DISEASE EPIDEMIOLOGY CLINICAL MECH TREATMENT DIAGNOSIS GROSS HISTO MISC.
Cerebral edema 1) Herniation 1) Vasogenic (BBB breakdown, BP), 2) Cytotoxic interstitial edema[1] 1) Mannitol, 2) Decompress (shunt), 3) thiopental 1) Appears soft, 2) Overfills vault, 3) gyri flattened & sulci narrowed, 4) ventricular cavity compressed
Subfalcine Herniation Anterior cerebral artery compression Assymetrical cerebral hemisphere expansion diplaces cingulate under falx cerebri
Transtentorial herniation 1) 3rd Cranial N. palsy, 2) posterior cerebral a. compression, 3) contralateral cerebral peduncle compression[2] Uncus compression/herniation against tentorium cerebelli
Tonsillar herniation 1) medulla oblongata compression [3] Cerebellar tonsills through foramen magnum
Hydrocephalus 1) dilated ventricle, 2) thinning cortex, 3) calvaria separation (infants) 1) Impaired flow or resorption, 2) Excessive CSF production[4] 1) imaging
Neural tube defects (Anencephaly) 1) NTD account for most CNS malformations, 2) 1 to 5 per 1000, 3) Females, 4) 28 day gestation Anterior neural tube closure failure 1) Absense of forebrain and calvaria, 2) area cerebrovasculosa[5]
Neral tube defects (Encephalocele) 1) NTD account for most CNS malformations 1) Diverticulum of malformed CNS through cranium defect
Neral tube defects (spina bifida) 1) Most common NTD, 2) 5% recurrence rate 1) lower extremety motor and sensory dysfnct, 2) bowl and bladder control Caudal neural tube closure failure Prevent w/ folic acid before pregnancy 1) imaging, 2) alpha-fetoprotein 1) Spina bifida occulta, 2) Myelomeningocele, 3) Meningocele[6]
Polymicrogyria Localized tissue injury during neuronal migration 1) small, numerous, irregular gyri, 2) meningeal entrapment
Microencephaly 1) chromosomal abnormalities, 2) fetal alcohol syndrome, 3) HIV 1) decreased neuroblast migration small brain
Lissencephaly (Miller-Dieker syndrome) 1) 90% have deletion at 17p13.3, 2) LIS1 gene defect 1) Seizures, 2) MR, 3) lissencephaly
Holoprosencephaly 1) Trisomy 13, 2) Diabetic mothers, 3) Sonic hedgehog mutations 1) cyclopia, 2) olfactory nerve absence 1) intrauterine ultrasound 1) incomplete cerebral hemisphere separation
Agenesis of Corpus callosum 1) Aicardi syndrome (lethal X-linked
Arnold-Chiari malformation 1) CSF obsruction (hydrocephalus), 2) lumbar myelomeningiocele neurosurgical intervention (type I) 1) Small posterior fossa, 2) Deformed cerebellum, 3) vermis extending into formamen magnum
Dandy-Walker malformation 1) Dysplasias of brain stem nuclei 1) cerebellar vermis absent, 2) enlarged posterior fossa, 3) midline cyste (expanded 4th ventricle)
Syringomyelia 1) Associated w/ Chiari I, intraspinal tumors, vertebral fusions, scoliosis, or trauma, 2) 2nd or 3rd decade of life, 3) Cervical most common 1)Progressive UE pain & temp. sensory loss, 2) retain motor and proprioception[7] 1) Ependyma expansion in central canal
Multiple Sclerosis 1) young adults (20-40), 2) irregular progressive course, 3) 1 in 1,000, 4) 15X higher risk in 1st degree relative 1) Optic neuritis w/ blindness (10-50%), 2) Random UMN signs CD4 Th1 cells react to myeline and activate Macs (IFN-g).  1) Oligoclonal bands[8] 1) Demylelination of white matter, 2) vascular damage & hemorrhage Naked axons w/ minimal remylemination. Inflammatory infiltrates w/ perivascular cuffing.
