CCC3: Radiology of HeadReasons to order a CT/MRI of brain/spine:

TraumaS/S for strokeVery severe headaches/back painNew onset seizure in adults

TraumaEpidural hematoma (extradural acute bleed with fracture), lenticular shapeSubdural hematoma (acute, subacute, chronic)

CTA – screen for potential vascular disease with contrast, done if suspected stroke

MRA – images of vessels without contrast

Carotid Ultrasound Imaging – depicts plaque that narrows arteries, detects narrowing, stenosis or carotid artery which increases the risk for stroke

Lacunar infarcts – small strokes within/around the vassal ganglia, could be an incidental finding

Hemorrhagic stroke: Intracerebral hemorrhage (HTN) or subarachnoid hemorrhage (aneurysm rupture)

Meningitis – not diagnosed by imaging, a clinical diagnosis!

Functional MRI – use blood-oxygen-level-dependant effects to localize regional cerebral blood flow changes during neuronal activity

*Map brain functions in relationship to intracranial tmors, seizure foci, or vascular malformations

PET scan – dye goes to metabolically active tissues

CCC6: Peripheral Nerve DisordersAxonal neuropathy – axon is primary site of injury with myelin sheath intactDemyelinating neuropathy – myelin sheet is primary site of injury with axon intact (segmental or diffuse)

History Nature of chief complaint: weakness, sensory disturbance, pain, autonomic dysfunction, atrophy. Time course of symptoms: acute, subacute, chronic.

Relapsing, recurrent,progressive Anatomic pattern of symptoms: symmetric, asymmetric, focal or diffuse

– Polyneuropathy, mononeuropathy, etc. Specific questions to help narrow etiology:

Trauma, Toxin exposures, infections, dietary deficiencies, medication used, presence of other medical conditions, constitutional symptoms. Family history

*Weakness = motor*Burning/numbness = sensory

Exam Cranial nerves involvement: Think Guillain-Barre syndrome(GBS), Sarcoid, carsinomatosis, diphtheria

Sensory examination– The sensory exam should include pinprick, vibration, toe position, and Romberg’s as a minimum; might

also do temperature sense and light touch. Most neuropathy have distal, symmetric, sensory loss in lower extremities first.

– Typical pattern is called ‘stocking hypesthesia’ in the lower limbs, and ‘glove hypesthesia’ in the upper limbs.

Motor examination1). Look for atrophy and distribution2). Distribution of weakness: most polyneuropathy affect distal muscles of lower extremities first. Most

demyelinating and certain acute motor and toxic neuropathy affects all muscles of limbs, trunk, neck and some facial muscles

3) The extensor digitorum brevis muscle is likely to be the first muscle to demonstrate atrophy.4) Fasciculations may be seen in the weakened muscles. (Fasciculations are a lower motor neuron sign.)

Reflex examination DTR’s are likely to be reduced or absent = LMN sign

Coordination and gait – Sensory ataxia if lost sense of proprioception

Autonomic involvement: edema, hair loss, skin reddening, impotence, incontinence, or gastroparesis.

LabsSerum general screen24-hour urine

Muscle StudiesNerve conduction velocity study - measures speed of conductionElectromyogram study - depends on health of nerve, measures inherent electrical activity of muscles

Etiologies:Diabetic neuropathy - Demyelination – MC pathological process

Prone to compressive/entrapment and cranial neuropathiesCarpal tunnel syndrome at wrist (median nerve)Cubital tunnel syndrome at elbow (ulnar nerve)Peroneal nerve entrapment at fibular headRadial nerve injury at humeral groove Bell’s palsy (VII weakness)Trigeminal/glossopharyngeal neuralgia

Proximal diabetic neuropathy (amyotrophy – atrophy due to neuropathy)Sudden onset of severe thigh pain weakness of proximal leg muscles atrophyEMG is diagnostic, opposite leg may be affected later than the first (milder too)

CIDPChronic, progressive demyelination where axons eventually degenerateProgressive sensory loss wkness atrophy autonomic changesTx: immunomodulators, plasmapheresis, chemo, IV Ig

Other causes of Peripheral Nerve Disorders:Guillian-Barre

Autoimmune, demyelination of peripheral nerve at junction of dorsal/ventral roots

Presents as rapidly progressive ascending polyneuropathy: wkness of feets or hands and quickly moves up the extremities, death usually results from respiratory compromise due to paralysis of respiratory muscles

Areflexic with minimal sensory symptomsMay follow a viral or C. jejuni infectionCSF = very elevated proteinDx: LP, NVC, EMG, serology studiesTM: plasmapheresis or IVIg

Toxic and Metabolic neuropathies:Alcoholic neuropathy – MC

Common, but mild in wkness – marked sensory changes and painAssociated with poor general nutrition/multifactoralDue to axonal degeneration

Endocrinopathies – hypothyroidism, acromegalyUremia – symmetric, distal sensorimotor polyneuropathy

RLS, cramps, severe burning of the feetAmyloidosis

Liver disease/general nutritionSensory or a sensorimotor neuropathy

Drugs, especially statins, chemo, cardiac drugs, colchicines, paclitaxel

AIDSSensory symptoms predominant in axonal, distal symmetric sensorimotor neuropathyOften inflammatory demyelination linked to autoimmune or infectionTm: immunomodulators

Vasculitis, Connective tissue diseasesPolyarteritis nodosa, allergic angiitis, Wegener’s, Giant cell arteritis, RA, SLE, Sjogren’s syndrome, Scleroderma, CMTD

NeoplasiaCommon nerve compressionInvasion of epineuriemParaneoplastic syndromes (immune-mediated)

Anti-Hu antibodies sensory neuropathy of DRG cellsPlasma cell dyscrasias – monoclonal serum antibodies

Monoclonal Gammopathy of Undetermined Significance

Hereditary motor/sensory neuropathiesCharcot-Marie-Tooth – MC hereditary

Nerves are enlarged, slowly progressive, sensorimotor forms or severe pain

CCC7: DementiasDementia – acquired loss of cognitive function due to an abnormal brain conditions. Requires functional decline that interferes with work or social activities plus cognitive decline.

Spheres of cognition:Memory – encoding, storage, and retrieval of info

Attention – orientation to and action upon sensory/cognitive operationsLanguage – evaluate comprehension, repetition, fluency, and naming

Aphasia – acquired disturbance in comprehension and formulation of verbal messagesExecutive function – coordination basic cognitive capacities and emotion, regulating behavioral responses to environmental demandsHigh sensory perceptionPraxis – skilled movements

Apraxia – failure of integration of motor function with visual perception, somatic sensation and/or motor intension = improperly executed motor function

Calculation - Emotion

Evaluation of Disordered CognitionMMSE – to assess cognitive mental status, detect impairment, follow courseo fillness, monitor response to txLabs: B12, thyroid, syphilis, ANA, HIV, ESR, Protein electrophoresis, Genetic testingNeurophysicalEEG – for seizures or encephalopathy, CJDNeuroimaging – CT, MRI, PET/SPECT

Common cognitive Disorders:Alzheimer’s disease – MC degenerative dementia

~Widespread cerebral cortical atrophy with neuritic(senile) plaques and neurofibrillary tangles~Loss of synapses~Deposition of amyloid in neuropil and cerebral vessels = NFT formation~ApoE status is 2nd MC risk factor, aging is 1st (ApoE4 allele increases risk)

Clinical features: dementia, apraxia, aphasia, agnosia, psychiatric symptoms, disturbed sleep/wake cycles, incontinence

Treatment: Acetylcholinesterase inhibitors, atypical antipsychotics, antidepressants

Vascular Dementia or Multi-infarct Dementia (MID)~Large cortical infarct or numerous small lacunar infarcts~Hx of HTN, sudden onset of dementia, step-wise progression of deficits~UMN signs (pseudobulbar affect w/ emotional lability)TM: control HTN, rule out stroke, antiplatelet therapy, AChE inhibitors often used

PseudodementiaMajor depression impairs cognition enough to be confused with primary demtnaiAttempt tx with appropriate antidepressant

Other common cognitive disorders:Pick’s disease (frontotemporal dementia)

Generalized cortical atrophy with significant atrophy or one lobe (usually frontal)Swollen Pick’s bodies, earlier onset than ADBehavioral changes are more signifant than in Alzheimer’s

Chronic subdural hematomaElderly, symptoms develop weeks/months after minimal head trauma

Ha confusion/memory loss/hemiparesis, DX on MRI/CTSx drainage could be curative

HIV dementiaSome degree of cortical atrophy and enlarged ventriclesLonger has disease, more likely to develop dementiaApathy, inertia, depression, behavioral changes, cognitive symptoms, motor abnormalities

Transmissible Spongiform EncephalopathySporadic form 90%Mental or physical deterioration with death w/I 6 months after onsetNo way to specifically diagnose or Treat.

Normal Pressure HydrocephalusResult of an imbalance between production/resorption of CSFTriad: progressive dementia + gait disturbance + urinary incontinenceTx: reduce CSF volume

Causes of DEMENTIAS:D – degenerative, depression, rageE – endocrineM – metabolic, myelinE – epilepsyN – nutrition, neoplasiaT – toxic, traumaI – infection, inflammation, infarctionA – atherosclerosis/vascularS – Structural, system

CCC8: Demyelinating DisordersMultiple Sclerosis – CNS demyelination

20-40 y/o with female predominanceYoung women w/ neurological symptoms = THINK MS!

Diagnosis LP multiple sclerosis panel: Oligoclonal bands, IgG index, cell count, protein, glucose, cultureSerum MS panel: Oligoclonal bands, IgG index*CSF should have higher IgG than serum = focal immune response*CSF should have higher oligoclonal bandsthan serum = immune inflammation going on in the CNS that is absent

from the serum

FIRST look at the clinical presentation – for diagnosis, the patient must have 2 neurological symptoms separated in space (2 locations in the nervous system) and time (more than a month apart) Sensory disturbances are the MC presenting symptom!!

Typical Hx + typical MRIORTypical Hx + positive LP (immune components on MS panel)

Typical MRI findings◦ Multifocal lesions in the periventricular regions of the brain◦ Spinal lesions increase the likelihood of MS in the correct clinical setting◦ Cervical spine lesions ◦ Enhancing lesions are highly suspicious for MS in the correct clinical setting

Acutely active inflammatory lesions – leakage of the gadlimium LP results

◦ IgG index elevated◦ 2 or more oligoclonal bands in the CSF

Paraclinical tests◦ Visual Evoked Potentials slow in optic neuritis◦ Somatosensory Evoked Potentials slow in spinal cord lesions

Tibial or median nerve, give impulse measure in brain – good but do not know where the demyelination is

Tx: Steroids, IV methylpredisolone daily for 5 daysImmunomodulators for MS to SLOW progression

Copaxone, Avonex, Rebif, BetaseronSymptomatic therapy: urinary incontinence, spasticity, pain, fatigue

Forms of MS Relapsing-Remitting

◦ 85% of patients start with RRMS – distinct relapses that improve to some degree◦ Disease itself never remits, constant inflammation in all parts of the nervous system and sometimes you

get an acute flare-up Relapsing-Progressive

◦ Relapses may improve, but between relapses there is functional decline Primary Progressive

◦ 10% of patients have a progressive functional decline from the onset – usually a more severe form of the disease

◦ Very difficult to manage (males + older age at onset more likely) Secondary Progressive

50% of patients with initially RRMS will go on to a steadily progressive course in about 10-15 years

Multiple Sclerosis Exacerbation = abrupt onset of new symptoms or worsening of old symptoms in response to some stressful situation

Tx: Corticosteroids to suppress immune system

Guillian-Barre – PNS demyelination~Tingling, rapid progression of weakness ~decreased/loss of reflexes = LMN/peripheral lesion~ascending paralysisVERY increased protein in CSFSelf-limiting disease but has a high risk of respiratory depression

Tx: IV Ig (cleans out the overabundance of patient Abs within 2-3 days)

Chronic Inflammatory demyelinating polyneuropathy – chronic form of GB

CCC11: Movement DisordersEssential Tremor

Tremor with action or sustension, not present at restWorse with:

Stress, sleep deprivation, meds, caffeineDDx: drug-induced, thyrotoxicosis, sedative/alcohol withdrawal, cerebellar tremor, parkinson’sTx: anything to dampen the CNS response, but if tremor doesn’t bother pt – don’t use drugs, drugs can do more harm than good

Beta blockersPrimidoneBenzodiazepinesAntiepileptics

Tourette’s Syndrome: Motor and vocal tics + young age + symptoms of longer than 1 yearTics do not hurt, more like an itch you have to scratch – sometimes worse if they suppress themCommon to also have OCD

DDx: simple tics, syndenham, dystoniaTx: Antipsychotics (haloperidol, pimozide, clonidine, fluphenazine)

