GNMD 6044 Final study guide CNS, PNS, Amyloidosis
1. Acute pyogenic meningitis (bacterial) – E, Age related, CF, M, C
a. It is an inflammatory process of the leptomeninges (aka thin meninges: pia & arachnoid is csf) and CSF
within the subarachnoidal space
b. Etiology (in the test)
 E. coli, group B streptococci (neonates)
 H. influenzae (infants, children)
 N. meningitidis (adolescents, young adults), epidemic
 Streptococcus pneumoniae, Listeria monocytogenes (adults, elderly)
 Klebsiella or anaerobics (immunosuppressed)
c. Clinically
 Starts with Fever, headache, N/V, photophobia, irritability, clouding of consciousness, and neck and
back stiffness. Kerning and Brudzinski positive.
 CSF – cloudy or purulent, increased pressure, 90,000 neutrophils/mm3, elevated protein level,
marked reduced glucose. Presence of bacteria in smears or cultures.
 Lumbar puncture, smear, culture, immunoelectrophoresis, CT.
 Extravasation of fluid  plasma protein, increased pressure
 Extravasation of cells  neutrophils in CSF
 Glucose is reduced because the bacteria eats the glucose
d. Morphology
 exudate within the leptomeninges, located at the base of brain (H. influenzae), h. Flu can cause
meningitis in children around the base of the brain…or at cerebral convexities near sagittal
sinus (Pneumococcus). Pneumococcus in convexities more common in adults
 Purulent Meningitis – A creamy exudate opacifies the leptomeninges. Probably Neisseria meningitides
or step pneumo

Histology – neutrophils fill the subarachnoid space
2. Brain abscess – E, CF, M
a. It is an acute focal suppurative infection of the brain. Severe
b. Etiology
 Direct implantation (trauma, direct infection), local extension (mastoiditis, paranasal sinuses),
hematogenous spread (heart, lungs, bones, tooth extraction)
 Risk factors – acute bacterial endocarditis, congenital heart disease with right-to-left shunt, chronic
pulmonary sepsis with bronchiectasis. Verrucae in the valves may detach and go to brain causing an
infarct but accumulation of the bacteria will cause the abscess--Tetralogy of falot
 Streptococci and staphylococci (common)
c. Morphology – lesions with central liquefactive necrosis, surrounded by fibrosis, and edema.
 Common in frontal, parietal lobes and cerebellum
 Clinically – focal deficits, raised intracranial pressure w/ N/V. CSF – increased pressure, increased
WBC and proteins, normal sugar content because it’s not in csf but in the area of abscess
d. Complications – Abscess may open up in the ventricles causing ventriculitis, meningitis, sinus thrombosis
e. Prognosis – mortality rate 10%
3. Syphilis – M,
a. It is developed during tertiary stage of syphilis in 10% of patients left untreated. Patients with HIV are at
increased risk
b. Morphology
 Meningovascular neurosyphilis – is a chronic meningitis involving the base of the brain, cerebral
convexities, and spinal leptomeninges. It may be associated with obliterative endoarteritis and
cerebral gummas (tumor like). Inflammation of the arteries with thrombosis. Seizure,
hemiparesis, hemiplegia.

Paretic neurosyphilis – Damage to the substance of the brain due to an inflammatory
processMemory mood and behavioral changes arriving to severe dementia: invasion of the brain by
Treponema pallidum, progressive loss of mental and physical functions, memory disturbances,
mood alterations, disturbed speech, optic nerve atrophy, and severe dementia.
 Histology – inflammatory meningeal lesions and parenchymal damage located at frontal lobe
(loss of neurons, proliferation of microglia and astrocytes, gliosis (around the dying
neurons), iron deposits, presence of spirochetes, granular ependymitis)

Tables dorsalis
 damage by the spirochetes to the sensory nerves in the dorsal roots complicated with
ataxia, loss of pain sensation, skin and joint damage (Charcot joints), “lightning pains”,
 loss of deep tendon reflexes,
 urinary and fecal incontinence.
