neuromuscular

Question 1

weakness = Vague chief complaint; what hx qs

Answer 1

-Incorrect diagnosis of generalized weakness as high as 50% in ED

Historical questions should assess:
-Fatigue or true weakness (neuromuscular)?
-Associated symptoms? Fever, exposures, prodromal illness, level of consciousness, sensory abnormalities, cortical findings (aphasia, hemineglect, agnosia, gaze preference, visual deficit), muscle cramping, bowel or bladder sxs.
-PMH: Lifestyle/med changes, psychiatric conditions, comorbidities
-Distribution of weakness? Bilateral vs unilateral. Upper vs lower. Monoradicular. Myotomal. Ocular (diplopia, ptosis), bulbar (voice change).
-Pattern? Proximal vs distal. Fluctuating weakness.

Duration of weakness?
-Acute (seconds to minutes): CVA, ICH, hypoglycemia, poisoning, spinal cord syndromes, periodic paralysis.
-Subacute (hours to days):Botulism, tetanus, Myasthenia gravis crisis, GBS, transverse myelitis, electrolytes (hypokalemia, hyponatremia), conversion disorder
-Chronic (weeks to months): Amyotrophic lateral sclerosis, psychiatric disorders (e.g. depression)

Question 2

motor pathway (a review) CORTICOSPINAL and CORTICOBULBAR

Answer 2

CORTICOSPINAL TRACT (PRYRAMIDAL TRACT)
-Upper motor neuroncell bodies lie in themotor cortex(within the precentral gyrus).
-Their axons travel in the subcortical white matter within the posterior limb of the internal capsule.
-They run through the cerebral peduncles into the ventral/anterior brainstem.
-They cross (decussate) at the junction of the medulla and the cervical spinal cord.
-They run down the posterolateral spinal cord.
-Finally, upper motor neuron axons synapse ontolower motor nerveswithin the anterior horn of the spinal cord grey matter

CORTICOBULBAR TRACT
-Primarily involved in carrying the motor function of the non-oculomotor cranial nerves (e.g. cranial nerves V, VII, IX, XII, and motor region of cranial nerve X.)
-The corticobulbar tract originates in the primary motor cortex of frontal lobe, just superior to the lateral fissure and rostral to the central sulcus in the precentral gyrus.
-It descends via corona radiata and genue of internal capsule with a few fibers in the posterior limb of internal capsule.
-In the midbrain the internal capsule becomes the cerebral peduncle.
-The corticobulbar fibers exit at the appropriate level of the brainstem to synapse on the lower motor neurons of the cranial nerves ( V, VII, IX, XII, the motor regions of cranial nerve X in the nucleus ambiguus.)
-The corticobulbar tract innervates cranial motor nuclei bilaterally with the exception of the lower facial nuclei (which innervates facial muscles below the eyes) and the genioglossus muscle, which are innervated only unilaterally by the contralateral cortex

Question 3

localizing weakness: UMN vs LMB

Answer 3

-LMN- peripheral nerves
-pronator drift- stroke
-hoffman sign- when you flick middle finger the pointer and thumb come together

Question 4

motor weakness: neuropathy vs myopathy vs NMJ disorder

Answer 4

Question 5

cerebral palsy overview and comorbidities

Answer 5

def: a group of permanent NON PROGRESSIVE neurologic disorders that affects pts ability to move and maintain balance and posture.
-MC motor disability in children
-injury during development of baby’s brain up to 3 years of age
-1.5 to 2.5 per 1000 live births - quite common
-Usually dx in first 2 years of life
-Symptomatology varies person to person
-There is NO cure, but there IS tx

Several co-morbidities:
- epilepsy (35-50%)*
- intellectual disability (30-50%)*
- others: feeding difficulties, visual abnormalities, hearing abnormalities, communication difficulties
-a motor problem! -> dont assume intellectual disability

Question 6

cerebral palsy risk factors

Answer 6

IDIOPATHIC

Prenatal:
-PREMATURITY MC*
-Low birth weight!
-Multiple gestations
-Intrauterine growth restrictions (IUGR)
-Maternal substance abuse
-Congenital brain malformations
-Intrauterine infections (TORCH)
-Intrauterine stroke
-Chromosomal abnormalities
-Radiation exposure

perinatal:
-Hypoxic-ischemic insults
-Central nervous system (CNS) infections
-Stroke
-Kernicterus: high bilirubin in babies

postnatal:
-Accidental and non-accidental trauma
-CNS infections
-Stroke
-Anoxic insults

