CH17 - Central Nervous System Pathology Flashcards
What are the developmental anomolies?
1) neural tube defects 2) cerebral aqueduct stenosis 3) Dandy Walker Malformation 4) Arnold Chiari Malformation
What do neural tube defects arise from?
They arise from incomplete closure of the neural tube
What happens to the neural plate early in gestation?
It invaginates to form the neural tube, which runs along the cranial caudal axis of the embryo
Regarding the neural plate, what forms the central nervous system?
The wall of the neural tube forms central nervous system tissue,
In the neural tube, what does the hollow lumen form?
the ventricles and spinal cord canal, and the neural crest forms the peripheral nervous system.
What are neural tube defects associated with?
low folate levels prior to conception
When are neural tube defects detected?
during prenatal care by elevated alpha-fetoprotein (AFP) levels in the amniotic fluid and maternal blood
What is anencephaly?
it is the absence of the skull and brain (disruption of the cranial end of the neural tube)
What does anencephaly lead to?
a frog like appearance of the fetus
What does anencephaly result in?
maternal polyhydramnios since fetal swallowing of amniotic fluid is impaired
What is spina bifida?
It is failure of the posterior vertebral arch to close, resulting in a vertebral defect (disruption of the caudal end of the neural tube).
How does Spina bifida occulta present?
as a dimple or patch of hair overlying the vertebral defect.
How does Spina bifida present?
with cystic protrusion of the underlying tissue through the vertebral defect
What is a meningocele?
protrusion of meninges
What is meningomyelocele?
protrusion of meninges and spinal cord
What is cerebral aqueduct stenosis?
congenital stenosis of the channel that drains cerebrospinal fluid (CSF) from the 3rd ventricle into the 4th ventricle
What does cerebral aqueduct stenosis lead to?
accumulation of CSF in the ventricular space; most common cause of hydrocephalus in newborns
What is the most common cause of hydrocephalus in newborns?
Cerebral aqueduct stenosis
What produces the CSF?
It is produced by the choroid plexus lining the ventricles
Decribe the flow of CSF?
from the lateral ventricles into the 3rd ventricle via the interventricular foramen of Monro, Flows from the 3rd ventricle into the 4th ventricle via the cerebral aqueduct, Flows from the 4th ventricle into the subarachnoid space via the foramina of Magendie and Luschka
What is the cerebral aqueduct?
Allows for the flow from the 3rd ventricle into the 4th ventricle
What allows the CSF to flow from the 4th ventricle into the subarachnoid space?
Via the foramina of Magendie and Luschka
What is the foramen of monro?
Allows for the flow of CSF from the lateral ventricles into the 3rd ventricle
What does cerebral aqueduct stenosis present with?
enlarging head circumference due to dilation of the ventricles (cranial suture lines are not fused)
What is a dandy walker malformation?
Congenital failure of the cerebellar vermis to develop
How does a dandy walker malformation present?
as a massively dilated 4th ventricle (posterior fossa) with an absent cerebellum; often accompanied by hydrocephalus
What is an Arnold chiari malformation?
Congenital extension of cerebellar tonsils through the foramen magnum
What might Arnold Chiari malformation result in?
Obstruction of CSF flow can result in hydrocephalus
What might Arnold chiari malformation occur in association with?
meningomyelocele and syringomyelia
What are the spinal cord lesions?
Syringomyelia, poliomyelitis, Werdnig-Hoffmann disease, amyotrophic lateral sclerosis, Friedreich ataxia
What is syringomyelia?
Cystic degeneration of the spinal cord
What does syringomyelia arise with?
trauma or in association with an Arnold-Chiari malformation
Where does syringomyelia usually occur?
at C8-T1
How does syringomyelia present?
as sensory loss of pain and temperature with sparing of fine touch and position sense in the upper extremities (cape like distribution)
What is the presentation of syringomyelia due to?
involvement of the anterior white commissure of the spinothalamic tract with sparing of the dorsal column
What does syrinx expansion result in?
involvement of other spinal tracts leading to 1. Muscle atrophy and weakness with decreased muscle tone and impaired reflexes 2. Horner syndrome with ptosis (droopy eyelid), miosis (constricted pupil), and anhidrosis (decreased sweating)
Why does the syrinx expansion result in muscle atrophy and weakness with decreased muscle tone and impaired reflexes?