Acute disseminated encephalomyelitis 1) Acute rapid onset 1-2 wks following virus infection or immunization, 2) 20% fatal, 80% recovery 1) Diffuse brain involvement, 2) headach, lethargy, coma Cross reactive Ab to viral antigen which attack CNS 1) PMN infiltration followed by mononuclear predomination (lipid laden), 2) Perivascular demylination
Central Pontine myelinolysis 1) Alcoholism, severe electrolyte or osmolar imbalance, orthotopic liver transplant 1) rapid quadriplegia 1) Demyelinaion at basis pontis due to rapid  correction of hyponatremia
Progressive Multifocal Leucoencephalopathy 1) Immunsuppressed (HIV), 2) JC polyoma virus infection 1) Focal symptoms of cereburm and cerebellum, 2) relentlesly progressive 1) HIV and JC interaction in oligodendrocytes = cell death = demyelination 1) random focal patches of demyelination 1) loss of myelin, 2) neoplastic like astrocytes, 3) oligo nuclear inclusions, 4) lipid-laden macs, 5) dec. axons
Leukodystrophy (Krabbe Disease) 1) Onset at 3 to 6mo., 2) survival beyond 2 uncommon, 3) rapid progression 1) Motor (weakness, stiffness), 2) feeding trouble 1) galactocerebroside B-galactosidase deficiency, 2) galactocerebroside --> galactosphingosine (cytotoxic)[9] 1) Pitted white matter w/ subcortical sparing of U-fibers Unique feature: Cerebroside filled Mac aggregation, forming multinucleated cells (globoid cells), around vessels
Metachromatic leukodystrophy 1) AR, 2) late infantile (most common), juvenille, and adult form Childhood (motor symptoms w/ gradual progression & death in 5-10yr); Adult (psychiatric/cognitive present w/ motor later) 1) Arylsulfatase A deficiency (lysosomal enzyme) = sulfatide accumulation = myelin breakdown Bone marrow transplant (promising) 1) Metachromasia in urine (toluidine blue phase shift) 1) demylination w/ gliosis, 2) vacuolated macs, 3) macs metachromatic w/ toluidine blue dye[10]
Adrenoleukodystrophy 1) CNS and peripheral nerve loss signs, 2) rapid progression 1) Peroxisome metabolism defect (defective very long chain fatty acid catabolism) VLCFA serum elevation
Leucoairosis 1) very common in elderly unknown unknown Periventricular CT & MRI signal changes
Binswanger disease Very rare UMN signs White matter infarcts
Amyotrophic lateral sclerosis 1) Middle aged adults, 2) slowly progressive, 3) lateral and ventral corticospinal tracts 1) Paralysis Loss of anterior horn motor neurons (accumulation of neurofilaments) 1) myleination fiber loss in lateral and ventral CST, 2) Atrophy of ventral roots
Infantile spinal muscular atrophy [11] 1) infants, 2) death within 1 yr, 3) rapidly progressive Loss of anterior horn motor neurons (accumulation of neurofilaments)
Myasthenia Gravis 1) Rapidly fading strength, 2) ptosis, 3) worsening as the day progresses, 4) thymic hyperplasia 1) autoantibodies angainst Ach receptor normal EM neuromuscular junction 1) post synaptic fold simplification, 2) compensatory presynaptic vessicles
Polymositis 1) Pain 1) Cytotoxic T cell, 2) Intrafascicular inflammation 1) Intrafascicular inflammation and atrophy
Dermatomyositis 2) Pain & rash 1) Humoral, 2) extrafascicular inflammation 1) extrafascicular inflammation and perifascicular atrophy
Inclusion body myositis 1) Steroid resistance 1) Degenerative, 2) Inclusions, rimmed vacuoles 1) rimmed vacuole  with an inclusion (pink)
Duchenne Muscular Dystrophy 1) X-linked, 2) high mutation rate, 3) onset age 5-6, 4) death late teens or early 20s, 4) born normal 1) Deficiency of dystrophin Histo changes: endomysial fibrosis and myofiber regeneration (blue fibers) 1) delta lesions (myofiber necrosis from Ca leakage and protease activation)
Becker Muscular Dystrophy 1) Truncated dystrophin (multiple of 3 base deletion)[12]
Myotonic Muscular Dystrophy 1) trinucleotide repeat disease
Central core congenital myopathy 1) fixed structural defects 2) weakness at birth, 3) nonprogressive Central palor (exclusion of mitochondria)
Rod body Congenital myopathy 1) fixed structural defects 2) weakness at birth, 3) nonprogressive rods in muscle
Centronuclear myopathy 1) fixed structural defects 2) weakness at birth, 3) nonprogressive Central nucleus
McArdle's (phosphorylase deficiency) 1) subsarcolemmal glycogen deposits
Pompe's (acid maltase deficiency) 1) glycogen filled myofiber
Mitochondrial defects ragged red fiber
Thyroid opthalmopathy 1) most common cause of proptosis in adults 1) Proptosis (bilateral, ofter asymmetric), 2) hypothyroid or euthyroid 1) autoinflammatory response of extraocular muscles with GAG deposition Imaging: hypertrophied medial rectus
Basal cell carcinoma 1) >90% eyelid malignancies, 2) lower eyelid (sun)
[1]
1) inflammatory disease, neoplasm
2) neuronal, flial, or endothelial cell membrane injury during a hypoxic or ischemic insult
[2]
1) mydriasis, extraoccular movement deficit
2) visual cortex ishemia
3) Kernohan's notch: ipsilateral hemiparesis
4) This may stretch brainstem and kink basilar artery (pons supply) and rupture vessels in pons causing Duret hemorrhage and death.
[3]
1) compromise ventilation and cardiac drive
[4]
1) tumors (i.e choroid plexus tumor) or cellular debris blocks cerebral aqueduct

[5]
2) flattened remnant of brain w/ admixed ependyma, choroid plexus, and meningothelial cells
[6]
1) asymptomatic bony defect, 2) CNS herniation through spinal column, 3) meningeal extrusion only
[7]
1) Separation of syrinx damages anterior white commisure = contralateral pain & temp. sensory loss
[8]
1) B cell proliferation results in multiple clonal antibodies in CSF
[9]
GBG deficiency lead to buildup of galactocerebroside which goes down an alternate pathwy, losing a fatty acid, becoming galactosphingosine, a neurotic iller of oligos.
[10]
should be blue but shift red
[11]
Werdnig-Hoffman disease
[12]
Dystrophin connects the F-actin to the extracelluar matrix through dystrophin-associated proteins (DAGs).  Abnormal dystrophin allow actin filaments to move independent of extracellular matrix which may rip the sarcolemma membrane.