Huntington’s DiseaseLoss of Ach neurons in the indirect pathway leads to decreased inhibition of the thalamus = increased excitation

of the cortex = need to block the dopamine!Autosomal dominant disease due to a trinucleotide repeat (CAG) with anticipation and 100% penetrance (if you

have the gene, you will get Huntingdon’s)

Parkinson’s diseaseLoss of dopaminergic neurons in the substantia nigra = lack of disinhibition of thalamus = inhibited thalamus =

inhibited cortex

Clinical features: pill-rolling, resting tremor, absent facies, depression, bradykinesia, gait imbalance, dysphagia, drooling, dry eyes, cognitive slowing and dysfunction

Tx: Dopamine agonists, Anticholinergics, ergotamines*Too much dopamine can produce dyskinesias

Syndenham’s choreaAutoimmune disorder caused by Group B Streptococcus (1 of PANDAS), affects basal ganglia and cerebellumSelf-limited, under age of 15Associated with personality changeBeware of streptococcal rheumatic disease

Tardive dyskinesia (orofacial dyskinesia)Previous exposure to dopamine blockersOrofacial movements prominent, progressive, rarely resolves, usually elderly

Lipsmacking, tongue movementsTx: withdraw offending agent, sedatives, antiepileptics

CCC12: Muscular DisordersI. Myasthenia Gravis

a. Definitioni. “Myasthenia gravis” means “grave muscle weakness”

ii. Myasthenia gravis is an autoimmune disease, in which the immune system is activated against the neuromuscular junction

iii. Acquired disorderiv. Fatigable muscle weakness, worse with exercise and better after rest

b. Clinical featuresi. Epidemiology

1. Affects 2/100,000 people2. Any age, either gender can be affected3. Most common in women under the age of 40 and men over the age of 604. Family members of people who have other autoimmune disorders such as rheumatoid

arthritis, lupus, or scleroderma may be at higher risk for developing myasthenia gravisii. Types of myasthenia

1. Approximately 85-90% of patients with myasthenia gravis have generalized muscle weakness, while 10-15% of patients have ocular myasthenia, which affects only extraocular muscles and eyelids

2. Lambert-Eaton myasthenic syndrome (LEMS) results from autoantibodies against the voltage-gated calcium channels in the presynaptic terminal of the neuromuscular junction; weakness actually improves with exercise in this form of the disease

3. The autoimmune myasthenia shows no direct inheritance pattern; however, there are rare genetic mutations that result in a myasthenic syndrome based on defects in the acetylcholine receptor or acetylcholinesterase proteins

4. Neonatal myasthenia affects 10-20% of children born to mothers with myasthenia. This form of myasthenia results from maternal antibodies affecting the newborn’s neuromuscular junction. The condition is usually temporary, with symptoms disappearing within 2-3 months after delivery

iii. Symptoms are variable, depending on which muscles are involved, and may be intermittent1. Ptosis2. Double vision/weakness of extraocular muscles3. Dysphagia4. Dysarthria5. Unsteady gait6. Limb weakness7. Shortness of breath8. Neck muscle weakness

iv. Myasthenic crisis1. Respiratory muscles weaken to the point that breathing becomes difficult2. Requires ventilation3. Triggers include

a. Infection or feverb. Pregnancyc. Medication reactiond. Physical overexertion or emotional stress

4. Treatmenta. Plasmapheresisb. IVIg

c. Etiology

i. Antibodies against the acetylcholine receptors at the neuromuscular junction prevent acetylcholine from completing the neurochemical transmission from nerve to muscle

ii. The thymus gland may contain lymphoid hyperplasia, clusters of immune cells that normally develop in the spleen and lymph nodes during an active immune response; 15% of myasthenic patients have a thymus tumor, and 60-80% of myasthenic patients have thymic hyperplasia

d. Diagnosisi. Diagnosis is often delayed, as weakness is a common complaint of many disorders, not just

myastheniaii. Exam often shows impaired extraocular movements, ptosis, and neck and limb muscle

weakness; loss of sensation is not a featureiii. Anti-acetylcholine receptor antibodies are frequently present in the bloodiv. Edrophonium test

1. Edrophonium is an acetylcholinesterase inhibitor and therefore increases acetylcholine at the neuromuscular junction.

2. A dose of edrophonium is given to the patient, and neurological examination is repeated to assess for improvement in muscle weakness

v. Nerve conduction studies/electromyography1. Repetitive nerve stimulation – an electrical stimulus is applied repeatedly to a nerve;

myasthenia is suggested if the response decreases with this repeated stimulation2. Single fiber EMG – single muscle fibers are given an electrical stimulus; repeated

stimuli result in reduced responsevi. Additional studies assist with management, not necessarily diagnosis

1. CT chest with and without contrast to evaluate for thymic hyperplasia or tumors2. Pulmonary function tests to assess respiratory function

e. Treatmenti. Neostigmine and pyridostigmine

ii. Immunosuppression1. Azathioprine2. Prednisone3. Cyclosporine

iii. Thymic resection reduces symptoms in young women even in the absence of thymoma and may be curative in some patients with thymic hyperplasia

iv. IVIg – especially useful in myasthenic crisisv. Plasmapheresis – also useful in crisis

f. Prognosisi. Myasthenia does not usually shorten life expectancy

ii. Myasthenia can spontaneously remit, with return of normal muscle strength and no need for medications; remissions are often temporary

iii. Thymectomy may be curative in some patients

II. Myopathies – Look for proximal weaknessa. Definition

i. Myopathy is a defect in the muscle fiber itself that produces weaknessb. Clinical features

i. Epidemiology1. Myopathies can occur in any age, either gender, any race2. Certain myopathies are more likely in different populations3. Symptoms from mitochondrial myopathies start in childhood or early adulthood4. Congenital myopathies produce symptoms in infancy5. Polymyositis, dermatomyositis, and inclusion body myositis are more common in older

patientsii. Types of myopathies (diverse group of disorders)

1. Congenital - skeletal and facial abnormalities usually present from birth2. Metabolic

a. mitochondrial (e.g.,Kearns-Sayre, MELAS, MERRF)b. glycogen storage diseases (e.g., Pompe’s, Andersen’s, and Cori’s) c. myoglobinurias (e.g., McArdle, Tanuia, DiMauro diseases)

3. Inflammatorya. dermatomyositis - inflammation of skin and muscleb. polymyositis

4. Myositis ossificans - bone grows in the muscles5. Familial periodic paralysis6. Inclusion body myopathy7. Neuromyotonia, stiff-man syndrome8. Common muscle cramps9. Tetany - spasms in the limbs10. Infectious

a. HIViii. Symptoms

1. Muscle weakness (usually proximal; causes problems rising from a chair and walking down stairs)

2. Muscle cramps3. Muscle tenderness (with myositis)4. Muscle stiffness5. Muscle spasms

c. Etiologyi. Due to genetic mutations or

ii. Inflammatory/auto-immune oriii. Congenital metabolic dysfunctioniv. Medication toxicity (-statin myopathy, steroid myopathy)v. Infections (HIV)

d. Diagnosisi. Electromyography often shows abnormalities of muscle action potentials - small amplitude

potentials at rest are characteristicii. Muscle biopsy with histochemical staining can identify certain myopathies

iii. Serum CK and aldolase are often elevated (CK is usually many hundred times normal in some of the myopathies, especially myositis)

iv. Metabolic panels to characterize metabolic myopathiesv. CSF analysis helps to identify some of the congenital and metabolic myopathies

vi. Labs to rule out muscle weakness from other reasons1. Calcium, phosphorous, potassium, magnesium2. Consider evaluation for myasthenia, if symptoms are suggestive3. TSH to evaluate for hypothyroidism4. Basic metabolic panel, cortisol levels to evaluate for hypoadrenalism

e. Treatmenti. Depends on the cause

1. Inflammatory myopathiesa. Anti-inflammatory medications (prednisone, etc.)

2. Congenital myopathiesa. Often no specific or curative treatmentb. Supportive care (braces to improve function, respiratory support in some

cases)3. Metabolic myopathies

a. No curative treatmentb. Creatine replacement in creatine deficiency myopathy has shown variable

efficacy in clinical trialsc. Lactic acidosis from mitochondrial myopathies must be addressed when it

occurs; vitamin C, menadione, niacin, riboflavin, and ubiquinone together have been used

f. Prognosisi. Depends on the myopathy

1. Most are progressive and without cure2. Disability due to worsening weakness, gait instability, falls, and (in some cases)

respiratory depression or cardiac arrhythmias

III. Muscular Dystrophiesa. Definition

i. Muscular dystrophies are inherited forms of muscle disease characterized by initially normal muscle development, followed by weakness, then finally muscle atrophy

ii. Although these are primarily considered muscular disorders, there may be a neuropathological component, as well

b. Clinical features i. Family history of muscle disease is common

ii. Weakness often develops before muscle atrophyiii. Distribution of the weakness and muscle wasting depends on the form of dystrophyiv. Reflexes are often depressed even before weakness developsv. In late stages, differentiation of which dystrophy is present is difficult due to diffuse muscle

weakness and wastingvi. Types of muscular dystrophy

1. Duchenne muscular dystrophya. Mode of inheritance: X-linked recessive; almost exclusively present in males

(rare female cases have been reported)b. Age of onset: first decadec. Distribution: proximal leg muscles, then shoulders, then spreads distallyd. Exam findings: Reflexes lost, except for ankle jerks; macroglossia;

pseudohypertrophy of the calves, deltoids, infraspinatus musclese. Associated features: EKG abnormalities, osteopenia, scoliosis, fatty heart

infiltrates, pathological fractures, respiratory infections, low IQ in 30% of patients, contractures

f. Treatment: Steroids initially help strength but do not affect overall prognosisg. Prognosis: Death from cardiac failure or respiratory infections within 6 years

of onset, frequently by age 202. Becker’s muscular dystrophy

a. Similar to Duchenne, but age of onset in teens to thirties and slower progression

3. Limb girdle dystrophya. Mode of inheritance: Autosomal recessive usually, but can also be dominant

or sporadicb. Age of onset: Second or third decadec. Distribution: Weakness in proximal muscles, either the pelvic or shoulder

girdle, with slow progression distallyd. Exam findings: Depressed proximal reflexes with spared ankle jerks,

pseudohypertrophy in calves, deltoids, and lateral quadricepse. Associated features: CK and aldolase may be slightly elevated or normalf. Treatment: Supportive; no specific treatmentg. Prognosis: No affect on expected lifespan

4. Facioscapulohumeral dystrophya. Mode of inheritance: Autosomal dominant, occasionally recessiveb. Age of onset: Second through fifth decadesc. Distribution: Face involved first, then shoulder girdled. Exam findings: Reduced reflexes at the biceps and triceps;

pseudohypertrophy of forearm muscles; true hypertrophy of deltoids

e. Associated features: Congenitally absent pectoralis, biceps, or brachioradialis; CK and aldolase elevated in approximately 50% of cases

f. Treatment: No specific treatmentg. Prognosis: No affect on lifespan

5. Myotonic dystrophya. Mode of inheritance: Autosomal dominantb. Age of onset: Any age, usually third decadec. Distribution: Generalized weakness in hands, ptosis, facial weakness,

weakness and atrophy of quadriceps and tibialis anteriord. Exam findings: Atrophy in arms, facial muscles, “swan neck” appearance,

“hatchet” face, depressed reflexes diffusely, EMG shows characteristic myotonic discharges

e. Associated features: Cataracts, frontal baldness, gynecomastia, bronchiectasis, testicular atrophy, slowed bowel motility, cardiac abnormalities

f. Treatment: No specific treatmentg. Prognosis: Premature death due to cardiac failure or respiratory infections

6. Myotonia congenitala. Mode of inheritance: Autosomal dominant; the autosomal recessive form

results in progressive weaknessb. Age of onset: At birthc. Distribution: Myotonia (inability to relax a muscle after contracting) present

diffuselyd. Exam findings: Diffuse muscle hypertrophy starting in the second decade,

slowed and stiff movements are worse in colde. Associated features: Nonef. Treatment: Procaineamide, phenytoin, or quinidine work well to reduce

myotoniag. Prognosis: Normal life expectancy

7. Ocular dystrophiesa. Mode of inheritance: Autosomal dominant or sporadic formsb. Distribution: Extraocular movement weakness, eyelid weakness, and facial

weakness; 25% of patients have limb girdle weakness, as wellc. Exam findings: Ptosis, eye movement abnormalities, dysphagia in halfd. Associated features: (in some families) retinitis pigmentosa, cerebellar

dysfunction, cardiac abnormalities, endocrine dysfunction, visual changes; EMG/nerve conduction studies indicate a neurogenic component in some

e. Treatment: No specific treatment

CCC13: Muscle Pain/MyopathiesInflammatory Myopathies (rare)