Its due to damage to lower motor neurons of the anterior horn
What is ptosis?
Droopy eyelid
What is miosis?
Constricted pupil
What is anhidrosis?
Decreased sweating
Why does the syrinx expansion lead to horner syndrome with ptosis (droopy eyelid), miosis (constricted pupil), and anhidrosis (decreased sweating)?
It?s due to disruption of the lateral horn of the hypothalamospinal tract
What is poliomyelitis?
Damage to the anterior motor horn due to poliovirus infection
How does poliomyelitis present?
with lower motor neuron signs?flaccid paralysis with muscle atrophy, fasciculations, weakness with decreased muscle tone, impaired reflexes, and negative Babinski sign (downgoing toes)
What is Werdnig-Hoffman disease?
It?s an inherited degeneration of the anterior motor horn and is autosomal recessive
How does Werdnig-Hoffman disease present?
as a floppy baby, death occurs within a few years after birth.
What is amyotrophic lateral sclerosis?
Degenerative disorder of upper and lower motor neurons of the corticospinal tract
In ALS, what does anterior motor horn degeneration lead to?
lower motor neuron signs?flaccid paralysis with muscle atrophy, fasciculations, weakness with decreased muscle tone, impaired reflexes, and negative Babinski sign.
In ALS what does lateral corticospinal tract degeneration lead to?
upper motor neuron signs ? spastic paralysis with hyperreflexia, increased muscle tone, and positive Babinski sign.
What is an early sign of ALS?
atrophy and weakness of hands is an early sign
What distinguishes ALS from syringomyelia?
Lack of sensory impairment
What are most cases of ALS?
they are sporadic, arising in middle age adults
What is present in some familial cases of ALS?
Zinc-copper superoxide dismutase mutation (SOD) is present in some familial cases; leads to free radical injury in neurons
What is Friedreich Ataxia?
Degenerative disorder of the cerebellum and spinal cord
What does degeneration of the cerebellum lead to?
ataxia
What does degeneration of multiple spinal cord tracts lead to?
loss of vibratory sense and proprioception, muscle weakness in the lower extremities, and loss of deep tendon reflexes
What is the cause of Friedreich Ataxia genetically?
Autosomal recessive; due to expansion of an unstable trinucleotide repeat (GAA) in the frataxin gene
What is frataxin?
it is essential for mitochondrial iron regulation; loss results in iron buildup with free radical damage.
How does Friedreich Ataxia present?
in early childhood; patients are wheelchair bound within a few years
What is Friedreich Ataxia associated with?
hypertrophic cardiomyopathy
What does the spinothalamic tract do?
Pain and temperature sensation
What is the first order neuron for the spinothalamic tract?
Peripheral nerves of posterior horn; cell body is in dorsal root ganglion.
What is the second order neuron for the spinothalamic tract?
It arises from posterior horn, immediately crosses over in anterior white commissure, and ascends via the spinothalamic tract to thalamus
What is the third order neuron for the spinothalamic tract?
thalamus to cortex
What is the Dorsal column-medial lemniscus responsible for?
pressure, touch, vibration, and proprioception
What are the first order neurons for the dorsal column-medial lemniscus?
Peripheral nerves to medulla via dorsal column; cell body is in dorsal root ganglion.
What is the second order neuron for the dorsal column-medial lemniscus?
Arises from medulla, crosses over, and ascends via the medial lemniscus to thalamus
What is the third order neuron for the dorsal column-medial lemniscus?
Thalamus to cortex
What is the lateral corticospinal tract responsible for?
voluntary movement
What are the first order neurons for the lateral corticospinal tract?
Pyramidal neurons in the cortex descend, cross over in medullary pyramids, and synapse on the anterior motor horn of the cord (upper motor neuron)
What is the second order neuron for the lateral corticospinal tract?
Arises from the anterior motor horn and synapses on muscle (lower motor neuron)
What are the third order neurons for the lateral corticospinal tract?
None
What is the hypothalamospinal tract responsible for?
sympathetic input of the face
What is the first order neuron for the hyothalamospinal tract?
It arises from the hypothalamus and synapses on the lateral horn at T1
What is the second order neuron for the hypothalamospinal tract?
It arises from lateral horn at T1 and synapses on the superior cervical ganglion (sympathetic)
What is the third order neuron for the hypothalamospinal tract?