Question 7

cerebral palsy hx and PE

Answer 7

History:
-Birth and prenatal history
-Slow reaching of development milestones
-Delayed MOTOR development (not regression)
-Poor feeding, poor sleeping
-Difficult to handle / cuddle
-Possible seizures or epilepsy

Physical exam:
-Micro or macro-cephaly
-Excessive irritability or diminished interaction
-Hyper or hypo- tonia (poor head control, back arching)
-Muscle weakness, spasticity, dystonia (inability to sit up at 8 months, abnormal posture)
-Persistent primitive reflexes
-if baby is only using one hand (they normally dont have preference) -> it may suggest the other hand is weak

Question 8

cerebral palsy classification

Answer 8

Spastic: MC, 75%
-Affected area: Brain cortex UMNs
-Movements are stiff and jerky
- SCISSOR gait or TOE WALKING
-↑ Tone, ↑ deep tendon reflex, +Babinski

Non-spastic types: abnormal involuntary movements that worsen with stress and stop with sleep

Dyskinetic ~20%:
-Affected area: Central brain esp BASAL GANGLIA
-Excessive involuntary movements leading to poor coordination and body posture
-can be assoc with Kernicterus- high bilirubin

Ataxic ~5%:
-Affected area: Cerebellum
-Balance problems, incoordination, intention tremors, hypotonia
-trouble sitting up right, hand to nose test failure

Mixed

Question 9

cerebral palsy dx

Answer 9

clinical dx:
-Serial examinations! of motor development
-Infectious Work-up (ToRCHS titers)
- Toxo is MC- cats, syphilis is up and coming
-Metabolic or genetic testing may be considered
-EEG – if seizures suspected
-Screen for: ID, ophthalmologic abnormalities, hearing/speech/language impairment, growth failure

Diagnostic imaging to detect causative lesions
-MRI brain- to r/o other stuff
-Cranial ultrasounds: intracerebral hemorrhage, structural abnormalities, hypoxic/ischemic injuries -> fontanelles arnt closed yet
-Specify subtype after 18-24 mo

Question 10

cerebral palsy management

Answer 10

Goal -> maximizing pt independence and treating symptoms
-Durable medical Equipment: motorized wheelchairs, communication systems, voice-activated computers, etc.

Treatment of spasticity, dystonia, other orthopedic issues
-OT/PT, orthotics, standers, braces, seating systems, medications, etc.
-Generalized spasticity: PO Baclofen or Benzos (First line)
-Localized spasticity: Botox injections
-Pain control
-Sleeping modalities

• Management of seizures (if present)
  -Vision and/or hearing impairment treatments
  -Speech/language therapy
  -Regular feeding/nutritional status assessments, monitor growth
  -Treat GI symptoms (dysmotility, constipation, GERD), respiratory problems (recurrent aspiration, lung disease, OSA,laryngomalacia), sialorrhea (excess drooling)
  -Preventive measures to prevent skin breakdown/ulcers – repositioning, pressure support devices, skin care
  -Manage urinary function, sleep problems, and recognize and treat pain

Question 11

34 year old female with no PMH
C/O L eye blurry vision and diplopia
On history, she also reports intermittent episodes of numbness and weakness that occur from her chest downwards, these began several years ago. Each episode lasted a few weeks.
Your motor and sensory exam is normal,
Your eye exam is abnormal showing internuclear ophthalmoplegia (see video)
With these intermittent neurologic symptoms and ocular findings, what is the likely diagnosis, and what is your next step in evaluation?

Answer 11

INO: cant adduct in - CN III
* But can still do convergence
-cant actively adduct the eye

MULTIPLE SCLEROSIS: ONLY INVOLVES UMN

Question 12

multiple sclerosis: definition, ethiology, epidemiology

Answer 12

Def: Autoimmune, inflammatory disease that causes demyelination of the CNS (oligodendrocytes), with degeneration of !white and gray! matter of the !brain, optic nerves, and spinal cord
-affects the UMN
-sends distorted messages
-Severe disability within 20-25 years in half 25% of patients
-shortens life span by about 7 years

Etiology is unknown
-Genetic predisposition: HLA-DRB1*15
-Environmental risk factors: Low vit D, cigarette smoking

Epidemiology:
-Caucasians and black population
-Young adults 20-40 yr
-FEMALE > Male (3:1)

