Brain Diseases/last bit of coursepack Flashcards
Alzheimer’s disease
Deposits of both tau (neurofibrillary tangles-intracellular) and amyloid (neuritic plaques)
Senile plaques-extracellular B amyloid core may cause amyloid angiography leading to intracranial hemorrhage (vascular walls thickening of basal membrane, stenosis of lumen, and fragmentation of internal elastic lamina)
AB plaques made by cleaving amyloid precursor protein (normally involved in synaptic info and repair)
Onset: after 65 years, early onset 40-65
Incidence: 10% familial, autosomal dominant
Usually sporadic, increased in individuals homozygous for apoE4 allele (Chr. 21), form of mutation in the presenilin 1 or presenilin 2 gene
Late onset: ApoE4
Protective: ApoE2
Location: cortex, hippocampus, entorhinal and perirhinal cortex, basal forebrain, basal nucleus of Meynert-(cholinergic neurons to cortex)
Clinical: presence of dementia and exclusion of other conditions
Behavioral changes, impaired judgement, loss of memory (short term) loss of intellect
Pathogenesis: amyloid deposition causes neuritic plaque formation-abnormal processing of normal molecule to amyloid B peptide. Overproduction and failure to adequately degrade or clear AB contributed to neurotoxicity
Loss of cholinergic neurons in basal nucleus of Meynert and in hippocampus leading to hippocampal atrophy
Decreased melatonin in CSF
Decreased cholineoacetyl transferase
Gross pathology: cortical atrophy, decreased brain weight, enlarged ventricles
Microscopic Patholgy: nerve cell loss initially in parietal or temporal lobes. Neuritic plaques (central amyloid core) , neurofibrillary tangles (hyper phosphorylated tau) in hippocampus and parietal and temporal lobes
Risk factors: age, history of head trauma, low education, family history, genetic mutations, presence of Apo E4 allele, Down’s syndrome
Dementia with Lewy bodies
Onset: elderly
Location: cortex. Especially limbic Basal ganglia, substantia nigra
Clinical: initially dementia with hallucinations, then Parkinsonism, fluctuation inseverity, not responsive to anti-parkinson meds, unexplained loss of consciousness
Gross Patholgy: cortical atrophy
Microscopic pathology: intraneuronal Lewy bodies in substantia nigra containing alpha synuclein and ubiquitin
Picks disease
Onset: late middle age, sporadic
AD
Location: cortex-frontotemporal
Clinical: similar to AD predominance of behavioral changes and personality changes, language deficits-repeat phrases
incontinence and gait disturbances
Pathogenesis: unknown associated with misprocessing of tau
Gross pathology: decreased brain weight, greater degree of atrophy than AD,
ATROPHY IN FRONTAL AND TEMPORAL LOBES
Kuru
Prion disease in New Guinea contracted via cannibalism rituals
Creutzfeldt-Jakob disease
Due to mutation of codon 178 from asp to asn and val at codon 129 in prion protein gene
Onset: between 40 and 80
Clinical: rapid dementia and, gait impairment, startle myoclonus
Motor disorders and cerebellar incoordination
Duration: death in 3-12 months
Transmission: sporadic, few familial, corneal transplants and contaminated GH implantable electrodes
Gross pathology: cortical atrophy and ventricular dilatation
Microscopic pathology: spongiform encephalopathy in gray matter and spinal cord. Severe neuronal loss and gliosis. Mild demyelination may occur
Presence of proteinase-K-resistant PrP-Sc I tissue, 14-3-3 protein in CSF
B pleated sheets resistant to proteases accumulate intracellularly
Periodic sharp wave discharges seen on EEG
Fatal familial insomnia
Sleep disturbances (can't sleep and die) Subcortical lesions Mutation at 178 asp to asn and met at codon 129 Neuronal loss and gliosis in Thalamic nuclei and inferior olivary nuclei
Delirium
Diagnosis: acute onset and fluctuating course, inattention, disorganized thinking, altered level of consciousness
Pathophysiology: poorly understood, generalized slowing of EEG, widespread reduction in cerebral oxidative metabolism, failure of cholinergic NTs
Causes:
Baseline: cognitive impairment, dehydration, severe illness, vision impairment
Precipitating factors: physical restraints, malnutrition, >3 medications, use of catheter, any iatrogenic event
Prognosis: improvement can be expected when underlying medical condition improves, slow improvement, some issues may not be reversible
