neuromuscular Flashcards
weakness = Vague chief complaint; what hx qs
-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)
motor pathway (a review) CORTICOSPINAL and CORTICOBULBAR
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
localizing weakness: UMN vs LMB
-LMN- peripheral nerves
-pronator drift- stroke
-hoffman sign- when you flick middle finger the pointer and thumb come together
motor weakness: neuropathy vs myopathy vs NMJ disorder
cerebral palsy overview and comorbidities
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
cerebral palsy risk factors
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
cerebral palsy hx and PE
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
cerebral palsy classification
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
cerebral palsy dx
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
cerebral palsy management
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
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?
INO: cant adduct in - CN III
* But can still do convergence
-cant actively adduct the eye
MULTIPLE SCLEROSIS: ONLY INVOLVES UMN
multiple sclerosis: definition, ethiology, epidemiology
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)
MS pathophysiology
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
MS: definitions of exacerbation, remission, pseudorelapse
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)
MS classifcations
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
MS clinical features overview
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
MS: demyelination of spinal cord tracts
-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
MS optic neuritis sx and description
-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
Other differentials for optic neuritis include:
-Infection (lyme, herpes, syphilis)
-Autoimmune disorders (SLE, Sarcoid)
-Methanol poisoning
-B12 deficiency
-Diabetes
MS dx criteria
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
MS testing/workup
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
MS tx:
-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
amyotrophic lateral sclerosis/ Lou Gehrig’s disease definition/overview and pathophysiology, life expectancy
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
ALS epidemiology
-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***
ALS symptoms: what is the MC presenting sx
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
ALS: how does weakness spread on body and what sx are absent
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…)
ALS PE
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
Mixed findings of UMN and LMN: think what ds
ALS!!!!
ALS dx
-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
ALS: EMG and NCS
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
ALS lab work and imaging
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
ALS diff dx
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
ALS tx
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.
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
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
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.
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
myasthenia gravis (MG): definition, prevalence, epidemiology
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)
myasthenia gravis (MG) pathophysiology
-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)!!!!!!!**
MG: complication: def, causes, treatment
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
MG signs and symptoms
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)
MG evaluation: imaging and labs
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
MG dx
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
MG tx
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
MG: drugs to avoid in pts
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
lambert-eaton myasthenic syndrome (LEMS) definition and association
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
LEMS- sx and presentation of muscle weakness
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
LEMS: bulbar involvement, autonomic dysfunction, respiratory failure (she didnt read these points in class)
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
LEMS dx and tx
-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
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 . . .
wound botulism
botulism definition
-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
botulism epidemiology
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
botulism clinical presentation
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)
DDx: descending weakness and cranial nerve palsies
- 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.
botulism dx and mangement - wound and food botulism
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 *.
approach to muscle weakness
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
major causes of myopathy
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!!!!!!
