Case 17

Case 17





EDX FINDINGS AND INTERPRETATION OF DATA


Pertinent EDX findings include the following:












These findings are diagnostic of a neuromuscular junction defect of the postsynaptic type and are consistent with myasthenia gravis. Normal CMAP amplitude at rest and the absence of CMAP increment after brief exercise exclude a presynaptic defect, as is seen with LEMS or botulism. The absence of denervation on needle EMG excludes a lower motor neuron disease (as seen with amyotrophic lateral sclerosis), which may be associated with a decremental response on slow repetitive stimulation.



DISCUSSION



Anatomy and Physiology



Neuromuscular Junction


The neuromuscular junction (NMJ) is the site where the motor neuron makes contact with the skeletal muscle fiber’s membrane (sarcolemma). It is near the center of the muscle fiber where there is a cup-shaped depression of the sarcolemma, called the endplate. The NMJ is a chemical synapse that is essential for transmitting action potentials from the terminal nerve branches to muscle fibers. This synapse utilizes acetylcholine (ACH) as a transmitter that binds to specific receptors in the junctional membrane, resulting local depolarizations that spread and trigger all-or-none muscle action potential. The NMJ is divided into a presynaptic terminal, a synaptic cleft, and a postsynaptic region (Figure C17-3).









Neuromuscular Transmission


Neuromuscular transmission involves the transmission of action potential from the motor neuron’s axon to the muscle fiber. The delay between the depolarization of the presynaptic terminal and the generation of endplate potential at the postsynaptic membrane is short (0.3–1 ms), and is mostly due to the exocytotic release of ACH from the presynaptic terminal. Neuromuscular transmission may be divided into three processes: (1) presynaptic terminal depolarization and ACH release; (2) ACH binding and ion channel opening; and (3) postsynaptic membrane depolarization and muscle action potential generation.







Clinical Features


Myasthenia gravis (MG) is the best understood and most thoroughly studied of all human organ-specific autoimmune diseases. It is characterized by a reduction of skeletal muscle postsynaptic ACH receptors resulting in a decrease in the EPP necessary for action potential generation. In the majority of patients, MG is caused by an antibody-mediated attack on the postsynaptic nicotinic ACH receptors in the neuromuscular junction. In a small number of patients, other antigenic targets, such as the muscle specific tyrosine kinase (MuSK), may exist. Myoid cells and other stem cells within the thymus gland, which is hyperplastic in at least two-thirds of patients with MG, may serve as autoantigens by expressing on their surface the ACH receptor or one of its protein components.


The prevalence of MG is between 50 and 125 cases per million population. There is strong evidence that its prevalence is increasing, which may be in part attributed to better case recognition and aging of the population. As with many other autoimmune disorders, the disease afflicts mostly women, affected nearly twice as often as men. The annual incidence of MG ranges between 1.1 and 6 per million. MG incidence has two distinct peaks: the first occurs in the second and third decades and affects mostly women; and the second peak strikes mostly men during the sixth and seventh decades.


The hallmarks of MG are muscle weakness and fatigability. The symptoms are intermittent and are usually worse with activity and improve after rest. Generally, patients are much better in the morning than in the evening. Ocular symptoms (diplopia and/or ptosis) are extremely common and are the presenting signs in more than one half of patients. Most importantly, almost all patients at some point during the course of their illness develop ocular manifestations. Also, the disorder continues to be restricted to the extraocular muscles in 15% of patients, hence the designation ocular myasthenia. Additionally, only 3–10% of patients with ocular myasthenia generalize if no other symptoms appear after three years from initial presentation. Bulbar muscle weakness is the initial presenting manifestation in about 20% of patients and is seen in over 30% of patients during the course of their disease. Bulbar weakness is a major contributor to disability throughout the course of the disease. It manifests as dysarthria, nasal speech, dysphagia, chewing difficulties, or nasal regurgitation. Occasionally, the jaw muscle weakness may be severe leading to a “jaw drop” and patients often hold their jaw closed, a highly pathognomonic manifestation of MG. Limb weakness, mostly of proximal muscles, is seen as the initial symptom in 20% of patients. At times, the generalized weakness is severe and involves the respiratory muscles, resulting in respiratory failure that requires mechanical ventilation, a situation often referred to as myasthenic crisis. Because of variable clinical severity, MG is usually classified into five main categories (Table C17-1).


Table C17-1 Myasthenia Gravis Foundation of America Clinical Classification






















































Class I Any ocular muscle weakness
May have weakness of eye closure
All other muscle strength is normal
Class II Mild weakness affecting other than ocular muscles
May also have ocular muscle weakness of any severity
   IIa Predominantly affecting limb, axial muscles or both
May also have lesser involvement of oropharyngeal muscles
   IIb Predominantly affecting oropharyngeal, respiratory muscles, or both
May also have lesser involvement of limb, axial muscles, or both
Class III Moderate weakness affecting other than ocular muscles
May also have ocular muscle weakness of any severity
   IIIa Predominantly affecting limb, axial muscles or both
May also have lesser involvement of oropharyngeal muscles
   IIIb Predominantly affecting oropharyngeal, respiratory muscles, or both
May also have lesser involvement of limb, axial muscles, or both
Class IV Severe weakness affecting other than ocular muscles May also have ocular muscle weakness of any severity
   IVa Predominantly affecting limb, axial muscles or both May also have lesser involvement of oropharyngeal muscles
   IVb Predominantly affecting oropharyngeal, respiratory muscles, or both
May also have lesser involvement of limb, axial muscles, or both
Class V Defined by intubation, with or without mechanical ventilation, except when employed during routine postoperative management. The use of a feeding tube without intubation places the patient in class IVb

The findings on neurologic examination parallel the symptoms, often revealing ptosis, weakness of extraocular muscles, flaccid dysarthria, or neck extensor or proximal muscle weakness. Although many muscles are fatigable, the most objective finding is fatigable eyelids, i.e., ptosis developing within 1–2 minutes of sustained upgaze. Deep tendon reflexes are preserved. Sensation is normal.


The diagnosis of MG may be made on clinical grounds, especially when reproducible fatigability of eyelids or extraocular muscles is confirmed. However, laboratory testing is frequently needed, and recommended, for confirmation (Table C17-2):



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Aug 12, 2016 | Posted by in CARDIOLOGY | Comments Off on Case 17

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