Superior cervical ganglion to eyelids, pupil, and skin of face
What is meningitis?
inflammation of the leptomeninges
What do the meninges consist of?
three layers (dura, arachnoid, and pia) that lie between the brain and the skull,
What are the leptomeninges?
Pia and arachnoid together
What is meningitis most commonly due to?
an infectious agent
What are the infectious agents that cause meningitis?
1) Group B streptococci, E coli, and Listeria monocytogenes (neonates) 2) N meningitidis (children and teenagers). Streptococcus-pneumoniae (adults and elderly), and H influenza (non vaccinated infants) 3. Coxsackievirus (children; fecal-oral transmission) 4. Fungi (immunocompromised individuals)
What is the infectious agent causing meningitis for neonates?
Listeria monocytes
What is the infectious agent causing meningitis for children and teenagers?
N. Meningitidis
What is the infectious agent causing meningitis for adults and elderly?
Streptococcus-pneumoniae
What is the infectious agent causing meningitis for non vaccinated infants?
H. Influenzae
What is the infectious agent causing meningitis for children; fecal-oral transmission?
Coxsackievirus
What is the infectious agent causing meningitis for immunocomprimised individuals?
fungi
How does meningitis present?
With a classic triad of headache, nuchal rigidity (neck stiffness), and fever; photophobia, vomiting, and altered mental status may also be present,
How is the diagnosis for meningitis made?
it is made by lumbar puncture (sampling of CSF)
How is a lumbar puncture performed?
by placing a needle between L4 and L5 (level of the iliac crest). Spinal cord ends at L2, but subarachnoid space and cauda equina continue to S2.
What are the layers crossed by the lumbar puncture?
include skin, ligaments, epidural space, dura, and arachnoid.
What are the CSF findings in LP for bacterial meningitis?
neutrophils with low CSF glucose; positive gram stain and culture often identify the causative organism.
What are the CSF findings in LP for viral meningitis?
lymphocytes with normal CSF glucose
What are the CSF findings in LP for fungal meningitis?
lymphocytes with low CSF glucose
Complications are usually seen with what type of meningitis?
bacterial meningitis
What is involved in cerebrovascular disease?
Neurologic deficit due to cerebrovascular compromise; major cause of morbidity and mortality
What is cerebrovascular disease due to?
ischemia (85% of cases) or hemorrhage (15% of eases)
What are neurons dependent on and what are the susceptible to?
serum glucose as an essential energy source and are particularly susceptible to ischemia (undergo necrosis within 3 - 5 minutes).
What is global cerebral ischemia?
Global ischemia to the brain
What are the major etiologies for global cerebral ischemia?
- Low perfusion (e.g., atherosclerosis) 2. Acute decrease in blood flow (e.g., cardiogenic shock) 3. Chronic hypoxia (e.g., anemia) 4. Repeated episodes of hypoglycemia (eg insulinoma)
What are the clinical features for global cerebral ischemia based on?
Its based on duration and magnitude of the insult.
What does mild global ischemia result in?
transient confusion with prompt recovery
What does severe global ischemia result in?
diffuse necrosis; survival leads to a vegetative state
What does moderate global ischemia lead to?
infarcts in watershed areas (eg area lying between regions fed by the anterior and middle cerebral artery) and damage to highly vulnerable regions
In moderate global ischemia, what are the vulnerable regions that may be damaged?
1) Pyramidal neurons of the cerebral cortex (layers 3, 5, and 6) 2) Pyramidal neurons of the hippocampus (temporal lobe) 3) Purkinje layer of the cerebellum
What does damage to the pyramidal neurons of the cerebral cortex (layers 3, 5, and 6) lead to?
laminar necrosis
What does damage to the pyramidal neurons of the hippocampus (temporal lobe) lead to?
Its important in long term memory
What does damage to the purkinje layer of the cerebellum lead to?
It integrates sensory perception with motor control
What is ischemic stroke?
Regional ischemia to the brain that results in focal neurologic deficits lasting > 24 hours
What happens in the symptoms last < 24 hours?
the event is termed a transient ischemic attack (TIA).
What are the subtypes for ischemic stroke?
They include thrombotic, embolic, and lacunar strokes.
