Pathoma: CNS Flashcards
Incomplete closure of neural tube
Neural Tube Defect
Low folate levels prior to conception
Neural Tube Defect
Detected by high AFP levels
Neural Tube Defect
Absence of skull and brain
Anencephaly
Frog-like appearance
Anencephaly
Result in maternal polyhydramnios
Anencephaly
Failure of posterior vertebral arch to close
Spina bifida
Dimple or patch of hair overlying vertebral defect
Spina bifida occulta
Cystic protrusion of underlying tissue through vertebral defect
Spina bifida
Protrusion of meninges
Meningocele
Protrusion of meninges and spinal cord
Meningomyelocele
Congenital narrowing of channel that drains CSF from 3rd to 4th ventricle
Cerebral Aqueduct Stenosis
Most common cause of hydrocephalus in newborns
Cerebral Aqueduct Stenosis
Presents with enlarging head circumference due to dilation of ventricles
Cerebral Aqueduct Stenosis
Congenital failure of cerebellar vermis to develop
Dandy-Walker Malformation
Presents as massively dilated 4th ventricle and absent cerebellum.
Dandy-Walker Malformation
Congenital downward displacement of cerebellar vermis and tonsils through foramen magnum
Arnold-Chiari Malformation Type II
Obstruction results in hydrocephalus
Arnold-Chiari Malformation Type II
May occur in association with meningomyelocele and syringomyelia
Arnold-Chiari Malformation Type II
Cystic degeneration of spinal cord
Syringomyelia
Cause: Trauma or Arnold-Chiari malformation
Syringomyelia
Occurs at C8-T1
Syringomyelia
Presents as sensory loss of pain and temperature with sparing of fine touch and position sense in uppper extremities (Cape-like distribution)
Syringomyelia
Expansion leads to damage of LMN’s of anterior horn (muscle atrophy) and damage of lateral horn of hypothalamospinal tract (Horner syndrome)
Syringomyelia
Damange to anterior motor due to poliovirus infection
Poliomyelitis
Presents with lower motor neuron signs (flaccid paralysis with muscle atrophy, fasciculations, weak muscles, impaired reflexes, and negative Babinski
Poliomyelitis
Inherited Degeneration of Anterior Motor Horn
Werdnig-Hoffman Disease
Autosomal Recessive
Werdnig-Hoffman Disease
Presents as floppy baby, with death within a few years
Werdnig-Hoffman Disease
Degenerative disorder of upper and lower motor neurons of corticospinal tract
ALS
Presents with lower motor neuron signs (flaccid paralysis with muscle atrophy, fasciculations, weak muscles, impaired reflexes, and negative Babinski
ALS
Presents with upper motor neuron signs (spastic paralysis with hyperreflexia, increased tone, positive Babinski sign
ALS
Atrophy and weakness of hands is an early sign
ALS
Lack of sensory impairment distinguishes this from syringomyelia
ALS
Most cases are sporadic arising in middle age adults
ALS
Zinc-copper superoxide dismutase mutation (SOD1) is present in some familial cases, leads to free radical injury
ALS
Degenerative disorder of cerebellum and spinal cord
Friedrich Ataxia
Presents with ataxia (cerebellum) and loss of vibratory sense and proprioception, muscle weakness in legs, and loss of deep tendon reflexes
Friedrich Ataxia
Autosomal recessive due to unstable trinucleotide repeat (GAA) in frataxin gene
Friedrich Ataxia
This mutated protein is essential for mitochondrial iron regulation
Friedrich Ataxia
Presents with iron buildup
Friedrich Ataxia
Presents in early childhood
Friedrich Ataxia
Associated with hypertrophic cardiomyopathy
Friedrich Ataxia
Inflammation of leptomeninges (pia and arachnoid)
Meningitis
Most commonly due to an infectious agent
Meningitis
Most common neonate meningitis causes
GBS, E. Coli, Listeria Monocytogenes
Most common children/teenager meningitis cause
N. Meningitidis
Most common adult and elderly meningitis cause
Streptococcus pneumoniae
Most common non-vaccinated infant meningitis
H. influenza
Most common viral cause of meningitis
Coxsackie virus
Most common immunocompromised cause of meningitis
Fungi
Classic triad of headache, nuchal rigidity, and fever
Meningitis
Diagnosis made by lumbar puncture
Meningitis
CSF finding: Neutrophils with decreased glucose
Bacterial Meningitis
CSF finding: Lymphocytes with normal glucose
Viral Meningitis
