Neuromuscular Neuromuscular DisordersDisorders

Saad Al Juma

R3

In MNLMNL : Poliomyelitis is the protypical disease In Poliomyelitis weakness can be

asymmetrical or more often symmetrical The cerebrospinal fluid analysis resembles

that of aseptic meningitis. Patients initially have a clinical picture similar

to that of viral meningitis

In MNLMNL : Amyotrophic lateral sclerosis is the

prototypical disease In Poliomyelitis weakness can be symmetrical

or more often asymmetrical The cerebrospinal fluid analysis resembles

that of viral meningitis. Patients initially have a clinical picture similar

to that of viral meningitis…..

In AmyotrophicAmyotrophic laterallateral sclerosissclerosis It affects the anterior horn cells and results in

lower motor neuron disease without sensory involvement

Results from a degeneration of the motor neuron with sensory involvement.

complain of dysarthria or ptosis findings include hyporreflexia, muscle

wasting, and fasciculation Pain is not a component of the clinical

picture….

In AmyotrophicAmyotrophic laterallateral sclerosissclerosis Poliomyelitis affects the anterior horn cells

and results in lower motor neuron disease without sensory involvement

Results from a degeneration of the motor neuron without sensory involvement.

complain of dysarthria or dysphagia findings include hyperreflexia, muscle

wasting, and fasciculation Pain is not a component of the clinical

picture….

In MNLMNL all are true exceptexcept : lesions at the level of the brainstem or above

produce bilateral weakness bilateral weakness caused by lesions above

the spinal cord is associated with a change in mental status or cranial nerve involvement

Lesions of the central nervous system result in spasticity, hyperreflexia, and extensor plantar reflexes

bilateral upper motor neuron signs with normal mental status, neuroimaging should focus on looking for a lesion in the spinal cord

In MNLMNL : lesions at the level of the brainstem or above

produce unilateral weakness bilateral weakness caused by lesions above the

spinal cord is generally associated with a change in mental status or cranial nerve involvement

Lesions of the central nervous system result in spasticity, hyperreflexia, and extensor plantar reflexes

when bilateral upper motor neuron signs are found in conjunction with normal mental status, diagnostic testing including neuroimaging should focus on looking for a lesion in the spinal cord

In NeuropathiesNeuropathies , all are true EXCEPTEXCEPT : a grip strength or foot-drop may be noted first patients usually note a slowly progressive

course of symptoms. A disorder of transmission often leads to

increased production of ACh receptors. Patients usually have intact sensation

sensation.

In NeuropathiesNeuropathies : a grip strength or foot-drop may be noted first patients usually note a slowly progressive

course of symptoms. A disorder of transmission often leads to

increased production of ACh receptors. Patients exhibit varying degrees of altered

sensation

In MyopathiesMyopathies , all are true EXCEPTEXCEPT: Myopathies produce generalized, symmetrical

weakness muscle tone is usually diminished, but

sensation is preserved. Generally cause muscle pain and tenderness Reflexes are present but diminished

In MyopathiesMyopathies Myopathies produce generalized, symmetrical

weakness muscle tone is usually diminished, but

sensation is preserved. Metabolic disorders affecting muscle strength

are painless in nature Reflexes are present but diminished

DISEASE HISTORY STRENGTHDEEP

TENDON REFLEX

SENSATION WASTING

MyelopathyTrauma, infection,

cancer

Normal to decreased

IncreasedNormal to decreased

No

Motor neuron disease (ALS)

Progressive difficulty

swallowing, speaking, walking

Decreased Increased Normal Yes

Neuropathy 

Recent infection

Ascending weakness

Normal or decreasedDistal > proximal

Decreased 

Decreased 

Yes 

Neuromuscular junction disease

Food (canned goods)

Tick exposureEasy

fatigability

Normal to fatigue

  

Normal  

Normal  

No  

Myopathy 

Thyroid diseasePrevious similar

episodes

DecreasedProximal >

distal

Normal 

Normal 

Yes 

In MGMG all the following are true exceptexcept: Normally, vital capacity values range from 60

to 70 mL/kg. the forced vital capacity reaches 15 mL/kg,

intubation is necessary Arterial blood gas is helpful as most of the

patients have sufficient protective reserve and hypercapnia develps early

presence of swallowing and a strong cough suggests that the patient has sufficient protective and ventilatory reserve