What is the thrombotic stroke due to?
rupture of an atherosclerotic plaque
Where does atherosclerosis usually develop?
at branch points (e.g., bifurcation of internal carotid and middle cerebral artery in the circle of Willis).
What does atherosclerosis result in?
a pale infarct at the periphery of the cortex
What is an embolic stroke due to?
thromboemboli.
What is the most common source of emboli?
It is the left side of the heart (e.g., atrial fibrillation).
What does an embolic stroke usually involve?
the middle cerebral artery
What does the embolic stroke result in?
a hemorrhagic infarct at the periphery of the cortex
When does a lacunar stroke occur?
Its secondary to hyaline arteriolosclerosis, a complication of hypertension.
What vessels does lacunar stroke most commonly involve?
lenticulostriate vessels, resulting in small cystic areas of infarction
In a lacunar stroke, what does the nvolvement of the internal capsule lead to?
a pure motor stroke
In a lacunar stroke, what does the involvement of the thalamus lead to?
a pure sensory stroke.
What does ischemic stroke result in?
liquefactive necrosis,
What is an early microscopic finding (12 hours after infarction) for ischemic stroke?
Eosinophilic change in the cytoplasm of neurons (red neurons)
What happens 24 hours into an ischemic stroke?
coagulative necrosis
What happens in days 1-3 in an ischemic stroke?
infiltration by neutrophils
What happens in days 4-7 in an ischemic stroke?
microglial cells
What happens in weeks 2-3 in an ischemic stroke?
granulation tissue (weeks 2-3) then ensue
An ischemic stroke results in the formation of what?
a fluid-filled cystic space surrounded by gliosis
What is an intracerebral hemorrhage?
Bleeding into brain parenchyma
What is an intracerebral hemorrhage classically due to?
rupture of Charcot-Bouchard microaneurysms of the leniiculostriate vessels
What is intracerebral hemorrhage a complication of?
hypertension; treatment of hypertension reduces incidence by half.
What is the most common site for intracerebral hemorrhage?
Basal ganglia
What does intracerebral hemorrhage present as?
severe headache, nausea, vomiting, and eventual coma
What is subarachnoid hemorrhage?
Bleeding into the subarachnoid space
What does subarachnoid hemorrhage present as?
a sudden headache (worst headache of my life) with nuchal rigidity
What does the lumbar puncture shows in a subarachnoid hemorrhage?
xanthochromia (yellow hue due to bilirubin breakdown)
What is a subarachnoid hemorrhage most frequently due to?
(85%) rupture of a Berry aneurysm; other causes include AV malformations and an anti-coagulated state,
What are Berry aneurysms?
they are thin-walled saccular outpouching that lack a media layer, increasing the risk for rupture.
What are Berry aneurysms most frequently located?
in the anterior circle of Willis at branch points of the anterior communicating artery
What are Berry aneurysms associated with?
Marfan syndrome and autosomal dominant polycystic kidney disease
What is an epidural hematoma?
Collection of blood between the dura and the skull
What is an epidural hematoma classically due to?
fracture of the temporal bone with rupture of the middle meningeal artery; bleeding separates the dura from the skull.
In an epidural hematoma, what is seen on CT?
Lens-shaped lesion on CT
When do you see neurologic signs in an epidural hematoma?
Lucid interval may precede neurologic signs.
What is a lethal complication for an epidural hematoma?
Herniation is a lethal complication.
What is a subdural hematoma?
Collection of blood underneath the dura; blood covers the surface of the brain
What is the subdural hematoma due to?
tearing of bridging veins that lie between the dura and arachnoid; usually arises with trauma
What is seen on CT in subdural hematoma?
Crescent-shaped lesion on CT
What does subdural hematoma present with?
progressive neurologic signs
In whom is there an increased rate of occurrence for subdural hematoma?
in the elderly due to age-related cerebral atrophy, which stretches the veins
What is a lethal complication for subdural hematoma?
Herniation
What is herniation (brain)?
Displacement of brain tissue due to mass effect or increased intracranial pressure
What is tonsillar herniation?
It involves displacement of the cerebellar tonsils into the foramen magnum.
What might tonsillar herniation lead to?
the compression of the brain stem leads to cardiopulmonary arrest
What is subfalcine herniation?
It involves displacement of the cingulate gyrus under the falx cerebri.
What would subfalcine herniation lead to?
