CNS- I Flashcards
1
Q
What is multiple sclerosis?
A
Autoimmune demyelinating disorder
- inflammation and selective destruction of CNS myeline (brain and spinal cord)
- autoreactive t-lymphocytes against myelin basic protein
- antibodies against myelin oligiodendrocytic glycoprotein
- periphearl nervous system is not affected
- immune mediated response in genetically susceptible people
- genetic and environmental factors (story about twins growing up in different climates. colder climate has higher likelihood of develping MS)
- (1st degree relative, 15 fold increase in having disease)
- HLA- DR2 haplotype have increased susceptibility
- genetic and environmental factors (story about twins growing up in different climates. colder climate has higher likelihood of develping MS)
2
Q
What is the role of myelin in CNS?
A
- Provides high electrical resistance and low capacitance–> increases speed!
- electrical insulator
- critical to impulse transmission
- CNS myelination: by oligodendrocytes
- Myelin in CNS enables fast axonal conduction, energy conservation and space conservation
- essential for survival of axons
3
Q
Pathophys of MS?
Where does the disease process mainly happen?
A
- Combination of inflammation, demyelination and axonal damage in CNS
-
Demyelination of nerve fibers in white matter of brain, spinal cord and optic nerve
- leads to decreased conduciton velocity and conduction blocks
- Lesions: hard, sharp edged demyelinated patches called “plaques” visible throughout the white matter of the CNS
- plaques are end result of myeline breakdown
- myeline breakdown is poorly understood
- plaques are end result of myeline breakdown
- Symptoms reflect areas of demyelinization in brain and spinal cord (every MS pt is different)
4
Q
What is the course of MS?
A
- inflmmatory period of about 2 weeks
- period of pronounced, acute disability
- as inflammation subsides, pt starts to recover
- Combination of acute, subacute and chronic lesions
- 2 stages:
- initial sequential develppment of small inflammatory lesions
- later extension, consolidation of smaller lesions and scarring, plaques and ultimately long lasting, permanent dysfunction
5
Q
MS Signs and symptoms?
A
- Progressive
- periods of remission and exacerbation
- eventually residual symptoms present even during remission
- spinal cord lesions: will see limb paresthesias, weakness, impotence, incontinence; ascending spastic paralysis (upper motor neurons)
- visual disturbancs: optic neuritis, loss of part of the visual field, diplopia
- Autonomic disturbances
- lack of coordination: involvement of cerebellum
- increased incidence of seizures
- cognitive and emotional disturbances
- increased body temperature causes exacerbation of symptoms
6
Q
What is Lhermitte sign? What is it a sign of?
A
Electrical sensation with neck flexion (sign of MS)
7
Q
What is relapsing/remitting MS?
A
- 85% of MS cases
- Discrete attacks over days to weeks with substantial or complete recovery over the ensuing weeks to months
- residual disability over time
- between attacks, patients are neurologically stable
- some people go months/years without attacks
8
Q
What is secondary progressive MS? (SPMS)
A
- Begins as RRMS (relapsing/remitting MS).
- At some point, a steady deterioration in function unassociated with acute attacks occurs
- great majority of RRMS ultimately evolves into SPMS
- Seen as “late stage relapsing-remitting”
9
Q
What is primary progressive MS?
A
- Accounts for 15% of cases
- these patients do not experience attacks but only a steady functional decline from disease onset; disability develops faster
- (more serious)
10
Q
What is progressive/relapsing MS?
A
- These patients experience a steady deterioration in their condition from disease onset but experience occasional attacks superimposed upon their progressive course
- exacerbation–> deterioration
- (most severe form)
11
Q
MS diagnosis?
A
- No one definitive tests
- look at clinical signs/symptoms
- oligoclonal abnormalities in immunoglobulins, increased gamma globulin in the CSF
- don’t expect immunoglobulin in CSF that’s not in blood
- Prolonged latency of evoked potential (decrease amplitude or delay)
- secondary to slowing of nerve impulse conduction
- White matter changes on MRI brain- hyperintense lesions
- can have a normal MRI with MS dx
- CT scan may be normal
12
Q
MS prognosis?