Inclusion Body myositisDistal limb weakness often confined to legsover 50 y/o, dyspagiaWkness of long finger flexors

Normal CKBeta-amyloid precur protein!!Inclusion body = lymphocytes that invade and destroy the muscle, inflammation is rarely seenDoes not respond to steroids

PolymyositisNeck and proximal limb weakness eventual total body weakness

Ocular movement sparedMay occur with collagen-vascular disorders

Onset after 35 y/o, progression over weeks reaches plateau and permanent disability

CK elevated 10x or more above normalCD8+ infiltrationAnti-Jo antibodies

Tx: Steroid responsive

DermatomyositisPeaks in puberty and around 40 y/oFemales > Males

1st manifestations simultaneous in SKIN and muscleRASH: butterfly distrubtion over nose, edema/erythema affect eyelids, periungal skin, extensor surfaces

of joints, upper chestMUSCLE: proximal weakness, ache, tender to palpation

Proximal wkness with decreased DTRs, dysphagia

CK elevated (not nearly as high as polymyositis)Abnormal EMGBiopsy: degeneration, regeneration, edema, lymphocytic infiltration (B cells)

Tx: steroid responsive

Sarcoid myopathyClinically similar to polymyositisGranulomas seen on muscle biopsiesACE levels are elevated

Eosinophilic myositisPatient has generalized pain w/ proximal > distal wknessBiopsy = eosinophilic infiltrate instead of lymphocytesSeen as response to drug, chemical or parasitic exposure = allergic response to toxin

Non-inflammatory disorders Myofascial pain syndrome – very common

Radiating pain in defined, localizing pattern (constant, aggravated with motion, worse upon awakening, ROM is restricted), taut bands and trigger points with radiation on palpation

Onset is typically after minor, repeated trauma or abruptly after severe traumaTrigger points are active or latentEMG is abnormal within trigger pointsBiopsy – normalNeuro exam – normal

Tx: stretching, massage, conditioning, trigger point injections, analgesics, relaxers, sleep aids, IV lidocaine, topical ketamine

Fibromyalgia syndrome7x MC in Females, numerous comorbidities

Clinical Symptoms– Chronic, diffuse musculoskeletal pain, with focal areas of tenderness in earlier stages, but more

widespread tenderness as disease progresses.• The pain often begins after trauma, whether physical or psychological. • Pain is described as deep aching and throbbing.• Pain is continuous with intermittent exacerbations often triggered by weather changes,

increased physical activity, trauma, or intercurrent illness.– Additionally, patients have affective and cognitive dysfunction, dizziness, chronic insomnia or non-

restorative sleep, nocturnal myoclonus, morning stiffness, abdominal or pelvic pain, dysuria, and diarrhea or constipation.

– FMS patients have abnormal reactivity to pain (similar to allodynia). Objective pain measurements indicate that FMS patients feel minimally painful stimuli as strongly painful.

– Comorbidities include TMJ syndrome, migraines, irritable bowel syndrome (IBS), interstitial cystitis (IC), dysmenorrhea, rheumatoid arthritis, depression, anxiety, and chronic fatigue syndrome.

• These comorbidities occur within FMS at a significantly higher rate than in the non-FMS population

Pathophys:Central sensitizationNeuroendocrine, neurosensory, and NT disturbances

Diagnostic CritieraWidespread pain in ¾ body quadrantsTenderness to palpation in 11/18 tender points on body

Tx: exercise, antidepressants, neuromodulators, analgesics, psychological support

Prognosis: non-fatal, but severely life-altering

CCC14: Cerebellar LesionsCerebellar anatomy – 3 lobes, 2 fissures, and 3 peduncles

Superior peduncle – connects cerebellum midbrainMiddle – connects cerebellum ponsInferior – connects cerebellum medulla (largest peduncle)

Cerebellar function:Coordination centerDiscrete, skilled movementsRegulates movements and posture indirectlyComparator – compares intension with performance, adjusts appropriately

Cerebellar lesions:COMMON findings = HANDS Tremor

H = hypotoniaA = asynergy (lack of coordination)N = nystagmus: abnormalities of target-directed eye movements

Slow-conjugate movement way from lesionD = dysarthria: slurred, garbled speech slow or staccato in nature S = station and gait (imbalance/ataxia)Tremor = course intension tremor

Cerebellar ataxia Ataxia of gait = incoordination of walking, steps are wide-based, unequal, zig-zaggedTruncal ataxia = incoordination of all truncal movements (extremities flail)

Dysmetria – inaccuracy in range/directionDysprosody – disturbance of stress, pitch, rhythm of speech

LocalizationMidline cerebellum truncal ataxia/musculature and body equilibrium

Rostral – stance/gaitCaudal – truncal ataxia

Hemispheres IPsilateral extremity dysmetriaPancerebellar entire cerebellum

Evaluation:Test motor skillsRomberg’s Test – tests cerebellar and posterior column function

Disorders:Cerebellar infarction

Thrombotic/embolic occlusion of vessel6 D’s: Decreased consciousness, Dz, Dysequilibrium, Diplopia, Dysarthria, DysphagiaMC = PICA infarct

Acute postinfectious cerebellitisChildren between 2-7 y/o M = FExplosive onset w/ ataxia at maximum at onsetSersorium is clear despite severe ataxiaSymptoms remit after a few days, normal gait requires 3 wks/5 months to regainDx of exclusion, Tx – self-limiting

Cerebellar hemorrhageAbrupt onset of vertigo, Ha, Vomiting, inability to stand/walk with absence of hemiparesis/hemiplegiaTendency for abrupt deterioration to coma/death

Cerebellar neoplasm50% of neoplasms in kids: Posterior fossa neoplasms:

Cerebellar astrocytomaMedulloblastomaEpendymoma of 4th ventricleBrainstem glioma

Rare in adults:

HemangioblastomaMetastatic tumorSchwannomaMeningioma

Freidreich’s AtaxiaMC early onset ataxiaSpinal cord may be thinner than normal = degeneration/sclerosis in posterior columns, SC tracts, and CS tractsGAA triplet repeat – deficiency of frataxin

Clinical features: gait ataxia, arm ataxia, scolio, dysarthria, l/o DTRs, l/o vibration/position sense, muscle wkness, atrophy, Hcardiomopathy, pes cavus, abnormal ocular motility, diabetes, deafness

Course: progression, cannot walk after 15 years of onset, death from infection or cardiac diseaseTx: nothing influences the course

*UMN + LMN symptoms!*

Cerebellar HerniationUpward (transtentorial) – obliterates aqueduct and cisterns = hydrocephalus/obtundation/comaDownward (tonsillar) – compression of medulla = respiratory arrest/death

CCC15: New Onset Seizures in Children75% of epilepsy presents before 20 years of age. If begin before 2 y/o – grave prognosis

Neonatal seizures:May be only symptom of CNS disorder or symptom of another treatable, serious conditionMajority are partial seizuresRisk factors: premie, low birth weight, HIEDiagnosis: observation w/ and w/o EEG

Classification – based on clinical manifestationSubtleTonicClonicMyoclonicAutonomic

Special types: Benign neonatal familial convulsion

1. Dominantly inherited, chromosome 20.2. Seizures occurring in the second or third day of life3. Characterized by clonic or apneic seizures 4. without specific EEG marker

Pyridoxine dependency and biotinidase deficiency1. Variable age of onset from neonatal period to later infancy2. Various seizure types

Benign neonatal sleep myoclonus 1. EEG and physical exam is normal and prognosis is excellent.

Treatment: determine cause, provide adequate ventilation/glucose, Phenobarbital/phenytoin

Common pediatric epileptic syndromesWest syndrome

Triad begins in 1st year of life: infantile spasms, hypsarrhythmic EEG, psychomotor delayFlexor spasms, extensor postures/focal motor features are commonEtiology: prenatal/perinatal brain injury, metabolic, degen disorders, neurocutaneous disorders, cerebral

malformationsNeurodevelopment is only normal in 10% of patientsTx: benzos, valproate, steroids, corticotrophin, vigabatrin, focal cortical dysplasiaPoor prognosis – onset before 3 months, symptomatic etiology, multiple seizure types

Lennox-Gastaut syndromeMultiple seizures types, MR, slow spike-wave EEG discharges beginning 1-7 y/oTonic, atonic, atypical absence, tonic-clonic seizures commonDevelopmental regression + gradual/abrupt onset of symptomsTx: Corticosteroids, ketogenic diet, valproate, lamotrigine, topiramate, felbamatePrognosis: POOR especially if onset is before 2 years/age

Febrile convulsionsMC seizures in early lifeSimple - <15 mins, lack focalityComplez - >15 mins, focal manifestations, recur within 24 hoursTx: rectal diazepam, avoid prophylactic AEDsPrognosis: 30% will have recurring seizure, only 2-5% develop afebrile seizure

Idiopathic partial epilepsy syndromeBECTs – most common epilepsy syndrome in childhood.

Partial seizures occur w/I hours of falling asleep = sensorimotor symptoms25% of pts develop secondarily generalized seizures

Tx: 1st line AEDs

Benign childhood epilepsy with occipital paroxysmsVisual phenomena including simple/complex hallucinations, visual distortions, hemianopsia, amaurosisMisdiagnosed as migraine oftenPrognosis: GoodTx: 1st line AEDs

Childhood absence epilepsy4-8 years with frequenc absence seizures40% develop tonic-clonic seizures when approaching pubertyNormal development, usually remit by adolenceTx: 1st line AEDs

Juvenile myoclonic epilepsyGeneralized tonic-clonic seizures after awakening beginning in adolescenceMyoclonus in dropping things, or unnoticed for yearsTx: valproate = DOC, indefinitely b/c less than 20% grow out of this.

CCC16: Pediatric Muscle Weakness and Cerebral Palsy (Hillary’s notes)See lecture for Muscle Weakness Lecture – it was mainly just a differential diagnosis listCerebral Palsy- Difficulty in neuromotor control, anonprogressive brain lesion, injury to the brain that occurred before it was fully

mature (<3 yrs), and a static encephalopathy must exist.

Prevalence- 2-5 / 1000 live births (rate decreases with age)- There is a definite correlation between birth weight/ gestational age and the incidence of CP.Etiology- Hypoxic/ischemic incidents occurring perinatally have been blamed for the majority of CP- In > 50% of CP pts, etiology may not be evident- Although prematurity is the MC antecedent of CP, the majority of infants were full termClassification- Neuroimaging techniques may help define the anatomic deficit, but will not reveal any pathology in the majority of

children- 20% to 30% of infants who appear to fit the criteria for the diagnosis of CP at 1 year of age will not show any

manifestations of a motor deficit by 7 years of age. - In the past decade, the number of patients who have spastic diplegiahas increased, proportional to increased

survival rates of preterm infants (33%).- Kernicterus and CP: Bilirubin encephalopathy with resulting kernicteruscausesathetosis-like CP

Diagnosis- Any infant whose has motor delay must be suspect for having CP. - Diagnosis is very difficult < 6 mo.- Delay in achieving motor milestones at an appropriate age is common for children who are retarded but who do

not have CP. (present w/ hypotonia)- Highly suspicious for CP if there is motor delay with normal cognitive development.- >50% of children with CP are retarded.- It is necessary to decide where the pathology exists anatomically:

- centrally (eg brain) – indicates CP- peripherally (eg spinal cord, anterior horn cell, peripheral nerve, myoneuraljxn, or muscle)

- Make sure it’s not progressive: clues are:- Regression (could be a late sign)- Consanguinity- Congenital skeletal anomalies such as pescavus or scoliosis- Neurocutaneous stigmata

TYPES:Athetoid CP (type of Dyskinetic) - Damage to Basal Ganglia or Cerebellum

- Kernicterus causes this type- Obligatory asymmetric tonic neck reflex.- Delay in achieving motor milestones- 12 -18 months of age: infant will show athetoid-dystonic posturing on voluntary movement.- Hypotonia gradually changes to increased tone of the rigid or cogwheel type. - Hypertonus and the involuntary movements may increase in severity over the next year.SPASTIC DIPLEGIA- Many preterm infants who have CP will develop spastic diplegia (33%)- Delayed sitting, crawling, standing, and ambulation - Low tone of the LE may be present.- 1 year of age hypertonia (spasticity)- Increased DTRs and occasionally unsustained bilateral clonus will be present.- Abnormal postural reactions, e.g., scissoring of the legs due to spasticity of the hip adductors.ATAXIC CP

- Low tone of trunk and extremities, usually with normal DTR’s- Support their weight with their knees extended so as to lock them in position, and use a very wide base for

support. (Rare to see any overt signs of ataxia)- May be a spastic component to the condition.- Infant usually will be hypotonic and not spastic, but hyperreflexia will indicate the presence of pyramidal tract

involvement. SPASTIC QUADRIPARESIS- Infants who have this type of CP also pass through a stage of hypotonia prior to the appearance of spasticity and

increased muscle tone.- Early manifestations of spasticity are similar to those described in other spastic clinical types and affect both lower

and upper extremities.

