Acquired Metabolic Disorders

1. ACQUIRED METABOLIC
DISORDERS
Mukesh Sah, MD
United Kingdom
Dr. Mukesh Sah

2. • A number of major general pathologic processes,
including metabolic disturbances (e.g., hypoxia and some
vitamin deficiencies), exogenous intoxications, and
various visceral lesions, can produce changes in the
central and/or peripheral nervous system.
• These changes, which are usually nonspecific, may show
regional variation in the CNS.
• The pathophysiologic bases of this phenomenon, is often
referred to as “selective vulnerability”
Dr. Mukesh Sah

3. SELECTIVE REGIONAL
VULNERABILITY
• Determines the anatomic distribution of the lesions.
• Most vulnerable are the hippocampus (CA1), the neocortex, the
cerebellar cortex (Purkinje cells), the thalamus (anterior and
dorso-medial), and the basal ganglia (spiny neurons).
• The hypothalamus, the brainstem, and the spinal cord are the
least vulnerable.
Dr. Mukesh Sah

4. PERMANENT GLOBAL ISCHEMIA:
BRAIN DEATH
• When CPP ( cerebral perfusion pressure) suddenly drops below a
critical value (about 40 mm Hg), cerebral circulation gradually
ceases.
• If blood flow is not restored, the nonperfused brain suffers total
and irreversible damage, eventually leading to irreversible
cessation of all functions of the brain, in both the cerebral
hemispheres and the brainstem.
Dr. Mukesh Sah

5. VARIATION OF LESIONS
ACCORDING TO ETIOLOGY
Dr. Mukesh Sah

6. CARBON MONOXIDE
POISONING
• produced by incomplete combustion of carbon-containing
substances.
• Humans are exposed to CO primarily through automobile
exhaust, improperly ventilated stoves or heaters, and tobacco
smoke
• The toxic effects of CO result primarily from the decreased
capacity of blood to transport oxygen
Dr. Mukesh Sah

7. CARBON MONOXIDE
POISONING
• Generally swollen and congested.
• Blood within vessels has a
characteristic cherry-red color of
carboxyhemoglobin and imparts
that color to the gross brain.
• Petechial hemorrhages may also be
present.
• The red color of the fresh brain
becomes less prominent with
prolonged formalin fixation
Dr. Mukesh Sah

8. CARBON MONOXIDE
POISONING
• Pallidal necrosis (usually bilateral) is classically associated
with delayed deaths from CO intoxication.
• Grossly discernible foci of tissue damage are encountered
most often in those individuals who have survived for 6 or
more days
Dr. Mukesh Sah

9. THIAMINE DEFICIENCY
• Wernicke-Korsakoff syndrome is caused by Vit B1 deficiency,
resulting from
• Inadequate B1 intake
• Significant nutritional deficit
• Gastric absorption defect
• It also complicates chronic dialysis and treatment with tolazamide
or zidovudine.
• It is most often encountered in patients with chronic alcoholism
Dr. Mukesh Sah

10. WERNICKE
ENCEPHALOPATHY
• Distribution of the lesions is characteristic
• The lesions are found in the periventricular areas, including the
medial aspect of the thalamus, hypothalamus, and mamillary
bodies; the periaqueductal region at the level of the third cranial
nerve; the reticular formations of the midbrain and the inferior
corpora quadrigemina; and the floor of the fourth ventricle.
• The mamillary bodies are the most frequently affected
structures and are involved in virtually all cases.
Dr. Mukesh Sah

11. WERNICKE
ENCEPHALOPATHY
• When patients die in
the acute stages of
the disease, petechial
hemorrhages involve
predominantly the
mamillary bodies
Dr. Mukesh Sah

12. WERNICKE
ENCEPHALOPATHY
• Less severe, chronic, or previously treated disease may have mildly
atrophic mamillary bodies that are gray to brown in color as a
result of hemosiderin deposition
Dr. Mukesh Sah

13. PELLAGRA
• Results from lack of P-P (pellagra preventive) factor (nicotinic acid or niacin).
• Results from either deficiency of niacin itself, or of tryptophan, an amino acid
precursor of niacin that is deficient in corn
• Has become very rare as the result of enriching common foods, such as bread,
with niacin.
• This vitamin deficiency is now encountered most often in patients with chronic
alcoholism
• Manifest typically by dermatitis, diarrhea, and dementia
Dr. Mukesh Sah

