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250 Cards in this Set
- Front
- Back
Dementia
*alzheimer's is MCC of dementia |
GRADUAL progression of multiple cognitive deficits
*Short-term memory affected more than long term memory Terms: - aphasia & paraphasic errors (grass is greel) - Apraxia: fail motor task despite normal strenth - Agnosia & Prosopagnosia - Distrubed executive functioning |
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ALZHEIMER'S
- GENETICS - AGE OF ONSET |
ONSET > 60 YO
- incidence doubles every 5 yr after 60 - more common in blacks & women Genetics: - Linkages to chrom 21, 14, 1 = EARLY onset - Chrom 19 apolipoprotein E4 allele = LATE onset **familial AD is only 7% of all AD cases Risk factors = VASCULAR - obesity, age, apo E4, hypercholesterolemia, HTN, insulin resistence *100% DOWN'S SYN = AD by 40 yo* |
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Pathology of AD
- cholinergic hypothesis - amyloid hypothesis |
1.B-Amyloid Plaques: Extracell
- can be normal 2. Neurofibrillary tangles: Intracell - tau & ubiquitin - also in PSP 3. Hippocampal Pyramidal cell degen - basal forebrain cholinergic neurons 4. Diffuse cerebral atrophy - Hydrocephalus ex vacuo Glutamate excitotoxicity & excess NMDA stim may play a role too amyloid hypothesis - plaques trigger inflamm, abnl tau phosphorylation, free radical tox --> neuronal loss & cholinergic dysfxn |
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SYMPTOMS & SIGNS OF AD
**ask family members about new deficits |
1. Loss of Insight
2. EARLY: mental slowing, lose interest, language problems, apraxia, spatial disorientation, impaired judgement, perseveration - family members take over finances, etc 3. Maintain Social Skills: friendly, jocular - pt looks normal superficially 4. LATE: become a different person – behavior, depression, delusions, hallucinations, frontal lob release signs 5. LATE MOTOR SIGNS: gait instability, parkinsonian - don’t respond to Parkinson meds |
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AD DX
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CLINICAL DX
- PT. HISTORY (family ) - MENTAL STATUS EXAM *atypical memory loss & FOCAL FINDINGS --> MRI MRI: DIFFUSE ATROPHY, HYPOMETABOLISM in temporo-parietal region, small hipocampus |
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AD MEDS:
**important to recognize & tx behavioral symptoms - agitation - psychosis - aggression |
AChE-inhibitors = mild-moderate
1. donepezil (aricept) = major 2. rivastigmine 3. galantamine 4. Memantine ( namenda): moderate-advanced AD - noncomp NMDA-R antagonist - blocks glutamate *use atypical neuroleptics for psych symptoms *Use antidepressant also if needed* |
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multi-infarct dementia
2nd / 3rd MCC dementia |
STEPWISE, ABRUPT DECLINES
- can be cortical or subcortical + FOCAL defects Subcortical: - pseudobulbar palsy - parkinsonian features - emotional incontinence - more apathy, depression, withdrawal, etc than cortical **dx is based on hx of multiple storkes & focal defects** |
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DEMENTIA W/ LEWY BODIES
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TRIAD:
1.EARLY: Fluctuating cognition w/ big variations in attn & alertness bw days & hours *2. Recurrent hallucinations (75% pts) 3. EARLY: motor signs of parkinson's - less tremors *hallucinations are huge |
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DLB PATHOLOGY
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1. Diffuse Lewy Bodies
- alpha-synuclein inclusions 2. Loss of Dopaminergic neurons in SN 3. Loss of Ach neurons in basal forebrain 4. Also senile plaques & hippocampal degeneration **subcortical AND cortical lewy bodies |
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PARKINSON'S VS AD
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PD: EARLY MOTOR, LATE DEMENTIA
+ TRAP AD: EARLY DEMENTIA, LATE MOTOR |
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HUNTINGTON'S VS AD
- path |
HUNTINGTON'S:
+ family hx & genetic testing - movement disorder: chorea - EARLY behavioral problems - late parkinsoniam features path: - gen. atrophy - focal atrophy of caudate nucleus |
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CREUTZFELDT-JAKOB DISEASE
- ONSET - DESCRIPTION - FEATURES - path & dx |
RARE, FATAL
onset: 50-70 TRIAD: 1. RAPIDLY PROGRESSIVE DEMENTIA 2. non-epileptic myoclonic jerks 3. ataxia - die w/in 6 mo onset PRION DISEASE - Spongy degen - neuronal loss - astrocytic proliferation dx: EEG: periodic sharp waves - elevated 14-3-3 PROTEIN IN csf |
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FRONTOTEMPORAL DEMENTIA
(FTD; PICK'S DISEASE) - ONSET - VS. AD) |
EARLIER ONSET THAN AD
FEATURES: - VERY SIMILAR TO AD - Spared motor & sensory - EARLY behavior & personality changes - Progressive aphasia (out of proportion to dementia) MRI: - FOCAL ATROPHY OF FRONTAL & TEMPORAL LOBES - PICK BODIES |
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KORSAKOFF'S SYNDROME
- THIAMINE DEF - OFTEN 2' CHRONIC ALCOHOLISM |
Sleep-confused patient (encephalopathy)
- Wernicke’s triad: ophthalmoplegia, encephalopathy, gait instable - precipitated by IV glucose admin in hospital - Korsakoff’s = residual amnesia: both antero & retrograde (PATHY MEMORY DEFICITS UNLIKE AD) Little insight & major confabulation (confuse imagination w/ real) |
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NORMAL PRESSURE HYDROCEPHALUS
- features - mechanism **VERY OVER-DIAGNOSED** |
1. EARLY Gait apraxia (initiation)
2. Subcortical dementia (depressed) 3. Urinary incontinence mechanism: Arachnoid granulations can't reabsorb CSF --> Communicating hydrocephalus - Ventricles enlarge & push against MIDLINE PATHWAYS --> urinary incontinenc & leg control *MRI: VERY LITTLE CORTICAL ATROPHY |
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AD vs. age-related cognitive decline
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NORMAL; PT OF AGING
- pt is still highly functional - NOT progressive memory loss - mildly diminished |
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AD vs. depression/pseudodementia
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SUBJECTIVE COMPLAINT
- onset is variable;esp in younger - abrupt onset; fluctuates - POOR effort; focuses on failures - sad, teary, personality changes evident - aware & distressed abt memory loss - Inconsistent, spotty deficits |
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ENCEPHALOPATHY VS DEMENTIA
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ENCEPHALOPATHY:
Acute/subactue onset - fluctuating course - attention is majorly impaired; sleepy - often reversible |
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EVALUATION OF HEADACHE:
OMINOUS SIGNS & SYMPTOMS (warranting further eval) |
1. NEW ONSET headache in person not previously predisposed to headaches
2. NEW ONSET of headache in older pt 3. SUDDEN ONSET 4. FEVER 5. FOCAL NEURO FINDINGS 6. Signs of increased ICP - drowsy, sleepy, papilledema |
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EVALUATION OF HEADACHE:
DIAGNOSIS: CONSIDER THE FOLLOWING IN ALLL PTS PRESENTING W/ HEADACHE |
1. Subarachnoid hemorrhage
neg Head CT --> lumbar puncture 2. MRI: non-migraine or tension headahce - r/o mass lesion 3. Temporal arteritis - sedimentation rate & temporal a. biopsy 4. Meningitis or pseudotumor cerebri - LP 5. Sinusitis: sinus series |
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NEUROVASCULAR THEORY OF MIGRAINES
- also genetics? - tx? |
BENIGN DISEASE PROCESS
Wave of neuronal excitation -->. Waves of cortical spreading depression --> Blood vessels dilate & constrict = Release of K+ & Glutamate --> CSD *PET shows dec CBF to brain areas involved in migraine *MEDS for serotonin receptors tx headaches 50% migraine pts = FAMILY HX |
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HEADACHES
- SYMTOMATIC VS ESSENTIAL |
LOOK AT THE TABLE!
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MIGRAINE HEADACHES
- ABORTIVE TX |
1. OTC: aspirin, tylenol, NSAIDs
- also used to tension type 2. CAFFEINE: CNS stimulant that vasoconstricts - assc'd with rebound headaches 3. Triptans = 5HT agonists - contraindicated in CAD & uncontrolled HTN - Frovatriptan: preventive; used for menstrual migraines 4. IV DA-blockers - antiemetics: Metoclopramide & Prochlorperazine 5. Narcotics: used in preggers w/ migraine |
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MIGRAINE HEADACHES
- PREVENTIVE TX |
1. TRICYCLIC ANTIDEPRESSANTS
- block NE & 5HT reuptake - SEs: confusion & urinary retention - esp. Nortriptyline: great SE profile 2. Beta-blockers: propranolol - Beta1-R: blocks NE release - inhibits Locus ceruelus firing - some effects on 5HT-R - AVOID in pts w/ asthma & depression 3. Anti-convulsants - Topiramate (topamax): #1 megraine prevention (also causes wt. loss) - other SEs: numbness, tingle, kidney stones, confusion, behavior change, word finding difficulty - Valproate is other option 4. BOTOX: expensive! - more effecitve in chronic daily headache |
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Categories of myelin diseases
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1. DE-myelinating (myelinoclastic)
- primary destruction of myelin (MS) - primary destruction of OG cell (PML) - primary destruction of axon (infarct or trauma) 2. DYS-myelinating (leukodystrophies) |
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PERIVENOUS ENCEPHALOMYELITIS (PEM)
aka postinfectious/postvaccinal encephalomyelitis |
CNS demyelinating diseases that are PRECEDED BY AN INFXN
- but the infectious agent is gone by the time of demyelination 1. Infxn precedes pathology 2. cellular immune response 3. lesions are perivenous 4. demyelination |
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PEM
- ADEM - AHLE |
Acute disseminated encephalomyelitis (ADEM)
- Viral infxns (MMR) Acute hemorrhagic leukoencephalitis (ahle) - systemic viral infxn or respt infxn (m. penumoniae) ** difference is severity/mortality: AHLE IS FATAL** |
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PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY
- causes - histo - viruses **IMMUNOCOMPROMISED*** |
SLOW viral infxn in immunodef pt. (lymphoma, AIDS, long term steroids)
- gray matter lesions also possible - virus grows in OG cells Histo: - focal loss of myelin - big OG nuclei with viral inclusions - Atypical, reactive astrocytes - foamy macros POLYOMA VIRUSES: - JCV - bk -sv40 |
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LEUKODYSTROPHIES
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DYSMYELINATING DISEASES (defects in formation or remodeling)
- genetic enzymopathies - diseases of childhood **mental retardation + neuro problems = most common finding ** - U FIBERS ARE SPARED (association fibers connecting gyri neighbors) - PNS myelin MAY be involved |
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METACHROMATIC LEUKODYSTROPHY (MLD)
- clinical - mechanism - genetic |
Prog. Motor disability & psychosis / behavioral problems in adulthood
**CNS & PNS MYELIN INVOLVED** - Lysosomal disorder: Aryl sulfatase A deficiency - Chr 22 recessive - Metachromatic macros & inclusions in white matter = red macros **no seizures ** |
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GLOBOID LUEKODYSTROPHY
(GLD) AKA KRABBE'S DISEASE |
- Developmental fail
- tonic spasms & myoclonic jerks - GAIT DISORDER - progressive spasticity - VISUAL disturbances - MICROcephaly - Lysosomal disorder: Galactocerebroside-beta-galactosidase deficiency - chr 14 recessive: 14q31 - multinucleated, globoid macros with tubular inclusions in white matter - severe diffuse dysmyelination - severe reactive astrocytosis - MICROCEPHALY |
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ADRENAL LEUKODYSTROPHY
(ALD) "Lorenzo's oil" BOARDS - NOT CAO - adult onset type: adrenal myeloneuropathy (more SC damage instead of adrenal problems) |
X-linked
- boys - adrenal glands & testis - storage of very LCFAs CLINICAL: FTT, seizures, retinal degen, hearing & educational problems, clumsiness, schizo, dementia - peroxisomal defect - diffuse demyelination (esp posterior cerebellum) - perivascular lymphocytic infiltration & foamy macros ** intracytoplasmic crystalloid structures in adrenal cortex & testis ** |
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ALEXANDER'S DISEASE
dON'T NEED TO KNOW! |
- macro-cephaly
- seizures, spasticity - psych problems & dementia - rosenthal fibers = excessive GFAP + gliosis - osmophilic densities |
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VINCRISTINE
- type of PN - type of drug - mechanism |
CHEMOTHERAPY DRUG (which are #1 cause of drug-induced PN)
MECH: Inhibits microtubule polymerization & interferes with axonal transport PN TYPE: - stocking glove dist. --> profound distal weakness (esp foot drop) **symptoms of PN may WORSEN for several months after you d/c vincristine** n biopsy: intra-axonal filaments |
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WHAT SURROUND MUSCLE BUNDLES vs FASCICLES vs. FIBERS??
