Disorders of Myelination Flashcards
A 21-year-old right-handed female student was working in the photography lab 1 week ago, which required standing all day. After that, she experienced a cold sensation in the left foot and her entire left leg fell asleep. The feeling lasted 4 to 5 days and then slowly went away. Her right lower extremity was fine. Coughing, sneezing, and the Valsalva maneuver did not worsen her symptoms. She had a slight back pain, which she thought was due to using a poor mattress. Past history includes an episode of optic neuritis in the left eye 2 years ago. At that time, she was reportedly depressed and was sleeping constantly. One day, her left eye became blurred and her vision went out. In 1 week, her vision returned to normal. Her vision now is 20/20. She has not had a repeat episode since then. She had an MRI of her brain, which was normal at that time. She drinks alco¬hol occasionally and does not use any illicit drugs. Her only medication is birth control pills. Examination is significant for brisk reflexes and sustained clonus at the right ankle. Babinski sign is present on the right. Testing is positive for oligoclonal bands.
- The most likely diagnosis in this case is
a. Seizure
b. Transient ischemic attack
c. Anaplastic astrocytoma
d. Multiple sclerosis
e. Parkinson’s disease
D
( Victor, pp 961–962.) This is a typical history for multiple sclerosis (MS). Multiple sclerosis is a progressive demyelinating disease of the central nervous system. Risk factors include a first time demyelinating episode such as optic neuritis. Patients are more commonly in the 20 to 30 age range, with a higher incidence in women. A transient ischemic attack is a brief period of brain ischemia causing neurological deficits that resolve within 24 h. Patients who have a transient ischemic attack are at increased risk for stroke. A seizure is abnormal rhythmic electrical brain activity with a clinical correlation. There is nothing in the history that suggests that this patient had a seizure or a seizure predisposing factor. Seizure predisposing factors include previous seizure, brain trauma, brain hemorrhage, and encephalitis. An anaplastic astrocytoma is a malignant high-grade brain tumor. These often present with a seizure or hemorrhage. Risk factors include previous brain tumor. Parkinson’s disease is caused by a loss of dopaminergic neurons. It is characterized by asymmetric slowness, rigidity, and tremor. Risk factors include family history.
A 21-year-old right-handed female student was working in the photography lab 1 week ago, which required standing all day. After that, she experienced a cold sensation in the left foot and her entire left leg fell asleep. The feeling lasted 4 to 5 days and then slowly went away. Her right lower extremity was fine. Coughing, sneezing, and the Valsalva maneuver did not worsen her symptoms. She had a slight back pain, which she thought was due to using a poor mattress. Past history includes an episode of optic neuritis in the left eye 2 years ago. At that time, she was reportedly depressed and was sleeping constantly. One day, her left eye became blurred and her vision went out. In 1 week, her vision returned to normal. Her vision now is 20/20. She has not had a repeat episode since then. She had an MRI of her brain, which was normal at that time. She drinks alcohol occasionally and does not use any illicit drugs. Her only medication is birth control pills. Examination is significant for brisk reflexes and sustained clonus at the right ankle. Babinski sign is present on the right. Testing is positive for oligoclonal bands.
- Oligoclonal bands are the
a. Wave frequency changes on the EEG during sleep
b. Markings about the iris
c. Pathologic features of Alzheimer’s disease
d. Chromosomal markings found with multiple sclerosis (MS)
e. Immunoglobulin patterns in the CSF with MS
E
( Victor, p 969.) Between 85 and 90% of patients with MS exhibit oligoclonal banding on electrophoretic studies of their CSF. This limited number of bands of excess immunoglobulin indicates that the species of IgG produced by the disease fall into a relatively small number of families. The proteins are not highly diverse, as would be the case with a polyclonal gammopathy.
A 21-year-old right-handed female student was working in the photography lab 1 week ago, which required standing all day. After that, she experienced a cold sensation in the left foot and her entire left leg fell asleep. The feeling lasted 4 to 5 days and then slowly went away. Her right lower extremity was fine. Coughing, sneezing, and the Valsalva maneuver did not worsen her symptoms. She had a slight back pain, which she thought was due to using a poor mattress. Past history includes an episode of optic neuritis in the left eye 2 years ago. At that time, she was reportedly depressed and was sleeping constantly. One day, her left eye became blurred and her vision went out. In 1 week, her vision returned to normal. Her vision now is 20/20. She has not had a repeat episode since then. She had an MRI of her brain, which was normal at that time. She drinks alcohol occasionally and does not use any illicit drugs. Her only medication is birth control pills. Examination is significant for brisk reflexes and sustained clonus at the right ankle. Babinski sign is present on the right. Testing is positive for oligoclonal bands.
