of life. CJEM. 2001;3(4):285-291.

12. O’Laoire SA, Crockard HA, Thomas DG. Prognosis for sphincter recovery after operation for cauda equina compression owing to lumbar disc prolapse. Br Med J (Clin Res Ed). 1981;282(6279):1852-1854.

13. Kuczkowski KM. The safety of anaesthetics in pregnant women. Expert Opin Drug Saf. 2006; 5(2):251-264.

14. Kuczkowski KM. Nonobstetric surgery during pregnancy: what are the risks of anesthesia? Obstet Gynecol Surv. 2004;59(1):52-56.

15. Birnbach DJ, Browne IM. Anesthesia for obstetrics. In: Miller RD, Eriksson LI, Fleisher LA, et al. Miller’s Anesthesia. Philadelphia, PA: Churchill Livingston, Elsevier Health Science; 2010: 2203-2240.

A 33-year-old woman in her 32nd week of pregnancy (gravida 3, para 2) presented to the emergency department (ED) with a five-day history of weakness and ascending numbness below the right knee. She related a two-week history of right-sided low back pain that radiated to the right buttock and was associated with severe right lower extremity (RLE) pain, most prominent in the posterolateral aspect of the right calf. She denied perianal numbness, incontinence, or other changes in bowel or bladder function. She also denied left lower extremity involvement or trauma.

The patient had had one uneventful pregnancy to date. Her medical history included hypothyroidism, treated with levothyroxine; and anxiety, for which she was taking sertraline. She denied any history of allergies, alcohol consumption, smoking, or illicit drug use. She had been evaluated twice and received reassurance in the two weeks before her presentation to the ED. She was admitted to the obstetric service secondary to pain, and a stat MRI rather than x-ray was ordered by obstetrics. An orthopedic consult was ordered. A spine surgeon happened to be on call.

Examination revealed that the patient walked plantigrade, with her right foot slightly externally rotated. She was unable to dorsiflex or plantarflex her right foot. She was unable to heel- or toe-walk on the right side, possessed 0 out of 5 strength at the right extensor hallucis longus and 2 to 3 out of 5 at the right tibialis anterior and gastroc soleus complex. She complained of pain with right leg elevation exceeding 30° and had very limited sensation to light touch in the right L5 and S1 dermatomes. Deep tendon reflex was absent at the right ankle. The patient refused a rectal exam or post-void evaluation. 

The initial diagnosis considered by the ED clinician was sciatica, with a differential diagnosis that included pelvic pain of pregnancy, lumbar sprain strain, sciatica, lumbar disk, herniated nucleus pulposus with radiculopathy, and cauda equina syndrome. Trauma was considered and ruled out, as were malignancies; inflammatory, infectious, or degenerative conditions; or other compressive processes.¹

Lumbar MRI demonstrated a very large, right-sided disk herniation at L5-S1 with an extruded fragment that was severely compressing the thecal sac and the right S1 nerve root, causing severe right foraminal stenosis at the level of L5-S1. Degenerative changes were noted at L4-5 with disk dessication and no lesions seen.

The patient was diagnosed with cauda equina syndrome, which was felt to be causing severe RLE weakness and ascending numbness. The options of observation, analgesia, physical therapy, and epidural injections were discussed with the patient; however, surgery was strongly recommended due to her profound weakness and the severity of pain she was experiencing, in addition to the size of the disk herniation. She opted for surgery.

The patient was given epidural anesthesia at the L3-4 level, with a catheter left in place during the procedure. A test dose of lidocaine (1.5 cc) with epinephrine was injected to ensure proper placement, and bupivacaine 0.5% was given in increments of 5.0 cc three times during the case. Propofol was administered for sedation, and a 2.0-mg dose of a long-acting morphine was given to the patient before removal of the epidural catheter. Fetal monitoring was performed by obstetrics throughout the procedure.

A laminotomy, partial facetectomy, and diskectomy were performed at L5-S1 with excision of a free fragment. Surgical pathology described the disk as fibrocartilaginous tissue measuring 3.5 cm x 1.4 cm x 0.6 cm.

DISCUSSION
Although nearly half of pregnant women experience low back pain, cauda equina syndrome (CES), a complication of lumbar disk herniation, is extremely rare in the gravid patient.² In a decade-long review of 48,760 consecutive deliveries, LaBan et al³ identified symptomatic lumbar herniated nucleus pulposus in only five patients (approximately one in 10,000 pregnancies). In pregnant women who do experience CES, symptoms most commonly develop between the fifth and seventh month of pregnancy.⁴ According to Small et al,⁵ “The major pitfall in diagnosis is not including CES in the back pain differential.”

True CES presents as a triad of symptoms: lower extremity weakness, altered sensation in the skin of the buttocks and upper posterior thighs (saddle anesthesia), and dysfunction or paralysis of the bowel and bladder. However, few patients present with all of the classic symptoms,⁶ and patients with CES are often dismissed by several clinicians in their search for relief before presenting to a subspecialist. Kostuik et al⁷ consider “unilateral sciatica with motor and sensory disturbance” a more common presentation of CES; also indicative of this condition, they report, is “urinary dysfunction combined with motor and sensory loss in the presence of a disc lesion.”

The polypeptide relaxin, which is secreted by the corpus luteum to promote joint laxity in late pregnancy, has been associated with low back pain and pelvic pain of pregnancy; it has also been suggested as a possible contributing cause of CES during pregnancy.^8,9 Additionally, increased lumbar lordosis with positional and postural stress may cause direct pressure by the gravid uterus on nerve roots. The great vessels may also be compressed by the uterus, resulting in ischemia of the neural element and back pain that radiates to the legs.¹⁰ Many cases of lumbar disk prolapse occur during the first and second trimesters. The most clinically incapacitated patients have been found to have the highest levels of relaxin.⁹

The Diagnosis
Early diagnosis of CES, through proper physical examination and radiologic studies, is paramount. A rectal examination should be performed to assess for sphincter tone (which may be diminished in 80% of patients) and to assess for perineal sensation.⁵ Catheterization yielding a postvoid residual urine greater than 100/200 cc is reported to have a specificity and sensitivity of 90% or greater for CES. Small et al⁵ recommend a straight leg raise maneuver to assess for radiculopathy.

Various studies in the literature support the use of MRI in the gravid patient to confirm the diagnosis of CES and to identify the degree and level of disk ­protrusion.^2-4,11

Treatment
CES requires urgent surgical decompression.¹¹ Early recognition of CES attributable to lumbar disk prolapse, report O’Laoire et al,¹² is essential to prevent irreversible sphincter paralysis. They liken the condition’s urgency to that of extradural hematoma in a head injury.

Disk surgery during pregnancy—preferably a team effort, with obstetrics performing perioperative fetal monitoring—has been deemed a safe management method.^2,4 Spinal or general anesthesia during nonobstetric surgery is generally considered safe for both mother and fetus.^13,14 Adequate oxygenation without risk for hyperventilation is considered essential.¹⁵

PATIENT OUTCOME
In the immediate postoperative period, the patient continued to complain of RLE pain, which abated significantly by the time she was discharged. When she was seen in follow-up four days later, she was able to heel- and toe-walk on the right side, and her strength had improved to 3 or 4 out of 5 at the RLE. She continued to experience diminished sensation to the plantar aspect of the right foot, which persisted at the one-month follow up. At that visit, the patient also reported occasional pain in the right buttock. Physical therapy was started to strengthen the RLE. 

By three months postsurgery, the patient had undergone uneventful vaginal delivery. She had an entirely benign exam with 5 out of 5 strength at the RLE and no neurologic deficits. She was cleared to return to light weightlifting with good technique and lumbar support but was told to refrain from running until the sixth month postsurgery.

CONCLUSION
Although the case patient did not have a “true” (ie, typical) presentation of CES, her symptoms warranted a full workup and treatment to prevent possible long-term sequelae. Medical practitioners should be familiar with the triad presentation of CES. They must differentiate lower back pain of muscular origin from lumbar disk herniation and be able to appreciate the degree of symptom severity reported by the gravid patient. A thorough history and physical assessment must be performed in every such case. When in doubt, the clinician must err on the side of caution, referring the patient for MRI and consulting with a specialist.

REFERENCES
1. Johnston RA. The management of acute spinal cord compression. J Neurol Neurosurg Psychiatr. 1993;56(10):1046-1054.

2. Brown MD, Levi AD. Surgery for lumbar disc herniation during pregnancy. Spine (Phila PA 1976). 2001;26(5):440-443.

3. LaBan MM, Perrin JCS, Latimer FR. Pregnancy and the herniated lumbar disc. Arch Phys Med Rehabil. 1983;64(7):319-321.

4. LaBan MM, Rapp NS, Van Oeyen P, Meerschaert JR. The lumbar herniated disk of pregnancy: a report of six cases identified by magnetic resonance imaging. Arch Phys Med Rehabil. 1995;76(5):476-479.

5. Small SA, Perron AD, Brady WJ. Orthopedic pitfalls: cauda equina syndrome. Am J Emerg Med. 2005;23(2):159-163.

6. Tay EC, Chacha PB. Midline prolapse of a lumbar intervertebral disc with compression of the cauda equina. J Bone Joint Surg. 1979;61(1):43-46.

7. Kostuik JP, Harrington I, Alexander D, et al. Cauda equina syndrome and lumbar disc herniation. J Bone Joint Surg Am. 1986;68(3):386-391.

8. Russell R, Reynolds F. Back pain, pregnancy, and childbirth. BMJ. 1997;314(7087):1062-1063.

9. MacLennan AH, Nicholson R, Green RC, Bath M. Serum relaxin and pelvic pain of pregnancy. Lancet. 1986;2(8501):243-245.

10. Ashkan K, Casey AT, Powell M, Crockard HA. Back pain during pregnancy and after childbirth: an unusual cause not to miss. J R Soc Med. 1998;91(2):88-90.

11. Busse JW, Bhandari M, Schnittker JB, et al. Delayed presentation of cauda equina syndrome secondary to lumbar disc herniation: functional outcomes and health-related quality of life. CJEM. 2001;3(4):285-291.

12. O’Laoire SA, Crockard HA, Thomas DG. Prognosis for sphincter recovery after operation for cauda equina compression owing to lumbar disc prolapse. Br Med J (Clin Res Ed). 1981;282(6279):1852-1854.

13. Kuczkowski KM. The safety of anaesthetics in pregnant women. Expert Opin Drug Saf. 2006; 5(2):251-264.

14. Kuczkowski KM. Nonobstetric surgery during pregnancy: what are the risks of anesthesia? Obstet Gynecol Surv. 2004;59(1):52-56.

15. Birnbach DJ, Browne IM. Anesthesia for obstetrics. In: Miller RD, Eriksson LI, Fleisher LA, et al. Miller’s Anesthesia. Philadelphia, PA: Churchill Livingston, Elsevier Health Science; 2010: 2203-2240.

CASE: Disoriented and delusional

Ms. P, a 53-year-old registered nurse, is admitted to the inpatient psychiatric unit with confusion, markedly disorganized thought processes, delayed verbal responsiveness, mood lability, and persecutory delusions. Shortly before hospitalization, Ms. P traveled approximately 360 miles from her daughter’s home with a male companion. Noting changes in her mental status, the man brought Ms. P to the local hospital. She was then transferred to our facility.

At admission, Ms. P is not oriented to time. She denies auditory or visual hallucinations and does not display psychomotor agitation or retardation. She reports her mood as sad and her affect is mildly labile. Insight and judgment are considered poor.

Five years ago, Ms. P and her mother were diagnosed with Fabry’s disease (FD) based on genetic analysis. Both women are carriers for the mutations and Ms. P’s mother was found to have almost absent galactosidase activity.

The authors’ observations

FD is an X-linked recessive glycolipid storage disease caused by deficient activity of the lysosomal storage enzyme α-galactosidase A. The disorder affects both men and women and leads to progressive intracellular accumulation of globotriaosylceramide and other related glycosphingolipids.^1,2 The earliest FD symptoms—burning pain and acroparesthesias—typically appear in childhood (Table 1).² FD often is misdiagnosed in women because women tend to display neurologic symptoms later than men, with typical symptom onset in the teenage years.^3,4 Often, these symptoms are confused with psychiatric disorders or vague neurologic or pain syndromes.⁵ In patients with no family history of FD, accurate diagnosis may not be made until adulthood.

