Vitamin B12 Cobalamine Deficiency

The intestinal absorption of vitamin B12 requires its binding to an intrinsic factor synthesized by the parietal cells of the gastric mucosa. An autoimmune gastritis, by interfering with the production or function of this intrinsic factor, is a major cause of the impaired absorption of vitamin B12. Other causes are gastrectomy, enteritis, malabsorption diseases, malignancies, and fish tapeworm infestation.

Subacute combined degeneration of the spinal cord and megaloblastic (pernicious) anemia are major disorders associated with vitamin B12 deficiency. The

table 10.2.

Wernicke-Korsakoff Encephalopathy

Clinical Features

Site of Pathology

Ocular: pupillary

Brainstem tegmentum

abnormalities: extraocular

muscle palsy; gaze palsy:

nystagmus

Autonomic dysfunction:

Hypothalamus

temperature;

Medulla: dorsal n. of

cardiocirculatory;

vagus

respiratory

Ataxia

Medulla: vestibular

region

Cerebellum

Depression of consciousness

Brainstem: periaqueductal

gray

Altered mentation: global

Diffuse cerebral

confusional state

dysfunction

Amnestic syndrome

Dorsomedial n. of

for recent memory

thalamus

Mammillary bodies

figure 10.2

Wernicke-Korsakoff encephalopathy in a 48-year-old man, a heavy drinker. A. Transverse section at thalamus level shows brownish discoloration of the mammillary bodies and fresh petechiae in the floor of the third ventricle. Macrosections show (B) hypercellularity in mammillary bodies due to proliferated astrocytes and macrophages (Cresyl-violet), and (C) demyelination of stria medullaris and pallor of myelin in the thalami (Weil stain). D. Mammillary body contains macrophages and proliferated astrocytes (HE).

figure 10.2

Wernicke-Korsakoff encephalopathy in a 48-year-old man, a heavy drinker. A. Transverse section at thalamus level shows brownish discoloration of the mammillary bodies and fresh petechiae in the floor of the third ventricle. Macrosections show (B) hypercellularity in mammillary bodies due to proliferated astrocytes and macrophages (Cresyl-violet), and (C) demyelination of stria medullaris and pallor of myelin in the thalami (Weil stain). D. Mammillary body contains macrophages and proliferated astrocytes (HE).

Brain Histological Weils Myelin Stain
„v- . • jvyy* —

^r *

J .

- a .

Wernicke-Korsakoff encephalopathy in an 87-year-old severely malnourished, anemic man. A. Transverse section at midbrain level shows hemorrhagic necrosis in dorso-medial aspects of pulvinars (habenular nuclei), grayish discoloration of ventricular wall and brownish-tan discoloration of lateral geniculate bodies, B. Upper pons shows hemorrhagic discoloration of locus ceruleus. C. Medulla shows symmetrically situated hemorrhages in the floor of fourth ventricle and (D) necrosis at the sites of hypoglossus nuclei (HE).

figure 10.4

Chronic Wernicke-Korsakoff encephalopathy in an 80-year-old man, chronic alcoholic. A. Macrosection of the thalami shows severe atrophy of the mammillary bodies. B. Higher magnification view shows neuronal losses and mild astrocytosis in the wall of third ventricle (LFB-CV).

figure 10.4

Chronic Wernicke-Korsakoff encephalopathy in an 80-year-old man, chronic alcoholic. A. Macrosection of the thalami shows severe atrophy of the mammillary bodies. B. Higher magnification view shows neuronal losses and mild astrocytosis in the wall of third ventricle (LFB-CV).

neurologic complication is attributed to the failure of a cobalamine-dependent enzyme necessary for the maintenance of myelin.

The disease has a subacute course, and manifests with paresthesias in the extremities, weakness and diminished or lost vibratory and position sensations in the lower extremities, positive Romberg sign, and a spastic ataxic (sensory) gait. Cerebral dysfunction, emotional lability, confusion, and intellectual decline may add to the clinical picture.

Pathology: Grossly, the spinal cord shows mild atrophy and grayish discoloration of the posterior and lateral columns. The histology is characterized by degeneration of myelin in the posterior and lateral columns, involving chiefly the corticospinal tracts. The degenerated tracts are vacuolated and spongy from the vacuolar dis tension of myelin (Fig. 10.5). In the acute stage, lipid-laden macrophages are numerous, but astrocytic reaction is not prominent in the chronic stage. Focal spongy myelin degenerations may also occur in the cerebral hemispheric white matter. Optic nerve degeneration is rare.

METABOLIC ENCEPHALOPATHIES Hepatic Encephalopathy

Hepatic encephalopathy may develop acutely, complicating a fulminant hepatic failure or progress slowly, complicating chronic cirrhosis or a porto-caval shunt. A disorder of nitrogen metabolism and elevated blood ammonia levels are implicated in the pathogenesis.

Acute hepatic encephalopathy presents with altered mentation, delirious state, seizures, and signs of raised intracranial pressure progressing rapidly to coma and death. Chronic hepatic encephalopathy presents with mild behavioral abnormalities, mental dullness, asterixis (flapping of outstretched hands), extrapyramidal symptoms (tremor, choreoathetosis), cerebellar ataxia, and dysarthria. In the terminal stage, altered mentation gradually progresses to stupor and coma. The blood ammonia level is elevated. EEG abnormalities consist of

Pernicious Anemia Spinal Cord Tracts

figure 10.5

Subacute combined degeneration of the spinal cord in vitamin B12 deficiency. Macrosection of the lumbar spinal cord shows spongy degeneration of myelin in the posterior columns and corticospinal tracts of the lateral columns (Weil stain).

figure 10.5

Subacute combined degeneration of the spinal cord in vitamin B12 deficiency. Macrosection of the lumbar spinal cord shows spongy degeneration of myelin in the posterior columns and corticospinal tracts of the lateral columns (Weil stain).

paroxysms of bilaterally synchronous slow or triphasic waves in the delta-range.

Pathology: Grossly, in acute hepatic encephalopathy, the brain is swollen (cytotoxic edema) and may have a greenish tint from bilirubin crossing the disrupted blood-brain barrier. In chronic encephalopathy, the brain is variably atrophic. Histologically, both acute and chronic encephalopathies are characterized by the presence of Alzheimer type 2 astroglia. These astrocytes have a large, round, less often lobulated or crescent-shaped vesicular nucleus with scanty chromatin and a prominent nucleolus. The perikaryon does not stain with eosin. They are usually immunonegative for GFAP but immunopositive for S-100 protein, and may contain glycogen inclusions (Fig. 10.6). These astrocytes are found in the deep cortical layers, basal ganglia, thalamus, and olivary and dentate nuclei. Additional characteristic features in chronic hepatic encephalopathy are necrosis and microvacuolation in the cerebral cortex at the junction with the white matter and in the basal ganglia and cerebellum.

0 0

Post a comment