Compression of the anterior cerebral artery leads to infarction
What does uncal herniation involve?
the displacement of the temporal lobe uncus over the tentorium cerebelli.
Uncal herniation leads to what?
1) eye moving (down and out) and a dilated pupil. 2) infarction of the occipital lobe (contralateral homonymous hemianopsia). 3) Duret (brainstem) hemorrhage.
With an uncal herniation, why is there eye movement down and out and a dilated pupil?
Compression of cranial nerve III (oculomotor)
With an uncal herniation, why is there infarction of occipital lobe?
(contralateral homonymous hemianopsia) compression of posterior cerebral artery
With uncal herniation, why is there Duret (brainstem) hemorrhage?
Rupture of the paramedian artery leads to Duret (brainstem) hemorrhage.
What are the demyelinating disorders?
1) leukodystrophies 2) multiple sclerosis 3) subacute sclerosing panencephalitis 4) progressive multifocal leukoencephalopathy 5) Central pontine myelinolysis
What does myelin do?
it insulates axons, improving the speed and efficiency of conduction
What myelinates the central nervous system?
oligodendrocytes
What myelinates the peripheral nervous system?
Schwann cells
What are demyelinating disorders characterized by?
destruction of myelin or oligodendrocytes; axons are generally preserved.
What are leukodystrophies?
They are inherited mutations in enzymes necessary for production or maintenance of myelin
What are the leukodystrophies?
metachromatic leukodystrophy, Krabbe disease, adrenoleukodystrophy
What is metachromatic leukodystrophy due to?
a deficiency of arylsulfatase (autosomal recessive)
What is the most common leukodystrophy?
metachromatic leukodystrophy
What is metachromatic leukodystrophy?
Myelin cannot be degraded and accumulates in the lysosomes of oligodendrocytes (lysosomal storage disease)
What is Krabbe disease due to?
a deficiency of galactocerebroside beta-galactosidase (autosomal recessive) resulting in galactocerebroside to accumulate in macrophages.
What is adrenoleukodystrophy due to?
impaired addition of coenzyme A to long-chain fatty acids (X-linked defect).
What does adrenoleukodystrophy result in?
accumulation of fatty acids damages adrenal glands and white matter of the brain.
What is multiple sclerosis?
Autoimmune destruction of CNS myelin and oligodendrocytes
What is the most common chronic CNS disease of young adults (20-30 years of age)?
Multiple sclerosis
In whom is multiple sclerosis more commonly seen?
in women
What is multiple sclerosis associated with?
HLA-DR2
In what region is multiple sclerosis more commonly seen?
in regions away from the equator
What does multiple sclerosis present with?
relapsing neurologic deficits with periods of remission (multiple lesions in time and space)
What are the clinical features for multiple sclerosis?
- Blurred vision in one eye (optic nerve) 2. Vertigo and scanning speech mimicking alcohol intoxication (brainstem) 3. Internuclear ophthalmoplegia (medial longitudinal fasciculus) 4. Hemiparesis or unilateral loss of sensation (cerebral white matter, usually periventricular) 5. Lower extremity loss of sensation or weakness (spinal cord) 6. Bowel, bladder, and sexual dysfunction (autonomic nervous system)
How is the diagnosis for multiple sclerosis made?
by MRI and lumbar puncture.
What does the MRI for multiple sclerosis reveal?
plaques (areas of white matter demyelination)
What does the lumbar puncture for multiple sclerosis show?
increased lymphocytes, increased immunoglobulins with oligoclonal IgG bands on high resolution electrophoresis, and myelin basic protein.
What does gross examination for multiple sclerosis show?
it shows gray-appearing plaques in the white matter
What is involved in the treatment of multiple sclerosis?
The acute attacks includes high-dose steroids and the long-term treatment with interferon beta slows progression of disease.
What is subacute sclerosing panencephalitis?
Progressive, debilitating encephalitis leading to death
What is subacute sclerosing panencephalitis due to?
slowly progressing, persistent infection of the brain by measles virus
For subacute sclerosing panencephalitis, when does the infection occur?
in infancy
For subacute sclerosing panencephalitis, when do the neurologic signs arise?
years later (during childhood)
What is subacute sclerosing panencephalitis characterized by?
viral inclusions within neurons (gray matter) and oligodendrocytes (white matter)
What is progressive multifocal leukoencephalopathy?
