Lecture 9 - The Leukodystrophies, Neuronal Storage D/o, Toxic Brain Injury and Vitamin Deficiencies

Question 1

Canavan’s Disease

aka?
deficiency of what?
characteristic pathology?

Answer 1

aka spongy luekodystrophy (WM)

Characteristic Pathlogy – “spongy” (big macules/vacuoles in white matter)

AR deficiency of aspartoacylase

“the caravan of sponges left asparta”

Question 2

Alexander Disease:

deficiency of what ?
localization?
Histopathology?
Presentation?

Answer 2

Sporadic Mutation in GFAP (intermediate filament of astrocytes)

More severe in Frontal Lobes

Histo – Rosenthal Fibers in astrocytes of white matter. Rosenthal Fibers and Myelin Loss

Presentation – FTT, white matter disease

“king alexander got shot with a rosenthal arrow in his frontal lobes while FAPing”

Question 3

Adrenoleukodystrophy (X Linked ALD)

deficiency in?
Localization?
Histology?

Clinical manifestation

Answer 3

X linked, ATP binding cassette transporter mutation. Leading to demyelination

Posterior hemisphere pathology (caudal to rostral gradient)

Histo –perivascular lymphocytic infiltrates

Adrenal insufficiency

“Lorenzo lost his Cassette..in the back”

Question 4

Metachromiac Leukodystrophy

deficiency of?
why is is called metachromatic?
Presentation?

Answer 4

AR, Arylsulfatase A deficiency; accumulate sulfatides in macrophages, leading to myelin destruction

Histo- – a Toludine Blue stain turns brown

Presentation – very heterogenous; some may not present until adulthood with psychiatric disease. Otherwise peripheral and central demyelination with ataxia and dementia

Question 5

Krabbe disease –

deficiency of what?

Characteristic pathology?

Presentation?

Answer 5

AR deficiency of Galactocerebrosidease leading to destruction of the myeline sheath

Microvascular/eosinophilic, globoid cell leukodystrophy

Hyper-irritable, hypertonic infant. FTT, optic atrophy.

Fatal

“Intergalactic Planetary” = The Beastie Boys (irritable kid) do the “Krabbe” walk when they forget the lyrics to “galactocerebrosidase Planetary”
PLanetary = Globoid Cells

Question 6

Neuronal Storage Disorder: Tay sachs

Deficiency of?

what is a classic finding on exam?

Answer 6

Hexosaminidase A deficinecy — accumulation of gangliosides in the GRAY MATTER

Classic finding: Cherry red spot on fundoscopy.

Question 7

Ethanol toxicity – classically associated with destruction of what structure?

Answer 7

Superior Vermis (of the cerebellum; think drunk people and ataxia)

Question 8

Carbon Monoxide poisoning – classically associated with …

Answer 8

bilateral necrosis of the Globus Pallidus

CO toxicity happens GLOBALLY

Question 9

methanol toxicity – -classically associated with….

Answer 9

Necrosis of the Putamen and the retinas

…“EYE, putamen in meth

Question 10

Vitamin B1 Deficiency –

name of the vitamin?
commonly in what population?
triad of symptoms
progression of disease?

Gross pathology?

Answer 10

Alcoholics; part of Beriberi

Wernike’s Encephalopathy – acute psychosis (delirium), opthalmoplegia, ataxia

can lead to…

Korsakoff Syndrome – Confabulation and memory distrubance

Gross path: Hemorrhagic lesions to the mamillary bodies

Question 11

Vitamine B12 Deficiency –
aka?

what vitamin?
degeneration of what?

Symptoms:

Answer 11

(perncious anemia)
Cobalamin

Subacute/combined Degernation – Degeneration of dorsal and lateral columns of the spinal cord

Symptoms:
Dorsal Columns: sensory –impaired position and vibration sense, paresthesias

lateral: , weakness and spasticity