L12- Demyelinating Diseases, Toxicology Flashcards
describe the 2 mechanisms of demyelinating diseases
1) Acquired: loss of myelination (demyelination) via damage to myelin or oligodendrocytes / schwann cells
2) Hereditary: dysmyelinating disorders of leukodystrophy (myelin not properly formed)
list the 3 common demyelinating diseases
(all acquired)
- Mutiple Sclerosis
- Post-infectious
- Myelinolysis
(1) is the most common demyelinating disorder affecting (males/females) more. (1) is characterized as (3) disorder with (4) as the main feature.
1- MS
2- females > males (2:1)
3- autoimmune disorder
4- episodes of disease activity separated by time => white matter lesions separated by space [patchy loss of myelin from multiple separate events]
list the risk factors for MS
(environmental)
- smoking
- low vitD
- h/o EBV infection
- move to endemic area before puberty
(genetic)
- genetics, HLA
- race, white
- maternal FHx
Although MS pathogenesis isn’t fully understood, (1) is the main mechanism of the disease process with (2) in the surrounding areas of (1). (3) cells are responsible for initiating MS by secreting (4) to allow for (5) progression.
1- autoimmune response against myelin sheath
2- perivascular inflammation
3- Th1, Th17
4- IFN-γ –> macrophage activation
5- leukocyte recruitment –> B-lymphocytes
MS:
- (1) gross appearance characteristics
- (2) common locations of lesions
1- plaque: grey-tan, discrete, slightly depressed, glassy appearance
2- near ventricles, optic nerves / chiasm, brainstem, other tracts
MS:
- (1) microscopic features of active plaques
- (2) microscopic features of inactive plaques
1- abundant macrophages, myelin breakdown, perivascular lymphocytic inflammation
2- (inflammation disappears w/o any myelin) myelin replaced by astrocytic proliferation and gliosis
describe the clinical features of MS
- Sxs related to extent of white matter injury severity via episodic attacks (different times, different areas)
- gradual step-wise accumulation of neurological deficits => any sort of motor, sensory, or cognitive deficits depending on lesion locations
- variable course w/ multiple relapses + remissions
CSF findings in MS
- elevated proteins
- in Igs (oligoclonal bands)
- moderate pleocytosis (inc WBCs)
describe the general mechanism of post-infectious demyelination
- follows mild viral disease, or occasionally vaccination
- Igs are created against Ags => cross-reactivity to myelin => myelin damage
what are the types of post-infectious demyelination
ADEM, acute disseminated encephalomyelitis:
- nonlocalizing symptoms (in comparison to MS) >1-2wks after infection
- rapid progression, potentially fatal
AHEM, acute hemorrhagic enephalomyelitis:
- worse than ADEM
- more common in children, young adults
Myelinolysis occurs after a (1) physiological state is rapidly corrected. Damage to (2) occurs and can suddenly result in (3). (4) is a secondary effect that may also result.
(aka central pontine myelinolysis) 1- hyponatremia 2- nonimmune damage to pons 3- rapidly evolving quadriplegia 4- extrapontine myelinolysis
Myelinolysis:
- (1) general pathogenesis
- usually occurs after the following events, (2)
1- unknown
2- (hyponatremia)
- renal or hepatic diseases
- severe vomiting or diarrhea
- CHF
- SIADH
(1) are the main dangerous nutritional diseases affecting the brain
(2) are the main dangerous metabolic diseases affecting the brain
1- thiamine deficiency
2- hypoglycemia, hyperglycemia, hepatic encephalopathy
Systemic effects from thiamine deficiency is termed (1) and can be associated with (2) characterized by the following triad, (3).
1- beri beri
2- Wernicke encephalopathy
3- encephalopathy, ocular palsies, ataxia
(1) are the biggest risks for thiamine deficiency. Delayed replacement of thiamine may result in (2) termed (3).
1- chronic alcoholism, gastric disorders (malabsorption)
2- irreversible memory disturbance
3- Korsakoff syndrome (no new memories + confabulation)
Thiamine deficiency will lead to (1) in (2) locations of the brain.
1- hemorrhage and necrosis
2- mamillary bodies, thalamus, periaqueductal gray matter
Hypoglycemia:
- (1) causes
- (2) most affected cells in the brain
- severity is correlated to (3)
- (4) clinical features
1- insulin overdose, insulinoma
2- Hippocampal pyramidal neurons (cerebellar Purkinje cells are relatively spared)
3- level and duration of hypoglycemia
4- global hypoxia features: neurological impairment –> death since same sets of neurons are affected most, see (2)
Hyperglycemia:
- (1) causes
- (2) cellular effect in brain
- (3) progression of signs and symptoms
- (4) treatment risk
1- poorly controlled DM
2- intracellular dehydration (hypertonic) => hyperosmolar state
3- confusion –> stupor –> coma
4- rapid glucose correction can => cerebral edema
list the effects of alcoholism on the brain
- peripheral neuropathy
- cerebellar degeneration
- Wernicke-Korsakoff syndrome: via malnutrition (thiamine deficiency)
- withdrawal => seizures
______ is a recreational drug that can cause intracerebral hemorrhaging
cocaine
______ is a prescribe medication that can cause peripheral neuropathy (hint- anticancer)
vincristine
______ are environmental toxins / elements that can cause PNS and CNS toxicity
(in addition to solvents and industrial products)
-Arsenic, Lead, Mercury