JC virus infection of oligodendrocytes (white matter)
What leads to reactivation of the latent virus?
Immunosuppression (e.g., AIDS or leukemia)
What does progressive multifocal leukoencephalopathy present with?
rapidly progressive neurologic signs (visual loss, weakness, dementia) leading to death
What is central pontine myelinolysis?
Focal demyelination of the pons (anterior brain stem)
What is central pontine myelinolysis due to?
Rapid intravenous correction of hyponatremia
In whom does central pontine myelinolysis occur?
in severely malnourished patients (e.g., alcoholics and patients with liver disease)
How does central pontine myelinolysis classically present?
as acute bilateral paralysis (locked in syndrome)
What are the dementia and degenerative disorders?
1) Alzheimer disease 2) vascular dementia 3) Pick disease 4) Parkinson Disease 5) Huntington Disease 6) Normal pressure hydrocephalus 7) spongiform encephalopathy
What are the dementia and degenerative disorders characterized by?
the loss of neurons within the gray matter
What are dementia and degenerative disorders often due to?
accumulation of protein which damages neurons
Degeneration of what leads to dementia?
the cortex
Degeneration of what leads to movement disorders?
the brainstem and basal ganglia
What is Alzheimer disease?
Degenerative disease of cortex; most common cause of dementia
What is the most common cause of dementia?
Alzheimer disease
What are the clinical features for Alzheimer disease?
1) Slow-onset memory loss (begins with short-term memory loss and progresses to long-term memory toss) and progressive disorientation 2) Loss of learned motor skills and language 3) Changes in behavior and personality 4) Patients become mute and bedridden; infection is a common cause of death. 5) Focal neurologic deficits are not seen in early disease.
In Alzheimer disease, what is the most common cause of death?
infection
What happens in most cases of Alzheimer disease
most cases (95%) are sporadic and seen in the elderly
The risk for developing Alzheimer disease increases with what?
age (doubles every 5 years after the age of 60)
What allele is associated with increased risk for Alzheimer disease?
Epsilon 4 allele of apolipoprotein E is associated with increased risk,
What allele is associated with decreased risk for Alzheimer disease?
Epsilon 2 allele is associated with decreased risk,
What is early-onset AD seen in?
it is seen in Familial cases and down syndrome
What are the Familial cases of early onset AD associated with?
presenilin 1 and presenilin 2 mutations
What is the relationship between down syndrome and early-onset AD?
commonly occurs by 40 years of age
What are the morphologic features for AD?
1) (diffuse) Cerebral atrophy with narrowing of the gyri, widening of the sulci, and dilation of the ventricles 2) Neuritic plaques 3) Neurofibrillary tangles 4) Loss of cholinergic neurons in the nucleus basalis of Meynert
What are Neuritic plaques?
Its an extracellular core comprised of Abeta (amyloid beta) amyloid with entangled neuritic processes
What is Abeta amyloid derived from?
amyloid precursor protein (APP), which is coded on chromosome 21. APP normally undergoes alpha cleavage; beta cleavage results in Abeta amyloid (cannot be broken down)
Where is amyloid precursor protein coded?
On chromosome 21
What normally happens to APP?
Normally undergoes alpha cleavage
What happens to APP in Alzheimer disease?
beta cleavage results in Abeta amyloid (cannot be broken down)
What is cerebral amyloid angiopathy?
Amyloid may also deposit around vessels, increasing the risk of hemorrhage resulting in cerebral amyloid angiopathy
What are neurofibrillary tangles?
They are intracellular aggregates of fibers composed of hyperphosphorylated tau protein
What is the Tau protein?
It is a microtubule-associated protein.
How is the diagnosis for Alzheimer disease made?
by clinical and pathological correlation. 1) Presumptive diagnosis is made clinically after excluding other causes, 2) Confirmed by histology at autopsy (when possible)
What is vascular dementia?
Multifocal infarction and injury due to hypertension, atherosclerosis, or vasculitis
What is the 2nd most common cause of dementia?
Vascular dementia
What is pick disease?
Degenerative disease of the frontal and temporal cortex; spares the parietal and occipital lobes
What is Pick disease characterized by?
round aggregates of tau protein (Pick bodies) in neurons of the cortex
What are the symptoms for Pick disease?
Behavioral and language symptoms arise early; eventually progresses to dementia
What is Parkinson disease?