- On briskly flexing the neck forward, a patient with this disease may report
a. Dystonic posturing of the legs
b. An electrical sensation radiating down the spine or into the legs
c. Bilateral wristdrop
d. Spontaneous evacuation of the bladder and bilateral extensor plantar responses
e. Rapidly evolving hemifacial pain
B
( Victor, p 962.) The peculiar sensory phenomenon in which the patient feels an electrical sensation radiating down the spine when the neck is passively flexed is called Lhermitte’s sign and is believed to signify spinal cord disease. Patients with MS who have little more than optic atrophy and no evidence of spinal cord involvement may report the sensation. Dystonic posturing may also occur in patients with MS, but the posturing is usually spontaneous. A massive Babinski response may produce bladder evacuation and extensor plantar responses as well as involuntary leg withdrawal in these same patients. This type of reflex response is usually elicited by stimuli to the feet or legs rather than by manipulation of the neck or spine.
A 21-year-old right-handed female student was working in the photography lab 1 week ago, which required standing all day. After that, she experienced a cold sensation in the left foot and her entire left leg fell asleep. The feeling lasted 4 to 5 days and then slowly went away. Her right lower extremity was fine. Coughing, sneezing, and the Valsalva maneuver did not worsen her symptoms. She had a slight back pain, which she thought was due to using a poor mattress. Past history includes an episode of optic neuritis in the left eye 2 years ago. At that time, she was reportedly depressed and was sleeping constantly. One day, her left eye became blurred and her vision went out. In 1 week, her vision returned to normal. Her vision now is 20/20. She has not had a repeat episode since then. She had an MRI of her brain, which was normal at that time. She drinks alcohol occasionally and does not use any illicit drugs. Her only medication is birth control pills. Examination is significant for brisk reflexes and sustained clonus at the right ankle. Babinski sign is present on the right. Testing is positive for oligoclonal bands.
- The CSF in persons with multiple sclerosis will typically exhibit
a. Glucose content of less than 20% of the serum content
b. Persistently elevated total protein content
c. Persistently elevated immunoglobulin G (IgG) content
d. Mononuclear cell counts of greater than 100 cells per µL
e. Erythrocyte counts of greater than 10 cells per µL
C
(Bradley, pp 1448–1449.) The IgG content of the CSF remains elevated even between acute exacerbations of the MS. The IgG has a distinctive κ light chain composition. This immunoglobulin typically accounts for more than 15% of the total protein content in the CSF of the patient with MS.
A 35-year-old man with multiple sclerosis initially presented 4 years ago with left eye optic neuritis. He did not receive steroids at that time. Two years ago he had loss of sensation in his hands that progressed over weeks to motor involvement, limiting his ability to write with the left hand. He received steroids at that time. He began interferon β-1A 4 years ago. One year ago, he developed right leg weakness, constipation, and urinary urgency. He received steroids at that time as well. He now presents with new symptoms that concern him about the start of a new flare. Two days ago, he noticed decreased sensation in the palm of his right hand that is worse when he exercises. This has gotten a little worse over the last 2 days. Yesterday, he noticed diminished sensation along the lower right trunk in the front and back. He has no pain, tingling, exacerbation of symptoms with neck movement, neck injury, incontinence, gait disturbance, diplopia, fever, chills, nausea, or vomiting. Examination findings include full visual fields with a left afferent pupillary defect. Bulk, strength, and tone are normal. Light touch is decreased over the left trunk and back over roughly the T8 to T12 dermatomes. Finger tapping, rapid alternating movements, finger-nose-finger, and heel tapping to shin are normal.
- The most appropriate pharmacological treatment for this patient at this time is
a. Interferon β-1B
b. Corticosteroids
c. Gabapentin
d. Glatiramer
e. Pramipexole
B
( Victor, p 973.) Corticosteroids are an appropriate treatment for a multiple sclerosis flare. They will reduce the length and severity of the flare in most cases, although they are not likely to change the
long-term disease outcome. Interferon β-IB and glatiramer are appropriate treatments to reduce the frequency of multiple sclerosis flares; however, they are not useful for the acute treatment of a flare. Gabapentin is an anti-convulsant medication that is also useful for the treatment of neuropathic pain, such as burning and allodynia. It will not help a multiple sclerosis flare. Pramipexole is a dopamine agonist used to treat parkinsonism. It has no role in the treatment of multiple sclerosis.