Question 13

MS pathophysiology

Answer 13

Pathophysiology not completely understood:
-Autoimmune inflammation, demyelination, axonal degeneration
-Common theory: Activation of T-lymphocytes -> inflammatory process -> focal demyelination with preservation of axons (plaques/scarring) -> loss of axons and atrophy of oligodendrocytes (chronic plaques) -> gliosis -> inadequate remyelination
-we see plaques and scars on MRI
-symptoms come and go and keep getting worse

Question 14

MS: definitions of exacerbation, remission, pseudorelapse

Answer 14

MS exacerbation - attack, relapse, flare:
- New or significant worsening symptoms of CNS demyelination ≥24 hrs

Remission: Period of recovery after exacerbation in which clinical sxs resolve or mostly resolve

Pseudorelapse: Recurrence or significant worsening due to stressors (infection, heat)

Question 15

MS classifcations

Answer 15

MC = relapsing-remitting- episodic exacerbations - 80-90%
-with time the damage builds up

secondary progressive
- relapse remitting that becomes progressive- 50%
-you had relapsing-remitting, now there is constant inflammation with flares

primary progressive disease
- decline without acute exacerbations- 10%
-no exacerbations but keeps getting worse

Question 16

MS clinical features overview

Answer 16

General features:
- sx last > 24 hr duration
- Frequency of episodes ~ 1 per year
- FATIGUE (85%), headache
-OPTIC NEURITIS is a classic finding: MC and specific + often the first sign (30%)

Internuclear ophthalmoplegia [INO]:
-Diplopia with lateral gaze due to weak medial rectus (but intact convergence)
-Due to lesion of the medial longitudinal fasciculus (MLF)
- ipsilateral cant adduct and contralateral abducting nystagmus

Cerebellar involvement: poor postural control (ataxia), imbalance, gait dysfunction, scanning speech, nystagmus, intention tremors, pronator drift

Demyelination of spinal cord tracts symptoms

Cranial nerve palsies:
-Trigeminal neuralgia (unilateral > bilateral)
-Diplopia, facial palsies

Autonomic dysfunction- Bladder, bowel incontinence or sexual dysfunction (impotence)

UTHOFFs phenomenon: symptoms worsen in HEAT

Question 17

MS: demyelination of spinal cord tracts

Answer 17

-LHERMITTEs sign: neck flexion causes lightning shock-like pain down the spine
-UMN: weakness, hyperreflexia, spasticity, Babinski
-Dorsal spinal column: loss of vibration and fine touch sensation, numbness, paresthesia’s, ataxia
-Neuropathic pain: Numbness, paresthesia’s, proprioception, temperature changes

Question 18

MS optic neuritis sx and description

Answer 18

-Optic neuritis! is a classic finding- MC and specific
-1st sign in up to 30% of MS
-Unilateral eye pain
-Worse with eye movements
-optic nerve is SENSORY
-Monocular vision loss and color blindness (esp RED)- dull colors
-Relative afferent pupillary defect (RAPD) aka Marcus gunn pupil – Delayed conduction of a swinging light to affected optic nerve causing pupil dilation -> she said just know these things exist

Question 19

Other differentials for optic neuritis include:

Answer 19

-Infection (lyme, herpes, syphilis)
-Autoimmune disorders (SLE, Sarcoid)
-Methanol poisoning
-B12 deficiency
-Diabetes

Question 20

MS dx criteria

Answer 20

Clinical diagnosis of exclusion. Episodes must be separated by “time and space”:
-≥ 1 objective and unprovoked clinical episode lasting >24h
-Time: 2nd clinical episode or new lesion on follow up MRI
-Space: Multifocal symptoms or multiple CNS lesions on MRI (different areas of your brain affected )
-Exclude mimics
-McDonald Criteria on MDCALC (dont need to know)
- Want repeat imaging the plaques can come and go -> resolves and pops up somewhere else until scar tissue is permanent

Question 21

MS testing/workup

Answer 21

Testing: MRI brain ± spinal cord w/ GADOLINIUM: test of choice*
-Multiple sclerotic plaques (T2 hyper densities)
-MC location: periventricular white matter
-Can have DAWSON fingers: finger-like radial extensions
-contrast enhanced active lesions often resolve after 2-8 weeks

Additional studies for differentials:
-CSF analysis: ↑ IgG (oligoclonal bands) – nonspecific, inflammatory, Exclude infectious pathology
-Visual evoked potentials -Slowed optic nerve conduction

Lab studies:
-CBC, B12, TSH, ANA, Lyme, RPR (syphilis), HIV, MMA

Question 22

MS tx:

Answer 22

-All pts should be referred to a neurologist for specialized management

Acute exacerbations:
-!!!!High dose IV/PO steroids x 3-5 days -> increases sugar so control this for diabetics, GI upset (consider PPI)
-Immune modulators (cyclosphamide)
-Plasmapheresis

Disease modifying treatments (DMT) :
-Beta-interferon (immunomodulator)
-Glatiramer acetate
-Monoclonal antibodies: Ocrelizumab or natalizumab

Symptom directed treatment:
-!Amantadine! for fatigue
-Botox for spasticity
-Ditropan for bladder dysfunction
-Antidepressants for pain
-Team based therapy

Other long term management:
-Life style modification (smoking cessation, exercise)
-Manage comorbidities
-Vitamin D supplementation

Question 23

amyotrophic lateral sclerosis/ Lou Gehrig’s disease definition/overview and pathophysiology, life expectancy

Answer 23

Def:
-Neurodegenerative disease of BOTH upper AND lower motor neurons!
-Entirely MOTOR
-Gradually lose the ability to initiate and control voluntary movements
-eventually affects breathing

Idiopathic:
-Smoking is a risk factor
-Insidious and progressive
-Will lead to eventual paralysis and death
-Most will die within 3-5 years from onset of symptoms***
-No cure

Question 24

ALS epidemiology

Answer 24

-2-3 per 100,000 per year (5600 new cases in US every year)
-M>F
-Caucasians
-Age of onset 40-70 years (mean 65 years)
-90-95% are sporadic, 5-10% are familial
-Most will die within 3-5 years from onset of symptoms***

Question 25

ALS symptoms: what is the MC presenting sx

Answer 25

most defining feature: insidiously progressive motor degeneration

Symptoms:
- Asymmetric limb weakness (80%) MC presentation!! -> dropping things, tripping
-Distal to proximal loss (stocking-glove weakness) **
-Hand/arm/shoulder weakness, cramping, fatigue, stiffening, pain **
-Leg weakness causing foot drop, stumbling, limping, change in gait **
-Bulbar symptoms: Dysarthria (speaking), dysphagia (swallowing), hoarseness, CHEWING -> aspiration
-Pseudobulbar affect syndrome (PBA)- inappropriate emotional reactions, laughing out loud at bad news
-Autonomic symptoms: constipation, urgency, early satiety bloating

Question 26

ALS: how does weakness spread on body and what sx are absent

Answer 26

Weakness: neuropathic - distal then proximal
- initially spreads within a segment: One arm, then other arm, then ipsilateral leg, then other leg, then bulbar muscles

ABSENCE of pain, sensory loss, sphincter dysfunction, ptosis, or extraocular nerve or muscle dysfunction.
-Sensory symptoms may occur in 20% of patients with ALS (tingling), but the sensory examination is usually normal
- Bowel and bladder and extraocular muscles tend to be conserved (unlike MG…)

Question 27

ALS PE

Answer 27

PE:
-Generalized limb weakness (more than truncal) with gait abnormalities

UMN symptoms (70-80%):
-!Weakness, hyperreflexia, spasticity,Primitive reflexes (esp Babinski), hypertonia, Clasp knife reflex, pronator drift

LMN symptoms (70-80%):
-Weakness, atrophy (reduced muscle bulk and tone),fasciculations, hypotonia, hyporeflexia

Cranial nerves (10-20%):
-Dysarthria, Hoarseness of voice (CN X), Dysphagia/choking (CN X,XII)

Pseudobulbar affect: Inappropriate and involuntary crying, laughing

Bowel and bladder and extraocular muscles tend to be conserved (unlike MG…)

Late signs: muscle atrophy, hyporeflexia, babinski positive, spasticity, weight loss, choking, respiratory failure

Question 28

Mixed findings of UMN and LMN: think what ds

Answer 28

ALS!!!!

Question 29

ALS dx

Answer 29

-No single test and rule in or rule out

Clinical dx:
- supported by its progressive, unrelenting course, and co-existing UMN/LMN signs.