Laboratory, dermatologic, and genetic tests can accurately determine the presence of FD.¹ However, because multiple organ systems are involved, initially attributing symptoms to FD is challenging, particularly in women.^1,3,5 For men, diagnosis can be established by measuring plasma or urinary globotriaosylceramide or plasma α-galactosidase A in addition to genetic analysis. In women, genetic analysis is a better diagnosis strategy because elevations in globotriaosylceramide or α-galactosidase A may not be prominent. An algorithm for diagnosing and assessing patients with FD has been proposed.²

Table 1

Typical signs and symptoms of Fabry’s disease

HISTORY: Cognitive deterioration

Ms. P has had psychiatric symptoms such as depression and anxiety since childhood. However, 3 years ago she started to experience psychological and cognitive deterioration. Medical records indicate that Ms. P described memory and concentration problems over the previous few years. She also reported pain, weakness, and numbness in her left leg after surgery for a work-related back injury, for which she received a financial settlement through workers’ compensation. Shortly thereafter, Ms. P separated from her third husband, moved in with her parents, and found work as a psychiatric nurse. She was dismissed after 6 weeks because she could not learn the electronic medical record system and had difficulty with memory and attention. Her performance on the Mini-Mental State Exam⁶ at that time was 28 out of 30, which was within normal limits.

After her parents died 3 years ago, Ms. P lived with her daughter, who became her primary caregiver and legal guardian. Ms. P’s daughter notes that her mother’s impulsive and risky behaviors grew more pronounced. Ms. P went on shopping sprees and became sexually promiscuous.

Ms. P’s psychiatric history includes childhood sexual abuse, hospitalization for a suicide attempt at age 19, and courses of psychotherapy and pharmacotherapy. In addition to FD, Ms. P’s medical history consists of coronary artery disease, type 2 diabetes mellitus, hypercholesterolemia, obesity, arthritis, back pain, fibromyalgia, and gastroesophageal reflux disease. Her family history is notable for alcohol abuse (both parents and a brother), lung cancer (mother), myocardial infarction (father), and Alzheimer’s disease (father).

The authors’ observations

Because α-galactosidase A is ubiquitous throughout the body, in addition to neurologic symptoms, FD involves multiple organ systems, with possible dermatologic, renal, gastrointestinal, cardiac, and cerebrovascular dysfunction. Despite growth in FD research, including the Fabry Outcomes Survey,³ the psychosocial and neuropsychiatric implications of the disease remain unclear.⁷ Behavioral presentations are idiosyncratic and unstable over time, depending on the structures impacted by progressive glycosphingolipid accumulation. Premature cardiovascular events (onset between age 30 and 40 for women), greater incidence of ischemic stroke or transient ischemic attack (7% to 30%), and frequent evidence of white matter lesions put FD patients at greater risk for developing presenile vascular dementia.^1,3 Nearly all male FD patients with dementia show some evidence of stroke or transient ischemic attack; cognitive functioning has not been well explored in female patients.⁴ In a heterogeneous sample of 15 FD patients age 7 to 61, Segal et al⁸ noted deficits in attention, processing speed, and executive function .75 to 1.95 standard deviations below normative means. No patients in this study had a history of stroke or transient ischemic attack; neuroimaging studies were not reported. Kolodny and Pastores⁹ suggested multiple mechanisms for cognitive disruption, suggesting that mild dementia late in the disease course could be secondary to diffuse leukomalacia, multiple strokes, or possibly to lipid storage in hippocampal and frontal lobe neurons.

Psychiatric comorbidity

Psychiatric illness, such as depression or a personality disorder, may be comorbid with FD, although pathologic mechanisms remain unclear.^7,10,11 Hypothesized mechanisms include:

• psychosocial stress from chronic disease
• white matter changes
• disruption of impaired L-arginine-nitric oxide pathways.^7,12

Crosbie et al¹³ noted that FD patients presented with greater psychological distress as measured by the Minnesota Multiphasic Personality Inventory-2 than patients with Gaucher disease or chronic heart disease. However, no significant differences were found between patients with FD and those diagnosed with a pain disorder. In the Segal et al study, out of 11 adult FD patients, 4 were diagnosed with major depressive disorder, 1 with schizophrenia, 2 with schizotypal personality disorder, and 1 with borderline personality disorder.⁸

EVALUATION: Brain abnormalities

Head CT scans (conducted 2 years ago and 6 months ago) revealed prominent cortical sulci likely caused by underlying volume loss, especially in bifrontal areas. A brain MRI performed 2 months ago indicated a moderate degree of subcortical atrophy in bilateral frontal and parietal regions. These radiology findings suggest mild to moderate frontal atrophy, mild degree of white matter changes, and slightly enlarged ventricles. An EEG showed background slowing and lack of an alpha rhythm, indicative of cerebral cortical dysfunction.

Ms. P’s α-galactosidase A level was within normal limits; however, normal enzyme levels frequently are reported in symptomatic and asymptomatic female FD patients.¹⁴ A dermatology consult confirmed the presence of skin findings characteristic of FD (ie, multiple cherry red papules extensively distributed throughout Ms. P’s chest, abdomen, and back, as well as upper and lower extremities).

Ms. P completed 2 neuropsychological assessments separated by 5 months. For a summary of the results of these tests, see the table titled “Ms. P’s neuropsychological assessment results”. Both assessments revealed grossly impaired intellectual capacity, memory, processing speed, and motor functioning. During the assessment, Ms. P could understand all directions with minimal changes from standardized protocols. Ms. P became insistent that she would not be able to complete memory tasks successfully. She gave up prematurely on tasks, saying they were too difficult. She admitted to guessing on several items because she did not want to continue the task.

Ms. P’s performance on tasks measuring effort and validity of a person’s neuropsychological presentation was consistent with someone exaggerating neurologic symptoms. A person with true dementia may perform as poorly as Ms. P did. However, Ms. P’s scores likely underestimated her level of functioning, even if she was experiencing dementia. Ms. P could not complete tasks individuals with severe dementia complete successfully, such as simple addition and subtraction and digit repetition. Ms. P recalled several recent and remote events, such as her breakfast menu and location of her first assessment, but could not recall words practiced multiple times. Although Ms. P’s scores on a complex card-sorting task were in the impaired range, a detailed review of her pattern indicated that although Ms. P could not generate any correct sorting categories, she made few repetitive responses and errors. This pattern is consistent with someone who understands task requirements, but deliberately avoids answering correctly. This suggests that she retained some ability for hypotheses generation and problem solving; however, because she exaggerated her symptoms, specific deficits could not be determined.

The authors’ observations

Ms. P presented with an interesting manifestation of neuropsychiatric symptoms in the context of FD; however, common cardiac and cerebrovascular features of the disease were not fully developed. Ms. P experienced progressive cognitive and behavioral changes for 2 years before her admission (Table 2), which may represent a prodromal period leading up to what appeared to be a frontally mediated dementia syndrome. Müller et al¹⁵ described a patient with FD who displayed a behavioral profile similar to Ms. P’s that included increasingly unstable mood for at least 3 years, borderline personality disorder features, and rapidly fluctuating mood. A case study reported that risperidone, 1 mg/d, used to treat psychosis in a male FD patient caused extrapyramidal symptoms.¹⁶

Ms. P presented with no evidence of stroke or transient ischemic attacks, which is atypical for FD patients with cognitive impairment. However, neuroimaging did reveal frontal atrophy that may be associated with her impulse control deficits, risk-taking behavior, emotional instability, and poor judgment. Her cognitive testing was notable for impairment and exaggeration of symptoms consistent with personality disorder symptoms. Possible reasons for exaggeration include a desire to maintain the sick role or secondary gain related to obtaining disability income.

Ms. P’s behavior pattern could be caused by dementia with frontal features, possibly secondary to FD, in combination with personality and psychiatric pathology.

The mainstay of FD treatment is enzyme replacement therapy (ERT), which addresses the underlying enzyme deficiency. Available research indicates that ERT may reduce symptom severity and slow disease progression; however, further studies are needed to determine if it will reduce outcomes such as stroke, ischemic heart disease, or renal disease.²

Table 2

Symptoms that preceded Ms. P’s admission

TREATMENT: Persistent deficits

Ms. P is started on risperidone rapidly titrated to 4 mg/d for delusional thinking and behavioral disturbance. After initially improving, she develops delirium when risperidone is increased to 4 mg/d. She has visual hallucinations, marked confusion with disorientation, worsened short-term memory, and an unsteady, shuffling gait. Risperidone is tapered and discontinued and Ms. P’s motor symptoms resolve within 2 days; however, she remains confused and delusional. We start her on quetiapine, 25 mg/d titrated to 50 mg/d, and her agitation and delusional thinking progressively decline. Memantine, titrated to 20 mg/d, and rivastigmine, started at 3 mg/d titrated to 9 mg/d, are added to address her cognitive symptoms.

Over several weeks, Ms. P’s mental status slowly improves and her drug-induced delirium completely resolves. However, she has persistent cognitive impairment characterized by compromised short-term memory and poor insight into her medical and psychological condition. She maintains unrealistic expectations about her ability to live independently and return to the workforce. The treatment team recommends that Ms. P’s daughter pursue guardianship and that she receive around-the-clock supervision after discharge from the hospital.

Table

Ms. P’s neuropsychological assessment results

Related Resources

• National Institute of Neurological Disorders and Stroke. Fabry disease information page. www.ninds.nih.gov/disorders/fabrys/fabrys.htm.
• National Fabry Disease Foundation. www.thenfdf.org.
• Rozenfeld P, Neumann PM. Treatment of Fabry disease: current and emerging strategies. Curr Pharm Biotechnol. 2011;12(6):916-922.

Drug Brand Names

• Donepezil • Aricept
• Memantine • Namenda
• Quetiapine • Seroquel
• Risperidone • Risperdal
• Rivastigmine • Exelon

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

CASE: Disoriented and delusional

Ms. P, a 53-year-old registered nurse, is admitted to the inpatient psychiatric unit with confusion, markedly disorganized thought processes, delayed verbal responsiveness, mood lability, and persecutory delusions. Shortly before hospitalization, Ms. P traveled approximately 360 miles from her daughter’s home with a male companion. Noting changes in her mental status, the man brought Ms. P to the local hospital. She was then transferred to our facility.

At admission, Ms. P is not oriented to time. She denies auditory or visual hallucinations and does not display psychomotor agitation or retardation. She reports her mood as sad and her affect is mildly labile. Insight and judgment are considered poor.

Five years ago, Ms. P and her mother were diagnosed with Fabry’s disease (FD) based on genetic analysis. Both women are carriers for the mutations and Ms. P’s mother was found to have almost absent galactosidase activity.

The authors’ observations

FD is an X-linked recessive glycolipid storage disease caused by deficient activity of the lysosomal storage enzyme α-galactosidase A. The disorder affects both men and women and leads to progressive intracellular accumulation of globotriaosylceramide and other related glycosphingolipids.^1,2 The earliest FD symptoms—burning pain and acroparesthesias—typically appear in childhood (Table 1).² FD often is misdiagnosed in women because women tend to display neurologic symptoms later than men, with typical symptom onset in the teenage years.^3,4 Often, these symptoms are confused with psychiatric disorders or vague neurologic or pain syndromes.⁵ In patients with no family history of FD, accurate diagnosis may not be made until adulthood.

Laboratory, dermatologic, and genetic tests can accurately determine the presence of FD.¹ However, because multiple organ systems are involved, initially attributing symptoms to FD is challenging, particularly in women.^1,3,5 For men, diagnosis can be established by measuring plasma or urinary globotriaosylceramide or plasma α-galactosidase A in addition to genetic analysis. In women, genetic analysis is a better diagnosis strategy because elevations in globotriaosylceramide or α-galactosidase A may not be prominent. An algorithm for diagnosing and assessing patients with FD has been proposed.²

Table 1

Typical signs and symptoms of Fabry’s disease

HISTORY: Cognitive deterioration

Ms. P has had psychiatric symptoms such as depression and anxiety since childhood. However, 3 years ago she started to experience psychological and cognitive deterioration. Medical records indicate that Ms. P described memory and concentration problems over the previous few years. She also reported pain, weakness, and numbness in her left leg after surgery for a work-related back injury, for which she received a financial settlement through workers’ compensation. Shortly thereafter, Ms. P separated from her third husband, moved in with her parents, and found work as a psychiatric nurse. She was dismissed after 6 weeks because she could not learn the electronic medical record system and had difficulty with memory and attention. Her performance on the Mini-Mental State Exam⁶ at that time was 28 out of 30, which was within normal limits.

After her parents died 3 years ago, Ms. P lived with her daughter, who became her primary caregiver and legal guardian. Ms. P’s daughter notes that her mother’s impulsive and risky behaviors grew more pronounced. Ms. P went on shopping sprees and became sexually promiscuous.

Ms. P’s psychiatric history includes childhood sexual abuse, hospitalization for a suicide attempt at age 19, and courses of psychotherapy and pharmacotherapy. In addition to FD, Ms. P’s medical history consists of coronary artery disease, type 2 diabetes mellitus, hypercholesterolemia, obesity, arthritis, back pain, fibromyalgia, and gastroesophageal reflux disease. Her family history is notable for alcohol abuse (both parents and a brother), lung cancer (mother), myocardial infarction (father), and Alzheimer’s disease (father).

