Trans 053 NMJ Disorders Flashcards
Most common NMJ Disease?
MG
When we say NMJ, we are talking of receptors and neurotransmitters, specifically ______
Ach
This substance block Ach release?
Botulinum Toxin
A drug that blocks Ach receptors? (poison darts)
Curare
What blocks acetylcholinesterase?
Organophosphates
3 mechanisms that causes NMJ problems?
- Decrease Ach release
- Decrease Ach effects on muscle cells
- Decreased acetylcholineesterase activity results in acetylcholine having a stronger effect on mm cell.
NMJ problems can be post or presynaptic, T or F?
T
Pattern of weakness in NMJ? proximal or distal?
Both
is extraocular and facial mm involved in weakness in NMJ?
Yes
NMJ is [variable/constant] within the day?
Variable:
Nagkakaroon kasi ng fatigue, so pag active na active, you need more and more of the Ach, so the patient will have weakness. So patients with NMJ disorders, esp. with myasthenia gravis, pag gising sa umaga, malakas pero by midday, mahina na sila.
Are sensory and tendon reflexes affected in NMJ disorders?
No
Fluctuating weakness is predominantly in proximal/distal muscles and associated with fatigability.
proximal
Ocular and bulbar muscles are frequently [more severely/not much affected]?
more severely
Generalized fatigue without true weakness is not atypical. T or F?
F. TYPICAL
Symptoms of sensory loss, paresthesia, or neuropathic pain are absent. T or F?
T
Autonomic symptoms of dry mouth, blurry vision, impotence, constipation, and difficulty with urination may be noted in
LEMS and botulism
Weakness with predilection for proximal limb, ocular, and bulbar muscles is not typical. T or F?
F. Typical
Extraocular and bulbar weakness are early and prominent in MG and botulism but less prominent in LEMS. If ocular weakness is an initial symptom, LEMS is unlikely. T or F?
T. If ocular weakness is an initial symptom, LEMS is unlikely.
Pupillary responses are usually reduced in
Botulism
Pupils are not affected in MG. T or F?
T
Reflexes are characteristically present/absent in presynaptic NMJDs but preserved/absent in postsynaptic NMJDs.
absent
preserved
Facilitation of reflexes with brief exercise is pathognomonic of
LEMS
NMJ DISORDERS can be subdivided into 3: what are those?
Toxin induced
Immune Mediated
Genetic
For toxin induced NMJ disorder what are the examplse?
Botulism
snake venoms
organophosphates
For Immune Mediated NMJ disorder, what are the example?
MG and LEMS
For genetic NMJ problem what is the example?
Congenital Myasthenic syndrome
in MG: Autoimmunity is directed toward the Ach receptor on the PRE/POST synaptic membrane?
postsynaptic membrane
In LEMS: Autoimmunity is directed toward voltage gated calcium channels at the PRE/POST synaptic nerve terminal.
PRE
mechanism of botulism
Botulinum toxin blocks neurotransmitter release at peripheral cholinergic nerve terminals (including skeletal muscle and autonomic nervous system).
CMS: There are [numerous/rare] CMSs with various mutations affecting the function of either presynaptic, synaptic, and postsynaptic NMJ transmission.
numerous
Serologic testing for MG:
Ach receptor antibodies (80%); muscle specific tyrosine kinase (MuSK) antibodies (10%); striational antibodies; antibody negative (5%- 10%).
serologic testing for LEMS?
P/Q type voltage gated calcium channel antibodies are present in atleast 85% of LEMS.
serologic testing for botulism?
Antibody testing is available to identify exposure to common subtypes.
Aside from serologic tests what other tests can we do for NMJ d/o?
1.Toxin and culture analysis of feces, serum, wound, and food may be considered depending on suspected route of exposure in cases of botulism. 2.Genetic tests is available for some CMS disorders
Typical result of Sensory nerve conduction studies in NMJDs
are typically normal in NMJDs and help exclude mimicking or coexistent conditions.
Some patients with LEMS may have these findings in Nerve conductuion testinfs
Some patients with LEMS may have a concomitant paraneoplastic sensory or sensorimotor neuropathy or chemotherapy related peripheral neuropathy.
Motor nerve conduction studies result p[ost synaptic NMJDs
are usually normal in postsynaptic NMJDs, but in severe cases, compound muscle action potential (CMAP) amplitudes may be slightly reduced while distal latencies and conduction velocities are normal.
is a specialized motor nerve conduction study used to assess NMJDs.
Ask the patient to raise their arms 20x up down up down, and try to see if the patient will have fatigue and compare it to a normal person.
RNS
Repetitive nerve stimulation
What’s the disease?
Reflex: normal or reduced CMAP: normal 3 Hz Stimulation: Decrement 50 Hz Stimulation: Decrement Autonomic symptoms: Absent
MG
What’s the disease?
Reflex: Absent CMAP:Reduced 3 Hz Stimulation:Decrement 50 Hz Stimulation: Increment Autonomic symptoms: Dry mouth , constipation, male impotence
LEMS
What’s the disease?
Reflex: Hyperactive or normal
CMAP: Normal amplitude; repetitive response to single stimulation, multiple spontaneous motor unit discharges
3 Hz Stimulation: Normal or decrement
50 Hz Stimulation: not performed
Autonomic symptoms: increased sweating or constipation
Neuromyotonia
What’s the disease?
