DNS Obj 2015

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DNS Lecture Objectives

Table of Contents

Neurological Diagnosis................................................................................................................... 2 Introduction to Neuropathology ................................................................................................. 5 Localizing Lesions in the Motor System................................................................................... 11 Localizing Somatosensory Lesions ........................................................................................... 17 Spinal Disorders ............................................................................................................................. 20 Neuromuscular Disease ............................................................................................................... 25 Neuropathology of Peripheral Nerve ....................................................................................... 31 Localizing Lesions of the Visual Pathways .............................................................................. 38 Cerebral Blood Flow & Metabolism .......................................................................................... 42 Ischemic Stroke and Intracerebral Hemorrhage .................................................................. 44 Intracranial Pressure & Head Injury ........................................................................................ 50 Subarachnoid Hemorrhage and Cerebral Vascular Malformations ................................ 53 Pathology of Circulatory Diseases of the CNS......................................................................... 56 Seizures and Epilepsy ................................................................................................................... 61 Sleep Disorders .............................................................................................................................. 64 Coma, Persistent Vegetative State, & Death by Neuro Criteria ......................................... 69 Pathology of CNS Tumors ............................................................................................................ 75 Headache .......................................................................................................................................... 85 Neurobiology of Rehabilitation ................................................................................................. 89 Aphasia ............................................................................................................................................. 92 Neglect .............................................................................................................................................. 94 Multiple Sclerosis .......................................................................................................................... 96 Pathology of Diseases of Myelin.............................................................................................. 101 Movement Disorders and Therapy ........................................................................................ 111 Dementia ....................................................................................................................................... 120 Pathology of Neurodegenerative Disease ............................................................................ 124 CNS Infections .............................................................................................................................. 132 Pathology of CNS Infections ..................................................................................................... 136


Neurological Diagnosis Define the levels of the neuroaxis and list the characteristic signs and symptoms associated with a lesion at each one

Level of Nervous System Dysfunction Peripheral Muscle Myopathy NMJ Nerve Neuropathy Plexus Plexopathy Root Radiculopathy Cell body (anterior horn cell or dorsal root ganglion) Lower motor neuron disease or ganglionopathy Spinal Cord Myelopathy Posterior fossa Cerebral hemispheres Encephalopathy (Subarachnoid space/meninges)

PNS Localization o All will have lower motor neuron type motor loss:

Flaccid weakness Atrophy Hypotonia May have: hyporeflexia, fibrillations (not visible, occur in individual muscle fibers), or fasciculations (visible, discharge of whole axons)

o Myopathy Motor only (proximal, symmetric)

Ex/ shoulders, hips; climbing stairs, getting out of low chair, reaching overhead Atrophy and reflex loss occur if severe Ex/ polymyositis, muscular dystrophy

o Neuropathy Single Nerve (ex/ carpal tunnel syndrome)

Motor, sensory (all modalities), reflex loss in distribution of specific nerve Polyneuropathy (ex/ diabetic polyneuropathy)

Motor, maybe sensory/autonomic (burning/pain) Legs before hands; more prominent distally Symmetric stocking-glove distribution Axonal (loss of one reflex), demyelinating (loss of all reflexes)

o Plexopathy Mixed nerve and root deficit: LMN weakness, sensory & reflex loss Brachial (C5-T1, usually upper or lower parts, Horners with C8 involvement) trauma Lumbosacral (T12-S4, bowel/bladder with pudendal involvement) neoplasm


o Radiculopathy (disc herniation C5-T1 & L4-S1 common) Segmental (dermatome) pain, sensory, LMN motor, and reflex loss Weakness/atrophy in distribution of affected spinal root (myotome)

o LMN Disease (anterior horn cell spinal muscular atrophy, polio) Motor loss only (no sensory loss) Diffuse or single limb; proximal & distal LMN weakness and reflex loss Involvement of paraspinal muscles

o Sensory Ganglionopathy (DRG paraneoplastic, Sjogrens, idiopathic) Sensory loss to all modalities (proprioception is most prominent) Usually proximal & distal (may involve face/trunk) Often asymmetric; diffuse reflex loss

Myelopathy (spinal cord spondylosis is common, MS, trauma) o UMN dysfunction BELOW the level of lesion

Interruption of corticospinal tract no atrophy) Spasticity, hyperreflexia, extensor plantar response

o LMN weakness AT level of lesion (if gray matter involved) o Sensory level or dissociated sensory loss

Posterior Fossa o Brainstem

CN deficits Impaired consciousness, impaired respiration Crossed/bilateral motor or sensory deficits (left facial, right body sensory loss w/ left lateral medullary lesion) Quadriplegia with pontine lesion

o Cerebellum Signs during movement or sustained posture (incoordination, ataxia, nystagmus, tremor) No weakness, sensory loss, reflex change Vermis = truncal deficit; Hemisphere = appendicular (arms/legs)

Supratentorial o Thalamus

(DENSE) hemisensory loss and/or pain Impaired consciousness, memory disturbance, hemiataxia, aphasia/neglect [[symptoms may mimic cortical defect]] Dysfunction most commonly due to stroke (vertebrobasilar)

o Basal ganglia (Parkinsons disease, Huntingtons chorea) Slow movement (bradykinesia) Signs at rest: muscle rigidity, involuntary movements

Chorea sudden, brief, irregular jerks (loss of caudate) Athetosis slow, writhing movements (caudate, putamen, GP, subthalamus) Dystonia slow, contorting posturing (caudate, putamen, thalamus) Ballismus flinging movement of limb or half of body (subthalamus, caudate, putamen, GP, thalamus) Tremor


o Cerebral cortex UMN loss: hemiparesis/spasticity/hyperreflexia Hemisensory deficits (different pattern than thalamic, integrative sensory disturbance or reduction in single modality) Hemianopia, aphasia/neglect, dementia, seizures

Subarachnoid space/meninges (meningitis, subarachnoid hemorrhage) o Headache, neck stiffness o Cranial nerve deficits o Altered level of consciousness

Distinguish among focal, multifocal, and diffuse localization and relate these to pathophysiology

Focal = single lesion (ex/ tumor, stroke) Multifocal = more than 1 discrete lesion (ex/ MS, mononeuritis multiplex) Diffuse = generalized process (ex/ encephalopathy, polyneuropathy)

o System Specific = diffuse dysfunction of specific system or pathway (ex/ anterior horn cell disease) Multiple Symptoms consider common anatomy, vascular supply, system, or pathophysiology

Use the presence or absence of neighborhood signs to support a proposed neuroanatomical localization

Ex/ facial nucleus in the pons and exits via cerebellopontine angle o Expect ipsilatral LR palsy with pons damage o Deafness with cerebellopontine angle deficit

When given a clinical scenario, determine the time-intensity profile of the neurological symptoms and how it relates to the pathophysiology of the disease process

Acute (min-hrs): metabolic dysfunction cerebral ischemia or seizure Subacute (days-weeks): expanding lesion tumor or abscess Recurrent-remittent (episodic with recovery) multiple sclerosis or migraine Chronic progressive (months-years): slow-growing tumor or degenerative Alzheimers or Parkinsons

Distinguish among positive, negative, secondary, and behavioral symptoms Negative: reduction or loss of function (weakness, numbness, blindness) Positive: exaggeration of a physiologic phenomenon (chorea, seizure, tingling, visual hallucinations) Secondary: mass effect (edema, herniation, obstruction of CSF) Behavioral: changes in personality/behavior (dementia, psychosis, neglect)

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Introduction to Neuropathology Identify the basic cell types of the nervous system and their characteristic histopathologic reactions

Neurons (>500 sub-types in the cerebral cortex alone) o Nonpathologic Neuronal Inclusions: lipofucsin (orange), neuromelanin (dark brown, found in substantia nigra and locus ceruleus residua of catecholamine metabolism) o Pathologic:

Alzheimers Neurofibrillary Tangles: silver-stained, abnormal cytoskeletal elements, hyperphosphorylated tau protein Lewy bodies: spherical, eosinophilic cytoplasmic inclusions Viral inclusion bodies: Herpes virus group (HSV, CMV), Negri bodies Storage Diseases: perikayal swelling with distinctive cytosomes

o Neuronal Necrosis: brightly eosinophilic (red) cytoplasm, pyknosis, disintegration

o Neuron loss: surrounding (satellite) cells form nodules of Nageotte in DRG, empty baskets of preterminal axons, microglial nodules o Central chromatolysis: regenerative response

Large, rounded appearance w/ eccentric nucleus & Nissl substance Pale pink central area of cytoplasm

o Axonal Changes: swelling at point of transection (spheroids) + Wallerian degeneration distally

o Spongiform Degeneration: typical of prion DZ, small vacuoles in perikarya

Glia:

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o Astrocytes Fx: structural support/repair, BBB formation, isolation of neuronal surfaces/NT metabolism, neural development IHC: GFAP (can view nucleus and extensive processes)

Primary (injury to astrocyte): number and size increase w/o typical reactive cytoplasmic changes Secondary (parenchymal brain injury)

Increased glial filaments + glassy eosinophilic cytoplasm plump cells called gemistocytes Loss of reactive cytoplasm with time dense gliotic scar May see bright red, irregular, rod-shaped bodies (Rosenthal)

o Oligodendrocytes Fx: synthesis and maintenance of myelin sheaths around CNS axons With LFB-PAS stain central myelin becomes bright blue Small, round hyperchromatic nuclei with clear halo (fried egg)

o Ependymal cells Fx: protective barrier and movement of CSF Monolayer of ciliated epithelial cells lining ventricular system

Microglia/macrophages

o Fx: resident cells of monocyte/macrophage lineage o Two routes of differentiation after activation by pathologic process:

Rod cell: found in aggregates (microglial nodule) a/w viral encephalitis Foamy macrophage: enlargement to spherical form w/ fluffy cytoplasm

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Vascular endothelial cells Choroid plexus epithelial cells

o Cuboidal epithelium in ventricular system (primarily lateral & fourth ventricles) o Fx: produce CSF

o Pituitary gland epithelial cells Pineal parenchymal cells

Discuss the pathologic sequelae of the brain being soft and the pathologic lesions that can arise from its packaging

Packaging: o Cranium = cardboard box; prevent compression o Meninges = Styrofoam; additional padding o CSF = gel foam; innermost padding

Lesions arise in packaging o Hematoma

Epidural: middle meningeal artery Subdural: potential space in young, actual space in old; exposes bridging veins that can shear with movement of dura Subarachnoid: commonly seen in the inferior surface of brain

o Tumors (meningioma) o Infections (meningitis)

Hydrocephalus (communicating and non-communicating) CSF plumbing defect Traumatic Injury: impact against hard packaging, parenchymal tears w/ acceleration/deceleration

o Distribution: protuberant ends at front/back of brain

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o o When healed, residual bits of iron are present (hemosiderin)

Contrast communicating and non-communicating hydrocephalus Communicating: flow of CSF is not blocked within the ventricular system Non-communicating: flow of CSF is blocked along one or more of the narrow pathways connecting the ventricles (often cerebral aqueduct)

Discuss the processes that occur in response to the presence of a space-occupying lesion within the cranium

Monro-Kellie doctrine: V(brain) + V(CSF) + V(blood) [+ V(mass)]= V(cranium) o Compensation redistribution of CSF or blood to accommodate mass o Rapidly growing mass: quickly reach point of decompensation; ICP increases o Slowly growing mass: brain itself can accommodate (through redistribution of ECF) so decompensation occurs later on (larger mass required for ICP to increase)

Herniation:

o

o o Under falx cerebri

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o Through tentorium cerebelli o Through foramen magnum

Duret hemorrhage: secondary brainstem hemorrhage from herniation o Bilaterally symmetric appearance (butterfly shape) o Downward displacement of brainstem overlying blood vessels (basilar artery) is fixed in place kinking/disruption of thin blood vessels

Describe the histologic changes that occur in response to ischemic neuronal death Lesion distribution correlates with vascular territory Early (hrs-days): edema, discoloration, hemorrhage

o Atrophic neurons w/ hypereosinophilic cytoplasm and dark, shrunken, pyknotic nuclei Intermediate (days-wks): soft material (remains soft when brain is fixed) Late (months-yrs): macrophages remove dead material, leaving cavitary infarct

o Absence of neurons o Reactive astrocytes/blood vessels at edge of cavity o Foamy macrophages within cavity

Explain the consequences of the permanence of neurons

Accumulation of pigment (lipofuscin) represent protein and lipid-containing residues of incomplete lysosomal digestion o Pathologic inclusions are common in neurodegenerative diseases

Most degenerative disorders are neural since lost neurons are not replaced o May have a paradoxically hypercellular appearance o Astrocytosis can be extensive

o Identify the pathologic process associated with focal cortical dysplasia and hippocampal sclerosis

Seizure disorders: abnormally synchronous electrical activity which can spread through the cortex Focal cortical dysplasia cytologically abnormal area of cortex (starting point) Hippocampal sclerosis (shrinkage and atrophy) unclear if cause or effect

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List the two places within the brain that cerebral metastases and septic emboli preferentially lodge and the reason for this finding

Gray-white junction: due to decreased caliber and increased tortuosity of vessels Vascular border zones: decreased rate of blood flow in these areas

Contrast gray matter and white matter Gray Matter White Matter

Pink when fresh, light brown when fixed Lower cell density High, uniform cell density Astrocytes/oligodendrocytes present Oligodendrocytes myelin sheaths Astrocytes (fewer than oligodendrocytes) Cell bodies of neurons Dendritic & axonal processes Synapses Projecting axons H&E: dark pink = cell bodies (pyramidal) Lighter pink = neuropil EM: tangled web of dendritic synapses/processes H&E: largely free of neurons; small, dark, round nuclei = oligodendrocytes Identify manifestations of defects in neural tube formation

Rostral end defect = anencephaly (open neural tube) Caudal end defect (more common) = myelomeningocele Complete failure = craniorhachischisis totalis

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Localizing Lesions in the Motor System

Paratonia/Gegenhalten: patient appears to hold or resist passive arm movements during tone testing; may improve on distraction Reflex Arc:

Alpha = innervate muscle fibers; Gamma = control spindle excitability Ia fiber: fire when muscle spindles stretch muscle contraction

Ib fiber: fire when GTO over-stretch muscle relaxation


Lesions decreased muscle tone + hypo-reflexia Discuss the motor signs and their pathophysiological mechanism in damage of:

Peripheral nerves/The lower motor neuron not discussed in lecture A certain level of the spinal cord

o UMN pattern below the level of injury o LMN pattern at the level of injury o Contralateral dorsal column/medial lemniscus (light touch, vibration, joint position) o Ipsilateral lateral spinothalamic tract (crude touch, pain & temperature) o Cauda Equina (spinal cord ends at L2) only LMN axons o Key Dermatomes:

C4: clavicle C8: fifth finger T4: nipples T10: umbilicus L1: inguinal ligament L3: anterior surface of thigh L5: great toe S1: lateral aspect of foot S3-5: perineum

o Key Myotomes: C3-5: Diaphragm C5: deltoid, biceps (biceps reflex) C7: triceps, extensors of wrist and fingers (triceps reflex) C8: interossei, abductor of fifth finger L2-4: quadriceps (knee jerk reflex) L5: long extensor of great toe, anterior tibial S1: plantar flexors, gastrocnemius (ankle jerk reflex)

The corticospinal tracts in the brainstem long tract signs o Normal Function:

Suppress increased muscle tone and hyper-reflexia mediated by the reflex arc Generates movements: (1) stimulates LMN, (2) modulates inter-neurons, (3) modulates muscle tone

o Often associated with sensory deficit o Hyper-reflexia o Spreading of stretch reflexes (Hoffman sign, crossed adductor reflex) o Spasticity velocity-dependent increased muscle tone o Clasp-knife reaction resistance to passive movement increases up to certain length/force sudden relaxation as GTOs are activated o Pain-sensing reflexes are hyperactive Babinski sign, triple flexion response o Clonus

Motor cortex Basal ganglia


o Normal Function: facilitation of wanted movements, suppression of unwanted movements, initiation/maintenance of movements

o Parkinson Disease loss of substantia nigra

Upregulation of D2 (loss of inhibition from SNc) Downregulation of D1 (loss of excitation from SNc) Overall increased inhibition of thalamus


Bradykinesia, rigidity, resting tremor, decrement on repetitive/alternating movements, dystonia, NO weakness

o Ballism & Hemiballism loss of subthalamic nucleus Inability to deselect undesired movements

o Huntington Disease loss of striatum

Early: loss of D2 inability to stop extraneous movements Late: loss of D2 and D1 inability to choose desired movements


Cerebellum

o Ipsilateral deficits (overshoot/undershoot) o Lateral cerebellum for limbs (limb ataxia/dysmetria and tremor) o Medial cerebellum for trunk (ataxic gait, trunk ataxia/titubation) o Hypotonia, but no loss of reflexes

Thalamus: many possible symptoms, but sensory symptoms predominate Brainstem (important for neighborhood signs):

o LMN lesion of cranial nerves at level of lesion + UMN lesion below level of lesion o Vestibular nuclei/vestibulospinal: posture control w/ head movement o Reticular nuclei/reticulospinal: somatosensory control of posture o Superior colliculi/tectospinal: visual control of posture o EX: facial nerve nucleus

Upper face has bilateral projections from cortex, lower face gets contralateral projections only Cortical lesions on one side:

Weak contralateral lower face Sparing of contralateral upper face Weak contralateral limbs

Brainstem lesions on one side gives crossed deficits: Weak ipsilateral upper/lower face Weak contralateral limbs

Describe the postural mechanisms and what happens when they are deprived of higher control

Decorticate posturing (cerebral hemispheres, internal capsule, thalamus) o Flexed upper extremities, extended lower extremitites

Decerebrate posturing o Brainstem damage below level of red nucleus (mid-collicular)


o Dorsal root transection eliminates signs (gamma motor neurons and spindles are involved) o Extended upper and lower extremities

Both indicate severe brain damage Progression from decorticatedecerebrate suggests further significant brainstem injury or compression

Explain how the supplementary motor area, premotor area, and prefrontal cortex contribute to the control of movement


Localizing Somatosensory Lesions Contrast peripheral nerve fiber types

Larger myelinated system: vibration, position sense, touch o Faster (good for temporal resolution) o More precise (good for spatial resolution)

Small fiber system: nociception o A-d: scantily myelinated o C: unmyelinated o Slow pain with diffuse character poorly localized

Identify patterns of sensory deficits associated with damage to peripheral nerve, plexus, and spinal nerve root

Peripheral Nerve Disease o Reflexes are decreased or absent o Pattern analysis

Distal polyneuropathy: most common (stocking-glove pattern, longest fibers affected first, combination of negative and positive symptoms) Mononeuropathy (pressure, trauma, vasculitis) anatomy is key

Ex/ Carpal Tunnel o Nerve conduction studies

Plexopathy (brachial, lumbar) Radiculopathy (disk disease, shingles)

o Radiation of pain o Segmental/dermatomal organization

Define referred pain Visceral sensation loss of parallel processing due to absence of proprioceptors in visceral organs Pain in pattern of peripheral dermatome

o Cardiac pain (left arm and neck pain) o Ureteral pain (groin/testicular region) o Diaphragmatic pain (neck)

