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Flashcards in Central Nervous System Deck (86):

Neural Tube Defects

Incomplete closure of the neural tube.
Associated with low folate levels PRIOR to conception
Detected by elevated alpha-fetoprotein (AFP) levels in the amniotic fluid and maternal blood



Absence of skull and brain resulting in "frog like appearance"
Results in maternal polyhydraminos since the swallowing of amniotic fluid by the fetus is impaired


Spina Bifida

Failure of the posterior vertebral arch to close resulting in a vertebral defect.
Spina Bifida occulta = dimple or patch of hair overlying the vertebral defect
Typically presents with cystic protrusion of the udnerlying tissue through the vertebral defect
Meningocele = protrusion of meninges into cyst
Meningomyelocele = protrusion of meninges and spinal cord



NTD with protrusion of meninges into cyst



NTD with protrusion of meninges and spinal cord


Pathway of CSF

CSF produced by choriod plexus lining the ventricles
Moves into 3rd ventricle via interventricular foramen of Monro
Flows from 3rd to 4th via cerebral aqueduct
flows from 4th ventricle into subarachnoid space via foramina of magendie and Luschka


Cerebral Aqueduct Stenosis

Presents with enlarging head circumference due to dilation of the ventricles (remember the cranial sutures have not yet fused)


Dandy Walker Malformation

Congenital failure of the cerebral vermis to develop
Presents as massively dilated 4th ventricle (posterior fossa) with an ABSENT cerebellum
Usually accompanied by hydrocephalus


Arnold Chiari Malformation (Type II)

Congenital downward dispalcement of the cerebellar vermis and tonsils through the foramen magnum
Obstruction of CSF flow commonly results in hydrocephalus
Can occur in association with meningomyelocele (most cases) and syringomyelia



Cystic degeneration of the spinal cord usually at C8-T1
Arises with trauma or in association with and Arnold Chiari Malformation
Presents as sensory loss of pain and temperature with sparing of fine touch and position sense in the upper extremities ("cape like" distribution) - due to involvement of the anterior white commisure of the spinothalamic tract with sparing of the dorsal column
Can expand to involve other tracts
1) Lower motor neurons of Anterior Horn = muscle atrophy and weakness with decreased muscle tone and impaired refelces
2) Lateral horn of Hypothalamic Tract - Horner's Syndrome,
ptosis (droopy eyelid), miosis (constricted pupil), anhidrosis (decreased sweating)


Horner's Syndrome

ptosis (droopy eyelid), miosis (constricted pupil), anhidrosis (decreased sweating)

Can be caused when get lesion of the hypothalamic tract



Poliovirus infects the anterior motor horn
Get lower motor neuron signs = flaccid paralysis with muscular atrophy, fasiculations, weakness with decreased muscle tone, impaired reflexes, and negative babinski sign


Lower Motor Signs

Seen with lesions of Anterior motor horn
flaccid paralysis with muscular atrophy,
weakness with decreased muscle tone,
impaired reflexes
negative babinski sign


Upper Motor Signs

Seen with lesions of Lateral Corticospinal tract
spastic paralysis with hyperreflexia,
increased muscle tone,
positive Babinski sign


Werdnig Hoffman Disease

Inherited degeneration of anterior motor horn, autosomal recessive
"floppy baby" and death occurs a few years after birth


Amyotrophic Lateral Sclerosis (ALS)

Degenerative disorder of upper and lower motor neuron signs
Earliest sign is usually atrophy and weakness of hands
LACK of sensory impairment distnguishes it from syringomyelia
Normally sporadic and occurs in middle aged but also see in inherited mutation in Zinc-copper superoxide dismutase mutation (SOD1)
Anterior horn = lower motor signs = flaccid paralysis with muscular atrophy, fasiculations, weakness with decreased muscle tone, impaired reflexes, and negative babinski sign
Lateral Corticospinal tract = upper motor neuron signs = spastic paralysis with hyperreflexia, increased muscle tone, and positive Babinski sign


Zinc-copper superoxide dismutase mutation (SOD1)