Management of CP- The long-range management of children who have CP addresses both motor dysfunction and associated nonmotor

deficits. Motor Development Goals- Improve function and prevent secondary complications of the musculoskeletal system. - Establish realistic expectations for the child’s motor function- Ensure that progressive contractures and deformities do not interfere with optimal outcome.- Promote gross motor skills. - Occupational therapy concentrates on eye-hand coordination and UE motor control to attain the highest level of

independence in self-care and other activities of daily life that involve hand fxn. - Pseudobulbar palsy in bilateral impairment of the motor system leads to oral motor dysfunction manifested as

early sucking, swallowing, and chewing difficulties, can lead to impaired speech. - Parental involvement and training in special feeding techniquesAssistive DevicesBiofeedbackBracingAntispasticity Medications- Affect muscle tone through different mechanisms of action. - Diazepam - a centrally acting muscle relaxant - Dantrolene -Na reduces spastic hypertonicity by the contractile properties of skeletal mm fibers- Baclofen - a gamma-aminobutyric acid derivative that is thought to inhibit neurotransmission.

- More effective for spasticity of spinal origin, but it may be used for adjunctive treatment in CP that is accompanied by severe spasticity.

- Topical injection of phenol, alcohol solution, or botulism toxin into the motor points or motor nerves of a spastic muscle creates a temporary neurolysis and consequent tone reduction lasting 4 to 6 months. Most often is applied to alleviate spasticity of the ankle plantar flexors and hip adductors.

Surgical TherapyOrthopedic- lengthening of a tight or contracted heel cord corrects toe walking and enhances the efficiency of gait. - release of spastic hip and knee flexors and tenotomy of the hip adductors- In severely affected children, the primary reason for surgery is to prevent progressive skeletal deformities that

inevitably follow spastic muscle imbalance.- Acquired hip dislocation, scoliosis are severe complications of spasms

Neurosurgical- Selective posterior rhizotomy is the current neurosurgical approach to alleviate spasticity.

- L2 to L5 laminectomy to localize the posterior roots in the caudaequina.- Electrical stimulation applied to the individual rootlets is monitored by electromyography.- Rootlets that produce clonic or sustain stimulus response, especially with spread to other muscle groups

are severed because they are thought to be responsible for spastic disinhibition- Recommended mostly for those children who have spastic diplegia but who can walk and have adequate strength,

motor control, balance, and reasonable intelligence. - Daily physical therapy for 6 to I 2 months after surgery

- Post-op complications are rare and include transient paresthesias and loss of bladder control. - Although the procedure reduces spastic hypertonicity, whether it significantly influences the natural course of

motor disability remains a matter of debate.

ASSOCIATED DYSFUNCTIONHearing- High-f hearing loss: 70% of athetoid CP - Other types have 30% frequency of sensori-neural hearing loss is approximately 30%Speech and language developmentUncontrolled drooling: sx of pseudobulbar palsy, improves spontaneously by 5-10 yo in someVision- Refraction errors and retinopathy of prematurity- High incidence of strabismus (75%) esp in spastic type– tx to prevent amblyopiaSeizures- ~50% of the children who have CP develop some form of seizure disorder. - highest incidence in spastic hemiparesis and quadriparesis. Mental Retardation: 50% of those affected, others may have LDWalking: Energy expenditure for walking and other physical activities is several times above normalOutcome- Walking is not expected of children who cannot sit by 4 years of age. - Motor control of the upper extremities is adequate to perform ADLs in diplegia and usually in cases of mild

ambulatory quadriparesis. - Some children who have quadriparesis&rely on wheelchair for mobility may achieve partial independence in self-

care. ~25% of this group requires help for all activities.

CCC17: Febrile vs. Non-febrile seizures (hillary’s notes)Febrile vs. Non-Febrile Seizures in ChildrenFEBRILE SEIZURESEPIDEMIOLOGY: about 5% in N. AmericaINCIDENCE- MC between ages of 6 months and 5 years (peak between 18-24 mo)RISK FACTORSGeneralPopulation- Family hx of febrile sz in 1st or 2nd degree relatives- Developmental delay- Nursery stay > 30 days- Daycare attendanceChildrenwithFebrileIllness- Family hx of febrile sz in 1st or 2nd degree relatives- Peak T during the illness (not T at time of sz)- Nature of underlying illness (eg. AGE, OM, HHV-6 or 7)PATHOPHYSIOLOGY- Pathophysiology is unclear, maybe IL-1, genetic factors, multifactorial- The PEAK temp is significant not the rate of rise or fallSUBTYPES AND CLINICAL FINDINGSCOMPLEX- Focal- Duration >15 minutes- Multiple sz within the same febrile illness (within 24

hr)- 15-20% of febrile szSIMPLE- Generalized- Duration < 15 minutes- About 75% of all febrile sz

DDx- CNS infection (encephalitis, meningitis)- Meds/Toxins (Shiga toxin, salicylates, anticholinergics, cocaine, tricyclics, amphetamines, etc)- Metabolic disorder (hypoglycemia, hypocalcemia)- Shaken baby syndrome- Head trauma- Underlying brain disease (epilepsy, tuberous sclerosis, etc.)

Diagnostic Workup: Hx, PE, neuro exam, look sick?, LP, Lytes, imaging, EEG

AAP GuidelinesLumbarPuncture- Strongly consider in infant < 1 y/o- Probably “mandatory” in infant < 6 m/o- Remember meningeal signs subtle to non-existent in 12 to 18 month age group- Not necessary in child > 18 m/o if H & P not suspicious for meningitis- Recommended in all children with complex febrile sz, especially if focal or prolongedBloodStudies- Children 6 m/o and over of limited value unless suspicious hx (eg. vomiting, diarrhea)- Infants < 6 m/o detailed lab studies may be helpful in select casesImagingStudies- Limited value and not necessary prior to LP- EXCEPTION: Neuroimaging indicated in febrile sz of 30 min or more (febrile status epilepticus). MRI is the

method of choice.EEG- Little role except for febrile status epilepticus

TREATMENT- No Tx for simple febrile seizures- For those at high risk for recurrence, rectal diazepam can be given as ABORTIVE THERAPY ParentalEducationandCounseling- Reassurance: sz won’t cause brain damage and chance of developing epilepsy small (2-10%)- Advise them it could recur especially in first 24 hours (30% recurrence in 1st year)- Teach mgmt of sz: lie child on side, maintain airway, call EMS if sz> 3 min- Morbidity and mortality essentially zero

NON-FEBRILE SEIZURESEPIDEMIOLOGY AND INCIDENCE- Overall incidence of childhood epilepsy from birth to 16 years is about 1-2%- 1% of children will have at least one afebrilesz by age 14 years- Epilepsy is the MC chronic neurologic disorder in childhood

CLASSIFICATION- Partial

o Simple partial: brief tonic-clonic movement of face, neck, extremities; head turning; eye deviationo Complex partial: consciousness impaired; children may pick at things, blink, and stareo Onset at any age

- Generalizedo Generalized tonic-clonic: alternating stiffening/shaking, tongue biting, LOC, incontinence, and postictal

recovery phaseo Generalized absence: brief LOC (rarely >30 sec) but w/o loss of postural tone

o Others: Myoclonic, tonic, clonic, atonic- Epilepsy syndromes: Seizure syndromes incl. infantile spasms, benign epilepsy of childhood, Lennox-Gastaut,

and juvenile myoclonic epilepsy

EVALUATION AND DIAGNOSISDDx- Generalized tonic-clonic: Syncope, breath-holding, cardiac arrythmia- Generalized absence: Behavioral staring, complex partial seizures, tic disorder- Complex partial: Sleep walking, night terrors, benign paroxysmal vertigo, migraine disorders, self-

stimulatory behavior- Epileptic myoclonus: Physiologic in sleep, startle myoclonusDiagnostic Workup- Hx, PE, EEG, MRI, LP,labsTreatment- AED selection based on seizure type- ~80% of pts w/1° generalized seizure epilepsy & 65% of pts w/ partial seizure epilepsy achieve satisfactory

control with AED tx

CCC18: Seizures in Adults Seizure: the clinical manifestation of an abnormal and excessive excitation and synchronization of a

population of cortical neurons. Seizure is a symptom, not a disease!! Occur b/c of too much excitation, too little inhibition = hyperexcitable network

Epilepsy: two or more recurrent seizures unprovoked by systemic or acute neurological insults. Epilepsy is a disease, a syndrome, or a neurological disorder.

Classification of Epileptic Seizures (refer to word document if further description is warranted) Partial Seizures( Seizures beginning locally)

1. simple partial seizures ( consciousness not impaired) 2. Complex Partial seizures ( With impairment of consciousness) 3. Partial seizures( simple or complex), secondarily generalized

Generalized Seizures - bilaterally symmetric, without localized onset, l/o consciousness 1. Absence seizures 2. Myoclonic seizures

3. Clonic seizures 4. Tonic seizure

5. Tonic-clonic seizures (“grand mal”) 6. Atonic seizures

Seizure risk factors– Family history– History of febrile seizures– History of head trauma– History of meningitis– History of stroke or other structural lesion

Evaluation of a 1st seizure:History, physical

Blood tests: CBC, electrolytes, glucose, Calcium, Magnesium, phosphate, hepatic and renal functionLumbar puncture only if meningitis or encephalitis suspected and potential for brain herniation is ruled outBlood or urine screen for drugsElectroencephalogramCT or MR brain scan

Seizure Precipitants Metabolic and Electrolyte Imbalance Stimulant/other proconvulsant intoxication Sedative or ethanol withdrawal Sleep deprivation Antiepileptic medication reduction or inadequate AED treatment Hormonal variations Stress Fever or systemic infection Concussion and/or closed head injury

Factors to consider for a woman with epilepsy:Drug if on OCP?Extra folate b/c seizures can lead to fetal malformation

Life style modifications: Adequate sleep Avoidance of alcohol, stimulants, etc. Avoidance of known precipitants Stress reduction — specific techniques

Non-medical treatment options for epilepsy Ketogenic diet ( Anti-seizure effect of ketosis) Vagal nerve stimulator (Intermittent programmed electrical stimulation of left vagus nerve) Epilepsy surgery

Psychogenic Seizures A common symptom of conversion or somatization disorder. Maintain a high degree of suspicion when seizure are refractory to therapy or when atypical features are

present. Diagnosis is made by recording typical events with video-EEG.

Status Epilepticus

Status epilepticus is defined as: 1) an episode of more than 30 minutes of continuous seizure activity, or 2) two or more sequential seizures spanning this period without full recovery between seizures. Clinically, however, most seizures last less than 5 minutes, and those persisting longer are unlikely to stop spontaneously.

Therefore, one should initiate treatment for the seizures lasting longer than 5 minutes. The incidence of status epilepticus is at least 60,000 cases/year in the U.S., with higher rates among the very young and very old. Status

epilepticus is an emergency because of its morbidity and mortality, and any seizure type may manifest as status epilepticus. The outcome of convulsive status epilepticus largely depends on etiology, but prompt treatment can improve outcome.

From a practical standpoint, status epilepticus may be divided into convulsive and nonconvulsive forms. The convulsive forms may be generalized or partial. The nonconvulsive forms are difficult to classify on clinical grounds, but are often divided electroencephalographically into absence status (in which the EEG demonstrates generalized spike-wave activity) and complex partial status (in which the EEG may show a variety of localized rhythmic discharges.

CCC19: Brain tumors 35% of Pediatric solid tumors occur in the CNS

Most come from supportive cells (astrocytes, oligodendrocytes, ependymal, pinealocytes)Only a few come from neurons

Cell of origin:Neural stem cells lead to gliomas

PrevalenceAdults: meningiomas > glioblastomas > other astrocytomasKids: Pilocytic astrocytomas > Medulloblastomas > other astrocytomas

Risk factors for childhood tumors:Prenatal x-raysCranial radiation in childhoodViruses, industrial chemicals, cell phones

HIV infection CNS lymphomaGenetic predisposition for NF1 (loss of NF1 tumor suppressor gene) and Li-Fraumeni (loss of p53 tumor suppressor gene)

S/S:*Head ache, behavioral change, GI upset, balance or gait change, “Alzheimer’s”, school work suffers, falling, shortened attention span, visual or hearing impairment, Mom is in your office more than once!*Pupillary changes, gait difficulties, papilledema, seizures, speech defect, neglect, memory changes, visual field cut, galactorrhea, menigismus.