Therapy addresses root cause Describe sensory deficits associated with lesions of spinal cord, thalamus, and cerebral cortex

Dorsal column medial lemniscus system o Uncrossed in the cord o Synapse & decussation at medullary level o Project to thalamus o Clinical testing vibration & proprioception

Spinothalamic system o Crossed path (mostly) o Anterolateral portion of cord o Projects to thalamus, reticular substance, tectum


o Clinical testing: sharp (pain), temperature Typical Findings of Spinal Cord Lesion

o UMN findings: spasticity, increased tone, hyperreflexia o LMN findings at level of the lesion o Bladder dysfunction o Find the sensory level to localize lesion

Syringomyelia cavitation of the central spinal cord (most often cervical) o Cape distribution of pain/temp loss o Sometimes segmental atrophy

Brown Sequard Syndrome (trauma or demyelinating lesion) o Contralateral pain/temperature loss o Ipsilateral proprioception/vibration loss

Thalamic Sensory Syndromes (from strokes, tumors) o Negative signs include all modalities (highest level where this occurs) o Full hemisensory deficit common o Ventrobasal thalamus relays to SS cortex o Intralaminar nuclei and central lateral thalamus involved in pain system

Cortical Sensory System o Components

SI (postcentral gyrus) somatotopic organization; all contralateral SII some bilateral input, less well-known function Parietal association areas

o Characteristics Cortical organization reflects the use of function Plasticity exists for cortical organization

o Positive symptoms generated by seizures o Testing function 2-point discrimination, graphesthesia, stereognosis

Discuss treatment approaches to pain associated with peripheral and central causes Peripheral Neuropathy Pain

o Optimize nutrition, protect feet, reassure o NSAIDs are of limited value o Anticonvulsants: stabilize neurons that can fire spontaneously

Gabapentin, pregabalin (more commonly used) Pregabalin binds to subunit of calcium channel modulates calcium influx, reduces NT release Pharmacologic effect requires binding at this site

Topiramate o Antidepressants: combination of serotonergic and adrenergic reuptake blockers

Amitriptyline, desipramine, duloxetine Diminish the incoming pain signal via descending inhibitory pathways

o Topical therapy (capsaicin) Capsaicin active ingredient in chili peppers VR1: responds to heat stimuli, pain, acidic environment Desensitizes receptors


o Opioids Carpal Tunnel

o Reduce edema Diuretics Stop NSAIDs stop sodium retention Treat hypothyroid myxedema

o Immobilize wrist splints o Surgical release

Radiculopathies o Reduce inflammation (NSAID, corticosteroid) o Surgical decompression if major functional compromise or chronic pain o Neuropathic pain therapies (as in peripheral)

Central Pain (cord lesions, thalamic pain syndromes) o Regulation of sodium channels may play significant role o Anticonvulsants o Antidepressants (augment the descending serotonin pathways) o Implanted stimulators o Surgical lesioning o TLR-4 antagonists

Inhibit the release of neuroexcitatory compounds and proinflammatory products by glia Opioids activate glia (oppose analgesia; enhance tolerance, dependence, reward, respiratory depression)


Spinal Disorders Describe the symptoms and signs of radiculopathy vs. myelopathy

Myelopathy: compression of spinal cord o Dysfunction of spinal cords ascending and descending tracts o Motor: Difficulty with fine motor fx weakness of multiple motor groups spastic paralysis (does not occur in a single nerve root distribution) o Sensory: Tingling diffuse numbness (does not occur in single root distribution) o Reflexes: hyper-reflexia, Hoffmans sign, Babinskis sign

Radiculopathy: compression of nerve roots o Motor: weakness of single motor groups o Sensory: numbness, tingling in a dermatomal pattern o Reflexes: diminished isolated reflexes

Describe the basic anatomy of the vertebral column and spinal cord Vertebral anatomy

o o Differences between cervical, thoracic, lumbar vertebrae

Highest range of motion in cervical spine

o Unique aspects of C1 & C2 provides majority of rotation for head

Ligamentous anatomy o C1-2 ligaments transverse ligament, right/left alar ligaments o Other important spinal ligaments anterior and posterior longitudinal ligaments, ligamentum flavum

Spinal cord anatomy o Dorsal and ventral roots o Differences between cervical thoracic, lumbar, sacral cord


o Tracts of the cord

Vascular anatomy: ASA (2/3) and PSA (1/3) Identify the location of the major tracts within the spinal cord (corticospinal, spinothalamic, dorsal column) and the deficits expected to result from interruption of each of them

Corticospinal tract: main voluntary motor

o 90% crossed (at pyramids brainstem) via lateral pathway o 10% - axial musculature uncrossed via anterior pathway o Unilateral lesion in pons contralateral loss of movement o Unilateral lesion in medulla cruciate paralysis o Unilateral lesion in cord ipsilateral loss of movement

Posterior/dorsal columns: proprioception and light touch o Crosses at level of medulla o Unilateral lesion in cord ipsilateral loss of sensation to light touch

Spinothalamic tract: pain/temperature o Crosses in spinal cord via anterior commissure (1-2 levels of entry) o Unilateral lesion in pons/medulla/spinal cord contralateral loss

List the expected motor, sensory, and reflex abnormalities associated with compression of each of the commonly involved cervical and lumbar nerve roots


Explain how the location of a herniated disk in the lumbar spine determines which nerve root is compressed

Most commonly extrude postero-laterally compressing the nerve root in the foramen radicular symptoms Cervical disk herniations can extrude posteriorly to compress spinal cord myelopathy Level of disk herniation can be accurately predicted by neurological exam findings

o L4/5 and L5/S1 most commonly affected Medial disk herniation compresses traversing nerve root (L4/5 L5) Lateral/foraminal disk herniation compresses L4 (L4/5 herniation)

Describe how to approach the patient with a suspected spinal cord injury Spinal trauma is common, should be suspected in high-energy trauma (car accidents, falls more than 5, assaults) Can be missed (1/3 of cervical injuries) associated intoxication, head injury, multisystem injury History + Physical Exam + Neuro Exam + Radiographic (lateral radiographs, flexion-extension radiographs, CT, MRI)


Radiograph evaluate anterior & posterior longitudinal and spinolaminar line Awake, cooperative, non-intoxicated patient

o No complaints of pain o No pain to palpation of the spine o Normal examination o Low-risk mechanism o Clinical clearance

Awake, cooperative, non-intoxicated patient o No complaints of pain o No pain to palpation of the spine o Normal examination o High-risk mechanism o AP/lateral radiographs

Awake, cooperative, non-intoxicated patient o Pain o Normal examination o AP/Lateral radiographs, CT, flexion-extension radiographs

Awake, cooperative, non-intoxicated patient o Neurological deficit o MRI (nerves), CT, flexion-extension radiographs

Intoxicated Patient o No neurological deficit AP/Lateral radiographs, CT, wait until alert o Neurological deficit MRI (neuro), CT, wait until alert

Diminished LOC o Expected early return AP/lateral radiographs, CT, clear after normal LOC o No expected early return AP/lateral radiographs, CT, MRI (24hrs), possible flexion-extension under fluoroscopy

Describe the neurological manifestations of the common spinal cord injury syndromes (Brown Sequard, anterior cord, posterior cord, central cord) and non-traumatic spinal cord syndromes

Brown Sequard hemisection of spinal cord (burst fractures) o Ipsilateral motor loss below level of lesion o Ipsilateral light touch loss below level of lesion o Contralateral pain/temperature loss below level of lesion (1-2 levels lower)

Anterior Cord Syndrome (central disc herniations compressing ASA) o Bilateral motor loss o Preserved light touch o Bilateral pain/temperature

Posterior Cord Syndrome (can be seen in fractures causing posterior compression) o Preserved motor o Bilateral loss of light touch o Preserved pain/temperature

Central Cord Syndrome (trauma in setting of pre-existing stenosis) o Motor loss: arms>legs; distal>proximal o Variable light touch loss


o Variable pain/temperature loss Secondary Injury

o Ischemia o Free radicals o Calcium cascade o Endogenous opioids o Inflammation

Tabes Dorsalis destruction of posterior roots at DREZ o Tabetic neurosyphilis (15-20 yrs after initial infection) o Lightning pains (most common in legs), ataxia (normal motor power), urinary incontinence o Absent LE reflexes, impaired vibration/position sense in feet, Romberg sign o Normal MRI, positive VDRL o Phenytoin/Tegretol (lightning pain), physical therapy

Subacute Combined Degeneration o Lack of IF B12 deficiency o Insidious onset: generalized mild weakness/paresthesia, gait disturbance o Symmetric loss of positional and vibrational sense (limbs/trunk), variable reflexes, associated mental signs o Diffuse, uneven degeneration of white matter tracts + swelling of myelin sheaths

ALS Lou Gehrigs disease o Loss of nerve cells in anterior horns of spinal cord, motor nuclei of lower brainstem o Weakness/stiffness/awkwardness of hands o Cramping/fasciculations of arms/shoulders o Unilateralbilateral (painless) o Mild spasticity in legs, hyperreflexia, muscle wasting in UE extensors, preserved sensation

Transverse Myelitis o Acute onset motor, sensory and/or autonomic dysfunction (no pre-existing disease or spinal cord compression) o Often multiple sclerosis (women>men; younger>older) o Diagnosis w/ MRI, clinical suspicion


Neuromuscular Disease Describe the important features of the clinical analysis, identification of the anatomical site of disease, and diagnostic testing to be considered in the neuromuscular evaluation

