USMLE AHMED SHEBL.pdf

USMLE ENDPOINT, NEUROLOGY DR. AHMED SHEBL Dr Ahmed Shebl [DATE] [COMPANY NAME] [Company...

USMLE ENDPOINT, NEUROLOGY DR. AHMED SHEBL Dr Ahmed Shebl [DATE] [COMPANY NAME] [Company address] https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl EMBRYOLOGY NEURAL DEVELOPMENT  Notochord (mesoderm) induces overlying ectoderm to differentiate into neuroectoderm and form neural plate.  Notochord induces differentiation by sonic hedgehog gene.  Neural plate gives rise to neural tube and neural crest cells.  Notochord becomes nucleus pulposus of intervertebral disc in adults.  Alar plate (dorsal): sensory. Basal plate (ventral): motor. Both have the same orientation as spinal cord. REGIONAL SPECIFICATION OF DEVELOPING BRAIN  Telencephalon is the 1st part.  Diencephalon is the 2nd part.  The rest are arranged alphabetically: mesencephalon, metencephalon, myelencephalon. Page 1 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl CENTRAL AND PERIPHERAL NERVOUS SYSTEMS ORIGINS  Neuroepithelia in neural tube form:  CNS neurons.  Ependymal cells (inner lining of ventricles, make CSF).  Oligodendrocytes.  Astrocytes.  Neural crest:  PNS neurons.  Schwann cells.  Ganglion (collection of neuronal cell bodies outside the CNS.)  Mesoderm  Microglia (like Macrophages). UW notes:  Anterior pituitary  from oral ectoderm (Rathke’s pouch) = surface ectoderm.  Posterior pituitary (neurohypothesis)  from neuroectoderm.  Neurofibromatosis type I arise from Schwann cells  neural crest cell origin. NEURAL TUBE DEFECTS  Neural plate deepens in the center to create the neural groove that is bound on both sides by neural folds.  The folds fuse to create a neural tube which is connected to the amniotic cavity by openings at the ends called anterior and posterior neuropores.  These openings close during the 4th week of fetal life.  Failure of the neuropores to close leads to the formation of neural tube defects (NTDs)  persistent connection between amniotic cavity and spinal canal.  Failure of the caudal neuropore to close  spina bifida.  Failure of the rostral (cranial) neuropore  anencephaly (complete absence of the brain).  ↑ α-fetoprotein (AFP) in amniotic fluid and maternal serum (except spina bifda occulta = normal AFP). (AFP also increases in any body wall defect)  ↑ Acetylcholinesterase (AChE) in amniotic fluid is a helpful confirmatory test.  Associated with maternal diabetes as well as low folic acid intake before conception and during pregnancy. Page 2 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl  Folic acid antagonists (anti-epileptic drugs, trimethoprim) during pregnancy are risk factors for neural tube defects. SPINA BIFDA OCCULTA  Failure of caudal neuropore to close, but no herniation.  Spinal tube fails to induce bone to form vertebral arch  missing spinous processes (bony defect).  Usually seen at lower vertebral levels. Dura is intact.  Associated with tuft of hair or skin dimple at level of bony defect.  Normal AchE & AFP. Page 3 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl SPINA BIFIDA CYSTICA  ↑ AFP (there is a body wall defect) + normal AChE (neural tissue is not exposed outside). MENINGOCELE  Meninges (but no neural tissue) herniate through bony defect. MENINGOMYELOCELE  Meninges and neural tissue (eg, cauda equina) herniate through bony defect.  Almost always has Chiari II malformation.  Hydrocephalus major cause morbidity (Obstruction 4th ventricular outflow due to compression by cerebellar herniation in Chiari II). MYELOSCHISIS  Also known as rachischisis.  Exposed unfused neural tissue without skin/meningeal covering.  ↑ AFP + ↑ AChE. ANENCEPHALY  Failure of rostral (anterior or cranial) neuropore to close  no forebrain, open calvarium.  'frog-like' appearance of the fetus.  ↑ AFP + ↑ AChE.  Associated with maternal polyhydramnios (fetal swallowing of amniotic fluid is impaired). Page 4 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl HOLOPROSENCEPHALY  Embryology:  Failure of left and right hemispheres to separate.  Usually occurs during weeks 5–6.  Etiology:  Genetic: o May be related to mutations in sonic hedgehog signaling pathway. o Seen in trisomy 13.  Environmental: o Fetal alcohol syndrome.  Clinical features: range of phenotypic findings:  Mild: closely set eyes (hypotolerism), cleft lip/palate.  Severe: single midline eye (cyclopia), primitive nasal structure (proboscis), midfacial clefts.  Imaging:  MRI A reveals monoventricle and fusion of basal ganglia (star in A). UW: It is an example of a congenital malformation. Page 5 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl POSTERIOR FOSSA MALFORMATIONS CHIARI I MALFORMATION  Ectopia of cerebellar tonsils (1 structure) A.  Congenital, usually asymptomatic in childhood, manifests in adulthood with headaches and cerebellar symptoms.  Associated with spinal cavitations (eg, syringomyelia). CHIARI II MALFORMATION  Herniation of low-lying cerebellar vermis and tonsils (2 structures) through foramen magnum with aqueductal stenosis  hydrocephalus.  Usually associated with lumbosacral meningomyelocele (may present as paralysis/sensory loss at and below the level of the lesion). DANDY-WALKER SYNDROME  Failure of foramen Luscka and Magendie to open  dilated 4th ventricle.  Agenesis of cerebellar vermis leads to cystic enlargement of 4th ventricle (arrow in B) that fills the enlarged posterior fossa.  Associated with:  Noncommunicating hydrocephalus:  Due to atresia of the foramina of Luschka and Magendie.  Resulting in symptoms of elevated intracranial pressure (eg, irritability, vomiting).  Spina bifida. Page 6 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl Red arrow  agenesis of cerebellar vermis. Blue arrow  cystic dilation of the fourth ventricle with posterior fossa enlargement SYRINGOMYELIA  Cystic cavity (syrinx) within central canal of spinal cord (yellow arrows in A). Syrinx = tube, as in syringe.  Most common at C8–T1  affecting the upper limbs.  Fibers crossing in anterior white commissure (spinothalamic tract) are typically damaged first. 1. Results in a “cape-like,” bilateral symmetrical loss of pain and temperature sensation in upper extremities. 