CNS Pathology Flashcards
Anencephaly is the absence of skull and brain due to failure of cranial closure of neural tube. This results in a ‘frog-like’ appearance of the fetus as well as maternal _______
Polyhydramnios
_____ ______ is failure of posterior vertebral arch to close, leading to meningocele or meningomyelocele. ______ _____ ______ leads to a dimple or patch of hair overlying the vertebral defect
Spina bifida; spina bifida occulta
Cerebral aqueduct stenosis is congenital stenosis of the channel that drains CSF from the _____________________, leading to accumulation of CSF in the ventricles and presents with enlarging head circumference
3rd and 4th ventricles
Congenital failure of the cerebellar vermis to develop, presenting as a massively dilated 4th ventricle with absent cerebellum; often accompanied by hydrocephalus
Dandy-Walker malformation
Congenital extension of cerebellar tonsils through foramen magnum in which obstruction of CSF flow may result in hydrocephalus; also may occur in association with meningomyelocele and syringomyelia
Arnold-Chiari Malformation
Cystic degeneration of the spinal cord that arises with trauma or in association with Arnold-Chiari malformation
Syringomyelia
Syringomyelia usually occurs at level ________, affecting the ________ ______ ________ of the spinal cord, resulting in sensory loss of _____ and _______.
If the syrinx expands into ________ horns, lower motor neuron signs may arise (muscle atrophy and weakness with decreased tone and impaired reflexes). If the _______ horns are affected, patient may present with Horner’s syndrome (ptosis, miosis, anhydrosis).
C8-T1; anterior white commissure; pain; temperature
Anterior; lateral
[Note that fine touch and position sense, which are located in dorsal commissure, are spared in the UE with syringomyelia!]
Poliomyelitis results in damage to _____________ of the spinal cord due to poliovirus infection. These patients present with ___________ signs
Anterior motor horn; lower motor neuron
Autosomal recessive inherited degeneration of anterior motor horn (presents similarly to poliomyelitis), presenting as “floppy baby”; death occurs within a few years after birth
Werdnig-Hoffmann Disease
_______ _______ ______ is a degenerative disorder of upper and lower motor neurons (_______ tract). Anterior motor horn involvement leads to LMN signs, while _______ ______ _____ involvement leads to UMN signs.
Amyotrophic Lateral Sclerosis; Corticospinal; Lateral corticospinal tract
Atrophy and weakness of hands is an early sign of ALS. How is ALS distinguished from syringomyelia?
Lack of sensory impairment distinguishes ALS from syringomyelia
Most cases of ALS are sporadic, arising in middle aged adults. However, a _______________________ mutation is present in some familial cases
Zinc-copper superoxide dismutase
[increased free-radical damage to neurons]
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 DTRs
Friedreich Ataxia
Inheritance and mutation associated with Freidreich Ataxia
Autosomal Recessive
Unstable trinucleotide repeat (GAA) in frataxin gene
Friedreich ataxia presents in early childhood and is associated with what cardiovascular condition?
Hypertrophic cardiomyopathy
Meningitis = inflammation of the ___________
Leptomeninges (pia and arachnoid)
Meningitis is most commonly due to an infectious agent. What are the 3 most common infectious agents that cause meningitis in neonates?
Group B strep
E Coli
L monocytogenes
Most common infectious cause of meningitis in children and teens
N meningitidis
Most common infectious cause of meningitis in adults and elderly
Strep pneumo
Most common infectious cause of meningitis in nonvaccinated infants
H flu
T/F: Coxsackievirus and fungi are capable of causing meningitis
True
[fungal causes more common in immunocompromised]
At what level is a lumbar puncture performed? What layers do you pass through?
L4-L5 at level of iliac crest
Skin —> ligaments —> epidural space —> dura —> arachnoid
[Spinal cord ends at L2 but subarachnoid space and cauda equina continue to S2]
T/F: while performing a lumbar puncture, you pass through the pia mater
False
Complications are more commonly seen with bacterial meningitis. What are the major complications?
Death
Hydrocephalus, hearing loss, seizures
Cerebrovascular disease is a neurologic deficit arising due to cerebrovascular compromise, either due to ischemia (85%) or hemorrhage (15%). One type of ischemia is global cerebral ischemia, which may be due to what 4 conditions?
