CNS Pathoma

Question 1

Neural Crest cells form what?

Answer 1

Peripheral Nervous System

Melanocytes

Schwann Cells

Neurons

Osteoblasts/Osteoclasts

Adipocytes

Chondrocytes

Question 2

Flow of CSF in the brain

Answer 2

CSF is produced by the choroid plexus lining the ventricles –> Flows from lateral ventricles into the 3rd ventricle via the interventricular foramen of monro –> from third ventricle to fourth via CEREBRAL AQUEDUCT –> 4th to subarachnoid space via the foramina of Magendie and Luschka

Question 3

Dandy Walker Malformation

Answer 3

• Congenital failure of the cerebellar vermis to develop.
• Presents as a massively dilated 4th ventricle (posterior fossa) with an absent cerebellum (often accompanied by hydrocephalus)

Question 4

Arnold-Chiari Malformation (Type II)

Answer 4

• Congenital downward displacement of the cerebellar vermis and tonsils through the foramen magnum
• Obstruction of CSF flow commonly results in hydrocephalus
• Often associated with meningomyelocele (type of spina bifida)

Question 5

Syringomyelia

Answer 5

Fluid filled cavity or cystic degeneration of the spinal cord that can arise with trauma or type 1 Arnold-Chiari Malformation

-Usually occurs C8-T1

Involves loss of anterior commissure so see sensory loss of pain and temp with sparing of fine touch and position with “cape-like” distribution

Question 6

Poliomyelitis

Answer 6

Damage to anterior motor horn due to poliovirus infection. Presents with lower motor neuron signs-flaccid paralysis with muscle atrophy, fasciculations, weakness with decreased muscle tone, impaired reflexes, and negative Babinski sign (downgoing toes)

-leading to asymetric weakness

Question 7

What three things can effect the anterior horn?

Answer 7

1. Poliomyelitis: lower motor neuron signs

2. Werdnig-Hoffman Disease: inherited degeneration of the anterior motor horn. AR. Presents as “floppy baby” Symmetric weakness

3. ALS: see LMN signs due to loss of anterior horn. NOTE that also see UMN signs due to loss of lateral corticospinal tract degeneration

Question 8

Amyotrophic Lateral Sclerosis (ALS)

Answer 8

• Degenerative disorder of UMN, LMN of corticospinal tract.
• Atrophy and weakness of hands is an early sign. Lack of sensory impairment distinguishes ALS from syringomyelia
• Most cases are sporatic, arising in middle age adults. Zinc-copper superoxide dismutase mutation (SOD1) is present in some familial cases that leads to free radical injury in neurons

TX: Riluzole

Question 9

Friedreich Ataxia

Answer 9

• Degenerative disorder of the cerebellum and spinal cord
• Sx: Ataxia, Loss of vibratory senses and proprioception, muscle weakness in the lower extremities and loss of DTR

AR, due to expansion of an unstable trinucleotide repeat (GAA) in the frataxin gene on Chromosome 9 (essential for mitochondrial iron regulation, loss of which results in iron buildup with free radical damage)

Also associated with hypertrophic cardiomyopathy

Question 10

Layers of meninges in brain

Answer 10

SKULL

DURA

ARACHNOID

PIA

BRAIN (in this order top to bottom). Can be said that there is a PAD over the brain

Question 11

Leptomeninges

Answer 11

Pia and Arachnoid together

Inflammation of the leptomeninges is what is responsible for meningitis

Question 12

Most common causes of neonatal meningitis (they all make sense!) (3)

Answer 12

Group B Strep (from vaginal canal)

E. Coli (from rectum during birth)

Listeria (from placenta)

**Ceftriaxone and Vancomycin empirically

Question 13

Most common cuase of children 6months-6 years meningitis (4)

Answer 13

Strep Pneumo (MOPS)

Neisseria Meningitis (type B)

H. Influenza (type B) (this has DECREASED greatly due to vaccinations)

Enterovirus

**Ceftriaxone and Vancomycin empirically

Question 14

Most common cause of meningitis in 6year old-60 year old (4, 2 bacteria 2 virus)

Answer 14

Strep Pneumo

Neisseria Meningitidis (#1 cause in teenagers, college age kids)

Enterovirus (esp Coxsackie Virus)

HSV (HSV-1 causing encephalitis)

**Ceftriaxone and Vancomycin empirically

Question 15

Most common cause of meningitis in >60 year olds (3)

