Decreased cognitive ability, memory, fxn, with intact consciousness.
Alzheimer's dz: Epidemiology? Groups at increased risk?
Most common cause of dementia in the elderly. Down syndrome pts are at increased risk of developing AD.
Alzheimer's dz: genetics?
Familial form (10%) assocaited w/ genes on chromosomes 1, 14, 19 (APOE4 allele; autosomal dominant), and 21 (APP) gene.
Alzheimer's dz: pathogenesis?
Widespread, accelerated cortical atrophy with decreased ACh. <
Senile plaques (extracellular, beta-amyloid core) May cause amyloid angiopathy --< intracranial hemorrhage.
NF tangles (intracellular, abnormally phosphorylated tau protein; tangles correlate w/ degree of dementia).
Dementia, aphasia, parkinsonian aspects, change in personality;
Pick bodies (intracellular, aggregated tau protein), frontotemporal lobe atrophy. Spares parietal lobe and posterior 2/3rds of superior temporal gyrus.
Lewy body dementia
Parkinsonism with dementia and hallucinations. Caused by alpha-synuclein defect.
Creutzfeldt-Jakob dz (CJD)
Rapidly progressive (wks-mos) dementia w/ myoclonus, spongiform cortex; associated w/ prions.
"Other" causes of dementia
Multi-infarct (2nd most common cause of dementia in the elderly) Syphilis HIV Vitamin B12 deficiency Wilson's dz, Nl pressure hydrocephalus
Multiple sclerosis: What is it?
Autoimmune inflammation and demyelination of CNS (brain and spinal cord).
Multiple sclerosis: How do pts present? What is the course of the dz?
Pts can present with: optic neuritis (sudden loss of vision) MLF syndrome (internuclear ophthalmoplegia) Hemiparesis Hemisensory Sx's Bowel/bladder incontinence. Relapsing and remitting course.
Multiple sclerosis: Who is affected?
Most often affects women in their 20s and 30s; more common in whites.
Findings in multiple sclerosis
Elevated protein (IgG) in CSF. Oligoclonal bands are dx!!! Periventricular plaques (areas of oligodendrocyte loss and reactive gliosis) w/ preservation of axons.
Charcot's traid of MS is a SIIIN :
S canning speech I ntention tremor (+I ncontinence, I nternuclear ophthalmoplegia) N ystagmus
Tx for multiple sclerosis
Beta-interferon or immunosuppressant therapy. Symptomatic Tx for neurogenic bladder, spasticity, and pain.
Guillan-Barre syndrome (acute inflammatory demyelinating polyradiculopathy) What is it/what are the main Sx?
Inflammation and demyelination of peripheral nerves and motor fibers of ventral roots (sensory effect less severe than motor), causing symmetric ascending muscle weakness beginning in distal lower extremities. Facial paralysis in 50% of cases. Autonomic fxn may be severely affected (e.g., cardiac irregularities, HTN, or hypotension).
Guillan-Barre syndrome (acute inflammatory demyelinating polyradiculopathy) What is the prognosis?
Almost all pts survive; the majority recover completely after wks to months.
Guillan-Barre syndrome (acute inflammatory demyelinating polyradiculopathy): Findings?
Elevated CSF protein w/ normal cell count (albuminocytologic dissociation). Elevated protein --< papilledema.
Guillan-Barre syndrome (acute inflammatory demyelinating polyradiculopathy): is associated with...?
Associated with infxns --< autoimmune attack of peripheral myelin due to molecular mimicry (e.g., Campylobacter jejuni or herpesvirus infxn), inoculations, and stress, but no definitive link to pathogens.
Guillan-Barre syndrome (acute inflammatory demyelinating polyradiculopathy): Management/Tx?
Respiratory support is critical until recovery. Additional Tx: plasmapheresis, IV immune globulins.
Progressive multifocal leukoencephalopathy (PML)
Demyelination of CNS due to destruction of oligodendrocytes. Associated w/ JC virus and seen in 2-4% of AIDS pts (reactivation of latent viral infxn). Rapidly progressive, usually fatal.