Diagnosis:MRI is the best test b/c it shows blood flow and water movement

Ring enhancement often means GBMCT’s miss low-grades

Herniation SyndromesUncal – temporal lobe impinges the PCA, contralateral peduncle, midbrain

Unilateral dilatd pupil (CNIII compression), oculomotor palsy, contra hemiparesis Central – midline tumors compress basal ganglia (midbrain symptoms)

Tonsillar – posterior fossa tumors compress downward into the foramen magnum*cough + pass out = tonsillar herniation

Emergency managementIncreased intracranial pressure can kill!SeizuresDeep Venous Thrombosis – brain tissue is clotagenic

Treatments:Resection surgery

Decision to operate includes: age, performance status, location of tumor, feasibility of debulking/complete resection, if recurrence – time since

Radiation TherapyGoal: damage DNA of tumor cells, so try to localize tx to spare normal brain and fractionate to exploit differences

in repair

Chemo principles – works best when tumor burden is small, combine active drugs

Radiosurgery = GammaKnife/Cyberknife/Synergy S

Glial Brain TumorsAstrocytes (provide blood vessel structure support)Low-Grade

Seizure as 1st signNot cured with resection alone unless a rare pilocytic tumor

High-grade (Anaplastic Astrocytoma- 3 year survival & Glioblastoma Multiforme (GBM 80% of high grade, survive 1 year))

Ring-like, enhancing, edematous – risk of herniation Don’t let the “capsule” fool you spreads, necrotic

Oligodendrocytes (provide axonal support)Low-grade

Present with seizure or subtle neurological impairmentMRIs show calcificationsChemosensitive

High-grade

MeningiomaB9, off the dura “dural tail”, 20% of all intracranial neoplasmsSx for symptomatic, sometimes discovered incidentally

Primary CNS LymphomaB-cell, non-Hodgkin’s LymphomaPrevalent in immunocompromisedTx: high dose methotrexate

Pituitary adenomaTumors of endocrine system, are they even cancer?Do not have high growth rates or metBig question: are they secreting or not? Are they causing mass effects or not?

Tx: may leave alone if asymptomatic, medical for secreting tumors, transsphenoidal resection if mass lesion, usually handled by endocrinologist

CCC20: Brain tumors in Kids 2/3 of pediatric brain tumors can be cured using some combination of rx, chemo, and/or radiation, but the younger brains are more susceptible to Side effects

Medulloblastomas 25% of pediatric tumors, less than 3 years/age usually

Cerebellum = medulloblastoma, clips off the 4th ventricleS/S: obstructive hydrocephalus, Ha, N/V, ataxia, and drowsiness Tx: managing the ICP + tumor resection then adjuvant therapies (sx will not cure alone)

Low Grade AstrocytomasPilocytic predominatesCerebellar – rare

EnpendymomaMajority in posterior fossa

Brain stem gliomasDiagnosis by MRI and suspicion (is not removed)

Intracranial Germ cell tumors Pineal region is the majorityS/S – panhypopituitarism, diabetes insipidus, visual disturbancesBiopsy – need to determine b/w germinoma vs. non-germa vs. teratoma

Pure Germinoma - Radiation alone is curativeNon-germanomatous – worse prognosis

CraniopharyngiomaEpithelial cells in Rathke’s pouchCalcification and cystic appearance are classic finding

CCC21: Cranial Nerve DisordersI. Cranial Nerve I (olfactory nerve)

a. Function(s)i. Special Somatic Afferent (SSA) – Smell

b. Anatomy (Moore & Dalley, p.1133; Blumenfeld, p. 465)i. Intranasal fibers run through the cribriform plate to the olfactory bulb

ii. Olfactory bulb to the olfactory tract just inferior to the frontal lobes and superior to the optic nerves and chiasm

iii. Enters anterior perforated substance and runs to the olfactory cortex; NOTE: there is no relay in the thalamus – this is the only sensory pathway that does not run through the thalamus

c. Symptoms of dysfunctioni. Inability to smell (anosmia)

ii. Disordered taste – often lack of taste or bad taste – because much of the taste of food is derived from smell rather than taste

d. Differential diagnosis of dysfunctioni. Trauma, either local or generalized head injury that tears the fragile fibers crossing the

cribriform plateii. Dry or clogged airways

iii. Allergic rhinitisiv. Nasal polypsv. Foreign bodies

vi. Autoimmune/inflammatory disease (e.g., Wegener’s granulomatosis)vii. Medications – antihistamines, antibiotics, anti-inflammatories, anti-thyroid, anti-

metabolitesviii. Tumors of the olfactory groove – meningiomas, craniopharyngiomas

ix. Bad smells (burning rubber, skunks) may occur in the setting of seizure, are intermittent, and are often followed by alteration in consciousness with or without generalized seizure activity

x. Sense of smell normally declines with agexi. Psychogenic

e. Evaluationi. Test sense of smell by occluding one nostril, ask patient to identify a smell through the

unoccluded nostril (peppermint, vanilla, lemon)ii. Brain imaging is very important to rule out structural lesion

II. Cranial Nerve II (optic nerve) (Moore & Dalley, pp. 1132-1136; Blumenfeld, pp. 431-453)a. Function(s)

i. Special Somatic Afferent (SSA) – Visionb. Anatomy

i. Special fibers in the retina collect data regarding light, color, movement, and shapesii. Retinal fibers join to form the optic nerve

iii. The optic nerve continues straight back from the back of the eye, below the frontal lobes, and then join one another at the optic chiasm

iv. The optic chiasm consists of crossing nasal fibers from each eye; the lateral edges of the optic chiasm contain non-crossing temporal fibers from each eye

1. NOTE 1: The nasal fibers are those fibers that arise from the nasal aspect of the retina; however, due to the lenses in the eyes, the nasal fibers actually pick up information from the temporal visual field in each eye. The temporal fibers in the optic nerve and chiasm arise from the temporal aspect of the retina but carry information about the nasal visual fields.

2. NOTE 2: Know and understand the diagrams on Moore & Dalley, p. 1134-1135 or Blumenfeld, p. 442)

v. The temporal fibers from the ipsilateral eye and the nasal fibers from the contralateral eye join to form the optic tract, which starts just posterior to the optic chiasm

vi. The optic tract synapses in the lateral geniculate nucleus (or body), LGN, just lateral to the midbrain.

vii. Optic radiations spread out from the LGN and travel through the temporal and parietal lobes to reach their destination in the visual cortex of the occipital lobes.

c. Symptoms of dysfunctioni. Loss of vision in one or both eyes

ii. Visual field cutsiii. Afferent pupillary defect (APD, or Marcus-Gunn pupil)

d. Differential diagnosis of dysfunctioni. Loss of vision in one eye (or both)

1. Optic neuritis (think multiple sclerosis)2. Microvascular damage to the nerve3. Trauma4. Tumor of the optic nerve or optic nerve sheath5. Intra-ocular pathology (does not usually cause APD)

ii. Visual field cut1. Bitemporal field cut – chiasmal lesion such as pituitary tumor or aneurysm2. Homonymous hemianopsia – contralateral hemispheric lesion such as stroke or

tumor3. Superior quadrantinopsia – contralateral temporal lobe lesion such as stroke or

tumor4. Inferior quadrantinopsia – contralateral parietal lobe lesion such as stroke or

tumor5. Homonymous hemianopsia or quadrantinopsia with macular sparing –

contralateral occipital lobe lesioniii. Afferent pupillary defect (No discussion in Moore & Dalley; use Blumenfeld, p. 541, 544-

545)1. A flashlight aimed into the normal pupil causes consensual pupil constriction;

when the flashlight is moved to the abnormal eye (“swinging flashlight test”), both pupils dilate because the abnormal optic nerve “sees” less light and triggers CN III to dilate both pupils

2. Also known as “Marcus-Gunn” pupil; a. caused by ischemia or demyelination/inflammation (optic neuritis) in

the optic nerve ipsilateral to the dilating pupil; think multiple sclerosis in a young person and ischemia in an older person

b. Other causes: tumor, traumae. Evaluation

i. Pupillary reflex (Afferent = CN II, Efferent = CN III)ii. Fundoscopic evaluation

iii. Loss of vision in one eye (or both)1. Opthalmology evaluation – look at the fundus with a fundoscope2. Think multiple sclerosis – brain MRI to look for lesions and spinal tap to

evaluate cerebrospinal fluid (CSF)3. Visual Evoked Response (VER) – the patient is shown a series of patterns on a

screen, and the electrical impulses from the eyes are measured in the brain; a slowed response indicates demyelinating lesion in the optic nerve

iv. Visual field cut1. Brain MRI to look for the structural lesion – know your anatomy; where are you

looking for the abnormality?2. Formal visual field tests – the patient’s head is positioned facing into a large

bowl; lights are flashed into the bowl, and the patient indicates to the technician when a light is seen. A map of the patient’s visual field is derived from the pattern of lights seen and not seen.

v. Afferent pupillary defect

1. Brain MRI to look for lesions and spinal tap to evaluate CSF for multiple sclerosis

III. Cranial Nerve III (oculomotor nerve) (Moore & Dalley, pp. 968-973; Blumenfeld, pp. 530-532)a. Function(s)

i. General Somatic Efferent (GSE) – Motor to levator palpebrae and all extraocular muscles other than superior oblique (CN IV) and lateral rectus (CN VI)

ii. General Visceral Efferent (GVE) – Parasympathetics to papillary constrictor and ciliary muscles for lens accommodation

b. Anatomyi. Leaves the posterior midbrain and tracks along the superior cavernous sinus and enters

the orbit through the superior orbital fissureii. The nerve fibers divide into superior and inferior divisions; the superior division carries

motor fibers to the superior rectus and levator palpebrae superioris; the inferior division carries motor fibers to the other oculomotor-innervated extraocular muscles and the parasympathetic fibers

iii. Parasympathetic fibers synapse in the ciliary ganglion (located just posterior to the eyeball in the orbital socket) and connect to the papillary sphincters

c. Symptoms of dysfunctioni. Double vision (diplopia)

ii. Inability to raise eyelid (ptosis)iii. Loss of pupil light response and dilated pupil on examination

d. Differential diagnosis of dysfunctioni. Horizontal double vision results from lack of conjugate eye movement in the horizontal

directions of gaze; oculomotor palsy causes failure of eye adduction on the side ipsilateral to the nerve lesion, e.g., intracranial mass or oculomotor nerve ischemia

ii. Ptosis results from oculomotor lesion ipsilateral to the lesion, e.g., intracranial mass or oculomotor nerve ischemia

iii. Dilated pupil results from compression of the oculomotor nerve. Autonomic fibers run on the surface of the nerve and, when compressed, result in pupillary dilation. Causes may include aneurysm, increased intracranial pressure (causes dilated, fixed pupils eventually), tumor, intracranial bleeding, fracture of the cavernous sinus.

iv. A complete CN III palsy includes ptosis, dilated pupil with loss of pupillary light response, and turning of the eyeball down and out (temporally)

e. Evaluationi. Careful examination to isolate which extraocular functions are affected, pupil

evaluation, and look for ptosis (ptosis in a CN III lesion is usually quite obvious)ii. Brain imaging – head CT or MRI to look for mass lesion (aneurysm, tumor, bleeding)

IIIb. Cervical Sympathetic Chain – OK, this isn’t a cranial nerve, but its anatomy is worth reviewing with CN III because damage to the chain causes symptoms that can be confused with CN III pathology if the examiner is not careful… (No discussion in Moore & Dalley; use Blumenfeld pp. 542-544)

a. Function(s)

i. Sympathetic innervation of the pupillary sphincter – causes pupil dilatation

b. Anatomy

i. Starts in the spinal cord at T1, runs to the superior cervical ganglion at the carotid bifurcation, where the nerves synapse

ii. Runs superiorly along the internal carotid into the superior orbital fissure to terminate on the pupillary dilators

c. Symptoms of dysfunction

i. Horner’s syndrome – ptosis, miosis, anhydrosis – all ipsilateral to the lesion

d. Differential diagnosis of dysfunction

i. Pancoast tumor in the upper lung lobe can compress the cervical sympathetic chain

ii. Carotid dissection or aneurysm interrupts the cervical sympathetic fibers

iii. Trauma to the neck from surgery, whiplash, etc.e. Evaluation

i. Consider the history – chest X-ray, carotid ultrasound or angiogram may be indicated