Low perfusion (atherosclerosis)
Acute decrease in blood flow (shock)
Chronic hypoxia (anemia)
Repeated episodes of hypoglycemia (insulinoma)
Clinical features of global cerebral ischemia depend on degree of ischemia, whether mild, moderate, or severe. A common example of mild global ischemia is with periodic hypoglycemia due to insulinoma. With moderate global ischemia, it is common to get infarcts in watershed areas, leading to damage to highly vulnerable regions. What are the 3 major “highly vulnerable regions” that may be affected?
Pyramidal neurons of the cortex (layers 3, 5, and 6 of the cortex — see cortical laminar necrosis)
Pyramidal neurons of the hippocampus
Purkinje layer of the cerebellum (see cerebellar signs)
What is the difference between an ischemic stroke and a TIA?
Ischemic stroke = regional ischemia that results in focal neurologic deficits for >24 hours
TIA = Symptoms <24 hours
3 ways in which you can develop an ischemic stroke
- Thrombosis —> pale infarct
- Embolism —> hemorrhagic infarct
- Lacunar stroke
Describe pathogenesis of a thrombotic stroke
Rupture of atherosclerotic plaque; usually develops at branch points
Results in a PALE infarct at the periphery of the cortex
Describe the pathogenesis of an embolic stroke
Due to thromboemboli; most common source is left side of heart
Usually involves the middle cerebral artery (classically in the setting of afib)
Results in a HEMORRHAGIC infarct at the periphery of the cortex
A lacunar stroke occurs secondary to ______ ________, and most commonly involves the ________ vessels
Hyaline arteriosclerosis; lenticulostriate
Ischemic stroke leads to _____ necrosis. ____ ________ are an early finding on microscopy. Neutrophils, microglial cells, and granulation tissue then ensue. The result is a fluid-filled cystic space surrounded by ______ (reactive astrocytes lining cystic space)
Liquefactive; Red neurons; gliosis
Intracerebral hemorrhage = bleeding into the brain parenchyma. This is classically due to what?
Rupture of Charcot-Bouchard microaneurysms (complication of HTN)
Intracerebral hemorrhage is classically due to rupture of Charcot-Bouchard microaneurysms as a complication of HTN. The most common site is the _____ _____; clinically presents with headache, nausea, vomiting, and eventual coma
Basal ganglia
Subarachnoid hemorrhage = bleeding into subarachnoid space. Presents as sudden headache with nuchal rigidity. Lumbar puncture shows _________
Xanthochromia
[yellow tinge to CSF due to bilirubin breakdown products]
Most common cause of subarachnoid hemorrhage
Rupture of berry aneurysm
The most common cause of a subarachnoid hemorrhage is rupture of a berry aneurysm, which is a thin-walled saccular outpouching that lacks a ______ layer, most frequently located in _______________
Media; anterior circle of willis (branch points of anterior communicating artery)
2 conditions classically associated with berry aneurysms
Marfan
ADPKD
Epidural hematoma = collection of blood between dura and skull. This is often due to fracture of __________ with rupture of the ________.
Presents with a ______-shaped lesion on CT. Note that a lucid interval may precede neurologic signs, and _______ is a lethal complication
Temporal bone; middle meningeal artery
Lens; herniation
Pathogenesis of subdural hematoma (collection of blood underneath dura)
Tearing of bridging veins between dura and arachnoid
[usually arises with trauma]
T/F: Subdural hematoma presents with progressive neurologic signs and, as with epidural hematoma, herniation is a lethal complication
True
Herniation = displacement of brain tissue due to mass effect or increased ICP. What are the 3 major types of herniation?
Tonsillar herniation (cerebellar tonsils)
Subfalcine herniation (cingulate gyrus)
Uncal herniation (uncus of temporal lobe)
Complications of tonsillar herniation
Cardiopulmonary arrest
[Cerebellar tonsils go through foramen magnum, compressing brainstem]
Complications of subfalcine herniation
Compression of anterior cerebral artery —> infarction
[cingulate gyrus herniates underneath falx cerebri]
Complications of uncal herniation
Compression of CN III —> eyes move down and out with dilated pupil
Compression of posterior cerebral artery —> infarction of occipital lobe
Pull on paramedian artery —> duret hemorrhages on brainstem
[herniation of uncus of temporal lobe into tentorium cerebelli]
Demyelinating disorders of the CNS are due to destruction of the ______ or ________. The axons are preserved, but the conduction of the impulse is impaired
Myelin; oligodendrocytes
_______ = general term for conditions in which there are inherited mutations in enzymes necessary for production or maintenance of myelin
Leukodystrophies
Most common leukodystrophy
Metachromatic leukodystrophy
Metachromatic leukodystrophy = deficiency of ________. Myelin cannot be degraded so it accumulates in _________
Arylsulfatase; lysosomes
Deficiency of galactocerebroside beta-galactosidase resulting in galactocerebroside accumulation in macrophages
Krabbe disease
Impaired addition of coenzyme A to long-chain fatty acids, thus fatty acids accumulate, damaging adrenal gland and white matter
Adrenoleukodystrophy
Autoimmune destruction of CNS myelin and oligodendrocytes; more commonly seen in regions away from the equator.