In MGMG : Normally, vital capacity values range from 60

to 70 mL/kg. the forced vital capacity reaches 15 mL/kg,

intubation is necessary Arterial blood gas is not necessarily helpful

because functional reserve can be severely diminished by the time a patient develops either hypercarbia or hypoxia

presence of swallowing and a strong cough suggests that the patient has sufficient protective and ventilatory reserve

In Diseases of the Neuromuscular Junction Repeated stimulation leads to diminishing motor strength, which is caused by :

the blockage of the receptors as in organophosphate poisoning

a decrease in the amount of ACh released as in botulism

inactivating Ach by irreversibly binding with it as in MG

Down regulation of the Ach receptors as in Atropinized patients

In Diseases of the Neuromuscular Junction Repeated stimulation leads to diminishing motor strength, which is caused by :

the blockage of the receptors as in MG a decrease in the amount of ACh released as

in botulism inactivating Ach by irreversibly binding with it

as in organophosphate poisoning Down regulation of the Ach receptors as in

Atropinized patients

decrease in the release of AChACh may produce exceptexcept decreased visual acuity low-grade fever dry, flushed skin Bradycardia urinary retention

decrease in the release of AChACh may produce: decreased visual acuity low-grade fever dry, flushed skin Tachycardia urinary retention

All are true about MyopathiesMyopathies , exceptexcept: generalized, symmetrical weakness Reflexes are present muscle tone is usually diminished sensation is lost Are always painful

All are true about MyopathiesMyopathies : generalized, symmetrical weakness Reflexes are present muscle tone is usually diminished sensation is preserved Are always painful

Lambert-EatonLambert-Eaton myasthenicmyasthenic syndromesyndromeall are false exceptexcept : 50% of cases are associated with non small

cell carcinoma of the lung Clinically includes weakness that improves

with use of muscles….. autonomic dysfunction, most commonly seen

as flushed skin. Management with IVIG has been reported to

be sufficient.

Lambert-EatonLambert-Eaton myasthenicmyasthenic syndromesyndrome: 50% of cases are associated with small cell

carcinoma of the lung Clinically includes weakness that improves

with use of muscles autonomic dysfunction, most commonly seen

as dry mouth. Management primarily focuses on treating the

underlying neoplastic disorder

Regarding MGMG , all are true exceptexcept: Age of onset is bimodal MG results from autoantibodies directed

against the nicotinic acetylcholine receptor (AChR) at the neuromuscular junction

Ocular symptoms are often the first manifestation of MG

Bulbar muscles are spared

Regarding MGMG : Age of onset is bimodal MG results from autoantibodies directed

against the nicotinic acetylcholine receptor (AChR) at the neuromuscular junction

Ocular symptoms are often the first manifestation of MG

Bulbar muscles may be involved

What is EdrophoniumEdrophonium testtest ?

What is EdrophoniumEdrophonium testtest ?Edrophonium (Tensilon) test:

measure distance from upper to the lower eyelid before and after IV edrophonium (AChE blocking agent)

give test dose first 1-2mg IV , if no ADR/no improvement 3mg, if no response 5mg (max 10mg) watch for bradycardia (only perform when pt on monitor with Atropine at bedside DUE TO BRADY AND SECRETIONS ISSUES.) contraindicated in COPD/asthma pts because of risk of secretions.

reports of FP with botulism

What is IceIce packpack testtest ?

What is IceIce packpack testtest ? it is applied to the affected eye for

approximately 2 minutes the distance between the lids is measured

again prospective evaluation of the ice bag

approach found the test result to be positive (an improvement in distance of at least 2 mm) in 80% of patients with MG and in no patients without MG.[7]

defined as respiratory failure leading to mechanical ventilation

Occurs in 15 to 20% of patients with MG within the first 2 years of disease onset precipitant may not be found in 3 % of cases

In MyasthenicMyasthenic CrisisCrisis all are true ExceptExcept:

In MyasthenicMyasthenic CrisisCrisis : defined as respiratory failure leading to

mechanical ventilation Occurs in 15 to 20% of patients with MG within the first 2 years of disease onset precipitant may not be found in 30% of cases