The authors’ observations

Because α-galactosidase A is ubiquitous throughout the body, in addition to neurologic symptoms, FD involves multiple organ systems, with possible dermatologic, renal, gastrointestinal, cardiac, and cerebrovascular dysfunction. Despite growth in FD research, including the Fabry Outcomes Survey,³ the psychosocial and neuropsychiatric implications of the disease remain unclear.⁷ Behavioral presentations are idiosyncratic and unstable over time, depending on the structures impacted by progressive glycosphingolipid accumulation. Premature cardiovascular events (onset between age 30 and 40 for women), greater incidence of ischemic stroke or transient ischemic attack (7% to 30%), and frequent evidence of white matter lesions put FD patients at greater risk for developing presenile vascular dementia.^1,3 Nearly all male FD patients with dementia show some evidence of stroke or transient ischemic attack; cognitive functioning has not been well explored in female patients.⁴ In a heterogeneous sample of 15 FD patients age 7 to 61, Segal et al⁸ noted deficits in attention, processing speed, and executive function .75 to 1.95 standard deviations below normative means. No patients in this study had a history of stroke or transient ischemic attack; neuroimaging studies were not reported. Kolodny and Pastores⁹ suggested multiple mechanisms for cognitive disruption, suggesting that mild dementia late in the disease course could be secondary to diffuse leukomalacia, multiple strokes, or possibly to lipid storage in hippocampal and frontal lobe neurons.

Psychiatric comorbidity

Psychiatric illness, such as depression or a personality disorder, may be comorbid with FD, although pathologic mechanisms remain unclear.^7,10,11 Hypothesized mechanisms include:

• psychosocial stress from chronic disease
• white matter changes
• disruption of impaired L-arginine-nitric oxide pathways.^7,12

Crosbie et al¹³ noted that FD patients presented with greater psychological distress as measured by the Minnesota Multiphasic Personality Inventory-2 than patients with Gaucher disease or chronic heart disease. However, no significant differences were found between patients with FD and those diagnosed with a pain disorder. In the Segal et al study, out of 11 adult FD patients, 4 were diagnosed with major depressive disorder, 1 with schizophrenia, 2 with schizotypal personality disorder, and 1 with borderline personality disorder.⁸

EVALUATION: Brain abnormalities

Head CT scans (conducted 2 years ago and 6 months ago) revealed prominent cortical sulci likely caused by underlying volume loss, especially in bifrontal areas. A brain MRI performed 2 months ago indicated a moderate degree of subcortical atrophy in bilateral frontal and parietal regions. These radiology findings suggest mild to moderate frontal atrophy, mild degree of white matter changes, and slightly enlarged ventricles. An EEG showed background slowing and lack of an alpha rhythm, indicative of cerebral cortical dysfunction.

Ms. P’s α-galactosidase A level was within normal limits; however, normal enzyme levels frequently are reported in symptomatic and asymptomatic female FD patients.¹⁴ A dermatology consult confirmed the presence of skin findings characteristic of FD (ie, multiple cherry red papules extensively distributed throughout Ms. P’s chest, abdomen, and back, as well as upper and lower extremities).

Ms. P completed 2 neuropsychological assessments separated by 5 months. For a summary of the results of these tests, see the table titled “Ms. P’s neuropsychological assessment results”. Both assessments revealed grossly impaired intellectual capacity, memory, processing speed, and motor functioning. During the assessment, Ms. P could understand all directions with minimal changes from standardized protocols. Ms. P became insistent that she would not be able to complete memory tasks successfully. She gave up prematurely on tasks, saying they were too difficult. She admitted to guessing on several items because she did not want to continue the task.

Ms. P’s performance on tasks measuring effort and validity of a person’s neuropsychological presentation was consistent with someone exaggerating neurologic symptoms. A person with true dementia may perform as poorly as Ms. P did. However, Ms. P’s scores likely underestimated her level of functioning, even if she was experiencing dementia. Ms. P could not complete tasks individuals with severe dementia complete successfully, such as simple addition and subtraction and digit repetition. Ms. P recalled several recent and remote events, such as her breakfast menu and location of her first assessment, but could not recall words practiced multiple times. Although Ms. P’s scores on a complex card-sorting task were in the impaired range, a detailed review of her pattern indicated that although Ms. P could not generate any correct sorting categories, she made few repetitive responses and errors. This pattern is consistent with someone who understands task requirements, but deliberately avoids answering correctly. This suggests that she retained some ability for hypotheses generation and problem solving; however, because she exaggerated her symptoms, specific deficits could not be determined.

The authors’ observations

Ms. P presented with an interesting manifestation of neuropsychiatric symptoms in the context of FD; however, common cardiac and cerebrovascular features of the disease were not fully developed. Ms. P experienced progressive cognitive and behavioral changes for 2 years before her admission (Table 2), which may represent a prodromal period leading up to what appeared to be a frontally mediated dementia syndrome. Müller et al¹⁵ described a patient with FD who displayed a behavioral profile similar to Ms. P’s that included increasingly unstable mood for at least 3 years, borderline personality disorder features, and rapidly fluctuating mood. A case study reported that risperidone, 1 mg/d, used to treat psychosis in a male FD patient caused extrapyramidal symptoms.¹⁶

Ms. P presented with no evidence of stroke or transient ischemic attacks, which is atypical for FD patients with cognitive impairment. However, neuroimaging did reveal frontal atrophy that may be associated with her impulse control deficits, risk-taking behavior, emotional instability, and poor judgment. Her cognitive testing was notable for impairment and exaggeration of symptoms consistent with personality disorder symptoms. Possible reasons for exaggeration include a desire to maintain the sick role or secondary gain related to obtaining disability income.

Ms. P’s behavior pattern could be caused by dementia with frontal features, possibly secondary to FD, in combination with personality and psychiatric pathology.

The mainstay of FD treatment is enzyme replacement therapy (ERT), which addresses the underlying enzyme deficiency. Available research indicates that ERT may reduce symptom severity and slow disease progression; however, further studies are needed to determine if it will reduce outcomes such as stroke, ischemic heart disease, or renal disease.²

Table 2

Symptoms that preceded Ms. P’s admission

TREATMENT: Persistent deficits

Ms. P is started on risperidone rapidly titrated to 4 mg/d for delusional thinking and behavioral disturbance. After initially improving, she develops delirium when risperidone is increased to 4 mg/d. She has visual hallucinations, marked confusion with disorientation, worsened short-term memory, and an unsteady, shuffling gait. Risperidone is tapered and discontinued and Ms. P’s motor symptoms resolve within 2 days; however, she remains confused and delusional. We start her on quetiapine, 25 mg/d titrated to 50 mg/d, and her agitation and delusional thinking progressively decline. Memantine, titrated to 20 mg/d, and rivastigmine, started at 3 mg/d titrated to 9 mg/d, are added to address her cognitive symptoms.

Over several weeks, Ms. P’s mental status slowly improves and her drug-induced delirium completely resolves. However, she has persistent cognitive impairment characterized by compromised short-term memory and poor insight into her medical and psychological condition. She maintains unrealistic expectations about her ability to live independently and return to the workforce. The treatment team recommends that Ms. P’s daughter pursue guardianship and that she receive around-the-clock supervision after discharge from the hospital.

Table

Ms. P’s neuropsychological assessment results

Related Resources

• National Institute of Neurological Disorders and Stroke. Fabry disease information page. www.ninds.nih.gov/disorders/fabrys/fabrys.htm.
• National Fabry Disease Foundation. www.thenfdf.org.
• Rozenfeld P, Neumann PM. Treatment of Fabry disease: current and emerging strategies. Curr Pharm Biotechnol. 2011;12(6):916-922.

Drug Brand Names

• Donepezil • Aricept
• Memantine • Namenda
• Quetiapine • Seroquel
• Risperidone • Risperdal
• Rivastigmine • Exelon

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

CASE: Disoriented and delusional

Ms. P, a 53-year-old registered nurse, is admitted to the inpatient psychiatric unit with confusion, markedly disorganized thought processes, delayed verbal responsiveness, mood lability, and persecutory delusions. Shortly before hospitalization, Ms. P traveled approximately 360 miles from her daughter’s home with a male companion. Noting changes in her mental status, the man brought Ms. P to the local hospital. She was then transferred to our facility.

At admission, Ms. P is not oriented to time. She denies auditory or visual hallucinations and does not display psychomotor agitation or retardation. She reports her mood as sad and her affect is mildly labile. Insight and judgment are considered poor.

Five years ago, Ms. P and her mother were diagnosed with Fabry’s disease (FD) based on genetic analysis. Both women are carriers for the mutations and Ms. P’s mother was found to have almost absent galactosidase activity.

The authors’ observations

FD is an X-linked recessive glycolipid storage disease caused by deficient activity of the lysosomal storage enzyme α-galactosidase A. The disorder affects both men and women and leads to progressive intracellular accumulation of globotriaosylceramide and other related glycosphingolipids.^1,2 The earliest FD symptoms—burning pain and acroparesthesias—typically appear in childhood (Table 1).² FD often is misdiagnosed in women because women tend to display neurologic symptoms later than men, with typical symptom onset in the teenage years.^3,4 Often, these symptoms are confused with psychiatric disorders or vague neurologic or pain syndromes.⁵ In patients with no family history of FD, accurate diagnosis may not be made until adulthood.

Laboratory, dermatologic, and genetic tests can accurately determine the presence of FD.¹ However, because multiple organ systems are involved, initially attributing symptoms to FD is challenging, particularly in women.^1,3,5 For men, diagnosis can be established by measuring plasma or urinary globotriaosylceramide or plasma α-galactosidase A in addition to genetic analysis. In women, genetic analysis is a better diagnosis strategy because elevations in globotriaosylceramide or α-galactosidase A may not be prominent. An algorithm for diagnosing and assessing patients with FD has been proposed.²

Table 1

Typical signs and symptoms of Fabry’s disease

HISTORY: Cognitive deterioration

Ms. P has had psychiatric symptoms such as depression and anxiety since childhood. However, 3 years ago she started to experience psychological and cognitive deterioration. Medical records indicate that Ms. P described memory and concentration problems over the previous few years. She also reported pain, weakness, and numbness in her left leg after surgery for a work-related back injury, for which she received a financial settlement through workers’ compensation. Shortly thereafter, Ms. P separated from her third husband, moved in with her parents, and found work as a psychiatric nurse. She was dismissed after 6 weeks because she could not learn the electronic medical record system and had difficulty with memory and attention. Her performance on the Mini-Mental State Exam⁶ at that time was 28 out of 30, which was within normal limits.

After her parents died 3 years ago, Ms. P lived with her daughter, who became her primary caregiver and legal guardian. Ms. P’s daughter notes that her mother’s impulsive and risky behaviors grew more pronounced. Ms. P went on shopping sprees and became sexually promiscuous.

Ms. P’s psychiatric history includes childhood sexual abuse, hospitalization for a suicide attempt at age 19, and courses of psychotherapy and pharmacotherapy. In addition to FD, Ms. P’s medical history consists of coronary artery disease, type 2 diabetes mellitus, hypercholesterolemia, obesity, arthritis, back pain, fibromyalgia, and gastroesophageal reflux disease. Her family history is notable for alcohol abuse (both parents and a brother), lung cancer (mother), myocardial infarction (father), and Alzheimer’s disease (father).

The authors’ observations

Because α-galactosidase A is ubiquitous throughout the body, in addition to neurologic symptoms, FD involves multiple organ systems, with possible dermatologic, renal, gastrointestinal, cardiac, and cerebrovascular dysfunction. Despite growth in FD research, including the Fabry Outcomes Survey,³ the psychosocial and neuropsychiatric implications of the disease remain unclear.⁷ Behavioral presentations are idiosyncratic and unstable over time, depending on the structures impacted by progressive glycosphingolipid accumulation. Premature cardiovascular events (onset between age 30 and 40 for women), greater incidence of ischemic stroke or transient ischemic attack (7% to 30%), and frequent evidence of white matter lesions put FD patients at greater risk for developing presenile vascular dementia.^1,3 Nearly all male FD patients with dementia show some evidence of stroke or transient ischemic attack; cognitive functioning has not been well explored in female patients.⁴ In a heterogeneous sample of 15 FD patients age 7 to 61, Segal et al⁸ noted deficits in attention, processing speed, and executive function .75 to 1.95 standard deviations below normative means. No patients in this study had a history of stroke or transient ischemic attack; neuroimaging studies were not reported. Kolodny and Pastores⁹ suggested multiple mechanisms for cognitive disruption, suggesting that mild dementia late in the disease course could be secondary to diffuse leukomalacia, multiple strokes, or possibly to lipid storage in hippocampal and frontal lobe neurons.