2. Fine touch sensation is preserved as it runs in the posterior column).  Associated with Chiari malformations (red arrow shows low-lying cerebellar tonsils in A) and other congenital malformations; acquired causes include trauma and tumors.  Syrinx expansion results in involvement of other spinal tracts leading to: 1. Muscle atrophy and weakness with decreased muscle tone and impaired reflexes- due to damage to lower motor neurons of the anterior horn cells. 2. Horner syndrome with ptosis (droopy eyelid), miosis (constricted pupil), and anhidrosis (decreased sweating) due to disruption of the lateral horn cells of the hypothalamospinal tract. Page 7 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl TONGUE DEVELOPMENT  Anterior 2/3  From 1st and 2nd branchial arches.  Thus sensation via CN V3, taste via CN VII.  Posterior 1/3  From 3rd and 4th branchial arches form  Thus sensation and taste mainly via CN IX, extreme posterior via CN X.  Motor innervation is via:  CN XII to hyoglossus (retracts and depresses tongue), genioglossus (protrudes tongue), and styloglossus (draws sides of tongue upward to create a trough for swallowing).  CN X to palatoglossus (elevates posterior tongue during swallowing). Page 8 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl ANATOMY AND PHYSIOLOGY CNS cells Non-neurons = Neurons glial cells macroglial microglial ependymal Astrocytes oligodendrocytes GLIAL CELLS  Support neurons.  Gliosis:  Proliferation/hypertrophy of glial cells.  Reaction to CNS injury.  Astrocytes undergo major changes.  Glioma:  Neoplasms of glial origin (astrocytomas, ependymomas, and oligodendrogliomas).  Stain positive for GFAP. Page 9 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl NEURONS  Signal-transmitting cells of the nervous system.  Permanent cells—do not divide in adulthood.  Signal-relaying cells with  dendrites (receive input)  Cell bodies and axons (send output).  Cell bodies and dendrites can be seen on Nissl staining (stains RER).  RER is not present in the axon.  Injury to axon  Wallerian degeneration:  Occurs in the segment of axon that has lost connection with the cell body.  Degeneration of axon and myelin distal to a point of injury.  Within a week the axon is destroyed and its fragments are digested by Schwann cells and macrophages.  Similar degenerative changes occur in the segment of axon that lies proximal to the injury. Degeneration of the proximal segment extends to the closest node of Ranvier.  Allows for potential regeneration of axon (if in PNS).  UW: Axonal regeneration does not occur in the central nervous system due to the persistence of myelin debris, secretion of neuronal inhibitory factors, and development of dense glial scarring.  Macrophages remove debris and myelin.  UW: CNS tumors of neuronal origin frequently stain positively for synaptophysin on immunohistology.  Synaptophysin is a protein found in the presynaptic vesicles of neurons, neuroendocrine and neuroectodermal cells. Page 10 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl  UW: In the peripheral nervous system:  Schwann cells sense the axonal degeneration and begin to degrade their myelin and secrete cytokines and chemokines that recruit macrophages.  This allows effective clearance of myelin debris which, along with trophic factor secretion by Schwann cells, stimulates formation of a growth cone from the stump of the proximal axon and facilitates nerve regeneration.  In the central nervous system:  Phagocytic macrophages/microglia are recruited more slowly because of the blood-brain barrier.  Myelin-producing oligodendrocytes also become inactive or undergo apoptosis and do not assist with phagocytosis.  This slows removal of the myelin debris, which can persist for years in the degenerating tracts and suppress axonal growth via myelin-associated inhibitory factors.  Astrocytes also release inhibitory molecules and proliferate in the weeks to months following injury, forming a glial scar that acts as a barrier to axon regeneration. NEURON ACTION POTENT IALS  Resting Membrane Potential:  Difference in charges across the cell membrane at rest.  Prevents free diffusion of ions.  Typically an excess of positive ions outside cell, excess of negative ions inside, giving rise to electrical potential difference that ranges from -60 to - 80 mV (typically -70 mV).  Caused by:  Efflux of K+ (high conductance, EK = -80 mV) = leak of K+.  With some influx of Na+ (low conductance, ENa = +60 mV).  Potential maintained by Na+/K+-ATPase.  Cl- contributes little to resting membrane potential  To depolarize:  Na channels open  allows Na into cell and raises voltage.  Na channels open along axon propagation.  At axon terminal, Ca channels open  Triggers release of neurotransmitter  Vesicles fuse with membrane exocytosis. Page 11 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl CLINICAL RELEVANCE  Agents that block Na channels will inhibit signals  inhibits depolarization.  Example: Local anesthetics:  Lidocaine, Benzocaine, Tetracaine, Cocaine, etc.  Some neurotoxins block Na channels: AXONAL TRANSPORT  Kinesin and dynein are microtubular motor proteins responsible for rapid axonal transport.  Kinesin participates in anterograde transport,  i.e. moving intracellular vesicles and organelles toward the plus (rapidly growing) ends of microtubules.  Anterograde transport is usually directed away from the nucleus, down the axon, toward the nerve terminal.  Dynein participates in retrograde transport.  i.e. moving organelles toward the nucleus.  Dynein also functions in ciliary and flagellar movement.  These two motor proteins derive energy for movement from ATP hydrolysis. Page 12 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl ASTROCYTES  Most common glial cell type in CNS.  Functions: 1. Physical support, repair. 2. Extracellular K+ buffer. 3. Removal of excess neurotransmitter. 4. Component of blood-brain barrier. 5. Glycogen fuel reserve buffer.  Reactive gliosis (hypertrophy and hyperplasia) in response to neural injury.  Derived from neuroectoderm.  Astrocyte marker: GFAP ―glial fibrillary acid protein‖. CLINICAL RELEVANCE  Astrocytoma: 1. Cerebellum of children. 2. GFAP positive.  