Answer 15

Strep Pneumo

Gram - Rods

Listeria (remember very old and very young)

*If listeria is suspected, give Ampicillin for tx*

Ceftriaxone and Vancomycin empirically

Question 16

CSF findings in bacterial vs fungal vs viral CSF

Answer 16

Bacterial: neutrophils with decreased glucose (bacteria eat glucose), and gram stain and culture

Viral: lymphocytes with normal CSF glucose (bacteria NOT eat glucose)

Fungal/TB: lymphocytes with decreased glucose

Question 17

Overview of cerebral vascular disease

Answer 17

Neurologic deficit due to cerebrovascular compromise

85% ischemia

15% hemorrhage

Neurons are dependent on serum glucose as an essential energy source and are susceptible to ischemia (undergo necrosis within 3-5 minutes)

Question 18

Global Cerebral Ischemia

Answer 18

• From low perfusion (atherosclerosis), acute decrease in blood flow (cardiogenic shock), chronic hypoxia (anemia), repeated episodes of hypoglycemia (insulinoma)
• Mild: transient confusion with prompt recovery
• Moderate: leads to infarcts in watershed areas (area lying between regions red by anterior and middle cerebral artery)
• Severe: diffuse necrosis. survival in vegetative state

Question 19

Laminar necrosis

Answer 19

Pyramidal neurons of the cerebral cortex (layers 3,5,6) leadings to laminar necrosis.

Question 20

Thrombotic Stroke (subtype of ischemic)

Answer 20

• Due to rupture of atherosclerotic plaque
• Atherosclerosis usually develops at branch points (bifurcation of internal carotid and middle cerebral artery in the circle of Willis)
• Results in a pale infarct at the periphery of the cortex

Question 21

Embolic Stroke (subtype of ischemic)

Answer 21

• Due to thromboemboli
• Most common source is from the Left Atrium (from AFIB)
• Usually involves the middle cerebral artery. Results in hemorrhagic infarct in the periphery of the cortex

Question 22

Lacunar Stroke

Answer 22

Occurs secondary to hyaline arteriolosclerosis, a complication of hypertension

Most commonly involves the lenticulostriate vessels, resulting in small cystic areas of infarction

• Involvement of the internal capsule leads to a PURE MOTOR stroke.
• Involvement of the thalamus leads to a PURE SENSORY stroke

Question 23

Necrosis associated with ischemic stroke and the timing (12h, 24h, 1-3d, 4-7,d 2-3w)

Answer 23

Liquefactive necrosis

12 hours: RED neurons due to eosinophilic changes in the cytoplasm of neurons

24 hours: NECROSIS

Days 1-3: Neutrophils

Days 4-7: Microglial cells

Weeks 2-3: Gliosis

Question 24

Intracerebral Hemorrhage

Answer 24

Bleeding in the brain parenchyma

Classically due to rupture of Charcot-Bouchard microaneurysms of the lenticulostriate vessels

-Complication of HTN

-Basal ganglia most common site

Presents as severe HA/N/V coma

Question 25

Subarachnoid Hemorrhage

Answer 25

Bleeding into the subarachnoid space Presents as sudden "**WORST HA OF LIFE**" w/ nuchal rigidity LP shows Xanthochromia (yellow hue due to bilirubin) **85% due to rupture of Berry Aneurysms**, or can be AV malformations and an anticoag state - Berry aneuryms **lack a media layer**, which increases risk of rupture - Most frequently in **anterior circle of willis at branch points of the anterior communicating artery** Associated with **Marfan and AD PKD**

Question 26

Epidural Hematoma

Answer 26

Collection of blood between dura and skull Classically due to fracture of temporal bone with rupture of middle meningial ARTERY\*\*\* The bleeding separates the dura from the skull (need a high force to separate these two) - Lens-shaped lesion on CT - Lucid interval may precede neurologic signs

Question 27

Subdural Hematoma

Answer 27

Collection of blood underneath the dura, blood covers the surface of the brain Due to tearing of **BRIDGING VEINS** that lie between the dura and arachnoid. Usually arise with trauma **CRESCENT SHAPED** Presents with progressive neurologic signs.