 Histology – loss of axons and myelin in the dorsal roots, and atrophy in the dorsal
columns of the spinal cords.

4. Viral encephalitis – E, M, CF
a. Arthropod-borne (Arbo) Viral Encephalitis
 It is an epidemic encephalitis most in tropical regions of the world. In the Western hemisphere, it is
caused by Eastern and Western equine, Venezuelan, St. Louis, and California types of arboviruses

b.
c.
d.
e.
f.
Clinically – reflex asymmetry, ocular palsies, seizure, confusion, delirium, stupor or coma.
 CSF – colorless, slightly elevated pressure, neutrophilic and lymphocytic pleocytosis,
elevated protein levels, normal sugar content
 Morphology – lymphocytic meningoencephalitis, multiple foci of necrosis of gray and white matter,
viral antigens inside the neurons, perivascular cuff, neuronophagia, gliosis (proliferation of
microglia around neuron).
Herpes Simplex Virus Type 1
 It causes encephalitis in children and young adults
 Clinically - alteration in mood, memory, and behavior.
 Subacute manifestations – weakness, lethargy, ataxia, seizure
 Morphology – encephalitis involves the temporal lobes, orbital gyri of the frontal lobes. Histology –
necrotizing (arteritis) and hemorrhagic lesions with intranuclear viral inclusion bodies in neurons and
glia.
Herpes Simplex Virus 2
 It causes severe encephalitis in 50% of neonates born by vaginal delivery to women with active
primary HSV genital infection
 In AIDS, it results in acute, hemorrhagic, necrotizing encephalitis
Varicella-Zoster Virus (Herpes Zoster)
 No neurologic manifestation with chickenpox
 Reactivation of virus in adults causes shingles – painful, self-limited, vesicular skin eruption in the
distribution of the dermatome, complicated with postherpetic neuralgia syndrome (10%)
 In AIDS patient (12%) - acute encephalitis, with early demyelination, necrosis, and inclusion bodies
in neurons and glia
Cytomegalovirus
 Common in fetuses (periventricular necrosis, microcephaly, periventricular calcifications) and
 AIDS patients (15-20%) with subacute encephalitis. Histology – ependymal and subependymal
regions of the brain are involved. Severe hemorrhagic necrotizing ventriculoencephalitis, and
chorioid plexitis. Prominent cytomegalic cells with intranuclear and intracytoplasmic inclusions
 CMV antigens demostrate intranuclear and intracytoplasmic inclusions in Purkinje cells of the
cerebellum.
Poliomyelitis
 It is caused by poliovirus a member of picorna group of enteroviruses
 In nonimmunized individuals it causes a subclinical or mild gastroenteritis, and in a small
fraction it involves the nervous system
 Clinically
 Subclinical (95%) Gastroenteritits, nonparalytic (meningitis), paralytic (post polio
syndrome)
 Meningeal irritation (fever, malaise, and headache)
 Paralysis (m. neck, trunk, four limbs, respiratory muscles); mild cases – asymmetric and
patchy paralysis in lower limbs; CSF – aseptic meningitis.
 Postpolio syndrome – it is developed 25-35 years after the resolution of the initial illness
with progressive weakness, decreased muscle bulk, and pain
 Morphology
 Loss of motor neurons with flaccid paralysis, muscle wasting, hyporeflexia, which are
permanent. Histology – mononuclear cell in perivascular cuffs and neuronophagia of
the anterior horn motor neurons of the spinal cord, with the presence of poliovirus
inside the cells
 Complications – mortality 5-25% - paralysis of respiratory muscles, myocarditis
g. HIV-1 Meningoencephalitis. Subacute encephalitis
 Clinically – dementia, mental slowing, memory loss, mood disturbances, apathy and
depression.
 Motor abnormalities, ataxia,
 Bladder and bowel incontinence, and seizure.
 X-ray – diffuse cortical atrophy, focal abnormalities in the white matter, ventricular
dilation
 Morphology – meninges are clear, dilation of ventricles, sulcal widening, abnormal cortical
thickness.