IV. Cranial Nerve IV (trochlear nerve) (Moore & Dalley, p. 1142; Blumenfeld, pp. 538-539)a. Function (s)

i. General Somatic Efferent (GSE) – Motor to the superior oblique muscle, which ANATOMICALLY pulls the eye down and out and intorts the eye medially; CLINICALLY, the muscle pulls the eye down when it is already adducted (the “cheating” muscle) and intorts the eye when it is already abducted

b. Anatomyi. Decussates completely around the periaqueductal gray matter – the only cranial nerve

to completely crossii. Exits from the posterior surface of the midbrain – the only cranial nerve to exit from the

posterior midbrainiii. Wraps forward around the brainstem, enters the cavernous sinusiv. Crosses over CN III to enter the posterior orbit through the superior orbital fissure and

terminates on the superior oblique musclec. Symptoms of dysfunction

i. Double vision when looking downwardii. The eye deviates upward and outward when CN IV is lesioned

iii. The person can rotate the head to compensate for the double vision – head tilt is to the side opposite the injured trochlear nerve

iv. Rare to have an isolated CN IV lesiond. Differential diagnosis of dysfunction

i. Head injury tears the fragile nerve, often bilaterallyii. Mass lesion to the dorsal midbrain – tumor, hemorrhage, aneurysm

iii. Congenital (children)iv. Ischemia (especially older adults)

e. Evaluationi. Careful extraocular movement evaluation, typically with a red lens (Right eye is covered

with a red lens, then a white light is shined into both eyes. The relationship of the red image to the white light is compared as the patient looks straight ahead, to the sides, up, and down – people go through fellowships to learn how to do this so don’t strain too hard right now to try to understand this test; just trust me that it can be done)

ii. Brain imaging with CT or MRI if mass is suspected; a mass typically causes a litany of other findings, not just an isolated trochlear palsy

V. Cranial Nerve V (trigeminal nerve) (Moore & Dalley pp. 1139-1142; Blumenfeld pp. 474-478)a. Function (s)

i. General Somatic Afferent (GSA) – Sensory fibers to the face, mouth, anterior two-thirds of the tongue, meninges, and nasal sinuses

ii. Special Visceral Efferent (SVE) – Motor fibers to muscles of mastication and tensor tympani in the ear

b. Anatomyi. Arises from the mid-pons, passes anterolaterally across the subarachnoid space, where

it forms a large ganglion just over the tip of the petrous bone; note that the trigeminal nuclei extend all the way into the upper cervical cord

ii. After the ganglion, the nerve divides into three branches1. V1 – Opthalmic branch (sensory only)

a. Passes through the cavernous sinus with CN IV, then enters the orbit through the superior orbital fissure

b. Branches run to the lacrimal gland, skin over the forehead and scalp, and sensory fibers to the cornea, medial eyelid, inner nose

2. V2 – Maxillary branch (sensory only)a. Passes through the inferior cavernous sinus, leaves the skull through

foramen rotundum, then enters the orbit through the inferior orbital fissure

b. Branches run to the skin of the maxillary region, teeth and bums of the upper jaw, upper lip, lower eyelid, and meninges. Two branches run to the sphenopalatine ganglion, which controls the secretion of the lacrimal gland

3. V3 – Mandibular branch (sensory and motor)a. One branch runs with CN VII to provide sensation to the auditory

meatus and tympanic membraneb. Other branches register sensation from the lower jaw, lower lip, lower

teeth, chin; and provide fibers to trigger salivation in the parotid, sublingual, and anterior lingual glands

c. Motor to the tensor tympani, mylohyoid, anterior digastric, and mastication muscles

c. Symptoms of dysfunctioni. Pain in one or more distributions of the nerve (trigeminal neuralgia, or tic doloreaux)

ii. Difficulty chewing, with mandible deviating ipsilateral to (toward) the lesioniii. Facial numbness, including loss of corneal reflex

d. Differential diagnosis of dysfunctioni. Trigeminal neuralgia may result from demyelinating lesion to the nerve as it exits the

mid-pons (as in multiple sclerosis), from herpes zoster, or from small vessels wrapping around and compressing the nerve

ii. Facial numbness and weakness of muscles of mastication may result from pontine stroke, trauma, tumors, herpes zoster, aneurysms, or meningeal infections

iii. Watch the associated symptoms; lesions of the spinal nucleus of the trigeminal nerve may present in conjunction with other spinal symptoms, including cervical spinal level, arm symptoms, etc.

e. Evaluationi. Corneal reflex (Afferent = CN V, Efferent = CN VII)

ii. Brainstem imaging (must be MRI; cannot use CT, which does not image the brainstem well because of artifact from nearby bone)

iii. Consider multiple sclerosis in cases of trigeminal neuralgia in younger people, especially women – to evaluate, perform MRI brain and cervical spine and spinal tap

VI. Cranial Nerve VI (abducens nerve) (Moore & Dalley, pp. 1142-1143; Blumenfeld, pp. 539-540)a. Function (s)

i. General Somatic Efferent (GSE) – Motor fibers to the lateral rectus muscle, which abducts the eye

b. Anatomyi. Leaves the brainstem at the pontomedullar junction, crosses the basilar artery in the

subarachnoid spaceii. Enters the dura over the clivus, bends over the petrous portion of the temporal bone,

then enters the cavernous sinusiii. Runs parallel to the internal carotid through the cavernous sinus, then enters the

posterior orbit and innervates the lateral rectus musclec. Symptoms of dysfunction

i. Double vision from inability to abduct the eye ipsilateral to the injured nerveii. At rest, the affected eye may deviate medially because of unopposed action of the

medial rectusd. Differential diagnosis of dysfunction

i. Isolated lesion of the abducens nerve from tumor or ischemic lesionii. Increased intracranial pressure causes the brain to compress the nerve as it passes over

the temporal bone; this compression is often bilateral, but not alwaysiii. Aneurysm of the Circle of Willis or the internal carotid in the cavernous sinusiv. Cavernous sinus thrombosis or tumor

e. Evaluationi. Vestibulo-ocular reflex or calorics (Afferent = CN VIII, Efferent = CN VI)

ii. Brain imaging (CT or MRI)

VIb. A special situation involving CN VI: Intranuclear opthalmoplegia (No discussion in Moore & Dalley; use Blumenfeld, p. 549)

A short tract connects the nucleus of CN VIII to the ipsilateral nucleus of CN VI. The medial longitudinal fasciculus (MLF) connects the nucleus of CN VI to the contralateral nucleus of CN III. Normally, when the head turns, CN VIII communicates with CN VI on the side away from the head turn so that CN VI tells the lateral rectus to hold the gaze by turning the eye laterally. At the same time, a signal travels from that CN VI (1) to suppress the movement of the contralateral CN VI and (2) through the MLF in the central midbrain to the contralateral CN III nucleus to tell the other eye to deviate medially.

In a lesion of the MLF, CN VI cannot communicate with CN III. As a result, the intact CN VI laterally deviates its eye, but the opposite eye does move past midline. The intact eye then develops nystagmus in lateral gaze, as if the eye is trying to recruit the other eye to move with it. This finding is called intranuclear opthalmoplegia. The lesion is in the MLF on the side of the eye that fails to medially deviate.

VII. Cranial Nerve VII (facial nerve) (Moore & Dalley, pp.1143-1146; Blumenfeld, pp.479-484)a. Function (s)

i. General Visceral Efferent (GVE) – Motor fibers to the muscles of facial expression, including platysma, frontalis, stapedius (dampens loud sounds), orbicularis

ii. General Somatic Afferent (GSA) – Sensation from the external auditory canal

iii. Special Visceral Afferent (SVA) – Taste from the anterior 2/3 of the tongueb. Anatomy

i. Both cerebral cortices supply fibers for the forehead to both facial nerve nuclei in the pons. The cerebral cortex supplies fibers for the cheek and jaw to only the contralateral facial nerve nucleus in the pons. (Text in Moore & Dalley, pp. 1143-1146; Illustration in Blumenfeld, p. 483)

ii. The nerve exits at the pontomedullary junction as a large motor nerve and a smaller intermediate nerve that carries sensory and parasympathetic fibers. The nerve passes across a long intraosseus course through the skull, sending off fibers to the chorda tympani (taste), stapedius muscle, and the greater petrosal nerve.

iii. The nerve exits the skull through the stylomastoid foramen and passes through the parotid gland, where it breaks into five major branches to the muscles of facial expression

1. Temporal TWO2. Zygomatic ZEBRAS3. Buccal BIT4. Marginal Mandibular MY5. Cervical CAT

c. Symptoms of dysfunctioni. This is the cranial nerve most likely to suffer injury

ii. Facial droop1. Upper motor neuron – droop of the nasolabial fold and lips contralateral to the

lesion, forehead spared2. Lower motor neuron – droop of the entire face ipsilateral to the lesion (Bell’s

palsy)iii. Loss of taste to the anterior 2/3 of the tongue (not usually evident clinically, as the other

side is typically functioning)iv. Hyperacusis ipsilateral to the lesion – hearing may be louder because the stapedius is

not dampening loud sounds in the inner eard. Differential diagnosis of dysfunction

i. Bell’s palsy1. Viral is most common cause2. Trauma3. Tumor, especially of the parotid gland

ii. Central lesion1. Stroke2. Tumor

e. Evaluationi. Corneal reflex (Afferent = CN V, Efferent = CN VII)

ii. Brain imaging (MRI is best to visualize the brainstem)

VIII. Cranial Nerve VIII (vestibulocochlear nerve) (Moore & Dalley, pp. 1146-1147; Blumenfeld, pp 484-494)a. Function (s)

i. Special Somatic Afferent (SSA) – Hearing through the cochlear portions of the nerveii. Special Sensory Afferent (SSA) – Fibers to the vestibular apparatus in the inner ear

b. Anatomyi. The nerve exits the upper medulla near the pontomedullary junction and extends

straight into the internal acoustic meatus, where it splits into the vestibular nerve to the vestibular apparatus and the cochlear nerve to the cochlea

c. Symptoms of dysfunctioni. Dysequilibrium, usually vertigo

ii. Loss of hearing – sensorineural deafnessd. Differential diagnosis of dysfunction

i. Vestibular schwannoma (a.k.a. acoustic neuroma) or cerebellopontine angle meningioma

ii. Ischemic damage to the nerveiii. Meniere’s diseaseiv. Brainstem strokev. Multiple sclerosis with lesion in the medulla

vi. Vascular anomaly or tumor in the medullae. Evaluation

i. Vestibulo-ocular reflex (Afferent = CN VIII, Efferent = CN IX)ii. Dix-Hallpike maneuver – have the patient lay backward quickly with the head turned 45

degrees toward the examiner; vestibular dysfunction will cause nystagmus within 1 minute after laying down with the head turned toward the malfunctioning nerve/ vestibular apparatus

iii. Electro- or video-nystagmogram – usually done by ENTs, a video or electronic measurement of nystagmus direction and intensity

iv. Brain imaging (CT or MRI) for vestibular schwannomav. Brain imaging (MRI is better) for brainstem stroke or MS

IX. Cranial Nerve IX (glossopharyngeal nerve) (Moore & Dalley, pp. 1147-1150; Blumenfeld, pp. 495-496)a. Function (s)

i. General Somatic Afferent (GSA) – Sensation from the posterior oropharynx, posterior 1/3 of the tongue, middle ear, and external auditory meatus

ii. Special Visceral Afferent (SVA) – Taste from the posterior 1/3 of the tongue and chemo- and baroreceptors of the carotd body

iii. Special Visceral Efferent (SVE) – Parasympathetic fibers to the parotid gland to mediate salivation

iv. General Visceral Efferent (GVE) – Motor fibers to stylopharyngeus muscleb. Anatomy

i. Nucleus in the upper medulla; fibers leave just inferior to the pontomedullary junction and leave the skull through the jugular foramen

ii. Fibers pass through the lesser petrosal nerve, synapse in the otic ganglion, and provide parasympathetics to the parotid gland

iii. Other fibers travel to their ultimate destinations in the tongue, carotid body, and eariv. Only muscle innervated by the glossopharyngeal is stylopharyngeus, which helps to

elevate the palatec. Symptoms of dysfunction

i. Lost sensation to the posterior oropharynxii. Glossopharyngeal neuralgia (intense, paroxysmal pain in the posterior oropharynx)

d. Differential diagnosis of dysfunctioni. Tumors near the jugular foramen, often in association with other cranial nerve palsies

ii. Deep neck injurye. Evaluation

i. Gag reflex (Afferent = CN IX, Efferent = CN X)ii. Brainstem imaging (MRI is best)