JC Virus infects astrocytes and oligodendrocytes  Causes PML in HIV patients. MICROGLIA  CNS macrophages:  Phagocytic scavenger cells  clean up injured areas.  Mesodermal, mononuclear origin.  Activated in response to tissue damage.  Not readily discernible by Nissl stain.  HIV can persist in the brain via microglia.  HIV-infected microglia fuse to form multinucleated giant cells in CNS. EPENDYMAL CELLS  Glial cells with a ciliated simple columnar form that line the ventricles and central canal of spinal cord.  Apical surfaces are covered in cilia (which circulate CSF) and microvilli (which help in CSF absorption). Page 13 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl MYELIN  Increases SPEED of impulse propagation in axon.  Saltatory conduction: 1. At the nodes of Ranvier, where there are high concentrations of Na+ channels.  allow the depolarization to jump from node to node. 2. Only need to depolarize Nodes of Ranvier. 3. Do not need to depolarize entire axon. 4. This makes process faster. 5. ↑ Conduction velocity. 6. ↑ Length constant = space constant:  A measure of how long the depolarization signal can propagate.  Demyelination  ↓ length constant due to increased charge dissipation along a nerve axon. 7. ↓ Time constant:  The time it takes for a change in membrane potential to achieve 63% of the new value.  Lower time constants allow quicker changes in membrane potential, thus increasing axonal conduction speed.  Demyelination would increase the time constant and lead to slower impulse conduction.  Synthesis of myelin by: 1. Oligodendrocytes in CNS (including CN I and II) 2. Schwann cells in PNS (including CN III-XII). COPS: CNS = Oligodendrocytes, PNS = Schwann cells.  Wraps and insulates axons (arrow in A): ↑ space constant and ↑ conduction velocity. What are the Nodes of Ranvier? They are areas of discontinuation of the myelin. What voltage gated channels are concentrated in the nodes of Ranvier? Voltage-gated Na channels. What is the function of these channels? Provide salutatory conduction  speeding up postconduction. What happen to these channels in individuals with demyelinating disease? They will not be concentrated in the nodes of ranvier, but they will spread all over the axon  slow down the impulse conduction. Page 14 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl SCHWANN CELLS o Each Schwann cell myelinates only 1 PNS axon. o Also promote axonal regeneration. o Derived from neural crest. o Injured in Guillain-Barré syndrome. OLIGODENDROCYTES  Myelinates axons of neurons in CNS. The optic nerve is the only cranial nerve that is myelinated by oligodendrocytes; so it is affected in MS.  Each oligodendrocyte can myelinate many axons (∼ 30).  Predominant type of glial cell in white matter. o Derived from neuroectoderm.  “Fried egg” appearance histologically.  Injured in multiple sclerosis, progressive multifocal leukoencephalopathy (PML), leukodystrophies. TYPES OF NERVE FIBER S  Classification by diameter, myelin: 1. A-alpha:  Large, myelinated fibers, 6 to 15 microns diameter Large.  Most efferent motor fibers.  Touch, vibration, and position. 2. A-delta (δ):  Small, myelinated fibers, 3 to 5 microns in diameter.  Cold, pain. 3. C fibers:  Unmyelinated fibers, 0.5 to 2 microns in diameter.  Warm, pain.  These small fibers are more easily blocked by local anesthetics. Page 15 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl SENSORY RECEPTORS Receptor Sensory neuron fiber type Location Senses type Free nerve  C—slow, unmyelinated  All skin, Pain, temperature. endings fibers epidermis  Aδ—fAst, myelinated  Some viscera fibers Meissner  Large, myelinated fibers.  Glabrous Dynamic, fine/light corpuscles  Adapt quickly. (hairless) skin touch, position sense Pacinian  Large, myelinated fibers.  Deep skin Vibration, pressure corpuscles  Adapt quickly. layers, ligaments, joints Merkel  Large, myelinated fibers.  Finger tips Pressure, deep static discs  Adapt slowly  Superficial skin touch (eg, shapes, edges), position sense Ruffini  Dendritic endings with  Finger tips, Pressure, slippage of corpuscles capsule. joints objects along  Adapt slowly. surface of skin, joint angle change PERIPHERAL NERVE  Endoneurium:  Invests single nerve fiber layers.  Inflammatory infiltrate in Guillain-Barré syndrome.  Perineurium (blood-nerve Permeability barrier)  Surrounds a fascicle of nerve fibers.  Must be rejoined in microsurgery for limb reattachment.  Epineurium  Dense connective tissue that surrounds entire nerve (fascicles and blood vessels).  Endo = inner. Peri = around. Epi = outer. Page 16 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl PERIPHERAL NERVE DAMAGE  Mild: Neurapraxia:  Focal demyelination.  Axon distal to injury intact.  Continuity across injury.  Excellent recovery.  Moderate: Axonotmesis:  Demyelination plus damage to axon.  Endoneurium, perineurium remain intact.  Severe: Neurotmesis:  Axon, myelin sheath irreversibly damaged.  External continuity of the injured nerve disrupted.  No significant regeneration occurs.  Bad prognosis. Page 17 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl AXONOTMESIS  Distal to the lesion: ―Wallerian degeneration”.  Axon degenerates, myelin sheath involutes.  Axon regrowth sometimes occurs.  Possible if Schwann cells maintain integrity.  Proximal to the lesion: “Axonal reaction”  The changes in the body of a neuron after the axon has been severed.  Also called central chromatolysis.  Up-regulation of protein synthesis for repair.  Cell body changes:  Swelling.  Chromatolysis (disappearance of Nissl bodies).  Nucleus moves to periphery.  Resolves with time.  Variable prognosis:  Extent of damage, distance to target, complexity of nerve.  Usually partial recovery.  Longer recovery time than neurapraxia. Page 18 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl CENTRAL NERVE DAMAGE ISCHEMIA  ~ 4-5 minutes of ischemia  irreversible damage.  Neurons more sensitive than glial cells.  Higher energy demands; lack glycogen.  Most sensitive neurons: Hippocampus Purkinje cells (Cerebellum) Neocortex Striatum (Basal ganglia). CHANGES AFTER INFARCTION Page 19 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl NEUROTRANSMITTERS NOREPINEPHRINE  Stress/panic hormone.  