Mutation can be inherited and lead to ALS
Get free radical injury in neurons


Friedrich Ataxia

Degenerative disorder of the cerebellum and spinal cord
Autosomal recessive, expansion of unstable trinucleotide repeat (GAA) in the frataxin gene = loss of mitochondrial iron regulation, buildup of Fe and get free radical damage
Get ataxia and then loss of different tracks can result in loss of vibratory sense and proprioception, muscle weakness in lower extremities, and loss of deep tendon reflexes
Often associate with hypertrophic cardiomyopathy
Presents in early childhood and patients are soon wheelchair bound


Frataxin Gene

Autosomal recessive loss = Friedrich Ataxia
Gene involved in mitochondrial Iron regulation.
Expansion of unstable trinucleotide repeat (GAA) leads to defective gene and get iron buildup and free radical damage that leads to the symptoms of Friedrich Ataxia


Layers of the meninges

Brain --> Pia --> Arachnoid-->Dura-->Skull



The pia and arachnoid together are termed the leptomeninges



Inflammation of the leptomeninges. Can be caused by bacteria, viral, or fungal.
Presents with triad of (1) headache (2) nuchal rigidity (3)fever but can also see photophobia (especially in viral), vomiting and altered mental status
Complications include death due to herniation secondary to cerebral edema, hydrocephalus/hearing loss/seizures due to fibrosis.
Bacterial meningitis is much more serious


Cause of Meningitis in neonates

Group B Strep (from vagina in the birthing canal)
E coli
Listeria Monocytogenes


Cause of meningitis in children and teenagers

N Meningitidis (enters through the nasopharynx then to blood and then to meninges)
Coxsackie virus (fecal-oral) can also cause meningitis in children


Cause of meningitis in Adults and elderly

Streptococcus pneumoniae


Cause of meningitis in non-vaccinated infants

H Influenza


CSF findings in bacterial meningitis

Neutrophils with decreased CSF glucose


CSF findings in Viral meningitis

Lymphocytes with normal CSF glucose


CSF Findings in Fungal Meningitis

Lymphocytes with decreased CSF glucose


Neutrophils with decreased CSF glucose

CSF findings in bacterial meningitis


Lymphocytes with normal CSF glucose

CSF findings in Viral meningitis


Lymphocytes with decreased CSF glucose

CSF Findings in Fungal Meningitis


Lumbar puncture and layers crossed

Sample CSF. Perform between L4 and L5 =illiac crest (since spinal cord ends at L2 but cauda equina continues to S2)
Cross skin, ligaments, epidural space, dura, and arachnoids


Etiologies of Global Cerebral Ischemia

Low perfusion (ex atherosclerosis)
Acute decrease in blood flow (cardiogenic shock)
Chronic hypoxia (anemia)
Repeated episodes of hypoglycemia (insulinoma)


Mild Global Cerebral Ischemia

transient confusion with prompt recovery
Often due to insulinoma


Severe Global Cerebral Ischemia

Diffuse necrosis, survivial leads to "vegetative state" and usually death


Moderate Global Cerebral Ischemia

Infarcts in watershed areas (areas lying between regions fed by the anterior and middle cerebral artery) and damage to highly vulernable regions including
1) Pyramidal Neurons of cerebral cortex (layers 3, 5 and 6) = laminar necrosis
2) Pyramidal neurons of the hippocampus (temporal lobe) = imparied long term memory
3) Purkinje layers of the cerebellum = problems integrating sensory perception with motor control


Transient Ischemic Attack

Regional ischemia with focal neurological deficitis but symptoms last less than 24hrs.


