Case Vignettes in Neurology

PATIENT CASE STUDIES

Case 23. 3/5/99 Multiple sclerosis
Case discussion A 30-year old female sought your medical attention for numbness and difficulty in walking. She had been well until 6 days previously, when she awoke with numbness on the left side of the face. This worsened over several hours. She also noticed considerable difficulty with balance. Over the next 3 days she became worse and then the symptoms stabilized. She also developed numbness of the right arm and hand, inability to close her left eye, double vision on looking to the left and difficulty with walking for reasons or imbalance. There was no headache or facial pain, fever or stiff neck. On physical examination on day 6 her gait was wide based and unsteady and occasionally she used her arms to counterbalance unexpected lurches. She joked: "You probably think I’ve been drinking!". She gave a clear history without any difficulty of language, articulation, cognition or memory. Her past history was of interest for her having an episode of difficulty with her vision in left eye at age 19 while a college student. The campus physician assured her it was a Case of "neuritis" and that it would resolve in two weeks, which it did. No investigations were performed at the time. There was no other pertinent history to suggest prior neurological illness, cardiovascular disease, systemic lupus erythematosus, or infection. There was no history of neurological illness in the family. The neurological examination showed there was decreased appreciation of light cotton touch and pinprick on the left side of the face, a depressed corneal reflex, and decreased movement of the left facial muscles upon command with incomplete eye closure. Left lateral gaze was incomplete with poor abduction of the left eye. There was a slight decrease in appreciation of touch, and pinprick of the right hand and forearm. Strength was preserved throughout all extremities. Coordinated movements were slightly impaired in the right upper and lower extremities compared to the left side and she was unable to walk heel to toe without falling. The knee and ankle reflexes on the right side were more active than the left and there was a right extensor plantar response. Two ancillary tests were performed at this time. Over the next two months, the symptoms and signs resolved slowly without treatment. She returned to her work in an art studio. For the next ten years, she had three recurrences of neurological problems. On one occasion she had recurrence of left eye blindness for two weeks. On a second occasion she developed weakness of the right side which lasted 6 weeks. On the third occasion she had recurrence of diplopia, left face and right body numbness. In addition over this 10-year period she had recurrent episodes of tiredness ("fatigue") that lasted for several days at a time. At her annual visit at age 40 years she had not had any more episodes, but her overall neurological function had deteriorated slightly. She observed that her mental skills were not as sharp as they had been. Mental status testing revealed slowness and uncertainty in mathematical calculations and spelling. Her mood was normal. There was a titubating tremor of the head and body while sitting and her gait was both mildly ataxic and stiff. There was increased tone and reflexes in her legs with bilateral extensor plantar reflexes. Her walking was slow and mildly unsteady and she chose to use a cane.
Summarize the Case in 1-2 sentences. This patient is a 40 y.o. woman who first presented at age 30 with recurrent, multifocal, and progressive neurologic complaints such as diplopia, temporary blindness, difficulty walking, difficulty with balance and numbness in her right hand, arm, left side of face. Physical exam demonstrated hemisensory of right arm, hand, and left side of face with decrease corneal reflex; hemiparesis of left face with incomplete eye closure and poor abduction of left eye; ataxic, stiff right upper and lower extremity; MSE revealed slowed cognitive functions. this is a tough case to summarize because of the number of attacks and change in the signs as the attacks resolved. the way you summarize it is not quite accurate as the exam is not her exam at the present at age 40 but rather her exam at age 30. Also hyperflexic or hypertonic are better terms than stiff. Discuss lesion localization on the basis of the physical examination. a. Spinal cord posterior columns: hemisensory right arm, hand b. Cranial nerves II, III, V, and VII: temporary blindness, poor left eye abduction, hemisensory and hemiparesis left side of face, depressed corneal reflex (respective to each mentioned cranial nerve) c. Cerebellum hemispheres: extremity ataxia, gait d. Cerebral hemispheres: decreased higher cognitive functioning (spelling, math) numbness left face and right upper extremity, left abduction palsy probably localizes to the brain stem (left side of pons); note crossed findings with ipsilateral cranial nerve findings and contralateral long tract signs localizes to the brain stem. left eye blindness would localize to the left optic nerve or left eye Discuss underlying pathogenesis on the basis of clinical course. Vascular, infectious and inflammatory lesions correspond with the acute/subacute and recurrent course. A metabolic lesion and a slowly expanding space occupying lesion correspond to the progressive course spanning years. good Indicate one likely clinical diagnosis. List (or classify) alternative diagnoses. Working diagnosis: Multiple Sclerosis Differential Dx: a. Vascular: emboli, vasculitis, b. Immunologic: Systemic Lupus Erythematous c. Infection: Lyme disease, syphilis d. Metabolic: Vit B1 and B12 deficiencies good Indicate 2 ancillary tests that would assist in confirming or refuting the clinical diagnosis. Indicate the test results that would confirm the clinical diagnosis. a. Brain MRI with contrast studies: look for periventricular lesions (white in T2 -weighted mode) due to damaged, leaky BBB b. CSF: presence of oligoclonal IgG and/or mononuclear pleocytosis 5-20 cells/uL pleocytosis is not usually present in MS though it can be; it does not help in confirming or refuting the dx. Indicate complications of the disease and ancillary tests that would help evaluate them. a. Patient history and exam: fatigue, progressive cognitive defects, depression b. Audio/Visual examination: optic neuritis, blindness, deafness c. Urodynamic testing: bladder functions good Discuss how the underlying pathophysiology is relevant in the management of this patient. Pathophysiology: The presence of IgG and pleocytosis of lymphocytes in the CSF suggests a chronic inflammatory process. Periventricular lesions on the MRI contrast study suggests inflammation and damage of the BBB. Management: Symptomatic management of recurrent spasticity with Baclofen (GABA agonist), be suspicious and treat major depressive or bipolar complications, prevent further systemic inflammatory states such as infections. Reduce chronic inflammation and stabilize damaged BBB with steroids. Enhance Ts cell activity with Glutiramer. ok; symptomatic management is based on pathophysiology; In MS there is a Th1 mediated immune reaction against a undetermined antigen. There are abnormalities in three spheres: 1) there is an increased percentage of systemic T cells circulating that are activated. 2) There is a breakdown of the BBB before and during attacks with enhancing lesions on imaging studies. 3) There is a Th1 mediated immune attack in the brain that results in demyelination and axonal loss. The Th1 cells secrete gamma interferon that activates macrophages. Most the demyelination occurs secondary to phagocytosis and release of cytokines eg TNF that macrophages release. Gamma interferon results in attacks MS and drugs such as beta interferons that reduce gamma interferon function prevent attacks and progression in MS. Management of the neurogenic bladder as you say is important as it prevents urinary tract infections. This is important as systemic infections lead to increased production of gamma interferon with increased likelihood of attacks. Since there is axonal damage and loss in MS it is likely that approaches designed to lead to neuroprotective therapies may prove useful. Steroids are used acutely to treat attacks as they strengthen the BBB and they particularly have an anti-macrophage effect.

