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Flashcards in Disorder of Myelination Deck (20):
1

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 rightlower extremity was fine. Coughing, sneezing, and the Valsalva maneuverdid 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 becameblurred 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 isbirth control pills. Examination is significant for brisk reflexes and sustainedclonus at the right ankle. Babinski sign is present on the right. Testing is positive for oligoclonal bands.266. The most likely diagnosis in this case is
a. Seizure
b. Transient ischemic attack
c. Anaplastic astrocytoma
d. Multiple sclerosis
e. Parkinson’s disease

266. The answer is d. ( Victor, pp 961–962.) This is a typical history formultiple 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 transientischemic 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 predisposingfactor. Seizure predisposing factors include previous seizure, brain trauma,brain hemorrhage, and encephalitis. An anaplastic astrocytoma is a malignanthigh-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.

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267. 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

267. The answer is e. ( Victor, p 969.) Between 85 and 90% of patientswith 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.

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268. On briskly flexing the neck forward, a patient with this disease mayreport
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

268. The answer is 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 thesensation. Dystonic posturing may also occur in patients with MS, but theposturing is usually spontaneous. A massive Babinski response may producebladder evacuation and extensor plantar responses as well as involuntary leg withdrawal in these same patients. This type of reflex responseis usually elicited by stimuli to the feet or legs rather than by manipulation of the neck or spine.

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269. 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 ìL
e. Erythrocyte counts of greater than 10 cells per ìL

269. The answer is c. (Bradley, pp 1448–1449.) The IgG content of theCSF remains elevated even between acute exacerbations of the MS. The IgGhas a distinctive ê light chain composition. This immunoglobulin typically accounts for more than 15% of the total protein content in the CSF of the patient with MS.

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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. Hereceived steroids at that time. He began interferon â-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 inthe front and back. He has no pain, tingling, exacerbation of symptomswith neck movement, neck injury, incontinence, gait disturbance, diplopia,fever, chills, nausea, or vomiting. Examination findings include full visualfields 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.270. The most appropriate pharmacological treatment for this patient atthis time is
a. Interferon â-1B
b. Corticosteroids
c. Gabapentin
d. Glatiramer
e. Pramipexole

270. The answer is b. ( Victor, p 973.) Corticosteroids are an appropriatetreatment 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 â-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 anticonvulsant medication that is also useful for the treatment of neuropathicpain, 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.

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271. Multiple sclerosis is the most common demyelinating disease in theUnited States, affecting approximately 1 person in
a. 100
b. 500
c. 1,000
d. 5,000
e. 10,000

271. The answer is 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.

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272. The evoked response pattern that is most often abnormal in patientswith 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

272. The answer is 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 anyproblem 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.

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273. 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 commonly consisting of increasing bilateral lower extremity weakness anddecreased sensation manifested as a heavy feeling, waxing and waning generalized fatigue, bilateral hand tingling, and occasional nondescript speechchanges that make her sound as though she has a slight accent. She has alsohad 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 oncyclophosphamide and methylprednisolone, originally every 4 weeks, and now every 6 weeks, with the last treatment 1 month ago. She has tried and failed interferon â therapy. For the 2 months prior to admission, the patienthas had worsening bilateral lower extremity weakness/heaviness, increasedfatigue, and mild low back numbness, as well as intermittent and alternatingdecreased 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

273. The answer is 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 forunstable trauma patients with a cranial component

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274. 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 medications 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

274. The answer is d. (Rowland, pp 155–156.) Adrenoleukodystrophy, MS, SSPE, PML, and metachromatic leukodystrophy are all demyelinatingdiseases, but PML is the only one confidently linked to a virus. The specificstrains of papovavirus most often implicated in PML are BK, JC, and SV40.The patients at risk for this often lethal demyelinating process are thosewith lymphomas, leukemias, and AIDS. Patients on immunosuppressantsface substantially less risk, but are at more risk than the general population.

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275. 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

275. The answer is d. ( Victor, pp 1000–1001.) Canavan’s disease mayproduce 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.

11

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.276. 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

276. The answer is c. (Bradley, p 1446.) This patient has a gradually progressivemyelopathy. 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 sometimesspinal 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 withoutclinical evidence of disease, but would not account for the patient’s spasticparaparesis.

12

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.277. 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

277. The answer is c. (Bradley, p 1440.) The patient with a spastic paraparesiswill 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. Thepatient usually complains of urgency or incontinence.

13

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.278. 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 bewhich of the following?
a. Cyclophosphamide
b. Baclofen
c. Gabapentin
d. Amitriptyline hydrochloride
e. Propranolol

278. The answer is 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.

14

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.279. 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

279. The answer is d. (Bradley, p 1441.) Patients with demyelinating diseasesoften 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.

15

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
280. 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)

280. The answer is a. ( Victor, pp 966–967.) Neuromyelitis optica producessigns 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 theseproblems may develop with MS, but cerebellar involvement, more scatteredcerebral 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 haveno other signs or symptoms of demyelination.

