Carbon Monoxide

Selective injury to the neurons of layers III and V of the cerebral

cortex, Sommer sector of the hippocampus, and Purkinje cells is the recognized consequence of carbon monoxide exposure

Bilateral necrosis of the globus pallidus may also occur, and is

more common in carbon monoxide-induced hypoxia than in hypoxia from other causes

Demyelination of white matter tracts may be a later event

Methanol
The pathologic findings of methanol toxicity are seen in the retina,
where degeneration of retinal ganglion cells may cause blindness

Selective bilateral putamenal necrosis and focal white matter

necrosis also occur when the exposure is severe

Ethanol
The effects of acute ethanol intoxication are reversible, but chronic alcohol abuse is associated with a variety of neurologic sequelae, including Wernicke-Korsakoff syndrome

The toxic effects of chronic alcohol intake may be either direct effects of ethanol or secondary nutritional deficits
Cerebellar dysfunction occurs in about 1% of chronic alcoholics, associated with a clinical syndrome of truncal ataxia, unsteady gait, and nystagmus The histologic changes are atrophy and loss of granule cells predominantly in the anterior vermis In advanced cases, there is loss of Purkinje cells and proliferation of the adjacent astrocytes (Bergmann gliosis) between the depleted granular cell layer and the molecular layer of the cerebellum

Thiamine (Vitamin B1) Deficiency

Thiamine deficiency may lead to the development of psychotic symptoms or ophthalmoplegia that begin abruptly, a syndrome termed Wernicke encephalopathy The acute stages, if unrecognized and untreated, may be followed by a prolonged and largely irreversible condition, Korsakoff syndrome, characterized clinically by memory disturbances and confabulation The syndrome is particularly common in the setting of chronic alcoholism, but may also be encountered in patients with thiamine deficiency resulting from gastric disorders, including carcinoma, chronic gastritis, or persistent vomiting Wernicke encephalopathy is characterized by foci of hemorrhage and necrosis, particularly in the mammillary bodies but also adjacent to the ventricle, especially the third and fourth ventricles

Vitamin B12 Deficiency

Deficiency of vitamin B12 often causes anemia, but its most severe and potentially irreversible effects are related to nervous system lesions

Complete paraplegia may occur, usually only later in the course of the disease
The combined degeneration of both ascending and descending tracts of the spinal cord is characteristic of vitamin B12 deficiency and has led to the designation of the disorder as subacute combined degeneration of the spinal cord

Hypoglycemia
Some regions of the brain are more sensitive to hypoglycemia than are others Glucose-deprivation initially leads to selective injury to large pyramidal neurons of the cerebral cortex, which, if it is severely involved, may result in pseudolaminar necrosis of the cortex, predominantly involving layers II to V The hippocampus is also vulnerable to glucose depletion, as it is to hypoxia, and may show a dramatic loss of pyramidal neurons in Sommer sector (area CA1 of the hippocampus) Purkinje cells of the cerebellum are also vulnerable to hypoglycemia, although to a lesser extent than to hypoxia If the level and duration of hypoglycemia are of sufficient severity, there may be widespread injury to many areas of the brain

Hyperglycemia

Hyperglycemia is most commonly found in the setting of inadequately controlled diabetes mellitus and can be associated with either ketoacidosis or hyperosmolar coma

The patient becomes dehydrated and develops confusion, stupor, and eventually coma The fluid depletion must be corrected gradually, otherwise severe cerebral edema may follow

Hepatic Encephalopathy
The cellular response in the CNS is predominantly glial Alzheimer type II changes are evident in the cortex and basal ganglia and other subcortical gray matter regions

Pathogenesis
A

Autoimmune Processes Blood-Brain Barrier

B

Clinical Course
Relapsing-Remitting (RRMS)
Most common type of MS Signs and symptoms evolve over several days Spontaneous improvement or in response to corticosteroids Full recovery or some residual deficit upon recovery

Secondary Progressive (SPMS)

Initially begins as relapsing-remitting MS Progressive deterioration with or without relapses

Primary-Progressive (PPMS)
Progressive deterioration without relapses and remissions Occasional plateaus and temporary minor improvements Tends to occur in older people