Multiple sclerosis
Multiple sclerosis is associated with what immunologic marker?
HLA-DR2
Clinical features of multiple sclerosis
Blurred vision in one eye (optic nerve involvement)
Vertigo and scanning speech (brainstem involvement)
Internuclear ophthalmoplegia (MLF involvement)
Hemiparesis or unilateral loss of sensation (cerebral white matter)
Lower extremity loss of sensation or weakness (spinal cord)
Bowel, bladder, and sexual dysfunction (ANS)
2 ways of diagnosing multiple sclerosis
MRI — reveals plaques
Lumbar puncture — shows increased lymphocytes, increased Ig with oligoclonal IgG bands, and myelin basic protein
Treatment of multiple sclerosis for acute attack vs. slowing the progression
High-dose steroids for acute attack
IFN-beta slows progression
Progressive, debilitating encephalitis leading to death; caused by slowly progressing, persistent infection of the brain by the MEASLES virus
Subacute Sclerosing Panencephalitis
Subacute sclerosing panencephalitis is due to a measles infection that begins in infancy, with neurologic signs arising years later. It is characterized by viral inclusion within _______ (gray matter) and _______ (white matter)
Neurons; oligodendrocytes
Progressive multifocal leukoencephalopathy is due to a ___________ infection of the oligodendrocytes in the setting of viral reactivation due to immunosuppression (AIDS, leukemia, etc). Clinically presents with rapidly progressive neurologic signs leading to death
JC virus
Central pontine myelinolysis is a focal demyelination of the pons. What causes this?
Rapid IV correction of hyponatremia, occurs in severely malnourished patients
Which of the CNS demyelinating pathologies classically presents as acute paralysis (‘locked in’ syndrome)?
Central Pontine Myelinolysis
Degenerative disease of the cortex and most common cause of dementia
Alzheimer disease
Alzheimers disease results from the breakdown of _____ into ______ which accumulates in the brain
APP; AB amyloid
There are 2 forms of Alzheimers disease: sporadic and early-onset form. Most cases are sporadic, seen in the elderly, and associated with increased risk with age. For the sporadic form, the _______ allele of ___________ is associated with increased risk, while the ______ allele is associated with decreased risk
E4; apolipoprotein E; E2
Early-onset Alzheimers disease is seen in younger patients. Familial cases are associated with _____ and _____ mutations. Patients with _________ are also at increased risk of early-onset Alzheimers disease
Presenilin 1; presenilin 2; Down syndrome
Histology of Alzheimers disease may reveal neurofibrillary tangles containing hyperphosphorylated ____ proteins
Tau
2nd most common cause of dementia; often caused by HTN, atherosclerosis, or vasculitis leading to multifocal infarction and injury
Vascular dementia
Degenerative disease of frontal and temporal cortex; spares parietal and occipital lobes; associated with aggregates of tau protein in neurons of cortex. Clinical features include early behavioral and language symptoms which progress to dementia
Pick disease
Parkinson disease is a degenerative loss of dopaminergic neurons in what part of the brain?
Substantia nigra pars compacta (basal ganglia)
Parkinsons disease is a common disorder related to aging but the etiology is unknown. Rare cases have been related to exposure to molecule called ______, which is a contaminant in illicit drugs
MPTP
Parkinsons is associated with ______ bodies on histology, which contain _________. These are the hallmark of Parkinson disease
Lewy; alpha-synuclein
T/F: one of the first clinical features evident in Parkinson disease is dementia
False — dementia is a common feature of LATE disease. Early-onset dementia suggests Lewy body dementia, which is characterized by dementia, hallucinations, and parkinsonian features with cortical Lewy bodies
Huntington disease is characterized by degeneration of GABAergic neurons in the _____ _____ of the basal ganglia. This disorder is autosomal ________ due to expanded trinucleotide repeats (CAG) in huntingtin gene. Further expansion occurs during development with _______, which is the feature to blame for anticipation in this disease
Caudate nucleus; dominant; spermatogenesis
What is hydrocephalus ex vacuo?