It?s a degenerative loss of dopaminergic neurons in the substantia nigra of the basal ganglia
What is the nigrostriatal pathway?
It is a part of the basal ganglia that uses dopamine to initiate movement.
In what population is Parkinson?s disease common?
it?s a common disorder related to aging; seen in 2% of older adults
What is the etiology for Parkinson?s disease?
Unknown etiology; historically, rare cases were related to MPTP exposure (a contaminant in illicit drugs).
What are the clinical features for Parkinson?s disease?
TRAP ? 1) Tremor 2) Rigidity 3) akinesia/bradykinesia 4) Postural instability and shuffling gait
Describe the tremor seen in Parkinson?s disease?
pill rolling tremor at rest; disappears with movement
Describe rigidity seen in Parkinson?s disease?
cogwheel rigidity in the extremities
Describe akinesia/bradykinesia in Parkinson?s disease?
slowing of voluntary movement; expressionless face
What does the histology for Parkinson?s disease reveal?
loss of pigmented neurons in the substantia nigra and round, eosinophilic inclusions of alpha-synuclein (Lewy bodies) in affected neurons.
What is a common feature of late Parkinson?s disease?
dementia
What is early-onset dementia suggestive of?
Lewy body dementia
What is Lewy body dementia characterized by?
dementia, hallucinations and parkinsonian features
What does histology for Lewy Body dementia reveal?
cortical Lewy bodies
What is Huntington disease?
It?s the degeneration of GABAergic neurons in the caudate nucleus of the basal ganglia
What is Huntington disease characterize by?
Its an autosomal dominant disorder (chromosome 4) characterized by expanded trinucleotide repeats (CAG) in the huntington gene
What should be taken into consideration when it comes to Huntington?s and previous generations?
Further expansion of repeats during spermatogenesis leads to anticipation (grandfather gets it at 60, but the father at 55 and the son at 50 for example)
What does Huntington?s disease present with?
chorea that can progress to dementia and depression; average age at presentation is 40 years.
What is a common cause of death in Huntington?s?
Suicide is a common cause of death.
What is normal pressure hydrocephalus?
Increased CSF resulting in dilated ventricles
What does normal pressure hydrocephalus cause?
Can cause dementia in adults; usually idiopathic
What does normal pressure hydrocephalus present as?
triad of urinary incontinence, gait instability, and dementia (wet, wobbly, and wacky)
What might improve symptoms in normal pressure hydrocephalus?
Lumbar puncture improves symptoms and treatment is ventriculoperitoneal shunting
What is spongiform encephalopathy?
Degenerative disease due to prion protein
What is the prion protein?
Prion protein is normally expressed in CNS neurons in an alpha-helical configuration (PrP).
When does spongiform encephalopathy arise?
with conversion to a beta-pleated conformation (PrP)
Why does the alpha form of the prion undergo conformational change to the beta form?
Conversion can be sporadic, inherited (familial forms of disease), or transmitted.
What does the Pathologic protein do once it is in the patient?
it is not degradable and converts normal protein into the pathologic form, resulting in a vicious cycle
In Spongiform encephalopathy what characterizes damage?
Damage to the neurons and glial cells is characterized by intracellular vacuoles (spongy degeneration).
What is CJD?
Creutzfeldt-Jakob disease (CJD) is the most common spongiform encephalopathy.
What is the most common form of spongiform encephalopathy?
CJD
Why does CJD usually arise?
Usually sporadic; rarely can arise due to exposure to prion-infected human tissue (e.g., human growth hormone or corneal transplant)
What does CJD present as?
rapidly progressive dementia associated with ataxia (cerebellar involvement) and startle myoclonus
What is seen on EEG for CJD?
Spike-wave complexes are seen on EEG.
What is the result of CJD?
Results in death, usually in < 1 year
What is variant CJD?
it is a special form of disease that is related to exposure to bovine spongiform encephalopathy (mad cow).
What is familial fatal insomnia?
it is an inherited form of prion disease characterized by severe insomnia and an exaggerated startle response
What are the CNS tumors?
1) glioblastoma multiforme 2) meningioma 3) schwannoma 4) oligodendroglioma 5) pilocytic astrocytoma 6) medulloblastoma 7) ependymoma 8) craniopharyngioma 9)
Are CNS tumor metastatic?