Criteria: (she didnt go over in class)
-Evidence of LMN degeneration by clinical, electrophysiological, or neuropathological examination.
-Evidence of UMN degeneration by clinical examination.
-Progressive spread of symptoms or signs within a region or to other regions, as determined by history or examination.
-AND Neuroimaging and labs exclude other causes

Question 30

ALS: EMG and NCS

Answer 30

Electromyography (EMG): features of acute and chronic denervation and reinnervation:
-Acute denervation: fibrillations and positive sharp waves
-Chronic denervation and reinnervation: large amplitude, long duration, complex motor unit action potentials (MUAPs).
-Fasciculations are considered indicative of an acute or ongoing denervation in muscles demonstrating evidence of chronic denervation

Nerve conduction Study (NCS): Sensory and motor nerve conduction studies usually normal

Question 31

ALS lab work and imaging

Answer 31

Lab work:
- CPK (may be elevated)
- calcium (rarely associated with hyperparathyroidism)
- serum protein electrophoresis with immunofixation, and urine protein electrophoresis with immunofixation (rare association with myeloma and lymphoma)
- Lyme titers, thyroid panel

Neuroimaging to r/o other causes:

Bedside swallow test:
-done by speech language pathologist
-Dysphagia test
-Positive if patient cannot drink continuously or coughs after swallowing test
-Positive tests require dietary modifications

Question 32

ALS diff dx

Answer 32

Spinal muscle atrophy (SMA): LMN only
Primary lateral sclerosis (PLS): UMN only
Cervical spondylosis: Spinous degenerative changes that irritate nerve roots
Stroke: Acute onset weakness localized to one side , risk factors
Guillain Barre: Younger patients, also LMN disorder due to autoimmune cause, acute onset of ascending paralysis
Myasthenia gravis: Acute onset, extraocular symptoms, smaller muscles more affected, worsens throughout day then improves with rest (ALS never improves)
Polio (Poliomyelitis): asymmetric flaccid paralysis, CSF will reveal polio virus
Thyrotoxicosis: Muscle pain and weakness, tremors, hyperreflexia

Question 33

ALS tx

Answer 33

Always refer to an ALS clinic for integrated services!!

Treatment: 3-5 yr life expectancy…
- supportive
- RILUZOLE: ONLY medication shown to increase survival in patients with ALS (~6 months)
- Inhibits glutamate release decreases glutamate excitotoxicity
-Prolongs survival and slows function decline ~3 months
-Muscle relaxers: cramps and spasticity (Baclofen, Zanaflex)
-Dextromethorphan/quinidin: pseudobulbar affect
-Palliative care consult: DNR/DNI status, living will etc.

Question 34

A 50 year old carpenter presents with progressive weakness of his right hand that is affecting his job. He is right hand dominant, otherwise healthy. Unable to lift his hammer for long on many days.
Right hand grip strength 3/5 - UMN
Right leg with spasticity and increased tone - UMN
Right biceps reflex 1+ - LMN
Left triceps reflex 1+ - LMN
R patellar reflex 4+ - UMN

Answer 34

Right hand grip strength 3/5 - UMN
Right leg with spasticity and increased tone - UMN
Right biceps reflex 1+ - LMN
Left triceps reflex 1+ - LMN
R patellar reflex 4+ - UMN
-UMN-
-LMN

Question 35

A 39-year-old female with no significant medical history presents with complaint of weakness. Symptoms have been present for the past three weeks. She describes difficulty climbing stairs and frequently has to take breaks before continuing. She reports that over the past 24 hours, she has been experiencing double vision when watching television and difficulty chewing.
Vital signs: T 98.8°F, HR 72, BP 136/78, RR 22, O2sat 97% on room air.
Physical Exam: The patient appears fatigued but is not in any distress. Breath sounds slightly diminished but otherwise clear. Upper and lower extremity strength is 3/5 bilaterally and weakness seems to worsen as the exam continues. Reflexes and sensation are normal. She has left eye ptosis and a deconjugate gaze.

Answer 35

Vital signs: T 98.8°F, HR 72, BP 136/78, RR 22, O2sat 97% on room air.
Physical Exam: The patient appears fatigued but is not in any distress. Breath sounds slightly diminished but otherwise clear. Upper and lower extremity strength is 3/5 bilaterally and weakness seems to worsen as the exam continues. Reflexes and sensation are normal. She has left eye ptosis and a deconjugate gaze.
myasthenia gravis
-proximal weakness- stair require quads
-3 weeks is a long time
-fatigue
-weak and worsens with exam

Question 36

myasthenia gravis (MG): definition, prevalence, epidemiology

Answer 36

Def: Autoantibodies that bind and destroy neuromuscular communication at the neuromuscular junction (NMJ)
-no contraction -> weak
-MC disorder of NEUROMUSCULAR transmission

