Path: Nervous System

Charcot Marie Tooth

most common hereditary peripheral neuropathy
Palpable nerves, muscle atrophy, onion bulbs

acquired metabolic neuropathy

Guillan Barre

Acute inflmmatory demyelinating polyradiculoneuropathy

inflammation and segmental demyelination following viral illness

VZV
latent infection of neurons

Muscular Dystrophy

CK: increased in muscle destruction
Duchenne and Becker
X linked, normal at birth
muscle biopsy shows number of changes ot muscle, no nerve involvement

Gene for dystrophin is abnormal
-minimal in becker
-none in duchenne

Inflammatory myopathies
-dermatomyositis
-polymyositis
-inclusion body myositis

Carpal Tunnel Syndrome: Compression neuropathy

Also morton's neuroma is a compression neuropathy on bottom of foot between toes

Wallerian degeneration of the distal nerve portion.

Myasthenia Gravis
Autoimmune
Loss of Muscle ACh receptors due to antibodies vs receptor
thymomas
fluctuating weakness, droopy eye
Anticholinesterase drugs improve

Congenital Myopathies
3 major diseases:
--central core dz
--nemaline myopathy
--centronuclear myopathy

Glioblastoma

Astrocytomas
Low grade WHO II/IV: ↑ cellularity
Anaplastic WHO III/IV: " " + mitosis, anaplasia
Glioblastoma WHO IV/IV: " "+ PALISADING NECROSIS

Medulloblastoma

Child, Cerebellum, May cause hydrocephalus
Cells with little cytoplasm (small blue cells), highly malignant, radiosensative

"Drop" mets: dissemiation through CSF with nodular masses throughout neuraxis including cauda equina

Microscopically composed of sheets of regular cells with round nuclei surrounded by clear halo of cytoplasm "fried eggs"

--contains anastamosing network of capillaries "chicken feet"
--Calcification in vast majority, may be massive

lcoated in white matter of cerebral hemisphere
better prognosis than astrocytomas

meningioma

predominantly benign tumor of adults

arise from meningothelial cell of arachnid, usually attached to dura

found along any external surface of brain as well as wtihin ventricle system

may be incidental finding

psammoma bodies

Schwannoma

Benign, located at the CPA, attached to 8th cranial nerve

Tinnitus, hearing loss
mixture of growth patterns: Antoni A, Antoni B

"40yo man complains of tinnitus and hearing loss in left ear"

1. Distinction between benign and malignant less evident in CNS than other organs
2. Ability to surgically resect infiltrating glial neoplasms without compromising neurologic fnx is limited
3. Anatomic site of neoplasm can have lethal consequences even if benign tumor
4. 1° CNS neoplasms rarely spread outside of the CNS
5. Subarachnoid space provides pathway for spread of some, look at CSF for tumor cells
6. 70% of 1* tumors arise in posterior fossa in childhood, while 70% in adults arise above tentorium

Pilocytic astrocytoma

Distinguished by pathologic appearance and relatively benign behavior
Children and young adults usually in cerebellum
Rosenthal fibers

Pilocytic astrocytoma

Distinguished by pathologic appearance and relatively benign behavior
Children and young adults usually in cerebellum
Rosenthal fibers

"15 yo girl complains she can't perform coordinated tasks as well as she did a year ago"

Arise next to ependymal lined ventricular system
first two decades in 4th ventricle
posterior fossa ependymomas present with hydrocephalus, obstruction of 4th ventricle
Px: poor despite slow growth
CSF dissemination is common

Familial
neurofibromas (plexiform and solitary)
shwannoma
gliomas optic nerve
cafe-au-lait
lisch nodules
neurofibromas can undergo malignant transformation

Familial Dz

bilateral schwannomas, multiple meningiomas

Familial Dz

Angiofibromas, siezures, mental retardation

unique tumor: subependymal giant cell astrocytoma

Familial Dz

Cerebellar Tumor Capillary hemagioblastoma

Von Hippel Lindau

Tuberous Sclerosis

Neurofibromatosis 2

neurofibromatosis 1

neurofibromas can undergo malignant transformation

Infantile Motor Disease (SMA)

Progressive neurologic illness, abnormality of anterior horn cells → destrx

AR, childhood/adolescent onset

large number of atrophic fibers, often involves entire fascicle: panfascicular atrophy

most common form: Werdnig-Hoffman Dz (SMA type 1) onset at birth or w/in 4 months, death within 3 years

(SMA type 1 Most common form of Infantil Motor Disease (SMA: Spinal Muscle Atrophy): onset at birth or w/in 4 months, death within 3 years