X. Cranial Nerve X (vagus nerve) (Moore & Dalley, pp. 1150-1151; Blumenfeld, pp. 496-498)a. Function (s)

i. Special Visceral Efferent (SVE) – Motor fibers to pharyngeal muscles (swallowing, gag reflex) and laryngeal muscles (voice box)

ii. General Visceral Efferent (GVE) – Parasympathetics to heart, lungs, and the upper GI tract (to the splenic flexure)

iii. General Somatic Afferent (GSA) – Sensation from pharynx, meninges, and a small area near the external auditory meatus

iv. Special Visceral Afferent (SVA) – Taste from epiglottis and pharynxv. General Visceral Afferent (GVA) – Chemo- and baroreceptors from the aortic arch

b. Anatomyi. Exits the brainstem from the upper medulla then enters the skull through the jugular

foramenii. After leaving the skull, this nerve spreads into fibers that go all over the place, including

oropharynx, aortic arch, GI tract, etc.c. Symptoms of dysfunction

i. Unusual to have a lesion just of the vagus nerveii. Palate droops on the side of the lesion, causing the uvula to deviate AWAY FROM the

lesion (uvula is drawn toward the normal side of the palate, which rises and pulls the uvula upward)

iii. Dysphagia (trouble swallowing)iv. Voice hoarseness due to laryngeal muscle weakness or recurrent laryngeal nerve injuryv. Aphonia (loss of voice) and inspiratory stridor

vi. Unusually, denervation of the heart results in resting tachycardiad. Differential diagnosis of dysfunction

i. Head and neck tumorsii. Neck surgery may traumatize the recurrent laryngeal nerve

iii. Thoracic surgery may traumatize the fibers of the vagus that travel to the heart and GI tract

e. Evaluationi. Clinical evaluation is best; very difficult to visualize this nerve in imaging or by other

methodsii. Valsalva maneuver and carotid body massage will produce bradycardia in a normally

functioning vagus nerve

XI. Cranial Nerve XI (spinal accessory nerve) (Moore & Dalley, pp.1151-1153; Blumenfeld, p. 499)a. Function (s)

i. Special Visceral Efferent (SVE) – Motor fibers to sternocleidomastoid and upper trapezius muscles to laterally rotate the head and elevate the shoulders (as in shoulder shrug)

b. Anatomyi. Arises from the upper cervical spinal cord, where the spinal accessory nucleus sits

between the horns of the spinal cord gray matterii. Fibers leave the nucleus and exit the lateral spinal cord just dorsal to the dentate

ligamentiii. After leaving the spinal cord, fibers ascend to leave the skull through the jugular

foramen and terminate in the sternocleidomastoid and upper trapezius musclesc. Symptoms of dysfunction

i. Inability to turn the head away from the lesionii. Inability to raise the shoulder on the side of the lesion

d. Differential diagnosis of dysfunctioni. Neck injury

ii. Jugular foramen tumore. Evaluation

i. Have the patient turn the chin into your hand (note: away from the side of the functioning sternocleidomastoid muscle and nerve); have the patient shrug the shoulders up against your hands

ii. Brainstem imaging (MRI is best)

XII. Cranial Nerve XII (hypoglossal nerve) (Moore & Dalley, pp. 1153-1154; Blumenfeld, pp. 499-500)a. Function (s)

i. General Somatic Efferent (GSE) – Motor fibers to the tongue intrinsic musclesb. Anatomy

i. Rootlets exit the ventral medulla and pass through the skull via the hypoglossal foramenc. Symptoms of dysfunction

i. Tongue deviation TOWARD the lesiond. Differential diagnosis of dysfunction

i. Neck injuryii. Skull base fracture

e. Evaluationi. Brainstem imaging (MRI is best)

ii. Skull base X-rays if trauma in the history

CCC22: Cephalgia without FeverFocus on DDX of Ha and medicines (not dosage)Most Has have a vascular origin.

Migraines (with and without aura)Designed to get your attention. Electrochemical/vascular problem

Diagnosis:*5 attacks lasting 4-72 hours with 2 of the 4 following characteristics:

Unilateral locationPulsating qualityModerate/severe intensity (inhibits daily activities)Aggravation by routine physical activities

*During HA, 1 of 2 must occur:Phonophobia/photophobiaNausea and/or vomiting

Migraine physiology:Some factor reaches a critical threshold neuronal depolarization from occipital lobe to frontal lobes (aura*Signals sent to Trigeminal nucleus = release of inflammatory factors producing vasodilation*trigeminal nucleus also stimulates thalamus = pain sensation signals to the cortex

Do not require further workup if:Neuro exam is normal, no change in frequency/severity/character, and within typical age range

Migraine Prevention:Antiepileptics (Valproic acid, topiramate, zonisamide, gabapentin, lamotrigine, levtiracetam)

Calm abnormal electric activity, use lower doses than you would for an epilepticBlood pressure meds (Propranolol, Verapamil)Vitamins/herbals (Mg, Riboflavin, Coenzyme Q10)

Antidepressants (Wellbutrin, any SSRIs, TCAs)

USE medicines AS SOON As HA starts!

Acute Migraine AttacksTreatment: IV, antiemetics, triptans, NSAIDs, isometheptene, muscle relaxants, other painkillers, narcotics

Tension HeadachesDiagnosis:

*Lasting 30 minutes to 7 days*At least 2 of the following:

Pressing/tightening qualityMild/mod intensity but does not prohibit activityB/L locationNo aggravation by routine physical activity

*Both of the following:No N/VPhoto/phonophobia are absent

Evaluation: PE, no imaging is useful

Pathophys:Tense muscles exert traction on lower meninges referred pain to frontal region B/LTension builds throughout the dayMechanical problem – meds do not work, require mechanical solutions

Cluster HeadachesDiagnosis:

*At least 5 attacks of severe unilateral orbital, supraorbital and/or temporal pain lasting 15-180 minutes untreated with one or more of the following signs occurring on the same side as the pain:

Conjunctival injection MiosisLacrimation PtosisNasal congestion eyelid edemaRhinorrhoeaForehead/facial sweating

*Frequency from one every other day to 8 per day

Eval: H & PTreatment: Prevention (Li, valproate, verapamil)

Acute: Oxygen, indomethacinRebound Headache

*Chronic, daily, can be worse than original headache, usually wake up with them in the morning*Due to analgesic overuse (triptans, *narcotics,* acetaminophen, NSAIDs, salicylates, caffeine

Treatment: start with a preventer, gently find other meds that they can take alternatively

Sinus Headaches – NOT a diagnosis anywhere but in the USUsually a migraine that causes nasal symptomsOnly acute, purulent sinusitis causes HA

Treatment: as for migraines + decongestant

Status Migrainosus - Debilitating migraine attack lasting for more than 72 hours, stuck in a migraine cycle

Diagnosis: Typical of previous attacks except for duration + Both of these (>72 hours, severe intensity) + no other disorders that could cause this

Someone you want to image, make sure they don’t have a fever.

Treatment: in or outpatient with “migraine breakers,” requires specific treatmentValproate, Robaxin, Solumedrol, Ergotamine, Topiramate, Combo of Aspirin, lorazepam,

diphenhydramine, and prochlorperazine

CCC23: Cerebrovascular Disease and StrokeFocus on localization, work-up and treatment, do not focus on stroke syndromes.

Stroke – vascular event leading to a focal brain injury lasting longer than 24 hours

80% ischemic (cardioembolic > lacunar > other) – part of brain lacks oxygen!Stenosis/occlusion of vessels due to atherosclerosis = large vessel disease

Atherothrombosis – thrombus along a vessel wall previously damaged by atherosclerosis, occur during/just after sleep when bp is low and flow is reduced

Embolism – from artery elsewhere (heart mc) and lodges at a bifurcation in the head, Abrupt onset fluctuating symptoms over 48 hoursOccur during activity, larger/more severe than thrombotic strokes

Hypovolemia/hypotension – reduced CO or hypovolemia = decreased perfusionEven without stenosis can cause a “watershed” infarctRisk factors: orthostasis, perioperative, hrt ischemia, arrythmias , stenosis

Vasospasm – resulting in focal hypoperfusion/focal tissue damageCaused by trauma, aneurysm rupture, certain drugs

Arterial dissectionIntracranial venous thrombosis – clot in draining veins of brain result in pressure buildup and

compression of surrounding tissues, could result in venous rupture/hemorrhagic strokeSmall vessel occlusive disease – occlude small penetrating arteries = lipohyalinosis related to HTN =

lacunar infarcts

20% HemorrhagicIntraparenchymal/intracerebralSubarachnoid hemorrhage – due to aneurysm rupture, AVM or trauma

Explosive Ha with alteration in consciousness, vomiting, stiff neck, feverComplications: hydrocephalus, arterial spasm, ischemia distal to rupture

Subdural hematoma – post blunt head trauma, due to tearing of bridging veins, slowly progressing symptomsEpidural hematoma – post sharp head trauma, tear in meningeal artery

Lucid interval, cerebral edema often develops

Stroke Diagnosis Mimics:Sudden onset of focal numbness/wkness HypoglycemiaDouble vision/visual loss TumorSpinning/vertigo SeizureSlurred speech, trouble speaking MS, encephalitisLimb/gait incoordination TraumaUnexplained, severe HA Hemorrhage

Evaluation:ABCs, IV fluids Neuro consultTreat hypoglycemia, hypoxia, hyperthermiaTrauma eval PT/PTT/INR/CBC/BMPCT for edema, hemorrhage r-tPA on standby (must be given within 1st 3 hrs)

Positive prognostic factors for acute episode:Younger age less severe deficitsNormal CT (CT without bleed/lg stroke) no diabetes or cardiac diseaseLow bp on admission

Positive prognostic factors for long term recovery:Young age small/rapidly improving deficitModifiable risk factors Early treatment

Treatment:GOAL = avoid stroke extension, protect from ischemic “penumbra - ” neural tissue that is rapidly killed in the

setting of vascular compromise

Normal saline, O2, regulate blood sugars/temperatureAspirin, Plavix or AggrenoxDo not lower bp unless >210/110, if you have to – lower it slowly

Early therapies: physical, occupational, speech/swallow = active or passive rehabilitation

Long term treatment: Aspirin ClopidogrelAspirin/extended release dipyridamole Anticoag with warfarin

Treatment (hemorrhage)Monitor closely for further bleeding/swelling may need neurosurgeryKeep bp <160/90 NO antiplatelets

Prevention:Treat risk factors (modifiable!)Meds: aspirin, plavix, aggrenox, warfarin (afib, valve disease, CHF, cardiac thrombus), statins

Pediatric StrokeIschemic strokes are deeper than corticalVascular occlusive lesions are intracranial vs. extracranialIntracerebral/subarachnoid hemorrhage are more common in kids than adults

TIA – vascular event leading to focal brain symptoms, not necessarily injuryLast less than 24 hours, resolve in about 1 hr

CCC24: Aphasias and Facial Nerve DisorderSDisorders of speech

Dysphonia – inability to vocalize due to laryngeal disorder/innervations problemDysarthria – lack motor control of speech organs = garbled speechAlexia – lose ability to read Agraphia – lose ability to write

Broca’s Aphasia/expressive/motor aphasiaBrodmann’s area 44 affected due to infarction, trauma, tumor, or infection

Nonfluent, reduced verbal output that is poorly articulated and takes a lot of effortMay or may not contain appropriate meaning, worse are sparseComprehension > verbal outputReading comprehension is ok, reading outloud is NOT, compromise in writing skills

Neuro Exam: R sided wkness/hyperreflexia with above speech deficits

Wernicke’s Aphasia/receptive/sensory aphasiaAuditory association cortex in the L temporal lobe due to infarction, trauma, tumor, infxn

Fluent verbal output but impaired comprehensionRapid empty speech devoid of meaning/fluent, well-articulated but meaninglessRepetition/naming impaired, writing is abnormal

2 varieties: comprehension of spoken worse than written vs. written worse than spoken

Neuro exam: Sensory loss, but mainly an unrevealing exam

Conduction AphasiaDifficulty in repetition and confrontational namingDisturbed writing

Global AphasiaAll Language functions are seriously impaired

Verbal output, comprehension of spoken/written language, repetition, naming, reading and writing Usually associated with hemiplegia, sensory deficits, visual field loss

Workup may include:CT LP CXR UA ABG

EKG D-dimer CBC ESR BMPCardiac enzymes glucose drug screen alcohol levelCoagulation panel

Bell’s Palsy – LMN lesions = affects one entire side of faceIdiopathic paralysis or paresis of half of the face involving CNVII distribution70-80% patients recover without treatmentViral prodrome in 60%

MC cause HSV infectionTx: Acyclovir and corticosteroids, prevent eyes from drying out

Neuro Exam: Asymmetric facial wkness, impaired hearing ipsilateralNumbness or pain of face/ear/tongueReduction in tearing/salivaEyelid may not close all the way

Supranuclear Facial Paresis – UMN lesions so wkness spares forehead on affected sideCauses: tumors, infarction, seizure, abscess

CCC25: Coma and EncephalopathiesConsciousness – a state of awareness of self and surroundings

Dependent on: intact Reticular activating system and both cerebral hemispheres 2 types of alterations in consciousness

Affect arousal – coma and encephalopathyAffect cognitive and affective mental function – dementia, delusion, psychiatric disorders

States of altered consciousnessAlert/awake – normal state of arousalLethargy – fatigued with minimal difficulty maintaining alertness

Stupor – mod reduction in alertness with decreased interest in environment, response to stimuliObtunded – unresponsive with arousal only to painful stimuliComatose – unresponsive to noxious stimuli

Glasgow Coma ScaleEye opening (4) 4 eyesVerbal response (5) Jackson 5Motor response (6) V6 motor

