CNS Pathology Flashcards by Sarah Gillen

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

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_____ ______ 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

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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

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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

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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

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Cystic degeneration of the spinal cord that arises with trauma or in association with Arnold-Chiari malformation

Syringomyelia

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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!]

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Poliomyelitis results in damage to _____________ of the spinal cord due to poliovirus infection. These patients present with ___________ signs

Anterior motor horn; lower motor neuron

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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

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_______ _______ ______ 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

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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

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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]

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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

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Inheritance and mutation associated with Freidreich Ataxia

Autosomal Recessive

Unstable trinucleotide repeat (GAA) in frataxin gene

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Friedreich ataxia presents in early childhood and is associated with what cardiovascular condition?

Hypertrophic cardiomyopathy

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Meningitis = inflammation of the ___________

Leptomeninges (pia and arachnoid)

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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

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Most common infectious cause of meningitis in children and teens

N meningitidis

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Most common infectious cause of meningitis in adults and elderly

Strep pneumo

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Most common infectious cause of meningitis in nonvaccinated infants

H flu

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T/F: Coxsackievirus and fungi are capable of causing meningitis

True

[fungal causes more common in immunocompromised]

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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]

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T/F: while performing a lumbar puncture, you pass through the pia mater

False

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Complications are more commonly seen with bacterial meningitis. What are the major complications?

Death

Hydrocephalus, hearing loss, seizures

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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

1. Thrombosis —> pale infarct 2. Embolism —> hemorrhagic infarct 3. 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