[Progressive neurologic illness, abnormality of anterior horn cells → destrx
AR, childhood/adolescent onset
--large number of atrophic fibers, often involves entire fascicle: panfascicular atrophy]

Thiamine (B1) Deficiency

Beriberi-slowly evolving
Wernicke's encephalopathy: acute psychosis
Korsakoff's Sro: untx'ed wernicke's: dementia
Common in chronic EtOHism,
Tx c Thiamine, Korsakoff's is permenant

Mamillary bodies: hemorrhage and necrosis

ALS Amylotrophic lateral sclerosis

loss of upper and lower motor neurons in corticospinal tracts and anterior horn

eventually involves respiratory muscles → recurrent pulmonary infx

Central Pontine Myelinosis

Loss of myelin in symmetrical pattern invovling basis pontis and portions of pontine tegmentum

believed to be 2° to rapid correction of hyponatremia
→ emergent quadroplegia

susceptible: Alcoholism, Severe elyte/osmolar imbalance, liver orthotopic transplants

Multiple Sclerosis: autoimmune demyelinating disorder

"distinct episodes of neurologic deficits, separated in time, attributable to white matter lesions that are separated in space"

Most common demyelinating disorder

CSF studies: mildly elevated protein
proportion of gamma globulin increased and most patients show oligoclonal banding

most common presentation: unilateral visual impaorment, optic nerve invovlement
Course: variable, relapsing/remitting with clusters of episodes
Multiple lesions scattered throughout white matter
plaques: sharply circumscribed, somewhate depressed, glassy gay-tan, irregularly shaped lesion, often around ventricles

Parkinson's

1. Diminished facial expression
2. Stooped Posture
3. Festinating Gait
4. Cogwheel rigidity
5. Pill rolling Trmor
6 Bradykinesia of voluntary mvmt

Damage to nigrostriatal dopaminergic system: grossly pallor substantia nigra, loss of pigmented catecholaminergic neurons with gliosis;
Lewy bodies remin in neurons
Can partially correct motor sro c L-Dopa, immediate precursor to dopamine

"65 yo man presents to doctor with resting hand tremor and mask like facies"

Huntington's

AD: clinically progresive mvmt disorder c dementia, histologically degeneration of striatal neurons

Relentless course, 15 years until death

Grossly brain is small with marked atrophy of caudate nucleus
↑ CAG repeats w/in huntingtin protein 11 → 34+, larger expansion = earlier onset

repeat expansion occurs in spermatogenesis: anticipation

onset 30's & 40's, motor first; earliest mental sx: forgetfullness, affective disorder, progresses to dementia.

"A 53 yo man complains of occasional involuntary movements"

Alzheimer's: MCC dementia 1% of 60 yo's, 40% of 90 yo's
rare before 50, slow but relentless 10 year course

Forgetfullness → memory disturbances → alterations of mood & behavior → language defecits, loss of math, loss of learned motor skills, → incontinent, bedridden, mute → pneumonia is terminal event

Gross: variable degree of cortical atrophy, compensatory ventruclar enalrgment (hydrocephalus ex vacuo)
Micro: --"tangles" of paired helical filaments (PHF) made from hyperposphorylated protein tau
--plaques: amyloid core predominantly AB, derived from APP amyloid precursor protein
--amyloid angiopathy: same AB protein as plaques

10% familial: --APP gene on chrom 21 (missense), ergo dose effect of trisomy 21
Also presenilins 1 and 2 on chroms 14 and 1, mutations ↑ prodnx of AB: early onset
(--splicing of PS1, missense mutations of PS1 or 2.)
Also ApoE on Chrom 19 ↑ risk alzheimers & early onset

all trisomy 21 beyond 45 demonstrate alzheimers.

definitive dx: pathologic exam
presentation + radiology 90% accurate

Ischemia- early in coagulatic necrosis
Toxic Injury

CMV or Syphillis

Infectious diseases: poolio, viral encephalitis

Neuronophagia for polio, viral encephalitis

Ependymal granulations for CMV or syphilis

Red neurons

Causes: any local mass or injury
Generalized in metabolic dz, malignant htn
SSx: Papilledema, HA, N/V

bilateral: no spinal tap (herniation)

unilateral: mass lesion

ventricular expansion 2° to brain atrophy:
-HIV
-Alzheimers

Any lesion which blocks 3rd and 4th ventricle

Ependymoma, Glioma-subependymoma, Choroid Plexus Papilloma, Medulloblastoma (esp ependymoma)

Malformations
"arnal curariae" --what does that mean?

