16-1 CNS and Muscle

q123456's version from 2016-06-01 18:44


Question Answer
Leukodystrophiesinherited dysmyelinating diseases in which the clinical symptoms derive from abnormal myelin synthesis or turnover
metachromatic leukodystrophy, krabbe disease
broca's and wernicke'smiddle cerebral artery (MCA)
inablity to produce language: speak or write>>broca's-->Expressive aphasia (***dysarthria: inability to move the muscles of the tongue)
Patient is aware of their problem

understand>>> Wernicke's>>>Aphasia/dysphasia
Inability to repeat phrases/understand language/read/write
speaks in long meaningless speech inablilty to use correct words to express the thoughts.
Patient is unaware of his problem
***the region of the temporal lobe also contain fibers of the visual radiations traveling to the the primary visual cortex.>>>also present with right upper quadrantanopia
B121)homocysteine >>>Methionine
2)methylmalonyl-CoA to succinyl-CoA by mutase

1 degeneration of the spinal cord>>>unstable gait, vibration sense is decreased over the lower extremities.
2 anemia>>>dyspnea, pallor and fatigability/Increased serum methylmalonic acid level
Degenerative diseases of the CNSalzheimer
Friedreich ataxia,
Huntington disease
frontotemporal dementiaatrophy of frontal&temporal lobes at early 50s
creutzfeldt jakob diseaseinfective prions(misfolded protein)>>>resistant to proteases, conversion of normal PrP to proteases resistant PrP
Bubble and holes spongiform change in gray matter
Alzheimer disease (AD)beta amyloid Aβ, positive with Congo red and apple-green birefringence with polarization
*Aβ is created when the transmembrane protein amyloid precursor protein (APP) is cleaved by β-amyloid converting enzyme and γ-secretase
chromosome 21>>>Down syndrome
most common cause of dementia in the elderly population.
cortical atrophy, plaques and neurofibrillary tangles, dilation of ventricles. MOST in the temporoparietal lobes and hippocampus, Occipital lobe is usually spared
risk factor: age, apolipoprotein E called ε4 (ApoE4).
B1wernicke syndrome
memmory loss
horizontal nystagmus
bilateral abducens palsy

chronic alcoholics (thiamine def)>>>atropy (loss of) cerebellar vermis and purkinje cells in the anterior lobes>>>gait and ataxia

glucose infusion must be accompanied by the admistration of thiamine since thiamine is a cofactor of enzymes responsible for glucose metabolism, infusion of glucose will exacerbate the preexisting thiamine deficiency, precipitating wernicke encephalopathy.

the role of ethanol in CNS: Increased GABA. withdrawal symptoms: shakes, tremor
malformation:defectA structural defect due to abnormal embryonic or fetal development.
cleft lip and cleft palate.
deformation: changeA change from the normal size or shape due to mechanical forces
virus infection CSFNormal glucose, elevated protein and lymphocytic pleocytosis
tension headache (bilateral)female, under stress, bilateral, muscle tenderness in the head/neck/shoulders
cluster headache (one side)one side headache+nasal congestion+eye tearing
headache, male, during sleep, behind one eye
The trigeminal nerve causes the eye pain associated with? Cluster headache
HSV-1temporal lobe involved encephalitis
lock incentral pontine myelinolysis: rapid correction of chronic hyponatremia -->
osmotic demyelination of the pons. 2-3 days after hyponatremia is corrected, difficulty speaking/swallow

large lesion in the brain stem (the base of the pons)
thrombotic stroke to the basilar artery
Measles subacute sclerosing panencephalitiskids+immigrated to the US
ataxia/myoclonus/visual problems
RNA virus in brain>>>hemagglutinin
normal pressure hydrocphalus NPHdistinguish normal pressure hydrocphalus (NPH) from Alzheimer:
the order of symptoms are important>>>gait disturbance+urinary incontinence>>>progressive demetia and emotional blunting

symmetrically enlarged ventricles>>>disrupts the periventricular pathways that transmit impulses from the cortex to the sacral micturition center>>> lack of inhibition from the cerebral cortex >>>frequent and uncontrolled micturition or urge incontinence>>>patient has no sensation of bladder fullness and no control over bladder function
Guillain-Barré syndromeacute demyelinating disorder
motor axons that results in ascending weakness that may lead to death from failure of respiratory muscles over a period of only several days

triggered by an infection (Campylobacter jejuni) or a vaccine, the most common lifethreatening diseases of the peripheral nervous system

Treatments include plasmapheresis (to remove offending antibodies)
intravenous immunoglobulin infusions (which suppress immune responses through unclear mechanisms)
supportive care, such as ventilatory support.
Diabetesthickness, hyalinization and narrowing of the walls of the arteries
hyperglycemia in peripheral nerve>>>increased cell osmolarity>>>facilitates water influx into the cell>>>osmotic damge to axons and schwann cells

autonomic neuropathy
changes in bowel, bladder, cardiac, or sexual function.