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What surrounds muscle bundles?
Epimysium What surrounds muscle fascicles? Perimysium What surrounds a muscle fiber? endomysium |
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WHAT IS ALS & WHAT KIND OF pathologic changes would you expect to see?
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Amyotrophic lateral sclerosis
- LMN problem muscle biopsy shows NEUROGENIC CHANGES (not myopathic) - Cn-HATR |
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TYPE 1 mm vs. TYPE 2 mm
(type 1 mnemonic) |
What is the mnemonic for Type 1 muscles?
One Slow Red Fat Ox: Type 1 Slow-twitch, sustained force Red - high Mb Wide z bands, abundant fat Oxidative *type 2 is opposite, fast, white, glycolytic, abundant glycogen, scant fat, & few mitos |
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5 types of neurogenic pathologic skeletal muscle reactions?
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"Cn-HATR" since a neurogenic pathologic reaction is Central Nervous (Cn) hater.
1. Central nuclei (normally @ edges) 2. Hypertrophy (grouped) 3. Atrophy (grouped) 4. Target fibers (re-innervation) 5. Ring fibers (myotonic dystrophy) + Angular fibers = Stain darkly; deinnervation **reinnervation: grouped type 1 or type 2 fibers (evangelize?) |
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What are the 5 types of myopathic pathologic reactions of skeletal muscle?
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1. Myophagocytosis = Necrosis
(Multiple nuclei 2' macros) 2. Inflammation - Infiltration of WBCs 3. Necrosis 4. Fiber-splitting 5. Central cores + more hypertrophy |
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What are the acquired neurogenic disorders?
Neurogenic --> 2' involvement of muscle (Denervation atrophy) Genetic = Spinal muscular atrophies (SMA) |
“TINI”
Trauma Inflammatory --> Guillan Barre Neoplasms Iatrogenic (Vincristine, drugs, surgery) + Endocrine --> Diabetes **Type II disuse atrophy: Assc'd with steroid use MECH: Damaged peripheral nerves, axonal degen, and/or demylination - Re-innervation can be seen after neurogenic changes --> Would change the muscle fiber type --> Mosaicism of fiber types |
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What are the acquired myopathic disorders?
1' disease of muscles |
Polymyositis**
Inclusion Body Myositis** Dermatomyositis Infections It's a "PIDI" to acquire a myopathic disorder |
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What are the category and examples of NMJ disorders?
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Neurogenic:
Myasthenia Gravis Lambert-Eaton (paraneoplastic) |
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What are the genetically determined myopathic disorders?
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X-linked:
Duchenne/Becker MD Autosomal: Congenital MD Limb-Girdle type Myotonic dystrophy |
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What is "floppy baby"?
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Spinal Muscular Atrophy (infantile motor neuron disease);
Abnormality of the anterior horn cells |
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MOST SEVERE SMA TYPE? genetics?
**SMA is like ALS for kids - Progressive LMN degeneration |
SMA type 1: Werdnig-Hoffman dz
= Floppy baby @ birth - dies w/in 3 years CHROM 5: deletion of SMN OR NAIP gene |
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SMA
- PATHOLOGY |
1. grouped atrophy of fibers = CLASSIC
(1 neuron feeds a motor unit) 2. Angular shrunken fibers (panfascicular) 3. Rare hypertrophic fibers (compensatory) |
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What are the early pathologic signs of DMD/BMD?
and what about late? |
EARLY:
Myopathic changes (necrosis, myophagocytosis, etc) Variation in fiber size, splitting, internal nuclei Raised serum CK (myolysis) LATE: Endomysial CT and fibrosis |
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What is the pathogenesis of DMD/BMD?
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Dystrophin on Xp21 encoding Dystrophin
DMD - no protein BMD - milder deficiency of protein DMD = Doesn't Make Dystrophin BMD = Badly Made Dystrophin |
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Course/Onset of DMD/BMD
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NORMAL AT BIRTH
- DMD onset = 5yo; pelvic girdle 1st - pseudo hypertrophy of calf - die by early 20s **BMD is way milder & more normal life span** |
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What is the pathogenesis of Limb-Girdle dystrophy?
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Mutation in sarcoglycan complex
AUTOSOMAL |
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What is the pathogenesis of Myotonic Dystrophy?
- basic presentation |
Type 1: Chr 19q13.2-13.3
= CTG rpts Type 2: Chr 3 AUTOSOMAL*** Myotonia, cataracts, heart problems, frontal balding |
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What is the pathogenesis of congenital dystrophies?
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Abnormalities of merosin gene expression
(Merosin-negative) autosomal (recessive) - neonatal hypotnia & delayed milestones |
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ION CHANNEL MYOPATHIES
- hyperkalemic = hyper/myotonia - Hypokalemia = hypotnia - Normokalemic - genetics & pathology *not on exams i don't think* |
AUTOSOMAL dominant
- intermyofibril vacuoles & electrolyte abnormalities |
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What triggers malignant hyperthermia?
results? |
What triggers malignant hyperthermia?
- Halogenated anesthetic agents What is the result of malignant hyperthermia? - Tachycardia, hyperpyrexia (Hypermetabolic state) *multiple genes are involved - Ca channel & Ryanodine *know for boards not cao |
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What is the characteristic pathology of mitochondrial myopathy?
- transmission? |
“ragged red fibers”
eg, MERFF: Myoclonic Epilepsy with Ragged Red Fibers maternal transmission usually |
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INFLAMMATORY MYOPATHIES
presentation? muscle biopsy? mechanism? - usually females (except IBM = males) |
PROXIMAL MUSCLE WEAKNESS
(except IBM) 1. Non-suppurative inflammation 2. Lymphocytic INFILTRATION in endomysium, perimysium 3. Muscle necrosis 4. Myophagocytosis 5. Regenerative activity (Myopathic changes) **AUTOIMMUNE PROCESS** |
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POLYMYOSITIS
- CAUSE - AGEGROUP - HISTO |
CAUSE: CD8+ T cells & macros destroy muscle
- trigger unknown SEE: lymphocytic infiltration & myophagocytosis - also myonecrosis: ^ nuclei (macrophages) Age group > 20 yo (doesn't affect kids like DM does) Triggers |
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DERMATOMYOSITIS (DM)
- ^ risk of? - age groups - cause - presentation - path |
INCREASED LUNG CA RISK
CAUSE: CD4+ T cells, B cells, IgG, IgM, MAC attack myocytes = Blood vessel disease of skeletal muscle (Microangiopathy & Atrophy) age groups: (PM does NOT affect kids) - Kids: Perifascicular atrophy - Adults: Active myositis LOOKS: racoon eyes (violet upper eyelids), face, trunk rash |
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What is shown on muscle biopsy of Inclusion Body Myositis (IBM)?
NOT ON EXAM |
Rimmed vacuoles with inclusions
OUTLIER of inflamm myopathies bc affects older MEN more & has more DISTAL mm weakness |
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What type of muscle fiber does steroid-induced myopathy cause atrophy of?
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Type 2
**Type 2 atrophy (disuse atrophy) also seen in denervation atrophy = neurogenic atrophy |
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What are the pathologic features of Myasthenia Gravis?
- muscle biopsy - tests - increased risk/assc'd findings - presentation? **Congenital MG has NO ACh-R Abs |
Near-normal light microscopic changes
Simplified post-synaptic membrane Reduced number of ACh-Receptors Increased circulation of ACh Receptor antibodies + Tensilon test & Decremental response on nerve conduction study ^ Risk of thymus issues - present w/ extra-ocular muscle problems (diplopia, droopy eyelid) |
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With what is Lambert-Eaton most associated with?
- also mechanism? - tests? |
Small cell carcinoma of the lung
- Pre-synaptic Ca2+ channel Abs - NEGative tensilon test & incremental response on nerve conduction study - Proximal muscle weakness |
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TOXIC MYOPATHIES
- cuases |
1. Thyrotoxic myopathy
2. Ethanol myopathy *also drug induced - Steroids (type 2 atrophy), statins, AZT, chloroquine |
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What are two types of immune-mediated neuropathies?
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AIDP (Guillain-Barre Syndrome)
CIDP (Chronic Inflammatory Demyelinating Polyradiculoneuropathy) |
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LMN PATHOLOGY
- segmental demyelination vs axonal degeneration |
1. Segmental: individual segments of myelin lost
- NO DAMAGE TO AXON 2. Axonal degen: - Axon damage --> secondary demyelination 3. Myopathy (denervation atrophy) |
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TYPES OF PERIPHERAL NEUROPATHIES
- Inflamm / Immune -mediated - Infectious - Hereditary - Acquired - Traumatic |
INFLAMM
1. AIDP (GBS): ascending weakness; PNS demyelination 2. CIDP: polyradiculoneruopathy Infectious: Leprosy, diphtheria, chickenpox Hereditary: - onion bulb formation (segmental demyel & remyel) - Charcot-Marie Tooth ACQUIRED - Diabetes, Uremia, Thiamin def, b12 def - CA - Drugs, chemicals TRAUMATIC: - laceration - Carpal Tunnel syndrome |
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What is the most common acquired metabolic neuropathy?
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Neuropathy from adult-onset diabetes mellitus
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ACUTE INFLAMM DEMEYLINATING POLYNEUROATPHY
(AIDP; GUILLAIN BARRE SYNDROME) - PRESENTATION - TX - CAUSES |
Preceded by flu-like illness
(C. jejuni infxn?) Present w/ Ascending weakness that starts at distal limbs - Also ANS: heart & Hypotension - CSF: ^ pressure, ^ protein, decreased cells PT NEEDS RESPIRATORY SUPPORT cause: PNS demyelination |
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INFECTIOUS POLYNEUROPATHY
- MECHANISM |
VASCULITIS
- WBC infiltration of blood vessels --> granulomas of nn --> neuropathy |
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NEUROPATH OF MEDICAL DISEASES
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READ YOUR EFFING HANDOUT IN WORD
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Superficial injuries & severity of the intracranial injury
- how are they related? |
THEY'RE NOT RELATED
DON'T JUDGE A BOOK/SCALP INJURY BY ITS COVER - the worst cases may have no external presentation |
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What distinguishes a laceration from an incision?