 Symetric demyelination in corona radiata

Histology – infiltrates of microglial nodules with multinucleated giant cells, tissue necrosis,
gliosis, located in subcortical white matter, diencephalon, and brain stem. Presence of HIV in
CD4 lymphocytes and multinucleate macrophages, diffuse astrogliosis
5. Rabies – M, L, CF
a. It is transmitted to humans by the bite of a rabid dog, or exposure to bats. Virus enter the CNS by ascend
along the peripheral nerves from the wound site. Incubation period 1-3 mo
b. Clinically- malaise, headache, fever, local paresthesias around the wound (diagnostic). Sometimes,
severe encephalitis with CNS excitability, painful touch, violent motor responses, convulsions. Contracture of
pharyngeal muscles on swallowing with foaming at the mouth (hydrophobia), meningismus, flaccid paralysis,
alternating mania and stupor, coma and death (respiratory center failure)
c. Morphology
 Brain edema and vascular congestion.
 Histology – neuronal degeneration, inflammatory reaction in the basal ganglia, midbrain, floor of the
fourth ventricle, and medulla.
 Negri bodies – cytoplasmic, round to oval, eosinophilic inclusions – in pyramidal neurons of
the hypocampus and Purkinje cells of cerebellum. Presence of rabies virus within Negri
bodies
6. Encephalitis (measles, JC virus, etc) – L, M
a. It is a viral encephalitis caused by polyomavirus (JC virus), characterized by demyelination (virus infects
oligodendrocytes)
b. It is present in immunocompromised individuals
c. Clinically – focal and progressive neurologic symptoms and signs.
 CT and MRI - multifocal lesions in the hemispheric or cerebellar white matter.
d. Morphology – patches of irregular, ill-defined destruction of the white matter from mm to cm, located in
the cerebrum, brain stem, cerebellum, and spinal cord.
e. Histology – patch of demyelination, with lipid-laden macrophages, reduced number of axons, bizarre giant
astrocytes, and oligodendrocytes that contain viral antigens in the periphery.
7. Subacute sclerosing panencephalitis – measles
a. It occurs in children or young adults, months or years after an initial infection with measles. It represents
a persistent but nonproductive infection of CNS by altered measles virus. Koplik spots are only found in
early stage rubeola exposure, not as a sequelae
b. Clinically – cognitive decline, spasticity of limbs, seizures.
c. Morphology – widespread gliosis, myelin degeneration, viral inclusions with measles virus within the
nucleus of oligodendrocytes and neurons, inflammation of white and gray matter, neurofibrillary
tangles,.
8. Cerutzfeldt-Jacob’s – E, CF, M
a. Transmissible Spongiform encephalopathy (Prion disease)
b. It is characterized by “spongiform change” caused by intracellular vacuoles in neural cells, dementia,
and the presence of prion protein PrP.
c. Pathogenesis - PrP is a normal protein in neurons. It becomes pathogenic when is changed from -helix
isoform PrPc to an abnormal -pleated sheet isoform PrPsc that is resistant to digestion with
proteases. This change occurs spontaneously and slowly (sporadic cases) or at a higher rate caused by
mutations (familial cases). PrPsc can corrupt the integrity of normal cellular components. CJD - point mutation
in PrPN gene (D178N) and Val at codon 129. Fatal familial insomnia - point mutation in PrPN gene (D178N)
and Met at codon 129. Aggregates of PrPsc protein inside the cell cause the neuronal death.
d. Morphology– spongiform transformation (gray matter) of the cerebral cortex, putamen, and caudate
nuclei.
e. Histology – small, apparently empty, microscopic vacuoles in the perikaryon/cytoplasm of the neurons.
Neuronal loss, reactive gliosis, no inflammation.
f. Fatal familial insomnia – not spongiform pattern, neuronal loss, reactive gliosis in thalamus.
g. Clinical
 rapidly progressive dementia with changes in memory, and behavior, involuntary jerking muscle
contractions, ataxia.
