Lecture 65 - Neuropathology: Toxic Metabolic and Nutritional Disorders

Question 1

Among Neurons, Oligodendroglial cells, and Astrocytes, which cell types are more susceptible to ischemic damage?

________ cells are the most Resistant to ischemic damage. Remember these are derived from _______, while Nerons, Oligodendroglial, and Astrocytes are derived from ________.

Neurons also have differing susceptibility to ischemic damage. _______ neurons of the Hippocampus are most susceptible, ________ cells in the Cerebellum are next, Neurons of layers ______ - ______ of the Cerebral cortex are next, and Neurons in the ______ and _____ _____ are Least susceptible.

Answer 1

Neurons > Oligodendroglial cells > Astrocytes

Endothelial cells

Mesoderm

Neuroectoderm

Pyramidal neurons of Hippocampus

Purkinje cells in the Cerebellum

Neurons in layers III - V of the cortex

Neurons in the Brainstem and Spinal Cord

Question 2

_______ enter into the brain following ischemic damage, and they leave behind cavitation of the brain matter once they’ve “cleaned it up.”

Answer 2

Macrophages

Question 3

A Non-perfused brain typically occurs transiently as a result of ________ pressure exceeding ______ perfusion pressure. This can occur if BP drops (e.g. severe hypovolemia secondary to hemorrhage, cardiac arrest, etc…)

Answer 3

Intracranial pressure

Arterial perfusion pressure

Question 4

Hepatic Encephalopathy is considered a _______ encephalopathy associated with hepatic failure. Clinically, look for patients to present with coma or stupor, seizures, or _______ (inability to hold arms outstretched for more than a brief moment).

Hepatic encephalopsthy symptoms occur from build up of ______ in the serum and resulting change in the nuclei of _______, causing them to become dysfunctional (so dysfunctional BBB) bc they selectively take up _____.

Keep in mind this is _______ (reversible or irreversible)!

Answer 4

Metabolic Encephalopathy

Asterixis

NH3 (ammonia)

Astrocytes

NH3

Question 5

Reye Syndrome is an encephalopathy related to acute fatty _______ with _______ dysfunction. It leads to massive brain edema and subsequent cerebellar tonsilar herniation. Keep in mind this occurs in children who have ingested ______.

Answer 5

Fatty Liver

Mitochondria

Aspirin

Question 6

_____-_____ disease (aka GM2 gangliosidosis) is most common among ______ ______. It occurs from an Autosomal ________ mutation in the Hexosaminidase gene on chromosome _____. There’s an accumulation of ganglioside in neurons, causing cells death. Keep in mind this is a “poliodystrophy,” so it occurs within the _____ matter.

Answer 6

Tay-Sachs

Ashkenazi Jews

Autosomal Recessive

Chromosome 15

Grey

Question 7

Leukodystrophies are genetic disorders that result in ___________, with loss of enzymes involved in myelin formation or maintenance. This leads to massive, confluent loss of myelin, with _____ (scarring) and relative preservation of ______.

_________ is one type that is ____-linked.

Answer 7

Dysmyelination

Gliosis

Axons

Adrenoleukodystrophy

X-linked

Question 8

Adrenoleukodystrophy results from an X-linked mutation in the ________ gene in the Xq28 locus. It codes for _________ membrane transporter protein.

Metachromatic leukodystrophy results from an autosomal _______ mutation in the ________ A gene. Variations in the gene lead to different ages of onset.

Answer 8

ABCD1 gene

Peroxisomal membrane protein

Autosomal Recessive

Arylsulfatase A gene

Question 9

Wernicke’s Encephalopathy is caused by deficiency in Vit _____ (thiamine). It can be caused by malnutrition, but it is commonly seen in _______. Patients will present with Acute ______ and ataxia. Look for lesions mainly in the _______ (especially in the mammillary bodies) and also in the periaqueductal region and floor of the fourth ventricle. In the acute phase, you’ll notce hemorrhage in these areas.

________ psychosis is a confabulatory dementia that results from chronic Wernicke’s encephalopathy, so it is commonly seen in ______.

Answer 9

Vit B1

Alcoholics

Acute Nystagmus and Ataxia

Hypothalamus

Korsakoff’s psychosis

Alcoholics

Question 10

Subacute combine degeneration of the Spinal cord results from a deficiency in Vit _____ (cobalamin). There is vacuolar degeneration of the _____ and ______ columns –> leads to weakness and spasticity as well as loss of proprioception and vibration. A similar lesion has been described in patients with ______ who have NORMAL cobalamin levels.

Answer 10

Vit B12

Lateral and Dorsal columns

AIDS

Question 11

Ethanol abuse/chronic use can cause toxic degeneration of the _______, leading to ataxia similar to Wernicke’s Encephalopathy. What’s the difference in these lesions?

Answer 11

Cerebellar degeneration

Ethanol toxicity is not hemorrhagic, while Wernicke’s encephalopathy IS.

Question 12

CO poisoning (Carboxyhemoglobin) can lead to ischemic disease. How would you expect a patient’s brain to appear in this case?

Answer 12

It would appear to have a pink color from the Carboxyhemoglobin.

Question 13

_______ toxicity causes degeneration of dopaminergic neurons in the substantia Nigra –> Pakinsonism that was irreversible

Answer 13

MPTP (Meperidine analog)