Increased levels in anxiety.  Decreased levels in depression.  Some antidepressants ↑NE levels (eg, SNRIs).  Its main source is locus ceruleus (in the posterior pons near 4th ventricle). DOPAMINE  Synthesized in:  Ventral tegmentum (midbrain)  Substantia nigra (midbrain)  Increased levels in schizophrenia.  Decreased levels in Parkinson’s and depression. Page 20 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl GABA  GABA is largely inhibitory.  Synthesized in nucleus accumbens (subcortex).  Important for pleasure/reward.  Research shows that it is activated in: o Drug addiction. o Fear.  Decreased levels in anxiety and Huntington’s disease.  GABA Receptor Anesthetics:  Etomidate, Propofol, Benzodiazepines, Barbiturates.  These drugs activate receptor  sedation.  GABA Receptor:  GABA binds to receptor allows Cl- into cell  more negative membrane potential (hyperpolarization)  make it harder to get depolarized  decreases the neuronal excitation  inhibitory.  GABA Synthesis:  Synthesized via glutamate decarboxylase in neurons.  Broken down by GABA transaminase.  Both enzymes need B6 cofactor. o B6 deficiency  seizures. Page 21 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl SEROTONIN  Synthesized in raphe nucleus (pons).  Decreased levels in anxiety & depression. SEROTONIN SYNDROME  Can occur any drug that that ↑serotonin (SSRIs, MAO inhibitors, SNRis, TCAs).  Classically triad: 1. Mental status changes:  Anxiety, delirium, restlessness, and disorientation. 2. Autonomic hyperactivity:  Diaphoresis, tachycardia, hyperthermia. 3. Neuromuscular abnormalities:  Tremor, clonus, hyperreflexia, bilateral Babinski sign.  Watch for patient on anti-depressants with fever, confusion, and rigid muscles.  Don’t confuse with NMS “neuroleptic malignant syndrome”  Both: muscle rigidity, fever, changes in mental status, and autonomic instability.  NMS: ―Lead pipe‖ rigidity, ↑CK.  SS: Clonus.  Treatment: cyproheptadine (5 –HT antagonist). ACETYLCHOLINE  Synthesized in basal nucleus of Meynert (subcortex).  Increased levels in REM sleep.  Decreased levels in Alzheimer’s & Huntington’s disease. Page 22 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl GLUTAMATE  Major excitatory neurotransmitter.  N-methyl-D-aspartate (NMDA) receptor is target.  Huntington’s: neuronal death from glutamate toxicity:  Glutamate binds NMDA receptor.  Excessive influx calcium  Cell death. PHENCYCLIDINE (PCP) (ANGEL DUST)  Antagonist to NMDA receptor.  Violent behavior.  Hallucinations.  Ataxia, nystagmus.  Hypertension, tachycardia, diaphoresis.  Can cause seizures, coma, or death. NEUROTRANSMITTER CHANGES WITH DISEASE Page 23 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl MENINGES  Three membranes that surround and protect the brain and spinal cord: 1. Dura mater  Thick outer layer closest to skull.  Derived from mesoderm. 2. Arachnoid mater  Middle layer, contains web-like connections.  Derived from neural crest. 3. Pia mater  Thin, fibrous inner layer that firmly adheres to brain and spinal cord.  Derived from neural crest.  CSF flows in the subarachnoid space, located between arachnoid and pia mater.  Epidural space—a potential space between the dura mater and skull containing fat and blood vessels. Page 24 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl BLOOD-BRAIN BARRIER  Prevents circulating blood substances (eg, bacteria, drugs) from reaching the CSF/ CNS.  Formed by 3 structures: 1. Tight junctions between nonfenestrated capillary endothelial cells. 2. Basement membrane. 3. Astrocyte foot processes.  Which substances to pass? : 1. Glucose and amino acids cross slowly by carrier-mediated transport mechanisms. 2. Nonpolar/lipid-soluble substances cross rapidly via diffusion.  A few specialized brain regions with fenestrated capillaries and no blood-brain barrier allow molecules in blood to affect brain function 1. Area postrema ―Chemoreceptor trigger zone‖  Caudal end of 4th ventricle in medulla.  Chemo agents affect this area.  Sends signals to vomiting center in the medulla vomiting after chemo. 2. OVLT [organum vasculosum lamina terminalis]  Osmotic sensing.  Anterior wall of the third ventricle. 3. Median Eminence of Hypothalamus:  Releases hormones into vascular system to pituitary.  Allows hypothalamus to regulate pituitary. 4. Posterior Pituitary Gland:  Oxytocin, ADH secretion. 5. Pineal Gland:  Melatonin. Page 25 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl  Infarction and/or neoplasm destroys endothelial cell tight junctions  vasogenic edema.  Other notable barriers include: 1. Blood-testis barrier. 2. Maternal-fetal blood barrier of placenta. UW: Tight junctions between nonfenestrated capillary endothelial cells:  Prevent the paracellular passage of fluid and solutes.  This barrier only permits the passage of substances from the blood to the brain via transcellular movement across the endothelial plasma membrane, which is limited by diffusion or carrier-mediated transport.  Transcellular movement of dopamine is limited by the molecule's low lipid solubility and the lack of dopamine-specific transport carriers. Page 26 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl VOMITING CENTER  Coordinated by nucleus tractus solitarius (NTS) in the medulla, which receives information from the chemoreceptor trigger zone (CTZ, located within area postrema in 4th ventricle), GI tract (via vagus nerve), vestibular system, and CNS.  CTZ and adjacent vomiting center nuclei receive input from 5 major receptors: muscarinic (M1), dopamine (D2), histamine (H1), serotonin (5-HT3), and neurokinin (NK-1) receptors. 1. 5-HT3, D2, and NK-1 antagonists used to treat chemotherapy-induced vomiting. 2. M1 and H1 antagonists used to treat motion sickness and hyperemesis gravidarum. Page 27 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl SLEEP PHYSIOLOGY  Sleep cycle is regulated by the circadian rhythm, which is driven by suprachiasmatic nucleus (SCN) of hypothalamus.  Circadian rhythm controls nocturnal release of ACTH, prolactin, melatonin, norepinephrine.  SCN  norepinephrine release  pineal gland  melatonin.  SCN is regulated by environment (eg, light).  