Case Vignettes in Neurology

PATIENT CASE STUDIES

Case 15 2/25/99 Peripheral neuropathy
Case discussion The Case of Willie Barr or the foot slapping mechanic. You are called to the emergency room at 2 am to evaluate a 32 year old male who presents with a progressive gait disorder. Mr. Barr is a cooperative but somewhat vague historian with slurred speech. He reports that he has had increasing difficulty walking over the past 4-5 days. He initially noted that he had problems raising his ankle to put his shoes on and that his feet seemed to slap on the pavement when he walked. Ambulating became increasingly difficult over the next 48 hours and by the third day he was only able to get out of a chair with great effort. This hospital visit was prompted when he noted that he was having increasing difficulty bringing his beer mug to his mouth. He complains of painful, unpleasant sensations in his legs without relationship to position. He denies any problems with bowel or bladder function. His past medical history is remarkable for insulin-dependent, juvenile onset diabetes which has been poorly controlled. A motor vehicle accident 4 years ago with head trauma resulting in a seizure disorder which has required Dilantin (phenytoin) therapy at high doses to maintain adequate levels. Currently being treated with Prozac (fluoxetine) for depression which occurred after he lost his job at the automobile shop when it was closed by inspectors who cited it for a ventilation system that did not meet code regulations. He is otherwise healthy except for a recent bout of flu-like symptoms 3 weeks ago. His family history reveals that his father (65 years old) retired at 45 years because of a progressive weakness in his legs and eventually in his hands. He has a two-year-old daughter who has undergone an orthopedic procedure for tightened heel cords which developed during the first year of life. Social history: He is divorced and lives alone in a caretakers cabin on a farm in the Central Valley. Examination reveals diffuse symmetric weakness, without wasting. DTRs are diffusely absent. There is no sensory loss. Extraocular muscles are not involved.
Summarize the Case in 1-2 sentences. This is a 32-year-old male with insulin-dependent diabetes, seizure disorder and depression, currently presenting to the ER 3 weeks after a flu-like illness with a 5-day history of progressive generalized muscular weakness, paresthesias in both legs, diffusely absent DTRs, and no sensory loss. good Discuss lesion localization on the basis of the physical examination. diffuse weakness, paresthesias, absent DTRs, no UMN signs: peripheral nerve good Discuss underlying pathogenesis on the basis of clinical course. 5-day subacute crescendo course is consistent with infection, inflammation, or a mass lesion. good Indicate one likely clinical diagnosis. List (or classify) alternative diagnoses. Guillain Barre Syndrome. Other causes of subacute, progressive, generalized weakness: Neurologic: spinal cord disease Infectious: poliomyelitis, botulism, tick paralysis, diphtheria Toxic: lead, thallium, or arsenic poisoning (work-related), alcoholic neuropathy Inflammatory: polymyositis, myasthenia gravis, Lambert-Eaton Metabolic: diabetic peripheral neuropathy, porphyria Hereditary: Charcot-Marie-Tooth CMT/etoh/diabetic neuropathy is not subacute over 3 weeks! The rest are ok. also etoh and diabetic sensory motor neuropathies are predmoninantly sensory not motor. Indicate 2 ancillary tests that would assist in confirming or refuting the clinical diagnosis. Indicate the test results that would confirm the clinical diagnosis. * nerve conduction studies: slowed conduction velocity, conduction blocks, and prolonged distal latencies. Motor root involvement can be studied by a special technique of testing retrograde conduction and reflection of signals from anterior horn cells. * CSF examination: elevated protein, normal pressure, acelllular (or only a few lymphocytes). with NCV, the important test component is the F wave test which is an antidromic stimulation to test the nerve roots. The characteristic change on csf analysis is albumino cytologic dissociation where the protein is increased but the cells are not. Indicate complications of the disease and ancillary tests that would help evaluate them. * Respiratory paralysis--admit and watch closely, tracheostomy/ ventilation my be necessary (blood gases are a late indicator of respiratory failure) * autonomic instability: blood pressure fluctuation, urinary retention * persistent disability: occurs in 10-20% of patients who progress to respiratory paralysis. * recurrence: about 3% lifetime chance * kidney damage from immune complex glomerulonephritis * 2% mortality rate dvt and pulmonary embolism are important causes of mortality in GBS patients; depression is also common Discuss how the underlying pathophysiology is relevant in the management of this patient. GBS is an autoimmune reaction directed at heterogeneous myelin and sometimes axonal components which have not been clearly identified. Previous hypotheses implicating myelin basic protein as the antigen have not been confirmed (Adams p. 1314). The immune response includes activated T cells as well as an antibody response, as shown by the findings that either T-cells or sera from experimental animals with a GBS-syndrome can cause meylin destruction. The preceding viral or bacterial infection is thought to sensitize the immune system against endogenous myelin antigens in susceptible individuals. Treatment is mainly supportive, including respiratory assistance in severe cases. Complete or nearly complete recovery is the rule in the majority of cases. Physical therapy is important in preserving and restoring muscle function after the disease. In severe cases, plasmapheresis has been found to be effective in several large, randomized trials. Corticosteroids have not been found effective in GBS. GBS is the best known example of autoimmune disease arising as a consequence to molecular mimicry. An immune attack directed against campylobacter jejuni or another bacterium or virus results in an autoimmune attack directed at targets on the nerve or myelin, often a ganglioside. The immune attack tends to be monophasic and tends to be antibody mediated. Plasmapheresis and IVIG consequently tend to be the mainstay of immune treatment.