lumbosacral radiculopathies
asymmetric pain that can progress to lower extremity weakness and muscle atrophy.

distal symmetric sensorimotor polyneuropathy:
1 paresthesias and numbness in diabetes
2 the most common form of diabetic neuropathy.
3 causes a decreased ability to move or feel because of nerve damage

unilateral CNIII >>>
acute onset diplopia"down and out" position
levator palpebrae>>>ptosis

Diabetes: the most common cause of peripheral neuropathy
intracranial mass stain positive for synaptophysin:the neoplastic cells originate from neurons not astrocytomas
amyotrophic Latearal sclerosisupper and lower motor neurons
mutated SOD1
Myasthenia Gravisautoantibodies that block the function of POSTsynaptic acetylcholine receptors at motor end plates, which results in the degradation and depletion of the receptors.
ptosis or diplopia
anti-acetylcholine receptor antibodies
hyperplasia of intrathymic B cells (thymic hyperplasia) and thymom
Lambert eaton syndromelung carconoma,
autoantibodies against PREsynaptic calcium channels (voltage gated ion channels)>>>reduces the release of acetylcholine into the synaptic cleft.
ptosis in small cell lung carcinoma
weakness/swallow difficulty/vision problem
spina bifida occulta:myelomeningocele: the spinal cord and meningeal membranes protrude through the opening
spina bifida occulta: the spinal nerves usually aren't involved
Meningocele: the vertebrae develop normally, but the meninges are forced into the gaps between the vertebrae.
myelinperipheral myelin is made by Schwann cells
CNS myelin is made by oligodendrocytes
each Schwann cell in a peripheral nerve provides myelin for only one internode KA36-22, while in the CNS, many internodes are created by processes coming from a single oligodendrocyte
ischemic neuronal changeliquefactive necrosis: thrombosis or embolism>>>irreversible ischemic changes in the neurons>>>release of lysomomal enzymes>>>degradation of the tissue>>>phagocytic cells migrate into the area and remove the necrotic tissue>>>leave a cavity/astrocytes proliferate (gliosis)

first 12 hours: red neurons, edema, swell
up to 48hours: neutrophilic emigration
2-3weeks: mononuclear phagocytic cells

embolic infarctins of brain: Atheromatous plaques within the carotid A and aortic arch, myocardial dysfuntion, valvular disease and AF

the most susceptible neurons to ischemic hypoxic injury? hippocampus and neocortex and Purkinje cells of the cerebellum.

ischemic hypoxic injury: Neurons are more susceptible to hypoxic injury than are glial cells

irreversible neuronal damage and death: astrocytes proliferate at the site of injury (astrocytosis or gliosis)

Degenerative diseases

Question Answer
ParkinsonismDepigmented substantia nigra>>>Causes deficiency of dopamine
Pallidotomy:destroy globus pallidus
CT: KA22-6, 23-22
lewy body: round, eosinophilic and intracytoplasmic inclusions
Friedreich ataxiaGAA, chr 9, AR
spinal cord atrophy ( The first symptom to appear is usually gait ataxia, or difficulty walking. The ataxia gradually worsens and slowly spreads to the arms and the trunk. There is often loss of sensation in the extremities) KA36-28
gracile and cuneate nuclei within dorsal root ganglia-
associated with hypertrophic cardiomyopathy
Huntington disease (HD)KA 34-9
degeneration of the striatum (caudate and putamen). CT image
CAG Trinucleotide,
ventricles are dilated and atrophy of the caudate nucleus
loss of GABA containing neurons>>>decreased GABA in the brain
Degenerative diseases of the CNSatrophy of temporoparietal lobes and hippocampus>>>alzheimers's
atrophy of caudate, putamen, globus pallidus>>>huntington disease
depigmentation of substantia nigra (CT image)>>>parkinsonism
atrophy of spinal cord>>>friedreich
widespread neuronal loss and gliosis in subcortical sites with sparing of the cerebal and cerebellar cortices>>>progressive supranuclear palsy: ophthalmoplegia, pseudobulbar palsy, axial dystonia and bradykinesia
multiple sclerosisFacial lesions (adenoma sebaceum),
hypopigmented "ash leaf spots" on skin *NF1: Cafe-au-lait spots (pigmented)
cortical & retinal hamartomas,
seizures, mental retardation,
renal cysts and renal angiomyolipomas,
cardiac rhabdomyomas