Psychiatric comorbidity

Psychiatric illness, such as depression or a personality disorder, may be comorbid with FD, although pathologic mechanisms remain unclear.^7,10,11 Hypothesized mechanisms include:

• psychosocial stress from chronic disease
• white matter changes
• disruption of impaired L-arginine-nitric oxide pathways.^7,12

Crosbie et al¹³ noted that FD patients presented with greater psychological distress as measured by the Minnesota Multiphasic Personality Inventory-2 than patients with Gaucher disease or chronic heart disease. However, no significant differences were found between patients with FD and those diagnosed with a pain disorder. In the Segal et al study, out of 11 adult FD patients, 4 were diagnosed with major depressive disorder, 1 with schizophrenia, 2 with schizotypal personality disorder, and 1 with borderline personality disorder.⁸

EVALUATION: Brain abnormalities

Head CT scans (conducted 2 years ago and 6 months ago) revealed prominent cortical sulci likely caused by underlying volume loss, especially in bifrontal areas. A brain MRI performed 2 months ago indicated a moderate degree of subcortical atrophy in bilateral frontal and parietal regions. These radiology findings suggest mild to moderate frontal atrophy, mild degree of white matter changes, and slightly enlarged ventricles. An EEG showed background slowing and lack of an alpha rhythm, indicative of cerebral cortical dysfunction.

Ms. P’s α-galactosidase A level was within normal limits; however, normal enzyme levels frequently are reported in symptomatic and asymptomatic female FD patients.¹⁴ A dermatology consult confirmed the presence of skin findings characteristic of FD (ie, multiple cherry red papules extensively distributed throughout Ms. P’s chest, abdomen, and back, as well as upper and lower extremities).

Ms. P completed 2 neuropsychological assessments separated by 5 months. For a summary of the results of these tests, see the table titled “Ms. P’s neuropsychological assessment results”. Both assessments revealed grossly impaired intellectual capacity, memory, processing speed, and motor functioning. During the assessment, Ms. P could understand all directions with minimal changes from standardized protocols. Ms. P became insistent that she would not be able to complete memory tasks successfully. She gave up prematurely on tasks, saying they were too difficult. She admitted to guessing on several items because she did not want to continue the task.

Ms. P’s performance on tasks measuring effort and validity of a person’s neuropsychological presentation was consistent with someone exaggerating neurologic symptoms. A person with true dementia may perform as poorly as Ms. P did. However, Ms. P’s scores likely underestimated her level of functioning, even if she was experiencing dementia. Ms. P could not complete tasks individuals with severe dementia complete successfully, such as simple addition and subtraction and digit repetition. Ms. P recalled several recent and remote events, such as her breakfast menu and location of her first assessment, but could not recall words practiced multiple times. Although Ms. P’s scores on a complex card-sorting task were in the impaired range, a detailed review of her pattern indicated that although Ms. P could not generate any correct sorting categories, she made few repetitive responses and errors. This pattern is consistent with someone who understands task requirements, but deliberately avoids answering correctly. This suggests that she retained some ability for hypotheses generation and problem solving; however, because she exaggerated her symptoms, specific deficits could not be determined.

The authors’ observations

Ms. P presented with an interesting manifestation of neuropsychiatric symptoms in the context of FD; however, common cardiac and cerebrovascular features of the disease were not fully developed. Ms. P experienced progressive cognitive and behavioral changes for 2 years before her admission (Table 2), which may represent a prodromal period leading up to what appeared to be a frontally mediated dementia syndrome. Müller et al¹⁵ described a patient with FD who displayed a behavioral profile similar to Ms. P’s that included increasingly unstable mood for at least 3 years, borderline personality disorder features, and rapidly fluctuating mood. A case study reported that risperidone, 1 mg/d, used to treat psychosis in a male FD patient caused extrapyramidal symptoms.¹⁶

Ms. P presented with no evidence of stroke or transient ischemic attacks, which is atypical for FD patients with cognitive impairment. However, neuroimaging did reveal frontal atrophy that may be associated with her impulse control deficits, risk-taking behavior, emotional instability, and poor judgment. Her cognitive testing was notable for impairment and exaggeration of symptoms consistent with personality disorder symptoms. Possible reasons for exaggeration include a desire to maintain the sick role or secondary gain related to obtaining disability income.

Ms. P’s behavior pattern could be caused by dementia with frontal features, possibly secondary to FD, in combination with personality and psychiatric pathology.

The mainstay of FD treatment is enzyme replacement therapy (ERT), which addresses the underlying enzyme deficiency. Available research indicates that ERT may reduce symptom severity and slow disease progression; however, further studies are needed to determine if it will reduce outcomes such as stroke, ischemic heart disease, or renal disease.²

Table 2

Symptoms that preceded Ms. P’s admission

TREATMENT: Persistent deficits

Ms. P is started on risperidone rapidly titrated to 4 mg/d for delusional thinking and behavioral disturbance. After initially improving, she develops delirium when risperidone is increased to 4 mg/d. She has visual hallucinations, marked confusion with disorientation, worsened short-term memory, and an unsteady, shuffling gait. Risperidone is tapered and discontinued and Ms. P’s motor symptoms resolve within 2 days; however, she remains confused and delusional. We start her on quetiapine, 25 mg/d titrated to 50 mg/d, and her agitation and delusional thinking progressively decline. Memantine, titrated to 20 mg/d, and rivastigmine, started at 3 mg/d titrated to 9 mg/d, are added to address her cognitive symptoms.

Over several weeks, Ms. P’s mental status slowly improves and her drug-induced delirium completely resolves. However, she has persistent cognitive impairment characterized by compromised short-term memory and poor insight into her medical and psychological condition. She maintains unrealistic expectations about her ability to live independently and return to the workforce. The treatment team recommends that Ms. P’s daughter pursue guardianship and that she receive around-the-clock supervision after discharge from the hospital.

Table

Ms. P’s neuropsychological assessment results

Related Resources

• National Institute of Neurological Disorders and Stroke. Fabry disease information page. www.ninds.nih.gov/disorders/fabrys/fabrys.htm.
• National Fabry Disease Foundation. www.thenfdf.org.
• Rozenfeld P, Neumann PM. Treatment of Fabry disease: current and emerging strategies. Curr Pharm Biotechnol. 2011;12(6):916-922.

Drug Brand Names

• Donepezil • Aricept
• Memantine • Namenda
• Quetiapine • Seroquel
• Risperidone • Risperdal
• Rivastigmine • Exelon

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Culture results go undiscussed, man suffers stroke

TWO WEEKS AFTER PROSTATE SURGERY, a 76-year-old man went to the ED because he was having trouble urinating. The ED physician catheterized the patient, ordered a urine culture, and discharged him.

The culture results, showing methicillin-resistant Staphylococcus aureus, were sent to a printer in the ED twice, as was the usual practice, but evidently no one saw them.

The patient returned to the ED 2 weeks after his initial visit with the same complaint of difficult urination and was seen by the same physician. The physician again discharged him with a catheter but without mentioning the culture results. Two days later, the patient suffered a stroke, which paralyzed his left side.

PLAINTIFF’S CLAIM The bacteria had spread from the patient’s urine to his bloodstream, sparking a cascade of events that led to the stroke.

THE DEFENSE No information about the defense is available.

VERDICT $2.25 million New Jersey settlement.

COMMENT The repeated missed opportunities to diagnose and treat this patient’s infection were regrettable—and costly.

Inadequate differential proves fatal

SHORTNESS OF BREATH led a 52-year-old woman to visit her medical group, where she was a long-time patient. The family practitioner who saw her noted tachycardia and ordered an electrocardiogram, which was abnormal. The physician also ordered a chest x-ray and, because the woman had a history of anemia, a complete blood count and a number of other blood tests. He subsequently called the patient at home to tell her that the blood tests were normal and she didn’t have anemia.

Three days later, the patient went to an urgent care center complaining of shortness of breath and tightness in her chest. A pulmonary embolism was diagnosed, and she was transferred to a hospital ED. Later that evening, a code blue was called and the patient was resuscitated. She died the following day.

PLAINTIFF’S CLAIM The doctor assumed that the patient had anemia and failed to develop a differential diagnosis. The patient had risk factors for pulmonary embolism—obesity and the use of an ethinyl estradiol-etonogestrel vaginal contraceptive ring—which should have prompted the doctor to consider that possibility. If he had done so, the pulmonary embolism would have been diagnosed and the patient’s death prevented.

THE DEFENSE The patient’s presentation wasn’t typical for pulmonary embolism, and there wasn’t any way to know whether an earlier diagnosis would have resulted in survival.

VERDICT $1.9 million California verdict.

COMMENT Although pulmonary embolism can be a challenging diagnosis to make, it needs to be considered carefully in all patients with shortness of breath, chest pain, or poorly defined pulmonary or cardiac symptoms.

The correct diagnosis comes too late

FLU-LIKE SYMPTOMS AND AN IRREGULAR HEART RATE prompted a man to go to the ED, where the physician diagnosed a viral infection, prescribed pain medication, and discharged him. The following day, a laboratory report indicating a staph infection was sent to an ED secretary, but the patient wasn’t told the results.

The patient returned to the hospital 2 days later in a confused state. Tests revealed a staph infection and meningitis, for which the patient received antibiotics. A week later, the patient suffered a stroke, resulting in diminished cognitive ability, impaired vision, and right-sided motor deficits.

PLAINTIFF’S CLAIM The white blood cell count and C-reactive protein level measured at the patient’s first visit to the ED would have led to a diagnosis of bacterial infection. The patient should have been admitted to the hospital and given antibiotics at that time.

THE DEFENSE The original diagnosis was reasonable.

VERDICT Confidential settlement with the hospital. $900,000 net verdict against the physician in New Jersey.

COMMENT Lab reports gone awry and the lack of a fail-safe for abnormal tests result in a $900,000 judgment. Do you have adequate systems in place to avoid a communication failure like this one?

Slow response turns a bad situation into a disaster

A 66-YEAR-OLD MAN on warfarin therapy for chronic atrial fibrillation and a transient ischemic attack underwent lithotripsy for kidney stones. Three days after the lithotripsy, he went to the ED complaining of severe flank pain. A computed tomography (CT) scan of the abdomen showed a large retroperitoneal hematoma and prominent perinephric and pararenal hemorrhages.

The patient remained on a gurney in the hallway of the ED in deteriorating condition until he was admitted to the intensive care unit, by which time his condition was critical. He died the next day.

PLAINTIFF’S CLAIM The ED physician and admitting urologists failed to monitor and treat the patient’s active hemorrhage for 9 hours. They didn’t order coagulation studies or respond to signs of escalating hemorrhagic shock. They failed to seek timely consults from surgery and interventional radiology.

THE DEFENSE No information about the defense is available.

VERDICT $825,000 Virginia settlement.

COMMENT Preventing complications of anticoagulation is hard enough; the lack of a timely response in this case made a bad outcome disastrous.

Were steps taken quickly enough?

SEVERE LOWER ABDOMINAL PAIN prompted a 52-year-old woman to go to the ED. She said she hadn’t had a bowel movement in almost a week. The ED physician, in consultation with the attending physician, admitted her to the hospital and ordered intravenous fluids and a soap suds enema, which didn’t relieve the constipation. The patient’s vital signs deteriorated, and she was crying and restless.

When the attending physician saw the patient almost 3 hours after admission, she had a fever of 101.4°F. He ordered additional tests, a computed tomography (CT) scan, and antibiotics, but didn’t order them STAT.

About 1½ hours later, a house physician examined the patient, and, after speaking with the attending physician, transferred her to a step-down telemetry unit. About 1½ hours after the transfer, a nurse called the house physician to report that the patient’s condition was worsening. The house physician ordered pain relievers and a second enema but didn’t come to the hospital.

Because the patient wasn’t in the intensive care unit, no one checked on her again for 3½ hours. When the nurse did check, she found the patient pale, cold, and turning blue. The nurse called the house physician, who came to the hospital. The patient had a fever of 102.4°F and her blood pressure couldn’t be measured.

After speaking with the attending physician, the house physician had the patient admitted to the ICU and also ordered a STAT surgical consultation and CT scan. In the meantime, the patient went into cardiac arrest and couldn’t be revived. Death was caused by peritonitis with sepsis resulting from a large intestinal obstruction.

PLAINTIFF’S CLAIM The patient showed early signs of sepsis. She should have undergone testing sooner and been transferred to the ICU earlier.

THE DEFENSE The doctors claimed that all their actions were appropriate and that the actions suggested by the plaintiff wouldn’t have resulted in the patient’s survival.

VERDICT $3.8 million Pennsylvania verdict.

COMMENT Prompt evaluation and monitoring of this patient might have prevented death and a substantial verdict.

2 analgesic calamities: Death by fentanyl patch …

AFTER A WEEK OF INCREASING BACK PAIN, which had begun to shoot down his right leg, a 37-year-old man went to the ED. He was examined and given prescriptions for pain killers, including acetaminophen and hydrocodone, and muscle relaxants and discharged with instructions to return in 3 days for magnetic resonance imaging (MRI).