Case 15 2/25/99 Peripheral neuropathy

Case discussion

The Case of Willie Barr or the foot slapping mechanic. You are called to the emergency room at 2 am to evaluate a 32 year old male who presents with a progressive gait disorder.

Mr. Barr is a cooperative but somewhat vague historian with slurred speech. He reports that he has had increasing difficulty walking over the past 4-5 days. He initially noted that he had problems raising his ankle to put his shoes on and that his feet seemed to slap on the pavement when he walked. Ambulating became increasingly difficult over the next 48 hours and by the third day he was only able to get out of a chair with great effort. This hospital visit was prompted when he noted that he was having increasing difficulty bringing his beer mug to his mouth. He complains of painful, unpleasant sensations in his legs without relationship to position. He denies any problems with bowel or bladder function.

His past medical history is remarkable for insulin-dependent, juvenile onset diabetes which has been poorly controlled. A motor vehicle accident 4 years ago with head trauma resulting in a seizure disorder which has required Dilantin (phenytoin) therapy at high doses to maintain adequate levels.

Currently being treated with Prozac (fluoxetine) for depression which occurred after he lost his job at the automobile shop when it was closed by inspectors who cited it for a ventilation system that did not meet code regulations. He is otherwise healthy except for a recent bout of flu-like symptoms 3 weeks ago.

His family history reveals that his father (65 years old) retired at 45 years because of a progressive weakness in his legs and eventually in his hands. He has a two-year-old daughter who has undergone an orthopedic procedure for tightened heel cords which developed during the first year of life.
Social history: He is divorced and lives alone in a caretakers cabin on a farm in the Central Valley.

Examination reveals diffuse symmetric weakness, without wasting. DTRs are diffusely absent. There is no sensory loss. Extraocular muscles are not involved.

Summarize the Case in 1-2 sentences.

This is a 32-year-old male with insulin-dependent diabetes, seizure disorder and depression, currently presenting to the ER 3 weeks after a flu-like illness with a 5-day history of progressive generalized muscular weakness, paresthesias in both legs, diffusely absent DTRs, and no sensory loss.

good

Discuss lesion localization on the basis of the physical examination.

diffuse weakness, paresthesias, absent DTRs, no UMN signs: peripheral nerve

good

Discuss underlying pathogenesis on the basis of clinical course.

5-day subacute crescendo course is consistent with infection, inflammation, or a mass lesion.

good

Indicate one likely clinical diagnosis. List (or classify) alternative diagnoses.

Guillain Barre Syndrome.

Other causes of subacute, progressive, generalized weakness: Neurologic: spinal cord disease Infectious: poliomyelitis, botulism, tick paralysis, diphtheria Toxic: lead, thallium, or arsenic poisoning (work-related), alcoholic neuropathy Inflammatory: polymyositis, myasthenia gravis, Lambert-Eaton Metabolic: diabetic peripheral neuropathy, porphyria Hereditary: Charcot-Marie-Tooth

CMT/etoh/diabetic neuropathy is not subacute over 3 weeks! The rest are ok. also etoh and diabetic sensory motor neuropathies are predmoninantly sensory not motor.

Indicate 2 ancillary tests that would assist in confirming or refuting the clinical diagnosis. Indicate the test results that would confirm the clinical diagnosis.

* nerve conduction studies: slowed conduction velocity, conduction blocks, and prolonged distal latencies. Motor root involvement can be studied by a special technique of testing retrograde conduction and reflection of signals from anterior horn cells.

* CSF examination: elevated protein, normal pressure, acelllular (or only a few lymphocytes).

with NCV, the important test component is the F wave test which is an antidromic stimulation to test the nerve roots. The characteristic change on csf analysis is albumino cytologic dissociation where the protein is increased but the cells are not.

Indicate complications of the disease and ancillary tests that would help evaluate them.

* Respiratory paralysis--admit and watch closely, tracheostomy/ ventilation my be necessary (blood gases are a late indicator of respiratory failure) * autonomic instability: blood pressure fluctuation, urinary retention * persistent disability: occurs in 10-20% of patients who progress to respiratory paralysis. * recurrence: about 3% lifetime chance * kidney damage from immune complex glomerulonephritis * 2% mortality rate

dvt and pulmonary embolism are important causes of mortality in GBS patients; depression is also common

Discuss how the underlying pathophysiology is relevant in the management of this patient.

GBS is an autoimmune reaction directed at heterogeneous myelin and sometimes axonal components which have not been clearly identified. Previous hypotheses implicating myelin basic protein as the antigen have not been confirmed (Adams p. 1314). The immune response includes activated T cells as well as an antibody response, as shown by the findings that either T-cells or sera from experimental animals with a GBS-syndrome can cause meylin destruction. The preceding viral or bacterial infection is thought to sensitize the immune system against endogenous myelin antigens in susceptible individuals.

Treatment is mainly supportive, including respiratory assistance in severe cases. Complete or nearly complete recovery is the rule in the majority of cases. Physical therapy is important in preserving and restoring muscle function after the disease. In severe cases, plasmapheresis has been found to be effective in several large, randomized trials. Corticosteroids have not been found effective in GBS.

GBS is the best known example of autoimmune disease arising as a consequence to molecular mimicry. An immune attack directed against campylobacter jejuni or another bacterium or virus results in an autoimmune attack directed at targets on the nerve or myelin, often a ganglioside. The immune attack tends to be monophasic and tends to be antibody mediated. Plasmapheresis and IVIG consequently tend to be the mainstay of immune treatment.