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Lacerations have "tissue bridges" or areas where the underlying tissue did not tear.
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types of scalp wounds
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1. Contusion / Hemorrhage
2. Abrasian 3. laceration 4. INCISION |
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WHAT FACTOR OF HEAD TRAUMA CORRELATES W/ THE SEVERITY OF INTRACRANIAL INJURY?
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THE LOCATION OF OF THE INJURY
- where was the force applied? - where did the hemorrhage or bleeding occur? - where was the infection? |
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Are most skull fractures associated with severe intracranial injuries?
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No, about 1/4th of fatal head injuries have no fractures. As with the scalp injuries (contusion, laceration, etc.), the severity of the intracranial injuries depends on where the force was applied.
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Linear Fractures: definition and clinical significance.
- types |
Types:
- closed ("simple") - break in the overlying skin ("compound") - Are significant normally because they indicate that trauma has occurred at a site. Sometimes they are of more significance b/c they cross a superficial artery (like the middle meningeal) - or open a space b/w two cavities and thus serve as a portal for infection. |
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Comminuted Fractures: definition and clinical significance.
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- Skull is broken into multiple fragments.
- Force may be the same as a linear fracture but the effects are different. Causes more intracranial injury than linear fractures b/c the fracture can be depressed. |
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Stellate Fracture: definition and clinical significance.
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- Multiple fracture lines radiate from a single focus.
- More commonly found in the curved areas of the skull. More commonly caused by being struck by a force (hammer) over a small area of contact. Can be confused with multiple blow trauma (false + for child abuse by radiologist) |
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Diastatic Fracture: definition and clinical significance.
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- Fractures that extend along a suture.
- Commonly occur before complete closure of the suture. (kids - child abuse?) |
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Depressed Fracture: definition and clinical significance.
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- One edge of the fracture is at least 1/2 the thickness of the skull below the original contour.
- Downward edges can cause significant lacerations and intracranial injuries. |
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What is the classic presentation of an epidural hematoma?
epidural: bw skull & dura - diploic vein lives here too |
1. Blow to the head
2. Rendered unconscious 3. Regain consciousness 4. Short period of alertness 5. SUDDENLY develops evidence of INCREASE intracranial pressure. - Headache, Nausea, Vomiting 6. Progresses slowly then rapidly to coma, if not treated. |
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What is the most common mechanism of epidural hematoma formation?
- what type of blood? **Incidence decreases w/ age bc dura adheres better to skull as you get older |
- Usually due to a LINEAR FRACTURE through the TEMPORAL BONE, which passes across the MIDDLE MENINGEAL ARTERY and associated veins, lacerating them.
*Thin Temporal Brain is not INITIALLY injured - 2' injury from increased ICP ARTERIAL BLOOD (subdural = venous) |
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EPIDURAL HEMATOMA
- GROSS appearance & changes seen in the handout pictures |
1. Brain edema (greater on hematoma side)
2. Midline shift 3. Cingulate and uncale herniations 4. Duret hemorrhage 5. Cortical infarcts 6. Dusky discoloration = respirator brain THERE IS NO BLOOD IN THE GYRI (but there was major increased ICP) |
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SUBDURAL HEMATOMAS
- classic presentation - mC pattern of injury - normal location? |
NO CLASSIC PRESENTATION - super variable
MC PATTERN: 1. rotary motion of brain relative to skull - usually associated with other cerebral injury (like atrophy) 2. TEAR bridging veins (bw arachnoid & superior sagittal sinu) - location is usually over dorso-lateral brain (UL bc falx cerebri stops it) VENOUS BLOOD (epidural hematoma is arterial) - slower increase in volume |
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Subdural Hematoma: Arterial or Venous Bleed?
- what causes increase in size of hematoma? |
VENOUS.
- the increase in volume is usually SLOWER than an Epidural Hematoma. - Sequelae is a pattern of bleeding, stabilization, healing, bleeding -> increase size of bleed. - Note: some believe that lysis of RBCs within the bleed and subsequent osmotic shift of fluid into the bleed is what causes the increase in size of the hematoma. |
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How do subdural hematomas heal?
acute hematoma: |
Formation of granulation tissue from the dura -> Neomembrane formation -> neomembrane (outer membrane thickness > inner membrane) extends from the edges of the hematoma -> cyst formation.
- Progression can be used to determine when the injury occurred, though this method determines a range and not a specific time like that seen in CSI. |
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What is the most common cause of subarachnoid hemmhorage?
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TRAUMA
2nd MC cause is...ruptured Berry Aneurysm (esp @ COW) **Sudden ^^ in Systolic BP can rupture a weak blood vessel** |
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SUBDURAL HEMORRHAGE
- gross appearance from handout pic |
1. NO blood in gyri still
2. Falx Cerebri: keeps the hematoma Unilateral 3. Compressed brain + Midlline shift --> Uncal & cingulate herniation 4. EDEMA 5. Fibrous membrane - cyst filled with blood? |
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How can a pathologist tell the difference b/w a contusion and an infarct in the brain?
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Contusions primarily affect the crowns of the gyri, are wedge-shaped, and SPARE THE SULCI.
Infarcts more commonly AFFECT THE DEEPER PORTIONS OF THE SULCI with less involvement or SPARING THE CROWNS OF THE GYRI. Learn one, know the other is the exact opposite. |
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Blunt Force Lesion Definitions: Coup
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An intracranial lesion BENEATH the site of IMPACT.
- Injury usually due to an actual collision of brain and interior skull structures. MC is to see frontal brain injuries in a Coup lesion due to the fact that the anterior skull has many fixed projections (cribiform plate, etc.) that can cause lacerations when the brain slides over these areas. |
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difference bw subarachnoid hemorrhage & basilar injury from distinct INJURY to blood vessels
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Distinct injury to blood vessels
- usually in vertebral arteries - follow blood here *lesions usually due to hyperextension or hyperrotation |
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Blunt Force Lesion Definitions: Contrecoup
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An injury that occurs OPPOSITE the site of IMPACT.
- Injury is usually due to rotational forces that are occurring to a brain being moved AWAY from the skull. Larger impacts actually cause a negative pressure gradient to form and subsequent bubble formation, which is also damaging to the brain. Coup and Contracoup injuries most frequently occur anteriorly, however. **most occipital impacts --> contrecoup injuries |
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Blunt Force Lesion Definitions: Intermediary Coup
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Injuries that occur ALONG THE LINE OF FORCE (in b/w one side of the skull and the other)
- Thought is that brain may be striking stationary structures such as the falx, tentorium, or foramina, that are more centrally located. |
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What is the most likely lesion you will see in an occipital impact?
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Contracoup: 90%
Coup: 17% Percentages must take into account that some pts get both contracoup and coup injuries at the same time. Since the force hits the back of the head, contracoup injuries are occurring to the anterior brain, WHICH IS THE MC SITE FOR DRAIN BAMAGE!!! |
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What is the most likely lesion you will see in an frontal impact?
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Coup: 93%
Contracoup: 21% Majority of brain injuries from blunt force trauma hit the anterior brain. MORE PROOF! |
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What is the most likely lesion you will see in a Lateral impact?
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Contracoup: 60%
Coup: 50% What type of injury should you see more of here...intermediary coup methinks. |
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Predict what injuries you will see in a stationary but moveable head struck by a moving object (watermelon to the face)?
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Coup injuries more common (watermelon hits skull, skull moves backwards, brain hovers in CSF, skull strikes brain).
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Predict what injuries you will see in a stationary and supported (unmoveable) head struck by a moving object?
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Most of the energy is transmitted to the SCALP and SKULL and not the brain (nothing hits the brain b/c the skull doesn't move). Thus, SCALP and SKULL INJURIES ARE MORE COMMON IN THIS INCIDENT.
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Define concussion.
- What is always present in a concussion? - When should you suspect a severe cerebral injury? - Can you see the injuries histiologically? |
Def: Temporary, reversible neurological deficiency caused by trauma which results in immediate, temporary loss of consciousness.
always present: RETROGRADE AND POST-TRAUMATIC AMNESIA BE CONCERNED IF: symptoms persist for >24 hours. NO HISTO changes only see non-specific signs of injury |
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What are the general cerebral consequences of trauma?
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Brain swelling secondary to EDEMA or HYPEREMIA (increased blood flow) in and around the site of injury.
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What are the vascular consequences of cerebral trauma?
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Vessels may be contused, lacerated, or have torn intimas. This increases risk for thrombosis, aneurysm formation, or AV malformation upon healing.
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Which cranial nerve is most commonly affected by brain injury?
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CN III (severe ptosis, mydriasis, downward and outward pointing eye).
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What are the systemic consequences of cerebral trauma?
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More common effects include pulmonary congestion, vagal effects in the heart (increased???), and GI ulceration.
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What are the delayed CNS effects of cerebral trauma?
- subarachnoid hemorrhage - contusions & intracerebral hemorrhages |
Healing of intracranial lesions in subarrachnoid hemorrhages may block CSF flow, leading to communicating hydrocephalus
**arachnoid granulations are all effed up** Contusions and intracerebral hemorrhages -> focal gliosis, seizures. |
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What type of brain trauma can occur from a broken femur?
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Fat emboli can travel from the site of trauma to the brain causing diffuse PETECHIAL hemorrhages in the WHITE MATTER. Decreasing cerebral function may ensue.
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Where do spinal injuries most commonly occur?
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Cervical or Lumbar spine (thoracic is supported by the ribs).