While he was at the hospital for the MRI, the patient returned to the ED because he was still in pain and his acetaminophen-hydrocodone prescription was running out. The ED physician prescribed a 0.75-mg fentanyl transdermal patch and instructed the patient to put it on his chest.

Three days later, the patient filled the prescription and applied the patch. The following day, his girlfriend found him dead in bed. Postmortem toxicology results showed a blood fentanyl level of 9.85 ng/mL, markedly higher than the therapeutic level. Respiratory failure caused by fentanyl toxicity was cited as the cause of death.

PLAINTIFF’S CLAIM The ED physician prescribed an excessive dose of fentanyl.

THE DEFENSE A defective patch or misuse of the patch caused the patient’s death.

VERDICT $1.2 million Indiana verdict.

… and methadone

A 36-YEAR-OLD MAN started treatment with a pain specialist for pain arising from a back problem, for which he had taken pain medication previously. The pain specialist prescribed methadone, 360 10-mg tablets. The prescription limited the patient to 2 tablets every 4 hours for a maximum dosage of 12 tablets (120 mg) per day.

Three days after the patient filled the prescription, he was found dead. An autopsy determined the cause of death to be drug toxicity from methadone. At the time the patient died, the bottle of methadone tablets contained 342 tablets, indicating that he had taken only 18 tablets, well within the maximum dosage authorized by the prescription.

PLAINTIFF’S CLAIM The prescribed methadone dosage was excessive for a patient just beginning to use the drug. A proper initial dosage is between 2.5 and 10 mg every 8 to 12 hours for a maximum of 30 mg per day.

THE DEFENSE No information about the defense is available.

VERDICT Confidential Utah settlement.

COMMENT These 2 cases have a common thread. The effects of opioids are often idiosyncratic. A plan for careful monitoring and follow-up should be prepared at initiation of treatment and when escalating the dosage.

Culture results go undiscussed, man suffers stroke

TWO WEEKS AFTER PROSTATE SURGERY, a 76-year-old man went to the ED because he was having trouble urinating. The ED physician catheterized the patient, ordered a urine culture, and discharged him.

The culture results, showing methicillin-resistant Staphylococcus aureus, were sent to a printer in the ED twice, as was the usual practice, but evidently no one saw them.

The patient returned to the ED 2 weeks after his initial visit with the same complaint of difficult urination and was seen by the same physician. The physician again discharged him with a catheter but without mentioning the culture results. Two days later, the patient suffered a stroke, which paralyzed his left side.

PLAINTIFF’S CLAIM The bacteria had spread from the patient’s urine to his bloodstream, sparking a cascade of events that led to the stroke.

THE DEFENSE No information about the defense is available.

VERDICT $2.25 million New Jersey settlement.

COMMENT The repeated missed opportunities to diagnose and treat this patient’s infection were regrettable—and costly.

Inadequate differential proves fatal

SHORTNESS OF BREATH led a 52-year-old woman to visit her medical group, where she was a long-time patient. The family practitioner who saw her noted tachycardia and ordered an electrocardiogram, which was abnormal. The physician also ordered a chest x-ray and, because the woman had a history of anemia, a complete blood count and a number of other blood tests. He subsequently called the patient at home to tell her that the blood tests were normal and she didn’t have anemia.

Three days later, the patient went to an urgent care center complaining of shortness of breath and tightness in her chest. A pulmonary embolism was diagnosed, and she was transferred to a hospital ED. Later that evening, a code blue was called and the patient was resuscitated. She died the following day.

PLAINTIFF’S CLAIM The doctor assumed that the patient had anemia and failed to develop a differential diagnosis. The patient had risk factors for pulmonary embolism—obesity and the use of an ethinyl estradiol-etonogestrel vaginal contraceptive ring—which should have prompted the doctor to consider that possibility. If he had done so, the pulmonary embolism would have been diagnosed and the patient’s death prevented.

THE DEFENSE The patient’s presentation wasn’t typical for pulmonary embolism, and there wasn’t any way to know whether an earlier diagnosis would have resulted in survival.

VERDICT $1.9 million California verdict.

COMMENT Although pulmonary embolism can be a challenging diagnosis to make, it needs to be considered carefully in all patients with shortness of breath, chest pain, or poorly defined pulmonary or cardiac symptoms.

The correct diagnosis comes too late

FLU-LIKE SYMPTOMS AND AN IRREGULAR HEART RATE prompted a man to go to the ED, where the physician diagnosed a viral infection, prescribed pain medication, and discharged him. The following day, a laboratory report indicating a staph infection was sent to an ED secretary, but the patient wasn’t told the results.

The patient returned to the hospital 2 days later in a confused state. Tests revealed a staph infection and meningitis, for which the patient received antibiotics. A week later, the patient suffered a stroke, resulting in diminished cognitive ability, impaired vision, and right-sided motor deficits.

PLAINTIFF’S CLAIM The white blood cell count and C-reactive protein level measured at the patient’s first visit to the ED would have led to a diagnosis of bacterial infection. The patient should have been admitted to the hospital and given antibiotics at that time.

THE DEFENSE The original diagnosis was reasonable.

VERDICT Confidential settlement with the hospital. $900,000 net verdict against the physician in New Jersey.

COMMENT Lab reports gone awry and the lack of a fail-safe for abnormal tests result in a $900,000 judgment. Do you have adequate systems in place to avoid a communication failure like this one?

Slow response turns a bad situation into a disaster

A 66-YEAR-OLD MAN on warfarin therapy for chronic atrial fibrillation and a transient ischemic attack underwent lithotripsy for kidney stones. Three days after the lithotripsy, he went to the ED complaining of severe flank pain. A computed tomography (CT) scan of the abdomen showed a large retroperitoneal hematoma and prominent perinephric and pararenal hemorrhages.

The patient remained on a gurney in the hallway of the ED in deteriorating condition until he was admitted to the intensive care unit, by which time his condition was critical. He died the next day.

PLAINTIFF’S CLAIM The ED physician and admitting urologists failed to monitor and treat the patient’s active hemorrhage for 9 hours. They didn’t order coagulation studies or respond to signs of escalating hemorrhagic shock. They failed to seek timely consults from surgery and interventional radiology.

THE DEFENSE No information about the defense is available.

VERDICT $825,000 Virginia settlement.

COMMENT Preventing complications of anticoagulation is hard enough; the lack of a timely response in this case made a bad outcome disastrous.

Were steps taken quickly enough?

SEVERE LOWER ABDOMINAL PAIN prompted a 52-year-old woman to go to the ED. She said she hadn’t had a bowel movement in almost a week. The ED physician, in consultation with the attending physician, admitted her to the hospital and ordered intravenous fluids and a soap suds enema, which didn’t relieve the constipation. The patient’s vital signs deteriorated, and she was crying and restless.

When the attending physician saw the patient almost 3 hours after admission, she had a fever of 101.4°F. He ordered additional tests, a computed tomography (CT) scan, and antibiotics, but didn’t order them STAT.

About 1½ hours later, a house physician examined the patient, and, after speaking with the attending physician, transferred her to a step-down telemetry unit. About 1½ hours after the transfer, a nurse called the house physician to report that the patient’s condition was worsening. The house physician ordered pain relievers and a second enema but didn’t come to the hospital.

Because the patient wasn’t in the intensive care unit, no one checked on her again for 3½ hours. When the nurse did check, she found the patient pale, cold, and turning blue. The nurse called the house physician, who came to the hospital. The patient had a fever of 102.4°F and her blood pressure couldn’t be measured.

After speaking with the attending physician, the house physician had the patient admitted to the ICU and also ordered a STAT surgical consultation and CT scan. In the meantime, the patient went into cardiac arrest and couldn’t be revived. Death was caused by peritonitis with sepsis resulting from a large intestinal obstruction.

PLAINTIFF’S CLAIM The patient showed early signs of sepsis. She should have undergone testing sooner and been transferred to the ICU earlier.

THE DEFENSE The doctors claimed that all their actions were appropriate and that the actions suggested by the plaintiff wouldn’t have resulted in the patient’s survival.

VERDICT $3.8 million Pennsylvania verdict.

COMMENT Prompt evaluation and monitoring of this patient might have prevented death and a substantial verdict.

2 analgesic calamities: Death by fentanyl patch …

AFTER A WEEK OF INCREASING BACK PAIN, which had begun to shoot down his right leg, a 37-year-old man went to the ED. He was examined and given prescriptions for pain killers, including acetaminophen and hydrocodone, and muscle relaxants and discharged with instructions to return in 3 days for magnetic resonance imaging (MRI).

While he was at the hospital for the MRI, the patient returned to the ED because he was still in pain and his acetaminophen-hydrocodone prescription was running out. The ED physician prescribed a 0.75-mg fentanyl transdermal patch and instructed the patient to put it on his chest.

Three days later, the patient filled the prescription and applied the patch. The following day, his girlfriend found him dead in bed. Postmortem toxicology results showed a blood fentanyl level of 9.85 ng/mL, markedly higher than the therapeutic level. Respiratory failure caused by fentanyl toxicity was cited as the cause of death.

PLAINTIFF’S CLAIM The ED physician prescribed an excessive dose of fentanyl.

THE DEFENSE A defective patch or misuse of the patch caused the patient’s death.

VERDICT $1.2 million Indiana verdict.

… and methadone

A 36-YEAR-OLD MAN started treatment with a pain specialist for pain arising from a back problem, for which he had taken pain medication previously. The pain specialist prescribed methadone, 360 10-mg tablets. The prescription limited the patient to 2 tablets every 4 hours for a maximum dosage of 12 tablets (120 mg) per day.

Three days after the patient filled the prescription, he was found dead. An autopsy determined the cause of death to be drug toxicity from methadone. At the time the patient died, the bottle of methadone tablets contained 342 tablets, indicating that he had taken only 18 tablets, well within the maximum dosage authorized by the prescription.

PLAINTIFF’S CLAIM The prescribed methadone dosage was excessive for a patient just beginning to use the drug. A proper initial dosage is between 2.5 and 10 mg every 8 to 12 hours for a maximum of 30 mg per day.

THE DEFENSE No information about the defense is available.

VERDICT Confidential Utah settlement.

COMMENT These 2 cases have a common thread. The effects of opioids are often idiosyncratic. A plan for careful monitoring and follow-up should be prepared at initiation of treatment and when escalating the dosage.

Culture results go undiscussed, man suffers stroke

TWO WEEKS AFTER PROSTATE SURGERY, a 76-year-old man went to the ED because he was having trouble urinating. The ED physician catheterized the patient, ordered a urine culture, and discharged him.

The culture results, showing methicillin-resistant Staphylococcus aureus, were sent to a printer in the ED twice, as was the usual practice, but evidently no one saw them.

The patient returned to the ED 2 weeks after his initial visit with the same complaint of difficult urination and was seen by the same physician. The physician again discharged him with a catheter but without mentioning the culture results. Two days later, the patient suffered a stroke, which paralyzed his left side.

PLAINTIFF’S CLAIM The bacteria had spread from the patient’s urine to his bloodstream, sparking a cascade of events that led to the stroke.

THE DEFENSE No information about the defense is available.

VERDICT $2.25 million New Jersey settlement.

COMMENT The repeated missed opportunities to diagnose and treat this patient’s infection were regrettable—and costly.

Inadequate differential proves fatal

SHORTNESS OF BREATH led a 52-year-old woman to visit her medical group, where she was a long-time patient. The family practitioner who saw her noted tachycardia and ordered an electrocardiogram, which was abnormal. The physician also ordered a chest x-ray and, because the woman had a history of anemia, a complete blood count and a number of other blood tests. He subsequently called the patient at home to tell her that the blood tests were normal and she didn’t have anemia.

Three days later, the patient went to an urgent care center complaining of shortness of breath and tightness in her chest. A pulmonary embolism was diagnosed, and she was transferred to a hospital ED. Later that evening, a code blue was called and the patient was resuscitated. She died the following day.

PLAINTIFF’S CLAIM The doctor assumed that the patient had anemia and failed to develop a differential diagnosis. The patient had risk factors for pulmonary embolism—obesity and the use of an ethinyl estradiol-etonogestrel vaginal contraceptive ring—which should have prompted the doctor to consider that possibility. If he had done so, the pulmonary embolism would have been diagnosed and the patient’s death prevented.

THE DEFENSE The patient’s presentation wasn’t typical for pulmonary embolism, and there wasn’t any way to know whether an earlier diagnosis would have resulted in survival.

VERDICT $1.9 million California verdict.

COMMENT Although pulmonary embolism can be a challenging diagnosis to make, it needs to be considered carefully in all patients with shortness of breath, chest pain, or poorly defined pulmonary or cardiac symptoms.