CSF finding: Lymphocytes with decreased glucose
Fungal meningitis
Major cause of cerebrovascular disease
Ischemia
Causes: Low perfusion, acute decrease in blood flow, chronic hypoxia, and repeated hypoglycemia
Global Cerebral Ischemia
Presents as transient confusion with prompt recovery
Mild Global Ischemia
Presents as diffuse necrosis with vegetative state
Severe global ischemia
Infarcts in watershed areas (between anterior and middle cerebral rtery
Moderate global ischemia
Damage in this results in laminar necrosis of pyramidal cortex neurons, damage to pyramidal hippocampus neurons, and damage to purkinje layer of cerebellum
Moderate global ischemia
Focal neurologic deficits lasting longer than 24 hours
Ischemic stroke
Focal neurologic deficits lasting less than 24 hours
Transient Ischemic Attack
Due to rupture of an atherosclerotic plaque
Thrombotic stroke
Usually involves the bifurcation of internal carotid and middle cerebral artery in circle of Willis
Thrombotic stroke
Results in pale infarct
Thrombotic stroke
Due to thromboemboli
Embolic stroke
Most common source is left side of heart
Embolic stroke
Usually involves the middle cerebral artery
Embolic stroke
Results in hemorrhagic infarct at periphery of cortex
Embolic stroke
Occurs secondary to hyaline arteriolosclerosis due to hypertension
Lacunar Stroke
Most involve the lenticulostriate vessels resulting in small cystic areas of infarction
Lacunar Stroke
Involvement of internal capsule leads to pure motor stroke
Lacunar Stroke
Involvement of thalamus leads to a pure sensory stroke
Lacunar Stroke
Results in liquefactive necrosis
Ischemic stroke
Presents as eosinophilic/red neurons within 12 hours of occureence
Ischemic stroke
Necrosis occurs by 24 hours
Ischemic stroke
Infiltration of neutrophils in days 1-3
Ischemic stroke
Microglial cells in days 4-7
Ischemic stroke
Gliosis in weeks 2-3
Ischemic stroke
Classically due to Charcot-Bouchard microaneurysms of lenticulostriate vessels
Intracerebral Hemorrhage
Basal ganglia is most common site
Intracerebral Hemorrhage
Presents as severe headache, flu-like, and eventual coma
Intracerebral Hemorrhage
Bleeding into brain parenchyma
Intracerebral Hemorrhage
Bleeding into subarachnoid space
Subarachnoid hemorrhage
Presents as sudden headache (Worst headache of my life) with nuchal rigidity
Subarachnoid hemorrhage
Lumbar puncture shows xanthochromia due to bilirubin breakdown
Subarachnoid hemorrhage
85% are due to berry aneurysm
Subarachnoid hemorrhage
Most frequently located in anterior circle of Willis at branch points of anterior communicating artery
Subarachnoid hemorrhage
Associated with Marfan syndrome and autosomal dominant polycystic kidney disease
Subarachnoid hemorrhage
Collection of blood between dura and skull
Epidural Hematoma
Clasically due to fracture of temporal bone with rupture of middle meningeal artery
Epidural Hematoma
Lens-shaped lesion on CT
Epidural Hematoma
Collection of blood underneath dura
Subdural Hematoma
Due to tearing of bridging veins that lie between the dura and arachnoid
Subdural Hematoma
Crescent-shaped lesion on CT
Subdural Hematoma
Presents with progressive neurologic signs
Subdural Hematoma
Displacement of brian tissue due to mass effect or increased intracranial pressure
Herniation
Displacement of cerebellar tonsils into foramen magnum
Tonsillar herniation
Compression of brain stem leads to cardiopulmonary arrest
Tonsillar herniation
Displacement of cingulate gyrus under falx cerebri
Subfalcine herniation
Compression of anterior cerebral artery leads to infarction
Subfalcine herniation
Displacement of temporal lobe uncus under the tentoriumcerebelli
Uncal herniation
Compression of cranial nerve III leads to eye moving down and out with dilated pupil
Uncal herniation
Compression of posterior cerebral artery leads to infarction of occipital lobe with contralateral homonymous hemianopsia
Uncal herniation
Rupture of paramedian artery leads to Duret hemorrhage
Uncal herniation
inherited mutations in enzymes necessary for production or maintenance of myelin
Leukodystrophies
Due to deficiency of arylsulfatase (autosomal recessive)
Metachromatic leukodystrophy