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NEURODEGENERATIVE DISEASES
- general characteristics - broad categories *neurodegenerative disorder = loss/abnormal activity of functionally related groups of neurons |
GENERAL CHARACTERISTICS:
1. Mostly old folk (rarely young pts) 2. Mostly PNS 3. Clinical manifestations vary depending on specific neuron population lost - cortical --> dementia - Basal ganglia --> movement - Cerebellar --> ataxia - Motor --> weakness BROAD categories: 1. Movement disorders - Involuntary ( PD, huntington's) - Voluntary (ALS) - Spinocerebellar (Friedrich Ataxia) 2. Cognitive / Dementia - Alzheimer's - Lewy Body - Pick's disease - Prion |
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KNOWN etiologies associated with neurodegenerative diseases
hint: alzheimer's |
APP gene on Chr 21 (familial alzheimer disease)
also: - trinucleotide rpts (huntington's - Virus (influenza) - toxins (MPTP) - oxidative stress lots others |
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NEURODEGENERATIVE DISEASES & LOCATIONS
- huntington's - Alzheimer's - Parkinson's - Friedreich ataxia - Amyotrophic lateral sclerosis |
1. HUNTINGTON:
caudate nucelus & frontal cortex 2. ALZHEIMER: frontal & hippocampal cortex 3. PARKINSON: Substantia nigra 4. FRIEDREICH ATAXIA: ONLY SC - posterior & lateral columns 5. ALS: - Lateral columns of SC |
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negative vs. positive symptoms in involuntary/extrapyramidal type movement disorders
(neurodeg dz) |
POSITIVE SYMPTOMS
- excess of involuntary movements NEGATIVE symptoms - reduction of voluntary movements |
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STRUCTURAL basis of involuntary movement disorders
(pathogenesis) |
Degenerative changes in NIGROSTRIATAL PATHWAYS
(brain stem & basal ganglia) - normally modulate feedback from thalamus to motor cortex **Accompanied by disturbnace in specific NTs (DA or GABA, etc) |
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PARKINSONISM
- clinical syndrome/symptoms - disorders in this group |
Negative & Positive symptoms
(TRAP - tremor, rigid, akinesia, postural instability) 1. Tremor 2. Rigidity 3. Bradykinesia 4. Forward propulsion 5. Pill-rolling movements 6. Mask-like facies ** Idiopathic PD ** Post-encephalitic Parkinsonism also: progressive supranuclear palsy, cortico-basal degen, multiple system atrophy |
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PARKINSON DISEASE (IDOPATHIC PD, PARALYSIS AGITANS)
- ONSET - POPULATION - Pathogenesis/genetics (Acute PD, familial PD |
SPORADIC disease in OLDER people
TRAP symptoms PATHOGENESIS - NOT ENOUGH DOPAMINE - acute PD = MPTP toxin (methylpheynltetrahydropyridine) - Familial = Alpha-synuclein |
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IDIOPATHIC PD
PATH & HISTO FINDINGS |
PATH:
- BS & basal ganglia - Pallor of Substantia nigra in midbrain and/or Locus Ceruleus in Pons HISTO: - ATROPHY of substantia nigra/locus ceruleus - Reduced pigmentation - LEWY BODIES!!! in these areas (eosinophilic inclusions) - Loss of dopa neurons going to striatum |
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POST-ENCEPHALITIC PARKINSONISM
(von economo's disease) - setting? |
Seen in aftermath of pan-influenza epidemic of 1914-19
(spanish influenza?) probalby NOT on the test bc it has almost vanished ever since |
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HUNTINGTON'S DISEASE
- clinical features - pathogenesis |
onset: 20-40 yrs
- Involuntary choreiform/dancey movements - Psych symtpoms (dementia & psychosis) - Can --> Parkinson's - Die in 10-15 yrs PATHOGENESIS: AUTO DOM - Chromsome 4p: Trinucleotide rpts --> Polyglutamine rpts --> Huntingtin protein aggregation & intraNUClear inclusions **Anticipation: Increasing severity & earlier onset w/ successive generations |
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HUNTINGTON'S DISEASE
- PATHOLOGY |
Anatmoc focus: Basal ganglia (caudate & putamen)
Gross: BL Caudate Atrophy **Lateral aspect of lateral ventricles become CONCAVE (normal = convex) MICROSCOPIC: - Atrophy of caudate - LOSS of medicum sized spiny neurons (normally utilize GABA - INTRANUCLEAR INCLUSIONS |
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AMYOTROPHIC LATERAL SCLEROSIS
(amyotrophic --> flaccid) (Lateral --> lateral columns) - clinical features & onset - pathology |
AFFECTS ALL AGE GROUPS
CLINICAL: UMN & LMN affected - Asymm weakness first - LMN problem: Atrophy & fasciculation - UMN prob: Weakness & spasticity (babinski) PATH: 1. Apoptosis of AHC & cranial nerve nuclei **EXCEPT EYE MOVEMENT** - SPARED 2. Atrophy of anterior spinal nerve roots 3. Neurogenic atrophy of skeletal muscles (Cn-HATR) 4. UMN: Betz cells in motor cortex atrophy --> CST atrophy |
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DEGENERATIVE DISORDERS AFFECTING THE SPINAL CORD
- LOCATIONS OF a. tabes dorsales b. FA c. als d. Subacute combined degeneration |
A. TABES DORSALIS
Meningovascular syphilis --> Fibrosis of meninges --> Pinches/kills dorsal roots going to Dorsal Columns & Clarke's nucleus = Stomping giat B. Freidreich ataxis: 1. Dorsal roots (afferent) --> Posterior columns & CLarke's 2. Desc UMN to CST 3. Ascending Spinocerebellar tracts C. ALS 1. UMN to CST 2. AHC D. SACD 1. Dorsal Columns 2. Spinocerebellar Tracts 3. AHC |
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SPINOCEREBELLAR DEGENERATION
- FEATURES - EXAMPLE - CLNICAL PRESENTATION |
Affects:
1. Cerebellar Cortex: Ataxia & balance messed up 2. Spinal Cord: - Spinocerebellar tracts - Dorsal columns/Clarke's nucleus - UMN: pyramidal nn. --> spastic 3. PNS: Dorsal roots Sensorimotor periph neuropathy *Example = Friedreich's ataxia - GAA rpts on Chromsome 9p13 (frataxin gene) NO DEMENTIA OR COGNITIVE CHANGES BC CEREBRUM IS NOT INVOLVED |
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DEMENTIA VS. MENTAL RETARDATIONS
2 common & 1 uncommon degenerative cause of dementia |
Dementia: Progressive deterioration of higher cognitive fxns
- you're losing previously attained knowledge Mental retardation: NEVER achieve certain milestones (Delirum = temporary; not relentlessly progressive) Common causes: Alzheimers (65%- frontal & hippocampus) & Dementia w/ Lewy bodies Uncommon cuase: Pick's dz (5%) = lobar sclerosis |
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ALZHEIMER'S DISEASE
- CLINICAL & PATHOGENESIS |
MCC of dementia
- onset: 50-65 yo CLINICAL FEATURES: - Progressive decline - LATE: psych,mood changes & mute, immobile PATHOGENESIS: 1. Early onset Familial AD - Chr 21 APP (amyloid precurosr protein) - Down's syndrome: < 45yo |
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ALZHEIMER'S DISEASE
- PATHOLOGY |
ANATOMIC FOCUS:
1st: Hippocampus & temporal cortex Later: Neocortex, deep grey, & BS + Cerebral aTROPHY + Senile Plaques a.) A beta-amyloid protein = extracellular b.) Tau Neurofibrillary Tangles = intracellular - correlate w/ clinical dementia (also see granulovacuolar degen & amyloid angiopathy) **Aggregates = neurotoxic |
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PICK'S DISEASE
(FRONTAL LOBE DEMENTIAS) |
Continuum of overlapping pathologic abnormalities
**Selective areas of lobar atrophy **Do a silver stain to see pick bodies*8 |
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PRIMARY VS METASTATIC TUMORS
|
PRIMARY:
- arise w/in CNS or coverings - Low or High - DO NOT METASTASIZE (exceptions) - MALIGNANT behavior even if benign bc it's inside the skull METASTATIC - Always HIGH grade - arises outside CNS - COMMON |
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TUMORS OF THE NERVOUS SYSTEM
- CNS VS. PNS --> primary vs. metastatic |
PNS:
- Schwannoma - Neurofibroma - Neurofibroscarcoma CNS: PRIMARY: 1. Neuroepithelial (glioma) - Astrocytoma - Oligodendroglioma - Epndymoma 2. Embryonal 3. Meningioma 4. Primary Lymphoma (also germinoma, choroid plexus papilloma, colloid cyst) METASTATIC 1. Lymphoma 2. Breast, GI, Lung (blood borne) ** Carcinomatous meningitis? |
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FACTORS TO CONSIDER IN MAKING UR DX
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1. Anatomic Distribution
2. Age of pt |
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DIFFERENTIATING A BENIGN FROM MALIGNANT GLIAL TUMOR
|
1. TYPE: histological appearance
2. GRADE: degree of malignancy - how ugly is it? 3. STAGE: metastasized? - not important in CNS tumors bc they rarely metastasize (EXCEPT for MEDULLOBLASTOMAS/PNETs) |
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MORPHOLOGIC (histologic) CRITERIA FOR GRADING TUMORS
|
More Important Criteria
1. MITOTIC ACTIVITY 2. NUCLEAR ANAPLASIA (ATYPIA) - how ugly it is 3. VASCULAR PROLIFERATION 4, NECROSIS Less Important Criteria - Abnormal Mitotic Figures - Degree of Phenotypic Differentiation - Cellular Density and Pleomorphism **numeric description **Descriptive = blastoma = HIGH grade |
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What are gliomas?
- MC types of gliomas? **nerve tumors are also types of neuroepithelial tumors |
What are gliomas?
Gliomas are a sub-category of neuroepithelial tumors. Neuroepithelium is anything derived from the embryological neural tube or its derivatives. What are the most common histological types of gliomas? 1. Astrocytoma 2. Oligodendroglioma 3. Ependymoma |
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What is an astrocytoma?
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A type of glioma that has...