Treatment: low dose of CNS active medications only when needed, avoid immobilization avoid sleep deprivation, treat dehydration and malnutrition, correct vision and hearing impairment
Avoid drug classes producing delirium
Treat underlying illness
Vascular dementia
Multi infarct dementia
Multiple strokes are identified on pathology
Location, infarct size, and total amount of ischemic tissue correlates with severity of symptoms
Temporal relationship between stroke and cognitive decline-stepwise loss in memory rather than gradual
Features: abrupt onset, assymetrical motor portions of exam, neuro imaging evidence of infarction, presence of cerebrovascular risk factors
Shorter lifespan than those with Alzheimer’s
Greater functional impairment and increased risk of cardiovascular disease
Risk factors: hypertension, smoking,age,hypercholesterolemia, carotid atherosclerotic disease, atrial fibrillation, valvular disease and cardiomyopathy
Treatment: risk factor modification, identification of likely mechanism for stroke and treatment accordingly
Vertigo
Sensation of movement
Disorder of vestibular system
Characteristics of central vertigo
Mild nausea Moderate to severe-imbalance Rare hearing loss Rare tinnitus Severe OSCILLOPSIA neurologic common-DYSARTHIA, WEAKNESS, NUMBNESS slow compensation immediate Nystagmus-pure vertical, unchanged with fixation, no fatigability, no latency
Peripheral vertigo characteristics
Severe nausea Moderate imbalance HEARING LOSS COMMON TINNITUS mild oscillpsia Rare neurologic Rapid compensation delayed Nystagmus mixed, amps with fixation, fatigability, latency post maneuver
Inner ear etiology: semicircular canal debris, vestibular nerve infection, Meineire disease
Sudden onset, interferes with walking, and causes nausea and vomiting
Benign paroxysmal positional vertigo
Peripheral vertigo
Most common cause of vertigo
Short lived episodes of vertigo precipitated by head movements especially neck extension
Lasts less than 45 seconds
Trauma is common antecedent event
Dix-hall pike testing-patient is rapidly moved from seated position to lying position with head tilted 45 degrees turned and extended. Stimulates posterior semi circular canal and precipitates nystagmus and vertigo
Nystagmus: slow phase down and clockwise, fast phase opposite direction
Nystagmus is fatigueable
Repositioning maneuvers are generally 75% effective with single 5 min treatment
Ménière’s disease
Peripheral vertigo
Caused by endo lymphatic regulatory dysfunction-increased endolymph due to defective resorption
Triad of tinnitus, vertigo, hearing loss (sensourinal)
Lasts hours-EPISODIC
Preceded by ear pressure/fullness, change in tinnitus and hearing function
Ask about history of fluctuating hearing loss and tinnitus
May be precipitated by high salt intake
Treatment: surgery, low salt intake, alcohol abstinence, diuretic medications, short courses of PRN vestibular suppressants
Narcolepsy
Excessive daytime sleepiness and disordered regulation of REM sleep
Narcolepsy-cataplexy subtype: excessive daytime sleepiness and cataplexy (sudden loss of postural Tone while awake)
Irresistible sleep attacks lasting 5 to 30 mins during the day
Precipitated by strong emotion especially laughter
Typically starts around adolescence
Sleep study results: period of REM sleep that occurs in first 15 mins of sleep
Pathogenesis: genetic predisposition and environmental triggers
Association between histocompatibility and narcolepsy-cataplexy
Hypocretin/orexin deficiency (in CSF) is the cause
decreaesed production in lateral hypothalamus involved in wakefulness
Hypnagogic and hypnopompic hallucinations
sleep paralysis
Treatment: modafinil (first line), amphetamines, nighttime sodium oxybate
Restless leg syndrome
Insomnia
Sensorimotor disorder affecting sleep
Strong urge to move the legs accompanied by a strange feeling in the leg
Episodes are precipitated by rest with inactivity and episodes are worse in the evening or night
Periodic leg movements may occur during sleep or while lying or sitting up awake
Disorder of the transition between wake and sleep
No profound frank sleepiness in the daytime
Fatigue and trouble concentrating during the day but do not fall asleep and appear to be overstimulated in the daytime
Causes: idiopathic iron deficiency, uremia, diabets, MS, parkinsons, antidepressants, metaclopramide, glucocorticoids, chronic kidney disease
Treatment: dopamine agonists and levodopa
