6. Resultados y Discusión
6.4. Identificación de proteínas que interaccionan con repetidos CA
Cerebral Edema: intracellular & extracellular types
Intracellular Edema: ↓serum Na (SIADH), dysfxnal Na/K ATPase pump
(global hypoxia)
Extracellular Edema: ↑vessel permeability, meningitis, metastasis Respiratory Acidosis, Hypoxemia: ↑cerebral vessel permeability,
enhance cerebral edema
Papilledema: sign of cerebral edema
Intracranial HTN: papilledema, bradycardia, projectile vomiting, HTN Pseudotumor Cerebri
o ↑ICP w/out evidence of tumor or obstruction o Most common in young obese women o ↓CSF resorption in arachnoid granulations o Headache, blurry vision, diplopia
Cerebral Hernation: complication of intracranial HTN
Subfalcine Herniation: compression of anterior cerebral artery Uncal Herniation
o compression of CN III, Posterior Cerebral Artery, parasympathetic fibers
o eye deviated down & out, mydriasis
Tonsillar Herniation: coning of cerebellar tonsils, cardiorespiratory arrest Hydrocephalus: enlargement of ventricles
CSF: produced by choroid plexus, reabsorbed by arachnoid granulations Communicating Hydrocephalus: ↑production CSF, ↓reabsorption CSF Noncommunicating Hydrocephalus: obstruction CSF outflow into
ventricles
Sylvius Aqueduct Blockage: most common cause of hydrocephalus in
newborns
Hydrocephalus
o Children: ventricles dilate & enlarge head circumference o Adults: no ↑ in head size, dementia, gait disturbance, urinary
incontinence
Hydrocephalus ex vacuo: dilated ventricles 2° to brain atrophy Normal Pressure Hydrocephalus
o dilated ventricles + triad—dementia, urinary incontinence, wide- based gait
o potentially reversible cause of dementia w/ shunting
o Wide-Based Gait/Urinary Incontinence: stretching of sacral motor fibers
o Dementia: stretching of limbic fibers
Developmental Disorders
Neural Tube Defects: failure of fusion of lateral folds of neural plate,
↑AFP
Maternal Folate level must be adequate BEFORE pregnancy Anencephaly: absence of brain, maternal polyhdraminos
54 Spina Bifida Occulta: dimple/tuft of hair overlying L5-S1
Meningocele: cystic mass w/ meninges
Meningomyelocele: cystic mass w/ meninges & spinal cord
Arnold-Chiari: caudal extension medulla/cerebellar vermis through
foramen, hydrocephalus, meningomyelocele, syringomyelia
Dandy-Walker: partial/complete absence of cerebellar vermis, cystic
dilation of 4th ventricle, hydrocephalus
Syringomyelia
o degenerative dz of spinal cord, usually cervical cord o cervical cord enlargement, fluid-filled cavity
o ↓pain/temp sensation in hands, loss intrinsic hand muscles o MRI shows cervical enlargement & cavity
Phakomatosis: neurocutaneous syndromes Neurofibromatosis
o Auto dom, incomplete penetrance
o Both Type 1 & 2—café au lait macules, neurofibromas
NF1
o optic gliomas, Lisch Nodules, axillary/inguinal freckling
o associations: pheochromocytoma, Wilm’s Tumor, CML (juvenile)
NF2: bilateral acoustic neuromas, juvenile cataracts, meningiomas Tuberous Sclerosis
o Auto dom
o Mental retardation, hamartomas in brain, kidneys
o Key Findings: seizures, mental retardation, angiofibromas, ash leaf lesions
o Rhabdomyoma of Heart: highly predictive of tuberous sclerosis
Sturge-Weber Syndrome: vascular malformations of face, ipsilateral
arteriovenous malformation in meninges in some pts
Head Trauma
Coup Injuries: site of impact
Contrecoup Injuries: opposite site of impact
Epidural Hematoma: temporoparietal skull fx, Middle Meningeal A. tear CT Scan: imaging test of choice
Subdural Hematoma
o Venous bleed between dura & arachnoid membranes o Most often caused by trauma, ↑ risk w/ cerebral atrophy o Tear of bridging veins producing venous blood clot o CT Scan: imaging test of choice
