A pain in the neck
What’s causing DH to have trouble swallowing?
Vol.19, No.06, August 2011

D.H. is a 71-year-old man with an unremarkable medical history, save for a 60-pack-year history of smoking. He lost 23 kg over 4 years and presented with a 6-month history of progressive difficulty swallowing and neck pain. He has trouble chewing solid food and can only drink with a straw; even then he chokes on liquids at times, and feels short of breath. He’s unable to close his jaw and describes it to be “dangling,” but denies any jaw pain. His symptoms started with neck pain. Since then he experiences pain, particularly when he looks forward and/or straight, and he often keeps his neck bent forward. He denies any change in his voice, nasal tone to voice, or symptoms of double vision or focal weakness. He says there’s no headache or dizziness but sometimes he feels weak and unsteady. He reports no GI symptoms i.e. heartburn, reflux, nausea or vomiting. Because of his history of weight loss, he underwent a CT scan of the chest over a year ago that showed benign reactive lymph nodes and emphysema.

His medications include trazodone, oxycocet and morphine for neck pain. He denies alcohol use.

Physical examination reveals a man of stated age but thinly built who’s emaciated in the head/neck area. Heart sounds are normal and lungs clear with increased expiration. Abdomen is soft and scaphoid. There’s no pedal edema. Neurological exam is non-focal and reflexes are 2+ and symmetrical. There’s atrophy and weakness of masseter muscles on both sides and he’s unable to clench his jaws. There’s also no ptosis. Tongue is central with normal movement. There are no fasciculations of the tongue or skeletal muscles. His sensations are normal and symmetrical, but his jaw reflex is absent.

Laboratory data: normal WBC 8.1, hemoglobin 131 g/L, serum potassium of 4.5 mmol/L, BUN of 4.0 mmol/L, serum creatinine of 95 µmole/L, albumin of 41 g/L. Recent chest x-ray showed some fibrotic changes and hyperinflation without masses. An abdominal ultrasound showed simple renal cysts, but was otherwise unremarkable.

What’s D.H.'s problem?

ANSWER
Myasthenia gravis

Severe weakness of bilateral muscles of mastication and inability to close his jaw, referred to as Dangling jaw syndrome, could result from motor neuron disease, neuromuscular transmission disorder or myopathy. The likelihood of both motor neuron disease and myopathy was low in view of absent fasciculations in the former and muscle pain in the latter. The possibility of neuromuscular pathology like myasthenia gravis (MG) was considered, although his symptoms were still atypical. Acetylcholine receptor antibody was requested and found to be markedly elevated at 7.67 nmol/L [normal < 0.40] and a CT scan of the chest showed a 2.8 cm solid mass in the anterior mediastinum, consistent with a diagnosis of thymoma, just anterior to main pulmonary artery and the aortic arch. In retrospect, this mass was present on his previous CT scan and was unchanged, but was not recognized or reported. He was started on pyridostigmine (Mestinon) and showed improvement in his symptoms, and referred to a tertiary care centre for thymectomy.

Myasthenia gravis is an uncommon (2 per 1 million population), acquired autoimmune disorder that results from impaired neuromuscular transmission at the neuromuscular junction (at motor end plate) and characterized clinically by weakness of the skeletal muscles with fatigability on exertion and improvement after rest. MG can present at any age but the mean age of onset is 28 years in women and 42 in men. It’s slightly more common in women.

The main pathological abnormality in MG is the presence of antibodies attached to acetylcholine receptor (AChR) sites on the post-synaptic membrane of the neuromuscular junction (NMJ) of the skeletal muscles. These antibodies are found in up to 80-90% of patients with MG.

Clinical features and diagnosis

Muscle weakness with abnormal fatigability and improvement after rest characterize MG. Symptoms tend to be worse at the end of the day, and after repetitive use of muscles of a particular task, e.g., chewing and swallowing may be harder towards the end of a meal. In D.H., however, the symptoms were persistent, likely because of its late stage. The distribution of muscle involvement is not uniform and occurs as follows:

Intercurrent illness or medication can exacerbate weakness, quickly precipitating a myasthenic crisis and rapid respiratory compromise. On examination, the weakness in the affected muscles can be significant in some while absent in others.