The correct diagnosis comes too late

FLU-LIKE SYMPTOMS AND AN IRREGULAR HEART RATE prompted a man to go to the ED, where the physician diagnosed a viral infection, prescribed pain medication, and discharged him. The following day, a laboratory report indicating a staph infection was sent to an ED secretary, but the patient wasn’t told the results.

The patient returned to the hospital 2 days later in a confused state. Tests revealed a staph infection and meningitis, for which the patient received antibiotics. A week later, the patient suffered a stroke, resulting in diminished cognitive ability, impaired vision, and right-sided motor deficits.

PLAINTIFF’S CLAIM The white blood cell count and C-reactive protein level measured at the patient’s first visit to the ED would have led to a diagnosis of bacterial infection. The patient should have been admitted to the hospital and given antibiotics at that time.

THE DEFENSE The original diagnosis was reasonable.

VERDICT Confidential settlement with the hospital. $900,000 net verdict against the physician in New Jersey.

COMMENT Lab reports gone awry and the lack of a fail-safe for abnormal tests result in a $900,000 judgment. Do you have adequate systems in place to avoid a communication failure like this one?

Slow response turns a bad situation into a disaster

A 66-YEAR-OLD MAN on warfarin therapy for chronic atrial fibrillation and a transient ischemic attack underwent lithotripsy for kidney stones. Three days after the lithotripsy, he went to the ED complaining of severe flank pain. A computed tomography (CT) scan of the abdomen showed a large retroperitoneal hematoma and prominent perinephric and pararenal hemorrhages.

The patient remained on a gurney in the hallway of the ED in deteriorating condition until he was admitted to the intensive care unit, by which time his condition was critical. He died the next day.

PLAINTIFF’S CLAIM The ED physician and admitting urologists failed to monitor and treat the patient’s active hemorrhage for 9 hours. They didn’t order coagulation studies or respond to signs of escalating hemorrhagic shock. They failed to seek timely consults from surgery and interventional radiology.

THE DEFENSE No information about the defense is available.

VERDICT $825,000 Virginia settlement.

COMMENT Preventing complications of anticoagulation is hard enough; the lack of a timely response in this case made a bad outcome disastrous.

Were steps taken quickly enough?

SEVERE LOWER ABDOMINAL PAIN prompted a 52-year-old woman to go to the ED. She said she hadn’t had a bowel movement in almost a week. The ED physician, in consultation with the attending physician, admitted her to the hospital and ordered intravenous fluids and a soap suds enema, which didn’t relieve the constipation. The patient’s vital signs deteriorated, and she was crying and restless.

When the attending physician saw the patient almost 3 hours after admission, she had a fever of 101.4°F. He ordered additional tests, a computed tomography (CT) scan, and antibiotics, but didn’t order them STAT.

About 1½ hours later, a house physician examined the patient, and, after speaking with the attending physician, transferred her to a step-down telemetry unit. About 1½ hours after the transfer, a nurse called the house physician to report that the patient’s condition was worsening. The house physician ordered pain relievers and a second enema but didn’t come to the hospital.

Because the patient wasn’t in the intensive care unit, no one checked on her again for 3½ hours. When the nurse did check, she found the patient pale, cold, and turning blue. The nurse called the house physician, who came to the hospital. The patient had a fever of 102.4°F and her blood pressure couldn’t be measured.

After speaking with the attending physician, the house physician had the patient admitted to the ICU and also ordered a STAT surgical consultation and CT scan. In the meantime, the patient went into cardiac arrest and couldn’t be revived. Death was caused by peritonitis with sepsis resulting from a large intestinal obstruction.

PLAINTIFF’S CLAIM The patient showed early signs of sepsis. She should have undergone testing sooner and been transferred to the ICU earlier.

THE DEFENSE The doctors claimed that all their actions were appropriate and that the actions suggested by the plaintiff wouldn’t have resulted in the patient’s survival.

VERDICT $3.8 million Pennsylvania verdict.

COMMENT Prompt evaluation and monitoring of this patient might have prevented death and a substantial verdict.

2 analgesic calamities: Death by fentanyl patch …

AFTER A WEEK OF INCREASING BACK PAIN, which had begun to shoot down his right leg, a 37-year-old man went to the ED. He was examined and given prescriptions for pain killers, including acetaminophen and hydrocodone, and muscle relaxants and discharged with instructions to return in 3 days for magnetic resonance imaging (MRI).

While he was at the hospital for the MRI, the patient returned to the ED because he was still in pain and his acetaminophen-hydrocodone prescription was running out. The ED physician prescribed a 0.75-mg fentanyl transdermal patch and instructed the patient to put it on his chest.

Three days later, the patient filled the prescription and applied the patch. The following day, his girlfriend found him dead in bed. Postmortem toxicology results showed a blood fentanyl level of 9.85 ng/mL, markedly higher than the therapeutic level. Respiratory failure caused by fentanyl toxicity was cited as the cause of death.

PLAINTIFF’S CLAIM The ED physician prescribed an excessive dose of fentanyl.

THE DEFENSE A defective patch or misuse of the patch caused the patient’s death.

VERDICT $1.2 million Indiana verdict.

… and methadone

A 36-YEAR-OLD MAN started treatment with a pain specialist for pain arising from a back problem, for which he had taken pain medication previously. The pain specialist prescribed methadone, 360 10-mg tablets. The prescription limited the patient to 2 tablets every 4 hours for a maximum dosage of 12 tablets (120 mg) per day.

Three days after the patient filled the prescription, he was found dead. An autopsy determined the cause of death to be drug toxicity from methadone. At the time the patient died, the bottle of methadone tablets contained 342 tablets, indicating that he had taken only 18 tablets, well within the maximum dosage authorized by the prescription.

PLAINTIFF’S CLAIM The prescribed methadone dosage was excessive for a patient just beginning to use the drug. A proper initial dosage is between 2.5 and 10 mg every 8 to 12 hours for a maximum of 30 mg per day.

THE DEFENSE No information about the defense is available.

VERDICT Confidential Utah settlement.

COMMENT These 2 cases have a common thread. The effects of opioids are often idiosyncratic. A plan for careful monitoring and follow-up should be prepared at initiation of treatment and when escalating the dosage.

ILLUSTRATIVE CASE

Mr. H, age 75, underwent radical prostatectomy for prostate cancer a year ago. Since then, he leaks urine when he coughs and occasionally has complete loss of bladder control. His lack of control has forced him to curtail many of his normal activities and he wants to know what help you can provide.

Routine prostate-specific antigen (PSA) screening has led to an increase in the diagnosis of localized prostate cancer, and prostatectomy is a common treatment. Approximately 90,000 US men undergo radical prostatectomy each year,² and most are left with some degree of incontinence.

Years later, bladder control problems remain
Surgical advances have attempted to minimize nerve and bladder neck damage, but some degree of incontinence is still common after radical prostatectomy. According to the 2000 Prostate Cancer Outcomes Study, 80% of men experienced some incontinence 6 months after radical prostatectomy. After 2 years, 68% of men still had some degree of incontinence,³ and 8% reported frequent or total incontinence. Five years after prostatectomy, only 35% of patients reported complete bladder control vs 87% presurgery.⁴

A 2004 systematic review showed that behavioral therapy (mostly biofeedback) reduced symptoms in patients with all types of urinary incontinence.⁵ Many studies, including a 2010 Cochrane review,⁶ have shown that women with incontinence benefit from pelvic floor muscle training. No randomized trials have assessed the benefit of behavioral therapy for men with incontinence related to postprostatectomy—until now.

STUDY SUMMARY: Behavioral therapy has long-term payoff

The study by Goode et al was an RCT of behavioral therapy for men who had urinary incontinence after radical prostatectomy and whose symptoms persisted more than a year later. It included patients with ≥3 episodes of incontinence per week. Men were excluded if they were undergoing other treatment for prostate cancer, had a high postvoid residual volume or a history of certain bladder surgeries, or were unable to reliably report symptoms. Participants were permitted to continue taking medication for incontinence, with the exception of anticholinergics.

Participants (n=208 from 3 sites) were randomized to one of 3 arms in a blinded fashion with concealed allocation: behavioral therapy alone, behavioral therapy and biofeedback with electrical stimulation, or a control group of men who could elect to try these therapies at a later date.

Behavioral therapy consisted of 4 visits with a physician or nurse practitioner over an 8-week period. At the first visit, patients received instruction in pelvic floor muscle training. Patients then practiced contraction and relaxation exercises and urinary flow control at home. At the second visit, patients learned techniques to avoid episodes of incontinence, such as performing pelvic muscle contractions with stress symptom triggers. During the final 2 visits, patients received advice about control of persistent problems identified in symptom diaries they were required to keep. In addition, continued daily pelvic floor exercises were recommended at the last session.

Men in the group that received biofeedback with electrical stimulation had the same visit schedule, but received additional pelvic floor training—with electrode-mediated feedback and electrical stimulation of pelvic floor muscles during each visit and daily at home. Patients in the control group had the same visit frequency but received no treatment. After 8 weeks, however, the controls were given the opportunity to try behavioral therapy.

Baseline characteristics and attrition rates were similar in all 3 groups. Outcomes were based on an intention-to-treat analysis. At 8 weeks, men receiving behavioral therapy, with or without electrical stimulation and biofeedback, experienced a 55% decrease in incontinence (from 28 episodes per week at baseline to 13 per week); patients in the control group had a 24% decrease (from 25 episodes to 20 per week) (P=.001). More patients in the behavioral groups were completely continent at 8 weeks (16% vs 6% for the controls); the number needed to treat to achieve complete continence was 10. Electrical stimulation and biofeedback provided no added benefit compared with behavioral therapy alone.

Patients in the 2 treatment groups also had clinically significant benefits in some quality-of-life measures (impact of urinary symptoms on travel, emotion, and voiding) and in symptom-specific quality-of-life scores. Patient satisfaction at 8 weeks was higher in the treatment groups: 26 of the 58 men who received behavioral therapy were “delighted, pleased, or mostly satisfied,” vs 9 of 60 in the control group (P=.006 for overall group difference).

Adherence to the behavioral therapy protocol was 100% at 8 weeks and remained high (91%) one year later. Improvement in symptoms continued at one year, with patients in both treatment groups reporting a clinically significant (50%) reduction in incontinence episodes compared with baseline.

WHAT’S NEW: We have evidence-based help for postprostatectomy incontinence

We now have evidence that an 8-week program of pelvic floor training and bladder control strategies reduces the frequency of incontinence in men who have undergone radical prostatectomy.

CAVEATS: The effects of time weren’t factored in

Patients were obviously aware of group assignment, so there is the possibility of treatment bias contributing to the positive self-reported outcomes. While the treatment groups showed both a greater initial improvement and persistent improvement in their symptoms at one year, symptoms of patients in the control group were not measured after a year, so the sustained improvement could reflect resolution of incontinence with time.

CHALLENGES TO IMPLEMENTATION: Locating clinicians who can train patients

The type of behavioral therapy featured in this study may not be easily accessible to all patients. The researchers suggest consulting the National Association for Continence (http://www.nafc.org), a private nonprofit organization whose members include physical therapists, nurses, and physicians. They also cite the Wound Ostomy and Continence Nurses Society (http://www.wocn.org) as a resource in locating nurses who provide these services.

Acknowledgement

The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Click here to view PURL METHODOLOGY

ILLUSTRATIVE CASE

Mr. H, age 75, underwent radical prostatectomy for prostate cancer a year ago. Since then, he leaks urine when he coughs and occasionally has complete loss of bladder control. His lack of control has forced him to curtail many of his normal activities and he wants to know what help you can provide.

Routine prostate-specific antigen (PSA) screening has led to an increase in the diagnosis of localized prostate cancer, and prostatectomy is a common treatment. Approximately 90,000 US men undergo radical prostatectomy each year,² and most are left with some degree of incontinence.

Years later, bladder control problems remain
Surgical advances have attempted to minimize nerve and bladder neck damage, but some degree of incontinence is still common after radical prostatectomy. According to the 2000 Prostate Cancer Outcomes Study, 80% of men experienced some incontinence 6 months after radical prostatectomy. After 2 years, 68% of men still had some degree of incontinence,³ and 8% reported frequent or total incontinence. Five years after prostatectomy, only 35% of patients reported complete bladder control vs 87% presurgery.⁴

A 2004 systematic review showed that behavioral therapy (mostly biofeedback) reduced symptoms in patients with all types of urinary incontinence.⁵ Many studies, including a 2010 Cochrane review,⁶ have shown that women with incontinence benefit from pelvic floor muscle training. No randomized trials have assessed the benefit of behavioral therapy for men with incontinence related to postprostatectomy—until now.

STUDY SUMMARY: Behavioral therapy has long-term payoff

The study by Goode et al was an RCT of behavioral therapy for men who had urinary incontinence after radical prostatectomy and whose symptoms persisted more than a year later. It included patients with ≥3 episodes of incontinence per week. Men were excluded if they were undergoing other treatment for prostate cancer, had a high postvoid residual volume or a history of certain bladder surgeries, or were unable to reliably report symptoms. Participants were permitted to continue taking medication for incontinence, with the exception of anticholinergics.