CNS Vascular Disorders Global Hypoxic Injury
o Hypotensive episodes, chronic CO poisoning
o Complications: cerebral atrophy, watershed infarcts, stroke
Red Neurons: apoptotic neuron
Hypoglycemia: ≈effect on brain as global hypoxia Strokes: ↑ incidence w/ age
Atherosclerotic Stroke
o Most common overall stroke, ischemic type
o Pale infarction extending to periphery of cerebral cortex
o Most occur in MCA distribution
o Infarction w/ liquefactive (NOT coagulative) necrosis
TIA: transient neurologic deficit lasting <24hr, microembolization of
plaque material
Amaurosis Fugax: temporary loss of vision, embolic material trapped at
bifurcation of retinal vessels
MCA Stroke: contralateral paresis/sensory loss in face/upper extremity,
head/eyes deviate to side of lesion
ACA Stroke: contralateral paresis/sensory loss in lower extremity
Embolic Stroke
o Ischemic type of stroke dt embolism
o Hemorrhagic infarction extending to periphery of cerebral cortex
Intracerebral Hemorrhage
o complication of HTN, rupture of aneurysm
o basal ganglia most common location
Rx HTN ↓ the incidence of stroke by more than 40%
Subarachnoid Hemorrhage
o Rupture of congenital Berry Aneurysm
o Severe occipital headache, described as “worst headache ever”
Berry Aneurysms: jxn of communicating branch w/ main cerebral
artery
Lacunar Strokes
o microinfarction <1cm
o hyaline arteriolosclerosis dt HTN/diabetes
55 CNS Infections
CNS Infection: most dt sepsis Meningitis
o inflammation of pia mater
o ↑CSF protein—bacterial, fungal & some viruses o ↓CSF glucose—bacterial, fungal
Bacterial Meningitis: majority of organisms originate in nasopharynx Viral Meningitis: most often transmitted by fecal-oral route
Encephalitis: inflammation of brain, headache, drowsiness, coma Cerebral Abscess: hematogenous, contiguous spread
Demyelination Disorders
Demyelination: destruction normal myelin/oligodendrocyte, abnormal
myelin
Multiple Sclerosis
o Most common demyelinating disease
o CD4 T cells react against self antigens in myeline sheath, cytokines activate macrophages that destroy myelin o Genetic factors & environmental triggers
o Blurry vision dt optic neuritis—MS most common cause
Demyelinating Plaques: white matter looks like gray mater
Sensory Dysfxn: paresthesis, loss pain/temperature/vibratory sensation Upper Motor Neuron Dysfxn: spasticity, ↑deep tendon reflexes, muscle
spasm, Babinski, weakness
Autonomic Dysfxn: urge incontinence, sexual dysfxn, bowel motility
dysfxn
SIN: scanning, speech, intention tremor, nystagmus
Bilateral Internuclear Ophthalmoplegia: pathognomonic for MS,
demyelination of medial longitudinal fasciculus
Lab: ↑CSF lymphs, CSF protein, CSF MBP, normal CSF glucose Oligoclonal Bands in High-Resolution Electrophoresis: sign of
demyelination
Central Pontine Myelinolysis: dt rapid IV correction of hypNa00usually in
an alcoholic
Adrenoleukodystrophy: XR, peroxisomal enzyme deficiency in β-
oxidation of fatty acids
Metachromatic Leukodystrophy: LSD, deficiency arylsulfatase A
Krabbe’s Dz: LSD, deficiency β-galactocerebrosidase w/ ↑ in β-
galactocerebroside in lysosomes
Degenerative Disorders Alzheimers
o Most common overall cause of dementia o Sporadic late onset type—most common type o Prevalence ↑s w/ age
o ↑phosphorylated Aβ neurotoxic
o ↑ density of NF tangles & senile *neuritic) plaques in brain, occipital lobe usually spared
o Prominent early sign—decline in short-term memory
o Presumptive dx w/ mental status testing, r/o all other causes of dementia
Activated GSK-3β: phosphorylates Aβ Aβ
o can be converted into amyloid, deposits in cerebral vessels o metabolic product of APP, coded for on chromosome 21