Medications precipitate MG crisis

Medications precipitate MG crisisCVS ABX Others

Beta-blockers Aminoglycosides Phenytoin

Calcium channel blockers Tetracyclines Neuromuscular blockers

Quinidine Clindamycin Corticosteroids

Lidocaine Lincomycin

Thyroid replacementProcainamide

Polymyxin B

Colistin

Regarding MGMG Management all are true EXCEPTEXCEPT: in the setting of acute exacerbation of MG ,

The use of intravenous pyridostigmine is recommended

the initiation of corticosteroids in patients with moderate to severe weakness may improve the outcome

Thymectomy is recommended for patients younger than 60

IVIG is preferred over PE due to the side effects of the later.

Regarding MGMG Management: in the setting of acute exacerbation of MG ,

The use of intravenous pyridostigmine is NOT recommended

the initiation of corticosteroids in patients with moderate to severe weakness may improve the outcome

Thymectomy is recommended for patients younger than 60

IVIG is preferred over PE due to the side effects of the later.

Regarding P.EP.E in M.GM.G : The fall in AChR levels is not associated with

improvement in symptoms of MG. complications include hypotension or

anticoagulation. It is safe in children. many case series showed long-term benefit in

myasthenic crisis.

Regarding P.EP.E in M.GM.G : The fall in AChR levels is associated with

improvement in symptoms of MG. There is a risk of complications from

hypotension or anticoagulation. Because of safety concerns, clinical trials have

not been done in children. Although there are no randomized controlled

studies, a review yielded many case series with short-term benefit, especially in myasthenic crisis.

Regarding Botulism Botulism , all are true exceptexcept: Most common type is infant Botulism Clostridium botulinum is an anaerobic, spore-

forming bacterium types A, B, and C toxins cause human

disease…. botulinum toxin works by binding irreversibly

to the presynaptic membrane of peripheral and cranial nerves, inhibiting the release of ACh at the peripheral nerve synapse

Regarding BotulismBotulism : Most common type is infant Botulism Clostridium botulinum is an anaerobic, spore-

forming bacterium types A, B, and E toxins cause human

disease…. botulinum toxin works by binding irreversibly

to the presynaptic membrane of peripheral and cranial nerves, inhibiting the release of ACh at the peripheral nerve synapse

In BotulismBotulism , all are true exceptexcept : There is no pain The onset of symptoms is 6 to 48 hours after

the ingestion of tainted food descending, symmetrical, flaccid paralysis diplopia, dysarthria, and dysphagia are the

first signs Pupils are often fixed and reactive to light…

In BotulismBotulism : There is no pain The onset of symptoms is 6 to 48 hours after

the ingestion of tainted food descending, symmetrical, flaccid paralysis diplopia, dysarthria, and dysphagia are the

first signs Pupils are often dilated and not reactive to

light…

Regarding BotulisimBotulisim antitoxin there is a risk of anaphylaxis and serum

sickness It is known to decrease ventilator dependence the antitoxin should be administered once the

toxin can be identified in serum and stool the antitoxin should be administered as soon

as possible An intravenous human botulism immune

globulin (BIG-IV) has been developed for treatment of wound related botulism

Regarding BotulisimBotulisim antitoxin there is a risk of anaphylaxis and serum

sickness although it is not clear that the antitoxin

decreases ventilator dependence the antitoxin should be administered as soon

as possible (clinical findings and exclusion of other processes)

An intravenous human botulism immune globulin (BIG-IV) has been developed for treatment of infantile botulism

In TickTick ParalysisParalysis, all are true exceptexcept an acute, ascending, flaccid motor paralysis Usually starts after 6-12 days from female tick

has attached and begun to feed fixed and dilated pupils associated with the

disease. Intubation may be necessary after tick

removal

In TickTick ParalysisParalysis an acute, ascending, flaccid motor paralysis Usually starts after 1-2 days from female tick

has attached and begun to feed fixed and dilated pupils associated with the

disease. Intubation may be necessary after tick

removal

In ThyrotoxicThyrotoxic PeriodicPeriodic ParalysisParalysis , all are true EXCEPTEXCEPT: It is due to decreased sodium-potassium

adenosine triphosphatase activity Treatment of the hyperthyroid symptoms

helps the treatment of the paralysis There is probably a genetic feature underlying