Can be metastatic (50%) or primary (50%)
How do metastatic CNS tumors characteristically present?
as multiple, well-circumscribed lesions at the gray-white junction.
What are the three most common sources that metastasize to the brain?
Lung, breast, and kidney are common sources
How are primary tumor classified?
according to cell type of origin (e.g., astrocytes, meningothelial cells, ependymal cells, oligodendrocytes, or neuroectoderm)
In adults what usually are CNS primary tumors?
they are usually supratentorial
What are the most common CNS tumors in adults?
they are glioblastoma multiforme, meningioma, and schwannoma.
In children what usually are CNS primary tumors?
they are usually infratentorial.
What are the most common tumors in children?
They are pilocytic astrocytoma, ependymoma, and medulioblastoma,
Describe primary malignant CNS tumors?
they are locally destructive, but rarely metastasize.
What is glioblastoma multiforme?
Malignant, high-grade tumor of astrocytes
What is the most common primary malignant CNS tumor in adults?
glioblastoma multiforme
How does glioblastoma multiforme usually arise?
in the cerebral hemisphere; characteristically crosses the corpus callosum (butterfly lesion)
What is glioblastoma multiforme characterized by?
regions of necrosis surrounded by tumor cells (pseudopalisading) and endothelial cell proliferation; tumor cells are GFAP positive.
What is the prognosis for glioblastoma multiforme?
poor
What is a meningioma?
Benign tumor of arachnoid cells
What is the most common benign CNS tumor in adults?
meningioma
What may meningioma present as?
seizures; tumor compresses, but does not invade, the cortex
What does the imaging of meningioma reveal?
a round mass attached to the dura
What does histology of meningioma show?
a whorled pattern; psammoma bodies may be present
What is schwannoma?
Benign tumor of Schwann cells
What does schwannoma involve?
cranial or spinal nerves; within the cranium,
Within the cranium what does schwannoma most frequently involve?
cranial nerve VIII at the cerebellopontine angle (presents as loss of hearing and tinnitus)
Schwannoma tumor cells are positive for what?
Tumor cells are S-100 positive
For Schwannoma, when are bilateral tumors seen?
in neurofibromatosis type 1
What is oligodendroglioma?
Malignant tumor of oligodendrocytes
What does the imaging for oligodendroglioma reveal?
a calcified tumor in the white matter, usually involving the frontal lobe;
Oligodendroglioma may present with what?
seizures
What is the appearance of oligodendroglioma on biopsy?
Fried-egg appearance of cells on biopsy
What is pilocytic astrocytoma?
Benign tumor of astrocytes
What is the most common CNS tumor in children?
it usually arises in the cerebellum
What does imaging for pilocytic astrocytoma reveal?
a cystic lesion with a mural nodule
What does biopsy for pilocytic astrocytoma show?
Rosenthal fibers (thick eosinophilic processes of astrocytes and eosinophilic granular bodies;
Pilocytic astrocytoma tumor cells are positive for what?
GFAP positive.
What is medulloblastoma?
Malignant tumor derived from the granular cells of the cerebellum (neuroectoderm)
In whom does medulloblastoma usually arise?
in children
What does histology reveal for medulloblastoma?
small, round blue cells; Homer-Wright rosettes may be present
What is the prognosis for medulloblastoma?
Poor prognosis;
What is there a poor prognosis for medulloblastoma?
tumor grows rapidly and spreads via CSF
What does medulloblastoma metastasize to?
to the cauda equine and is termed drop metastasis
What is ependymoma?
Malignant tumor of ependymal cells
In whom is ependymoma usually seen?
in children
Where does ependymoma most commonly arise?
in the 4th ventricle
What might an ependymoma present with?
hydrocephalus
What is a characteristic finding for ependymoma?
Perivascular pseudorosettes are a characteristic finding on biopsy
What is a craniopharyngioma?
Tumor that arises from epithelial remnants of Rathke’s pouch
What does craniopharyngioma present as?
a supra tentorial mass in a child or young adult
What might a craniopharyngioma lead to?
It may compress the optic chiasm leading to bitemporal hemianopsia
What is commonly seen on imaging for craniopharyngioma?
Calcifications are commonly seen on imaging (derived from tooth-like tissue)
Is craniopharyngioma malignant or benign?
Benign, but tends to recur after resection