1. GFAP (Glial Fibrillary Acidic Protein) - int. filament protein 2. Elongated, broad-based processes with a star-like appearance (exception: gemistocytic astrocytes are large and round/oval) |
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THE ONLY TUMORS YOU NEED TO REMEMBER SAYS CAO
- DIVIDE THEM BY THE AREAS WHERE THEY ARE |
1. Glioma (cerebrum)
2. Meningioma (meninges) 3. Ependymoma (fourth ventricle) - mostly benign 4. Pontine Glioma 5. Astrocytoma of childhood (cerebellum) 6. Medulloblastoma (vermis of cerebellum) 7. Acoustic Schwannoma 8. Craniopharyngioma: above pituitary |
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TYPES OF ASTROCYTOMAS
(general) |
1. Diffuse: poorly demarcated; diffuse margins
2. Special variants: well-demarcated - mostly below the tentorium (cerebellar) - maybe removed totally by sx? |
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DIFFUSE ASTROCYTOMAS
- what are they ? - characteristics (originate, prevalence, prognosis) - classic picture |
Low-Grade Astrocytomas
- diffuse infiltration of neuropile --> low grade always turns into high grade 1. Originates & infiltrates WHITE matter 2. MC POST-childhood astrocytoma (adult) 3. POOR prognosis - so diffuse; hard to resect/radiate **Fibrous, germistocytic, & protoplasmic types are all diffuse CLASSIC picture of diffuse astrocytoma - swollen temporal lobe (diffuse infiltration) - hippocampus involved - NO HEMORRHAGE OR NECROSIS** |
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ASTROCYTOMA GRADING
- numeric vs descriptive **grading based on cellular density, nuclear atypia, mitotic index, vascular proliferation, & necrosis** |
1. Astrocytoma: Grade 1 & 2
2. Anaplastic Astrocytoma: Grade 3 + Mitosis, but NO vasc proliferation or necrosis 3. Glioblastoma = Grade 4 UGLIEST + mitosis, necrosis, AND vasc. proliferation most cellular, severest anaplasia & pleomorphism |
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DIFFUSE ASTROCYTOMAS & AGE OF PT
- ADULTS VS. KIDS |
ADULTS:
2/3 supratentorial (cerebrum) & 2/3 are anaplastic @ dx **more likely high-grade** CHILDREN: 2/3 Infratentorial (mostly cerebellar) - 2/3 low grade @ dx (grade 1 or 2) |
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LOW-GRADE DIFFUSE ASTROCYTOMA
- BEHAVIOR - exceptions |
Grow SLOWLY
- spread along intact myelinated axons - do NOT destroy axons or BBB *Symptoms start when tumor bulk = ^ ICP (brain stem gliomas are early symptomatic) 2 EXCEPTIONS to slow growth/symptom onset 1. Tumor associated intracranial HEMORRHAGE 2. Invasion of grey matter --> SEIZURES |
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HIGH GRADE DIFFUSE ASTROCYTOMAS
- behavior |
1. Grow faster
2. Wide variety of symptoms (depending on location) **majority of glioblastoma originate from low-grade diffuse astrocytomas** = ticking time bomb (by the time it becomes malignant, it's already infiltrated a huge area of the brain) |
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GLIOBLASTOMA
- what is it? - what does it look like (and on ct?) |
HIGHEST GRADE ASTROCYTOMA
- ugliest 1. Ugly, highly anaplastic cells 2. Necrosis (jigsaw shapes) 3. Vascular Tufts = glomeruli-ish 4. Ring-like lesions on CT ?? **butterfly glioblastoma** - crosses the corpus callosum |
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SPECIAL VARIANT OF ASTROCYTOMA THAT CAO WILL TEST ON
- characteristics/differences from a regular low grade astrocytoma - histo features - neuroanatomical sites hint: ben carson |
1. Low grade
2. Well-demarcated margins (NOT diffuse) 3. MUCH better prognosis =) PILOCYTIC ASTROCYTOMA 1. Bipolar astrocytes w/ 2 long hair-like processes - degenerated vacuolated cells 2. Rosenthal fibers (eosinophilic sausagey extracellular stuff) 3. Lack of overt mitotic activity **YOUNG PATIENTS** MOST ARE IN CEREBELLUM - not in cortex |
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PILOCYSTIC ASTROCYTOMA
- where is it usually? - how does it grow? |
Special variant of low-grade astrocytoma
Childhood tumor mostly in CEREBELLUM 1. As tumor grows it degenerates 2. Forms small cysts 3. Become confluent & form larger cysts --> necrotic 4. Cyst wall beocmes gliotic scar w/ only nidus/rest of viable tumor **Total removal of NIDUS stops growth of tumor |
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OLIGODENDROGLIOMA
- what is it? - what does it look like? - where do you usually find it? |
1. Type of glioma (neuroepithelial tumor)
2. Round dark nuclei (size of lymphocyte) surrounded by clear cytoplasm - looks like a NORMAL OG cell 3. Found in WHITE matter (duh) - tendency to INFILTRATE gray matter (more gross infiltration than astrocytoma) --> SEIZURES |
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OLIGODENDROGLIOMA
- MICROSCOPIC FEATURES |
1. Sheets of clear cells ~ Honeycomb / fried egg
2. Calcifications 3. Spontaneous bleeding (2' neovascularization) 4. Chicken wire patten from capillaries |
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EPENDYMOMA
- prevalence - site - results - special features |
3RD MC glial tumor
- originates in periventricular area (site of normal ependyma) - esp 4th ventricle** **Forms epndymal ROSETTES** = perivascular pseudorosette (central blood vessel) - look like precursors of normal ependyma --> NONCOMMUNICATING HYDROCEPHALUS |
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MEDULLOBLASTOMA
(primary cerebellar PNET) - what is it? - site - characteristics - grade **PNET = primitive neuroectodermal tumor** - medulloblastomas that occur elsewhere in the brain |
Embryonal tumor; undifferentiatied w/o any phenotypic expression
- HIGH GRADE (blastoma) that originates from brain stem CHARACTERISTICS: 1. Cerebellar tumor (vermis - can grow into 4th ventricle 2. Smal blue cells! - also in Rb & small cell CA of lung - High nuclear:cytoplasmic ratio 3. Anaplastic nuclei 4. TONS of mitotic figures 5. Metastasizes along SC (LOVES to grow in Subarachnoid space --> compress SC) ALWAYS GRADE 4 DAMMIT - but quite txable |
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OTHER PRIMARY CNS TUMORS
- germinoma - choroid plexus papilloma - Colloid cyst |
1. GERMINOMA: germ cell tumors CAN occur in the brain
- usu midline 2. Choroid plexus papilloma - benign, intraventricular, hypersecretion of CSF = communicating hydrocephalus 3. COLLOID CYST: tumor like ** CHANGE IN POSITION CAUSING ^ ICP ** - located in lateral ventricle near foramen of Munro - acts like ball valve: pt. leans forward & makes obstructive, noncommunicating hydrocephalus - |
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PNS NERVE SHEATH TUMORS
- schwannoma vs. neurofibroma |
Schwannoma does NOT infiltrate the nerve
- it's just pushing on it & causing dysfxn - Can be resected --> restore fxn - ONLY schwann cells (no fibroblasts) - they NEVER progress to neurofibrosarcoma NEUROFIBROMA diffusely infiltrates nerve - need to sacrifice the nerve to remove it - find Schwann cells AND fibroblasts - HIGH risk of progressive to neurofibrosarcoma |
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SCHWANNOMAS
- biphasic histological pattern - acoustic neuroma |
ANTONI A: NUCLEAR PALLISADING
- stacks of parallel, elongated nuclei KNOW THIS COLD ANTONI B: Macro/microvesicular degeneration/necrosis *Acoustic neuroma = schwannoma of VESTIBULAR portion of CN8 DOES NOT INFILTRATE THE NERVE |
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NEUROFIBROMA
- MC type - what is it? - histo features |
MC is Solitary types
- benign nerve sheath tumor - associated w/ neurofibromatosis (neurocutaneous syn; Von Recklinhausen dz) + Cafe-au-lait spots (hyperpig'd spots) HISTO: - >1 elongated cell type (schwann, fibroblasts) - loose matrix w/ wavy spindle cells *HIGH CHANCE OF TURNING INTO NEUROFIBROSARCOMA - esp w/ radiation |
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MALIGNANT PERIPHERAL NERVE SHEATH TUMOR
- neurofibrosarcoma & malignant schwannoma characteristics? |
1. Extremely infiltrative
2. Can metastasize 3. Assc'd w/ Neurofibromatosis 4. Can result from prior irradiation (increased risk) |
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MENINGIOMA
- WHAT IS IT? - HOW IT HARM? - MORPH? |
INTRADURAL TUMOR
- do NOT invade CNS 1. Compress 2. Increase ICP --> ischemia, edema, herniation 3. Obstruct CSF (non-communicating hydrocephalus) MORPH: 1. Well demarcated; shell it out 2. Sheets of syncytial cells 3. WHORLS (transitional type) 4. Psammoma bodies (calcified spheres) 5. Meningothelial rests *malignant meningiomas infiltrate the neuropile |
|
SCHWANNOMAS
- biphasic histological pattern - acoustic neuroma |
ANTONI A: NUCLEAR PALLISADING
- stacks of parallel, elongated nuclei KNOW THIS COLD ANTONI B: Macro/microvesicular degeneration/necrosis *Acoustic neuroma = schwannoma of VESTIBULAR portion of CN8 DOES NOT INFILTRATE THE NERVE |
|
NEUROFIBROMA
- MC type - what is it? - histo features |
MC is Solitary types
- benign nerve sheath tumor - associated w/ neurofibromatosis (neurocutaneous syn; Von Recklinhausen dz) + Cafe-au-lait spots (hyperpig'd spots) HISTO: - >1 elongated cell type (schwann, fibroblasts) - loose matrix w/ wavy spindle cells *HIGH CHANCE OF TURNING INTO NEUROFIBROSARCOMA - esp w/ radiation |
|
MALIGNANT PERIPHERAL NERVE SHEATH TUMOR
- neurofibrosarcoma & malignant schwannoma characteristics? |
1. Extremely infiltrative
2. Can metastasize 3. Assc'd w/ Neurofibromatosis 4. Can result from prior irradiation (increased risk) |
|
MENINGIOMA
- WHAT IS IT? - HOW IT HARM? - MORPH? |
INTRADURAL TUMOR
- do NOT invade CNS 1. Compress 2. Increase ICP --> ischemia, edema, herniation 3. Obstruct CSF (non-communicating hydrocephalus) MORPH: 1. Well demarcated; shell it out 2. Sheets of syncytial cells 3. WHORLS (transitional type) 4. Psammoma bodies (calcified spheres) 5. Meningothelial rests *malignant meningiomas infiltrate the neuropile |
|
PRIMARY CNS LYMPHOMA
- incidence - where? |
Increasing incidence (2' AIDS)
LIKE WHITE MATTER (periventricular) - Start in VR spaces; perivenular - Diffusely infiltrate parenchyma (edema & necrosis) - Usually B cell type (high grade) **reticulin stain = concentric rings of perivascular tumor** |
|
METASTATIC LYMPHOMA
- where? - characteristics |
Originate from OUTSIDE CNS
- usually involve subdural (hodgkin's) or SAH spaces & Meninges - multiple tumor deposits - similar phenotype to primary lymphoma from which they originate |
|
METASTIC CNS TUMORS
- FROM WHERE? - routes |
KILL BIL
(Breast, GI, Lung) uncommon tumors that like to go to cns - Melanoma**deadliest - Choriocarcinoma ROUTE = BLOOD mainly also adj stuff & along nerves |
|
CARCINOMATOUS MENINGITIS
- WHAT IS IT? |
Meningeal carcinomatosis
- metastasis to Subarachnoid space |
|
LAYERS OF MENINGES
- spaces |
1. DURA: periosteum of the skull
+ venous blood 2. LEPTOMENINGES: arachnoid & pia - meningitis is usually here + arteries - Epidural space: potential space; doesn't normally exist - Subdural: very narrow - Subarachnoid space |
|
CSF FLOW
|
4 ventricles
- foramen of Monro connects lateral ventricles - Sylvian aqueduct connects 3rd & fourth ventricle OUTLETS: - 2 foramina of Luschka - Foramen of Magendie --> SAS --> Arachnoid granulations --> Venous sinuses (mostly superior saggital sinus **when arachnoid granulations are occluded by pus/hemorrhages (meningitis) --> COMMUNICATING HYDROCEPHALUS |
|
INFLAMM OF THE CNS
- meningitis - ventriculitis - encephalitis - cranial neuritis **MC routes of entry** |
MC routes of entry for meningitis = OM & Sinusitis & Meningeal vessels (hematogenous)
Leptomeningitis = Meningitis - Pachymeningitis = dura - Subdural inflamm = Subdural empyema Ventriculitis: rare in meningitis bc of direction of CSF flow Encephalitis: inflamm of brain parenchyma or Myelitis of SC - still rare bc difficult to penetrate the pia (unless infarct) - cranial neuritis = inflamm of cranial nn. |
|
Types of meningitis
(7) |
1. Bacterial/purulent