obstruction along subarachnoid: enlargement of the entire system
meningitis

intrauterin toxo, perinatal group B strep

cingulate gyrus slides under falx
ACA compression & infarction → takes out right frontal cortex

uncinate transtentorial herniation: medial temoral lobe (uncus) compressed vs free margin of tentorium cerebelli
CN3 compromise, PCA compromise & visual loss: PEERL affected!
Duret hemorrhage of brainstem, flame shaped hemorrhage due to tearing of veins → coma

autonomic shutoff: respiatory failure & death

any ↑ ICP will do this and esp if tap below it

Related to deficiency of folic acid, maternal diabetes

↑ maternal serum α-fetoprotein

neural tube defects 2° to folae deficiency

--spina bifida: ∅ cosure of caudal NT & posterior verrtebral arches
--spina bifida occulta: defect limited to ≤2 vertebrae, ∅ ↑ [MSαFP]
--spina bifida cystica: herniation of meninges thru vertebral defect
--meningiocele: herniation of meninges trhough dkull or vertebrae
--meningiomyelocele: includes spinal cord
--spyringo-myelocele: herniation of central canal
--encephalocele: malformed CNS through cranium w/ foramenous center

occurs at d28
mother has polyhydramnios because baby has no hypothalamus/posterior pituiatry → urinating all the time

lack of fetal movement
disorganized substance: no diencephalon, no prosenephalon

FAS, CMV, any trisomy

Lissencephaly: agyria, absence of foldings 2° to chrom deletion, freq assoc. w/ microcpehaly

maternal diabetes, trisomy 13

failure of the cerebral hemispheres to separate: one single ventricle and fused basal ganglia

Manifestations range form aSx to reading with each eye separately

key is the batwing deformity of the lateral ventricles

Enlarged posterior fossa
absent cerebellum
posterior fossa midline cyst

Nonprogressive neurologic motor deficit

periventricular white matter softening (leukomalaica)
mostly 2° to prenatal injury of unknown cause
minority related to perinatalhypoxia

1st onset may be poor feeding

associated w/ prematurity

premature infants at risk,
50% of infants <1500g

hemorrhage w/in germinal matrix: junx of thalamus & caudate nucleus

may remain localized, may extend : damages brain substance: sudden increases in ICP → tonsillar herniation & cardiorespiratory depression

classically: diastatic (crosses sutures) fx over MMA or basal skull fx involving MMA

they concuss ± Δconsciousness → lucid → rapid progression

when hernia goes away they can completely recover, clot can be removed before damage

does not req trauma, classically young elderly, or traumatic with long delayed onset

∅ focal deficits: headache, confusion, deterioration

sequelae common after evacuation (it's been so long)

bruise on the brain (not a concussion)

coup: head immobile injury occurs at point of contact

contracoup: head mobile: injury occurs opposite point of contact
as long as the head is free to move: contracoup cord injury

Metabolic injury of the brain

by definition reversible neurologic dysfnctions due to change in momentum

postconcussive sx may occur

blow to side of head or occiput

consequences are meninigitis from leaking fluid and orbital ecchymosis and mastoid ecchymoses

Hypotension/nonperfusion injuries:

Watershed infarct: wedge shaped
laminar necrosis from lack of perfusion
loss of cerebellar perkinjie
necrosis of Sommers CA1 sector of hippocampus
pyramidal cells in cortical gray matter.

75% due to htn
occur when a small parenychmal blood vessel suffers a charcot bouchard microaneyruism

vast majority: ganglionic hemorrhages: putamen basal ganglia

else lobar region, those are cocaine, cerebral amyloid angiopathy

In Situ Thrombotic Stokes:
1. Carotid
2. MCA at its trifurcation
3. Basilar

Embolitic Strokes:
-post MI mural wall thrombi
-vegitative endocarditis
-afib is the one you dont' suspect
-carotid

Embolitic Strokes become hemorrhagic once blood begins to reperfuse the dead ts

Lacunar Infarcts

prolonged htn → arteriolar damage → liquifactive necrosis

tend to be multi-infarct from multiple arterioles enduring the same conditions

most common locations:pons and basal ganglia (lenticulostriate arteries)

left internal carotid infarction

Right internal carotid infarction

Right MCA infarction

Left MCA infarction

basal infarction
leads to coma

40% ACA
33% MCA
20% ICA bifurcation
5% Basilar/PCA bifurcation

There is a congenital predisposing defect in the walls
Gap in circular muscle at bifurcation → only elastic membrane hold s it in → elastic membrane failure = aneurysm

