Topic 116-119:CNS infections, demyelination and degeneration

Question 1

Degenerative neurological diseases can be separated into two categories:

what is the most common cause of neurodegenerative disorders?

Answer 1

Dementia - where loss of memory is the primary symptom but there is preservation of consciousness and function otherwise

degenerative disease- dementia is a symptom but other neurological issues are present such as motor control. Alzheimers, parkinsons, huntingtons, amyotrophic lateral sclerosis

–abnormal protein aggregation and accumulation is the most common cause of neurodegenerative issues

Question 2

alzheimer’s is associated with which symptoms?

Answer 2

memory loss, immobility, loss of speech, mood and behavior changes

Question 3

most cases of alzheimer’s are sporadic (late onset, 90-98%) but familial alzheimer’s (early onset, 1-10%) is associated with which genes?

Answer 3

-Amyloid precursor protein is cleaved by gamma-secretase to form Beta amyloid (AB)
Note: APP is located on chrom 21 so down’s syndrome is always associated with early alzheimer’s

-30% of alzheimer’s pt are positive for at least one allele of apo-protein E4

Question 4

accumulation of AB has what effect on the brain?

Answer 4

• small aggregates alter neurotransmission

- larger deposits form plaques and start inflam

Question 5

parkinson’s disease is what and associated with what symptoms? how would it be diagnosed?

Answer 5

death of the dopamine producing cells in the substantia nigra either spontaneously or via certain drugs and conditions

-diminished facial expressions, slowness or quick movements, rigidity, tremors

diagnosis is based on clinical response to L-DOPA and any history that may suggest parkinson’s (drugs)

Question 6

what are the familial parkinsons associated genes?

Answer 6

Autosomal dom: alpha-synuclein mutations/duplications

Recessive: Parkin, PINK, PARK gene mutations

Question 7

What are lewy bodies? how are they associated with parkinson’s ?

Answer 7

lewy bodies are neurons of s. nigra and locus coeroleus and when alpha-synuclein proteins accumulate in the cell bodies, it can be a diagnostic feature of Parkinsons.

+ pale lewy bodies or lewy neurites - parkinsons

Question 8

what is another protein that is associated with parkinsonism when there is accumulation?

Answer 8

tau deposition in neurons and glial cells

Question 9

Huntingtons disease is what? what are the symptoms?

Answer 9

Autosomal dominant disease with CAG repeats in the DNA
29 repeats - normal
up to 36 repeats - carrier
36-120 repeats - affected

more repeats = earlier onset

jerky, ataxic movements, behavior changes, dementia

Question 10

where are the CAG repeats located? what is the function/cause of degeneration caused by the repeats?

Answer 10

Located on chromosome 4

not really known but the CAG repeats encode huntington proteins which

• accumulate
• interfere with transcription factors thus reducing production of critical proteins
• interferes with mitochondrial function

Question 11

Amyotrophic lateral sclerosis is what?

Answer 11

ALS/Lou Gehrig’s disease is a group of diseases associated with the degeneration of motor neurons in the ventral horn. can affect upper and lower motor neurons

Question 12

the majority of cases are sporadic, but 10% are familial. what are the mutated genes?

Answer 12

SOD-1- superoxide dismutase on chrom. 21 causes about half of the familial cases

Question 13

Brain infections occur via 4 routes of infection

Answer 13

• Hematogenous - most common
• direct - post traumatic or even iatrogenic (lumbar puncture)
• local - migration from a local infection (pharyngitis)
• peripheral nerves - some pathogens travel in the nerves (rabies, VZ virus)

Question 14

Meningitis in what? what are the types?

what is meningoencephalitis?

Answer 14

inflammation of meninges and csf within the subarachnoid spaces

meningoencephalitis is inflam of brain parenchyma and meninges

• infectious
• non-infectious

Question 15

What are the types of infectious meningitis?

Answer 15

• acute pyogenic meningitis - bacterial. diagnostic via lumbar puncture with elevated neutrophils, proteins and lower glucose
• aseptic menigitis - viral. most commonly enterovirus (70%). lumbar puncture shows high lymphocytes, slight inc in proteins, glucose is the same
• chronic menigitis - TB and syphilis.
• • tb menigitis has a parenchymal mass (tuberculoma) and arachnoid fibrosis–> hydrocephalus
• -neurosyphilis - rare, invasion of brain by bacteria, mostly asymptomatic

Question 16

encephalitis is what? it can be caused by which agents?