Confirmation of diagnosis

Once suspected, the diagnosis of MG may be confirmed by:

  • Anti-acetylcholine receptor antibody (AchR Ab): found in up to 80% of patients with generalized myasthenia and about 50% with ocular myasthenia. Antibody titer is higher in those with more severe disease, although titer is not predictive of severity in an individual patient. Change in AChR Ab titer correlates with long-term improvement induced by prednisone or azathioprine.
  • Antistriated muscle (anti-SM) antibody: present in about 84% of patients with thymoma > 40 years and less often in those without thymoma. Its presence should prompt a search for thymoma in these patients. In individuals < 40 years, anti-SM Ab can be present without thymoma.
  • Thyroid function tests should be done to evaluate for coexistent thyroid disease.
  • Chest x-ray and CT of anterior mediastinum: About 10-15% of patients with MG have a thymoma and up to 50-60% show thymic hyperplasia. Both may enlarge the thymus, which can be detected in either a chest x-ray, or CT scan if the chest x-ray is negative.
  • EMG studies: sometimes it’s helpful to show that the amplitude of the muscle action potential, recorded by surface electrodes over a muscle, decreases on repetitive nerve stimulation (RNS) at 2-3 Hz. The other method is performing single-fibre electromyography (SFEMG) and evaluating neuromuscular block, jitter and fibre density. SFEMG is more sensitive than RNS in MG. However, SFEMG is technically more difficult and much more dependent on the experience and skill of the testing physician. Thus, RNS is the most frequently performed neurophysiological test of neuromuscular transmission.

Treatment

Even though no rigorously tested treatment trials have been reported and no clear consensus exists on treatment strategies, MG is one of the most treatable neurologic disorders. Several factors (e.g., severity, distribution and rapidity of disease progression) should be considered before initiating or changing therapy. AChE inhibitors and immunomodulating therapies are the mainstays of treatment. Most patients with generalized MG require additional immunomodulating therapy.

  • Oral anticholinesterase (AChE) inhibitors: useful in the mild form of the disease. Pyridostigmine or prostigmine are used initially during the day and work quite effectively.
  • Immunomodulating therapy: Immuno-suppression by prednisone, azathioprine or cyclosporin. In patients with disabling symptoms inadequately controlled by oral AChE inhibitors, suppression of the antibody can radically improve muscle strength.
  • Intravenous immunoglobulin: High-dose IVIg successfully treats MG. Like plasma exchange, it has a rapid onset of action, but effects last only a short time. Best used in crisis management (e.g., myasthenic crisis and perioperative period).
  • Plasmapheresis (PE): thought to act by removing circulating humoral factors (AChE Ab) and immune complexes. It’s an effective treatment in preparation for surgery or as short-term management of an exacerbation. Improvement in strength may help to achieve rapid postoperative recovery and to shorten the period of assisted ventilation. Weakness improves within days, but the improvement lasts only 6-8 weeks. PE usually is used as an adjunct to other
    immunomodulatory therapies and as a tool for crisis management. Long-term regular PE on a weekly or monthly basis can be used if other treatments can’t control the disease.
  • Thymectomy: Remission or improvement can be expected in 60-80% of patients after thymectomy and must be considered in all patients. This is an important treatment, especially if a thymoma is present. Even though no controlled trial to assess the efficacy of thymectomy in MG has been reported, thymectomy has become the standard of care and should be done in all patients with thymoma and considered in patients aged 10-55 years without thymoma but with generalized MG.

Prognosis

Recent advances in treatment and care of critically ill patients have resulted in a marked decrease in mortality rate. The mortality rate is now 3-4% (decreased from 30-40%), with principal risk factors being age < 40 years, short history of severe disease, and thymoma.

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