Epidemiology: Can be associated with:
-usually autoimmune
-THYMOMA 10-15%!!!!
-Other autoimmune diseases (e.g., hashimotos, sarcoidosis, hyperthyroidism, lupus, rheumatoid arthritis, polymyositis).
-Lymphoma
-Bimodal distribution : 20-40s (F>M), 40-70s (M>F)

Question 37

myasthenia gravis (MG) pathophysiology

Answer 37

-B cells produce autoantibodies which
-Bind to Acetylcholine (ACHr) NICOTINIC postsynaptic receptors(80-90%) on SKELETAL muscle which impairs muscle function
-Rarer seronegative type will has no ACHr antibodies, but may have muscle-specific tyrosine kinase antibodies (MuSK)
-!!!Repeated muscle use = increased skeletal muscle weakness/fatigue (improves with rest)!!!!!!!**

Question 38

MG: complication: def, causes, treatment

Answer 38

Myasthenic crisis!!!!
-Rare, Life threatening condition
-Extreme weakness causing respiratory failure requiring mechanical ventilation
-Affects up to 20% of patients with MG, usually in first 3 years
-Triggered by infections, medications, electrolyte derangements, surgery or poor tapering of immunosuppressants etc.

Rapid sequence intubation may require dosing adjustments:
-Increase dose of depolarizing neuromuscular blockers (succinylcholine)
-Decrease dose of non-depolarizing neuromuscular blockers (rocuronium)
-Don’t memorize this!^

TX: High dose steroids PLUS either Plasma exchange or IVIG

Question 39

MG signs and symptoms

Answer 39

Ocular involvement is the most common initial symptom:
-Ptosis more noticeable with upward gaze!!!!!!!!!!!!!!!!!!
-Diplopia due to extraocular muscle weakness
-No pupil involvement, can be unilateral > bilateral

Fluctuating asymmetric muscle weakness over the first few years worsens with use, improves with rest!!
-by the end of the day there is weakness
-Proximal muscle weakness > distal! ( -> Myopathy: bigger muscles first - shoulder, glutes, thighs )
-Arms > Legs!
-Head drop!

Generalized type:
- Ocular sx
- bulbar (dysarthria, dysphagia, jaw weakness, hypophonia), facial, limb, respiratory
-No sensation or reflex involvement (severe weakness can cause ↓ DTR in late stages)

Question 40

MG evaluation: imaging and labs

Answer 40

Always do CT: CHECK FOR THYMOMA
- Tx: remove thymoma

Labs:
-!!+ Acetylcholine receptor antibodies (anti-AChR) specific
-!!!+ Muscle specific receptor tyrosine kinase antibodies (anti-MuSK)

Tests:
- ice pack test: ptosis improves in 2-5 mins
- edrophonium test (ACh inhibitor ) sx willl improve with it; discontinued by FDA
- repetitive nerve stimuation: decreased amplicated with repeated stimulation**
- single fiber EMG: jitter, more sensitive than EMG

Question 41

MG dx

Answer 41

Edrophonium (Tensilon) test:
-Edrophonium = Acetylcholinesterase inhibitor with rapid onset, short acting
-Prolongs Ach Prescence in the NMJ causing marked improvement
-Can improve weakness in other diseases… ALS, poliomyelitis etc. so it was discontinued by the FDA
-SE- SLUGE

Ice pack test
-Place ice on eyelid with ptosis for 2-5 minutes and see improvement

Routine EMG usually normal
-Single fiber EMG will show “jitter” and is more sensitive

Repetitive nerve stimulation (RNS) : decreased amplitude with repeated stimulations

Question 42

MG tx

Answer 42

Acetylcholinesterase inhibitors prolong Ach action in NMJ
-!!!PYRIDOSTIGMINE 1st line, Neostigmine
-S/E: abd pain, diarrhea, cholinergic crisis (SLUDGE)

Steroids (also most effective for ocular MG)

Immunomodulating agents to decrease antibody production (Azathioprine)

Surgery: Thymectomy

Myasthenic crisis: IVIG and/or plasmapheresis

Question 43

MG: drugs to avoid in pts

Answer 43

main ones highlighted:
- abx:Aminoglycosides, fluoroquinolones, MACROLIDES
- iodinated radiocontrast dye: can cause myasthenis crisis