 Sporadic 85%
 peak incidence 7th decade
 iatrogenic transmission – cornel transplantation, deep implantation electrodes, contaminated
preparations of GH. Fatal within 7 mo.
h. Variant CJD vCJD – young adults , like CJD, related with the ingestion of beef from cows with bovine
spongiform encephalopathy.
i. GSS – inherited disease with mutation of PrPN gene, chronic cerebellar ataxia, and progressive dementia.
Fatal in several years
j. Fatal familial insomnia – sleep disturbances, ataxia, autonomic disturbances, stupor, coma, fatal within 3 y.
9. Multiple sclerosis – CF, M
a. It is characterized by episodes of neurologic deficit, separated in time, and white matter lesions (sclerotic
plaques), separated in space. Incidence 1/1000 individuals.
b. Female/male 2:1, 20-30y/o
c. Relapse and remission that last for many year (time)
d. Lesions (WM) Spread in brain an SpC (space)
e. Pathogenesis
 Environmental (infection roseola virus, trauma, pregnancy), genetic, and immune factors. 15fold higher risk in HLA-DR2 individuals, and in first-degree relatives.
 Cell-mediated immunity (Autoimmunetype 4 HS) with infiltration of CD4+ and CD8+ lymphocytes and
macrophages that induce oligodendrocyte injury.
 Antibody-mediated damage of myelin (type 2 HSR)
 Genetic: Pregnancy may awaken the dz

Morphology
 Multiple, well-circumscribed, depressed, glassy, irregular plaques associated with
surrounding sclerosis of the white matter throughout the CNS (lateral ventricles, optic nerve
and chiasm, brain stem, cerebellum, spinal cord)

Clinical
 Unilateral visual impairment for a few days (optic neuritis, retrobulbar neuritis), ataxia,
nystagmus, weakness, numbness, tingling (sensorimotor), spasticity (central),
dysarthria, difficulty in controlling of bladder, dementia
 CSF – mildly elevated proteins, gamma globulin is increased showing oligoclonal bands,
moderate pleocytosis (B cells)- b cells are basically producing the G globulins (antibodies
against myelin)
Complications
 respiratory paralysis, UTI
Variants
 Devic disease (RAPID progression), neuromyelitis optica - bilateral optic neuritis and
prominent spinal cord involvement. It is rapidly progressive, with more destructive lesions
 Acute MS, Marburg form – young individuals, fulminant course in several months. Large and
numerous plaques


10. Alzheimer’s disease – M, CF, P
a. Degenerative diseases are characterized by progressive loss of neurons in patients without previous neurologic
deficit
b. Alzheimer’s is a degenerative disease affecting the Cerebral cortex
c. It is the most common cause of dementia in the elderly, starting after 50y; 5-10% familial; in Down syndrome
after 45y/o
d. Clinically
 alteration in mood and behavior (sleeplessness, agitation, wandering, anxiety, and depression),
progressive disorientation, memory loss, language deficit, loss of mathematical skills, loss of learned
motor skills, aphasia, Dementia, and after 5-10y – pts becomes incontinent, mute, and immobile.