Gather data (history & exam) and organize data (describe clinical syndrome) Process data localize lesion, differential diagnosis, labs, diagnosis, treatment Anatomic Localization

o Arms vs. Legs vs. Cranial Common legs early in disease Unusual arms only at disease onset

o Proximal vs. Distal Common: proximal (myopathy, neuronopathy), distal (axonal neuropathy) Uncommon: very proximal (respiratory failure, posterior neck weakness)

o Symmetry Asymmetric myopathies are rarely treatable Asymmetric neuropathies are often treatable after nerve biopsy

o Focal regions shorter differential diagnosis, especially w/ specific weakness Functional Patterns

o Motor: weakness (large vs. small muscle involved), abnormal movement o Sensory: loss (small vs. large axons), gain (pain, paresthesia) o Autonomic

Temporal Patterns o Short vs. Long Term

Long: acute (days-wks), chronic (months-years), episodic, hereditary Short: minutes-hrs, fatigue

o Onset Age Pediatric: neonate & child Adult: 20-60 y/o vs. >60 y/o

Potential Labs o Serum biomarkers (i.e., creatine kinase, aldolase) indicate tissue involved and disease activity o Electrophysiology nerve conduction studies and electromyography

Nerve conduction: maximally stimulate nerve, record evoked action potentials (muscle CMAP, sensory SNAP) Ex/ CMAP small potential size axon loss/myopathy vs. slow velocity

myelin pathology EMG: electrical activity detected by needle in muscle (motor units and single muscle fibers)


Define the characteristic clinical, electrophysiologic, and laboratory findings in muscle disease

Clinical Findings o Weakness: proximal, constant o Muscle size: early normal/increased late atrophy/increased o Sensory exam & tendon reflexes are normal

Lab Findings o Serum creatine kinase (CK): high

EMG: indicates small motor unit size o Motor unit potentials have small amplitude and brief duration o Single muscle fibers show spontaneous activity & occasional fibrillation

o Muscle Biopsy

o Variable fiber size; small rounded shape (no compression to create polygon) o Necrosis (phagocytic cells) + regeneration (basophilic w/ large, immature nuclei) + increased endomysial connective tissue o

Clinical example: Duchennes Dystrophy (absence of dystrophin w/ staining) o Western blot can quantify dystrophin protein (milder Becker MD) o Genetic testing (Southern blot) indicates out of frame deletion exon 45-48 o Pathogenesis: altered muscle membrane mechanical stability o X-linked recessive (seen in males); progressive disease can involve heart o Treatments: corticosteroids, manage dysfunction o Future treatments: protein replacement, gene repair

Define the characteristic clinical, electrophysiologic, and laboratory findings in disorders of the neuromuscular junction


Clinical Findings o Weakness proximal, distal, bulbar o Post-synaptic disorders (myasthenia gravis) decrement/fatigue o Pre-synaptic disorders (Lambert-Eaton) increment w/ repetition o Sensory & tendon reflexes are normal o Chronic disease that rapidly changes with physical activity/treatment

Repetitive Nerve Stimulation o MG: CMAP size decrement that improves w/ AChE inhibition o o LEMS: CMAP is small with increment after RNS or exercise; improves with 3,4-diaminopyridine (facilitates presynaptic vesicle release via Ca influx)

o Laboratory Findings

o MG: serum antibodies to postsynaptic antigens (AChR 85%, MuSK 5%, LRP4 5%) Damage to post-synaptic membrane (simplified folds, wide cleft) Decreased number +/- function of AChRs

o LEMS: serum antibodies to presynaptic antigen (P/Q calcium channel) Reduced release of synaptic vesicles

Clinical Example: Myasthenia Gravis o Focal weakness & fatigue: eyes, face, bulbar, arms>legs o Limited eye movements improve after Tensilon treatment o Treatment: pharmacologic (anti-AChE) and immunosuppression o Look for thymoma (neoplasm association)

Clinical Example: Lambert-Eaton Myasthenic Syndrome o Proximal weakness w/ sensory (distal, symmetric)& autonomic neuropathy o Ataxia o Treatment: 3,4 diaminopyridine & immunosuppression o Look for small cell lung cancer, neoplasm association

Define the characteristic clinical, electrophysiologic, and laboratory findings in diseases of nerve due to damage of the AXON

Clinical Findings o Weakness: distal>proximal; asymmetric or symmetric; constant over time o Atrophy of muscle size o Distal (stocking-glove) pattern of sensory loss o Reduced distal tendon reflexes (others are relatively spared)


o Symmetry is variable EMG: indicates large motor unit size (sprouting from nearby neuron)

o Motor unit potentials have large amplitude, long duration o Single muscle fibers show spontaneous activity, fibrillations

o Nerve conduction testing: loss of axons w/ normal-mildly slow conduction velocity

o Loss of axons: small action potentials seen in CMAPs o Normal velocity: remaining axons conduct w/ normal mildly slow velocity

Muscle biopsy o Varied size; small fibers show angular appearance from denervation o Denervation + re-innervation grouped atrophy w/ angular pattern o Fiber type grouping demonstrates re-innervation (normal=checkerboard) o Normal endomysial connective tissue

o Nerve biopsy shows axonal loss (of small and/or large axons)

o (sprouting) Clinical example: Immune Microvasculopathy

o Asymmetric axonal neuropathy w/ sensory involvement & disability o Nerve biopsy shows differential fascicular loss of axons w/ subperineurial edema (patchy disease) o Staining for C-5b9 complement component showed deposits on endoneurial capillaries o Treatment: immunomodulation (corticosteroids)

Define the characteristic clinical, electrophysiologic, and laboratory findings in diseases of nerve due to damage of the MYELIN


Clinical findings o Weakness: distal & proximal, constant, mostly symmetric o Normal muscle size o Distal, mild sensory loss o Diffusely reduced tendon reflexes (out of proportion to weakness)

Nerve conduction testing o Axons conduct abnormally conduction block with slow velocity o Distal nerve stimulation gives normal evoked motor amplitudes o Proximal nerve stimulation gives reduced evoked motor amplitudes o Focal areas of myelination with some re-myelination (shorter internodes)

Nerve Biopsy o Myelin sheaths show segmental loss with thin myelin sheets

o o Schwann cell basal lamina onion bulb formations

o Clinical Example: Guillain-Barr syndrome

o Acute onset with progression over 2-30 days after prodromal illness Molecular mimicry (infectious agent + neural antigen)

o Weakness is diffuse (proximal & distal) & can be severe (respiratory failure) o Early paresthesia + pain distal sensory loss, especially vibration o Reduced tendon reflexes early in course o Autonomic involvement o Treatment: plasma exchange, IV immunoglobulin, NOT corticosteroids

Define the characteristic clinical, electrophysiologic, and laboratory findings in diseases of nerve due to damage of the NEURON

Clinical Findings o Selective modality loss motor or sensory, but rarely both o Distribution: proximal + distal, cranial, not length dependent, asymmetric o Motor: weakness, atrophy, fasciculations o No improvement with treatment

Electrodiagnostic changes o NCV: selective modality loss o EMG: proximal and distal involvement that is not length dependent

Clinical Example: ALS


o Weakness is proximal and distal, respiratory involvement, asymmetric o Variant involves no upper motor neuron signs o A4V mutation: rapidly progressive (death < 1yr) o Dominant inheritance (SOD1 gene mutation) o Accounts for 1-2% of all ALS


Neuropathology of Peripheral Nerve Describe the structure and composition of peripheral nerves

Sural nerve: 6-12 individual fascicles of axons Each fascicle surrounded by flattened cells of perineurium Epineurium (outside perineurium) contains connective tissue and anastomic vascular network (distributed to endoneurium)

Myelinated axons: 2-18 microns; myelin thickness related to axonal diameter Unmyelinated axons are examined with electron micrograph Skin Biopsies

o Allows examination of minute nerve endings in punch biopsies o Limited to examination of small sensory terminal axons o May show findings not found on sural nerve biopsy

Characterize the two processes in peripheral nerve pathology axonal degeneration and segmental demyelination which are the pathologic substrates of most diseases of peripheral nerve

Axonal Degeneration (often distal is preferred)

o o Axonal degeneration starts w/ digestion of axon & myelin w/in Schwann cell


o Macrophages remove axonal and myelin debris, migrate to endoneurial blood vessels and leave the nerve

o o Schwann cell processes w/in original basal lamina band of Bungner

Collapse of basement membrane

o Though multiple axons begin to grow, one predominates o After regeneration, internode length is shorter

Segmental Demyelination

o o Intermodal length differs along the individual axon; some lack myelin


Correlate clinical patterns of peripheral nerve disease with their pathologic substrates, identifying discrete classes of pathology (e.g., neuropathies arising from ischemic, autoimmune, and metabolic insults)

Toxin-Induced Neuropathies (prefers distal aspects of nerves; lower extremities) o Axonopathies (agents targeting axonal transport)

Effects of selected toxins or metabolic dysfunction on a phase of axonal transport (may be selective) Ex/ hexacarbons target neurofilament transport axonal swelling Vinblastine, vincristine, taxol interrupt microtubule function (inhibit axonal transport neuropathy)

o Myelinopathies

Lead, diphtheria toxin, hexachlorophene Toxins directed at Schwann cell and/or myelin sheath w/ axonal sparing

o Motor, sensory, and/or autonomic symptoms o Acute, subacute, or chronic presentation o Some involve selected functions

Ischemic Neuropathies o Clinical Presentation

Development of sensory, motor or autonomic dysfunction (hrs - days) Typically involves distribution of individual nerves (asymmetric) Mononeuritis multiplex pattern hits on multiple nerves

o Vascular supply to peripheral nerve, if substantially decreased, disrupts fx o Vasculitidies are patchy/focal thorough sampling of biopsied nerves o Polyarteritis Nodosa prototypic vasculitic ischemic neuropathy

Epineurial arteries destroyed PMN leukocytes, macrophages, monocytes, fibrin Patchy pattern adjacent axons may be minimally involved Fibrotic vessels w/ recanalization previous sites of damage


o Collagen Vascular diseases o Other: paraneoplastic, cranial arteritis, AIDS, Lyme disease, diabetes, amyloid & sickle cell disease

