pathology III Flashcards
Dementia triad
Aphasia, apraxia, agnosia
What is apraxia
inability to perform preprogrammed motor tasks
What is agnosia?
inability to correctly interpret senses -cant recognize people, full bladder, pain
Presentation of parkinsons disease
tremor rigidity akinesia (or bradykinsea) postural instability shuffling gait
Which drug contaminant presents similarly to parkinsons disease?
MPTP - metabolized to MPP+ which is toxic to substantial nigra
histological findings of parkinsons disease
loss of dopaminergic neurons of substantia nigra pars compacta AND lewy bodies
What are lewy bodies?
intracellular eosinophilic inclusion composed of alpha-synuclein seen in Parkinson disease
Cause of huntingtons disease
Autosomal dominant trinucleotide repeated (CAG) expansion gene on chromosome 4
Symptoms of huntingtons disease
chorea, athetosis, aggression, depression, dementia
pathophys of huntingtons
Increased dopamine, decreasd GABA and Ach
Neuronal death via NMDA-R binding and glutamate excitotoxicity
Gross findings in huntington disease
Atrophy of caudate and putamen with ex vacuo ventriculomegaly
Why do down syndrome patients have increased risk of Alzheimer disease?
APP is located on chromosome 21
ApoE2 is associated with..
DECREASED risk of the sporadic form of Alzheimers
ApoE4 is associated with…
INCREASED risk of the sporadic form of Alzheimers
What are the familial altered proteins seen in Alzheimers disease
APP, presenilin-1, presenilin-2
Gross findings of Alzheimers
widespread cortical atrophy especially in the hippocampus. Narrowing of gyri and widening of sucli
Histological findings of alzheimers
senile plaques in gray matter: extracellular B-amyloid core; may cause amyloid aniopathy ->intracranial hemorrhage
Neurofibrillary tangles: intracellular hyperphosphorylated tau protein
What are neurofibrillary tangles
intracellular hyperphosphorylated tau protein - insoluble cytoskeletal elements; number of tangles correlates with degree of dementia
frontotemporal dementia aka
picks disease
presentation of frontotemporal dementia
Early chagnes in personality and behaviour (behavioural variant) or aphasia
Gross findings of frontotemporal dementia
frontotemporal lobe degeneration
Histological findings of frontotemporal dementia
inclusions of hyperphosphoryalted tau (round pick bodies) or ubiquinated TDP-43
Lewy body dementia presentation
visual hallucinations, dementia with fluctuating cognition/alerntess, REM sleep behaviour disorder and parkinsonism
histological findings of lewy body dementia
intracellular lewy bodies primarily in cortex
vascular dementia presentation
multiple arterial infarcts or chronic ischemia lead to a stepwise decline in cognitive ability with late-onset memory impairment
MRI/CT findings of vascular dementia
multiple cortical and/or subcortical infarcts
Creutzfeldt-Jakob disease presentation
Rapidly progressive dementia with myoclonus and ataxia
What will you see on an EEG of Creutzfeldt-Jakob disease?
periodic sharp waves
What will you find in the CSF of someone with Creutzfeldt-Jakob disease?
increased 14-3-3 protein
gross findings of Creutzfeldt-Jakob disease?
spongiform cortex
histological findings of Creutzfeldt-Jakob disease?
Prions (PrPc->PrPsc sheet results in beta pleated sheet resistant to proteases)
Idiopathic intracranial hypertension aka
pseudotumour cerebri
risk factors for idiopathic intracranial hypertension
female, tetracyclines, obesity, vitamin A excess, danazol
clinical findings of idiopathic intracranial hypertension
headache, tinnitus, diplopia, no change in mental status.
Impaired optic nerve axoplasmic flow - > papilloedema.
Enlarged blind spot and peripheral constriction.
Lumbar puncture with increased opening pressure that provides temporary relief of headaches
treatment of idiopathic intracranial hypertension
weight loss, acetazolamide, invasive procedures for refractory cases (CSF shunt, optic nerve sheath fenestration surgery)
What causes communicating hydrocephalus?
Decreased CSF uptake from arachnoid granulations (eg. arachnoid scarring post-meningitis)
Presentation of communicating hydrocephalus
Increasd ICP, papilledema, herniation
Presentation of normal pressure hydrocephalus
urinary incontenence, gait apraxia, cognitive dysfunction
Treatment of normal pressure hydrocephalus
CSF shunt placement
What causes normal pressure hydrocephalus?