Case 23. 3/5/99 Multiple sclerosis

Case discussion

A 30-year old female sought your medical attention for numbness and difficulty in walking. She had been well until 6 days previously, when she awoke with numbness on the left side of the face. This worsened over several hours. She also noticed considerable difficulty with balance. Over the next 3 days she became worse and then the symptoms stabilized. She also developed numbness of the right arm and hand, inability to close her left eye, double vision on looking to the left and difficulty with walking for reasons or imbalance. There was no headache or facial pain, fever or stiff neck. On physical examination on day 6 her gait was wide based and unsteady and occasionally she used her arms to counterbalance unexpected lurches. She joked: "You probably think I’ve been drinking!". She gave a clear history without any difficulty of language, articulation, cognition or memory. Her past history was of interest for her having an episode of difficulty with her vision in left eye at age 19 while a college student. The campus physician assured her it was a

Case of "neuritis" and that it would resolve in two weeks, which it did. No investigations were performed at the time. There was no other pertinent history to suggest prior neurological illness, cardiovascular disease, systemic lupus erythematosus, or infection. There was no history of neurological illness in the family.

The neurological examination showed there was decreased appreciation of light cotton touch and pinprick on the left side of the face, a depressed corneal reflex, and decreased movement of the left facial muscles upon command with incomplete eye closure. Left lateral gaze was incomplete with poor abduction of the left eye. There was a slight decrease in appreciation of touch, and pinprick of the right hand and forearm. Strength was preserved throughout all extremities. Coordinated movements were slightly impaired in the right upper and lower extremities compared to the left side and she was unable to walk heel to toe without falling. The knee and ankle reflexes on the right side were more active than the left and there was a right extensor plantar response. Two ancillary tests were performed at this time.

Over the next two months, the symptoms and signs resolved slowly without treatment. She returned to her work in an art studio. For the next ten years, she had three recurrences of neurological problems. On one occasion she had recurrence of left eye blindness for two weeks. On a second occasion she developed weakness of the right side which lasted 6 weeks. On the third occasion she had recurrence of diplopia, left face and right body numbness. In addition over this 10-year period she had recurrent episodes of tiredness ("fatigue") that lasted for several days at a time.