Metabolic Neuropathies o Diabetes

Symmetrical sensori(motor) polyneuropathy Variable degrees of axon loss in distalmost portions Multiple ischemic hits summate, produce symmetrical and uniform axon loss distally Skin biopsies examine density and appearance of terminal epidermal projections of sensory axons Intraepidermal nerve fibers show large swellings (impaired heat and pain thresholds) Patchy loss of axons, thickened endoneurial microvasculature due to failure to properly turnover glycated proteins

Asymmetric Neuropathies

Lumbosacral plexus neuropathy, truncal radiculopathy Upper limb mononeuropathy, cranial nerve (III) palsies May involve autoimmune component inflammatory vasculitis

Distal Autonomic Neuropathy (sympathetic, parasympathetic, visceral sensory and enteric) Markedly enlarged dystrophic nerve terminals w/ neurofilaments in the absence of substantial neuron loss


Autoimmune Neuropathies

o Guillain-Barre syndrome Acute inflammatory demyelinating polyneuropathy (AIDP)

Monophasic paralytic illness (days-weeks after inciting event) Rapid worsening paralysis & respiratory dependence Sensory + autonomic dysfunction may be superimposed Generally spares CNS functions Improvement is the rule w/ residua common (mortality


Genetic Neuropathies o Charcot-Marie-Tooth Neuropathy (PMP22 gene mutation)

History of motor weakness/ataxia Atrophy, chiefly muscles of lower limb stork leg/inverted champagne bottle Lesser sensory and autonomic involvement Family history typical, can extend over several generations Onion-bulb (concentric rings of Schwann cell processes & collagen) neuropathy with demyelinated axons

o Hereditary Neuropathy w/ Pressure Palsies (HNPP)

Dominantly inherited w/ deletions in PMP-22 Marked focal hypermyelination; redudant myelin folds, demyelination & remyelination

Amyloid Neuropathies o Predominantly sensory symptoms w/ painful burning extremities o Lower extremities > upper extremities o Autonomic symptoms common: postural hypotension, bowel/bladder dysfunction, impotence, sweating abnormalities o Endoneurial deposits of amyloid, often perivascular

o Infectious Neuropathies

o Herpes Zoster Latent virus in dorsal root ganglion emerges to give shingles Neuronal and satellite cell intranuclear inclusions


o Leprosy o AIDS

Distal sensory NP Large numbers of macrophages in peripheral nerve

Toxic anti-retroviral drug rx NP Mononeuritis multiplex NP (vasculitic/CMV) Inflammatory demyelinating NP (Guillain-Barre, CIDP) Opportunistic infectious (CMV polyradiculopathy, HZ radiculopathy) Neoplastic (lymphomatous) NP Diffuse infiltrative CD8+ lymphocytosis

o Lyme disease Traumatic Neuropathy

o Loss of normal nerve continuity terminal swelling (mass of axons)

o o Mini-fascicles of nerve can be seen w/ disorganized aggregate of collagen


Localizing Lesions of the Visual Pathways List the principle eye muscle tested in each of the diagnostic gaze positions

Identify the eye movement findings associated with palsy of cranial nerves III, IV, VI

Abducens Palsy:

o Nuclear: No esotropia Paralysis of gaze toward the side of lesion; eyes remain aligned Ipsilateral facial nerve paralysis w/ involvement of CNVII

o Subnuclear/Fascicular: brainstem syndromes w/ ipsilateral esotropia + associated neighborhood signs o Peripheral: esotropia (inward turning) of involved eye

Trochlear Palsy: eye is high and excyclotorted; vertical deviation is exaggerated when eye moves into adduction Oculomotor Palsy: affected eye deviates out and down + ptosis + mydriasis

o Pupillary fibers congregated toward outer edge ischemic lesions (DM/HTN) affect deep fibers for lid/EOM pupil-sparing CN3 palsy o Compressive lesions affect both pupils and EOM

Describe the pathways for conjugate horizontal gaze saccades and pursuits Saccades

o Frontal eye field (FEF) paramedian pontine reticular formation (PPRF) o PPRF VI and contralateral CN III (via medial longitudinal fasciulus)

CN VI nucleus is center for all horizontal eye movements except vergence movements (convergence tied to accommodation)


Internuclear ophthalmoplegia (INO) lesion of MLF Complete adduction deficit in severe cases Adducton delay (all cases) Abducting nystagmus in eye contralateral to adduction deficit Young MS; old MLF stroke

VOR: acts entirely within brainstem tests integrity of brainstem pathways in unconscious/comatose patients Optkinetic nystagmus (OKN): steady entire visual world as it slips across retina

o Principal movement of eyes is in direction of slow phase (opposite direction of object movement) o Fast phase compensatory movement

Smooth pursuits o Highly accurate; requires visual concentration and slowly moving target o Open-Loop/Ballistic phase: faster than object movement to catch up to target o Closed-Loop: lock on to target once caught-up o Retina occipital lobe TPO junction cerebellum CN nuclei (via nucleus prepositus hypoglossi)

Discuss the pupillary responses associated with the dorsal midbrain syndrome Edinger-Westphal nucleus Marcus-Gunn Pupil Afferent Pupillary Defect (APD)

o Decreased input into light reflex from one optic nerve o Poorer constriction of both pupils when light is shone in involved eye o Retina (massive destruction >70%) o Optic nerve any lesion o Optic chiasm if vision loss is asymmetric, APD in more affected eye o Optic tract APD is contralateral to the lesion

Anisocoria efferent abnormality of the pupil (not related to APD) o May be sympathetic or parasympathetic defect o Is the anisocoria greater in the dark or the light?

Dark abnormal pupil is small, not dilating sympathetic Light abnormal pupil is large, not constricting parasympathetic

Describe the pathway by which visual information is processed Photoreceptors bipolar cells ganglion cells (optic nerve) Optic nerve optic chiasm (nasal retinal fibers decussate) lateral geniculate nucleus LGN optic radiations (parietal & temporal lobes) primary visual cortex

Define visual acuity and how it is expressed The eyes ability to distinguish details Fraction: numerator test subject is standing at 20 feet; denominator distance from which a normal subject can read the same image Simple & quick, but does not help localize the lesion

Differentiate normal from abnormal visual field plots (perimetry)


Perimetry: focus on small target with lights of varying size/intensity presented in various positions relative to fixation point

Describe the visual field deficits associated with a lesion of the eye, optic nerve, optic chiasm, optic radiations, and occipital lobe

Sensory Eye Lesion o Field defect in one eye only o Follows boundaries of retinal nerve fibers

Optic Nerve Lesions o Field defect in one eye only o No anatomical boundaries for loss (central vision highly affected) o

Optic Chiasm o Damage to central chiasm affects nasal retinal fibers (temporal visual field) o Bitemporal hemaniopsia o

Optic Tract o Right optic tract carries information from the left visual field of both eyes o Complete contralateral homonymous hemianopsia o

Optic Radiations o Inferior portion (temporal lobe, Meyers loop) represents superior field o Superior portion (parietal lobe) represents inferior field o No anatomical demarcation between upper/lower; horizontal meridian is not generally respected o

Occipital Lobe o Superior and inferior visual field halves separated by calcarine fissure o Tip of occipital lobe (macula) dual blood supply: PCA & MCA


o Pupils Color Acuity


Cerebral Blood Flow & Metabolism Describe the effects of arterial pCO2 and arterial oxygen content on cerebral blood flow

CBF responds to acute changes in arterial carbon dioxide o Reduced pCO2 (hyperventilation) = reduced CBF

Can be used to reduce ICP (briefly) W/ prolonged hyperventilation, CBF gradually increases When pCO2 abruptly returns to normal, CBF rebounds to higher than normal values (taper the return to normal)

o Increased pCO2 (COPD) = increased CBF o These changes are lost when the brains vascular system is damaged (as in ischemia) lose sensitivity to CO2

CBF responds to chronic arterial O2 content o Reduced CaO2 (anemia) = increased CBF o Increased CaO2 (polycythemia) = decreased CBF

Describe the effect of local neuronal activity on cerebral blood flow and metabolism Normal: CBF matches CMR-O2 matches CMR-gluc Increase in local neuronal activity

o Increase in local CBF o Increase in CMR-gluc o No increase in CMR-O1 activated brain relies on non-oxidative metabolism of glucose o Local cerebral venous oxygen content increases (not being used)

MR sequences sensitive to deoxyhemoglobin fMRI: increased oxygen content = decreased venous deoxyhemoglobin = increased signal intensity

Describe the regional relationship between cerebral blood flow and metabolism Increased blood flow to active neurons Corresponds to an increase in glucose metabolism, but NOT oxygen utilization

Illustrate the compensatory mechanisms used in the face of reduced cerebral perfusion pressure

Autoregulation: changes in CPP (~60-150 mmHg) have little effect on CBF o Systemic hypotension dilation of vessels o Below threshold, vessels collapse (intramural pressure is too low) o Chronic arterial hypertension shifts autoregulatory curve to right

The lower limit of autoregulation is higher than normal Little change in limit is seen after 8-12 mo of treatment Difficult to predict where the lower limit is

o This response is impaired when the cerebral vasculature is already dilated in response to other vasodilatory stimuli Anemia, hypoxemia, reduced CPP

Oxygen Extraction Fraction


o Brain normally extracts 30-40% of available oxygen o When autoregulation fails, oxygen extraction increases

CBF drops CMR-O2 is maintained OEF increases

o When this compensatory mechanism fails (normal adults CBF ~20ml/100g/min), cerebral function declines and infarction may occur