+ pus (except meningococcal - hemorrhagic) 2. Fungal/Granulomatous - chronic or acute 3. Parasitic - cysticercosis or amoebic 4. Viral: lymphocytic 5/6: Allergic / Chemical: also lymphocytic 7. Carcinomatous meningitis: assc'd with neoplasia of SAS |
|
ACUTE BACTERIAL MENINGITIS
- gross features |
CLOUDY MENINGES = PUS
- tons of neutrophils (PMNs) (Meningococcal meningitis = exception) - Pus on cerebral convexitis (sulci) & Posterior SC - Bacteria grows in SAS & ventricles --> immune response (Igs & neutrophils) - encaphlitis is NOT usually an issue (tough pia) EMPIRICAL TX IS IMPORTANT |
|
bacteria causing meningitis in the usa
- neonates - infants/kids - adolescents / young adults - elderly /debilitated |
NEONATES: Fecal contamination
- E. coli - GBS (strep agalactiae) ( & Listeria?) INFANTS/KIDS: - H. influenzae (no Abs) ADOLESCENTS/OUNG ADULTS - Neisseria Meningitidis ELDERLY/DEBILITATED - S. pnuemo - Listeria monocytogenes |
|
ACUTE EFFECTS OF BACTERIAL MENINGITIS
- long term dreaded effects |
1. Vascular thrombosis & vasospasms --> Infarcts (and 2' infxn of infarcts)
2. Edema --> ^ ICP --> herniations 3. Neurotoxicity = blindness & deaf (permanent) 4. Plugged arachnoid granulations = Acute obstructive communicating hydrocephalus **LONG TERM DREADED EFFECTS** - dead/blind - hydrocephalus - mental retard |
|
meningococcal meningitis
(neisserial) - why is it particularly worrisome? |
1. Kill's pt w/o prodromal symptoms
2. High mortality rate (50=90%) 3. Necrotizing vasculitis of the SKIN & many other organs - including adrenal glands (waterhouse-Friderichsen syn) - hemorrhage **PROPHYLACTIC rifampin or serum if contact is suspected** ALSO, IT'S NOT CLOUDY; MORE HEMORRHAGIC |
|
FUNGAL MENINGITIS
- which organisms - basic forms |
1. cryptococcus neoformans (MC in both types)
2. Coccidiodes immitis 3. Blastomyces Dermatitis 4. Histoplasma capsulatum A.) Chronic - non-opportunistic - GRANULOMATOUS meningitis (Epithelioid cells, giant multinucleated cells, lymphs) B.) ACUTE: opportunist - mixed cellular meningitis - can be hemorrhagic |
|
VIRAL MENINGITIS
- assc'd with? - characteristics |
MILD disease; usu transiet, nonspecific symptoms
- high LYMPHs - NORMAL glucose - assc'd with VIRAL ENCEPHALITIS** (hsv encephalitis) |
|
PARASITIC MENINGITIS
- organisms - characteristics |
1. Cysticercosis (T. solium) = Chronic
- Chronic granulomatous rxn 2. Acute = Amebic (naegleria*) 3. Meningitis caused by flukes/worms (helminths) - ABUNDANT EOSINOPHILS - common in immigrants |
|
LYMPHOCYTIC MENINGITIS
- what kinds of infections? |
common in
- viral - chemical / allergic (also show eosinophils) - Lymphomas involving SAS **CSF has almost all lymphs |
|
CSF PROFILES OF MENINGITIS
- DIFFERENTIATE BW Bacterial / Granulomatous (fungal, TB) / Parasitic / Viral / Carcinomatous KNOW THIS COLD - cell type is best guide in making distinctions (then cx & serology) |
ALL HAVE ELEVATED PRESSURE (carcinomatous can be normal)
1. Bacterial - HIGHEST cells - mostly PMNs - HIGHEST protein - LOWEST glucose 2. Granulomatous Meningitis = Fungal/TB ^ Cells Mostly Lymphs ^ Protein Normal or decreased Glucose 3. Parasitic ^ cells lymphs, monocytes, plasma cells, EOSINOPHILS ^ Protein Normal-Dec Glucose 4. Carcinomatous: - can have normal opening pressure Mononuclear cells; can see tumor cells Mild ^ Protein Normal-Dec Glucose 5. VIRAL: - NORMAL glucose ^ lymphs ^ protein |
|
BRAIN ABSCESS
- WHAT IS IT? - TYPES? - SOURCES OF INFXN |
Focal, well demarcated collections of purulent tissue confined
tYPES: - Intra cerebral - subdural empyema - epidural SOURCES: - MC = blood (bacteremia; infected embolus) - also OM/mastoid or trauma |
|
ACUTE ABSCESS
- what is it? - when is it lethal? - characteristic pathology |
NON-encapsulated abscess
- can form a capsule and become chronic Lethal in IMMUNOCOMPROMISED PATH: - Necrotic - Microorg is present - CNS edema - Neovascularization |
|
COMMON microorganisms causing abscess
(same for acute & chronic) |
1. Bacteria: Strep / Bacteroides / Staph aureus
(SBS) 2. FUNGI: Candida aLBICANS, aspergillus, Zygomycetes 3. Parasites = Toxoplasma, Amoebae (GI) - usu Entamoeba histolytica **chronic abscess are more common in immunocompetent pts |
|
CHRONIC ABSCESS
- WHAT IS IT? - DESCRIBE THE LAYERS |
Chronic abscess are more common in immunocompetent pts
= ENCAPSULATED ABSCESS Three layers: 1. Necrotic, pus filled center 2. Intermediate: fibrous capsule (+ Collagen - rare in CNS) 3. Periph: Reactive astrogliosis (inflamm cells) **Clinically silent = protects CNS from further spread, but resistant to abx --> surrounding edema & space occupying lesion --> herniation?? + Neovascularization --> Edema |
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TUBERCULOSIS OF THE CNS
- agent - types |
Mycobacterium TB & atypical forms
TYPES: 1. Miliary TB --> Meninges or parenchyma (Little foci of TB all over ur body) 2. Granulomatous: Similar to fungal meningitis - meninges only - thick secretions @ base of skull --> communicating hydrocephalus - Caseating necrosis, lymphs, epithelioid histiocytes, giant cells **AIDS pt WONT' have granuloma** - just see histiocytes w/ organisms (like in TB) 3. Tuberculomas (parenchyma) - Embolus; few sites of inxn |
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ENDARTERITIS OBLITERANS
- WHAT IS IT? - WHEN DO YOU SEE IT? - RESULTS? |
Huebner's arteritis
- Occlusive proliferation of the intima of large blood arteries - Seen in TB & Tertiary syphilis --> MASSIVE CEREBRAL INFARCTS |
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AIDS infections of CNS
- common opportunists |
Cryptococcus neoformans
- frequent in Ohio valley --> Granulomatous meningitis or Cerebritis/enceph **Toxoplasma will do same thing** NO GRANULOMATOUS INFLAMM IN AIDS PTS - just histiocytes w/ organism dx: PAS or GMS (silver) stain for crypto (india ink?) |
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CNS SYPHILIS
- main presentations - time course - asymptomatic |
1. Meningovascular (7 yrs post-infxn)
- Inflamm causes vascular compromise - Obliterated endarteritis = cerebral infarcts 2. Tabes Dorsalis (stomp around) - 15-20 yrs post-infxn - DRG compromised --> dorsal roots killed --> Atrophy of dorsal columns --> 2' joint damage (excess wear) 3. General Paresis of the insane / Dementia Paralytica - 10-20 yrs post-infxn - severe atrophy of brain (dementia) - major prolif of microglial cells 4. Asymptomatic: - no real neuro symptoms - CSF pleocytosis (reactive lypmhocytosis) - Increased Ig concentration + csf syphilis serology *also gummatous syphilis, congenital neurosyphilis, syphilitic meningitis--> 1-2 yrs post-infxn |
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VIRAL CNS INFXNS TO KNOW
- polio - rabies - measles - mumps - JC **what type of virus |
RNA:
- Polio: Picorno - Rabies: Rhabdo - Measles/Mumps: Paramyxo (SSPE / Encephalitis) - HIV Retro DNA: - HSV (encephalitis) - JC = Human papova virus (PML) **symptoms depend on distribution of the brain - NOT the type of virus |
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CNS VIRAL INFXNS
DX, ANATOMICAL SITE, EXAMPLE - Polioencephalitis - Poliomyelitis - Leukoencepahlitis - Panencephalitis |
1. POLIO ENCEPH
- Cerebral GRAY matter - EEE 2. POLIOMYELITIS - SC GRAY matter - polio = AHC & Bulbar motor nuclei 3. LEUKOENCEPH - Cerebral WHITE matter - PML 4. PANENCEPH - BOTH cerebral & SC, gray AND white matter = SSPE (cerebrum) |
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DISTRIBUTION OF LESIONS IN VIRAL ENCEPHALITIDES
- HSV - PML - SSPE - PRION CJD - POLIO - RABIES |
1. SSPE: Cerebrum
2 PML: cerebral white matter (JC virus --> oligodendroglia) 3. CJD: Cerebral cortex & cerebellum 4. Polio: AHC & Bulbar motor nuclei (Poliovirus --> motor neurons) 5. Rabies encephalitis - BS & Cerebellum 6. HSV enceph - temporal lobe = Hallucinate!! |
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ROUTES OF CNS VIRAL INFXN
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MOSTLY BLOOD VIREMIA
- along the nerves = Rabies (retrograde axoplasmic flow) |
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conventional viral infection
- characteristics - neuronal changes seen in conventional type |
1. Conventiional
- Pathology follows limited period of incubation - Virus can be Isolated from Lesion GRAY MATTER IS AFFECTED Neuronal changes: 1. Neuronal dropout (apoptosis) 2. Neuronophagia (gitter cells) 3. Cytopathic changes (cellular atypia) 4. Inclusion bodies (Nonspecific) 5. Perivascular Cuffing - Lymphs aggregate around blood vessels (VR space connects to SAS) --> lymphs can go into CSF and look like meningitis 6. Microglial nodule: esp in HIV/AIDS |
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3 types of cns viral infxns
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1. conventional
2. Slow 3. Atypical (prion) **see perivascular cuffing in slow & conventional types** |
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types of inclusion bodies seen in viral CNS infxns
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**inclusion bodies are nonspecific**
HSV: intranuclear Cowdry Type A Rabies: Negri = intra cytoplasmic JCV: Big huge intranuclear mass in oligodendroglia - obscures nucleus **mostly eosinophilic** |
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POLIOVIRUS
- results - where? - agent - targe |
Encephalitis / Myelitis
- poor immunization Enterovirus (Picorna) - RNA Target: Motor neurons of SC, brain stem, or cortex (myelitis, bulbitis, encephalitis) |
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HERPES SIMPLEX VIRUS
- results - prevalence - characteristics - where? |
MC non opportunistic spontaneous viral encephalitis
DX: CT/MRI - Characteristic mesial temporal hemorrhagic/necrotic lesions - become BL over time Cowdry type A inclusions = intra nuclear |
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HIV-1/AIDS associated nervous system lesions
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1. Vacuolar myelpathy
- vacuolarization of neurons/nerves 2. Opportunists - Toxo - Crypto - CMV encephalitis - Mycobacterial infxns - HSV & Herpes zoster 3. PML (JCV) |
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slow viral infections
- characteristics - examples |
LONG TIME bw infection & clinical manifestation of symptoms
- see perivascular cuffing examples: 1. Subacute sclerosing panecephalitis - Measles virus Lesions: Panenceph, Extensive necrosis, Cowdry Type A inclusions 2. PML - JCV - Leukoencephalitis - huge intranuclear lesion |
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ATYPICAL OR UNCONVENTIONAL (PRION) INFECTIONS OF CNS
- main result - main organisms - tranmission - path |
"Evangelism"
- mutant protein converts normal proteins 1. Spongiform encephalopathy - dementia - vacuolation (holes in neuropile) 2. Reactive astrocytosis/gliosis 3. No infectious microorg 4. Instead, mutant prion protein 5. Latent period (slow) 6. NO EVIDENT INFLAMM OR NEURONOPHAGIA******** Mostly a gray matter process - cerebellum & deep grey can be affected Human forms = dementia - CJD - Kuru: cerebellum mainly = ataxia |
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conventional viral infection
- characteristics - neuronal changes seen in conventional type |
1. Conventiional
- Pathology follows limited period of incubation - Virus can be Isolated from Lesion GRAY MATTER IS AFFECTED Neuronal changes: 1. Neuronal dropout (apoptosis) 2. Neuronophagia (gitter cells) 3. Cytopathic changes (cellular atypia) 4. Inclusion bodies (Nonspecific) 5. Perivascular Cuffing - Lymphs aggregate around blood vessels (VR space connects to SAS) --> lymphs can go into CSF and look like meningitis 6. Microglial nodule: esp in HIV/AIDS |
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3 types of cns viral infxns
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1. conventional
2. Slow 3. Atypical (prion) **see perivascular cuffing in slow & conventional types** |