Question 28

Three types of herniation

Answer 28

Displacement of brain tissue due to mass effect or increased ICP 1. Tonsillar Herniation: displacement of cerebellar tonsils into foramen magnum 2. Subfalcine Herniation: displacement of cingulate gyrus under the falx cerebri 3. Uncal Herniation: displacement of temporal lobe uncus under tentorium cerebelli - compression of CNIII (down and out eye) - compression of posterior cerebral artery leads to infarction of occipital love - rupture of paramedian artery leads to Duret (brainstem) hemorrhage

Question 29

Metachromatic leukodystrophy (leukodystrophy = inherited mutation in enzymes nexessary for production or maintenance of myelin)

Answer 29

Due to **deficiency of arylsulfatase**. AR. Most common leukodystrophy -Sulfatides cannot be degraded and accumulate in the lysosomes of oligodendrocytes (**accumulation of cerebroside sulfate**)

Question 30

Krabbe Disease

Answer 30

Due to deficiency of **galactocerebrsidase**. AR. **Galactocerebroside** accumulates in **MACROPHAGES** -peripheral neuropathy, developmental delay, optic atrophy, globoid cells

Question 31

Adrenoleukodystrophy

Answer 31

X-linked genetic disorder typically affecting males. Disrupts metabolism of very-long-chain fatty acids excessive buildup in nervous system, adrenal gland, testes. Progressive disease that can lead to long-term coma/death and adrenal gland crisis. ## Footnote **-Impaired addition of coenzyme A to long chain fatty acids**

Question 32

MS is associated with which HLA

Answer 32

HLA-DR2

Question 33

Diagnosis of MS

Answer 33

- Made by MRI and LP - MRI reveals plaques (areas of white matter demyelination) - LP shows increased lymphocytes, increased immunoglobulins with oligoclonal IgG bands on high resolution electrophoresis

Question 34

Progressive Multifocal Leukoencephalopathy

Answer 34

**JC virus infection of oligodendrocytes** **Immunosuppression** (AIDS, Leukemia) leads to reactivation of the latent virus Presents with rapidly progressive neurologic signs Happens when **CD4\<200** (start prophalactic **TMP-SMX)** Increased risk associated with **natalizumab**, **rituximab**.

Question 35

Alzheimer Disease General Principle

Answer 35

APP is a receptor that is cleaved and broken down. If cleaved by alpha, OK. If cleaved by beta, results in AB amyloid that deposits in brain Results in widened sulci, narrowing gyri, dilation of ventricles (hydrocephalus due to loss of parenchyma) 1. Neuritic Plaques: AB amyloid from APP (chr 21) that underwent Beta cleavage 2. Neurofibrillary tangles: intracellular aggregates of fibers composed of hyperphosphorylated tau proteins. Tau is a microtubule-associated protein 3. Loss of Cholinergic neurons in the nucleus basalis of Meynert

Question 36

Alzheimer Genetics

Answer 36

Early or Sporatic **Early:** due to familial cases associated with **presenilin** 1 and 2 mutations. Also seen in **Down Syndrome** due to chr 21 having APP **Sporatic (95% of cases):** risk doubles every 5 years after the age of 60. **E4 allele of apolipoprotein (APOE)** is associated with increased risk, E2 allele with decreased risk

Question 37

Vascular Dementia

Answer 37

Multifocal infarction and injury due to hypertension, atherosclerosis or vasculitis 2nd most common cause of dementia Step-wise decline in cognitive ability with late- onset memory impairment \*essentially a concequence of moderate global cerebral ischemia\*

Question 38

Frontotemporal Dementia (Pick Disease)

Answer 38

Degenerative disease of the frontal and temporal cortex, spares the parietal and occipital lobe - Characterized by round aggregates of tau protein (Pick bodies) in neurons of the cortex - Behavioral and language symptoms arise early

Question 39

Parkinson Disease pathophys

Answer 39

- Degenerative loss of dopaminergic neurons in the substantia nigra of the basal ganglia - The nigrostriatal pathway of basal ganglia uses dopamine to initiate movement Rare cases due to MPTP exposure (illicit drugs)

Question 40

Parkinson Disease treatment

Answer 40

Want to get more DA. **BALSA.** **B**romocriptine (DA agonist) **A**mantadine (decrease reuptake, also used in infleunza) **L**evodopa (with carbidopa) **S**elegiline (and COMT inhibitors block breakdown of DA) **A**ntimuscarinics

Question 41

Clinical features of Parkinson

Answer 41

**TRAP** **T:** Tremor- pill rolling tremor at rest, not seen with movement **R:** Rigidity - cogwheel rigidity in the extremities **A:** akinesia/bradykinesia - slowing of voluntary movement, expressionless face **P:** postural instability and shuffling gate