Ischemic Stroke and Intracerebral Hemorrhage Summarize the major risk factors/causes for ischemic stroke and intracerebral hemorrhage (ICH)

Ischemic Stroke o Age o Gender: rate is higher in men (1.25), but women live longer, so they have more strokes per year o Race/ethnicity: AA, HA>white o Hypertension o Cardiac Disease o Cigarette Smoking o Diabetes Mellitus o Hyperlipidemia

Pediatric Risk Factors o Cardiac disease o Heme disorder o Vasculopathy o Infection

Non-traumatic ICH o Prolonged hypertension

Rupture of small arterioles Basal ganglia, thalamus, cerebellum, pons, [lobar white matter]

o Abnormal arteries Amyloid angiopathy rupture of small arterioles damaged by beta-amyloid deposition

Predilection for lobar sites (especially posterior) Occurs in older individuals, often in concert with dementia

o Clotting abnormalities o Increased venous pressure

Describe the cerebrovascular changes that occur in the brain following ischemic stroke

CT Imaging (Ischemic) o Initially normal, subtle changes ~3 hrs in some (hyperdense vascular supply, cortical effacement, loss of G-W differentiation, effacement of insular ribbon) o Low density 12-24 hrs

MRI Imaging (Ischemic) o Greater sensitivity than CT o Increased signal on DWI, decreased on ADC within minutes o Can estimate time of stroke onset based on findings on MRI sequences

In the first week: 10% get worse; 1% have recurrent stroke CT (ICH): well-defined area of high density surrounded by rim of low density MRI (ICH): determine approximate age of hematoma (esp T2* MRI)

Describe the causes of neurological deterioration after ischemic stroke and ICH


Ischemic stroke o Brain factors

Cerebral edema can result in herniation syndrome Bleeding into stroke Progressive thrombosis Stroke recurrence Seizure

o Systemic Factors Lungs: pneumonia, PE Heart: heart failure, MI, arrhythmia Metabolic/infectious: kidney failure, liver failure, fever/infection, SIADH, drugs

o Hemorrhagic Transformation Incidence within 5 days is 9% Predictors: large lesion size, cardioembolic source, hyperglycemia, thrombolytic treatment Associated w/ poor outcome, only when exerts mass effect

ICH o Hematoma Enlargement (usually within first 3 hrs): associated with decline in consciousness when >33% growth

Factor VIIa reduces hematoma expansion, does not improve functional outcome, death, or disability at 90 days Illustrate the time course of recovery after ischemic stroke

Mortality after 1st Ischemic Stroke o 5% in first 30 days ~5%/year o Recurrence: 4% (30 days) 12% (1 year) 5% (per year thereafter)

Hemiplegia generally plateaus by about 3 months (improvement beyond this point will be smaller) Disability is common; at 6 months

o 50% hemiparesis o 30% walk w/ assistance o 26% dependent in ADLs o 35% depression o 26% institutionalized in nursing home o At 5 years: ~50% disabled and dependent

Use location of infarct or ICH to predict likely underlying pathophysiology. Explain limitations of this approach

Global/Multifocal Cerebral Ischemia o Hypotension, hypoperfusion, low flow states o Increased venous backpressure o Diffuse vascular occlusion o Functional vascular impairment

Cardioembolic Stroke (focal or multifocal) o Atrial fibrillation/acute MI/ischemic or dilated cardiomyopathy


o Rheumatic valve disease/prosthetic valve/endocarditis/intracardiac tumor o Abnormal passage from venous to arterial circulation

Borderzone Infarction o Arterial vascular disease or systemic arterial hypotension o Infarction in watershed areas between major cerebral arterial territories

Important Distinction: Carotid vs. Vertebrobasilar system o Poor reliability of historical features o Some deficits may occur with lesions in either system

Isolated motor or sensory deficits Language deficits and neglect

o Anatomic variants Variability in territory supplied by major cerebral arteries Fetal PCA (originating from ICA rather than basilar artery)

ICA Territory (Anterior) o MCA Structure Deficit Primary motor area Contralateral hemiparesis (face/arm>leg) Primary sensory areas Contralateral sensory loss (face/arm>leg) Gaze pathways Ipsilateral gaze deviation Visual pathways Contralateral visual field cut Language center (left) Aphasia -nonfluent (superior MCA) -fluent (inferior MCA) -global (complete MCA) Spatial attention center (right) Neglect o ACA

Primary leg motor/sensory areas Contralateral weakness +/- sensory loss of leg>>arm (face spared) Behavioral deficits, apraxia

o Akinetic mutism lack of verbal/motor responsiveness o Abulia decrease in spontaneous speech & activity with increased response latency, decreased persistence with tasks o Utilization behaviors difficulty resisting the impulse to operate or manipulate objects that are in reach o Apraxia loss of ability to carry out learned movement not due to weakness, sensory loss, etc

o Ophthalmic Artery Monocular blindness (transient: amaurosis fugax)

Vertebrobasilar Territory (posterior) o Vertebral artery o Basilar artery


o PICA o AICA o SCA o PCA

Midbrain: hypersomnolence/cma, vertical gaze palsy, vivid visual hallucinations (rare) Thalamus: contralateral sensory loss/pain, contralateral ataxia, aphasia (left), neglect (right), impaired consciousness/cognition/memory Occipital lobe: contralateral hemianopia, cortical blindness (bilateral), visual association cortex involvement visual agnosia Inferior temporal lobe: may have amnesia (left side)

o Brainstem: crossed or bilateral findings with cranial nerve abnormalities and/or disorder of consciousness o Cerebellum:

Hemisphere: ipsilateral dysmetria (+/- tremor), fall towards side of lesion Vermis: truncal/gait ataxia Dyscoordinated speech and eye movements Often associated brainstem signs

Lacunar Syndromes

o Given the clinical scenario of a patient with ischemic stroke or ICH, discuss the most appropriate evidence-based acute interventions and therapies to prevent recurrence

Proven Benefit: o IV tPA

Within 3 hrs of onset: 30% more likely to have minimal disability Between 3-4.5 hrs: 16% more likely Only 5-10% of patients receive this treatment (time window, exclusion criteria)

o Clot retrieval (stentrevier) More rapid recanalization + reduced hemorrhage risk Risks: distal embolization, vessel injury, increased costs, delay in treatment MR CLEAN retrievable stent + IV tPA w/in 6 hrs of onset safe & effective (in pts with proximal anterior circulation occlusion)

o Aspirin o Low dose heparin


o Stroke unit admission o Hemicraniectomy

For cerebral infarction with massive edema Relieves pressure on midline structures Early (


Compare the prognosis of ischemic stroke and ICH

Early Prognosis of ICH 1 month mortality is 50% (1/2 in first 2 days) o Predictors of poor outcome: large ICH, low GCS, older age o Care is withdrawn in 75% of patients who die in hospital (subject to withdrawal of care biases self-fulfilling prophesy)

Long-term prognosis of ICH o 6 months 50% of survivors are independent o Recurrence rate 2-4%/year; mortality is 8%/year


Intracranial Pressure & Head Injury Describe the major factors regulating intracranial pressure

Monro-Kelly Doctrine: volume (constant) = brain + blood + CSF To a certain extent, the volumes of blood (venous) and CSF can compensate for intracranial masses or for increasing brain size (edema)

Describe the primary compensatory mechanisms for increased intracranial pressure Translocation of intracranial (venous) blood volume to extracranial vessels Translocation of CSF to extracranial vessels via arachnoid villi Translocation of CSF to spinal subarachnoid space Molding of brain to a mass by deformation and/or reduction in ECF space Brain shift/extrusion (herniation syndromes)

Contrast the pathophysiologic mechanisms, clinical manifestations, and radiographic appearance of epidural vs. subdural hematoma

Epidural o 1-3% of head trauma (M:F = 4:1) o Pathophysiology: temporal skull fracture avulses middle meningeal artery

Arterial bleeding dissects between dura and inner table of skull 85% are arterial (as above), 15% from bleeding of dural sinus or middle meningeal vein

o Clinical: Classic: LOC + lucid interval deterioration w/ coma, contralateral hemiparesis, ipsilateral pupil dilation Mortality: 20-55%

o Imaging: biconvex (lenticular) hyperdense clot, constricted by suture lines

Subdural

o 24% of severe HI (75% male; 50% vehicular; avg age 41) o Degree of impact damage is higher than in EDH (more lethal) o Pathophysiology:

Laceration of bridging vessels (rapid acceleration-deceleration) Accumulation due to rupture of parenchymal injury

o Clinical: Often occurs with elderly patient who has fallen (on anticoagulant) Mortality: 50-90%

o Imaging: concave/crescentic hyperdense clot, diffuse, crosses suture lines


May be along convexity, falx in interhemispheric fissure, or layering on tentorium

Subacute: isodense clot Chronic: hypodense clot

Discuss the complications of severe head injury Monetary cost: $60 billion/year Primary Damage: external forces acting to cause brain injury

o Macroscopic: Shearing of WM tracts Contusions Intracranial hematomas Diffuse swelling

o Microscopic/Cellular: Rupture of vessels/microhemorrhages Cell membrane microporation Ion channel dysfunction Protein changes

Secondary Damage: differs by 1* injury mechanism; processes last hrs-days o NT release (glutamate): ion channel activation, swelling, edema o Free-radical generation and Ca-mediated damage: early necrotic cell death o Gene activation: pro-apoptotic proteins (caspases) o Mitochondrial dysfunction: decreased ATP synthesis, cell death programs o Inflammation

Poor Prognostic Indicators o SBP < 90 mmHg; PaO2 < 60 mmHg; age > 40 y/o o Elevated, uncontrolled ICP (sustained ICP >20-25 a/w 50% mortality) o Low score on Glasgow Coma Scale (


o Persistent vegetative state o Severe disability o Moderate disability still independent o Good recovery normal life +/- neuropsychological deficits