A
- Most patients with clinically evident MS ultimately experience progressive neurologic disability
- some MS patients have a benign variant of MS and never develop neuro disabiilty (~20%)
- benign MS 15 years after onset are unlikely to have issues
- Pregnant MS patients experience fewer attacks during gestation (especially in last trimester) but more attacks in the first 3 months postpartum
- immunosuppressed during pregnancy
- after baby is born, first 3 months, woman is susceptible to attack of MS
13
Q
MS treatment?
A
No cure
3 arms of therapy
- 1) treament of acute attacks (glucocorticoids- IV and then oral taper)
- no proof that coricosteroids prevent any long term damage or improve long-term outcomes
- 2) treatment with disease-modifying agents that reduce the biologic activity of MS: disease modifying agents, interferon- beta and others
- interferon- reduces immune response and MS exacerbation, but make you feel like you have the flu constantly!
- 3) symptomatic therapy: address spasticity, pain, bladder dysfuction, depression, fatigue, sexual dysfunciton
14
Q
What is guillian-barre syndrome?
A
- Acute, life threatening polyneuropathy with an immune mechanism- unsure of exact etiology
-
demyelination of multiple peripheral nerves
- longest axons typically inovlved first: begins in the legs
- may be motor, sensory or mixed
-
ANS involvement possible- can be hemodynamically unstable. Risk of SCD.
- postural hypotension, arrhythmias, resting tachycardia, facial flushing, abnormal sweating, urinary retention
- Lower motor neuron involvement: flaccid paralysis
15
Q
Pathophys of GBS?
A
- Uncertain: strong, but still inconclusive evidence that autoantibodies play an important role in GBS
- 70% of cases preceded by an acute infectious process (1-3 weeks earlier)
- strong evidence linking certain infections with GBS (campylobacter jejuni, CMV, EBC, mycoplasma pneumoniae)
- Theory- antigens create an immune response against nerve fibers and/or block presynaptic voltage-gated Ca channels and postsynaptic nAChR channels= NM weakeness
- complete spontaneous recovery is possible!
- rare association with immuniations
- risk <1 per illion (higher risk of getting it following illness with the flu)
16
Q
GBS symptoms?
A
- Rapid, progressive limb weakeness and loss of DTR’s
- frequently preceded by an acute flu-like illness (2/3 of patients)
- paralysis begins in legs and ascends cephalad
- bulbar involvement (old word for brain stem): bilateral facial paralysis (50% of those affected)
- pharyngeal muscle weakness: difficulty swallowing
- intercostal muscle paralysis: impaired ventilation
- associated with pain/paresthesa
- ANS dysfunction can be life threatening
- May have SEVERE orthostatic hypotension
- high risk for VTE due to immobility
17
Q
GBS diagnosis?
A
- progressive, bilateral weakeness
- starts in legs and then ascends
- >50% have burning, aching pain in back and thights
- areflexia (no reflexes)
- progression over 2-4 weeks
- symmetry of symptoms
- Cranial nerve inovlvmenet<– can affect CV, resp centers
- ANS dysfunction
- decreased nerve conduciton velocity
- NO fever
CSF: elevated concentration of protein in CSF with normal cell oucnts
- CNS often normal for 48 h after symptom onset
18
Q
GBS treatment?
A
- Time sensitive
- high-dose intravenous immune globulin or plasmapheresis: equally effective and one should be considered for all patient
- needs to be started within 2 weeks of symptom onset. after myelin is degraded, not much help
- Supportive care
- mechanical ventilation after vc <15 mL/kg and or ABG results indicate need
- 30% will require vent support
- Cuffed ETT/trach to prevent aspiration (weak pharyngeal muscles)
- early consideration for trach is recommended
- treatment of hyper or hypotension with meds (vasopressors, beta blockers, etc)
- mechanical ventilation after vc <15 mL/kg and or ABG results indicate need
19
Q
GBS outcomes?
A
- 85% achieve full functional recovery
- 3-8% mortality
- respiratory failure, sepsis, PE, cardiac arrest- ANS dysfunction
- segmental demyelination only- recovery in a couple of weeks
- axonal connection remain intact
- recovery is rapid as remyelination occurs
- Axonal degeneration- recovery incomplete and takes months
- axons have degenerated and become disconnected from their targets (NMJ)
- Must regenerate for recovery to take place
- 5-10% of patient with typical GBS have one or more late relapses
20
Q
What is parkinson’s disease?