A 35-year-old man with multiple sclerosis initially presented 4 years ago with left eye optic neuritis. He did not receive steroids at that time. Two years ago he had loss of sensation in his hands that progressed over weeks to motor involvement, limiting his ability to write with the left hand. He received steroids at that time. He began interferon β-1A 4 years ago. One year ago, he developed right leg weakness, constipation, and urinary urgency. He received steroids at that time as well. He now presents with new symptoms that concern him about the start of a new flare. Two days ago, he noticed decreased sensation in the palm of his right hand that is worse when he exercises. This has gotten a little worse over the last 2 days. Yesterday, he noticed diminished sensation along the lower right trunk in the front and back. He has no pain, tingling, exacerbation of symptoms with neck movement, neck injury, incontinence, gait disturbance, diplopia, fever, chills, nausea, or vomiting. Examination findings include full visual fields with a left afferent pupillary defect. Bulk, strength, and tone are normal. Light touch is decreased over the left trunk and back over roughly the T8 to T12 dermatomes. Finger tapping, rapid alternating movements, finger-nose-finger, and heel tapping to shin are normal.
- Multiple sclerosis is the most common demyelinating disease in the United States, affecting approximately 1 person in
a. 100
b. 500
c. 1,000
d. 5,000
e. 10,000
C
(Bradley, p 1436.) Approximately 250,000 people in the United States carry the diagnosis of MS. Most of the affected persons live in northern states, but no state is exempt from reports of MS. Because there is no test to unequivocally establish the diagnosis, the exact number of active cases in the United States can be approximated only very roughly.
A 35-year-old man with multiple sclerosis initially presented 4 years ago with left eye optic neuritis. He did not receive steroids at that time. Two years ago he had loss of sensation in his hands that progressed over weeks to motor involvement, limiting his ability to write with the left hand. He received steroids at that time. He began interferon β-1A 4 years ago. One year ago, he developed right leg weakness, constipation, and urinary urgency. He received steroids at that time as well. He now presents with new symptoms that concern him about the start of a new flare. Two days ago, he noticed decreased sensation in the palm of his right hand that is worse when he exercises. This has gotten a little worse over the last 2 days. Yesterday, he noticed diminished sensation along the lower right trunk in the front and back. He has no pain, tingling, exacerbation of symptoms with neck movement, neck injury, incontinence, gait disturbance, diplopia, fever, chills, nausea, or vomiting. Examination findings include full visual fields with a left afferent pupillary defect. Bulk, strength, and tone are normal. Light touch is decreased over the left trunk and back over roughly the T8 to T12 dermatomes. Finger tapping, rapid alternating movements, finger-nose-finger, and heel tapping to shin are normal.
- The evoked response pattern that is most often abnormal in patients with early MS is the
a. Brainstem auditory evoked response (BAER)
b. Far-field somatosensory evoked response (SSER)
c. Visual evoked response (VER)
d. Jolly test
e. Sensory nerve conduction test
C
(Bradley, pp 1438–1439.) Optic neuritis occurs early and often in many patients with MS. This involves inflammation and demyelination of the optic nerve and slows conduction along the optic nerve. Components of the VER may be slowed or even absent. That an evoked response is disturbed is not proof that the patient has MS, as any problem that produces optic neuritis will disturb the VER. The Jolly test is an evoked response involving muscles. A peripheral nerve is shocked at 5 to 15 times per second, and the pattern of action potentials elicited in the muscle innervated is recorded. Sensory nerve conduction studies also involve an evoked response to a shock with the resulting signal tracked in the sensory nerve stimulated. Muscle and peripheral nerve function is typically normal in patients with MS, unless they have an unrelated disease of the peripheral nervous system.