Acute disseminated (postinfectious) encephalomyelitis
Multifocal perivenular inflammation and demyelination after infxn (e.g., chickenpox, measles) or certain vaccinations (e.g., rabies, smallpox)
AR lysosomal storage dz, most commonly due to arylsulfatase A deficiency. Builup of sulfatides leads to impaired production of myelin sheath.
Charcot-Marie Tooth disease (aka hereditary motor and sensory neuropathy HMSN)
defective production of proteins involved in the structure and fxn onf peripheral nerves or the myelin sheath.
Characterized by synchronized, high-frequency neuronal firing. Variety of forms.
Partial seizures vs Generalized seizures
1 area of brain. Most commonly originates in the mesial temporal lobe. Often preceded by seizure aura; can secondarily generalize.; Diffuse
2 types of partial seizures
1.) Simple partial (consciousness intact): motor, sensory, autonomic, psychic 2.) Complex partial (impaired consciousness)
5 Types of generalized seizures
1.) Absence (petit mal) 2.) Myoclonic - quick, repetitive jerks 3.) Tonic-clonic (grand mal) - alternating stiffening and movement 4.) Tonic - stiffening 5.) Atonic - "drop" seizures (falls to floor); commonly mistaken for fainting
A d/o of recurrent seizures (febrile seizures are not epilsepsy)
Causes of seizures by age: Children?
Genetic, Infxn (febrile), Trauma, Congenital, Metabolic
Causes of seizures by age: Adults?
Tumors, Trauma, Stroke, Infxn
Causes of seizures by age: Elderly?
Stroke, Tumor, Trauma, Metabolic, Infxn
Pain due to irritation of structures such as dura, cranial nerves, or extracranial structures, not brain parenchyma itself.
4-72 hours of unilateral pulsating pain w/ nausea, photophobia, or phonophobia. +/- "aura" of neurologic Sx before HA, including visual, sensory, speech disturbances. Due to irritation of CN V and release of substance P, CGRP, vasoactive peptides.
> 30 minutes of bilateral steady pain. Not aggravated by light or noise; no aura.
Repetitive brief headaches characterized by unilateral periorbital pain associated w/ ipsilateral lacrimation, rhinorrhea, Horner's syndrome. Much more common in males. Tx inhaled O2 or Sumatriptan
Illusion of movement, not to be confused w/ dizziness or lightheadedness.
More common type. Inner ear etiology (e.g., semicircular canal debris, vestibular nerve infxn, Meniere's dz). Positional testing --< delayed horizontal nystagmus.
Brain stem or cerebellar lesion (e.g., vestibular nuclei, posterior fossa tumor). Positional testing --< immediate nystagmus in any direction; may change directions.
Neurocutaneous disorders: Sturge-Weber syndrome
Congenital d/o w/ port-wine stains (V1 distribution), pheochrom, and ipsilateral leptomeningeal angioma. Can cause glaucoma, seizures, hemiparesis, and mental retardation. Occurs sporadically.
Neurocutaneous disorders: Tuberous sclerosis;
AD; Hamartomas in cns & skin, Adenoma sebaceum (cutaneous angiofibromas), Mental retardation, Ash-leaf spots, Rhabdomyoma, Angiomyolipoma, seizures
Neurocutaneous disorders: NF type I (von Recklinghausen's disease)
100% penetrant, variable expression. Café-au-lait spots, Lisch nodules (pigmented iris hamartomas), Neurofibromas in skin. Mutated NF-1 gene on chrom 17.
Neurocutaneous disorders: von Hippel-Lindau dz
AD; Cavernous hemangiomas in skin, mucosa, organs; bilateral renal cell carcinoma, hemangioblastoma in retina, brain stem, cerebellum. Pheochrom; Mutated tumor suppressor VHL on chrom 3
Primary brain tumors
Clinical presentation due to mass effects (e.g., seizures, demential, focal lesions); Primary tumors rarely undergo metastasis. The majority of adult primary tumors are supratentorial, while the majority of childhood primary tumors are infratentorial. Note: half of adult brain tumors are metastases (well circumscribed; usually present at the gray-white junction).
