Demyelinating/Degenerative/Genetic/Toxic/Eye Flashcards
Generally describe the characteristics of demyelinating diseases
Acquired
Damage myelin by preserve axon
–Immunological vs inherited
Describe multiple sclerosis
Autoimmune demyelinating DO with neuro deficits separated by time and region of the body
Relapses decrease frequency but increase in intensity
What are some common neurologic symptoms and signs of multiple sclerosis
Unilateral vision impairment: frequent initial symptom
10-50% Pts with optic neuritis develop MS
Ataxia and nystagmus
Motor and sensory impairment with spasticity
Describe the epidemiology of MS
Women 2X to men
There is a genetic component DR2 gene and IL-2 and IL-7 receptors
What would you see on gross pathology of someone with MS
multiple well circumscribed, slightly depressed lesions, irregularly shaped plaques around ventricles
You see a histo slide of a patient with ongoing MS. On the slide you see an abundance of macrophages, perivascular inflammatory infiltrate at outer edge of plaque. Overall there is relative preservation of the axons. What type of plaque is observes
Active Plaque
You see a histo slide of a patient with ongoing MS. On the slide you see no inflammation. There is an absence of myelin, oligodendrocyte nuclei, and decreased axons. However astrocytosis and gliosis are prominent. What type of plaque is observed.
Inactive Plaque
Describe a shadow plaque in MS
Thinned out myelin sheaths with partial & incomplete remyelination by surviving oligos. Not well circumscribed
What are the CSF findings in MS
Elevated protein
Pleocytosis
IgG increase
Oligoclonal IgG bands in immunoelectrophoresis
Describe Neuromyelitis optica
Synchronous BL optic neuritis with SC demyelination
How does a spinal tap from a person with neuromyelitis optica compare to that of one from someone with bacterial meningitis
Elevated neutrophils with opening pressure but NO change in glucose.
*** could be good compare question.
Describe Acute Disseminated Encephalomyelitis (ADEM)
Perivenous Encephalomyelitis - diffuse monophasic demyelinating disease that follows either viral infection
Describe the morphology of Acute Disseminated Encephalomyelitis (ADEM)
Grayish discoloration around white matter vessels. Myelin loss, axon preservation
Accumulation of lipid laden macrophages
Describe the key features of Acute Necrotizing Hemorrhagic Encephalomyelitis (ANHE)
Children and young adults
Fulminant syndrome of CNS demyelination
Recent URI
Fatal in most cases
Describe Central Pontine Myelosis
Loss of myelin in symmetric pattern involving basis pontis and portions of the pontine tegmentum
Describe the symptomology of Central Pontine Myelosis
Acute paralysis Dysphagia Dysarthria Diplopia Coma
From Hyponatremia over correction!
Can you make a true Alzheimer’s Dx while they patient is alive
nope need the brain
**seems like a putoff distinction but who knows
Describe neuritic (senile) plaques in alzheimer’s disease
focal spherical collections of dilated tortuous neuritic processes around amyloid core
(congo red)
Describe diffuse plaques in Alzheimer’s disease
No amyloid core!
Early stage of plaque development
Down syndrome: early onset of AD
To remember neurofibrillary tangles of specific neural cells use this mnemonic, or dont
Pyramidal cells - Flame (pyramid schemes go down in flames)
Round - Globus (globes are round)
Basophilic fibrillary structures - Bilschowsky stain (B with B)
Do # of tangles or # of plaques correlate better to degree of dementia
of tangles
What is granulovacuolar degeneration
small clear intraneuronal cytoplasmic vacuoles which contain granules. Normal in aging but hella in AD
What are hirano bodies
Elongated glassy eosinophilic bodies in hippocampal pyramidal cells.
Describe Pick Disease
Rare, early onset behavioral changes due to frontal lobe deterioration and language disturbances (temporal lobe)
Knife edge thin gyri of only the front 1/3 of superior temporal gyrus
Describe progressive supranuclear palsy
Truncal rigidity with dysequilibrium & nuchal dystonia, abnormal speech, ocular disturbances
Males >females 5-7 decade
Fatal within 5-7 years of onset
Describe the histology of Progressive supranuclear palsy
Globose neurofibrillary tangles: 4R tau straight filaments
Describe vascular dementia
if due to vasculitis, improves with treatment
progressive cognitive disorders associated with vascular injury -> widespread areas of infarction
What areas are usually affected by strategic infarcts
Hippocampus
Dorsomedial Thalamus
Cingulate gyrus of frontal cortex
Describe the clinical syndrome of parkinsonism
Diminished facial expression Stooped posture Slowness of voluntary posture Festinating gait Rigidity Pill rolling tremor
Describe parkinson disease
progressive L-dopa-responsive signs of parkinsonism
Autosomal Dominant a-synuclein 4q21
juvenile is AR parkin
describe gross morphology and histology of parkinson disease
Pallor of substantia nigra
Lewy bodies - cytoplasmic, eosinophilic inclusions with a dense core
Describe Multiple system atrophy
sporadic disorder characterized by cytoplasmic inclusions of a-synuclein
Describe the three distinct neuroanatomic systems involved in Multiple System Atrophy
Striatonigral circuit (parkinsonism) Olivopontocerebellar circuit ( ataxia) ANS (autonomic dysfunction)
Describe huntington disease
Autosomal Dominant
Movement disorder with dementia
caused by polyglutamine trinucleotide repeats 4p16.3
CAG repeats (10-35 copies normal); age of onset determined by number of repeats
What is anticipation and what is its relationship with HD
Repeat expansions during spermatogenesis leads to earlier presentation for offspring
What are the main areas of atrophy in HD
Caudate Nucleus; Putamen later
Globus Pallidus
Frontal lobes
What are the two spinocerebellar ataxias
Friedreich ataxia
Ataxia-telangiectasia
Describe Friedreich ataxia
Autosomal recessive
GAA trinucleotide repeat 9q13 Frataxin protein
Onset 1st decade with gait ataxia then hand clumsiness
What are associated comorbidities and causes of death in patients with friedreich ataxia
Cardiac arrhythmias and CHF
DM in 10%
COD: Intercurrent pulmonary infection & heart disease
Describe Ataxia-Telangiectasia
Autosomal recessive
childhood onset with CNS, conjunctival and skin telangiectasias.