- A 37-year-old woman with progressive multiple sclerosis is being admitted for intravenous glucocorticoid therapy. She was diagnosed with multiple sclerosis 10 years ago after presenting with bilateral decreased visual acuity. She had an abnormal MRI at that time. She has been hospitalized approximately nine times since presentation, with her flares com-monly consisting of increasing bilateral lower extremity weakness and decreased sensation manifested as a heavy feeling, waxing and waning generalized fatigue, bilateral hand tingling, and occasional nondescript speech changes that make her sound as though she has a slight accent. She has also had bilateral optic neuritis and one transient episode of aphasia in the past. She was last hospitalized 3 years ago. For the past 2 years she has been on cyclophosphamide and methylprednisolone, originally every 4 weeks, and now every 6 weeks, with the last treatment 1 month ago. She has tried and failed interferon β therapy. For the 2 months prior to admission, the patient has had worsening bilateral lower extremity weakness/heaviness, increased fatigue, and mild low back numbness, as well as intermittent and alternating decreased hearing in both ears at work. She has also noticed mild unsteadiness walking. Included among her admission orders should be
a. Heart-healthy diet
b. Ranitidine 150 mg bid
c. Neurological checks every hour for the first 48 h
d. Placement of central venous line
e. Stat head CT for change in mental status
B
(Braunwald, p 2459.) Gastric disturbances are a common side effect of corticosteroid use. Ranitidine is an appropriate prophylactic treatment. Patients with high cholesterol should be given a heart-healthy diet. Neurological checks every hour, central venous line, and stat head CT for change in mental status are all things that should be done for unstable trauma patients with a cranial component.
- A 29-year-old man contracted HIV-1 through homosexual activity 5 years ago. He had been doing well on HAART, but stopped taking his med¬ications 8 months ago because he thought that he would be better off. Two months ago he was successfully treated for Pneumocystis carinii pneumonia. A papovavirus infection of the central nervous system (CNS) in this person would be most likely to produce
a. Adrenoleukodystrophy
b. Multiple sclerosis
c. Subacute sclerosing panencephalitis (SSPE)
d. Progressive multifocal leukoencephalopathy (PML)
e. Metachromatic leukodystrophy
D
(Rowland, pp 155–156.) Adrenoleukodystrophy, MS, SSPE, PML, and metachromatic leukodystrophy are all demyelinating diseases, but PML is the only one confidently linked to a virus. The specific strains of papovavirus most often implicated in PML are BK, JC, and SV40. The patients at risk for this often lethal demyelinating process are those with lymphomas, leukemias, and AIDS. Patients on immunosuppressants face substantially less risk, but are at more risk than the general population.
- A 3-month-old child has a rapid regression of psychomotor function and loss of sight. There is increased urinary excretion of N-acetyl-L-aspartic acid. A preliminary diagnosis of Canavan’s disease (Canavan-van Bogaert-Bertrand disease; spongy degeneration of infancy) is made. This is a demyelinating disease that produces retardation in infants, is inherited in an autosomal recessive pattern, and results in
a. Anencephaly
b. Microcephaly
c. Porencephaly
d. Macrocephaly
e. Dolichocephaly
D
( Victor, pp 1000–1001.) Canavan’s disease may produce developmental regression at about 6 months of age. The infant develops extensor posturing and rigidity. Myoclonic seizures may develop. Underlying the disease is a defect in N-acetylaspartic acid metabolism. Elevated levels of this material can be detected in the blood and urine, but elevated levels in the brain establish the diagnosis. Changes in brain white matter are widespread and may result in a spongiform appearance.
A 58-year-old man with a basilar tip aneurysm is referred by a neurosurgeon. He has a 4-year history of progressive spastic paraparesis. He has recently had urge incontinence of urine. He also has numbness in the right toes more than the left, and pain in the thighs and back. There have been some gradual fluctuations, but no clear, discrete episodes of deterioration. He has had no disturbances of vision, eye movement, or motor control of the upper extremities. He was referred when surgical clipping of the aneurysm 3 months ago failed to help his symptoms.
- Which of the following would be the most appropriate next diagnostic test?
a. Cerebral angiography
b. Spinal angiography
c. MRI of the spinal cord
d. Spinal cord biopsy
e. VER
C
(Bradley, p 1446.) This patient has a gradually progressive myelopathy. The differential diagnosis is broad, but MS is high on the list. A subset of patients with MS consists of middle-aged men with a progressive form of the disease. An MRI of the spinal cord could show MS plaques in the cord or other abnormalities intrinsic to the spinal cord parenchyma, and could also exclude compressive lesions. Vascular malformations of the spinal cord can also be seen in this way, although sometimes spinal angiography is required for definitive diagnosis. Cerebral angiography would not be helpful, except to evaluate for residual aneurysm, which is unlikely to be related to this patient’s problem. Spinal cord biopsy is unwarranted in this case unless a specific indication is provided on neuroimaging. Visual evoked responses may be abnormal in MS, even without clinical evidence of disease, but would not account for the patient’s spastic paraparesis.