Participants (n=208 from 3 sites) were randomized to one of 3 arms in a blinded fashion with concealed allocation: behavioral therapy alone, behavioral therapy and biofeedback with electrical stimulation, or a control group of men who could elect to try these therapies at a later date.

Behavioral therapy consisted of 4 visits with a physician or nurse practitioner over an 8-week period. At the first visit, patients received instruction in pelvic floor muscle training. Patients then practiced contraction and relaxation exercises and urinary flow control at home. At the second visit, patients learned techniques to avoid episodes of incontinence, such as performing pelvic muscle contractions with stress symptom triggers. During the final 2 visits, patients received advice about control of persistent problems identified in symptom diaries they were required to keep. In addition, continued daily pelvic floor exercises were recommended at the last session.

Men in the group that received biofeedback with electrical stimulation had the same visit schedule, but received additional pelvic floor training—with electrode-mediated feedback and electrical stimulation of pelvic floor muscles during each visit and daily at home. Patients in the control group had the same visit frequency but received no treatment. After 8 weeks, however, the controls were given the opportunity to try behavioral therapy.

Baseline characteristics and attrition rates were similar in all 3 groups. Outcomes were based on an intention-to-treat analysis. At 8 weeks, men receiving behavioral therapy, with or without electrical stimulation and biofeedback, experienced a 55% decrease in incontinence (from 28 episodes per week at baseline to 13 per week); patients in the control group had a 24% decrease (from 25 episodes to 20 per week) (P=.001). More patients in the behavioral groups were completely continent at 8 weeks (16% vs 6% for the controls); the number needed to treat to achieve complete continence was 10. Electrical stimulation and biofeedback provided no added benefit compared with behavioral therapy alone.

Patients in the 2 treatment groups also had clinically significant benefits in some quality-of-life measures (impact of urinary symptoms on travel, emotion, and voiding) and in symptom-specific quality-of-life scores. Patient satisfaction at 8 weeks was higher in the treatment groups: 26 of the 58 men who received behavioral therapy were “delighted, pleased, or mostly satisfied,” vs 9 of 60 in the control group (P=.006 for overall group difference).

Adherence to the behavioral therapy protocol was 100% at 8 weeks and remained high (91%) one year later. Improvement in symptoms continued at one year, with patients in both treatment groups reporting a clinically significant (50%) reduction in incontinence episodes compared with baseline.

WHAT’S NEW: We have evidence-based help for postprostatectomy incontinence

We now have evidence that an 8-week program of pelvic floor training and bladder control strategies reduces the frequency of incontinence in men who have undergone radical prostatectomy.

CAVEATS: The effects of time weren’t factored in

Patients were obviously aware of group assignment, so there is the possibility of treatment bias contributing to the positive self-reported outcomes. While the treatment groups showed both a greater initial improvement and persistent improvement in their symptoms at one year, symptoms of patients in the control group were not measured after a year, so the sustained improvement could reflect resolution of incontinence with time.

CHALLENGES TO IMPLEMENTATION: Locating clinicians who can train patients

The type of behavioral therapy featured in this study may not be easily accessible to all patients. The researchers suggest consulting the National Association for Continence (http://www.nafc.org), a private nonprofit organization whose members include physical therapists, nurses, and physicians. They also cite the Wound Ostomy and Continence Nurses Society (http://www.wocn.org) as a resource in locating nurses who provide these services.

Acknowledgement

The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Click here to view PURL METHODOLOGY

ILLUSTRATIVE CASE

Mr. H, age 75, underwent radical prostatectomy for prostate cancer a year ago. Since then, he leaks urine when he coughs and occasionally has complete loss of bladder control. His lack of control has forced him to curtail many of his normal activities and he wants to know what help you can provide.

Routine prostate-specific antigen (PSA) screening has led to an increase in the diagnosis of localized prostate cancer, and prostatectomy is a common treatment. Approximately 90,000 US men undergo radical prostatectomy each year,² and most are left with some degree of incontinence.

Years later, bladder control problems remain
Surgical advances have attempted to minimize nerve and bladder neck damage, but some degree of incontinence is still common after radical prostatectomy. According to the 2000 Prostate Cancer Outcomes Study, 80% of men experienced some incontinence 6 months after radical prostatectomy. After 2 years, 68% of men still had some degree of incontinence,³ and 8% reported frequent or total incontinence. Five years after prostatectomy, only 35% of patients reported complete bladder control vs 87% presurgery.⁴

A 2004 systematic review showed that behavioral therapy (mostly biofeedback) reduced symptoms in patients with all types of urinary incontinence.⁵ Many studies, including a 2010 Cochrane review,⁶ have shown that women with incontinence benefit from pelvic floor muscle training. No randomized trials have assessed the benefit of behavioral therapy for men with incontinence related to postprostatectomy—until now.

STUDY SUMMARY: Behavioral therapy has long-term payoff

The study by Goode et al was an RCT of behavioral therapy for men who had urinary incontinence after radical prostatectomy and whose symptoms persisted more than a year later. It included patients with ≥3 episodes of incontinence per week. Men were excluded if they were undergoing other treatment for prostate cancer, had a high postvoid residual volume or a history of certain bladder surgeries, or were unable to reliably report symptoms. Participants were permitted to continue taking medication for incontinence, with the exception of anticholinergics.

Participants (n=208 from 3 sites) were randomized to one of 3 arms in a blinded fashion with concealed allocation: behavioral therapy alone, behavioral therapy and biofeedback with electrical stimulation, or a control group of men who could elect to try these therapies at a later date.

Behavioral therapy consisted of 4 visits with a physician or nurse practitioner over an 8-week period. At the first visit, patients received instruction in pelvic floor muscle training. Patients then practiced contraction and relaxation exercises and urinary flow control at home. At the second visit, patients learned techniques to avoid episodes of incontinence, such as performing pelvic muscle contractions with stress symptom triggers. During the final 2 visits, patients received advice about control of persistent problems identified in symptom diaries they were required to keep. In addition, continued daily pelvic floor exercises were recommended at the last session.

Men in the group that received biofeedback with electrical stimulation had the same visit schedule, but received additional pelvic floor training—with electrode-mediated feedback and electrical stimulation of pelvic floor muscles during each visit and daily at home. Patients in the control group had the same visit frequency but received no treatment. After 8 weeks, however, the controls were given the opportunity to try behavioral therapy.

Baseline characteristics and attrition rates were similar in all 3 groups. Outcomes were based on an intention-to-treat analysis. At 8 weeks, men receiving behavioral therapy, with or without electrical stimulation and biofeedback, experienced a 55% decrease in incontinence (from 28 episodes per week at baseline to 13 per week); patients in the control group had a 24% decrease (from 25 episodes to 20 per week) (P=.001). More patients in the behavioral groups were completely continent at 8 weeks (16% vs 6% for the controls); the number needed to treat to achieve complete continence was 10. Electrical stimulation and biofeedback provided no added benefit compared with behavioral therapy alone.

Patients in the 2 treatment groups also had clinically significant benefits in some quality-of-life measures (impact of urinary symptoms on travel, emotion, and voiding) and in symptom-specific quality-of-life scores. Patient satisfaction at 8 weeks was higher in the treatment groups: 26 of the 58 men who received behavioral therapy were “delighted, pleased, or mostly satisfied,” vs 9 of 60 in the control group (P=.006 for overall group difference).

Adherence to the behavioral therapy protocol was 100% at 8 weeks and remained high (91%) one year later. Improvement in symptoms continued at one year, with patients in both treatment groups reporting a clinically significant (50%) reduction in incontinence episodes compared with baseline.

WHAT’S NEW: We have evidence-based help for postprostatectomy incontinence

We now have evidence that an 8-week program of pelvic floor training and bladder control strategies reduces the frequency of incontinence in men who have undergone radical prostatectomy.

CAVEATS: The effects of time weren’t factored in

Patients were obviously aware of group assignment, so there is the possibility of treatment bias contributing to the positive self-reported outcomes. While the treatment groups showed both a greater initial improvement and persistent improvement in their symptoms at one year, symptoms of patients in the control group were not measured after a year, so the sustained improvement could reflect resolution of incontinence with time.

CHALLENGES TO IMPLEMENTATION: Locating clinicians who can train patients

The type of behavioral therapy featured in this study may not be easily accessible to all patients. The researchers suggest consulting the National Association for Continence (http://www.nafc.org), a private nonprofit organization whose members include physical therapists, nurses, and physicians. They also cite the Wound Ostomy and Continence Nurses Society (http://www.wocn.org) as a resource in locating nurses who provide these services.

Acknowledgement

The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Click here to view PURL METHODOLOGY

Nausea, Vomiting, and Weakness for 4 days prompted a 76-year-old woman to seek care at our hospital. She was admitted for possible large bowel obstruction and severe dehydration. Her medical history was significant for a metastatic lung cancer to the mediastinal lymph nodes and to the left hip (for which she underwent a hip replacement 4 months earlier), anemia, and diverticulosis.

On Day 1 of her hospital stay, the patient became hypotensive and developed labored breathing. She also had mottled skin and cool fingertips with poor capillary refill. Her abdomen was distended, firm, and diffusely tympanic with diffuse pain to deep palpation and absent bowel sounds.

Her laboratory values revealed leukocytosis (with a significant left shift), metabolic acidosis, and an elevated lactic acid level. Her upright chest x-ray (FIGURE) is shown. The patient was transferred to the intensive care unit for further management.

FIGURE
Upright chest x-ray

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Diagnosis: Pneumoperitoneum

This patient had free air under her diaphragm (due to a viscus perforation) and concomitant septic shock. Free air in the peritoneal cavity—pneumoperitoneum— indicates visceral perforation in 85% to 95% of cases.^1,2 A ruptured intra-abdominal viscus is considered a surgical emergency. Pneumoperitoneum is often linked to peptic ulcer disease and is seen in 50% of cases of bowel perforations.³ This condition has a higher prevalence in the elderly and carries a higher mortality rate (up to 30% compared with 19% in a younger population).⁴

A picture that shifts according to the patient’s age
Physical findings suggestive of visceral perforation include sharp abdominal pain with a rigid abdominal wall. Patients will usually lie still because of the peritoneal irritation. Tachycardia and tachypnea are seen early in the disease process, while hypotension and fever usually develop within 4 to 6 hours.⁵

Elderly patients, however, can present with milder or nonspecific symptoms. Rather than pain, they may complain of the urge to defecate. Physical exam findings such as tachycardia or fever can also be absent due to autonomic dysregulation or medication. Furthermore, laboratory analysis is commonly within normal limits, making the diagnosis even more challenging in this population.^5,6

Imaging confirms the Dx

The standard imaging test used to confirm pneumoperitoneum is a standing chest x-ray that will detect free air in almost 80% of cases.⁷ The sensitivity is influenced by the location of the perforation: Free air will be seen in 69% of gastroduodenal perforations, 30% to 41% of distal small bowel perforations, and 37% to 46% of large bowel perforations.¹ Abdominal computed tomography scans have been reported to be more sensitive (up to 100%), especially in identifying small pneumoperitoneum.^8,9

Surgery is the next step

Management of pneumoperitoneum includes a prompt surgical consult for a possible emergent laparotomy, nasogastric suctioning, supportive measures for blood pressure, and broad-spectrum antibiotics such as a fourth-generation penicillin or a third-generation cephalosporin plus metronidazole.¹⁰

The end of the fight
Given the high mortality rate and the atypical presentation of perforated viscus in the elderly, it is important to maintain a high index of suspicion in this population and to intervene rapidly to improve the outcome.

In the case of our patient, the family followed her wishes and declined surgery. She was aggressively managed with broad-spectrum antibiotics, IV fluids, and vasopressors—but unfortunately died 2 days later.

CORRESPONDENCE Balaji Yegneswaran, MD, University of Pittsburgh Medical Center, 651, Scaife Hall, Pittsburgh, PA 15261; byegneswaran@gmail.com

Nausea, Vomiting, and Weakness for 4 days prompted a 76-year-old woman to seek care at our hospital. She was admitted for possible large bowel obstruction and severe dehydration. Her medical history was significant for a metastatic lung cancer to the mediastinal lymph nodes and to the left hip (for which she underwent a hip replacement 4 months earlier), anemia, and diverticulosis.

On Day 1 of her hospital stay, the patient became hypotensive and developed labored breathing. She also had mottled skin and cool fingertips with poor capillary refill. Her abdomen was distended, firm, and diffusely tympanic with diffuse pain to deep palpation and absent bowel sounds.

Her laboratory values revealed leukocytosis (with a significant left shift), metabolic acidosis, and an elevated lactic acid level. Her upright chest x-ray (FIGURE) is shown. The patient was transferred to the intensive care unit for further management.