Severe TBI: poorer outcome, little improvement over time Uncal Herniation: uncus of temporal lobe shifts into incisura

o Impairment of consciousness o Dilation of ipsilateral pupil o Ipsilateral or contralateral hemiparesis o +/- decerebrate or decorticate posturing

Axial or Central Herniation: symmetrical shift of diencephalon & upper brainstem into tentorial incisura o Impairment of consciousness o Dilation of pupils (usually bilateral) o Decerebrate or decorticate posturing

Recognize concussion and the post-concussion syndrome Concussion: traumatically-induced transient disturbance of brain function

o LOC, blindness, aphasia, loss of visual-spatial orientation, loss of situational awareness, memory impairment Post-Concussion Syndrome

o Headache, nausea, dizziness o Impairment of concentration, learning disability, memory difficulties o Symptoms usually resolve w/in days month o Diagnosis/management complicated by mood disorders, ADD/ADHD, and headache disorders

Management: cognitive & physical rest; neuropsychological testing for persistent symptoms Discuss guidelines for return to play after concussion

Premature return to cognitive or physical activity prolongs neurological dysfunction Second injury before recovery further metabolic derangements + worsening of cognitive deficits w/ possible long-term consequences


Subarachnoid Hemorrhage and Cerebral Vascular Malformations Recognize the presenting clinical syndrome of subarachnoid hemorrhage

Thunderclap headache abrupt onset of severe headache o Loss of consciousness may also occur o Less severe character/diplopia may be a warning (sentinel) hemorrhage

Physical Exam Signs o Nuchal rigidity o Kernigs sign: pain in posterior aspect of upper legs when thigh is flexed and knee is extended o Brudzinskis sign: patients neck is flexed, involuntarily flex hips o Third nerve palsy

Diagnosis o Noncontrast CT if positive, usually dont need LP o LP: sequential RBC count bloody fluid from hemorrhage or traumatic tap

Xanthochromia breakdown of hemoglobin leads to discoloration of CSF (more specific for a subarachnoid hemorrhage) o MRI not useful in making diagnosis

Describe the diagnostic evaluation of cerebral aneurysms Vascular imaging: catheter cerebral angiogram or CT angiography Cerebral Angiography gold standard CT angiography 95% sensitive (vs. cerebral angiography)

o Advantage: non-invasive, can be obtained immediately after CT shows SAH o Disadvantage: miss small aneurysms, bone artifact, highly operator dependent

Describe management of aneurysmal subarachnoid hemorrhage Surgical Management:

o Early surgery reduces risk of rebleeding o Pterional craniotomy + operating microscope o Spring-loaded clips separate aneurysm from circulation o Morbidity/mortality is related to location (vertebrobasilar aneurysms > anterior circulation) and size (max dimension > 25mm) o Better long-term protection in patients < 40 y/o

Endovascular Management: o Placing a coil into the aneurysm o Increased chance of re-bleeding (small amount of aneurysm is left at base)

Peri-operative Management: o Monitoring for and treating complications o Anti-fibrolytic drugs keep clot in place to reduce re-bleeding rates

Discuss the complications of subarachnoid hemorrhage and how they are managed Cerebral Vasospasm

o Progressive arterial narrowing (4-10 days post-hemorrhage)


May be due to oxyhemoglobin accumulating in subarachnoid space on adventitial surface of the vessel Loss of endothelial-dependent relaxation, inflammation, and free oxygen radicals may contribute

o Can lead to cerebral ischemia o Occurs in 1/3 of patients may have radiographic evidence without symptoms; more likely in patients with thick subarachnoid clots o Patients w/ poor neurological function at onset are at higher risk o S/Sx: lethargy, fever, focal neurological deficits (hemiparesis, dysphasia) o Treatment:

Calcium Channel Blockers (nimodipine) Lessening severity of delayed cerebral ischemia Can be associated w/ hypotension or cardiac dysrhythmia

Hemodynamic Therapy volume expansion to induce hypervolemia (+/- pressors dopamine, phenylephrine) Endovascular balloon catheter placement Intra-arterial administration of verapamil

Hydrocephalus o Occurs in 15% of patients more likely in pt w/ intraventricular hemorrhage or severe subarachnoid hemorrhage o S/Sx: new onset lethargy CT scan o Management:

Initial: intraventricular catheter via frontal burr hole Later: ventriculoperitoneal or ventriculoatrial shunt placement

Hyponatremia & other fluid/electrolyte problems o Hypovolemia & total sodium depletion o Do NOT treat with fluid restriction worsening of vasospasm o Management: isotonic or hypertonic saline w/ monitoring of central filling pressures

Discuss clinical presentation and management of cerebral arteriovenous malformations

Direct shunting of arterial blood into cerebral venous system Tendency to enlarge after formation in fetus mass lesion, seizure, ischemia Symptoms occur in 2nd, 3rd, 4th decade of life

o Intracerebral/subarachnoid hemorrhage (occurs in 40-50%) If present w/ bleed, more likely to re-bleed

o Seizures (~17-40%) o Headaches or other neurological deficit

CT: enhancing mass of abnormal vessels MRI: allows assessment of contiguity of functional brain structures Grading: size, eloquence of adjacent brain, pattern of venous drainage Treatment:

o Young pt w/ moderate size AVM in non-eloquent area of brain remove o Microsurgical removal: craniotomy (after embolization therapy)

Pro: eliminate hemorrhage risk acutely


Con: invasive, surgical risk, prolonged recovery o Stereotactic radiosurgery lesions < 3-4cm

Progressive obliteration of arterial and venous components Disadvantage latency between administration of treatment and effect of obliteration (up to 3 years)

o Embolization: less-invasive, but limited cure rate


Pathology of Circulatory Diseases of the CNS Describe the anatomy of the CNS circulation

Internal Carotid System: ACA + MCA + short circumferential vessels (internal capsule and basal ganglia) + paramedian vessels (base of brain) Vertebro-Basilar System: PCA + SCA + AICA + PICA + short circumferential vessels + small paramedian vessels

Discuss the most common etiologies of CNS vascular injury Infarction (too little blood flow)

o Global Hypoxia Ischemic Hypoxia (most common): cardiac arrest, hypotension, marked increase in ICP Hypoxic Hypoxia (reduced blood O2 content):

Reduced quantity of Hb: hemorrhage, severe anemia Reduced oxygenation of Hb: respiratory arrest, status epilepticus, carbon monoxide poisoning

Histotoxic Hypoxia (defective O2 utilization): cyanide poisoning Hemorrhage (too much blood flow) Atherosclerosis

o Develops at branch points & other sites of turbulent flow

o o Narrowing of vasculature; thick, non-pliable vessel walls

Embolism o Major Sources

Heart thrombus, endocarditis (infectious/non-infectious), calcific material from aortic valve Aorta & carotid arteries plaque rupture/thrombus Peripheral vessels neoplasm, fat

o Shower of emboli from endocarditis scattering of small cavitations

o Small Vessel Disease (arteriolosclerosis)

o Often seen in the white matter


o Concentric thickening (circumferential) of wall not irregular on one side o Hyaline appearance pink & glassy w/ surrounding parenchymal retraction

o o Pref. affects: basal ganglia, thalamus, pons, hemispheric white matter

Arteritis o Giant Cell Arteritis fibrinoid necrosis of vessel wall

o Watershed (Boundary Zone) adult and neonatal pattern

o Adults: ACA/MCA, MCA/PCA border zones o Neonates: periventricular white matter (adjacent to edge of ventricle)

Venous (sagittal sinus & cortical vein thrombosis) o Old: uncontrolled fevers/dehydration in children sluggish blood stasis o Now: mostly caused by oral contraceptives

o Hypertension

o Causes 50% of non-traumatic intracerebral hemorrhages o Sites: putamen/thalamus (60%), cerebral hemispheres (20%), cerebellum (13%), pons (7%) o Most feared involve basal ganglia, pons, cerebellum


o Subarachnoid Hemorrhage/Berry Aneurysm

o 90% in anterior circulation (ACA, ICA, MCA); 10% posterior

o Cerebral Amyloid Angiopathy

o 12% of non-traumatic ICH; most common cause of lobar ICH o Strongly associated with Alzheimers disease o Carries considerable risk of bleeding (20%)

o Vascular Malformations

o Irregular tangles of blood vessels with large caliber vessels in parenchyma o Hybrid appearance of vascular channels arteries become veins w/o intervening capillary plexus

o Germinal Matrix (pediatric)

o Occurs in premature infants same distribution as watershed infarcts o Delicate area around ventricle fine network of capillaries prone to fluctuations in blood pressure

Correlate gross and microscopic features with the temporal evolution of an infarct


Gross Features o Recent soft, discolored, pale (or hemorrhagic)

o o Remote atrophy, cavitation, tract degeneration

o Acute Hypoxia/Ischemic Damage (hours day)

o Hypereosinophilic cytoplasm (red and dead) o Shrunken nuclei no visible nuclear substructure o Microvacuoles may be present

o o Selective Neuronal Vulnerability

Hippocampus: CA1, CA4 >> CA2 Neocortex: laminae III & V neurons Cerebellum: Purkinje neurons

Subacute (day to week): macrophages, proliferative capillaries


o Chronic (month year): macrophages, reactive astrocytes, cavitation

o Discuss the gross and microscopic features of hemorrhagic lesions; given a pathologic or radiographic image of an intracranial hemorrhage, identify the most common etiology

Can occur w/ reperfusion of an area of infarction large bleed or many punctate bleeds

o Loss of blood vessel wall integrity spilling of RBC, WBC

o


Seizures and Epilepsy Explain what seizure first aid is

Turn person on side; head inclined to ground keep airway clear; protect from nearby hazards Transfer to hospital if:

o Multiple seizures/status epilepticus o Person is: pregnant, injured, diabetic o New onset seizures