Pneumonia causes death. Accurate dx only in 80-90%
 Neurons that produce Acetylcholine are lost (important to know for test perhaps)
 MMB-Mood Memory Behavior
 Atherosclerosis can cause dementia
e. Morphology
 Cortical atrophy, narrow gyri, widening of cerebral sulci in frontal, temporal (hippocampus), and
parietal lobes, and ventricular enlargement
f. Histology – neurofibrillary tangles (bundles of filaments in the cytoplasm of the neurons that displace or
encircle the nucleus. Paired helical filaments, protein tau, ubiquitin, and amyloid -peptide)
 senile (neuritic) plaques (focal, spherical collections of dilated, tortuous silver-staining neuritic
processes surrounding a central amyloid core. The dominant component of plaque core is A-peptide
that derives from APP)
 amyloid angiopathy (amyloid deposition around the blood vessels)- brain becomes malnourished
 Granulovacuolar degeneration – small intraneuronal vacuoles which contain an argyrophilic granule
 Hirano bodies – rod like, elongated, glassy, eosinophilic bodies containing actin in hypocampal
pyramidal cells, red/pin color from stain
g. Pathogenesis
 Amyloid -peptide – Amyloid precursor protein APP is a transmembrane protein with unknown
function. APP is broken down by - and -secretases which generate A-peptide from APP. Apeptide aggregates and generates the amyloid that is found in the brain and is neurotoxic for the
neurons
 Hyperphosphorylated Tau protein (also neurotoxic)
 Presenilins – in familial Alzheimer disease, there is mutation in genes for presenilin-1 and
presenilin-2 that are responsible for increased production of A- peptide, and they are target for
cleavage by caspase proteases, playing a role in apoptosis of neurons
 Apolipoprotein E – mutation in 4 loci of Apo E gene increases the risk (early onset) for Alzheimer
disease. Apo E is present in plaques
 Mutation in 2-macroglobulin increases the risk of Alzheimer disease
11. Parkinson’s – CF, M, P
a. Parkinsonism is a syndrome characterized by
 diminished facial expression
 stooped posture
 slowness of voluntary movements
 progressively shortened, accelerated steps
 rigidity
 “pill-rolling” tremor
b. There is damage to nigro-striated dopaminergic system
c. Idiopathic Parkinson Disease (Paralysis agitans)
 It shows an autosomal dominant inheritance
 Pathogenesis – Mutation in the gene for -synuclein, a protein in the presynaptic terminal, causes
accumulation of it in inclusions characteristic for IPD, the Lewy bodies
 Morphology
 pallor of the substantia nigra and locus ceruleus
 loss of the pigmented, dopaminergic neurons in the above regions with gliosis
 Lewy bodies – single or multiple intracytoplasmic, eosinophilic inclusions with a dense core
and a pale halo - inside the neurons; located - cerebral cortex, amygdala, and brain stem
neurons
 Clinically- Parkinson syndrome, dementia
12. Huntington’s chorea – Inheritance, Etiology E, morphology M, clinical features CF, Complications C, Pathology P
a. Not congenital but inherited in Autosomal dominant pattern
b. characterized by progressive movement disorders, dementia, and degeneration of striatal neurons
c. Pathogenesis
 the loss of striatal inhibitory output from the degeneration of GABA-containing neurons, to the
external portion of the globus pallidus. The gene responsible for the disease is located on chrom.4, and
it shows unstable CAG trinucleotide repeats. Protein Huntingtin. Increased number of repeats –
anticipation
d. Morphology – small brain with atrophy of the caudate nucleus, and putamen, and dilation of the third and
fourth ventricles. Histology – severe loss of striatal neurons – GABA, enkephalin, and substance P neurons
e. Clinically – the disease starts at the 3rd or 4th decade; dementia and chorea (jerky, hyperkinetic or dystonic
movements affecting all parts of the body); later – parkinsonism, bradykinesia, and rigidity. Increased risk of
suicide and infections. Death within 15y.
13. Amyotrophic lateral sclerosis – CF, M,
a. Degenerative Diseases affecting Motor Neurons
b. It is characterized by problems in the nerve that causes atrophy of muscle, cortex and spinal cord affected.
c. Neuronal muscle atrophy (amyotrophy) and hyperreflexia due to loss of lower motor and upper motor
neurons in the anterior horns of the spinal cord and corticospinal tracts, respectively. Men, fifth decade. 5-10%
familial with autosomal dominant inheritance
d. Pathogenesis – cause unknown. In familial cases, missense mutation in copper-zinc superoxide
dismutase gene on chrom.21 which causes and accumulation of oxide free radicals (it’s usually an antioxidant)
e. Morphology: Ventral root is motor neurons
f.
Clinical
 Asymmetric weakness of the hands, dropping objects, difficulty performing fine motor movements,
cramping, and spasticity of the arms and legs.