Adult peak incidence tumors: Glioblastoma multiforme (grade IV astrocytoma)
Most common primary brain tumor. Prognosis grave; > 1yr life expectancy. Found in cerebral hemispheres. Can cross corpus callosum ("butterfly glioma" [below]) Stain astrocytes for GFAP.
"Pseudopalisading" pleomorphic tumor cells -- border central areas of necrosis and hemorrhage
Glioblastoma multiforme (grade IV astrocytoma)
Adult peak incidence tumors: Meningioma
2nd most common primary brain tumor. Most often occurs in convexities of hemispheres and parasagittal region. Arises from arachnoid cells external to brain. Resectable.
Spindle cells concentrically arranged in a whorled pattern; psammoma bodies (laminated calcifications).
Adult peak incidence tumors: Schwannoma
3rd most common primary brain tumor. Cerebellopontine angle. often localized to CN VIII --< acoustic schwannoma. Resectable. Bilateral schwannoma found in NF type II.
Adult peak incidence tumors: Oligodendroma
Relatively rare, slow groing. Most often in frontal lobes. Chicken-wire capillary pattern.
Oligodendrocytes = "fried egg" cells -- round nuclei w/ clear cytoplasm. Often calcified
Adult peak incidence tumors: Pituitary adenoma
Most commonly prolactinoma. Bitemporal hemianopia (due to pressure on optic chiasm) and hyper- or hypopituitarism are sequelae. Rathke's pouch.
Childhood peak incidence tumors: Pilocytic (low-grade) astocytoma
Usually well circumscribed. posterior fossa. May be supratentorial. GFAP positive. Benign; good prognosis.
Rosenthal fibers -- eosinophilic, corkscrew fibers. gross (cystic AND solid)
Pilocytic (low-grade) astocytoma
Childhood peak incidence tumors: Medullo-blastoma
Highly malignant cerebellar tumor. A form of primitive neuroectodermal tumor (PNET). Can compress 4th ventricle, causing hydrocephalus.
Rosettes or perivascular pseudorosette pattern cells. Small blue cells. Radiosensitive. gross (solid).
Childhood peak incidence tumors: Ependymoma
found in 4th ventricle. Can cause hydrocephalus. Poor prognosis.
perivascular pseudorosettes. Rod-shaped blepharoplasts (basal ciliary bodies) found near nucleus.
Childhood peak incidence tumors: Hemangioblastoma
cerebellar; a/w vHL syndrome when found w/ retinal angiomas. Can produce EPO --< secondary polycythemia. Foamy cells and high vascularity
Childhood peak incidence tumors: Craniopharyngioma
Benign childood tumor, confused w/ pituitary adenoma (can also cause bitemporal hemianopia). Most common childhood supratentorial tumor. Derived from remnants of Rathke's pouch. Calcification is common (tooth enamel-like).
Herniation syndromes: Cingulate (subfalcine) herniation under falx cerebri
Can compress anterior cerebral artery.
Herniation syndromes: Cerebellar tonsillar herniation into the foramen magnum
#4 below: <img src="426a Herniation syndromes.JPG" />
Hernation syndromes: what is the biggest danger?
Coma and death result when these hernations compress the brain stem.
Clinical signs of uncal herniation: Ipsilateral dilated pupil/pstosis; (hint: Uncus = medial temporal lobe)
Stretching of CN III (innervates levator palpebrae)
Clinical signs of uncal herniation: Contralateral homonymous hemianopia w/ macular sparing
Compression of ipsilateral posterior cerebral artery
Clinical signs of uncal herniation: Ipsilateral paresis
Compression of contralateral crus cerebri (Kernohan's notch)
Clinical signs of uncal herniation: Duret hemorrhages -- paramedian artery rupture
Caudal displacement of brain stem.
Metastases, abscesses, toxoplasmosis, primary CNS lymphoma
ring enhancing lesion
met lymphoma, meningioma, mets
uniformly enhancing lesion
heterogeneously enhancing lesion