Thrombotic Stroke

Rupture of an atherosclerotic plaque that usually develops at branch points (bifurcation of internal carotid and MCA of Circle of Willis)
Results in pale infarct at periphery of the cortex


Embolic Stroke

Thromboemboli (usually from L side of heart during A fib)
Usually involves the middle cerebral artery
Get hemmorhagic infarct at periphery of the cortex


Lacunar Stroke

Occur secondary to hyaline arteriosclerosis which is a complication of hypertension.
Lenituculostriate arteries brnach off to feed depp structures like internal capsule (motor area) or the thalamus (sensory area)


Pathologic Changes of Ischemic Stroke

See liquefactive necrosis
12-24hrs = eosinophilic change in cytoplasm of neurons= RED NEURONS
24hrs = necrosis
Day1-3 = infiltration by neutrophils
Days 4-7 Microglial cells
Weeks 2-3 = gliosis
All results in a fluid filled cystic space surrounded by gliosis


Intracerebral Hemmorhage

Bleeding into the brain parenchyma. Classically arises due to rupture of Charcot-Bouchard microaneurysms of lenticulostriate vessels.
Usually a complication of hypertension and basal ganglia is the most common site.
Presents as severe headache, nausea, vomitting, and eventual coma


Subarachnoid Hemmorhage

"Worst headache of my life" with nuchal rigidity due to bleeding into the subarachnoid space.
LP shows xanthochromia (due to bilirubins breakdown in CSF)
A "bleed on the bottom of the brain"
Most frequently results from Berry aneurysm but also seen in AV malformations or anticoagulated state
Associated with Marfan syndrome and sutosomal dominant polycystic kidney disease

Remeber Berry Aneurysm is a thin walled saccular outpouching that LACKS MEDIA layer, increasing risk for rupture. Typically occurs at anterior circle of Willis at branch points of the anterior communicating artery


Berry Aneursym

thin walled saccular outpouching that LACKS MEDIA layer, increasing risk for rupture. Typically occurs at anterior circle of Willis at branch points of the anterior communicating artery.

Can result in subarachnoid hemmorhage. A "bleed on the bottom of the brain"


Epidural Hematoma

Collection of blood between the dura and skull following a trauma that typically fractures the bone and ruptures the Middle Meningeal Artery.
See lens shaped lesion on CT.
Lucid interval may preced neuro signs


Subdural Hematoma

Collection of blood underneath the dura allowing blood to cover the brain. Tear the bridging veins between dura and archnoid. Higher incidence in elderly cus brain starts to atrophy and these bridging veins are already being strecthed.
Cresscent shaped lesion and see progressive neuro signs



Displacement of brain tissue due to mass effect or increased intercranial pressure


Tonsilar Herniation

Cerebellar tonsials displaced into formaen magnum and compress the brain stem leading to cardiopulmonary arrest


Subfalcine Herniation

Displacement of the cingulate gyrus under the falx cerebri and compresses the anterior cerebral artery leading to infarction


Uncal Herniation

Displacement of temporal lobe uncus under the tentorium cerebelli.
1) Compression of Oculomotor (CrIII) leads to "down and out" and dilated pupil
2) compression of posterior cerebral artery leads to infraction of occipital lobe = contralateral homonymous hemianopsia (cant see visual field opposite that of the lesion)
3) Rupture of paramedian artery leads to Duret (brainstem) hemmorhage



Myelinate the CNS


Schwann Cells

Myelinate the PNS



Inherited mutations in enzymes necessary for production or maintenance of myelin


Metachromatic Leukodystrophy

Autosomal recessive inheritance of deficient arylsulfatase that leads to inability to to degrade sulfatides so they accumulate in the lysosome of oligodendrocytes


Krabbe Disease

Autosomal recessive deficiency of galactocerebrosidase so galactocerebroside accumulates in macrophages



X-linked defect characterized by impaired addition of coenzymeA to long-chain fatty acids. Accumulation of fatty acids damages adrenal glands and white matter of the brain


Multiple Sclerosis
Who it affects

Autoimmune Destruction of CNS myelin and OLIGODENDROCYTES.