 Later, diminished muscle strength, and mass
 Respiratory infections due to involvement of respiratory muscles
 In some pts, anomalies of deglutition and phonation dominate
14. Chronic alcoholism – M
a. Niacin deficiency- pellagra
 Features - dermatitis (exposed areas: face, hands, knees), diarrhea, dementia - psychosis, glossitis
- inflammation and edema cause a large, red tongue
b. Thiamine (B1) deficiency, Beriberi
 Wernicke-Korsakoff syndrome (dry Beriberi) – ataxia, ophthalmoplegia, polyneuropathy, retrograde
amnesia and confabulations. Common in Chronic alcoholism
 Morphology – petechial hemorrhage and necrosis in mammillary bodies, and paraventricular
regions: third and fourth ventricles
c. Wernicke encephalopathy, because of thiamine deficiency. Mental confusion, ataxia, abnormal ocular
motility, polyneuropathy
d. Korsakoff psychosis - retrograde amnesia, confabulatory symptoms
e. Alcoholic cerebellar degeneration: unsteadiness of gait, ataxia, incoordination, there is destruction of
Purkinje cells in the (upper) cerebellum
f. Central pontine myelinolysis - progressive weakness of bulbar muscles that causes dysphagia and
dysarthria, and inability to swallow. Quadriparesis, coma, death
g. Polyneuropathy - deficiency of thiamine and other B vitamins, Numbness, paresthesias, pain, weakness,
ataxia
15. Gliomas (most common brain tumors) – types T, L
a. Brain tumors in general: 20% of cancer of childhood, and 70% arise in posterior fossa, while in adults, in
cerebral hemispheres.
 Gliomas
 Neuronal tumors
 Poorly differentiated neoplasms
 Meningiomas
b. Gliomas: They include astrocytomas, oligodendrogliomas, and ependymomas
 Astrocytomas: Fibrillary Astrocytoma and Glioblastoma Multiforme
 80% of adult primary tumors; in cerebral hemispheres; 4-6 decade
 Clinically – seizures, lethargies, headache, and focal neurologic deficit. They become
more anaplastic with time
 Fibrillary astrocytoma, mostly benign but if it stays there for too long becomes more aggressive
(gliobastoma multiforme)
 Morphology





◊ Diffuse Fibrillary Astrocytoma is well-differentiated (less cells and bv), or evolves
to less differentiated (more cell, bv)Anaplastic astrocytoma and Glioblastoma
multiforme
 Genetics
◊ low grade astrocytoma - inactivation of p53 gene, and overexpression of PDGF-A and
its receptor genes; higher grade astrocytomas – mutation in Rb gene; glioblastomas –
amplification of EGFR gene
 Pilocytic Astrocytoma: Common in children and young adults; located in cerebellum;
Morphology – cystic tumor with a nodule in the wall of the cyst. Prognosis – slow grow; pts
survive for 40y after total resection
 Pleomorphic Xanthoastrocytoma: Children and young adults; temporal lobe; history of
seizure. Morphology – neoplastic astrocytes, with abundant reticulin deposits, and
inflammatory infiltrate
Oligodendroglioma
 5-15% of gliomas; located in cerebral hemispheres; present in 4-5th decade
 Clinically – several years of neurologic complaints, and seizure
 Morphology – well-circumscribed, gelatinous, gray mass with cysts, hemorrhage, and
calcifications
 Prognosis – better prognosis than astrocytomas. 5-10y survival rate
Ependymomas
 5-10% of tumors in 2nd decade; located near the fourth ventricle.
 Morphology – solid or papillary masses extended from the floor of the ventricle.
 Clinically – hydrocephalus, N/V, CSF dissemination.
 Prognosis – poor, 4y survival rate
Myxopapillary ependymomas – occur in filum terminale of the spinal cord
Subependymomas – solid, calcified, slow growing nodules attached to the ventricular lining and
protruding into the ventricle
Choroid plexus papillomas – in children in lateral ventricles, in adults in 4th ventricle. Hydrocephalus.