Death in 2nd decade from Lymphoid neoplasms, gliomas, and carcinomas
Immunodeficiency
Failure to remove cells with DNA damage
What gene is mutated in Ataxia Telangiectasia
ATM 11q22-q23
Very susceptible to X-ray
Describe Amyotrophic lateral sclerosis
loss of lower motor neurons in SC and Brain stem and upper motor neurons that project into corticospinal tracts
Presents in 5th decade or later
SOD1 mutation chr 21
What is the specific pathology of ALS
Anterior roots of SC are thin with decrease anterior horn neurons
Precentral gyrus may be atrophic
Neurons contain bunina bodies (PAS+)
Skeletal muscles undergo neurogenic atrophy
What are the symptoms of ALS
Early: Asymmetric weakness of hands, dropping objects
Fasciculations
Progressive atrophy
Progressive bulbar palsy (difficulty speaking and swallowing
50% alive at 2 years
Which degenerative diseases have Tau inclusions
Alzheimer’s
Frontotemporal lobar degeneration
Progressive Supranuclear palsy
Corticobasilar degeneration
Which degenerative diseases have a-synuclein inclusions
Parkinson disease
Multiple system atrophy
What are the protein inclusions in ALS
TDP-43
SOD-1(familial disease)
Describle leukodystrophies
autosomal recessive (adrenoleukodystrophy is X-linked)
Involvement of white matter -> deterioration of motor skills, spasticity, hypotonia and ataxia
Describe mitochondrial encephalomyopathies
Oxphos disorders
involve gray matter and skeletal muscle
Describe tay-sachs
HEXA gene (hexosaminidase A) chr 15
GM2 Gangliosides never go away
cherry red spots on maculae
presents at 1 y/o dead 2-3 y/o
Describe MELAS
Mitochondrial Encephalopathy
Lactic Acidosis
Stroke
tRNA mutations
Most common mitochondrial neuro syndrome
what is the symptomatology of MELAS
Muscle involvement with lactic acidosis
Stroke episodes produce REVERSIBLE deficits that do not correspond to vascular territories
Describe MERRF
Myoclonic Epilepsy
Ragged Red Fibers
tRNA mutations
What is the symptomatology of MERRF
Myoclonus seizure disorder, w/ evidence of myopathy
Ataxia
What is Kearn-Sayre Syndrome
Ophthalmoplegia Plus
Sporadic disorder often associated with a large mitochondrial DNA deletion/rearrangement
What is the symptomatology of Kearn-Sayre syndrome
Cerebellar ataxia
Progressive external ophthalmoplegia
Pigmentary Retinopathy
Cardiac Conduction Defects
Describe leigh syndrome (subacute necrotizing encephalopathy)
Presents in early childhood with
Lactic acidemia Arrest of psychomotor development Feeding problems seizures Hypotonia
What are the neurologic effects of B12 deficiency
Numbness, tingling, slight ataxia
progress to spastic weakness
describe histology of b12 deficiency
swelling of myelin layers -> vacuoles form at midthoracic level
both ascending and descending tracts degenerate
What is the main difference between Wernicke and Korsakoff syndrome
Wernicke may reverse with thiamine while Korsakoff is largely irreversible with confabulation and memory disturbances
What layers of the cortex are most effected with CO poisoning
Layers III and V of cerebral cortex, sommer’s sector, purkinje cells
Also have BL necrosis of globus pallidi
Brain will be nice and red opposed to grey/tan
What is the main area affected by methanol and what is the toxic byproduct
Retina
Selective BL putaminal necrosis
Formate is toxic byproduct
How does Graves Orbitopathy affect the eye
hyperthyroidism most common cause of uni/bilateral exophthalmos
Enlargement of the extraocular muscles; increase of glycosaminoglycans
how does sarcoid affect the eye
systematic disease -> granulomatous UVeitis and sympathetic ophthalmia
- -mutton fat (keratic ppt in anterior segment)
- -Candle wax drippings
What is the most common tumor of periocular skin
Basal cell carcinoma
- younger patients
- nodulo-ulcerative
Who is most affected by squamous cell carcinoma
> 40 y/o asian women
2/3 upper eyelid, meibomian gland
What is masquerade syndrome
unilateral keratoconjunctivitis unresponsive to therapy
What is a pinguecula
thin epithelium (hyperplastic or dysplastic collagen)
basophilic degeneration
appears on sclera of the eye
What is a pterygium
encroaches onto cornea in winglike fashion
What is the most common primary intraocular tumor in adults
uveal melanoma
GNAQ & GNA11 in 85% of uveal melanomas
Describe open-angle glaucoma
complete open access to trabecular meshwork, resistance to aqueous outflow
–primary most common form
What are the risk factors for glaucoma
Age
Race (AA and hispanics)
Family Hx
DM
What is the leading cause of blindness in the us
age related macular degeneration
What is the most common symptom of retinoblastoma
Leukocoria (white pupillary reflex)