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types of inclusion bodies seen in viral CNS infxns
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**inclusion bodies are nonspecific**
HSV: intranuclear Cowdry Type A Rabies: Negri = intra cytoplasmic JCV: Big huge intranuclear mass in oligodendroglia - obscures nucleus **mostly eosinophilic** |
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POLIOVIRUS
- results - where? - agent - targe |
Encephalitis / Myelitis
- poor immunization Enterovirus (Picorna) - RNA Target: Motor neurons of SC, brain stem, or cortex (myelitis, bulbitis, encephalitis) |
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HERPES SIMPLEX VIRUS
- results - prevalence - characteristics - where? |
MC non opportunistic spontaneous viral encephalitis
DX: CT/MRI - Characteristic mesial temporal hemorrhagic/necrotic lesions - become BL over time Cowdry type A inclusions = intra nuclear |
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HIV-1/AIDS associated nervous system lesions
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1. Vacuolar myelpathy
- vacuolarization of neurons/nerves 2. Opportunists - Toxo - Crypto - CMV encephalitis - Mycobacterial infxns - HSV & Herpes zoster 3. PML (JCV) |
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slow viral infections
- characteristics - examples |
LONG TIME bw infection & clinical manifestation of symptoms
- see perivascular cuffing examples: 1. Subacute sclerosing panecephalitis - Measles virus Lesions: Panenceph, Extensive necrosis, Cowdry Type A inclusions 2. PML - JCV - Leukoencephalitis - huge intranuclear lesion |
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ATYPICAL OR UNCONVENTIONAL (PRION) INFECTIONS OF CNS
- main result - main organisms - tranmission - path |
"Evangelism"
- mutant protein converts normal proteins 1. Spongiform encephalopathy - dementia - vacuolation (holes in neuropile) 2. Reactive astrocytosis/gliosis 3. No infectious microorg 4. Instead, mutant prion protein 5. Latent period (slow) 6. NO EVIDENT INFLAMM OR NEURONOPHAGIA******** Mostly a gray matter process - cerebellum & deep grey can be affected Human forms = dementia - CJD - Kuru: cerebellum mainly = ataxia |
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POLYSOMNOGRAPHY
- what are you measuring? |
1. EEG: brain potentials
2. Elecctroculogram: EOG - eye movements 3. EMG: muscle activity - submentalis muscle of the chin |
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EEG FREQUENCIES
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Delta: < 4 hz
Theta: 4-7 hz Alpha: 8-14 hz Beta: > 13 Hz |
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STAGES OF SLEEP
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2 States:
1. NREM Stage 1: Low amp theta Stage 2: K-complexes & sleep spindles Stage 3: 20-50% high amp delta Stage 4: > 50% high amp delta - no eye movements excpet maybe slow rolling ones in stage I, reduced EMG activity - Stage II is present > 50% of sleep - Stages 3 & 4 diminish as sleep progresses 2. REM: - EEG pattern similar to NREM Stage I - Low ampt, mixed freq waves + Rapid conjugate eye movments - ABSENT EMG activity (muscle paralysis) |
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ORGANIZATION OF HUMAN SLEEP
NORMAL **dreams occur during alll stages of sleep. - vivid dreams with good story lines usually seen in REM |
After sleep onset
- Progress through Stages I-IV in 46-60 min. - Slow wave (stage 3 &4) dominate first third of the night (15-25% of total nocturnal sleep in young adults) **After 1st slow wave sleep episode, progression of nREM stages reverses --> Then you get REM sleep Average cycle: 90-110 minutes (4-6 cycles / night) **After first REM, intervals bw successive REMs decrease through the night - Length of REM increases each time. REM = 20-25% OF SLEEP Stage 2 = 50% Stage 3 & 4 = 15% |
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EFFECT OF AGE ON SLEEP PATTERNS
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Daily sleep requirements DECREASE WITH AGE
- level off during middle age - decline further with old age BABIES: greater REM sleep (50% vs 25% adults) - elderly have even less rEM STAGE 4 Declines throughout developing/middle years --> disappears after 60 yrs |
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NEUROANATOMY OF SLEEP
- BRAIN AREAS INVOLVES |
1. RAS
- induce sleep & wakefulness - Rostral RAS: needed to wake up - Caudal RAS: needed to fall asleep **Raphe nuclei & Nucleus of the solitary tract in medulla also involved in falling asleep (?) 2. Suprachiasmatic Nucleus - of the hypothalamas - "Biologic clock" for circdatian rhythms - regulates diurnal secretion ofhormones - direct input from the retina (retinohypothalamic fibers) --> helps reset intrinsic rhythmicity of the suprachiasmatic nucleus (coincides w/ day/night) |
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NEUROCHEMISTRY OF SLEEP
- MAIN NT? |
SEROTONIN
- raphe nuclei in the brain stem - promotes sleep - w/o it = insomnia |
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TYPES OF INSOMNIA
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1. Sleep misperception syndrome
2. Pschophysiologic insomnia: - not on exam - poor sleep habits acquired during stress persist 3. Psychopathological insomnia - of anxiety/depression 4. Limb Movement Insomnia - Nocturnal myoclonus: bothers spouse - Restless legs syndrome: bothers pt 5. Circadian rhythm insomnia - jet lag |
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PSYCHOPATHOLOGICAL INSOMNIA
anxiety vs depression |
Insomnia associated w/ emotional disturbances
Anxiety: Difficulty falling asleep Depression: early awakenings **chronic schizophrenics actually sleep well |
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LIMB MOVEMENT INSOMNIA
- RESTLESS LEG SYNDROME VS - NOCTURNAL MYOCLONUS |
Restless legs: Bother pt more
- creepy crawlies in their legs - get up to move around and feels better - delays sleep onset - tx w/ DA agonists (parkinson's med) like Ropinerol & Pramiprexole - SEs: hallucinations, gambling, nausea 2. Nocturnal Myoclonus: Bothers spouse more - Pt is asleep - Let twitches every 20-40 seconds during STAGE 1 AND 2 SLEEP |
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TREATMENT OF INSOMNIA
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1. Benzodiazepenes: DOC for insomnia
- potent suppressors of deep slow wave sleep - enhange subjective quality of sleep - sharply reduce the # of microwakes = more restorative/refreshing sleep - NOT long term drug 2' tolerance 2. TCAs: - long term tx of insomnia AND migraines 3. Barbiturates are NO LONGER USED - rapid tolerance --> rebound intolerance - suppress REM sleep |
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PARASOMNIA
- types of disorders - what stage of sleep? |
Undesirable behavior that occurs during sleep or is exacerbated by sleep
1. Nocturnal Enuresis: Stage 4 - more in boys/young adults - maturational lag in neurological control 2. Somnambulism: Stage 3-4 - sleep walking; remain unconscious 3. Night terrors: Stage 3-4 4. REM Behavior Disorder: REM |
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NIGHT TERRORS VS. NIGHTMARES
- memory - stage - intensity |
Nightmare
- Stage: REM - STRONG memory when you wake up - Intense Night Terror: - Stage 3-4 - NO MEMORY when you wake up (memorable for the parents) - SUPER DUPER INTENSE + ANS activity *occurs during first several hours of sleep |
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PSYCHOPATHOLOGICAL INSOMNIA
anxiety vs depression |
Insomnia associated w/ emotional disturbances
Anxiety: Difficulty falling asleep Depression: early awakenings **chronic schizophrenics actually sleep well |
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LIMB MOVEMENT INSOMNIA
- RESTLESS LEG SYNDROME VS - NOCTURNAL MYOCLONUS |
Restless legs: Bother pt more
- creepy crawlies in their legs - get up to move around and feels better - delays sleep onset - tx w/ DA agonists (parkinson's med) like Ropinerol & Pramiprexole - SEs: hallucinations, gambling, nausea 2. Nocturnal Myoclonus: Bothers spouse more - Pt is asleep - Let twitches every 20-40 seconds during STAGE 1 AND 2 SLEEP |
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TREATMENT OF INSOMNIA
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1. Benzodiazepenes: DOC for insomnia
- potent suppressors of deep slow wave sleep - enhange subjective quality of sleep - sharply reduce the # of microwakes = more restorative/refreshing sleep - NOT long term drug 2' tolerance 2. TCAs: - long term tx of insomnia AND migraines 3. Barbiturates are NO LONGER USED - rapid tolerance --> rebound intolerance - suppress REM sleep |
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PARASOMNIA
- types of disorders - what stage of sleep? |
Undesirable behavior that occurs during sleep or is exacerbated by sleep
1. Nocturnal Enuresis: Stage 4 - more in boys/young adults - maturational lag in neurological control 2. Somnambulism: Stage 3-4 - sleep walking; remain unconscious 3. Night terrors: Stage 3-4 4. REM Behavior Disorder: REM |
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NIGHT TERRORS VS. NIGHTMARES
- memory - stage - intensity |
Nightmare
- Stage: REM - STRONG memory when you wake up - Intense Night Terror: - Stage 3-4 - NO MEMORY when you wake up (memorable for the parents) - SUPER DUPER INTENSE + ANS activity *occurs during first several hours of sleep |
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REM Behavior disorder
- population - tx |
OLDER MEN
NO normal muscle paralysis during REM - patients act out their dreams - injure themselves or sleeping partners tx: anti-convulsants work very well |
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HYPERSOMNIA
- types of disorders |
1. SLEEP APNEA
- Obstructive: upper airway obstruction - Central: rare; Myotonic dystrophy is related to it (damaged brain stem centers) - Mixed: Central respiratory pause followed by obstructive ventilatory efforts 2. Narcolepsy: 4 symptoms |
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SLEEP APNEA
- clinical features - complications - epidemiology |
FEATURES:
- Loud pharyngeal snoring - nighttime apnea - day time HYPERSOMNOLENCE - MORNING HEADACHES*** COMPLICATIONS: - Pickwickian syndrome (obese) - pulmonary issues + right heart failure & polycythemia Epidemiology: more common in older obese men |
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SLEEP APNEA TX
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1. WT LOSS. 1ST TX
2. CPAP: "pneumatic splint" of the airway - people don't liek the mask 3. Sx: enlarge upper airway *don't need to know drugs for this |
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NARCOLEPSY
- DEFINITION - EPIDEM |
REM sleep INTRUSION into wakeful
--> excessive sleepiness & abnormalities of REM sleep EPIDEM: - Onset: 15-35 - Can persist into old age - family hx - autosomal dominant |
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NARCOLEPSY SYMPTOMS
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1. Excessive daytime somnolence
- occurs in boring, sedentary situation - alleviated by motor activity & mental simulation - CAN'T be fully relieved by any amt of sleep - Brief episodes of sleep --> wake up feeling good & super refreshed - vivid dreams can occur here 2. CATAPLEXY: - muscular weakness/paralysis - precip'd by excitement/emotion - pt is conscious - complete paralysis excpet respiratory & eye muscles 3. Sleep paralysis - inability to move during the onset of sleep or on awakening 4. Hypnagogic hallucinations: dreams while you're awake - accompany the onset of sleep or awakening 1 & 2 = PRESENT ALL THE TIME 3 & 4 = present 50% of the time |
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NARCOLEPSY PATHOPHYSIOLOGY
- sleep study |
REM sleep occurs at the ONSET of sleep or within 10 MIN.
