Neuro Pathology (Pathoma) Flashcards
Neural Tube Defects
Arise from incomplete closure of the neural tube
Associated w/ low folate levels prior to conception*
Detected during prenatal care by elevated AFP in amniotic fluid and maternal blood
Anencephaly
Rostral neural tube closure defect.
Abscence of skull and brain.
Eyes become prominent –> like appearance of the fetus
Polyhydramnios (inability to swallow)
Spina bifida
Failure of posterior vertebral arch to close
Can lead to a dimple or patch of hair overlying vetebral defect (spina bifida oculta)
Spina bifida can lead to meningocele or meningnomyelocele
Cerebral Aqueduct Stenosis
Congenital stenosis of the channel that drains CSF from 3rd and 4th ventricles
Leads to accumulation of CSF in ventricles (inability to drain)
Presents w/ enlarging head circumference.
Dandy-Walker Malformation
Congenital failure of cerebellar vermis to develop
Presents w/ massively dilated 4th vent w/ an absent cerebellum; often accompanied by hydrocephalus
Arnold-Chiari Malformation
Herniation of cerebellar tonsils through the foramen magnum.
Obstruction of CSF flow may result in hydrocephalus
May occur in association w/ meningomyelocele and syringomyelia
Type I = Usually Benign
Type 2 = Symptomatic
Syringomyelia
Cystic degeneration of the spinal cord.
Arises w/ trauma or in association w/ Arnold-Chiari
Occurs at C8-T1
Sensory loss of pain and temp bilaterally in upper extremety.
Fine touch and position is spared.
Lower motor neurons can be damaged as well. Eventually sympathetic input in lateral horn can be affected –> Horner’s (PAM).
Poliomyelitis
Damage to anterior motor horn due to poliovirus infection (fecal-oral).
Lower-motor neuron disease
Wernig-Hoffman
Genetic lower motor neuron disease
Autosomal recessive
Floppy baby presentation
Death by a couple years.
Amyotrophic Lateral Sclerosis
Degenerative disorder of upper and lower motor neurons (corticospinal tract)
Anterior motor horn involement leads to LMN signs
Lateral corticospinal tract involvement leads to UMN signs.
Atrophy and weakness of hands is an early sign (lack of sensory impairment distinguishes ALS from syringomyelia)
Most cases are sporadic and arises in middle aged adults
*Zinc-copper superoxide dismutase mutation is present in some familial cases –> free radical damage of neurons
Friedrich Ataxia
Degenerative disorder of cerebellum and spinal cord tracts
Presents as ataxia (cerebellum) with loss of vibratory sense and proprioception, muscle weakness in lower extremities, and loss of DTR.
AR disorder
Unstable trinucleotide repeat disorder (GAA) in frataxin gene. (fenton reaction –> free radical damage)
Presents in early childhood
Associated w/ hypertrophic cardiomyopathy.
Meningitis
Inflammation of leptomeningies (Pia and arachnoid –> PAD)
MC due to an infectious agent
Neonates: GBS, E. coli, and Listeria
Children/Teens: Neisseria Meningitidis –> enters through nasal pharynx –> blood –> meninges
Adults and elderly –> Strep pneumo
Nonvaccinated infant –> Hib
Coxsackievirus –> MC viral cause
Immunocompromised –> Fungi
Present w/ headache, neck stiffness, and fever
Photophobia, vomiting, and altered mental status
Dx w/ LP (L4-L5 without going through pia:
Bacterial: Nphils, low glucose, posiitve gram stain and culture
Viral - lymphocytes and normal CSF glucose
Fungal - lymphocytes w/ low glucose
Complications are seen w/ bacterial meningitis: Death, hydrocephalus, hearing loss, and seizures (Healing issues)
Cerebrovascular Disease
Ischemic 85% or hemorrhagic (15%)
Global Cerebral Ischemia
Low perfusion (atherosclerosis of large vessel)
Acute decrease in blood flow (shock)
Chronic hypoxia (anemia)
Repeated episodes of hypoglycemia (insulinoma)
Clinical features:
Mild (transient confusion w/ recovery)
Severe (Diffuse necrosis –> death or coma)
Moderate global ischemia (infarcts in watershed areas and damage to highly vulnerable regions –> cortical laminar necrosis. I.e. pyramidal neurons in cerebrum, purkinje layer in cerebellum, and pyramidal neurons elsewhere)
Ischemic Stroke
Regional ischemia that results in focal neurologic deficits for >24 hrs.
Symptoms pale infarction at periphery of cortex due to an atherosclerotic plaque rupture at a branch point
- Embolic –> hemorrhagic infarciton at periphery of cortex usually from the left side of the heart. MC in MCA from AFIB.
- ) Lacunar stroke –> Secondary to hyaline arteriolosclerosis esp. in lenticulostriate vessel. Lake like infarction. Deep structures of brain.
Ischemic stroke leads to liquefactive necrosis.