Progressive-Relapsing (PRMS)
Rare Progressive course from the onset Acute relapses that may or may not result in complete recovery

67 An 86-year-old man has become progressively unable to live independently for the past 10 years, and he now requires assistance with bathing, dressing, toileting, feeding, and transfers in and out of chairs and bed. On physical examination, he has no motor or sensory deficits. He cannot give the current date or state where he is. Six months later, he suddenly becomes comatose and dies. At autopsy, there is a large superficial left parietal lobe hemorrhage. Histologic examination of the brain shows numerous neocortical neuritic plaques and neurofibrillary tangles. The peripheral cerebral arteries and the core of each plaque stain positively with Congo red. Which of the following mechanisms is most likely responsible for his disease?

A. Aggregation of A peptide B. Conformational change in the prion protein (PrP) C. Mutations in the tau gene D. Mutations in the frataxin gene E. Dopamine deficiency F. Expansion of polyglutamine repeats

Question. 40

A 68-year-old woman has been placed in a nursing home by her son because she can no longer be cared for at home. She has difficulty keeping her room in order. She misplaces articles of clothing and sometimes dresses herself in an odd fashion. These problems have gotten progressively worse over the past 6 years. She has been continually wandering away from the house and getting lost in the neighborhood over the past 6 months. She took early retirement as an accountant because she was having trouble keeping her clients accounts in order. There is no history of trauma. She has no history of seizures. Which set of histopathologic findings is most typical for her underlying disease process?

A. Atrophy of caudate nucleus and gliosis B. Wallerian degeneration and gliosis

C. Substantia nigra depigmentation and loss of neurons

D. Grouped atrophy of muscle with anterior horn cell loss E. Cortical neuritic plaques

A previously healthy 42-year-old former major league baseball player developed progressive, symmetric muscular weakness of his upper extremities along with fasciculations over the course of 3 years. Then he developed difficulty speaking and swallowing. He did not have myalgias or arthralgias. He remained afebrile. His mental function never became diminished. Which of the following is the most likely diagnosis?

The course is progressive. Bulbar involvement can lead to problems speaking and eating, with risk for aspiration. This disease often goes by the eponym of another baseball player, Lou Gehrig, who could not play first base
anymore once the disease became advanced.

A. B. C. D. E.

Amyotrophic lateral sclerosis von Recklinghausen disease Multiple sclerosis Werdnig-Hoffman disease Guillain-Barr syndrome

13 A 55-year-old man dies of aspiration pneumonia after a 6-year illness, characterized by progressive, symmetric muscular weakness. At autopsy, the brain and spinal cord appear normal on gross examination. Microscopic sections show gliosis in the motor cortex, pallor of the lateral corticospinal tracts, and neuronal loss in the anterior horns of the spinal cord. What is the most likely underlying cause of death?

A. Becker muscular dystrophy B. Neurofibromatosis type 2 C. Guillain-Barr syndrome D. Creutzfeldt-Jakob disease E. Amyotrophic lateral sclerosis

Question. 43

16 A 62-year-old man has had increasing difficulty with voluntary movements because of muscular rigidity. On physical examination, he has difficulty initiating movement, but he can keep moving if he follows someone walking ahead of him. He has an expressionless facies. When he is sitting, his hands have a pill-rolling tremor. Which pathologic finding in the brain is most likely to be present?

A. Hippocampal neurofibrillary tangles B. Neuronal loss with gliosis in caudate C. Hemosiderosis and gliosis of mamillary bodies D. Loss of pigmented neurons in substantia nigra E. Alzheimer type II gliosis in basal ganglia

Question. 45

30 A 42-year-old man has had increasing difficulty performing activities of daily living for the past year because of worsening choreiform movements. His family reports that his behavior has changed, although his memory remains intact. His older brother is similarly affected. On physical examination, he is afebrile and normotensive. Cranial nerves are intact. He has no motor weakness and no sensory deficits. Which of the following findings in the CNS is most likely to be present?

A. Loss of pigmented neurons in the substantia nigra B. Congophilic angiopathy of the cerebral cortex C. Atrophy and gliosis of the caudate nuclei D. Loss of motor neurons in the cerebral cortex and brainstem E. Multiple lacunar infarcts within the basal ganglia

Question. 01

Several members of a large family are affected by the onset of decreasing mental function and motor coordination when they reach middle age. Their extremity movements are marked by choreoathetosis. Genetic testing reveals increased trinucleotide CAG repeats. Which of the following intracranial structures is most likely to appear grossly abnormal at autopsy of these affected persons?