Most common in: Smokers, HTN, Adult Polycystic Kidney Dz, Turner's, Ehlers Danlos, Marfans, Neurofibromatosis

Complications: Subarachnoic hemorhage fatal in up to half of pts

AV malformation: arteries connect directly to veins → Fatal SAH/ IC bleed

most commonly MCA distribution

most commonly hematogenously
else basal skull fracture, osteomyelitis

meningitis & encephalitis

2 ascending infections: herpes & rabies

Acute meningitis

Neonates (≤28 days): GBS, E coli, Listeria
Infants: Pneumococcus, N meningitids, H influenza prior to immunization
[Choldhood - Young Adult: N meningitidis
Elderly: Pneumococcus]

Neonates (≤28 days): GBS, E coli, Listeria
Infants <2: H influenza prior to immunization
<5: Pneumococcus, N meningitids,
Choldhood - Young Adult: N meningitidis
Elderly: Pneumococcus

Complications: Deafness (10%), Arachnoiditis, Communicating hydrocephalus, Seizures

NB: Neisseria meningitis: DIC, Waterhouse-Friedrichsen Sro: acute adrenocortical hemorrhage with hypocortism and adrenal collapse

see slide 55

Pts with cardiac or pulmonary infections

fibroblast proliferation

PMN's, pus, necrotic debris in center
increasing blood vessels = our ring enhancing lesion on x rays

cause: Coccy (Spherules, Giant cells), Cryptococcus (Thick capsule), Aspergillus, Mucor

Crypto + Immunocompromised = colonies: soap bubbles of gelatinous colonies, no immune response
In immunocompetant granulomatous vasculitis

Brain abscess

Brain abscess

increased blood vessels around the periphery of an abscess

Crypto, Mucor, Aspergillus

→ infarction

3 possible manifestations:

Meningovascular (infarctions)

Frontal lobe neuronal loss/atrophy: Paresis (PAREsis) ΔPersonality, Δaffect, hyper-Reflexia, Eyes: accomodate to near vision but do not react to light (aka paretic syphilis/leutic dementia)
--Micro morphology: ependymal granulations/granular ependymitis + rod cell microglia

Tabes dorsalis: classic slapping gait: pick it up high and land hard because they have lost their proprioception; consequence: Charcot Joint; pain from inflammation of dorsal root column

Argyll-Robertson pupil

a sign of paresis in neurosyphilis

Frontal lobe neuronal loss/atrophy: Paresis (PAREsis) ΔPersonality, Δaffect, hyper-Reflexia, Eyes: accomodate to near vision but do not react to light (aka paretic syphilis/leutic dementia)

Micro morphology: ependymal granulations/granular ependymitis + rod cell microglia

Tabes Dorsalis: slapping gait

2° to posterior column degneration of neurosyphilis: lost proprioception

consequence: Charcot Joint

pain is from inflammation of dorsal root column

Buzz word for Viral Encephalitis

Perivascular Cuffing
Neruonophagia
Glial Nodules

Buzz word for Viral Encephalitis

Perivascular Cuffing, Neruonophagia, Glial Nodules

Buzz word for Viral Encephalitis

Perivascular Cuffing, Neruonophagia, Glial Nodules

Herpes Simplex

Behavior Changes Immediately with Headache because you lose the temproal lobes

CMV

Cytoplasmic Eosinophilic Inclusions

Rabies

Affects Hippocampus and Cerebellar Purkinje cells

Progressive Multifocal Leukoencephalopathy

JC polyoma virus, an opportunistic virus allowed by AIDS

Subacute Sclerosing Panencephalitis:
ie measles before the age of 2

giant cell groups/clusters

opportunistic infx:
--JC polyoma virus → PMLE

Creutzfeldt-Jakob Dz, Sporadic most common

Death in less than a year

Conformational change of PrPc → PrPsc → chain rxn

Morphology: Cytoplasmic Vacuoles, Kuru Plaques, Neuronal Death

Rapidly progressive dementia
Startle Myoclonus
Periodic Spike Wave Complexes on EEG

Sporadic most common
Death in less than a year

Morphology: Cytoplasmic Vacuoles, Kuru Plaques, Neuronal Death

Tuberculoid: Macular Lesions, Paucibacillary, Nerve destrx via Inflammation, Granulomas, Skin test +, No Complexes; Does not die of dz;

Lepromatous: Macular Lesions + Skin Nodules, Multibacillary, M∅ contain AFB, Nerve destrx via Bacillus infiltration, Skin test negative, inappropriate CD8 response Antigen-antibody complexes: Erythema Nodosum, Glomerulonephritis, vasculitis; infectious bacterial shedding. Dies of disease