Secretases: β-secretases followed by γ-secretases cleave APP Aβ Insulin Degrading Enzyme: involved in clearance of Aβ
Apo Gene E, Allele ε4: sporadic early onset AD Activated GSK-3β: hyperphosphorylates tau protein
Neurofibrillary Tangle: hyperphosphorylated tau protein in neuron PIN1 Enzyme: dephosphorylates hyperphosphorylated tau protein,
deficient in some cases of AD
Senile (Neuritic) Plaques: core of Aβ surrounded by neuronal cell
processes w/ tau protein
Amyloid Angiopathy: risk for cerebral hemorrhage Confirmation of AD: must be made at autopsy Parkinsonism
o Alteration in dopaminergic pathways involved in voluntary muscle movement
Dopamine: principle NT in nigrostriatal tract Idiopathic Parkinsons Dz
o most common cause of Parkinsonism
o depigmentation substantia nigra neurons, ↓dopamine o Clinical: rigidity, resting tremor, bradykinesia
o Expressionless face, blepharospasm, seborrheic dermatitis
56
o Auto dom, trinucleotide repeat disorder
o Atrophy of caudate nucleus, putamen, globus pallidus o Chorea, oculomotor abnormalities
Friedreich’s Ataxia
o Auto rec, trinucleotide repeat disorder, deficiency frataxin o Degeneration Sites: dorsal root ganglia,
posterior/spinocerebellar/corticospinal tracts
o Hypertrophic cardiomyopathy, type I diabetes mellitus
Amyotrophic Lateral Sclerosis
o Degeneration of Lower & Upper Motor Neuron o Atrophy of intrinsic muscles of hand—1st
LMN sign o No sensory Δs, bowel & bladder fxn intact
Werdnig-Hoffmann Dz: Lower Motor Neuron dz in children Toxic & Metabolic Disorders
Wilson’s Dz: cystic degeneration of basal ganglia
Lenticular Nucleus—putamen & globus pallidus in the basal ganglia Acute Intermittent Porphyria
o Urine colorless when 1st
voided, exposure ot light produces color o Deficiency uroporphyringoen synthase, “bellyful of scars”,
peripheral neuropathy, dementia
o Rx: carbohydrate loading inhibits ALA synthase
Vitamin B12 Deficiency: subacute combined degeneration, dementia Wernicke-Korsakoff Syndrome
o hemorrhage in mammillary bodies
o confusion, ataxia, nystagmus, ophthalmoplegia
Alcoholics receiving IV infusion w/ glucose: supplement IV w/ thiamine
to prevent acute Wernicke’s Encephalopathy
CNS Tumors
Glioblastoma Multiforme: most common 1° CNS tumor in adults Childhood Tumors: cystic astrocytoma & medulloblastoma—both in
cerebellum
Clinical: headache, seizures, intracranial HTN Astrocytoma: most common neuroglial tumor
Glioblastoma Multiforme: grade IV astrocytoma, often crosses corpus
callosum, hemorrhagic/cystic
Meningioma
o Most common benign brain tumor in adults
o Female predominance o Psammona bodies
Ependymoma: 4th ventricle in kids & cauda equina in adults
Medulloblastoma: small cell tumor in cerebellum Oligodendroglioma: frontal lobe calcifications in an adult 1° CNS Lymphoma: occurs in AIDS, EBV-mediated cancer Metastasis: most common brain malignancy
Peripheral Nervous System Disorders
Sensory Δs: demyelination—parethesias, “glove & stocking” distribution Motor Δs: axon degeneration—muscle fasciculations, atrophy
Charcot-Marie-Tooth Dz
o Most common hereditary neuropathy
o Lower legs have “inverted bottle” appearance
Guillain-Barre Syndrome
o Most common acute peripheral neuropathy
o Preceding Infections: M. pneumonia, C. jejuni, viruses o Causes ascending paralysis
o Rx: IV immunoglobulin or plasma exchange
Diabetes Mellitus: most common cause of peripheral neuropathy Idiopathic Bell’s Palsy
o Facial muscle paralysis dt inflammation of CN VII o HSV most common association
Upper Motor Neuron Bell’s Palsy: contralateral weakness lower face,
sparing of upper face
Drugs: vincristine, hydralazine, phenytoin
Vitamin Deficiencies: thiamine, pyridoxine, vitamin B12 Schwannoma: benign Schwann cell tumor