16. Medulloblastoma – M, location L, age A
a. common in children;
b. located in midline of cerebellum; vermis
c. well-circumscribed, gray, friable tumor composed of sheets of
d. anaplastic cells forming Homer-Wright rosettes.
e. Very malignant, disseminates through CSF; radiosensitive
17. Meningiomas – L, A
a. Benign tumors of adults
b. Morphology – well-defined, encapsulated tumor masses arising from meningothelial cells of arachnoid, with
their base on dura compressing the brain (pushing the brain down, not in the brain. Psammoma bodies
(calcifications) are present
c. Clinically – slow growing, express progesterone receptors and grow during pregnancy
d. Metastatic tumors
 Primary tumor is located in the lungs, breast, skin (melanoma), kidney, GI tract
18. Schwannoma – L, M
a. Schwann Cells, line axons and responsible for the production of myelin
b. Well circumscribed, encapsulated masses that are attached to the nerves. Tumors show cellular areas with
Verocay bodies, and looser, myxoid regions
c. Clinically – common location in the cerebellopontine angle involving the eight nerve – tinnitus, hearing
loss (acoustic neuroma), trigeminal nerve, and dorsal roots. Associated with neurofibromatosis type 2.
19. Guillain-Barre syndrome – E, M, CF, C
a. Disease of the Peripheral Nerves: Inflammatory Neuropathies:
b. (Acute Inflammatory Demyelinating Polyradiculoneuropathy)
c. It is the most common life-threatening disease of PNS, characterized by ascending paralyses, inflammation
and demyelination of peripheral nerves and spinal nerve roots (radiculoneuropathy)
d. Autoimmune disease type 4 hsrxn
e. Type 2 association with circulating myelin antobodies
f. Pathogenesis
 Preceded by a viral infection (Campylobacter jejuni, cytomegalovirus, Epstein-Barr virus, and
Mycoplasma pneumoniae), vaccines, surgery
 T cell-mediated immune response is generated – segmental demyelination of axon by macrophages
and lymphocytes. Circulating antibodies (Anti-GM1) are present
g. Morphology
 Inflammation of peripheral nerve – perivenular and endoneurial infiltration by lymphocytes,
macrophages, and plasma cells located in the spinal and cranial motor roots. Segmental
demyelination. Oligoclonal bands involved
h. Clinical course
 Ascending paralysis (legs, arms, face), weakness, disappearance of deep tendon reflexes;
Sensory (Pain, parasthesias, dysesthesias); Autonomic (tachycardia, hypo/ hypertension,
flushing, sweating, sphinchters); elevation of CSF protein due to inflammation
i. Complications
 Respiratory paralysis, autonomic instability, complications of tracheostomy
j. Prognosis – Most (good recovery), 10-20% disability, 3% relapses, mortality rate 2-5%
20. Diabetic neuropathy - type, M
a. Diabetes in bv’s induces atherosclerosis
b. In small bv’s –hyaline arteriosclerosis
c. Several patterns: distal symmetric sensory or sensor-motor neuropathy, autonomic neuropathy, focal or
multifocal asymmetric neuropathy
d. Most common is distal symmetric sensorimotor neuropathy characterized by decreased sensation in
distal extremities, loss of pain sensation, ulcers, less evident motor neuropathy
e. Morphology
 Segmental demyelination, relative loss of axon fibers. Arteriolo-hyalinization of Endoneural
vessels (vaso nervorum)
f. Clinically
 Peripheral neuropathy involves 50% of diabetics after 25y of diabetes.
 100% have conduction abnormalities,
 autonomic neuropathy in 20-40%
21. Carpal tunnel syndrome – E, CF,
a. Compression neuropathy – a nerve is compressed or entrapped within an anatomic compartment
b. Carpal tunnel syndrome – compression of median nerve at the level of wrist by transverse carpal ligament
c. Predisposing factors – pregnancy, osteoarthritis, hypothyroidism, amyloidosis, excessive usage of the wrist
d. Clinically – Mostly sensory, numbness and paresthesias of the tip of the thumb and first two fingers
e. Pathology - ischemia, edema of myelin sheath, demyelination
22. Bell’s palsy paralysis no wrinkles form, in stroke paralysis wrinkles form
23. Thoracic outlet syndrome - E, M, CF, C
a. Compression of blood vessels/nerves in the space between clavicle and first rib
b. Neurogenic
 Brachial plexus - spasm/hypertrophy of scalene m.