Both Damage Nerves → Loss of Sensation Injury
→ Claw Hand, Charcot Joint,

Infects the RBC's

West Coast of Africa req's Duffy Antigen

Survival Benefits from: Duffy -, G6PD deficiency, Thalassemia

M∅ cause hepatosplenomegaly and pigmentation, you can rupture a big liver

some people die from hemolysis with a hemoglobinuria and an ATN death: blackwater fever

most vicious form was falciparium: multiple parasites in single cell, malaria likes to attach to walls of blood vessels → MI, die of ring shaped hemorrhages in the brain

mechanism of death of falciparum malaria

falciparum malaria particularly vicious: multiple parasites/cell, likes to adhere to walls of blood vessels,

Death due to depressed respiratory drive &Vfib

Complications:
infx, Rhabdo, ATN, [Ileus, GI bleed, hepatic dysfnx]

Injury due to ice crystals destroying cells

Ischemia 2° to endothelial activation → gangrene;
--tx ischemia with thrombolytics

Edema
Acute Mountain Sickness: HA, Lassitude, Difficulty sleeping
Retinal Hemorrhages
"Deterioration" over 14kft
Pulmonary & Cerebral Edema

Rhabdo w/ ARF
Arrhytmias
Cerebral Edema
ARDs
Renal Failure
DIC
[GI hemorrhage, Acute hepatic failure]

1st Degree: no problems other than pain and discomfort

2nd: necrosis c risk infx, depending on amt: fatal hypovolemic shock

3rd degree: below level of skin appendages: require skin graft

Fern Pattern: RBC's fixed in veins for 24h

Fetal loss in 1/2 of pregnants
Cardiac asystole
apnea
Hearing loss: both ruptured ear drum &U sensineural
Cataracts
Rhabdo
Fx
Ruptured Liver
Areflexia
Personality Changes

Flame shaped & dot-and-blot hemorrhages

Cotton wool spots: infarcts of nerve fiber layer

Macular star: exudate accumulation around macula in spoke fasion (malignant htn)

Optic disc edema

AV Nicking: atherosclerosis

Hypertensive Retinopathy:

Flame shaped & dot-and-blot hemorrhages

Cotton wool spots: infarcts of nerve fiber layer

Macular star: exudate accumulation around macula in spoke fasion (malignant htn)

Optic disc edema

AV nicking: atherosclerosis

Diabetic Retinopathy

neovascularization on top of hemorrhages
hemorrhages started as ruptured aneurisms and revascularization from vEGF

Diabetic Retinopathy

neovascularization on top of hemorrhages
hemorrhages started as ruptured aneurisms and revascularization from vEGF

Single Cherry Red Spot (Macula Densa) on pallor field

can be thrombotic, atherotic, embolotic

Retinal Artery Occlusion

Red Spot is Macula Densa

occlusion can be thrombotic, atherotic, embolotic

Massive Hemorrhagic & Pappiledema

better outcome than retinal artery occlusion

any hypercoagulable state

Retinal Vein Occlusion

better outcome than retinal artery occlusion

any hypercoagulable state

Old Folks

Dry slowly progressive form
drusen: yellow thickenings (german for stony nodule)
geographic pigmentary retinal atrophy resulting in scarring

there is a rapidly progressive wet form with vascularization of the mascula, has to be of the macula

Sign: metamorphosia: wavy lines on amlser grid

(diabetic does cause macular edema but not vascularization)

Retrolental Fibroplasia

mediated by vEGF

reticulated "bone spicule" pattern of pigmentation

pigmented a disease of retinal pigmentary epithlium or pigment in some way

young adults progressive blindness

Getic defects in photoreceptor proteins leads to apoptosis of rods and cones

Retinitis Pigmentosa

reticulated "bone spicule" pattern of pigmentation

pigmented a disease of retinal pigmentary epithlium or pigment in some way

young adults progressive blindness

Getic defects in photoreceptor proteins leads to apoptosis of rods and cones

Secondary to nutritional deficiency: tobacco-alcohol amblyopia

Secondary to toxins
--Methanol; lead

Acquired mitochondrial defects: toxins, formic acid, low folate

Hereditary mitochondrial defects: Leber hereditary optic neuropathy

Vision loss secondary to demyelination of the optic nerve

First manifestation of many cases of multiple sclerosis; ~ 40% develop MS w/in 5 years* (*80% cited in recent lecture by specialist in MS)

May fully recover vision w/o sequelae or other manifestations of systemic disease