14. PELLAGRA
• Isolated neuronal changes of
central chromatolysis type
without associated glial or
vascular alterations.
• In order of decreasing frequency,
Betz cells, pontine nuclei, dorsal
nucleus of the vagus, gracile and
cuneate nuclei, nucleus
ambiguus, trigeminal nerve
nuclei, oculomotor nuclei,
reticular formations, and anterior
horn motor neurons of the spinal
cord
Dr. Mukesh Sah

15. TOXIC ENCEPHALOPATHIES
• Ethanol has many effects upon the central nervous system.
• It is well known that alcoholism potentiates infections,
contributes to traumatic injuries, and may increase the risk of
stroke, especially hemorrhagic stroke.
• Alcoholism is also implicated in associated peripheral neuropathy
and myopathy
Dr. Mukesh Sah

16. ACUTE ALCOHOL
INTOXICATION
• Blood alcohol levels over 450–500mg/dl are generally
considered potentially lethal, although there is considerable
individual variation.
• Brains from individuals dying of acute alcohol intoxication
usually show only cerebral edema or no morphologic
abnormalities.
Dr. Mukesh Sah

17. CHRONIC ALCOHOLISM
• Hepatic encephalopathy
• Cerebral lesions due to vitamin deficiency include
• Wernicke-Korsakoff encephalopathy secondary to deficiency of vitamin B1 absorption
caused by alcoholic gastritis
• Pseudopellagra encephalopathy
• Alcoholic cerebellar degeneration
• Central pontine myelinolysis
• Marchiafava-Bignami disease
• Morel laminar sclerosis
Dr. Mukesh Sah

18. HEPATIC ENCEPHALOPATHY
• occurs in the course of severe hepatic insufficiency with
terminal coma in cases of severe hepatic cirrhosis or
hepatitis, in portocaval anastomosis, and in Wilson
hepatolenticular degeneration
• characterized by the presence of Alzheimer type II glia.
• The lesions predominate in the pallidum but may also
involve the cerebral cortex and the dentate nuclei.
Dr. Mukesh Sah

19. ALCOHOLIC CEREBELLAR
DEGENERATION
• May occur as an isolated lesion or in association with other
alcohol-related lesions
• Morphologically similar but generally milder cerebellar vermal
atrophy can also occur as an age-related phenomenon independent
of alcoholism
Dr. Mukesh Sah

20. ALCOHOLIC CEREBELLAR
DEGENERATION
• vermal atrophy can be demonstrated by CT and MRI, but the
degree of atrophy does not correlate well with the severity of
clinical manifestations
• lesions involve the rostral vermis and to a lesser extent, the
superior surface of the cerebellar hemispheres
Dr. Mukesh Sah

21. ALCOHOLIC CEREBELLAR
DEGENERATION
• The folia are pale,
sclerotic, and separated
by widened interfolial
sulci.
Dr. Mukesh Sah

22. ALCOHOLIC CEREBELLAR
DEGENERATION
• The lesions consist of loss of Purkinje cells with proliferation of
Bergmann glia and variable depopulation of the internal
granular cells.
• They are associated with lesions of the dorsal laminae of the
inferior olives.
• The cerebellar white matter remains relatively unaffected
Dr. Mukesh Sah

23. CENTRAL PONTINE
MYELINOLYSIS
• form of myelin damage that was first described in chronic
alcoholics but which may be seen in other conditions in
which severe metabolic or electrolyte disturbances are
present, especially following excessively rapid correction or
overcorrection of chronic hyponatremia.
Dr. Mukesh Sah

24. CENTRAL PONTINE
MYELINOLYSIS
• Diagnosis can be made by MRI.
• At autopsy, the typical lesion of central
pontine myelinolysis appears as a
discolored, necrotic area in the basis
pontis that may be centrally cavitated
Dr. Mukesh Sah

25. CENTRAL PONTINE
MYELINOLYSIS
• ill-defined brown discoloration
Dr. Mukesh Sah

26. CENTRAL PONTINE
MYELINOLYSIS
• The lesions are often
triangular, T-shaped, or
diamond-shaped and vary
from a few millimeters
across to lesions that involve
nearly the entire basis
pontis.
Dr. Mukesh Sah

27. CENTRAL PONTINE
MYELINOLYSIS
• Demyelination with
relative preservation of
axons and neuronal
perikarya
• Acute lesions contain
numerous lipid-laden
macrophages but few or no
inflammatory cell
infiltrates
Dr. Mukesh Sah

28. THANK YOU
Dr. Mukesh Sah