-those that affect neuromuscular function
-1. Anticonvulsants: Phenytoin , ethosuximide, magnesium sulfate, barbiturates, lithium.
-!!!!!!!2. Antibiotics: Aminoglycosides, fluoroquinolones, MACROLIDES
-3. Cardiovascular: Beta blockers, quinidine, lidocaine, procainamide, verapamil, statins.
-4. Steroids: are standard treatment for myasthenia, but may cause transient worsening during the first two weeks.
-!!!!!!!!!5. Iodinated radiocontrast dye- myasthenic crisis****
-6. Chloroquine and hydroxychloroquine.
-!!!!!!!!!!7. Botulinum toxin
-8. Desferrioxamine
-9. D-penicillamine
-10. Succinylcholine
-11. Thyroid replacement therapy
-12. Narcotic analgesics
-13. Psychotropics: Haloperidol, lithium, amitriptyline.
-14. Eye drops: Timolol, echothiophate

Question 44

lambert-eaton myasthenic syndrome (LEMS) definition and association

Answer 44

Autoimmune disorder affecting the neuromuscular junction
-Affects the voltage-gatedcalciumchannels(VGCC) at thepresynaptic membrane = ↓ ACH release

Strong association with:
- small cell lung carcinoma- Paraneoplastic syndromes!!!!!!!
-Also other autoimmune disorders such as Hashimoto’s thyroiditis and DM1
-Rare with prevalence of 2.8 per million persons

Question 45

LEMS- sx and presentation of muscle weakness

Answer 45

Symmetrical PROXIMAL MUSCLE WEAKNES
-Slow, progressive
-(Paraneoplastic LEMS may have more rapid progression)
-Achy, stiff muscles, fatigue, cramping
-Lower extremities more commonly involved
-Shoulder hips thighs
-Difficult to rise out of a chair or climb stairs
-Deep tendon reflexes (DTRs) are decreased (hyporeflexia) or, more rarely, absent (areflexia).

Post-exercise facilitation:
-!Warming up phenomenon: DTRs and muscle strength improve with brief, vigorous muscle activation****
- Lambert’s sign: Grip becomes more powerful on repeated evaluation of muscle strength
-symptoms get better with use
-Important note: absence of sensory symptoms/findings

Question 46

LEMS: bulbar involvement, autonomic dysfunction, respiratory failure (she didnt read these points in class)

Answer 46

bulbar involvement:
-not as common or severe as inMG
-Ptosisandophthalmoplegia
-Diplopia, Dysphagia, Dysarthria
-Difficulty chewing

Autonomic dysfunction:
-Dry mouth
-Sluggish pupillary response (symmetrical)
-Blurred vision
-Impaired sweating
-Erectile dysfunctionin men
-Orthostatichypertension
-Constipation

respiratory failure:
-Respiratory weakness is mild to moderate in LEMS.
-Respiratory failure is rare and only occurs in progressed disease.
-Associated with increased mortality

Question 47

LEMS dx and tx

Answer 47

-DDX: Inflammatory muscle diseases such as polymyositis, dermatomyositis

Diagnosis:
-Anti-VGCC antibodies
-Electrodiagnostic testing (NCS, EMG)
-Chest CT to look for SCLC

Treatment:
-If SCLC -> treat the malignancy
-If no cancer: treat inflammatory process
-Steroids
-Pyridostigmine- ↑ Ach availability
-IV immunoglobulin therapy– Binds and neutralizes the auto antibodies
-Plasmapheresis

Question 48

A 42-year-old man with a history of subcutaneous heroin use presented to the hospital with slurred speech, diplopia, and dysphagia. The physical examination showed bilateral ptosis (Picture A), a sluggish pupillary response to light, bilateral sixth-cranial-nerve palsies, and multiple skin abscesses on his arms and legs. Shortly after admission, the dysphagia progressed, necessitating intubation for airway protection. Single-fiber electromyography suggested a disorder of neuromuscular transmission, and a clinical diagnosis of wound botulism was made. He received empirical treatment with equine serum trivalent botulism antitoxin and antimicrobial therapy, and the abscesses were surgically debrided (Picture B). Subsequently, botulinum toxin was detected . . .

Answer 48

wound botulism

Question 49

botulism definition

Answer 49

-Botulism is a toxin-mediated NMJ disorder that causes !acute weakness! leading to respiratory failure!
-Caused by toxins from !clostridium botulinum bacteria, rare but fatal!
-doesnt let Ach out of nerve -> weakness
-Since botulinum toxin is a protein, it doesn’t penetrate the CNS
-spores - harder to treat

Question 50

botulism epidemiology

Answer 50

Food botulism (preformed toxin in food, MCC in adults):
-home-canned food (boiling without pressure-cooking kills most bacteria, but not C. botulinum spores)
-fermented fish or seal meat, seal oil, and alcohol made from potatoes in prisons.
-Incubation period: Clinical botulism typically occurs ~12-36 hours after ingestion (although onset may be earlier, or delayed for up to ten days).