Do not put rigid object in mouth or restrain Recognize the common presentations of seizures

Epileptic Aura o Symptom at onset, precedes seizure by seconds minutes o Implies partial onset of seizure o Non-specific symptoms noticed for hrs days before seizure

Generalized Tonic-Clonic Seizures o Last < 1 minute; 10-20 s tonic phase; often toxic or metabolic disorder o Brief flexion

Muscles contract Eyelids open, eyes look up Arms elevated, abducted, externally rotated; semiflexed elbows Legs less involved, may be flexed

o Extension phase more prolonged First in back and neck Cry may occur (2-12 seconds) Arms extend Legs extend, abduct, externally rotate

o Tremor Repetitive relaxation of tonic contraction 8/s 4/s Leads to clonic phase

o Absence Epilepsy

o Brief (5-10 s) episodes of lapse of consciousness w/o aura or postictal symptoms o Onset: 4-8 y/o; typical spontaneous remission by mid-adolescence o 3 Hz spike and wave pattern on EEG o Treatment with AED is efficacious in 80-95%


Juvenile Myoclonic Epilepsy o Onset: 12-18 y/o o Myoclonic jerks occur mostly in morning; generalized tonic-clonic seizures in 90-95% of cases o EEG: generalized polyspike and wave discharges o Typically no spontaneous remission o Control with AED in 90% of patients

Partial Seizures o Begin in focal area of brain o S/Sx vary according to site of onset o Can be associated w/ underlying structural brain lesion o Frontal Lobe

Jacksonian motor seizures primary motor cortex May involve more complex motor symptoms

o Temporal Lobe Associated with aura Mesial Temporal Lobe epilepsy sclerosis of hippocampus and surrounding structures Onset: before/at time of puberty Resistant to AED

Be able to classify seizure types and select an appropriate anti-epileptic drug (AED) Generalized:

o Absence o Myoclonic o Tonic-clonic o Tonic o Clonic o Atonic

Partial: o Simple no altered consciousness o Complex consciousness impaired o Secondarily generalized Seizure Type Antiepileptic Drug Broad spectrum (ALL TYPES) Clobazam, felbamate, lamotrigine, levetiracetam, rufinamide, topiramate, valproate, zonisamide Narrow: Partial seizures all subtypes Carbamazepine, eslicarbazepine, ezogabine, gabapentin, lacosamide, oxcarbazepine, perampanel, phenobarbital, phenytoin, pregabalin, primidone, tiagabine, vigabatrin Absence seizure Ethosuximide

Know the common causes of seizures and how to diagnose them


DDx: seizure, syncope, migraine, cerebral ischemia, movement disorder, sleep disorder, metabolic disturbance, psychiatric disturbance Precipitants

o Low blood glucose (less often, high) o Hyper and hypo-natremia o Hyper and hypo-calcemia o Hyper and hypo-magnesemia o Stimulant/proconvulsant intoxication o Sedative withdrawal o Severe sleep deprivation

Know the indications for epilepsy surgery Medically refractory epilepsy in adults

Discuss the role of EEG in the evaluation of seizures and epilepsy EEG: measurement of electrical potentials from brain, recorded over scalp

o Interictal EEG o Video EEG telemetry monitoring continuous synchronized video and EEG recording; gold standard in making diagnosis

Used to clinically diagnose epilepsy o Initial EEG: discharge in 29-55% of patients o Serial EEG: 80-90% of patients o Repeat studies + sleep deprivation + extended recording times

Normal: Posterior Rhythm o 8-13 hz higher voltage over occipital areas o Eyes closed, physical relaxation, relative mental inactivity o Blocked/attenuated by attention (visual, mental effort)

o Abnormal

o Focal supports partial seizure diagnosis o Generalized supports generalized seizure diagnosis

Generalized poly-spike and wave discharge Predominance over bi-frontal regions Common interictal pattern in juvenile myoclonic epilepsy


Sleep Disorders Describe normal sleep architecture

Qualitative and quantitative description of a persons sleep o Onset & duration of sleep o Consolidation of sleep, sleep fragmentation, wake time after sleep onset (WASO) o Time and cycling between different sleep stages

EEG-based, polysomnographic features o EEG electrodes on scalp to evaluate brain wave activity o Eye leads to identify REM sleep o EMG to determine atonia (REM sleep), lower limb (PLMs) o Air flow monitoring (nose + mouth) & snore microphone o Chest & abdominal belts to assess respiratory effort o Oximetry, CO2 monitoring o ECG

Sleep Stages o Awake posterior dominant rhythm

o N1 (stage 1, drowsiness)

Slow rolling eye movements Low amplitude theta & delta Alpha dropout

o N2 (stage 2, light sleep) K complexes Sleep spindles

o N3 (stage 3 & 4, slow wave sleep, deep sleep) >50% is delta activity (1-3 Hz > 150mV)

o REM Atonia, low chin EMG activity Heart and respiratory variability Low amplitude, high frequency EEG activity

o Cycles: occurs ~90 min intervals


Provide a differential diagnosis of excessive daytime sleepiness and discuss how to evaluate a patient presenting with this complaint

Definition: drowsiness or sleep onset that occurs during inappropriate or undesirable times Evaluation: Epworth sleepiness scale (score >10/24 = abnormally sleepy)

o o Differentiate from fatigue or tiredness

Possible Etiologies o Inadequate sleep time o Sleep fragmentation (sleep apnea, sleep related movement disorder RLS, neurological or medical disorders, medications) o Primary sleep disorders e.g., narcolepsy o Circadian disorders

o Insomnia

Consequences o Cognitive: impaired function, judgment, recall and response time

EPWORTH SLEEPINESS SCALE - Please estimate your risk of falling asleep in the following situations, using the scale below.

SITUATION CHANCE OF DOZING

Sitting and Reading 0= None 1 = Slight 2 = Moderate 3=High Watching TV 0= None 1 = Slight 2 = Moderate 3=High Sitting inactive in a public place (e.g. theatre or meeting) 0= None 1 = Slight 2 = Moderate 3=High As a passenger in a car for an hour without a break 0= None 1 = Slight 2 = Moderate 3=High Lying down to rest in the afternoon when circumstances permit 0= None 1 = Slight 2 = Moderate 3=High Sitting and talking to someone 0= None 1 = Slight 2 = Moderate 3=High Sitting quietly after a lunch without alcohol 0= None 1 = Slight 2 = Moderate 3=High In a car, while stopped for a few minutes in traffic 0= None 1 = Slight 2 = Moderate 3=High MEDICATION OR NON-MEDICATION ALLERGIES


o Metabolic: impaired immune/hormonal function, reduced glucose utilization, reduced physical endurance & increased perceived effort during exercise o Each hour of wakefulness after 10 hrs = 0.004% rise in BAC (24 hrs = 0.1)

Describe the clinical presentation, health impact, and treatment options for patients with obstructive sleep apnea

Disorder characterized by repetitive episodes of complete or partial upper airway occlusion during sleep o Sleep symptoms: habitual loud snoring, witnessed apneas

Snorting, gasping, nocturnal awakenings, nocturia GERD, dry mouth, night sweats, difficulty sleeping supine

o Waking symptoms: excessive daytime sleepiness, fatigue Morning headache, neuropsychiatric/mood changes Sore throat, optic neuropathy, hearing loss

Diagnosis: five or more score-able respiratory events (apnea, hypopnea, RERA) per hour of sleep on polysomnography Health Impact (5% of population, higher in hospital, more common in men)

o Oxygen desaturation, arousal/awakenings at termination of event o Cardiovascular Effects: HTN, CV disease, CAD, HF o or more patients with acute stroke or TIA have sleep disordered breathing

Treatment o Positive airway pressure CPAP, BIPAP o Mandibular advancement devices o Positional therapy o Surgical treatment in selected cases

Relieve nasopharyngeal obstruction Adenotonsillectomy (especially in kids) Uvulopalatopharyngoplasty (UPPP) Tracheostomy Bariatric surgery

Discuss the presenting symptoms of narcolepsy and standard treatment for excessive daytime sleepiness and cataplexy in a narcolepsy patient

Clinical Tetrad o Cataplexy (pathognomonic for narcolepsy)

Muscle weakness; can be triggered by emotion Consciousness preserved, eyes closed Hypotonic, areflexic REM atonia

o Hypersomnolence o Hallucinations (hypnogogic going to sleep/hyponopompic waking) o Sleep paralysis

Sleep fragmentation, weight gain, depression/OCD Diagnosis supported by negative PSG and MSLT: sleep onset REM episodes in > 2 nap tests Treatment

o Stimulants for excessive sleepiness


Provigil (modafinil) Amphetamines Methylphenidate

o Tricyclics for cataplexy amitriptyline o Sodium oxybate (GHB, Xyrem)

Extremely short half life take at night Unclear mechanism

Discuss the clinical presentation and treatment options for patients with restless leg syndrome and periodic limb movement disorder

Periodic Limb Movements o 0.5-5 s burst of limb movement (EMG amplitude >25% of baseline) o Intervals of > 5 s (usually 20-40 s, up to 90s) o Repetitive, at least 4 o Associated w: sleep disordered breathing, narcolepsy, medications, ADD, pregnancy, secondary disease (renal failure, neuropathy, iron deficiency, low ferritin, Parkinsons) o Diagnosis: sleep disturbance w/ daytime symptoms, PLM index >5/hr (children) and 15/hr (adults)

Restless Leg Syndrome o Mostly idiopathic, estimated 5% of general population o May emerge in pregnancy, then resolve after o Many cases autosomal dominant w/ high penetrance o Secondary neuropathy, renal disease, spinal cord l

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DNS Obj 2015