A
- 2nd most common neurodegenerative dx, exceeded only by alzheimer’s disease
- disturbance in dopaminergic pathways b/w substantia nigra and basal ganglia
- mean age of onset is 60 years; frequency increases with aging
21
Q
Pathophys of parkinson’s disease? hallmark?
A
- Hallmarks: degernation of dopaminergic neurons in the substantia nigra
- reduced striatal dopamine
- intracytoplasmic proteinacous inclusions known as lewy bodies that primarily contain the protein alpha synuclein
- Clinical signs secondary to decreased produciton *70-80%) of dopamine in neurons of basal ganglia leading to the putamen and caudate nucleus
- dopamine has inhibitory role in EPS
- Without dopamine, cholinergic neurons are unopposed, EPS motor symptoms devleop
- progressive disease over 10-15 years
- death usually form fall or infection (r/t immobility)
22
Q
What are lewy bodies?
A
hallmark of parkinsons’s disease
- intracytoplasmic proteinacous inclusions that contain protein alpha synuclein
23
Q
Occurence of parkinson’s disease?
A
- Most cases (85%) offuce sporadically and have no known cause
- 15% familial: specific mutation and gene associations ahve been ID’ed
- NO environmental factor has been proven to cause parkinsons
- association with TBI might make pt more susceptible
- Epidemiological associations
- increased risk with exposure to pesticides, rural living and drinking well water
- reduced risk with cigarette smoking and caffeine
- “double hit” theory: interaction b/w gene mutaiton that induces susceptibility coupled with expsoure to toxic environmental factor
24
Q
What is secondary parkinsonism?
A
- Can occur as a result of drugs, stroke, tumor and infection , or exposure to toxins such as carbon monoxide or manganese
- Drugs:
- most common: dopamine blocking agnets such as the neuroleptics (used in psychiatry)
- metoclopramide and chlorpromazine are also neuroleptic agents
- other drugs: tetrabenazine, some CCB, amiodarone and litium
25
Q
What are some cardinal features of PD?
A
- bradykinesia
- rest tremor
- rigidity
- gait disturbance/postural instability- don’t move arms when walking or don’t turn head when turning body
26
Q
What are other motor features with PD?
A
- Micrographia- handwriting changes, small writing
- masked facies (hypomimia)
- reduced eye blinking
- soft voice (hypophonia)
- dysphagia
- freezing
27
Q
What are some nonmotor features of PD?
A
- Anosmia
- snesory disturbances (pain)
- mood d/o (depression)
- sleep disturbance
- autonomic disturbance
- orthostatic hypotension
- GI disturbance
- GU disturbance
- sexual dysfunction
- Cognitive impairment (MCI/dementia)
28
Q
What is the mainstay of parkinson’s treatment?
A
- Levodope
- purpose: dopamine precurosr
- prescribed in combo with peripheral decarboxylase inhibitor (carbidopa)
- prevents preipheral metabolism ot dopamine
- reduces N/V due to activaiton of dopamine receptors in the area postrema that are not protected by BBB and redices peripheral CV effects
29
Q
What is role of selegiline in parkinson’s treatment?
A
- Type B MAOI
- inhibit catabolism of dopamine in the CNS
30
Q
What is amantadine in PD?
A
- antiviral agent: MOA Unknown
- used for advnaced dyskinesia
45
Q
What is spondylolysis?
A
congenital or degenerative/psottraumatic absence of the pars interarticularis between the superior and inferior articular processes, frequently associated with spondylolisthesis
term used for stress fracture through the pars
49
Q
Back pain occurence? frequent patho?
A
- 70% of adult population suffers from low back pain at some point during their lifetime
- spondylosis is most frequent in the cervical and lumbar spine, the most mobile regions of spinal column
- lumbar canal stenosis most commonly involves L4-L5 level, followed by L3-4
-
Lumbar spondylosis patho- process of disk degerneration, bilateral facet joint arthropathy and osteophyte formation
- facet joint cartilage destruction and capsular laxity can lead to subluxation and segmental lumba instability