Most common leukodystrophy
Metachromatic leukodystrophy
Sulfatides can’t be degraded and accumulate in lysosomes of oligodendrocytes
Metachromatic leukodystrophy
Autosomal recessive deficiency of galactocerebrosidase
Krabbe disease
Accumulates in macrophages
Krabbe disease
Impaired addition of coenzyme A to long-chain fatty acids (X-linked defect)
Adrenoleukodystrophy
Accumulation of fatty acids damages adrenal glands and white matter of brain
Adrenoleukodystrophy
Autoimmune destruction of CNS myelin and oligodendocytes
Multiple Sclerosis
Most common chronic CNS disease of young adults, more commonly seen in women
Multiple Sclerosis
Associated with HLA-DR2
Multiple Sclerosis
More commonly see in regions away from equator
Multiple Sclerosis
Presents with relapsing neurologic deficits with periods of remission
Multiple Sclerosis
Presents with blurred vision in one eye and internuclear opthalamoplegia
Multiple Sclerosis
Presents with vertigo and scanning speech mimicking drunkeness
Multiple Sclerosis
Presents with hemiparesis or unilateral loss of sensation, lower extremity loss of sensation or weakness, and bowel, bladder & sexual dysfunction
Multiple Sclerosis
Diagnosis is made by MRI and lumbar puncture
Multiple Sclerosis
MRI reveals plaques and lumbar puncture shows increased lymphocytes, IG’s with oligoclonal IgG bands, and myelin basic protein
Multiple Sclerosis
Treatment of acute attacks is high-dose steroids
Multiple Sclerosis
Treatment long-term is interferon beta
Multiple Sclerosis
Due to slow progressing, persistent infection of brain by measles virus
Subacute Sclerosing Pancencephalitis
Infection occurs in infancy with neurologic signs years later
Subacute Sclerosing Pancencephalitis
Characterized by viral inclusions within neurons of gray matter and oligodendrocytes of white matter
Subacute Sclerosing Pancencephalitis
JC virus infection of oligodendrocytes
Progressive multifocal leukoencephalopathy
Immunosuppression leads to reactivation of latent virus
Progressive multifocal leukoencephalopathy
Presents with progressive neurologic signs (Visual loss, weakness, dementia) leading to death
Progressive multifocal leukoencephalopathy
Focal demyelination of the pons
Central pontine myelinolysis
Due to rapid intravenous correction of hyponatremia
Central pontine myelinolysis
Occurs in severely malnourished patients (alcoholics and liver disease)
Central pontine myelinolysis
Classically presents as acute bilateral paralysis (locked in syndrome) with only exception being the eyes
Central pontine myelinolysis
Degeneration of cortex
Dementia
Degeneration of brainstem and basal ganglia
Movement disorders
Most common cause of dementia
Alzheimer Disease
Presents as slow-onset memory loss (short-term first) and progressive disorientation
Alzheimer Disease
Loss of learned motor skills and language
Alzheimer Disease
Changes in behavior and personality
Alzheimer Disease
Most cases are sporadic and seen in elderly
Alzheimer Disease
Risk of this increases with age
Alzheimer Disease
ApoE4 is associated with increased risk
Alzheimer Disease
ApoE2 is associated with decreased risk
Alzheimer Disease
Seen in presenilin 1 and presenilin 2 mutations
Early-Onset Alzheimer Disease
Seen in Down syndrome
Early-Onset Alzheimer Disease
Cerebral atrophy with narrowing of the gyri, widening of sulci, dilation of ventricles
Alzheimer Disease
Neuritic plaques of A-Beta amyloid with entangled neuriti cprocesses
Alzheimer Disease
APP on chromosome 21 is the source of protein to be turned into Beta amyloid
Alzheimer Disease
Presents with neurofibrillary tangles: aggregates of hyperphosphorylated tau protein
Alzheimer Disease
Diagnosis of exclusion
Alzheimer Disease
Diagnosis confirmed upon autopsy
Alzheimer Disease
Multifocal infarction and injury due to HTN, atherosclerosis, or vasculitis
Vascular Dementia
2nd most common cause of dementia
Vascular Dementia
Degenerative disease of frontal and temporal cortex
Pick Disease
Characterized by round aggregates of tau protein
Pick Disease
Presents with behavioral and language symptoms early
Pick Disease
Degenerative loss of dopaminergic neurons in substantia nigra of basal ganglia