Question 42

Histology of parkinson disease

Answer 42

-Loss of pigmented neurons in substantia nigra and round, eosinophilic **inclusions of alpha-synuclein (Lewy bodies)**

Question 43

Huntington Disease

Answer 43

Degeneration of GABAergic neurons in the caudate nucleus of the basal ganglia - AD Chr 4 expansion of CAG in huntingtin gene - Anticipation (due to further expansion of the trinucleotides in spermatogenesis) - Presents with chorea that can progress to dementia and depression

Question 44

Normal Pressure Hydrocephalus

Answer 44

**Increased CSF** resulting in dilated ventricles -Can cause dementia in adults _Classic Triad:_ **1. Urinary Incontinence** **2. Gait instability** **3. Dementia** **"Wet-Wobbly-Wacky"**

Question 45

What happens with spongiform encephalopathy to the prions

Answer 45

**Normal**: in alpha-helical configuration PrP^c **Abnormal**: conversion to a b-pleated conformation PrP^sc

Question 46

Creutzfeldt-Jacob Disease (CJD)

Answer 46

most common spongiform encephalopathy Usually sporatic: rarely can arise due to exposure to prion-infected human tissue (HGH or corneal transplant) -Presents as RAPIDLY PROGRESSIVE DEMENTIA associated with ataxia and startle myoclonus Variant CJD: Mad cow disease. exposure to bovine spongiform encephalopathy

Question 47

Basic principles of CNS tumors

Answer 47

50% metastatic/50% primary Lung, Breast, Kidney are common sources **Adults are primarily supratentorial** (glioblastoma, meningioma, schwannoma) **Kids are primarily infratentorial** (pilocytic astrocytoma, ependymoma, medulloblastoma)

Question 48

Glioblastoma Multiforme (GBM)

Answer 48

-Malignant, high-grade tumor of astrocytes Most common primary malignant CNS tumor in adults Usually arise in the **cerebral hemisphere,** characteristically **cross the corpus callosum (butterfly** appearance) Regions of necrosis surrounded by tumor cells (pseudopalisading) and endothelial cell proliferation **GFAP +**

Question 49

Meningioma

Answer 49

Benign tumor of **arachnoid cells** **MOST COMMON BENIGN CNS** tumor in ADULTS W\>M Present as **seizures** as tumor compresses cortex (not invade) Round mass attached to the dura **Whorled Pattern w/w/o psammoma bodies**

Question 50

Schwannoma

Answer 50

Benign tumor of schwann cells Invades cranial or spinal nerves within the cranium. Most frequently involves **cranial nerve VIII at the cerebellopontine angle** (presents as loss of hearing and tinnitus) Tumors are **S-100 + (neural crest)** Bilateral tumors seen in **neurofibromatosis type 2**

Question 51

Oligodendroglioma

Answer 51

Malignant tumor of oligodendrocytes **Calcified** tumor in white matter, usually involving the frontal lobe, may present with seizures **Fried-egg appearance of cells on biopsy**

Question 52

Pilocytic Astrocytoma

Answer 52

Benign tumor of **astrocytes** Most common CNS tumor in **CHILDREN**, usually arise in **cerebellum** Imagine reveals a **cystic lesion with a mural nodule** Biopsy shows **Rosenthal** **fibers** (thick eosinophilic processes of astrocytes) **GFAP+**

Question 53

Ependymoma

Answer 53

Malignant **tumor of ependymal cells (cells that line ventricles)**, usually seen in children Most commonly arises in the **4th ventricle**, may present with hydrocephalus **Perivascular pseudorosettes** are characteristic finding

Question 54

Medulloblastoma

Answer 54

Malignant tumor derived from the granular cells of the cerebellum (neuroectoderm) Usually arise in children Histology reveals small, round blue cells Homer-wright rosettes may be present Poor prognosis. tumor grows rapidly and spreads via CSF via 4th ventricular space If mets to cauda equina called "drop metastasis"

Question 55

General overview of where the types of CNS tumors originate

Answer 55

Question 56

Craniopharyngioma

Answer 56

Tumor that arises from **epithelial remnants of Rathke's Pouch (anterior pituitary)** Presents as a **supratentorial mass in a young adult**. May compress the optic chiasm leading to **bitemporal hemianopsia** **Calcifications** common seen on imaging (derived from tooth-like tissue)