Central Nervous System

Question 1

Neural Tube Defects

Answer 1

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

Question 2

Ancephaly

Answer 2

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

Question 3

Spina Bifida

Answer 3

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

Question 4

Meningocele

Answer 4

NTD with protrusion of meninges into cyst

Question 5

Meningomyelocele

Answer 5

NTD with protrusion of meninges and spinal cord

Question 6

Pathway of CSF

Answer 6

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

Question 7

Cerebral Aqueduct Stenosis

Answer 7

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

Question 8

Dandy Walker Malformation

Answer 8

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

Question 9

Arnold Chiari Malformation (Type II)

Answer 9

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

Question 10

Syringomyelia

Answer 10

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)

Question 11

Horner’s Syndrome

Answer 11

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

Can be caused when get lesion of the hypothalamic tract

Question 12

Poliomyelitis

Answer 12

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

Question 13

Lower Motor Signs

Answer 13

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

Question 14

Upper Motor Signs

Answer 14

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

Question 15

Werdnig Hoffman Disease

Answer 15

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

Question 16

Amyotrophic Lateral Sclerosis (ALS)

Answer 16

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

Question 17

Zinc-copper superoxide dismutase mutation (SOD1)

Answer 17

Mutation can be inherited and lead to ALS

Get free radical injury in neurons

Question 18

Friedrich Ataxia

Answer 18

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

Question 19

Frataxin Gene

Answer 19

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

Question 20

Layers of the meninges

Answer 20

Brain –> Pia –> Arachnoid–>Dura–>Skull

Question 21

Leptomeninges

Answer 21

The pia and arachnoid together are termed the leptomeninges

Question 22

Meningitis

Answer 22

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

Question 23

Cause of Meningitis in neonates

Answer 23

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

Question 24

Cause of meningitis in children and teenagers

Answer 24

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

Question 25

Cause of meningitis in Adults and elderly

Answer 25

Streptococcus pneumoniae

Question 26

Cause of meningitis in non-vaccinated infants

Answer 26

H Influenza

Question 27

CSF findings in bacterial meningitis

Answer 27

Neutrophils with decreased CSF glucose

Question 28

CSF findings in Viral meningitis

Answer 28

Lymphocytes with normal CSF glucose

Question 29

CSF Findings in Fungal Meningitis

Answer 29

Lymphocytes with decreased CSF glucose

Question 30

Neutrophils with decreased CSF glucose

Answer 30

CSF findings in bacterial meningitis

Question 31

Lymphocytes with normal CSF glucose

Answer 31

CSF findings in Viral meningitis

Question 32

Lymphocytes with decreased CSF glucose

Answer 32

CSF Findings in Fungal Meningitis

Question 33

Lumbar puncture and layers crossed

Answer 33

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

Question 34

Etiologies of Global Cerebral Ischemia

Answer 34

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

Question 35

Mild Global Cerebral Ischemia

Answer 35

transient confusion with prompt recovery | Often due to insulinoma

Question 36

Severe Global Cerebral Ischemia

Answer 36

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

Question 37

Moderate Global Cerebral Ischemia

Answer 37

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

Question 38

Transient Ischemic Attack

Answer 38

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

Question 39

Thrombotic Stroke

Answer 39

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

Question 40

Embolic Stroke

Answer 40

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

Question 41

Lacunar Stroke

Answer 41

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)

Question 42

Pathologic Changes of Ischemic Stroke

Answer 42

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

Question 43

Intracerebral Hemmorhage

Answer 43

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

Question 44

Subarachnoid Hemmorhage

Answer 44

"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

Question 45

Berry Aneursym

Answer 45

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"

Question 46

Epidural Hematoma

Answer 46

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

Question 47

Subdural Hematoma

Answer 47

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

Question 48

Herniation

Answer 48

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

Question 49

Tonsilar Herniation

Answer 49

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

Question 50

Subfalcine Herniation

Answer 50

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

Question 51

Uncal Herniation

Answer 51

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

Question 52

Oligodendrocytes

Answer 52

Myelinate the CNS

Question 53

Schwann Cells

Answer 53

Myelinate the PNS

Question 54

Leukodystrophies

Answer 54

Inherited mutations in enzymes necessary for production or maintenance of myelin

Question 55

Metachromatic Leukodystrophy

Answer 55

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

Question 56

Krabbe Disease

Answer 56

Autosomal recessive deficiency of galactocerebrosidase so galactocerebroside accumulates in macrophages

Question 57

Adrenoleukodystrophy

Answer 57

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

Question 58

``` Multiple Sclerosis Who it affects Presentation Diagnosis Treatment ```

Answer 58

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

Question 59

Subacute Sclerosing Panencephalitis

Answer 59

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

Question 60

Progressive Multifocal Leukoencephalopathy

Answer 60

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

Question 61

Central Pontine Myelinosis

Answer 61

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)

Question 62

Alzheimer Disease Clinical features

Answer 62

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

Question 63

Alzheimer Disease Morphologic Features

Answer 63

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

Question 64

Diagnosis of Alzheimers Disease

Answer 64

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

Question 65

Early onset Alzheimers Disease

Answer 65

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

Question 66

Risk Factors for Alzheimers Disease

Answer 66

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

Question 67

Vascular Dementia

Answer 67

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

Question 68

Pick Disease

Answer 68

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

Question 69

Parkinson Disease Pathophysiology

Answer 69

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.

Question 70

Parkinsons Disease Etiology, clinical, histology

Answer 70

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

Question 71

Lewy Body Dementia

Answer 71

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

Question 72

Huntington Disease

Answer 72

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

Question 73

Normal Pressure Hydrocephalus

Answer 73

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)

Question 74

Spongiform Encephalopathy

Answer 74

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

Question 75

Creutzfeld Jakob Disease

Answer 75

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.

Question 76

Variant CJD

Answer 76

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

Question 77

Familail Fatal Insomnia

Answer 77

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

Question 78

CNS Tumors Basics

Answer 78

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

Question 79

Glioblastoma Multiforme

Answer 79

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

Question 80

Meningioma

Answer 80

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

Question 81

Schwannoma

Answer 81

BENIGN tumor of SCHWANN cells Involves crainial or spinal nerves...typically nerve VIII at cerebellopontine angle = loss of hearing and tinitus S-100+ Bilateral tumors seen in neurofibromatosis type 2

Question 82

Oligodendroglioma

Answer 82

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

Question 83

Pilocytic Astrocytoma

Answer 83

BENIGN tumor of ASTROCYTES 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 GFAP+

Question 84

Medulloblastoma

Answer 84

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"

Question 85

Ependymoma

Answer 85

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

Question 86

Craniopharyngioma

Answer 86

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