10 year old boy, epilepsy, mental retardation, ovoid hypopigmented areas on the trunk, a red, yellow papules on the face and mouth (angiofibromata)

the most common of the demyelinating disorders
not hereditary, immune related (cell mediated response against white matter antigens), VITAMIN D related!!!
exacerbations and remissios over many years
e.g a 60 year old woman dies from a chronic progressive neurologic disease characterized by multiple periods of exacerbation and remission.

white matter of CNS oligodendrocyte depletion>>>reduced saltatory conduction
Duchenne and Becker Muscular DystrophyX chromosome,
dystrophin gene
Progressive replacement of muscle tissue by fibrosis and fat
causes dilated cardiomyopathy!!!
Myotonic dystrophyAbnormally slow relaxation of muscls>>>difficulty loosening one's grip after a handshake or inability to release the doorknob lately

the dystrophia myotonica protein kinase (DMPK) mutation

CTG repeats in the non coding region of DMPK
most common of muscular dystrophy in adult
prolonged muscle contractions not able to relax after use

Manifests in late childhood with gait abnormalities due to weakness of foot dorsiflexors, with subsequent progression to weakness of the intrinsic muscles of the hands and wrist extensors, atrophy of the facial muscles, and ptosis
hypertensive arteriolar sclerosisinternal capsule
Dermatomyositisthe most common inflammatory myopathy in children
red rash+ muscle weakness (starts in the neck and arm)
Mitochondrial myopathiesmaternal inheritance, proximal muscle weakness and ocular musculature
Cingulate gyrus
anterior cerebral artery

Medial portion of the temporal lobe
cranial nerve III
Eye is deviated down and out.
Pupil is mydriatic (dilated)

displacement of the cerebellar tonsils through the foramen magnum.
it causes brain stem compression and compromises vital respiratory
and cardiac centers in the medulla.
Tuberous sclerosisAD, hamartomas
biconvex or lens shape hyperdense lesion
do not cross suture lines on CT>>>Epidural hematomas
rupture of the middle meningeal ARTERY
skull fractures>>>epidural hemorrhage

superior cerebral veins (“bridging veins”).
crescentic shape

anterior communicating artery>>>berry aneurysms in the circle of wilis
subarachnoid bleeding>>> severe headache, berry aneurysms
subarachnoid hemorrhage: arterial vasospasm several days after the initial insult


CNS tumors

Question Answer
CNS Tumors"fried egg" tumor cells
1) Oligodendroglioma
2) Seminoma testicular tumor
3) pineal germinomas

"psammonma body" tumors
1) meningioma
2) papillary thyroid
3) serous papillary ovarian

astrocytomas: bipolar
meningioma: psammonma body
ependynoma: canals and pseudorosettes
Medulloblastoma: small/mitotic
glial tumorsastrocytomas,
Oligodendroglioma"fried egg" cells, spherical nuclei surrounded by a clear halo of cytoplasm (Seminoma testicular tumor)
CNS Tumors in adultsGlioblastoma(high grade astrocytoma)

Loss-of-function mutations in the p53 and Rb tumor suppressor pathways
gain-of-function mutations in the oncogenic PI3K pathways
Bizarre pleomorphic tumor cells
necrosis and hemorrhage

Meningioma "psammoma body"
Arise from arachnoid meningothelial cells.
psammoma bodies
Meningothelial cells of the arachnooid membrane,
NF2 and radiation history
compression of adjacent brain structures,
new-onset serzures/personality changes

Ependymoma: "canals and pseudorosettes"
can form embryologic ependymal canal and pseudorosettes
near the ventricular system.
CNS Tumors in childrenin the posterior fossa in kids
Astrocytoma and meulloblastoma

Pilocytic Astrocytoma "bipolar"
activating mutations in the serine-threonine kinase BRAF
bipolar cells with long, thin hair like processes ,
Spindle cells/rosenthal fibers/granular eosinophilic body in cerebellum

Medulloblastoma "small/mitotic"
gait instability/ataxia (cerebellum)
posterior fossa mass
small cells with little cytoplasm and hyperchromatic nuclei, mitoses are abundant
Germinomagerm cell
pineal gland,
pineal germinomas: the most common tumor of the pineal gland
resembles testicular seminoma "fried egg">>>facial hair growth, enlarged genitalia, pubic hair growth
impaired upward gaze (parinaud syndrome)
brain tumor -markersneurons, neuroectodermal and neuroendocrine cells: SYNAPtophysin
pheochromocytomas: SYNAPtophysin
gliomas: Glial fibrillary acidic protein (GFAP)
neural crest cells: melanocytes and schwann cells: s100+
schwann cells: spindle cells with regular oval nuclei.
CNS Metastatic tumorsThe most common primary sites are lung, breast, skin (melanoma), kidney, and gastrointestinal tract

Section 5