- impaired sleep-wake regulation (not an excessive NEED for REM sleep) Day time sreepies bc REM intrudes into wakefulness - hallucinations, paralysis, & cataplexy are dissociated manifestations of REM |
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NARCOLEPSY DX
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1. Tetrad of Symptoms
2. Positive family hx 3. Multiple sleep latency test - onset of REM sleep w/in 10 minutes - observe for day time somnolence (fall asleep w/in 10 min of laying down) - direct transitions from wakefulness --> REM sleep |
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NARCOLEPSY TX
|
Not on exam really
- Hypersomnolence: CNS stimulants (Methylphenidate or dextroamphetamine) - Other symptoms: give SSRIs (cataplexy, sleep paralysis, hypnagogic hallucinations) |
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DEFINE
- COMA - STUPOR - OBTUNDATION - LETHARGY |
COMA
Total or near total unresponsiveness STUPOR Severely impaired arousa - SOME response w/ VIGOROUS stimuli OBTUNDATION NOT as severe - some response to TOUCH/VOICE LETHARGY/somnolence Decreased arousal, but still maintained; esp with light stimulation |
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DEFINE:
- CONFUSION / ENCEPHALOPATHY - DELIRIUM |
CONFUSION:
Impaired attention but aroused enough to perform certain mental tasks DELIRIUM: Confusion PLUS periods of agitation, hypervigilence, irritability, & hallucinations - alternating w/ periods of decreased arousal |
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PATHOPHYSIOLOGY OF COMA
- Main areas of consciousness - excitatory inputs to cortex |
Main areas = Cerebral hemispheres & BS-RAS
- need at least 1 hemisphere & RAS --> UL strokes don't usually cause coma EXCITATORY INPUTS (bypass thalamus) 1. Basal forebrain (Ach) - Alzheimer's 2. Raphe nuclei (serotonin) 3. Locus ceruleus (NE) 4. Substantia Nigra: VTA (DA) 5. Posterior hypothalamus (Histamine) |
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4 general causes of coma
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Coma: BL stroke or BS lesion (around RAS)
1. Supratentorial Mass Lesions - head trauma: epidural/subdural hematoma - HTN --> intracranial hemorrhage - cerebral abscess - Massive stroke w/ edema **find ASYMMETRICAL FINDINGS** 2. INFRATENTORIAL MASS LESIONS - BS or cerebellar strokes/hemorrhages/tumors --> compress RAS --> BS signs **CROSS FINDINGS*** (Ipsilat CNs & CL hemisphere) 3. METABOLIC: diffuse cortical knockout - drug OD - severe electrolyte disorders - glucose - sAH, meningitis, renal fail, etc ***BS FXN USUALLY REMAINS INTACT** 4. PSYCHOGENIC COMA: - physiologically awake; appears comatose (doesn't respond to environment) - WILL respond to painful stimuli |
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NEUROLOGIC EXAM IN COMATOSE PATIENTS
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1. ASK THEM A QUESTION
- test language fxn 2. USE PAINFUL STIMULI - if pt doesn't respond to verbal - deep nailbed, sternal rub, cotton swab in nasopharynx --> report grimace, asymm, withdrawal, etc. **glasgow coma scale** - motor / verbal / eye response |
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Spontaneous respirations
- from what lesion? - progression |
Abnormal patterns of respiration
- MC in supratentorial mass lesion causing Brain Herniation Patient Deteriorates --> Progress: 1. Cheyne-Stokes - BL hemispheres/diencephalic - Hyperpnea & Apnea - least specific 2. Central neurogenic hyperventilation - Hypothalamic - Midbrain damage - rostral BS tegmentum 3. APNEUSTIC breathing - prolonged inspiratory cramp (pause w/ full breath) - Uncommon; most specific - Mid/Caudal-pontine lesion 4. Ataxic/Biot's breathing - Medullary damage - Deep & shallow breaths together - Reticular formations of medulla (normal to-fro breathing) |
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Medullary / Upper cervical cord lesions
- what kind of breathing problems results? |
Anatomical separation of AUTOMATIC and VOLUNTARY influences on breathing
- Lesion in medullary reticulospinal projections to SC (--> automatic respirations) **Spared CST --> Spinal respiratory motor neurons (voluntary breathing) Patients have to "remember" to breath - PROBLEMS AT NIGHT = ONDINE'S CURSE |
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PUPILLARY SIZE
- what is it dependent on? - SMALL VS LARGE - WHAT KIND OF LESION? **BRAIN DEAD PATIENTS HAVE FIXED AND DILATED PUPILS |
Balance bw
1.) Paraysym (CN 3 - miosis) 2.) Sym (mydriasis) SMALL: (pinpoint pupils) - Mess up desc. sympathetic paths - Pontine lesion (#3 MC HTN hemorrhage) --> BL, small, fixed pupils - UL miosis & ptosis = HORNER'S (ipsilateral brain stem) LARGE: broad causes - Central herniation --> BL CN 3 palsies - Uncal herniation: IL CN3 palsy - PCOM: CN3 palsy + headahce - SAH: comatose/lethargic too! |
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DAMAGE TO PRETECTAL AREA
- what is it? - what results? (eye) |
Pretectum: Region of neurons found between the thalamus and midbrain. It receives binocular sensory input from retinal ganglion cells of the eyes, and is the region responsible for maintaining the pupillary light reflex.
**Damage pretectal area - interrupts pupllary light reflex - spared accomodation - nonreactive 2 light - retained ciliospinal reflex (dilates to painful stimulation) |
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EYE MOVEMENTS
- Doll's eyes - when do you use this? |
COMATOSE PATIENTS
Oculocephalic (Doll's eyes) - CN8 carries info from Semicirc canals --> CL PPRF - Right SCC tells eyes to move Left *Warm water stimulates this pathway *Cold water INHIBITS this pathway |
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EYE MOVEMENTS
- COLD CALORIC TESTING IN COMATOSE PTS - results in cortical vs. BS lesion vs. brain dead pt. |
COLD CALORIC TESTING
- Cold water in ear INHIBITS oculocephalic reflex a.) SLOW nystag to IPSI - opp SCC is taking over b.) FAST nystag to CL - brain compensates (normal response - BS & Cortex intact) ex// Cold water in RIGHT ear causes LEFT beating nystagmus - named for fast phase 1.) Lesion in hemispheres (BL) - Cold in RIGHT ear - SLOW Right nystag - ABSENT fast nystag (no cortical function) **r/o brain stem pathology** 2.) Lesion in BRAIN STEM - asymm eye movements w/ cold calorics 3.) BRAIN DEAD - NO RESPONSE (slow or fast) 4.) Psychogenic coma: normal slow/fast phase |
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TESTS TO DO IN COMATOSE
**DIFFERENTIATE BW PSYCHOGENIC & REAL** |
1.) MENTAL STATUS
- Painful stimulation 2.) Spontaneous respirations? - Cheyne Stokes, Central neurogenic hypervent, Apneustic, Biot's, Ondine's curse 3.) Small vs Large pupils - light reflex 4.) Eye movements - Doll's eyes - Cold caloric testing 5.) Motor: - Decorrical vs. Decerebrate posturing 6.) Reflexes - Bainski, clonus, hyperreflexia 7.) Sensory - painful stimulation - look for asymm response |
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MOTOR RESPONSE IN COMATOSE PATIENTS
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Response to painful stimuli
- look for asymm 1.) Decortical posturing - Flexed arms & Extended legs - Lesion @ Diencephalon or above (Above BS; Thalamus or higher) 2.) Decerebrate posturing - Extended arms & legs - Overactive Lateral vestibulospinal tract (powerful extensor pathway) - Rostral/upper BS lesions (midbrain; upper pons) **In brain herniation, pt can progress from decorticate --> decerebrate posturing as lesion progresses deeper |
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DIAGNOSTIC STUDIES TO RUN ON COMATOSE PATIENTS
|
1. Blood studies
- infxn? - OD? - LIVER or renal failure? - metabolic issue? 2.) Urine Tox screen & Blood alcohol level - drug & alcohol abuse = causes for confusion & coma 3.) HEAD CT / MRI scan - look for supra/infra tentorial structural lesion - CT: r/o hemorrhagic (less sensitive ,but fast) 4.) LP - if normal CT/MRI 5.) EEG: - Non-convulsive status epilepticus |
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AUDITORY PATHWAY
|
1. Cochlear n.
2. cochlear nucleus 3. Acoustic striae - crosses midline - largest = trapezoid body 4. Sup. olivary nucleus (CL) 5. Lateral lemniscus 6. Inferior colliculus 7. Medial geniculate body (thalamus) 8. Auditory cortex (heschl's gyrus) |
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Fxn of
- superior olivary nucleus - lateral lemniscus - medial geniculate body |
SON
- detects time differences in sound arrival - useful in directionality - uses low Freq sounds LATERAL LEMNISCUS - startle response / reflex MEDIAL GB - ability to focus/discern specific quality of sound - cocktail party effect |
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PATHWAYS TO DAMPEN SOUND
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DESTRUCTION OF ANY OF THESE PATHWAYS
= HYPERACUSIS & icreased startle response 1. Descending efferents - inhibitory - lets you tune in to specific sounds 2. CN 7 : dampen ossicles via stapedius muscle 3. CN 5: Dampens tympanic membrane |
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Causes of auditory hallucinations
|
1.) CNS tumor/lesion in 1' auditory cortex or association cortex
- LOUD ROARING coming from unaffected hemisphere 2. AV malformation - bruits 3. PONS lesions - tapping, buzzing, tones 4. PSYCHOENIC - schizphrenia or other neurosis 6. Tympanic membrane lesion - hear heart beats/vascularity |
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AUDITORY GO/NO-GO TEST
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Response to taps
- abnormal: frontal release signs = frontal lobe damage |
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CENTRAL VS PERIPHERAL VERTIGO
AND TESTS |
CENTRAL: Cerebellar + BS
- less common - can reflect posterior fossa hemorrhag eor stroke - also see neuro deficits - IMMEDIATE ONSET OF NYSTAGMUS w/ positional testing *no adaptation* PERIPHERAL - INNER EAR - DELAYED onset of vertigo w/ positional testing - never vertical nystag - ADAPTATION IS PRESENT |
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What kinds of vertigo do you tx w/ diuretics
|
1. Benign positional vertigo
- calcium carbonate crystals 2. Meniere's disease - endolymphatic hydrops/high pressure |
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VESTIBULAR NERVE INFXNS
- TX & SEs |
Vestibular neuritis
- horrible awful vertigo for weeks to months TX; Neurectomy, Gentamicin otic drops SEs: permanent hearing loss - destory labyrinth |
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TREATMENTS OF
PARTIAL VS GENERALIZED SEIZURES - mech of treating partial vs generalized seizures |
PARTIAL SEIZURES: inactivate V-gate Na+ or Increased GABA
1.) Simple / Complex / with 2' generalization a. carbamazepine b. phenytoin c. phenobarbital d. valproate new meds: a. lamotrigine b. gabapentin c. topiramate** d. levetiracetam** e. tiagabine f. zonisamide GENERALIZED SEIZURES: V-gate Ca2+ - thalamaocortical radiations New meds: Lamotrigine for ALL Conventional meds: valproate for all - absence: can give ethosuximide too |