UW: Melatonin supplementation is recommended for the treatment of insomnia associated with jet lag (Ramelteon).  Two stages: rapid-eye movement (REM) and non-REM.  Alcohol, benzodiazepines, and barbiturates are associated with ↓ REM sleep and delta wave sleep.  Norepinephrine also ↓ REM sleep.  Benzodiazepines are useful for night terrors and sleepwalking by ↓ N3 and REM sleep. Page 28 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl CEREBRAL CORTEX REGIONS FRONTAL LOBE  Motor function (initiation of movements), planning movements, thinking, feeling, imagining, making decisions.  Key Areas: Motor cortex, Frontal Eye Fields, Broca’s speech area, Prefrontal Cortex. PRIMARY MOTOR AREA:  Site:  Floor of central sulcus & posterior part of precentral gyrus.  Function :  Initiation of voluntary motor activity of the opposite side of the body through the pyramidal (A) tract.  In this area the body is represented upside down. Page 29 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl  Lesion:  Irritative: o Contralateral motor Jacksonian fits: there are convulsions involving the muscles of one side of the body. o The fit has a focal onset either in the thumb, angle of the mouth or big toe (depending on whether the irritative lesion starts in the lower or upper part of the motor area). o The fit spreads in a march course e.g. thumb  arm  shoulder  trunk  L.L.  Destructive: Contralateral paralysis usually affecting one limb (monoplegia). PREMOTOR AREA (AREA 6):  Site: anterior part of the precentral gyrus.  Function: 1. Partly supplies pyramidal tract. 2. Gives extra pyramidal fibers. 3. This area inhibits the muscle tone & the deep reflexes on the opposite side of the body.  Lesion: 1. Contralateral hypertonia & exaggerated deep reflexes. 2. Contralateral fanning of the lateral 4 toes on eliciting the plantar reflex  positive babiniski. FRONTAL EYE FIELDS  Site: posterior part of middle frontal gyrus.  Function:  Voluntary conjugate eye movement to the opposite side.  e.g. while reading the action of passing from the end of one line to the beginning of the next line; this movement is usually rapid & is termed "saccadic."  Lesion:  Irritative: attacks of conjugate eye deviation to the opposite side of the lesion.  Destructive: both eyes deviate to side of lesion. Page 30 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl BROCA’S SPEECH AREA  Site: posterior part of inferior frontal gyrus of DOMINANT hemisphere  Function:  Speech production (not comprehension).  Moves muscles for speech (motor center for speech).  Makes speech clear, fluent.  Responsible for all communicative motor planning (lesion  difficulty writing and signing).  Lesion:  Destruction “expressive” aphasia: o Know what you want to say but cannot express speech. o Short sentences, stutters, stops. o Watch for “broken” speech: stuttering, stop/start.  DD: Wernicke’s aphasia:  Located in temporal lobe – LEFT hemisphere.  Speech comprehension (not production).  Destruction ―fluent‖ aphasia. Fluent, but meaningless speech.  Watch for LACK of stutters, starts/stops (unlike Broca’s aphasia).  DD: Global Aphasia  Both Broca's and Wernicke's (left side).  Patient’s often mute.  Cannot follow commands.  Can occur immediately following stroke.  Usually occurs with extensive CNS damage (right Hemiparesis, right visual loss). EXNER'S AREA (AREA 45) :  Site: adjacent to the Broca’s area in the DOMINANT hemisphere.  Function: center for writing.  Lesion: agraphia; the patient cannot express his ideas in written words. Page 31 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl PREFRONTAL CORTEX  Site: Anterior 2/3 of frontal lobe.  Functions: 1. Higher center for mentality, personality & behavior. 2. Inhibition of primitive reflexes which are present normally in the newborn.  Lesion: 1. Mentality, personality & behavioral changes: lack of attention & judgment, disinterest in people & surroundings, lack of personal hygiene, ending in dementia. 2. Reappearance of primitive reflexes. PARACENTRAL LOBULE:  Site: medial surface of the superior frontal gyrus, adjacent to the foot & leg area.  Function: cortical inhibition (control) of bladder & bowel voiding.  Lesion: incontinence of urine & faeces. PARIETAL LOBES PRIMARY SOMATOSENSORY AREA:  Site: post-central gyrus.  Function:  Perception of cortical sensations from the opposite side of the body; like in the motor area, the body is represented upside down.  Lesion:  Irritative: o Contralateral sensory Jacksonian fits in the form of numbness or tingling with focal onset & a march course. o It may be followed by a motor fit if the irritation extends to the adjacent motor area.  Destructive: contralateral cortical sensory loss. Page 32 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl ANGULAR GYRUS:  Site: in the postero-inferior part of the parietal lobe.  Function:  In the DOMINANT hemisphere, it is concerned with reading i.e. the recognition & recall of letters & numbers.  Lesion:  Alexia; the patient who could read before the lesion, becomes unable to do so, because he cannot understand the letters & numbers which he sees. BAUM’S LOOP:  Part of visual pathway.  Damage: Quadrantic Anopia.  Damage to right (non-dominant) parietal lobe: spatial neglect:  Contralateral (left) agnosia.  Can’t perceive objects in part of space.  Despite normal vision, somatic sensation is impaired.  Failure to report or respond to stimuli affected side. TEMPORAL LOBE PRIMARY AUDITORY CORTEX:  Site: superior temporal gyrus.  Function: auditory sensory area.  Lesion:  Irritative: auditory hallucinations.  Destructive: Slight hearing impairment, never deafness as hearing is bilaterally represented. AUDITORY ASSOCIATIVE AREA:  Site: adjacent to areas primary auditory cortex.  Function: recognition & recall of sounds.  Lesion: Auditory agnosia: the patient hears but does not understand (recognize) what he hears. Page 33 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl WERNICKE’S SPEECH AR EA:  Lesions  Wernicke’s aphasia.  UW: The middle cerebral artery supplies Broca's area (superior division) and Wernicke's area (inferior division). OLFACTORY BULB:  Destruction ipsilateral anosmia.  