Examination of Comatose PatientVerbal response Eye openingSpontaneous eye moving Oculocephalic responses

Oculovestibular responses Respiratory patternMotor responses DTRs Tone

Pupillary ResponsesNormal – not a structural lesion of the CNS

Unilateral dilation – structural injuryB/L dilation unresponsive to light “fixed” – severe brain injuryB/l midposition unresponsive to light – midbrain injurySmall pinpoint pupils – medication effect or pons injury

Respiratory PatternsCheyne-Stokes – b/l hemisphere dysfxnCentral neurogenic hyperventilation – b/w midbrain/ponsApneustic breathing – pons dysfxnAtaxic breathing – medullary dysfxn, close to death!Coma with hyperventilation - metabolicComa with hypoventilation – drug OD, COPD

Response to pain:Purposeful Semi-purposefulRandom, non-purposeful DecorticateDecerebrate

Emergency AssessmentABCs

Stat labs (glucose, electrolytes, CVC, BUN, Cr, osmolality, ABG, LP, tox screen, LFTs, ammonia, coags, TSH, cortisol, AED levels, Bcx, UCx, EEG/SSEP)

Signs of Increased ICP/HerniationUnilateral dilated pupil or b/l small poorly reactive pupils3rd/6th nerve palsiesPapilledemaDeterioration in metal status, pupils or motor examWithdrawal to pain withdrawal to flexor (decorticate) extensor posturing (decerebrate)

Treatment of ICPHyperventilation reduces immediatelyMannitol Mannitol + FurosemideCase hyperosmolality with 3% NaCl

DDX of ComaMetabolic

Symmetric motor findings + small reactive pupilsAsterixis, myoclonus, tremor, and seizures are common

InfectiousCheck hx, fever, nuchal rigidity, kernigs, brudzinski, rash

Bacterial meningitis vs. Subarachnoid hemorrhage – check CT, but start empiric therapy and do an LP

Etiologys: VITAMIN D & EV – vascular D - drugsI – infectious &T – trauma and toxins E – endocrine/epilepsy/emotional

A – AnoxicM – metabolicI – iatrogenicM - neoplasm

Conditions that mimic comaLocked-in syndrome: quadriplegic with lower cranial nerve palsy, but completely alert/awarePersistent vegetative state: absent cognitive function but retained vegetative componentsCatatonia: mute, with marked decrease in motor activity

Prognosis of ComaCannot be predicted 100% unless patient is brain deadOnly about 15% in a nontraumatic coma make a satisfactory recoveryFunctional recovery is related to cause of coma

Worst: structural damageIntermediate: hypoxia-ischemiaBest: metabolic causes

Longer coma lasts, less like patient will regain independent functioning

Traumatic coma – do better than nontraumatic patients

EncephalopathyDiffuse cerebral dysfunction leading to alteration in cortical function and disturbance of consciousness ranging

from mild confusion to comaDysfunction in Reticular activating system or both hemispheres

Creutzfeldt-Jakob Disease – Seizures + massive incoordination + dementiaSporadic – MC form, normal prion protein in brain is changed to abnormalGenetic- inherited abnormal prion proteinIatrogenic – accidentally transmitted through medical procedures (Growth hormome in kids)

Toxins:Arsenic – rise in temp + Ha + vertigo + V + anxiety + seizures

Hyperexcitability lethargy coma deathLead

Kids: listlessness + confusion + ataxia coma, seizures, respiratory arrestAdults: sleep disturbance, loss of libidos, irritability, memory loss, delirium, coma

CO – DZ, Ha, N, impaired visionManganese – asthenia, anorexia, apathy, Has, personality changes

Diagnosis of exclusion

Anoxic/hypoxic/ischemicTypically occurs with cardiac arrest, is reversible if cardiac event is brief

Renal failureAcute – encephalopathy, tremor, myoclonus, seizures, eventual posturingChronic – mild confusion slowing progressing to dementia

Hepatic failure – liver’s inability to clear the blood leads to build up of toxins in the CNS

Pulmonary failure – Ha, somnolence, confusion, papilledema, asterixis, myoclonus, confusion, coma

Hypernatremia HTNHypocalcemia Hyponatremia

Wernicke’s – ataxia + confusion + opthalmoparesisNystagmus, 6th nerve palsy, horizontal gaze palsy, gait ataxia

Vitamin B12 – PNS complaints normally B6 deficiency – seen in general malnutritionDrug-inducedHypothyroidism/myxedema madness – coma, hypothermia, respiratory depression, areflexiaHyperglycemia – diabetic ketoacidosis and hyperosmolar non-ketotic hyperglycemia lead to impairedHypoglycemia – due to insulin overdose Epilepsy

CCC26: Spinal Cord Disorders Anatomy – from the atlas to L1 in adult, L3 at birth

31 pairs of spinal nervesGray matter in cord has dorsal/ventral horns (dorsa = sensory, ventral = motor)

Anterior horn – efferent motor neurons, LMN lesionPosterior horn – afferent sensory neurons, sensory deficits

Lateral horn – T1-L2 preganglionic sympathetic & S2-S4 of parasympathetic = auto dysfxnWhite matter in cord has ascending/descending tracts

Spinothalamic Tracts (course touch, pain/temperature)Posterior funiculus: fasiculis gracilis (upper limb) and faciculus cuneatus (upper limb)Spinocerebellar tracts (proprioception)

Major ascending tracts – sensory goes UPLateral spinothalamic = pain/temperatureSpinoreticulothalamic =poorly localized painVentral spinothalamic = light touchDorsal colum = discriminative touch/proprioception

Descending tracts – motor goes DOWNCorticospinal (pyramidal) – voluntary motor function, UMN lesion

Arises from contralat hemisphere, crosses in pyramids and descends

LMN syndrome: UMN Syndrome (everything up!):Flaccid weakness spastic weaknessDecreased tone increased toneDecreased DTR increased DTRS, + babinki’sProfound muscle atrophy minimal atrophyFasciculations no fasciculations

Syndromes:Complete spinal cord transaction

All motor, sensory, autonomic function is gone from below the site of lesion.DTRs increased and + babinski’s below lesion

Disease: Transverse myelopathyAcute, inflammatory process localized over several segments in the cord, functionally, transects

primarily demyelinates, could be asymmetricSymptoms progress over Occurs in trauma, tumor, MS, vascular disorders, herniated disks, parainfectious

*Sudden onset of wkness/sensory disturbance in legs/trunk is presenting feature. Paresthesia occurs firstEventually sphincter dysfunction occurs.

HemisectionLoss of pain/temperature contralateral to hemisectionIpsilateral loss of priorprioceptionIpsilateral spastic weaknessSegmental LMN and sensory signs at level of lesion

Disease: Brown-Sequard SyndromeOccurs with trauma or extrinsic compressiom (tumor, infectious mass)

Central Cord Syndrome (syringomyelia)Spinothalamic tract decussating fibers are compromised initially

Posterolateral column syndromes

L/o proprioception, vibration sense in legs with sensory ataxia and + Romberg’s signB/L corticospinal tract dysfunction = spasticity, hyperreflexia, b/l Babinski’s

Disease: Vitamin B12 deficiency, AIDS, HTLV, Cervical spondylosis, Tabes dorsalisSensory changes: paresthesias in feetLoss of propriocetion/vibrationPain/temp remain intact

Anterior Horn Cell syndromesDiffuse weakness, atrophy, fasciculation in muscles, tone reducedReflexes depressed or absentSensory tracts are spared

Diseases: variations of Spinal muscular atrophy (Werdnig-hoffman, intermediate, Kugelberg-welander, progressive SMA)

Diffuse weakness, atrophy, fasciculations. Reduced muscle tone, depressed DTRs

Combined anterior horn cell and pyramidal tract syndromesLMN + UMN signs

Diseases: ALSDegenerative changes in the anterior horn cell and the cortico-spinal tractDiffuse LMNs and UMN dysfunctions

Vascular SyndromeMost involve the anterior spinal artery or watershed areas

ASA supplies anterior 2/3 of the spinal cordASA – preservation of posterior column, l/o pain/temp, LMN signs early, UMN late, bladder/bowel incontinence

Disease: ASA infarctAbrupt onset, radicular or “girdle pain”Loss of motor function within minutes/hours below lesion Impaired bowel/bladder controlPreservation of the dorsal column (Posterior spinal arteries)

Other disorders:Conus medullaris lesions

Saddle anesthesia, urinary incontinenceCaused by trauma and infection

HIV/AIDSSelf Assessment Quizzes:

• HIV causes human disease primarily by disrupting the immune system and this is measured by what?– Measured by CD4 cell depletion

• How is the Diagnosis of AIDs made?– CD4 <200 or the presence of an AIDS deficing/complicating illness or cancer

• Does a patient with a CD4 cell count of 400/uL and an active TB infection with pneumonia have the Diagnosis of AIDS?

– YES• The average course of HIV infection is the median time to AIDS from diagnosis is 10 years. T or F

– True• The number of new HIV cases diagnosed since the 1990s is Increased? Decreased? Or Remained

Constant?– Remained constant

• The relationship of the US to the World in people living with AIDS is: 1.1 million compared to 36 million? 39.4 million? 73 million?

• Which is true?– The rapid test for HIV is 99% effective and is fully determinate of HIV.– The rapid test for HIV is 99% effective and requires a Western Blot to determine disease.

• Which is true?– An indeterminate test for 6 mos. means cross over antibodies rather than true HIV.– An indeterminate test means end stage disease when the humoral activity is waning.– Both of the above statements are true?–

Discern whether each statement below is true or false and what would make them a true statement if false:• It is as important to target the patients who have HIV for prevention strategies as to target those who are

HIV negative. TRUE• It is imperative to screen HIV positive patients for prior mental health problems. TRUE• It is not imperative to screen HIV positive patients regarding substance abuse as they already have the

disease. FALSE, it IS imperative• Pap smears should be obtained in patients who are HIV positive every three years FALSE – every 6

months• Immunizations should be avoided in patients with HIV due to immuno-compromised state and risk of

complication. FALSE – give new immunizations to pts• Hepatitis C risk is high (30-40 %) in patients with HIV, while Hepatitis B risk is low

(< 1 % ). FALSE, both are high• A fasting lipid profile and body fat assessment is important in HIV positive patients as when on retroviral

therapy both body fat and lipids tend to drop to very low levels. TRUE• A patient with prior treatment who returns for treatment after an interrupted treatment should be

screened as an initial visit plus have CD4, HIV RNA testing, and HIV resistance testing. TRUE• A little bit of treatment for HIV even if interrupted for some time is better than no treatment at all. TRUE•

The six most common opportunistic infections include?• Candidiasis, • Pneumocystis Jirovecci pneumonia, • CMV end organ disease, • Cryptococcosis, • Disseminated Mycobacterium Avium complex, and • Toxoplasmosis.

The most common malignancies now being seen in patients who are on long term therapy are?• Invasive SCC of the cervix, anus, and Chronic Hepatitis B or C.

The best prognostic information for HIV infected patients with Hepatitis B and Hepatitis C as far as their liver disease is?

• Liver biopsyThe best prognosis in patients with Hepatitis C and HIV is in patients with HCV genotypes 1 or 3?

• Liver biopsyA HIV infected patient who presents with diarrhea for greater than one month has a differential diagnosis of which opportunistic infections?

• Cryptosporiadosis A HIV infected patient who presents with a pneumonia has a differential diagnosis of which opportunistic infections and in what order?

• Pneumocystic carinii, Histoplasma, S. pneumo, H. influenzae A patient with long term HIV treatment for AIDS has become confused with some motor abnormalities as well. What is the differential diagnosis?

• Toxoplasmosis, Cryptococcal meningitis, HIV associated encephalopathy, multifocal leukoencephalopathy

Which of the following demand treatment?• CD4 of 200/uL or less• CD4 of 350/uL or less• Hepatitis C and CD4 of 350/uL• Chronic Salmonella with Septicemia and CD4 of 400/uL

True of False: Treatment regimens have become less complex offering several agents in one dose.

True of False? Since the advent of HAART, Metabolic lipid and glucose abnormalities are recognized in patients being treated for AIDS.

HAART involves a minimum of 3 drug regimen that includes which of the following (may have more than one):• 1 nucleoside analogue, one NNRT, and one Protease inhibitor• 2 nucleoside analogues and one NNRT• 2 nucleoside analogues and one Protease inhibitor• 2 nucleoside analogues, one NNRT and one Protease inhibitor• 2 nucleoside analogues, and two Protease inhibitors, such as lopinavir/ritonavir.

Which of the following are true?• Prior to HAART the mortality rate of AIDS was 100 %• HAART does not cure AIDS but does have the potential to fully suppress viral replication and allow for

adequate immune system recovery.• All AIDS patients eventually die from Cancer