16

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
281. Two weeks after recovering from a febrile illness associated with a productive cough, a 19-year-old man complains of headache and neck stiffness. These complaints are associated with fever and are soon followed by deteriorating cognitive function. He becomes disoriented, lethargic, and increasingly unresponsive. MRI reveals widespread damage to the white matter of the cerebral hemispheres. (SELECT 1 DIAGNOSIS)

281. The answer is d. ( Victor, pp 975–978.) Acute disseminatedencephalomyelitis is often fatal. On examination of the brain, damage tosmall blood vessels and to perivascular tissues in the white matter of thecerebral hemispheres is extensive and coalescent. The diagnosis is suggestedby the MRI or CT picture of rapidly evolving white matter damage associated with a high erythrocyte sedimentation rate (ESR) and a cerebrospinal fluid (CSF) under increased pressure with elevated red cell and white cell counts and elevated protein content. The CSF glucose content isusually normal.

17

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
282. A 24-year-old man has progressive loss of vision over the course of 5 years. A visual field examination reveals a centrocecal scotoma. Two of his cousins have similar problems with visual loss. Both of the affected relatives are male and in their twenties. Genetic testing reveals a mutation of mitochondrial DNA. (SELECT 1 DIAGNOSIS)

282. The answer is f. ( Victor, pp 1164–1165.) The optic neuritis of MSproduces enlargement of the physiologic blind spot, but rarely to the pointwhere it impinges on central vision. When the blind spot extends into centralvision, it is called a centrocecal scotoma. A young man presenting with this pattern of visual loss is much more likely to have Leber’s optic atrophy or another cause of optic atrophy (e.g., tobacco-alcohol amblyopia, tertiary syphilis, or vitamin deficiencies) than to have multiple sclerosis. That other men in the family are similarly affected supports the diagnosis of the hereditary Leber’s optic atrophy. This condition is caused by one of several possible mutations in mitochondrial DNA.

18

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
283. Two brothers, 4 and 7 years of age, exhibit limb ataxia, nystagmus, and mental retardation. MRI of their brains reveals areas of abnormal signal in the white matter. Cerebellar involvement is substantial. Both boys also have abnormally low serum cortisol levels. (SELECT 1 DIAGNOSIS)

283. The answer is h. ( Victor, pp 1034–1036.) Adrenal dysfunction inassociation with a progressive degenerative disease of the white matter suggests adrenoleukodystrophy. Some types are X-linked defects, and the factthat two brothers are affected in similar ways suggests that they have theX-linked form of adrenoleukodystrophy. X-linked adrenoleukodystrophy produces rapidly evolving brain damage in male infants or boys, with survival from onset of symptoms usually limited to 3 years. The underlying defect in this X-linked disorder is an ATP-binding transporter in the peroxisomal system responsible for long-chain fatty acid metabolism. Long-chain fatty acids accumulate in adrenal cortical and other cells. Pathophysiologically similar to, but otherwise distinct from, adrenoleukodystrophy is adrenomyeloneuropathy. It may develop in heterozygous women and usually involves less pronounced damage to the brain and more obvious damage to the spinal cord and peripheral nerves. Persons with adrenomyeloneuropathy routinely develop spastic paraparesis, problems with bladder and bowel control, and sensory disturbances in the legs.

19

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
284. A 3-month-old boy exhibits nystagmus and limb tremors unassociatedwith seizures. Over the next few years, he develops optic atrophy, choreoathetotic limb movements, seizures, and gait ataxia. He dies during status epilepticus and at autopsy is found to have widespread myelin breakdown with myelin preservation in islands about the blood vessels. The pathologist diagnoses a sudanophilic leukodystrophy to describe the pattern of staining observed on slides prepared to look for myelin breakdownproducts. (SELECT 1 DIAGNOSIS)

284. The answer is e. ( Victor, p 1000.) Pelizaeus-Merzbacher disease is ademyelinating disorder that belongs to a group of degenerative diseases known as sudanophilic leukodystrophies. Leukodystrophy refers to the disturbance of white matter, and sudanophilic refers to the Sudan staining characteristics of the involved white matter. Children with Pelizaeus-Merzbacher disease typically become symptomatic during the first months of life, but survival may extend into the third decade of life. Most affectedpersons are male.

20

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
285. A 54-year-old alcoholic man is brought to the emergency room withprofound agitation. He is believed to be suffering from delirium tremens and is treated with thiamine and intravenous fluids. His serum sodium is noted to be markedly depressed, and intravenous supplements are adjusted to rapidly correct this hyponatremia. He becomes acutely quadriplegic and unresponsive and dies within 24 h. (SELECT 1 DIAGNOSIS)

285. The answer is b. (Rowland, pp 794–796.) Rapid correction of hyponatremia in an alcoholic may precipitate central pontine myelinolysis(CPM), a rapidly fatal, demyelinating disorder of the brainstem. With CPMthere is demyelination in the basis pontis. The destruction of myelin sheaths is usually quite symmetric and appears to begin in the median raphe. There is no inflammation associated with the demyelination, even though the changes occur acutely and progress rapidly. Death usually occurs within days or weeks of the first signs of neurologic disease. Affected persons often have hypokalemia, hypochloremia, and hypomagnesemiaas well as hyponatremia. Many have a low serum osmolality associated with a normal urine osmolality, findings consistent with the syndrome of inappropriate antidiuretic hormone (SIADH). The signs of CPM may be similar to those occurring with Wernicke’s encephalopathy (i.e., disturbed ocular motor function, gait disturbances, and altered consciousness and cognition). That this patient did not have Wernicke’sencephalopathy was suggested by his having received thiamine before theadministration of intravenous solutions, a measure usually sufficient to reduce or eliminate the risk of Wernicke’s encephalopathy.