Psychomotor epilepsy:  Sights, sounds, smells that are not there.  Can result from irritation olfactory bulb.  Part of temporal lobe epilepsy ―commonly with HSV encephalitis‖.  Rare, olfactory groove meningiomas:  About 10% of all meningiomas.  Cause anosmia. MEYER’S LOOP:  Part of the visual pathway. HIPPOCAMPUS:  Very sensitive to hypoxic damage.  Lesion:  Anterograde amnesia: Cannot make new memories.  Can be damaged by infarction in:  Hippocampal branches PCA.  Anterior choroidal arteries. AMYGDALA:  Temporal lobe nuclei. Part of limbic system.  Important for decision making, higher functions.  Kluver-Bucy Syndrome  Damage to bilateral amygdala (temporal lobes).  Hyperphagia - Weight gain.  Hyperorality - tendency to examine all with mouth.  Inappropriate Sexual Behavior (hypersexuality) o Atypical sexual behavior, mounting inanimate objects.  Visual Agnosia: o Inability to recognize visually presented objects.  Rare complication of HSV1 encephalitis. Page 34 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl OCCIPITAL LOBE  Visual Sensory Area: for the reception of visual images.  Visual Associative Area:  Function: 1. Recognition & recall of images. 2. Center for reflex conjugate eye movement to the opposite side e.g. while reading, following the words of a line, one after the other; this movement is usually slow & is termed "pursuit."  Lesion to the visual areas results in:  Irritative: Unformed visual hallucinations e.g. sparks, lines, flashes...; this occurs e.g. in the aura of classic migraine or in epilepsy when the occipital lobe is involved.  Destructive:  Cortical blindness  Homonymous Hemianopsia with macular sparing. o Dual blood supply to the macula: MCA and PCA. o PCA strokes often spare the macula..  Visual Agnosia: the patient sees (e.g. a familiar face) but does not recognize what he sees.  Paralysis of reflex conjugate eye movements.  Blood supply PCA. Page 35 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl HOMUNCULUS  Topographic representation of motor (shown) and sensory areas in the cerebral cortex.  Distorted appearance is due to certain body regions being more richly innervated and thus having ↑ cortical representation. MCA: Upper limb, face. ACA: Lower limb. Page 36 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl MOTOR SYSTEM  The motor system consists of 4 main components: THE PYRAMIDAL SYSTEM (U.M.N.):  It originates in the primary motor area & premotor area.  Terminates at the anterior horn cells (A.H.C.) of the different levels of the spinal cord.  It supplies the opposite side of the body. THE EXTRAPYRAMIDAL (EXTRA A) SYSTEM:  It originates from centers situated at various levels of C.N.S. mainly the Basal Ganglia.  It controls the opposite side of the body. THE CEREBELLAR SYSTEM:  It is composed of the Neo, Archi & Paleo-cerebellum.  It coordinates the movements of the same side of the body. THE LOWER MOTOR NEURON (L.M.N.)  It is formed of A.H.C. s & peripheral motor nerves (which transmit the motor impulses to the voluntary muscles). Page 37 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl UPPER MOTOR NEURONS VS LOWER MOTOR NEURONS DECUSSATION  UMN cross just below medulla.  Lesions above decussation  contralateral dysfunction.  Lesions below decussation  ipsilateral dysfunction. BULBAR  Bulbar muscles are supplied by CN in brainstem V (jaw), VII (face), IX (swallowing), X (palate), XI (head), XII (tongue). BULBAR VS. PSEUDOBULBAR  Bulbar palsy  Cranial nerve damage  LMN signs.  Absent jaw/gag reflex.  Tongue flaccid/wasted.  Pseudobulbar palsy  Corticobulbar tract damage  UMN signs.  Exaggerated gag reflex. Page 38 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl CEREBRAL PERFUSION  Brain perfusion relies on tight autoregulation.  Cerebral perfusion is primarily driven by Pco 2 (Po2 also modulates perfusion in severe hypoxia).  Cerebral perfusion relies on a pressure gradient between mean arterial pressure (MAP) and ICP.  ↓ Blood pressure or ↑ ICP  ↑ cerebral perfusion pressure (CPP).  Therapeutic hyperventilation  ↓ Pco2  vasoconstriction  ↓ cerebral blood flow  ↓ intracranial pressure (ICP). May be used to treat acute cerebral edema (eg, 2° to stroke) unresponsive to other interventions.  CPP = MAP – ICP. If CPP = 0, there is no cerebral perfusion  brain death.  Hypoxemia increases CPP only if Po 2 < 50 mm Hg.  CPP is directly proportional to Pco 2 until Pco2 > 90 mm Hg. CEREBRAL ARTERIES—CORTICAL DISTRIBUTION Page 39 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl WATERSHED ZONES  Sites:  Cortical border zones:  Between anterior cerebral/middle cerebral, posterior cerebral/middle cerebral arteries (blue areas in A).  typically appear as bilateral wedge-shaped strips of necrosis over the cerebral convexity, parallel and adjacent to the longitudinal cerebral fissure  Internal border zones:  Between the superficial and deep vascular territories of the middle cerebral artery (red areas in A).  Damage by severe hypotension.  Symptoms of watershed area damage:  If internal border zone stroke:  Weakness of the shoulders and thighs.  Sparing of the face, hands, and feet.  Bilateral symptoms.  A "man-in-a-barrel―  If posterior cerebral/middle cerebral cortical border zone stroke:  Higher order visual dysfunction. Page 40 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl CIRCLE OF WILLIS  System of anastomoses between anterior and posterior blood supplies to brain. Page 41 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl A  basilar artery. B & C  PCA. D  superior cerebellar artery (SCA). E  parapontine perforating artery. F  anterior inferior cerebellar artery (AICA). VENTRICULAR SYSTEM  Lateral ventricles  3rd ventricle via right and left interventricular foramina of Monro.  3rd ventricle  4th ventricle via cerebral aqueduct of Sylvius.  4th ventricle  subarachnoid space via:  Foramina of Luschka = Lateral.  Foramen of Magendie = Medial. Page 42 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl CEREBROSPINAL FLUID (CSF)  Made by ependymal cells of choroid plexus.  Travels to subarachnoid space via foramina of Luschka and Magendie.  Reabsorbed by arachnoid granulations.  