Usually idiopathic, but expansion of the ventricles results in distortion of the fibers in the corona radiata
What causes noncommunicating hydrocephalus?
structural blockage of CSF
Ex vacuo ventriculomegaly presentation
Appearance of increased CSF on imaging but its ACTUALLY due to decreased brain tissue and neuronal atrophy
Causes of ex vacuo ventriculomegaly
azheimers, advanced HIV, pick disease, huntington disease
Presentation of aquaductal stenosis
enlarging head circumference
Aquaductal stenosis cause
X-linked congenital narrowing
Can be from inflammation in utero
What is multiple sclerosis?
autoimmune inflammation and demyelination of CNS with axonal damage
Possible presentations of multiple sclerosis
Acute optic neuritis
Brain stem/cerebellar syndromes
Pyramidal tract demyelination
Spinal cord syndromes
How does acute optic neuritis present?
painful unilateral vision loss associated with Marcus Gunn pupil
How do spinal chord syndromes present?
electric shock-like sensations, neurogenic bladder, paraparesis, sensory manifestations
Who is multiple sclerosis most common in?
Women aged 20 to 30 and farm from the equator
Symptoms of multiple sclerosis may present with what?
increased body temp (hot back, exercise)
findings in CSF of someone with multiple sclerosis
Increased IgG level and myelin basic protein
Oligoclonal bands - DIAGNOSITC
What will be seen on MRI of someone with MS?
periventricular plaques and multiple white matter lesions disseminated in space and time
Treatment of multiple sclerosis
Disease modifying therapies - B-interferon, glatiramer, natalizumab.
Treat acute flares with IV steroids.
Symptomatic treatment for neurogenic bladder, spasticity and pain
What is cerebral amyloid angiopathy?
Recurrent hemorhagic strokes from B-amyloid deposits in artery walls (that make them weak and prone to rupture)
Osmotic demyelination syndrome aka
Central pontine myelinosis
Pathophys of osmotic demyelination syndrome?
massive axonal demylination in pontine white matter secondary to rapid osmotic changes - most commonly from correction of hyponatremia but can be from shifts of other osmolytes
Presentation of osmotic demylination syndrome
acute paralysis, dysarthria, dysphagia, diplopia, loss of consciousness - causes locked in syndrome
if you raise sodium too fast what happens?
osmotic demyelination syndrome
if you decrease sodium too fast what happens?
cerebral edema/herniation
most common type of acute inflammatory demyelinating polyradiculopathy
guillain-barre syndrome
What cell type is destroyed in GBS?
Schwann cells
Pathophys of GBS
autoimmune destruction of schwann cells via inflammation and demyelination of motor fibers, sensory fibers, peripheral nerves. Facilitated by molecular mimicry and triggered by inoculations or stress.
GBS may be associated to which pathogen?
Campylobacter jejuni
Presentation of GBS
symmetric ascending muscle weakness/paralysis and depression/absent distal tendon reflexes
Facial paralysis and respiratory failure common
May present with autonomic dysregulation (cardiac irregularities, hypertension, hypotension) or sensory abnormalities.
CSF findings in GBS
increased protein with normal cell count (albuminocytologic dissociation)
Treatment of GBS
respiratory support is critical until recovery. Disease-modifying treatment; plasmapheresis or IV immunoglobulins.
Acute disseminated (postinfectious) encephalomyelitis pathophys
Multifocal inflammation and dyemylination after infection or vaccination
Presentatino of acute disseminated (postinfectious) encephalomyelitis
rapidly progressive multifocal neurologic symptoms and latered mental status
Charcot-Mari-Tooth disease aka
hereditary motor and sensory neuropathy
Deformities seen in Charcot-Mari-Tooth disease?
pes cavus, hammer tow
other symptoms seen in Charcot-Mari-Tooth disease?
foot drop/lower extremity weakness and sensory deficts
What causes Charcot-Mari-Tooth disease?
Autosomal dominant disorder caused by defective production of proteins involved in peripheral nerves
Most common type of Charcot-Mari-Tooth disease?
CMT1A
Mutation in CMT1A?
PMP22 gene duplication
What is progressive multifocal leukoencephalopathy?
demylination of CNS due to destruction of oligodendrocytes (from reactivation of JC virus)
Which virus causes progressive multifocal leukoencephalopathy?
JC virus
Which population gets progressive multifocal leukoencephalopathy?
aids patients with CD4 <200
outlook of progressive multifocal leukoencephalopathy?
Rapidly progressive and usualyl fatal
which brain areas are involved in progressive multifocal leukoencephalopathy?
parietal and occipital - visual symtpoms common
which drug is associated with progressive multifocal leukoencephalopathy?
natalizumab