At her annual visit at age 40 years she had not had any more episodes, but her overall neurological function had deteriorated slightly. She observed that her mental skills were not as sharp as they had been. Mental status testing revealed slowness and uncertainty in mathematical calculations and spelling. Her mood was normal. There was a titubating tremor of the head and body while sitting and her gait was both mildly ataxic and stiff. There was increased tone and reflexes in her legs with bilateral extensor plantar reflexes. Her walking was slow and mildly unsteady and she chose to use a cane.

Summarize the Case in 1-2 sentences.

This patient is a 40 y.o. woman who first presented at age 30 with recurrent, multifocal, and progressive neurologic complaints such as diplopia, temporary blindness, difficulty walking, difficulty with balance and numbness in her right hand, arm, left side of face. Physical exam demonstrated hemisensory of right arm, hand, and left side of face with decrease corneal reflex; hemiparesis of left face with incomplete eye closure and poor abduction of left eye; ataxic, stiff right upper and lower extremity; MSE revealed slowed cognitive functions.

this is a tough case to summarize because of the number of attacks and change in the signs as the attacks resolved. the way you summarize it is not quite accurate as the exam is not her exam at the present at age 40 but rather her exam at age 30. Also hyperflexic or hypertonic are better terms than stiff.

Discuss lesion localization on the basis of the physical examination.

a. Spinal cord posterior columns: hemisensory right arm, hand
b. Cranial nerves II, III, V, and VII: temporary blindness, poor left eye abduction, hemisensory and hemiparesis left side of face, depressed corneal reflex (respective to each mentioned cranial nerve)
c. Cerebellum hemispheres: extremity ataxia, gait
d. Cerebral hemispheres: decreased higher cognitive functioning (spelling, math)

numbness left face and right upper extremity, left abduction palsy probably localizes to the brain stem (left side of pons); note crossed findings with ipsilateral cranial nerve findings and contralateral long tract signs localizes to the brain stem. left eye blindness would localize to the left optic nerve or left eye

Discuss underlying pathogenesis on the basis of clinical course.

Vascular, infectious and inflammatory lesions correspond with the acute/subacute and recurrent course. A metabolic lesion and a slowly expanding space occupying lesion correspond to the progressive course spanning years.

good

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

Working diagnosis: Multiple Sclerosis

Differential Dx:
a. Vascular: emboli, vasculitis,
b. Immunologic: Systemic Lupus Erythematous
c. Infection: Lyme disease, syphilis
d. Metabolic: Vit B1 and B12 deficiencies

good

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

a. Brain MRI with contrast studies: look for periventricular lesions (white in T2 -weighted mode) due to damaged, leaky BBB

b. CSF: presence of oligoclonal IgG and/or mononuclear pleocytosis 5-20 cells/uL

pleocytosis is not usually present in MS though it can be; it does not help in confirming or refuting the dx.

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

a. Patient history and exam: fatigue, progressive cognitive defects, depression
b. Audio/Visual examination: optic neuritis, blindness, deafness
c. Urodynamic testing: bladder functions

good

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

Pathophysiology: The presence of IgG and pleocytosis of lymphocytes in the CSF suggests a chronic inflammatory process. Periventricular lesions on the MRI contrast study suggests inflammation and damage of the BBB. Management: Symptomatic management of recurrent spasticity with Baclofen (GABA agonist), be suspicious and treat major depressive or bipolar complications, prevent further systemic inflammatory states such as infections. Reduce chronic inflammation and stabilize damaged BBB with steroids. Enhance Ts cell activity with Glutiramer.

ok; symptomatic management is based on pathophysiology; In MS there is a Th1 mediated immune reaction against a undetermined antigen. There are abnormalities in three spheres: 1) there is an increased percentage of systemic T cells circulating that are activated. 2) There is a breakdown of the BBB before and during attacks with enhancing lesions on imaging studies. 3) There is a Th1 mediated immune attack in the brain that results in demyelination and axonal loss. The Th1 cells secrete gamma interferon that activates macrophages. Most the demyelination occurs secondary to phagocytosis and release of cytokines eg TNF that macrophages release. Gamma interferon results in attacks MS and drugs such as beta interferons that reduce gamma interferon function prevent attacks and progression in MS. Management of the neurogenic bladder as you say is important as it prevents urinary tract infections. This is important as systemic infections lead to increased production of gamma interferon with increased likelihood of attacks. Since there is axonal damage and loss in MS it is likely that approaches designed to lead to neuroprotective therapies may prove useful. Steroids are used acutely to treat attacks as they strengthen the BBB and they particularly have an anti-macrophage effect.