Myaesthenia Gravis

Telithromycin may lead to respiratory failure.

Myasthenia gravis is the principal disease affecting the neuromuscular junction. In this process, the fundamental defect is not a deficiency of ACh or its release, but rather a failure of ACh to attach to the postsynaptic receptor, as a result of blockade by an antibody at the receptor site or of destruction of the membrane by antibody attack. 

B i.e. Neuromuscular junction

Myasthenia gravis is a neuromuscular disorderQ characterized by weakness and fatiguability of skeletal muscle. The underlying defect is a decrease in the number of available nicotinic Ach receptor at the Neuromuscular junction due to an antibody mediated autoinunune attack.Q

Ans. is ‘a’ i.e., Edrophonium

• Edrophonium (anticholinesterase) injected slowly i.v improves muscle strength only in myaesthenia gravis and not in other muscular dystrophies.

Ans. is ‘a’ i.e., Azathioprine

o Tetracycline, aminoglycoside and quinidine can aggravate mysthenia gravis.

A i.e. Gallamine; C i.e. Aminoglycoside

Answer is D (Decreased Myoneural junction transmission):

The primary defect in Myaesthenia gravis is decreased transmission across the myoneural junction due to decrease in the number of Acetylcholine receptors.

The fundamental defect is Myaesthenia gravis is a decrease in the number of Acetylcholine Receptors at the postsynaptic muscle membrane, which results in decreased efficiency of neuromuscular transmission’ — Harrison

Answer is B (Absent deep tendon reflexes):

‘Despite the muscle weakness, deep tendon reflexes are preserved’ — Harrison 16^th/2519; Harrison 17^th/ 2673

‘Suspect Myaesthenia gravis in a case of weakness with fatiguability, without loss of reflexes & impairment of sensations’ — Harrison

Mvaesthenia Gravis : Review :

Etiology :

Autoimmune disorders mediated by specific Anti ACH receptor antibodies.

Fundamental defect :

Decrease in number of available ACH receptors at post synaptic muscle membrane.

Age / Sex :

All ages are affected

Most prevalent in women in twenties/ thirties and men in fifties & sixties.

Women are affected more frequently than men^Q. (3 : 2)

Features :

Weakness : in characteristic distribution as elaborated below

Fatiguability:

Weakness increases on repeated use and may improve following rest or sleep

A variable course marked by remissions and exacerbations (remissions are rarely complete or permanent)

Association :

Thymic abnormalities and Thymomas (Neoplastic)

Autoimmune disorders : Rheumatoid Arthritis, SLE, Perenicious anemia, hyperthyroidism, ulcerative colitis, polymyositis etc.

Answer is D (Single Fiber Electromyography (SFEMG)) :

Single Fiber Electromyography (SFEMG) is the single most sensitive assay of neuromuscular function dysfunction in myasthenia gravis

`SFEMG is the single most sensitive assay of neuromuscular function dysfunction in myasthenia gravis having a sensitivity of greater than 95% when applied to clinically affected muscle’ – Merrit’s Neurology 12^th(2009) /389

`Single fiber electromyography is the most sensitive diagnostic test for MG, but abnormalities are not specific’.

– ‘Neuromuscular Junction Disorders: Diagnosis & Treatment (2003)/109

`Single fiber EMG is the most sensitive electrophysiological test for myasthenia gravis’

– Adult Neurology’ 2^nd (Blackwell publishing) /299

Taken from ‘Neuromuscular Junction Disorder’s: Diagnosis & Treatment (2003) /109

Edrophonium test / Tensilon test

• Highly sensitive test with 85% sensitivity in ocular and 95% sensitivity in systemic myasthenia -Kanski
• Diagnosis is highly probable if test in unequivocally positive
• An initial dose of 2mg of edrophonium is given intravenously.
• If improvement occurs the test is considered positive and terminated.
• If there is no change an additional 8mg are given intravenously .

Acetylcoline Receptor antibodies

• Sensitivity of 80-90% in systemic myasthenia – CMDT
• Highly specific and presence of Anti ACH Receptor
• Antibodies is virtually diagnostic of M. gravis 85% positive in generalized M.G.
• 50% positive in ocular M.G.
• Definitive if positive
• Negative test does not exclude M.G.
• 40% of Anti antibody negative patients have Anti-Musk antibodies.

 Repetitive nerve stimulation / Electrodiagnostic test

• Helpful diagnostic evidence
• Best when weak muscles/ proximal ms. groups are tested
• Amplitude of evoked muscle end potential is measured

– No change in normal patients

– Reduction by > 10-15 % in myasthenic patients.

Single fiber electromyography

• Demonstrates blocking and jitter with normal fiber density
• Most sensitive diagnostic test for MG with sensitivity of greater than 95%
• Confirmatory but not specific
• Often performed in conjunction with repetitive nerve stimulation test (Oxford handbook)

Answer is A (Should be done in all cases) :

• Thymectomy should be carried out in all patient with generalized Myasthenia gravis between the ages of puberty and 55 years of age – Harrison 17111/2675
• Thymectomy should be considered in all patients with generalised M. gravis younger than 60 years of age.
• Done even in those case, controlled by medical treatment: The advantage of thymectomy is that it offers the possibilities of long term benefit.
• It may diminish or even eliminate the need for continuing medical treatment.
• This is why it is done even in those cases, controlled by medical treatment.
• Done in those cases also, where thymoma is not associated: 85% of patients without a Thymoma, also experience improvement after thymectomy.
• 55% to an extent that they may achieve drug free remission.
• This is why thymectomy is done in those cases also, where thymoma is not associated.
• Only 10% of patients with M. Gravis have an associated thymoma. [Thymus is abnormal in approximately 75% but in the majority (65%), the thymus is only hyperplastic and does not have a tumor]
• Thymectomy is not indicated if weakness is restricted to extraocular muscles – CMDT 2001 pg.1024

Answer is D (Pyridostigmine):

Pyridostigmine is the most widely used anticholinesterase medication in Myaesthenia Gravis.

Pyridostigmine’s the single best answer of choice amongst the options provided.

Ans. B i.e. Nicotinic receptor proteins

Myasthenia gravis

• It is an autoimmune neuromuscular disease leading to fluctuating muscle weakness and fatigability.
• It is an autoimmune disorder, in which weakness is caused by circulating antibodies that block acetylcholine receptors at the postsynaptic neuromuscular junction, inhibiting the excitatory effects of the neurotransmitter acetylcholine on nicotinic receptors throughout neuromuscular junctions.
• Myasthenia is treated medically with acetylcholinesterase inhibitors or immunosuppressants, and, in selected cases,thymectomy.

Ans. B: Tubocurare

Drugs contra-indicated in myasthenia gravis

• Absolute contraindication:

–         Curare

–        D-penicillamine Botulinum toxin

–        Interferon alpha

• Contraindicated

—  Antibiotics — aminoglycosides (gentamycin, kanamycin, neomycin, streptomycin, tobramycine); macrolides (erythromycin, azithromycin, telithromycin,) Fluoroquinolones (ciprofloxacin, norfloxacin, levofloxacin);

—        Quinine, quinidine, procainamide,

—        Magnesium salts, iv magnesium replacement.

• Caution- may exacerbate weakness in some myasthenics

–        Calcium channel blockers

–        Beta blockers

–        Lithium

–        Statins

Iodinated contrast agents

Ans. is ‘b’ i.e., Type II 

• Myasthenia gravis is antibody mediated (type II) hypersensitivity