FIGURE
Upright chest x-ray

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Diagnosis: Pneumoperitoneum

This patient had free air under her diaphragm (due to a viscus perforation) and concomitant septic shock. Free air in the peritoneal cavity—pneumoperitoneum— indicates visceral perforation in 85% to 95% of cases.^1,2 A ruptured intra-abdominal viscus is considered a surgical emergency. Pneumoperitoneum is often linked to peptic ulcer disease and is seen in 50% of cases of bowel perforations.³ This condition has a higher prevalence in the elderly and carries a higher mortality rate (up to 30% compared with 19% in a younger population).⁴

A picture that shifts according to the patient’s age
Physical findings suggestive of visceral perforation include sharp abdominal pain with a rigid abdominal wall. Patients will usually lie still because of the peritoneal irritation. Tachycardia and tachypnea are seen early in the disease process, while hypotension and fever usually develop within 4 to 6 hours.⁵

Elderly patients, however, can present with milder or nonspecific symptoms. Rather than pain, they may complain of the urge to defecate. Physical exam findings such as tachycardia or fever can also be absent due to autonomic dysregulation or medication. Furthermore, laboratory analysis is commonly within normal limits, making the diagnosis even more challenging in this population.^5,6

Imaging confirms the Dx

The standard imaging test used to confirm pneumoperitoneum is a standing chest x-ray that will detect free air in almost 80% of cases.⁷ The sensitivity is influenced by the location of the perforation: Free air will be seen in 69% of gastroduodenal perforations, 30% to 41% of distal small bowel perforations, and 37% to 46% of large bowel perforations.¹ Abdominal computed tomography scans have been reported to be more sensitive (up to 100%), especially in identifying small pneumoperitoneum.^8,9

Surgery is the next step

Management of pneumoperitoneum includes a prompt surgical consult for a possible emergent laparotomy, nasogastric suctioning, supportive measures for blood pressure, and broad-spectrum antibiotics such as a fourth-generation penicillin or a third-generation cephalosporin plus metronidazole.¹⁰

The end of the fight
Given the high mortality rate and the atypical presentation of perforated viscus in the elderly, it is important to maintain a high index of suspicion in this population and to intervene rapidly to improve the outcome.

In the case of our patient, the family followed her wishes and declined surgery. She was aggressively managed with broad-spectrum antibiotics, IV fluids, and vasopressors—but unfortunately died 2 days later.

CORRESPONDENCE Balaji Yegneswaran, MD, University of Pittsburgh Medical Center, 651, Scaife Hall, Pittsburgh, PA 15261; byegneswaran@gmail.com

Nausea, Vomiting, and Weakness for 4 days prompted a 76-year-old woman to seek care at our hospital. She was admitted for possible large bowel obstruction and severe dehydration. Her medical history was significant for a metastatic lung cancer to the mediastinal lymph nodes and to the left hip (for which she underwent a hip replacement 4 months earlier), anemia, and diverticulosis.

On Day 1 of her hospital stay, the patient became hypotensive and developed labored breathing. She also had mottled skin and cool fingertips with poor capillary refill. Her abdomen was distended, firm, and diffusely tympanic with diffuse pain to deep palpation and absent bowel sounds.

Her laboratory values revealed leukocytosis (with a significant left shift), metabolic acidosis, and an elevated lactic acid level. Her upright chest x-ray (FIGURE) is shown. The patient was transferred to the intensive care unit for further management.

FIGURE
Upright chest x-ray

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Diagnosis: Pneumoperitoneum

This patient had free air under her diaphragm (due to a viscus perforation) and concomitant septic shock. Free air in the peritoneal cavity—pneumoperitoneum— indicates visceral perforation in 85% to 95% of cases.^1,2 A ruptured intra-abdominal viscus is considered a surgical emergency. Pneumoperitoneum is often linked to peptic ulcer disease and is seen in 50% of cases of bowel perforations.³ This condition has a higher prevalence in the elderly and carries a higher mortality rate (up to 30% compared with 19% in a younger population).⁴

A picture that shifts according to the patient’s age
Physical findings suggestive of visceral perforation include sharp abdominal pain with a rigid abdominal wall. Patients will usually lie still because of the peritoneal irritation. Tachycardia and tachypnea are seen early in the disease process, while hypotension and fever usually develop within 4 to 6 hours.⁵

Elderly patients, however, can present with milder or nonspecific symptoms. Rather than pain, they may complain of the urge to defecate. Physical exam findings such as tachycardia or fever can also be absent due to autonomic dysregulation or medication. Furthermore, laboratory analysis is commonly within normal limits, making the diagnosis even more challenging in this population.^5,6

Imaging confirms the Dx

The standard imaging test used to confirm pneumoperitoneum is a standing chest x-ray that will detect free air in almost 80% of cases.⁷ The sensitivity is influenced by the location of the perforation: Free air will be seen in 69% of gastroduodenal perforations, 30% to 41% of distal small bowel perforations, and 37% to 46% of large bowel perforations.¹ Abdominal computed tomography scans have been reported to be more sensitive (up to 100%), especially in identifying small pneumoperitoneum.^8,9

Surgery is the next step

Management of pneumoperitoneum includes a prompt surgical consult for a possible emergent laparotomy, nasogastric suctioning, supportive measures for blood pressure, and broad-spectrum antibiotics such as a fourth-generation penicillin or a third-generation cephalosporin plus metronidazole.¹⁰

The end of the fight
Given the high mortality rate and the atypical presentation of perforated viscus in the elderly, it is important to maintain a high index of suspicion in this population and to intervene rapidly to improve the outcome.

In the case of our patient, the family followed her wishes and declined surgery. She was aggressively managed with broad-spectrum antibiotics, IV fluids, and vasopressors—but unfortunately died 2 days later.

CORRESPONDENCE Balaji Yegneswaran, MD, University of Pittsburgh Medical Center, 651, Scaife Hall, Pittsburgh, PA 15261; byegneswaran@gmail.com

Various media outlets have sensationalized your article on colon cleansing, “The dangers of colon cleansing” (J Fam Pract. 2011;60:454-457). The article has been perceived by many as a generic criticism of many forms of colon cleansing, with some inappropriate conclusions about widespread harm.

The article included 2 case reports that were incomplete and unclear; no specific diagnosis was made in either case. Authors Mishori et al tried to ascribe negative outcomes to colon cleansing, but the co-mingling of different treatments is apparent in their writing. In other words, colonic hydrotherapy and laxative agents are 2 quite distinct treatments used to facilitate the passage of stool, with different mechanisms of action and potential outcomes, beneficial or otherwise. The authors, in effect, compared apples and oranges, then reached conclusions about colon cleansing that were potentially misleading, generalized, or even naïve.

The first case report described an alleged negative outcome of colon hydrotherapy (colonic irrigation), which may or may not have been directly attributable to the procedure. Furthermore, the procedure was undertaken in an individual with Crohn’s disease, a clear contraindication. To conclude from this case report that colon hydrotherapy is harmful overall has no scientific basis.

The second case report involved the consumption of some form of herbal laxative formula that is not disclosed by the authors. The gastroenterologist who performed a colonoscopy and biopsy on this patient reached a “diagnosis” of “herbal intoxication,” in the presence of some histological evidence of both acute and chronic inflammation.

In both case reports, the actual underlying diagnosis is not clear. One could construct a differential diagnosis that could explain the complaints of these patients as a consequence of events unrelated to the act of colon cleansing.

While I agree that a clear evidence base to support the widespread practice of colonic irrigation is not available in current scientific literature, the procedure should not be summarily condemned. Many individuals report beneficial outcomes of colon hydrotherapy, even if such data are anecdotal and not archived with consistency.

My principal criticism of this article is that it did not present a complete or balanced perspective on the alleged dangers of the procedures in question. The authors failed to acknowledge that the frequency of reported complications of colon hydrotherapy may be significantly less than those reported with various diagnostic tests, such as barium enema examination, sigmoidoscopy, or colonoscopy.

I encourage your readers not to summarily reject “colon cleansing.” I submit that Mishori et al failed to fulfill the criteria for concluding that the act of colon cleansing is overly dangerous or ineffective when applied in an appropriate or medically indicated manner.

Stephen Holt, MD, DSc
Little Falls, NJ

Various media outlets have sensationalized your article on colon cleansing, “The dangers of colon cleansing” (J Fam Pract. 2011;60:454-457). The article has been perceived by many as a generic criticism of many forms of colon cleansing, with some inappropriate conclusions about widespread harm.

The article included 2 case reports that were incomplete and unclear; no specific diagnosis was made in either case. Authors Mishori et al tried to ascribe negative outcomes to colon cleansing, but the co-mingling of different treatments is apparent in their writing. In other words, colonic hydrotherapy and laxative agents are 2 quite distinct treatments used to facilitate the passage of stool, with different mechanisms of action and potential outcomes, beneficial or otherwise. The authors, in effect, compared apples and oranges, then reached conclusions about colon cleansing that were potentially misleading, generalized, or even naïve.

The first case report described an alleged negative outcome of colon hydrotherapy (colonic irrigation), which may or may not have been directly attributable to the procedure. Furthermore, the procedure was undertaken in an individual with Crohn’s disease, a clear contraindication. To conclude from this case report that colon hydrotherapy is harmful overall has no scientific basis.

The second case report involved the consumption of some form of herbal laxative formula that is not disclosed by the authors. The gastroenterologist who performed a colonoscopy and biopsy on this patient reached a “diagnosis” of “herbal intoxication,” in the presence of some histological evidence of both acute and chronic inflammation.

In both case reports, the actual underlying diagnosis is not clear. One could construct a differential diagnosis that could explain the complaints of these patients as a consequence of events unrelated to the act of colon cleansing.

While I agree that a clear evidence base to support the widespread practice of colonic irrigation is not available in current scientific literature, the procedure should not be summarily condemned. Many individuals report beneficial outcomes of colon hydrotherapy, even if such data are anecdotal and not archived with consistency.

My principal criticism of this article is that it did not present a complete or balanced perspective on the alleged dangers of the procedures in question. The authors failed to acknowledge that the frequency of reported complications of colon hydrotherapy may be significantly less than those reported with various diagnostic tests, such as barium enema examination, sigmoidoscopy, or colonoscopy.

I encourage your readers not to summarily reject “colon cleansing.” I submit that Mishori et al failed to fulfill the criteria for concluding that the act of colon cleansing is overly dangerous or ineffective when applied in an appropriate or medically indicated manner.

Stephen Holt, MD, DSc
Little Falls, NJ

Various media outlets have sensationalized your article on colon cleansing, “The dangers of colon cleansing” (J Fam Pract. 2011;60:454-457). The article has been perceived by many as a generic criticism of many forms of colon cleansing, with some inappropriate conclusions about widespread harm.

The article included 2 case reports that were incomplete and unclear; no specific diagnosis was made in either case. Authors Mishori et al tried to ascribe negative outcomes to colon cleansing, but the co-mingling of different treatments is apparent in their writing. In other words, colonic hydrotherapy and laxative agents are 2 quite distinct treatments used to facilitate the passage of stool, with different mechanisms of action and potential outcomes, beneficial or otherwise. The authors, in effect, compared apples and oranges, then reached conclusions about colon cleansing that were potentially misleading, generalized, or even naïve.

The first case report described an alleged negative outcome of colon hydrotherapy (colonic irrigation), which may or may not have been directly attributable to the procedure. Furthermore, the procedure was undertaken in an individual with Crohn’s disease, a clear contraindication. To conclude from this case report that colon hydrotherapy is harmful overall has no scientific basis.

The second case report involved the consumption of some form of herbal laxative formula that is not disclosed by the authors. The gastroenterologist who performed a colonoscopy and biopsy on this patient reached a “diagnosis” of “herbal intoxication,” in the presence of some histological evidence of both acute and chronic inflammation.

In both case reports, the actual underlying diagnosis is not clear. One could construct a differential diagnosis that could explain the complaints of these patients as a consequence of events unrelated to the act of colon cleansing.

While I agree that a clear evidence base to support the widespread practice of colonic irrigation is not available in current scientific literature, the procedure should not be summarily condemned. Many individuals report beneficial outcomes of colon hydrotherapy, even if such data are anecdotal and not archived with consistency.

My principal criticism of this article is that it did not present a complete or balanced perspective on the alleged dangers of the procedures in question. The authors failed to acknowledge that the frequency of reported complications of colon hydrotherapy may be significantly less than those reported with various diagnostic tests, such as barium enema examination, sigmoidoscopy, or colonoscopy.

I encourage your readers not to summarily reject “colon cleansing.” I submit that Mishori et al failed to fulfill the criteria for concluding that the act of colon cleansing is overly dangerous or ineffective when applied in an appropriate or medically indicated manner.

Stephen Holt, MD, DSc
Little Falls, NJ