Reflex: Usually normal CMAP: Normal in ACHR deficiency 3 Hz Stimulation: Normal/decrement 50 Hz Stimulation: not performed Autonomic symptoms: Absent
Congenital myasthenic syndromes
Pathophy of NMJ: Immunoglobulin G (IgG) directed attack on the NMJ, aimed specifically at the what receptor
nicotinic ach receptos
Damage to the Ach receptor and postsynaptic membrane involves several steps:
- First, binding of the antibody to the receptor can directly block the binding of Ach.
- Second, there is a complement-directed attack, with destruction of the Ach receptor and post junctional folds.
- Third, antibody binding can result in an increase in the normal removal of Ach receptors from the postsynaptic membrane.
> Resulting in a smaller endplate potential and a reduced safety factor of NMJ transmission.
ocular findings in MG?
- Unilateral painless ptosis without ophthalmoplegia will most often prove to be due to myasthenia.
- Normal pupillary responses to light and on accommodation in the face of weakness of extraocular muscles and orbicularis oculi are virtually diagnostic of myasthenia gravis.
- Attempts to overcome the ptosis may impart a staring expression
- Bright sunlight is said to aggravate the ocular signs and cold to improve them.
Ice test
put the ice on a piece of cloth, and put it on the patient for about 5 min, and ask the patient to open the eyes. If wider than the previous, then most likely it is myasthenia gravis
classification/ distribution of weakness in MG
Class 1 Class 2 (2A and 2B) Class 3 (3A and 3B) Class 4 (4A and 4B) Class 5
1- ocular 2- mild generalized 2A-limb axial 2B oropharyngeal/respiratory muscles 3 - moderate generalized 3A - limb axial 3B - oropharyngeal/respiratory 4 - severe generalized 4A - limb axial 4B oro/respi 5 _intubation
- Infants born of myasthenic mothers
- Self limited
- Transplacental transfer of AchR
- Antibodies
what type of pediatric MG?
Neonatal
What type of pediatric MG?
- Nonmyasthenic mother
- Tends to be permanent
- Onset anytime from birth to puberty
Juvenile
drugs that may induce MG?
• Drugs may worsen syndromes
- Polymixin and aminoglycoside antibiotics
- Antiarrhythmic agents (procainamide, quinidine)
- b-adrenergic blockers (propranolol, timolol)
- Phenothiazines, lithium
- Succinylcholine, curare, and related drugs
- Trimethaphan
- Methoxyflurane
- Magnesium given parentally or in cathartics
Result of Anti-Achr radioimmunoassay?
85% positive in generalized MG; 50% in ocular MG
40% of AChR antibody-negative patients with generalized MG have anti-MuSK antibodies. T or F?
T
- Repetitive nerve stimulation: decrement of >10% at 3 Hz: highly probable
- Single-fiber electromyography: blocking and jitter, with normal fiber density; confirmatory, but not specific • Edrophonium chloride (Tensilon) 2 mg + 8 mg IV; highly probably diagnosis if unequivocally positive • For ocular or cranial MG: exclude intracranial lesions by CT or MRI
T or F?
T
is most commonly used for diagnostic testing because of the rapid onset (30s) and short duration (5 min) of its effect
Edrophonium
• This test evaluates weakness (eg. Ptosis, partial or complete ophthalmoplegia, and forced hand grip) in an involved group of muscles before and after IV administration
Edrophonium
How to do the edrophonium test?
- 1 mg (0.1 ml) of edrophonium is given intravenously; if this dose is tolerated and no definite improvement in strength occurs after 45s, another 3 to 6 mg is injected. If there is no response after another 45 s, an additional 3 to 5 mg may be given over approximately 1 min.
- A total dose of 10 mg is rarely necessary.
- Most patients who respond do so after 3 to 5 mg have been administered.
If the patient is symptomatic, what is the manafement?
- Cholinesterase inhibitors: Block hydrolysis of Ach at cholinergic synapses, which allows Ach to accumulate and have a prolonged effect.
- Potassium channel antagonist: 3,4-Diaminopyridine (3,4 DAP) prolongs the presynaptic nerve action potential thus facilitating calcium influx. 3,4 DAP is very effective in the treatment of LEMS and some forms of CMSs, but it is an investigation medication available only on a compassionate use basis in the United States.
immunomodulatory management in NMJDs?
- Corticosteroids
- Immunosuppressant agents: Allow for steroid sparing or additive effects in disease modification. Examples: azathioprine, mycophenolate mofetil, cyclosporine, cyclophosphamide, and methotrexate.
- Rescue therapies: Intravenous immunoglobulin and plasma exchange are used for severe or life-threatening symptoms for rapid (but transient) improvement.
prophylactic management for NMJDs?
- Low calorie, low salt diet when managed with corticosteroids.
- Agents for bone health maintenance when managed with corticosteroids.
- Antibiotic pneumocystis pneumonia prophylaxis when multiple immunomodulatory agents are implemented.
MG treatment options?
- Long acting anticholinesterase
- Pyridostigmine bromide
- Neostigmine bromide
- Immunosuppressives
- Systemic Steroids
- Azathioprine
- Cyclosporine A
- Methotrexate
- Cyclphosphamide
- Surgical thymectomy
- Plasmpharesis
- IV Immunoglobulin