Usually presents in20-30yrs of age, more common in WOMEN, and AWAY from EQUATOR

Presents with relapsing neuro deficits with periods of remission.
1) Blurred vision in one eye (optic nerve
2) Vertigo and SCANNING SPEECH (brainstem)
3) Internuclear Opthalmoplegia (MLF)
4) Hemiparesis or unilateral loss of sensation (cerebral white matter, usually periventricular)
5) Lower extremity loss of sensastion or weakenss (spinal cord)
6) Bowel, bladder, and sexual dysfunction (autonomic nervous system)

Diagnose = MRI reveals plaques (areas of white matter demyelination, LP shows increased lymphocytes, increased Ig (oligoclonal IgG bands) and myelin basic protein

Treat acute attacks with high dose steroids and long term with beta interferon


Subacute Sclerosing Panencephalitis

Measles virus infection in child slowly progresses to form viral inclusions within neurons and oligodendrocytes. Progressive debilitation that leads to death


Progressive Multifocal Leukoencephalopathy

JC virus infection of oligodendrocytes (white matter) initially but then becomes latent. With immuncompromised patient virus reactivates and get rapidly progressive neuro signs leading to death


Central Pontine Myelinosis

Rapid IV correction of hyponatremia occurs leads to focal demyelination of the pons. Classically presents as acute bilateral paralysis (Locked in syndrome)
More common in severely malnourished patients (alcoholics and patients with liver disease)


Alzheimer Disease Clinical features

Degenerative disease of the cortex, most common cause of dementia.
1)Slow onset of memory loss (short term first then long term)
2) Loss of learned motor skills and language
3) Changes in behavior and personality
4) Patients become mute and bedridden
5) Infection is common cause of disease
6) focal neuro deficits NOT seen


Alzheimer Disease Morphologic Features

1) Cerebral atrophy with narrowing of gyri, widening of the sulci, and dilation of the ventricles.
2) Neuritic plaques - extracellular core comprised of Abeta amyloid with entangled neuritic processes (dervied from APP on chromosome 21. Can also deposit around blood vessels and increase the risk for hemmorhage
3) Neurofibrillary Tangles = intracellular aggregates of fibers composed of hyperphosphorylated tau protein
4) Loss of cholinergic neurons in the nucleus basalis of Meynert


Diagnosis of Alzheimers Disease

Presumptive diagnosis based on clinical features and excluding other diseases
Can only be officially diagnosed by histology on autopsy


Early onset Alzheimers Disease

Familial Cases - assoicated with presenelin 1 and 3 mutations
Also commonly seen in Down Syndrome (extra 21)


Risk Factors for Alzheimers Disease

Risk increases with age
epsilon 4 allele of apolipoprotein E (APOE) is associated with increased risk while epsilon 2 has a decreased risk


Vascular Dementia

Multifocal infarction and injury due to hypertension, atherosclerosis, or vasculitis


Pick Disease

Degenerative disroder of frontal (behavior) and temporal (language) cortex.
Characterized by round aggregates of tau protein (Pick bodies) in neurons of the cortex.
Behavioral and language disabillities first then progresses to dementia


Parkinson Disease Pathophysiology

Degenerative loss of dopeminergic Neurons in the substantia nigra(SN) of the basal ganglia(BG). Dopamine of SN goes to BG and excites the stimulatory pathways via D1 receptors and inhibits the inhibitory pathway via D2, overall leads to increased stimulation of cortex normally to increase movements. When lose this dopamine it becomes harder to initiate movement.


Parkinsons Disease Etiology, clinical, histology

Etiology = unknown but associated with MPTP in some illicit drug users

Clinical = TRAP
Tremor- pill rolling tremmor at rest that dissapears with movement
Rigidity = in extremities
Akinesia/bradykinesia = slowing of voluntary movements, expresionless faces
Only see dementia later on in the disease

Histology = loss of pigmented neurons in substantia nigra and round eosinophilic inclusions of alpa-synuclein (Lewy bodies) in affected neurons


Lewy Body Dementia

Parkinsonian symptoms with EARLY onset dementia. Additionally see hallucinations.
See CORTICAL (gray matter of cortex) lewy bodies


Huntington Disease

Degeneration of GABAergic neurons in the caudate nucleus of the Basal Ganglia.
Autosomal Dominant (chromosome 4) characterized by expansion of trinucleotide (CAG) repeat in the huntingtin gene. Further expansion of repeats during spermatogenesis leads to anticipation (see disease earlier in next generation)
Presents with chorea (unpredictable jumpy movements), Athetosis (slow involuntary snake like movements of fingers), and progresses to dementia and depression.
Typically presents at 40yo