Expansion and increase in volume of ventricles due to loss of surrounding brain matter
[NOT due to increase in CSF volume]
______ ______ ______ = increased CSF due to decreased absorption into arachnoid granulations, thus resulting in dilated ventricles and stretching of the corona radiata. Can cause dementia in adults; usually idiopathic
Normal pressure hydrocephalus
Triad of Normal Pressure Hydrocephalus
Urinary incontinence
Gait instability
Dementia
[Wet, wacky, wobbly]
Treatment for normal pressure hydrocephalus
Lumbar puncture improves symptoms; treatment is VP shunt
Spongiform encephalopathy is a degenerative disease due to accumulation of prion protein. Normal prion protein is present in the brain in the ________ configuration. If this gets converted to ______ configuration, it becomes pathologic because it cannot be degraded and also feeds back to the normal configuration to continue producing the pathologic configuration
Alpha (PrPc); beta (PrPsc)
Accumulation of the pathologic form of prion protein (beta or PrPsc) results in damage to neurons and glial cells, and this damage is characterized by _______ _______ in brain parenchyma
Intracellular vacuoles
Spongiform encephalopathy arises with conversion of alpha configuration of prion protein to the beta configuration. What are the 3 primary etiologies?
Sporadic
Inherited
Transmission (aka infectious)
Most common form of spongiform encephalopathy
CJD
CJD is usually sporadic, but rarely arises due to exposure to prion infected human tissue. What is the clinical presentation, findings on EEG, and prognosis?
Clinically presents with rapidly progressive dementia associated with ataxia and startle myoclonus
EEG shows spike-wave complexes
Results in death, usually in <1year
_______ is related to exposure to bovine spongiform encephalopathy (‘mad cow’)
______ ______ ______ is inherited form of prion disease characterized by insomnia and exaggerated startle response
vCJD
Familial fatal insomnia
T/F: Malignant tumors are locally destructive and rarely metastasize.
True
Most common malignant CNS tumor in adults
Glioblastoma multiforme
Glioblastoma multiforme is a malignant, high-grade tumor of ______
Astrocytes
Most common benign CNS tumor; F>M, may present with seizures due to compression of cortex
Meningioma
A meningioma is a benign tumor of _______ cells; imaging reveals a round mass attached to the _____.
Histology shows _______ pattern with ______ bodies
Arachnoid; dura
Whorled; psammoma
Schwannomas are benign tumors of schwann cells that can involve cranial or spinal nerves, especially ________ at _______.
These tumors are ______ positive.
Bilateral schwannomas are seen with ________
CN VIII; CPA
S-100
NF2
Oligodendrogliomas are malignant tumors of oligodendrocytes. These are calcified tumors in the white matter, usually involving the _____ lobe. They may present with ______
Frontal; seizures
Most common CNS tumor in children; usually arising in cerebellum
Pilocytic astrocytoma (benign tumor of astrocytes)
Pilocytic astrocytoma on imaging and histology
Imaging — cystic lesion with a mural nodule
Histology — astrocytes with rosenthal fibers (thick eosinophilic processes), GFAP+
CNS tumor characterized on histology by small, round blue cells; Homer-Wright rosettes may be present
Medulloblastoma
Medulloblastoma is a malignant tumor derived from ______ cells of the _______; usually arises in children and has a poor prognosis, since the tumor grows rapidly and spreads via ______ (“drop metastases”)
Granular; cerebellum; CSF
Ependymoma is a malignant tumor of ependymal cells; usually seen in children. Most commonly arises in ________; may present with _______
4th ventricle; hydrocephalus
Ependymoma key histo finding
Perivascular pseudorosettes
Craniopharyngioma is a tumor that arises from epithelial remnants of ____________; presents as a supratentorial mass in a child or young adult. Optic chiasm compression leads to ______ _______
Rathke’s pouch; bitemporal hemianopsia
Craniopharyngioma appears with ________ seen on imaging. It is benign, but tends to recur after resection.
Calcifications