A. Caudate nucleus B. Midbrain C. Temporal lobe D. Locus ceruleus E. Dorsal root ganglion

Question. 00

The family of a 63-year-old woman noticed that she has become more forgetful over a period of 6 weeks. One month later, the woman has difficulty ambulating and is unable to care for herself. On physical examination, she has myoclonus. She is afebrile. CT scan of the head shows minimal cerebral atrophy, which is nearly consistent for age. An EEG shows low-amplitude, slow background activity with periodic complexes and occasional repetitive sharp waves with intervals of 0.5 to 1 second. Which of the following histologic abnormalities is most likely to be found in the cerebral cortex?

A. Numerous neuritic plaques B. Plaques of demyelination C. Lewy bodies D. Microglial nodules E. Spongiform encephalopathy

Question. 01

A clinical study is performed to assess neurologic abnormalities associated with chronic alcohol abuse in adult patients from 30 to 70 years of age. The physical examination findings are analyzed. Which of the following neurologic findings are these patients most likely to exhibit?

Cerebellar disease often manifests with ataxia. Patients with chronic alcoholism can develop anterior vermian atrophy. Truncal and gait ataxia suggests spinocerebellar involvement.

A Choreiform movements B Nystagmus C Truncal and gait ataxia D Tremor at rest that diminishes or disappears with movement E Short-term memory loss

A 72-year-old woman has a five year history of worsening mental functioning with trouble remembering things. She has no problems with movement. MR imaging of the brain shows symmetrically increased size of the lateral ventricles along with cerebral cortical atrophy in a mainly frontal and parietal distribution. A lumbar puncture reveals a normal opening pressure, and analysis of the clear, colorless cerebrospinal fluid reveals a glucose and protein which are in normal ranges. Cell count on the CSF shows 3 WBCs (all lymphocytes) and 1 RBC. Her funduscopic examination is normal. Which of the following abnormalities is most likely to be associated with her underlying disease process?

She has findings characteristic for Alzheimer disease. The neuritic plaques have amyloid cores, and patients may also have a congophilic angiopathy. Persons with the e4 allele of apoE are at increased risk for developing Alzheimer disease.

A B C D E

Loss of gamma aminobutyric acid Presence of the e4 allele of apolipoprotein E Increased numbers of Lewy bodies Perivascular mononuclear inflammation Decreased numbers of Betz cells

A 66-year-old man is finding that he has more difficulty moving about for the past year. He is annoyed by a tremor in his hands, but the tremor goes away when he performs routine tasks using his hands. His friends remark that he seems more sullen and doesn't smile at them, but only stares with a fixed expression on his face. He has not suffered any loss of mental ability. Which of the following diseases is he most likely to have?

A. B. C. D. E.

Amyotrophic lateral sclerosis (ALS) Alzheimer disease Parkinson disease Niemann-Pick disease Tuberous sclerosis

An 18-month old girl exhibits poor psychomotor development since birth, along with seizures. On examination her muscle strength and tone are poor. Brain MR imaging shows multifocal abnormalities with loss of tissue in periventricular regions of midbrain, pons, thalamus, and hypothalamus. Laboratory studies show plasma lactate of 4.2 mmol/L. Which of the following is the most likely diagnosis?

(A) CORRECT. Leigh disease is a form of mitochondrial encephalopathy that appears at a young age. There is a genetic mutation in one of the genes coding for enzymes in the oxidative phosphorylation pathway

A B C D E

Leigh disease Cytomegalovirus infection Wernicke disease Herpes simplex encephalitis Metachromatic leukodystrophy

Question. 01

A clinical study is performed to assess neurologic abnormalities associated with chronic alcohol abuse in adult patients from 30 to 70 years of age. The physical examination findings are analyzed. Which of the following neurologic findings are these patients most likely to exhibit?

A. B. C. D. E.

Choreiform movements Nystagmus Truncal and gait ataxia Tremor at rest that diminishes or disappears with movement Short-term memory loss