 Paresthesia in arm/fingers, pain in neck/shoulder/hand, weakening grip, atrophy of thenar/hypothenar
eminences
c. Vascular
 Subclavian vein/artery
 Veins - arm swelling, cyanosis, pain
 Arteries - muscle cramping, coldness/blanching of hand
d. Unknown/nonspecific
 Chronic pain in the area of thoracic outlet that worsens with activity, but specific cause of pain cannot
be determined
e. Etiology
a. Anatomical defects, posture, trauma, repetitive activity, overweight, pregnancy
24. Amyloidosis – primary, secondary, familial, isolated, types of proteins, morphology, clinical
a. It is a disease that is characterized by deposition of Amyloid protein in different organs
b. Common components of Amyloid
 Amyloid P
 Laminin, collagen IV, proteoglycans
 Apo E
c. Two types of Amyloid
 AL – Primary amyloidosis, MM, B-cell lymphoma
 Ig light chain
 excess production of immunoglobulin and abnormal assembly in MM, and B cell
lymphoma (excess light chains)
 AA – Secondary amyloidosis (RA, Ankylosing Sp, SLE, Lung abscess, TB, osteomyelitis), FMF,
Cancer (Hodgkin’s, renal cell ca)
 AA from serum amyloid protein
d. Stain red w/Congo red
e. Beta-pleated sheet
f. Diagnosis – biopsy
 Gingiva
 Rectum
 Abdominal subcutaneous fat
 Usually deposited in the framework of tissues in b/w cells, in the connective tissue that forms the
framework of tissue.
 Dentists can dx because of swelling of tongue
g. Clinical Classification of Amyloidoses
 Systemic deposition
 Primary
 Secondary
 FMF - pyrin
 Isolated
 Single organs – heart, kidney, GI, skin, joints, etc
 Aorta atherosclerosis – medin derives from lactadherin, produces by SMC
◊ Medin is the amyloid material produced in smooth muscle cells
 Alzheimer disease – Aß amyloid (peptide) derived from AßPP in the cell membrane
◊ AB peptide deposited in the neurons, (neurofibrillary tangles Alzheimers)- forming to
so called senile plaques near BV’s  amyloid angiopathy
 DM type 2 – amylin a variant of calcitonin
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◊ Deposition of amyloid material in between beta cells in the islets of langherhan’s,
damage to islets= more severe diabetes
Senile cardiac amyloidoses – tranthyretin secreted by liver, transports T3, T4
Spongiform Encephalopathy – PrP protein
◊ Spongiform prions inside vacuoles in neurons. Dementia chorea
Medullary carcinoma of thyroid gland – amyloid is procalcitonin
◊ Pink material in cancer from procalcitonin medullary
AL amyloid - Ig light chain
AA amyloid
◊ Derives from Serum amyloid A SAA
◊ SAA is acute phase protein produced by the liver in acute/chronic inflammation
◊ Amyloid enhancing factor AEF promotes formation of amyloid (found inside
Macrophages)
h. Morphologic features of Amyloidoses
 Amyloid is deposited in the stromal network of the tissues. It increases the size of organs
 Deposition around blood vessels causes ( lower O2 and block nutrition/nourishment) atrophy
(Alzheimer)
 Blocks blood supply to the cells
 Intoxicate cells; Death of cells
i. Clinical features of Amyloidoses
 Kidney
 MM, Chronic inflammation, FMF complicated with nephrotic syndrome may have
Amyloidosis
 It progresses to renal failure
 Heart
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Amyloidoses causes restrictive cardiomyopathy, arrhythmia, sudden death
◊ Heart doesn’t fill with blood as well- amyloidosis and hemochromatosis are the most
common cause of restrictive myopathy
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Ganglia, BV, SMC of submucosa – reduces motility and absorption
Constipation, diarrhea, malabsorption
Enlarged tongue - dysphagia, dysarthria
GI