Then drains into dural venous sinuses. HYDROCEPHALUS  ↑ CSF volume  ventricular dilation +/- ↑ ICP. COMMUNICATING  Ventricles can communicate with each other. COMMUNICATING HYDROCEPHALUS  ↓ CSF absorption by arachnoid granulations  ↑ ICP.  Usually due to arachnoid scarring post-meningitis or subarachnoid/intraventricular hemorrhage.  Presentation:  Headache.  Key sign: papilledema.  CT Hallmark: Dilation ALL ventricles.  Can cause herniation. NORMAL PRESSURE HYDROCEPHALUS (NPH)  Pathophysiology:  Gradual decline in the reabsorptive capacity of the arachnoid villi, with slow accumulation of CSF, is the root of the problem.  Pressure remains normal in NPH because gradual ventricular distention accommodates the CSF increase.  Enlarged ventricles on imaging  Compression of corona radiate  triad:  Urinary incontinence (urge incontinence).  Gait apraxia (magnetic gait).  Cognitive dysfunction (sometimes reversible). ―Wet, wobbly, and wacky‖. Page 43 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl  Normal opening pressure on LP:  CSF pressure elevated only episodically.  Does not result in increased subarachnoid space volume.  Gradual ventricular distention.  Affects the elderly; idiopathic.  Suspected mechanism: impaired absorption CSF.  Treatment: Ventriculoperitoneal (VP) Shunt  Drains CSF to abdomen.  UW: Micturition reflex (urination) is regulated by the following centers: 1. Sacral micturition center - located in S2-S4 level and responsible for bladder contraction. Parasympathetic fibers travel from S2-S4 ventral white matter within pelvic nerves and stimulate cholinergic receptors in the bladder wall. 2. Pontine micturition center - located in the pontine reticular formation. It coordinates relaxation of external urethral sphincter with bladder contraction during voiding. 3. Cerebral cortex - inhibits sacral micturition center. NONCOMMUNICATING (OBSTRUCTIVE)  Ventricles cannot communicate with each other’s. NONCOMMUNICATING HYDROCEPHALUS  Structural blockage of CSF flow within ventricles.  Often congenital.  Many etiologies:  Aqueductal stenosis.  Chiari Malformations.  Dandy Walker malformation.  Colloid cyst blocking foramen of Monro.  Tumor B. AQUEDUCTAL STENOSIS  Blocked drainage from 3rd to 4th ventricle.  Congenital narrowing (X-linked in boys)  Inflammation due to intrauterine infection (eg, Rubella, CMV, toxo, syphilis)  Presentation: Enlarging head circumference Page 44 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl HYDROCEPHALUS MIMICS  Ex vacuo ventriculomegaly  Appearance of ↑ CSF on imaging C, but is actually due to ↓ brain tissue and neuronal atrophy (eg, Alzheimer disease, advanced HIV, Pick disease, Huntington disease).  ICP is normal; NPH triad is not seen.  Dx: Increase size of ventricles: o IN PROPORTION to increase size of sulci. IDIOPATHIC INTRACRANIAL HYPERTENSION (IIH)  Also known as pseudotumor cerebri.  ↑ ICP with no apparent cause on imaging (eg, hydrocephalus, obstruction of CSF outflow).  Risk factors include female gender, Tetracyclines, Obesity, vitamin A excess, Danazol (female TOAD).  Symptoms: o Intractable, disabling headache.  Worse with lying flat and improves with standing. o Pulsatile tinnitus:  Rushing water or wind sound.  Transmission of vascular pulsations. o Diplopia (usually from CN VI palsy).  Physical examination: o Impaired optic nerve axoplasmic flow  papilledema. o Visual field testing shows enlarged blind spot and peripheral constriction. o No change in mental status.  Lumbar puncture: o ↑ Opening pressure (CSF pressure > 250 mmHg with normal analysis). o Provides temporary headache relief.  Treatment: o Weight loss, acetazolamide, invasive procedures for refractory cases (eg, CSF shunt placement, optic nerve sheath fenestration surgery for visual loss). Page 45 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl DURAL VENOUS SINUSES  Large venous channels.  Travel through dura.  Drain blood from cerebral veins.  Receive CSF from arachnoid granulations (superior sagittal sinus).  Empty into internal jugular vein.  Venous sinus thrombosis:  Presents with signs/symptoms of ↑ ICP (eg, headache, seizures, focal neurologic deficits).  May lead to venous hemorrhage.  Associated with hypercoagulable states (eg, pregnancy, OCP use, factor V Leiden). Page 46 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl CAVERNOUS SINUS  Collection of venous sinuses on either side of pituitary.  Bilateral, between temporal/sphenoid bones.  Collects blood eye/cortex.  Drains into internal jugular vein.  Structures:  Many nerves: CN III, IV, V1, V2, VI, sympathetic fibers (all traveling to orbit).  Also portion of internal carotid artery CAVERNOUS SINUS SYNDROME  Causes:  Compression by tumor (pituitary tumor), thrombus, fistula.  Infections of face, nose, orbits, tonsils, and soft palate can spread to cavernous sinus (septic thrombosis) through the valveless veins.  Carotid-cavernous fistula.  Symptoms: ―CN VI is most susceptible to injury.‖  Headache.  Swollen eyes.  Impairment of ocular motor nerves (ophthalmoplegia).  Horner's syndrome.  Sensory loss 1st/2nd divisions trigeminal nerve. Page 47 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl SUBCORTICAL STRUCTURES Structures that lie between the cortex and the brain stem and include: (Thalamus, Hypothalamus, Limbic System, Basal Ganglia). You should be able to identify these structures anatomically and by imaging. THALAMUS  ―Gateway to the cortex‖  major relay for all ascending sensory information to the cortex except olfaction.  Epithalamus = pineal gland. Page 48 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl  UW: Thalamic stroke  complete contralateral pure sensory loss (eg, touch, pain/temperature, vibration/proprioception). Severe proprioceptive defects may cause unsteady gait. THALAMIC SYNDROME  Neuropathic pain due to thalamic lesions. Occurs in 10% of stroke patients.  Usually a lacunar stroke in the thalamus.  Contralateral sensory loss:  Face, arms, legs.  All sensory modalities.  Resolution can lead to long term chronic pain:  Initial paresthesias followed in weeks to months by allodynia (ordinarily painless stimuli cause pain) and dysesthesia “unpleasant, abnormal sense of touch‖.  Contralateral side.  Sensory exam normal.  