Red neurons early–> neutrophils, microglial cells, and granulation tissue then ensues –> eventually results in fluid-filled cystic space surrounded by gliosis. 1 day; 1 week; 1 month
Intracerebral Hemorrhage
Bleeding into the brain meninges
MC due to rupture of Charcot-Bouchard aneurysms of lenticulostriate vessels resulting in damage to the basal ganglia (strong assn w/ HTN)
Subarachnoid Hemorrhage
Bleeding in subarachnoid hemorrhage
Presents as sudden headache w/ nuchal rigididty
LP shows xanthochromia (from heme breakdown; can be bloody or yellow)
Gross: Hemorrhage at base of brain.
Most frequently due to the rupture of berry anuerysm
Berry Aneurysm
Thin walled saccular outpouching;* lacks a media layer
Most frequently located in anterior circle of Willis (branch points of ACA)
*Associated w/ Marfans and ADPKD
Epidural Hematoma
Bleed above dura (tough to severe –> arterial pressure needed)
- Secondary to fracture and rupture of Middle Meningeal Artery
- Lens shaped CT
- “Talk and Die” syndrome –> lucid interval (hrs. to 1 day) –> rupture/expansion –> fatal herniation
Subdural hematoma
Bleed under the dura.
Usually associated w/ trauma and subsequent rupture of bridging veins.
Risk factors = cortical atrophy (alcoholic, elderly, dehyrdration, shaken baby)
Presents w/ progressive neurological signs –> Herniation is lethal complication
Tonsillar Herniation
Herniation of cerebellar tonsils through foramen magnum which compresses the brainstem and can cause cardiopulmonary arrest.
Subfalcine herniation
Herniation under Falx Cerebri –> can compress Anterior Cerebral Artery –> Infarction
Uncal herniation
Herniation of uncus through tentorum cerebelli compressing CN III, PCA, and duret hemorrhages in brainstem
Metachromatic Leukodystrophy
Deficiency of arylsulfatase; MC leukodystrophy
Myelin can’t be degraded; accumulates in lysosomes
Krabbe Disease
Deficiency of galactocerebroside B-galactosidase
Galactocerebroside accumulates in macrophages
Adrenoleukodystrophy
Impaired addition of coenzyme A to long chain fatty acids
FAs accumulate damaging adrenal gland and white matter.
MS
AI destruction of CNS myeling and oligodendrocytes
Associated w/ HLA-DR2 (My mom has MS, but I want to be a Dr. Too!)
Associated w/ distance from equator
Women>Men.
Clinical features: Blurred vision in one eye (optic); verigo and scanning speech (brainstem –> sound drunk); and internuclear opthalmoplegia (MLF). Depends on region involved.
Can also involve: Hemiparesis or unilateral loss of sensation (cerebral white matter); lower extremity loss of sensation or weakness (spinal cord); Bowel, bladder, and sexual dysfunction (autonomic nervous system)
Dx: MRI reveals plaques, LP shows increased lymphocytes, increased Ig w/ oligoclonoal IgG bands, and myelin basic protein.
Rx: Acute : high dose steroids
Chronic: B-interferon
Subacute Sclerosing Panencephalitis
Progressive debilitating encephalitis leading to death
*Due to slowly progressing, persistent infection of the brain by measles.
Infection in infancy; neuro signs later.
Characterized by viral inclusions in both gray and white matter
Progressive Multifocal Leukoencephalopaty
*JC virus infection of oligodendrocytes.
Immunosuppression leads to reactivation of latent virus
Presents w/ rapidly progressive neuro signs leading to death
Central Pontine Myelinolysis
Focal demylination of pons
Due to rapid IV correction of hyponatremia (esp. in alcoholic or malnourished
Classically presents as locked-in-syndrome
Alzheimer’s Disease
Degenerative disease of the cortex.
MCC of dementia
Breakdown of amyloid precursor protein by Beta –> can’t be broken down –> plaques
Clinical features: Slow-onset memory loss. Progressive disorientation. Loss of learned motor skills and language. Behavior and personality changes. Patients become mute and bedridden.
*Focal neurologic deficits not seen early
Most cases are sporadic. (major risk factor is age; Epsilon4 allele of APDE –> increased AB-amyloid and decreased risk of Epsilon 2 allele (4>2!)
Early forms:
- ) presenilin1 (and 2)mutation
- ) Downsyndrome (amyloid precursor protein is found on chromosome 21)
Pathologic features: Diffuse cerebral atrophy –> narrowing of gyri and widening of sulci –> dilated ventricles = hydrocephalus ex vacuo.
Development of neuritic plaques made of AB-amyloid with entrapped neuritic processes. AB amyloid can deposit around blood vessels –> cerebral amyloid angiopathy
Neurofibrillary tangles –> flame shaped cells –> contain hyperphosphrylated Tau protein
Dx: Presumptive dx is made clinically after excluding other causes. Confirmed on autopsy.
Vascular Dementia
Multifocal infarction and injury
Due to HTN, atherosclerosis, or vasculitis (i.e. consequence of moderate global cerebral ischemia –> hippocampus)
2nd MCC of dementia
Frontotemporal Dementia (Pick’s Disease)
Degenerative disease of frontal and temporal cortex; spares parietal and occipital lobes
Round aggregates of tau protein in neurons and cortex
Behavioral and language sx arise early; progresses to dementia.