Wound botulism
-subcutaneous injection of black tar heroin, or from severe trauma (e.g., extremity crush injury).
-Incubation period: Botulism may not occur for days or weeks after wound infection
-no GI symptoms bc not ingested

Iatrogenic botulism may result from use of excessive doses of commercial botulinum toxin (e.g., for cosmetic procedures)
-dont give to kids < 1 yo

Question 51

botulism clinical presentation

Answer 51

Descending symmetric flaccid paralysis:
-Paralysis almost always starts with cranial nerve involvement (e.g. ptosis, diplopia, dysarthria, dysphagia, facial weakness, PUPIL INVOLVMENT) *.
-Subsequently, paralysis descends to involve the limbs.
-Reflexes are generally normal, unless there is severe weakness
-Respiratory failure can lead to death

Peripheral anticholinergic autonomic effects:
-Dilated and nonreactive pupils (50% of patients).
-Pupillary involvement may be extremely helpful if present, since this is unlikely in many other conditions (e.g., myasthenia gravis) *.
-Dry mouth.
-Ileus, urinary retention.

Food botulism: early GI symptoms (nausea, vomiting, cramping, diarrhea)

Wound botulism: Wound may look benign, or there may be associated features of fever and infection.

Findings consistent with botulism *
-Normal mental status, sensation, blood pressure and heart rate (maybe slight bradycardia)
-Absence of fever (although fever can occur in wound botulism)

Question 52

DDx: descending weakness and cranial nerve palsies

Answer 52

• Myasthenia; might complain after a month
• Botulism: keeps getting worse and worse
  -Organophosphate intoxication *.
  -Presents with manifestations of cholinergic excess. The dominant clinical features include bradycardia, miosis, lacrimation, salivation, bronchorrhea, bronchospasm, urination, emesis, diarrhea, diaphoresis, and generalized weakness.
  -Guillain-Barre syndrome (especially the Miller Fisher variant).
  -Diphtheria infection.
  -!!!Myasthenia gravis (diplopia and ptosis are common)- botulism is continuously progressive
  -Tick paralysis- Afebrile ascending flaccid weakness, paralysis and ataxia, without sensory involvement, When the bulbar nerves and diaphragm become involved, respiratory failure ensues.
  -Pontine infarction.

Question 53

botulism dx and mangement - wound and food botulism

Answer 53

Diagnosis: clinical findings + exclusion of other processes

management:
-!!Antitoxins in all cases
-!Secure the airway if there is respiratory compromise.
-Severe botulism may necessitate mechanical ventilation for months

Wound botulism: Debridement then antibiotic therapy (penicillin G, metronidazole).
-Antibiotic administration may lyse bacteria, thereby releasing botulinum toxin. Antitoxin and debridement first.

Food botulism
-There is no role for antibiotic therapy.
-Whole bowel irrigation may be considered to reduce ongoing absorption of botulinum toxin from the gut, if the contaminated food was recently ingested *.

Question 54

approach to muscle weakness

Answer 54

Is neuromuscular and not something else causing fatigue?
-Example: Those with cardiac or pulmonary disease, or limited by joint pain or stiffness, etc
-Neuro exam to localize the site of the lesion
-What is distribution of weakness? Generalized, distal, proximal, or localized
-Is it CNS, PNS, neuromuscular junction, or muscle?

Labs: Electrolytes, calcium, magnesium, phosphate, creatine kinase, lactate dehydrogenase, serum aminotransferases, and thyroid stimulating hormone.
-In suspected rheumatic disease: antinuclear antibodies (ANA), and myositis specific antibodies.
-Electrophysiologic nerve and muscle testing (ie, measurement of nerve conduction velocity, sensory action potentials, and electromyography) may be helpful in localizing the site of peripheral neuromuscular disorders.
-EMG: motor units are brief duration and low amplitude

!!!!!If no drug, toxin, metabolic, or endocrine disorder can be identified as the cause of a myopathy, then muscle biopsy is the next step

Question 55

major causes of myopathy

Answer 55

MCC of weakness: viral, electrolyte imbalances
- Want to r/o medical organic causes and rule out meds
- LDH
- TSH

If no drug, toxin, metabolic, or endocrine disorder can be identified as the cause of a myopathy, then muscle biopsy is the next step!!!!!!