Toxic Metabolic

Question 1

Acute effects of alcohol?

Answer 1

massive cerebral edema and death seen with acute intoxication / binge drinking

Question 2

Chronic effects of alcohol?

Answer 2

brain atrophy
meningeal fibrosis
earliest effects appear to be on white matter
cerebellar degeneration / drop out of perkinje fibers
ESPECIALLY SUPERIOR VERMIS

Question 3

We see cerebellar degeneration in chronic alcoholism … what is important to note about the cause?

Answer 3

may be due to vitamin deficiency as well as direct toxicity

Question 4

Where do we see atrophy of superior vermis? (perkinje and granule cell neurones)

Answer 4

chronic alcoholism

Question 5

what is Hepatic encephalopathy related to?

Answer 5

elevation of blood ammonia - ammonia readily crosses BBB - taken up by astrocytes which are rich in glutamine synthetase - neurotoxicity

Question 6

Symptoms of hepatic encephalopathy?

Answer 6

confusion

asterixis - (hand flap tremor)

Question 7

HE - pathologic substrate?

Answer 7

edema
alzheimer’s type II cells (cortex and basal ganglia)
neuronal destruction in deeper cortical layers and putamen (in addition to alzheimer II astrocytes)

known as chronic acquired non-wilsonian hepatocerebral degeneration

Question 8

Wilsons

Answer 8

an inherited disorder of copper metabolism - causes liver cirrhosis - produces identical changes as HE cns damage -

thus, brain damage in Wilsons disease is due to repeated bouts of HE and not copper toxicity -

Can manifest with jaundice or movement disorder (12 years old avg)

Question 9

do most toxic disorders have morphologic correlates?

Answer 9

no, most do not

we looked at those that do :)

Question 10

Kwashiorkor with edema –> effects glial formation - synaptic branching - myelin formation - can we restore normal neurologic development?

Answer 10

most children can have restoration of normal neurologic development if proper nutrition is restored

Question 11

What causes Wernicke Korsakoff syndrome?

Answer 11

Vitamin B1/Thiamine deficiency

Question 12

Presentation of Wernicke-Korsakoff

Answer 12

syndrome of oculomotor abnormalities and mental symptoms

most common in alcoholics or hyperemetics

ocular motility problems, nystagmus (involuntary eye movement), ataxia, confusion —- presenting problems are variable

Question 13

Wernicke’s encephalopathy

Answer 13

example of a toxic metabolic problem that shows selective vulnerability ?
Involves mammillary bodies 
- Hypothalamus
- medial thalamus
- periaqueductal grey 
- floor of 4th ventricle 

histology varies with stage and severity

edema, necrosis, demyelination, neuron loss, gliosis

often see confabulation with Wernicke’s encephalopathy

Question 14

example of a toxic metabolic problem that shows selective vulnerabilty

Answer 14

Wernicke’s encephalopathy

Question 15

If we see a person with ataxia, nystagmus, and demonstrated lesions in the mammilary bodies, medial thalami, and PAG, what should we be thinking?

Answer 15

Wernicke’s encephalopathy which is due to vitamin B1 / thiamine deficiency

Question 16

Which vitamin deficiency disease often fucks with mammillary bodies?

Answer 16

Wernicke’s encephalopathy - vitamin B1 deficiency

Question 17

What does vitamin B1 do?

Answer 17

pentose phosphate shunt in the nervous system

Wernicke’s encephalopathy is associated with decreased blood transketolase activity

Question 18

So we see thiamine deficiency leading to wernicke’s encephalopathy in alcholics - but who else?

Answer 18

we can see in patients who have undergone bariatric surgery - because vitamin stores can be depleted in a few weeks - thiamine is stored in the heart, kidneys, liver, brain, muscles

Apparently IV glucose in patient with borderline deficiency can trigger disease?

Question 19

Korsakoff’s syndrome

Answer 19

sequelae of Wernicke’s encephalopahty usually due to alcoholism / vitmain B1 deficiency - major symptoms include

• anterograde amnesia
• retrograde amnesia
• confabulation
• minimal content in convos
• lack of insight
• apathy

Question 20

Vitamin B12 deficiency (cobalamin)

what is our source?

Answer 20

meat and dairy

Question 21

vitamin b12 (cobalamin) 
what does it do?

Answer 21

in stomach vitamin b12 (cobalamin) is bound to IF - a glycoprotein produced by the parietal cells of the stomach - the complex binds to receptors and is absorbed - therefore strict vegan diets or problems with malabsorpton are the main cause of vitamin b12 deficiency

stored for many years 3-4

Question 22

why does vit b12 deficiency (cobalamin) dmage nervouse system?

Answer 22

incorporation of fatty acids into biological membranes results in myelin instability

subacute combined degeneration

may also affect DNA synthesis

Question 23

vitamin b12 deficiency and spinal cord?

Answer 23

spinal cord disease is characterized by involvement of ascending sensory and descending motor tracts -

symptoms develop over weeks, usually with inital slight ataxia, numbness, and tingling in lower extremities - can progress into spastic weakness or paraplegia

Question 24

vitamin b12 deficiency - nuerological complications -

Answer 24

cognitive deficits

subacute combined degeneration

Question 25

Early symptoms of subacute combined degeneration due to vitamin b12 (cobalamin) deficiency

Answer 25

sensory symptoms NOS
Lower limb paresthesias
loss of vibration / position
loss of fine touch

Question 26

late symptoms of SCD due to cobalamin (vitb12) deficiency

Answer 26

spastic paraparesis
ataxia
lower limb and trunk sensory deficits

Question 27

signs of vitamin B12 deficiency / consequences

Answer 27

long term permanent structural damage of spinal cord

Question 28

what is messed up in b12?

Answer 28

myelin effects both ascending and descending tracts

Question 29

can we help vitamin b12 deficient patients with SCD?

Answer 29

Yes reconstitution can help

Question 30

Central pontine myelinolysis

Answer 30

due to sustained hyponatremia - has serum sodium rapidly corrected

selective sites of vulnerabilty in ventral pons and at extrapontine sites rich admixture of gray and white matter

Question 31

Symptoms of central pontine myelinolysis

Answer 31

pontine dysfunction with pseudolobar palsy - difficulty swallowing - increased spasticity of tongue - slurred speech - quadriparesis

effects gray white junction