Parkinson’s Disease
Degenerative loss of dopaminergic neurons in the substantia nigra pars compacta (basal ganglia)
BG modulates movement. Dopamine from SNpC increases signal to cortex (stimulates excitatory D1 and inhibits inhibitor D2)
Common disorder related to aging. Unkown etiology; rare cases related to drug MPTP
Clinical Features = TRAP T -remor R-igidity A-kinesia/bradykinesia P-ostural instability and shuffling gate
Round eosinophilic inclusions of alpha-synuclein in BG = Lewy Body
Dementia is a common LATE disease
Early-onset dementia suggests Lewy body dementia
Lewy Body dementia
Early onset dementia w/ dementia, hallucinaitons, and parkinosnian features with CORTICAL Lewy bodies
Huntington’s Disease
Degeneration of GABAergic neurons in Caudate nucleus of BG.
Loss of GABA (inhibitory) neuron –> loss of inhibitory hold on cortex–> chorea
AD disorder from trinucleotide repeats of CAG in huntingin gene
Further expansion of trinucleotide repeat occurs during *spermatogenesis –> anticipation
Presentation:
Depression; Chorea; Athetosis; Dementia.
Suicide is a common cause of death
Normal Pressure Hydrocephalus
Increased CSF results in dilated ventricles
Can cause dementia in adults; usually idiopathic
Presents as triad of : urinary incontinence, gait instability, and dementia (Wet, Wacky and Wobbly)
LP improves sx; treatment is VP shunt.
Stretching of corona raidata
Spongiform Encephalopathy
Due to the accumulation of misfolded prion protein (PrPc–> PrPsc (Beta-pleated sheet).
Damages to neurons and glial cells –> vaculization of cytoplasm. Spongy degeneration
Can be sporadic, inherited, or transmitted
Most common form is CJD. other forms include vCJD (mad cow in young people w/ exposure; and familial fatal insomnia (inherited form characterized by insomnia and exaggerated startle response)
CJD
Usually sporadic; rarely arises due to exposure to prion infected tissue
Presesnts w/ RAPIDLY progressive dementia associated w/ ataxia and startle myoclonus.
*Spike-wave complexes seen on EEG
Results in death, usually in
Metastatic Tumors
About 50% metastatic and 50% primary
Present as multiple-well circumscribed lesions at the Gray-white junciton.
MCC: 1.Lung, 2.Breast 3.Kidney
Pilocy(S)tic Astrocytoma
Benign tumor of astrocytes
MC CNS tumor in children; usually arises in the cerebellum
Cystic lesion w/ a nodule growing on its wall on imaging.
Histology shows rosenthal fibers (astrocytes w/ thick eosinophilic processes)
GFAP positive
Glioblastoma Multiforme
Malignant, high-grade tumor of astrocytes
MC malignant primary CNS tumor in adults
Often crosses corpus callosum (butterfly glioma)
Histology: Pseudopallisading necrosis. Endothelial cell proliferation.
GFAP is intermediate filament present.
Ependymoma
Malignant tumor of ependymal cells; usually in children
MC arises in 4th ventricle; may present w/ hydrocephalus*
Peri-vascular pseduorosettes.
Medulloblastoma
Malignant tumor derived from granular cells of cerebellum
*Derived from Neuroectoderm origin
Usually arises in children (MC malignant CNS tumor)
Small round blue cells; Homer-Wright rosettes may be present
Poor prognosis; tumor grows rapidly and spreads via CSF (drop metastsis*)
Meningioma
Benign tumor of arachnoid cells
MC benign tumor in adults
F>M (tumor expresses estrogen receptor)
May present w/ seizures
Imaging reveals a round mass attached to the dura and compresses cortex.
Histology:Whorled cells and psammoma bodies
Adult primary brain tumors
Usually supratentorial
Glioblastoma Mutliforme is MCC
Olidendroglioma and meningiomas (women) also.
Child Brain Tumors
Usually infratentorial
Pilocytic Astrocytoma
Ependymoma
Medulloblastoma
Schwannoma
Adult benign tumor of Schwann cells
Involves cranial or spinal nerves; esp 8th cranial nerve at cerebello-pontine-angle
Presents w/ tinnitus often or hearing deficits.
S100 positive (neurocrest origin)
Bilateral tumors seen in NF2
Oligodendroglioma
Adult malignant tumor of oligodendrocytes
Calcified tumor in the white matter; usually involving the frontal lobe
May present w/ seizures.
Fried egg appearance on histology (I’d like to have some (oligo) fried eggs).
Craniopharyngioma
Tumor that arises from epithelial remnants of Rathke’s pouch. Sits on top of Sella Tursica.
Presents w/ supratentorial mass in child or young adult
Optic chiasm compression leads to bilateral hemionopsia (ddx. vs pituitary adenoma**)
Calcified on imaging (from roof of mouth –> teeth are calcified.)
Benign but tends to recur after resection