Parkinson Disease
Rare cases related to MPTP exposure
Parkinson Disease
Tremor
Rigidity
Akinesia/Bradykinesia
Postural instability/Shuffling Gait
Parkinson Disease
Loss of pigmented neurons in substantia nigra
Parkinson Disease
Eosinophilic inclusions of alpha-synuclein (Lewy bodies)
Parkinson Disease
Usually the cause of early-onset dementia
Parkinson Disease
Degeneration of GABAergic neurons in caudate nucleus of basal ganglia
Huntington Disease
Autosomal dominant disorder of CAG trinucleotide repeat of gene on chromosome 4
Huntington Disease
Further expansion of repeats during spermatogenesis leads to anticipation
Huntington Disease
Presents with chorea that progresses to dementia and depression
Huntington Disease
Suicide is common cause of death
Huntington Disease
Increased CSF resulting in dilated ventricles and stretching of nerves
Normal Pressure Hydrocephalus
Presents as triad of urinary incontinence, gait instability and dementia
(Wet, Wacky, Wobbly)
Normal Pressure Hydrocephalus
Lumbar puncture improves symptoms
Normal Pressure Hydrocephalus
Treatment is ventriculoperitoneal shunting
Normal Pressure Hydrocephalus
Degenerative disease due to prion protein
Spongiform Encephalopathy
Disease arises with conversion to a Beta-pleated conformation
Spongiform Encephalopathy
Damage to neurons and glial cells characterized by intracellular vacuoles
Spongiform Encephalopathy
Most common spongiform encephalopathy
Creutzfeldt-Jakob Disease
Presents as rapidly progressive dementia with ataxia and startle myoclonus
Creutzfeldt-Jakob Disease
Periodic sharp waves are seen on EEG
Creutzfeldt-Jakob Disease
Related to exposure to bovine spongiform encephalopathy
Variant Cruejtzfeldt-Jakob Disease
Inherited form of prion disease characterized by severe insomnia and exaggerated startle response
Familial Fatal Insomnia
Most common primary malignant CNS tumor in adults
Glioblastoma Multiforme
Malignant, high grade tumor of astrocytes
Glioblastoma Multiforme
Arises in cerebral hemisphere and crosses the corpus callosum to form a butterfly lesion
Glioblastoma Multiforme
Characterized by regions of necrosis surrounded by tumor cells (Pseudopalisading) and endothelial cell proliferation
Glioblastoma Multiforme
Tumor cells are GFAP positive
Glioblastoma Multiforme
Benign tumor of arachnoid cells
Meningioma
Most common benign CNS tumor in adults
Meningioma
More commonly seen in women due to being estrogen sensitive
Meningioma
Present as seizures
Meningioma
Findings: Round mass attached to dura, whorled pattern and possible psammoma bodies
Meningioma
Benign tumor of Schwann cells
Schwannoma
Involves cranial or spinal nerves, most frequently CN VIII at cerebellopontine angle
Schwannoma
Presents as loss of hearing and tinnitus
Schwannoma
Tumor cells are S-100 positive
Schwannoma
Bilateral forms of this are seen in neurofibromatosis type 2
Schwannoma
Malignant tumor of oligodendrocytes
Oligodendroglioma
Calcified tumor in white matter usually in frontal lobe
Oligodendroglioma
Presents as seizures
Oligodendroglioma
Fried egg appearance of cells on biopsy
Oligodendroglioma
Benign tumor of astrocytes
Pilocytic astrocytoma
Most common CNS tumor in kids
Pilocytic astrocytoma
Imaging reveals cystic lesion with a mural nodule
Pilocytic astrocytoma
Biopsy shows Rosenthal fibers and eosinophilic granular bodies
Pilocytic astrocytoma
Tumor cells are GFAP positive
Pilocytic astrocytoma
Malignant tumor derived from granular cells of cerebellum in kids
Medulloblastoma
Small round blue cells with Homer-Wright rosettes
Medulloblastoma
Metastasis of this to cauda equina is termed drop metastasis
Medulloblastoma
Malignant tumor of ependymal cells in kids
Ependymoma
Most commonly arises in 4th ventricle and may presents with hydrocephalus
Ependymoma
Primary finding are perivascular pseudorosettes
Ependymoma
Tumor that arises from epithelial remnants of Rathke’s pouch
Craniopharyngioma
Presents as a supratentorial mass in a child or young adult
Craniopharyngioma
May compress the optic chiasm leading to bitemporal hemianopsia
Craniopharyngioma
Calcifications are commonly seen on imaging (derived from tooth-like tissue)
Craniopharyngioma