this disorder all patients have thyroid function testing done

after a first episode of hypokalemic paralysis

In Thyrotoxic Periodic ParalysisThyrotoxic Periodic Paralysis It is due to increased sodium-potassium

adenosine triphosphatase activity Treatment of the hyperthyroid symptoms

helps the treatment of the paralysis There is probably a genetic feature underlying

this disorder all patients have thyroid function testing done

after a first episode of hypokalemic paralysis

In Familial Periodic Paralysis all are true EXCEPTEXCEPT: autosomal-dominant disorders of ion channels intermittent attacks of flaccid extremity

weakness associated with either hyperkalemia or hypokalemia

bulbar and respiratory muscles may be affected. The onset of symptoms often follows a high

carbohydrate intake and a period of rest. An electrocardiogram, which should be done

immediately

In Familial Periodic Paralysis:

autosomal-dominant disorders of ion channels intermittent attacks of flaccid extremity

weakness associated with either hyperkalemia or hypokalemia

bulbar and respiratory muscles not affected. The onset of symptoms often follows a high

carbohydrate intake and a period of rest. An electrocardiogram, which should be done

immediately

Which of the following statements is true?

a. Herpes zoster is often associated with motor dysfunction with or without a rash.

b. Acute rabies infection typically begins as a Ramsay-Hunt syndrome before progressing to severe throat spasm and to cardiac and renal failure.

c. Weakness or diplopia when fatigued may be the only complaint with multiple sclerosis.

d. Treatment for polymyositis is early administration of systemic steroids.

e. Serum calcium should be measured in patients with recurrent generalized weakness that follows periods of heavy exertion or that is present upon awakening.

The answer is c. Ramsay-Hunt syndrome refers to herpes zoster involving

the tympanic membrane, ear canal, and other areas in the distribution of the sensory branches of the facial nerve.

Herpetic zoster may result in motor abnormalities in up to 25% of cases.

Weakness or diplopia only on exertion is a common complaint in early cases of multiple sclerosis. Another early presenting sign is retrobulbar neuritis; in fact, 50–75% of cases occur in patients who develop multiple sclerosis.

Steroids may transiently exacerbate weakness in patients with polymyositis and should not be started on patients who will be discharged from the ED.

Acute periodic paralysis appears to involve abnormalities in cellular function, possibly related to potassium transport. The disease is most common in young men. No specific physical findings may be found and it is often misdiagnosed as hysterical in origin

2. A 34-year-old woman with known myasthenia gravis presents in respiratory distress. She is unable to move without assistance. Her vital signs are: temperature 36◦C (96.8◦F), heart rate 50/min, blood pressure 100/60 mm Hg, respiratory rate 35/min and shallow. She is drooling and has upper airway rhonchi and bilateral wheezing. Her respiratory rate appears to be decreasing. You immediately:

a. Administer 2–4 mg of intravenous edrophonium.b. Perform endotracheal intubation.c. Administer 1 mg of atropine; if there is an

improvement in her wheezing, administer pralidoxime.d. Start an intravenous atropine drip.e. Arrange emergent hyperbaric therapy.

The answer is b

You should be able to differentiate a myasthenic crisis from a cholinergic crisis.

Both can present with progressive muscle weakness and respiratory depression, dysphagia, and other physical signs. Bradycardia, wheezing, and salivation suggest cholinergic crisis.

A common error is to mistake a cholinergic as a myasthenic crisis and administer additional acetylcholinesterase inhibitor.

The immediate treatment for either type is ABCs and intubation at the first clinical signs of respiratory failure.

In a cholinergic crisis, atropine can be used for the muscarinic symptoms, but it is not a substitute for airway management and ventilatory assistance.

A 13-year-old girl presents with a 3-day history of malaise, low-grade fever, and double vision with unilateral ptosis. The potential diagnosis of botulism is best supported by finding:

a. Acute renal failure.b. Cardiac failure.c. Bilateral numbness of hands and feet.d. Acute urinary retention.e. Pseudomembranous pharyngitis.

The answer is d Both botulism and diphtheria may present with

acute bulbar nerve palsies, weakness of any or all extremities, and cholinergic manifestations, such as urinary retention and colicky pain.