Normal Pressure Hydrocephalus

Arachnoid granulations pop up into dura and come into contact with venous sinuses. The CSF normally circulates up through these projections and is reabsorbed into venous sinuses to maintain normal pressure. In this disease for unknown reasons get decrease absorption of CSF, the increase in CSF pushes on the corona radiata and get triad of
1) Urinary incontinenece (WET)
2) Gait instability (WOBBLY)
3) Dementia (WACKY)


Spongiform Encephalopathy

Degenerative disease due to prion protein (normally alpha helical PrP^c but become beta pleated PrP^sc). The conversion to beta pleated can be sporadic, inherited, or transmitted/infectious.
Once get abnormal beta protein starts vicious cycle cus it is essentially a seed and it causes the normal proteins to take on the beta pleated sheet form. The beta pleated sheet form cannot be degraded and damages neurons and glial cells characterized by intracellular vacoules.
Get Creutzfeld Jakob Disease, vCJD and Familal Fatal Insomnia


Creutzfeld Jakob Disease

Usually sporadic but rarely see exposure to prion infected human tissue (HGH or corneal transplant)
Presents as rapidly progressive dementia associated with ataxia and startle myoclonus. See sharp spike wave complexes on EEG and death within 1 year.


Variant CJD

Prion disease that occurs after exposure to bovine spongiform encephalopathy = "MAD COW"


Familail Fatal Insomnia

Inherited form of prion disease characterized by severe insomnia and an exaggerated startle response


CNS Tumors Basics

Metastatic tumors mostly come from lung breast, and kidney and present as well circumscribed lesions at the gray-white junctions
Primary tumors are locally destructive but rarely met
In adults primary tumors are SUPRATENTORIAL while in children they are INFRATENTORIAL


Glioblastoma Multiforme

MALIGNANT, high grade tumor of ASTROCYTES
Most common primary MALIGNANT in ADULTS
Usually occurs in the cerebral hemisphere and CROSSES the corpus callosum (butterfly lesion)
Characterized by regions of necrosis surrounded by tumor cells (pseudopalisading) and endothelial cell proliferation
GFAP positive
Poor prognosis



BENIGN tumor of ARACHNOID cells
Most common BENIGN tumor in ADULTS (Female more common as tumor is ER+)
Tumor compresses but NOT invade the cortex and cuases seizures
Imaging displays round mass attached to the dura
Histology shows WHORLED pattern and PSAMMOMA bodies



BENIGN tumor of SCHWANN cells
Involves crainial or spinal nerves...typically nerve VIII at cerebellopontine angle = loss of hearing and tinitus
Bilateral tumors seen in neurofibromatosis type 2



Calcified tumor in white matter, usually in FRONTAL LOBE and present with SEIZURES.
FRIED EGG appearance on biopsy


Pilocytic Astrocytoma

most common CNS tumor in children, and usually arises in the cerebellum
see cystic lesion with morula nodule
Biopsy shows ROSENTHAL FIBERS (thick eosinophilic processes of astrocytes) and eosinophilic granular bodies



MALIGNANT tumor derived from GRANULAR cells of CEREBELLUM (neuroectoderm)
Usually seen in children
Small, round blue cells; Homer-Wright rosettes
Poor prognosis, tumor grows rapdily and spread via CSF
Mets to cauda equina termed "drop metastasis"



MALIGNANT tumor of EPENDYMAL cells, usually seen in children
Usually arises in the 4th ventricle and presents as hydrocephalus
Perivascular pseudorosettes are characteristic findings on biopsy



Tumor from epithelial remnants of RATHKE'S POUCH
Supratentorial mass in child or young adult...may compress the optic chiasm and lead to BITEMPORAL HEMIANOPSIA
Calcifications derived from tooth like tissue seen on imaging
Benign but tends to recur following resection