Answer 16

inflammation of the brain

• bacterial - syphilis, any bacterial menigitis infection technically
• viral
• fungal
• parasitic

Question 17

viral encephalitis

Answer 17

know the viruses that cause it, too vague to write quick cards

Question 18

what are the 4 types of fungi that can cause encephalitis?

Answer 18

• candida
• mucor
• aspergillus
• cryptococcus

Question 19

Prion disease stems from what? what are the three types of disease?

Answer 19

Prion disease stems from abnormally misfolded forms of the prion protein called PrPc. it is a normal animal protein that is heavily present in the brain tissue.

• Sporadic - random mutation
• Inherited - inherited mutation
• acquired - consuming infected meat, mad cow and kuru

Question 20

Prion disease is associated with what symptoms? what does the prion protein do when it causes the disease?

Answer 20

-rapidly progressing dementia, fatal after 7 months

• abnormal prion protein can:
• -make other prion proteins become mutated/misfolded = neural toxicity
• -resistant to proteolysis

Question 21

what other disease is associated with prion disorder

Answer 21

fatal (familial or sporadic) insomnia

Question 22

remember schwann cells are on PNS nerves and oligodendrocytes are on the CNS, ok? so myelination diseases won’t affect both at the same time because they are different cells!.

Answer 22

ok.

Question 23

what are the two types of myelin diseases?

Answer 23

• demyelination - damage to previously normal myelin. can be immune mediated, viral, drug or toxin induced
• dysmyelination - defective structure and function of myelin sheaths due to mutations in the proteins needed. also called leukodystrophy

Question 24

What is the most common demyelinating disease? who is more likely to get it?

Answer 24

Multiple sclerosis is an autoimmune disease in which the myelin sheaths are damaged, causing demyelination and neurological defects

-women are twice as likely to get it. there is a genetic prevalence as well

Question 25

MS is associated with what clinical picture?

Answer 25

typically there are recurrent episodes of neurological deficits followed by worsening relapses.

there are a wide range of manifestations, however most common are:

• visual impairment
• brain stem symptoms - cranial nerve symptoms
• spinal cord symptoms - problems with motor control and bladder function
• cognitive function

Question 26

what are two other demyelinating diseases to know?

Answer 26

• post-infectious demyelination

- central pontine myelinolysis

Question 27

what is postinfectious demyelination? how are they different from MS? what are the two forms?

Answer 27

demyelinating disease that follows a systemic infections

• –not due to the infectious agent BUT an immune response to the pathogen antigens that cross react with myelin antigens!!
• –Monophasic and abrupt onset
• Acute disseminated encephalomyelitis
• acute necrotizing hemorrhagic encephalomyelitis

Question 28

central pontine myelinolysis is due to what?

Answer 28

With correction of the severe hyponatremia with intravenous fluids, the extracellular tonicity increases, followed by an increase in intracellular tonicity.

When the correction is too rapid, not enough time is allowed for the brain’s cells to adjust to the new tonicity. If the serum sodium levels rise too rapidly, the increased extracellular tonicity will continue to drive water out of the brain’s cells. This can lead to cellular dysfunction and the condition of central pontine myelinolysis, where the myelin sheath surrounding the nerve axons becomes damaged in the part of the brain called the pons. Hyponatremia should be corrected at a rate of no more than 8-12 mmol/L of sodium per day

Question 29

symptoms of central pontine myelinolysis?

Answer 29

rapidly evolving quadriplegia

Question 30

demyelinating diseases involve which enzymes? what are the symptoms?

Answer 30

abnormalities in

• lysosomal
• peroxisomal
• myelin proteins

occurs in children, first seen in deteriorating motor skills. the earlier the onset, the more severe

Question 31

what are the metabolic disorders of the brain?

Answer 31

hypoglycemia
hyperglycemia
hepatic encephalopathy

Question 32

what are some toxins that affect the brain?

Answer 32

• ethanol - brain swelling
• carbon monoxide - hypoxia
• lead - diffuse encephalopathy
• methanol - blindness from retinal damage
• radiation - coagulative necrosis in white matter
• chemotherapy - neurotoxicity