In both diseases, the most common early neurologic findings are ptosis, double vision, and difficulty in accommodation.

Diphtheria is an acute febrile illness. A primary symptom is a severe pseudomembranous pharyngitis presenting with severe throat pain and excessive saliva production.

In diphtheria, cardiotoxic and renal abnormalities are direct results of the elaborated bacterial toxin.

A 34-year-old woman with myasthenia gravis presents with flank pain and fever of 103.4◦F. She is allergic to penicillin, and despite boluses of intravenous fluid and antibiotic therapy, she becomes hypotensive. A medicine that you can safely use in her management is:

a. Gentamicin.b. Vecuronium.c. Lidocaine.d. Procainamide.e. Succinylcholine.

The answer is c Aminoglycoside antibiotics have some curare-

type effects on the motor endplate; if they are used in the myasthenic patient, the physician should be prepared to treat paralysis and respiratory arrest. Obviously, these patients are more susceptible to muscle-paralyzing agents as well. Phenytoin, quinidine, procainamide, and lithium can also adversely affect patients with myasthenia gravis.

Curare (Chondodendron tomentosum),

•a South American vine native to the Amazon Basin. •The undersides of the leaves are white-tomentose. •An extract from the bark and stems is the source of a potent isoquinoline alkaloid used in the deadly poison curare. Amazonian Indians use the gummy extract to coat the poison darts of their blowguns. The alkaloid D-tubocurarine blocks acetylcholine receptor sites at neuromuscular junctions, causing relaxation and paralysis of muscles, including respiratory organs and the heart.• In fact, D-tubocurarine has been used to relax the heart muscle during open heart surgery. •It has also been used to treat the spastic paralysis of tetanus toxin from the bacterium Clostridium botulinum. Tetanus toxin causes uncontrollable muscle contraction throughout the body.

Neuropathy is differentiated from myopathy in that:

a. Neuropathies progress proximally.b. Myopathies affect distal and proximal muscle

groups equally.c. Myopathies and neuropathies both have

prominent sensory findings.d. Myopathies often have striking weakness of

the small muscles of the hands.e. Myopathies have relatively preserved deep

tendon reflexes.

The answer is a Neuropathies tend to have the following

characteristics: proximal progression of symptoms sensory deficits often in a stocking glove

distribution early loss of DTRs.

Myopathies characteristically present with proximal motor weakness myalgias delayed loss of DTRs CPK enzymes may be elevated.

There are exceptions to these generalizations.

Lambert-Eaton Myasthenic Syndrome results from an autoimmune attack directed against the

voltage-gated calcium channels (VGCCs) on the presynaptic motor nerve terminal.

This results in a loss of functional VGCCs at the motor nerve terminals. The number of quanta released by a nerve impulse is diminished.

However, because presynaptic stores of ACh and the postsynaptic response to ACh remain intact, rapid repetitive stimulation or voluntary activation that aids in the release of quanta will raise the endplate potential above threshold and permit generation of muscle action potential.

As neuromuscular transmission is completed at additional neuromuscular junctions, a transient increase will occur in the strength of the muscle.

Parasympathetic, sympathetic, and enteric neurons are all affected.

Clinically, this phenomenon is noted by the appearance of previously absent tendon reflexes following a short period of strong muscle contraction by the patient.

Myasthenia Gravis Autoantibodies (immunoglobulin G [IgG]) develop against ACh

nicotinic postsynaptic receptors for unknown reasons, although certain genotypes are more susceptible.2

Cholinergic nerve conduction to striated muscle is impaired by a mechanical blockage of the binding site by antibodies and, ultimately, by destruction of the postsynaptic receptor.

Patients become symptomatic once the number of ACh receptors is reduced to approximately 30% of normal. The cholinergic receptors of smooth and cardiac muscle have a different antigenicity than skeletal muscle and are not affected by the disease.

The role of the thymus in the pathogenesis of myasthenia gravis is not entirely clear, but 75% of patients with myasthenia gravis have some degree of thymus abnormality (eg, hyperplasia in 85% of cases, thymoma in 15% of cases). Given the immunologic function of the thymus and the improvement in the clinical condition of patients following thymectomy, the thymus is suspected to be the site of autoantibody formation. However, the stimulus that initiates the autoimmune process has not been identified