Severe pain in paroxysms or exacerbated by touch. Page 49 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl HYPOTHALAMUS  Maintains homeostasis by regulating: 1. Thirst and water balance. 2. Controlling Adenohypophysis (anterior pituitary) and Neurohypophysis (posterior pituitary) release of hormones produced in the hypothalamus. 3. Regulating Hunger, Autonomic nervous system, Temperature, and Sexual urges (TAN HATS).  Inputs (areas not protected by blood-brain barrier): 1. OVLT (senses change in osmolarity). 2. Area postrema (found in medulla, responds to emetics). Lateral nucleus  Hunger. Lateral injury makes you  Destruction  anorexia, failure to Lean. thrive (infants).  Stimulated by ghrelin, inhibited by leptin. Ventromedial  Satiety. VentroMedial injury makes nucleus  Destruction (eg, you Very Massive. craniopharyngioma)  hyperphagia.  Stimulated by leptin. Anterior  Cooling. Anterior nucleus = cool off nucleus  Parasympathetic (VD to cool). (cooling, pArasympathetic). A/C = anterior cooling. Posterior  Heating. Heating controlled by nucleus  Sympathetic (VC to heat). Posterior hypothalamus (―Hot Pot‖). If you zap your posterior hypothalamus, you become a poikilotherm (cold- blooded, like a snake). Suprachiasmatic  Circadian rhythm. You need sleep to be nucleus charismatic (chiasmatic). Supraoptic and  Synthesize ADH and oxytocin. ADH and oxytocin are carried paraventricular by neurophysins down axons nuclei to posterior pituitary, where these hormones are stored and released. Preoptic nucleus  Thermoregulation, sexual behavior.  Releases GnRH.  Failure of GnRH-producing neurons to migrate from olfactory pit  Kallmann syndrome. Page 50 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl HYPOTHALAMIC SYNDROME  Diabetes insipidus (loss of ADH).  Fatigue (loss of CRH low cortisol).  Obesity.  Loss of temperature regulation. LIMBIC SYSTEM  Collection of neural structures involved in emotion, long-term memory, olfaction, behavior modulation, ANS function.  Consists of hippocampus (red arrows in A), amygdalae, mammillary bodies, anterior thalamic nuclei, cingulate gyrus (yellow arrows in A), entorhinal cortex.  Responsible for Feeding, Fleeing, Fighting, Feeling, and Sex. Page 51 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl A  fornix B  mammillary body C  pons D  thalamus E  inferior colliculus Page 52 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl WERNICKE-KORSAKOFF SYNDROME  Wernicke: Acute encephalopathy.  Korsakoff: Chronic neurologic condition.  Usually a consequence of Wernicke.  Both associated with:  Thiamine (B1) deficiency from alcoholism.  Macroscopic:  Atrophy of mammillary bodies (emotion and memory) common finding.  Associated with damage to thalamic nuclei (anterior and dorsomedial).  Triad Wernicke:  Confusion.  Gait ataxia. Wernicke precipitated by  Visual disturbances/nystagmus. glucose without thiamine:  Often reversible with thiamine.  Korsakoff: Amnesia: Thiamine co-factor glucose  Recent memory affected more than metabolism (pyruvate remote. dehydrogenase enzyme).  Can’t form new memories. Alcoholic or malnourished  Confabulation: Can’t remember so make patients should receive things up.  Lack of interest or concern. intravenous thiamine  Personality changes. supplementation before  Usually permanent. intravenous dextrose administration because giving dextrose without prior thiamine can precipitate a Wernicke encephalopathy. Page 53 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl DOPAMINERGIC PATHWAYS  Commonly altered by drugs (eg, antipsychotics) and movement disorders (eg, Parkinson disease). Pathway Symptoms of Altered activity Notes Mesocortical ↓ Activity  ―negative‖ symptoms Antipsychotic drugs have (eg, anergia, apathy, lack of limited effect. spontaneity). Mesolimbic ↑ Activity  ―positive‖ symptoms (eg, 1° therapeutic target of delusions, hallucinations). antipsychotic drugs  ↓ positive symptoms (eg, in schizophrenia). Nigrostriatal ↓ Activity  extrapyramidal Major dopaminergic pathway symptoms (eg, dystonia, akathisia, in brain. parkinsonism, tardive dyskinesia). Significantly affected by movement disorders and antipsychotic drugs. Tuberoinfundibular ↓ Activity  ↑ prolactin  ↓ libido, sexual dysfunction, galactorrhea, gynecomastia (in men). Page 54 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl CEREBELLUM  Function:  Posture/ balance.  Muscle tone.  Coordinates movement. CEREBELLAR PEDUNCLES  In and Out Pathways. Page 55 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl INFERIOR CEREBELLAR PEDUNCLE  Major pathway INTO cerebellum from spine.  Numerous inputs: Spinocerebellar tract, Cuneocerebellar tract, Olivocerebellar tract, Vestibulocerebellar tract.  Ipsilateral spinal cord information: proprioception from spinal cord. MIDDLE CEREBELLAR PEDUNCLE  Pontocerebellar tract fibers.  Fibers from contralateral pons. SUPERIOR CEREBELLAR PEDUNCLE  Major pathway OUT of cerebellum.  Axons from deep cerebellar nuclei.  All outputs originate from deep nuclei.  Fibers to red nucleus and thalamus to modulate the cortical movement. PURKINJE CELLS  Cerebellar neurons.  Receive numerous inputs.  Project to deep nuclei.  Inhibitory  Release GABA. DEEP NUCLEI Deep nuclei (lateral  medial)— Dentate, Emboliform, Globose, Fastigial. Don’t Eat Greasy Foods.  Projections OUT of cerebellum. Page 56 of 235 https://t.me/USMLEEndopoint https://t.me/USMLEEndopoint  USMLE ENDPOINT, NEUROLOGY Dr. Ahmed Shebl  Dentate nucleus:  The most important & the most lateral.  Projects to contralateral VA/VL nuclei of thalamus to modify the movements.  The same projection as the basal ganglia.  Interposed nuclei: globose/emboliform  To contralateral red nucleus.  Fastigial:  To vestibular nuclei and reticular formation CEREBELLUM INPUT:  Contralateral cortex via middle cerebellar peduncle.  Ipsilateral proprioceptive information via inferior cerebellar peduncle from spinal cord. CEREBELLUM OUTPUT:  The only output of cerebellar cortex = Purkinje cells (always inhibitory)  deep nuclei of cerebellum  contralateral cortex via superior cerebellar peduncle. CEREBELLUM CONTROL  In general, cerebellum controls IPSILATERAL side.  Cerebellar fibers contralateral cortex.  Contrala