A 58-year-old man with a basilar tip aneurysm is referred by a neurosurgeon. He has a 4-year history of progressive spastic paraparesis. He has recently had urge incontinence of urine. He also has numbness in the right toes more than the left, and pain in the thighs and back. There have been some gradual fluctuations, but no clear, discrete episodes of deterioration. He has had no disturbances of vision, eye movement, or motor control of the upper extremities. He was referred when surgical clipping of the aneurysm 3 months ago failed to help his symptoms.
- Cystometrographic analysis of bladder function in this patient is likely to show which of the following abnormalities?
a. Bladder hypotonia
b. Large residual volume of urine
c. Premature bladder emptying
d. Good voluntary control of bladder emptying
e. Urinary tract infection
C
(Bradley, p 1440.) The patient with a spastic paraparesis will also often have a spastic bladder. There is little or no residual urine in the bladder after emptying because bladder contractility is good, but distensibility is poor. The bladder does not distend substantially because of corticospinal tract disease, which produces spasticity. The patient usually complains of urgency or incontinence.
A 58-year-old man with a basilar tip aneurysm is referred by a neurosurgeon. He has a 4-year history of progressive spastic paraparesis. He has recently had urge incontinence of urine. He also has numbness in the right toes more than the left, and pain in the thighs and back. There have been some gradual fluctuations, but no clear, discrete episodes of deterioration. He has had no disturbances of vision, eye movement, or motor control of the upper extremities. He was referred when surgical clipping of the aneurysm 3 months ago failed to help his symptoms.
- Three months later, the patient has worsening leg weakness. He has severe spasms of his legs bilaterally, and is increasingly unable to ambulate because of this. A reasonable symptomatic treatment option would be which of the following?
a. Cyclophosphamide
b. Baclofen
c. Gabapentin
d. Amitriptyline hydrochloride
e. Propranolol
B
(Bradley, p 1453.) Baclofen is an antispasmodic agent that may be used in MS. Additional agents that may be used include tiazidine or benzodiazepines. Cyclophosphamide is an immunosuppressive drug that may be used to treat MS, but would not be considered a symptomatic therapy.
A 58-year-old man with a basilar tip aneurysm is referred by a neurosurgeon. He has a 4-year history of progressive spastic paraparesis. He has recently had urge incontinence of urine. He also has numbness in the right toes more than the left, and pain in the thighs and back. There have been some gradual fluctuations, but no clear, discrete episodes of deterioration. He has had no disturbances of vision, eye movement, or motor control of the upper extremities. He was referred when surgical clipping of the aneurysm 3 months ago failed to help his symptoms.
- Which of the following factors might be expected to worsen his condition?
a. Bright lights
b. Red wine
c. Tyramine-containing compounds
d. Hot weather
e. Amantadine
D
(Bradley, p 1441.) Patients with demyelinating diseases often notice that their symptoms become worse in conditions of increased temperature. In fact, one old way of diagnosing MS called for the patient to be submerged in a tub of warm water; if the deficits worsened, this was considered a sign of MS. This heat sensitivity, also called Uhthoff’s phenomenon, explains why patients often feel worse in the summer or on taking hot showers. MS is worth considering when seeing a patient who complains of exercise-induced symptoms, because the increased heat that is generated by exercise may be enough to exacerbate the deficits.
- A 23-year-old woman awakens with bilateral leg weakness and numbness, urinary retention, and impaired bowel control. She has had several episodes of blurred vision over the previous 2 years, but these had always been attributed to idiopathic papillitis. (SELECT 1 DIAGNOSIS)
a. Neuromyelitis optica (Devic’s disease)
b. Central pontine myelinolysis
c. Marchiafava-Bignami disease
d. Acute disseminated encephalomyelitis
e. Pelizaeus-Merzbacher disease
f. Leber’s optic atrophy
g. Alexander’s disease
h. Adrenoleukodystrophy
i. Canavan’s disease
A
( Victor, pp 966–967.) Neuromyelitis optica produces signs and symptoms of bilateral optic neuritis in association with a transverse myelitis. The paraparesis, bladder and bowel dysfunction, and
sensory deficit signal a transverse myelitis-that is, an inflammatory demyelinating lesion that transects much of the spinal cord. In some cases, the pathology shows a necrotizing process in the spinal cord. All of these problems may develop with MS, but cerebellar involvement, more scattered cerebral involvement, and a generally less circumscribed pattern of deficits are more likely. Adults are especially likely to develop a pattern more typical of relapsing-remitting MS after an initial episode of neuromyelitis optica. Children presenting with neuromyelitis optica may have no other signs or symptoms of demyelination.
