Endgames Case Report

A 90 year old man with difficulty swallowing and proximal muscle weakness

BMJ 2012; 344 doi: http://dx.doi.org/10.1136/bmj.e461 (Published 04 April 2012) Cite this as: BMJ 2012;344:e461
  1. H U Rehman, clinical associate professor
  1. 1Department of Internal Medicine, Regina Qu’Appelle Health Region, Regina, SK, Canada, S4P 3X1
  1. Correspondence to: H Rehman habib31{at}sasktel.net

A 90 year old man presented with progressive dysphagia, generalised weakness, and malaise. He had lost 30 lb (13.6 kg) in the past six months, and his mobility had deteriorated because of progressive leg weakness. He had no visual or constitutional symptoms apart from weight loss and denied any bladder or bowel problems. He had a 25 pack year history of smoking and did not drink alcohol.

Examination showed signs consistent with bilateral pneumonia. His speech was dysphonic, the gag reflex was absent, but other cranial nerves were intact. He had wasting and weakness of the small muscles of the hands and weakness of the proximal muscles of the lower limbs. Reflexes were absent in the lower limbs. Strength in the remaining muscle groups—including ankle dorsiflexion, planter flexion, knee extension, and flexion—was normal. Proximal muscle groups in the upper extremity were strong, although reflexes were reduced bilaterally. No fasciculations were seen and he had no evidence of fatigable ptosis. Sensory examination was normal. Examination of the cardiovascular and abdominal systems was unremarkable.

Investigations showed a white blood cell count of 5.9×109 cells/L (reference range 4.0-10.0), haemoglobin 117 g/L (140-180), platelets 332×109 (320-360), random glucose 10.8 mmol/L (3.6-11), urea 25.3 mmol/L (3.0-7.1), creatinine 191 μmol/L (60-130), thyroid stimulating hormone 5.72 mIU/L (0.49-4.67), and free thyroxine 9.2 pmol/L (9.0-19.0). Results of serum electrolytes, creatine kinase, serum protein electrophoresis, urinary Bence Jones proteins, and a short synacthen test were in the normal range.

Computed tomography of the chest, abdomen, and pelvis showed bibasilar consolidation, with associated small pleural effusions. No serious abnormalities were detected in the abdomen and pelvis—in particular, no evidence of malignancy was seen. Gastroscopy showed a normal oesophagus and stomach and mild duodenitis. Colonoscopy was normal. Pooling of contrast medium in the vallecula was seen with thin and thick liquids, as well as with pudding and mixed solid food on modified barium swallow. Aspiration was seen with sips of thin fluids.

Nasogastric tube feeding was instituted, and after obtaining blood cultures he was started on antibiotics. Further investigations were ordered.

Questions

  • 1 What is the most likely neurological diagnosis?

  • 2 What further investigations would you order to confirm the underlying neurological diagnosis?

  • 3 What is the main differential diagnosis?

Answers

1 What is the most likely neurological diagnosis?

Short answer

Lambert-Eaton myasthenic syndrome.

Long answer

Lambert-Eaton myasthenic syndrome is an autoimmune disease in which antibodies are directed against the presynaptic voltage gated calcium channels. It can occur sporadically or as a paraneoplastic syndrome, most often as a result of small cell lung cancer. The syndrome usually presents with proximal weakness, which is greater in the lower extremities than in the upper extremities.1 Like myasthenia gravis, weakness is exacerbated by exercise and heat. Muscle wasting is not a feature of this syndrome and was probably secondary to cachexia in our patient. Autonomic dysfunction occurs in 75% of patients, manifesting as dry mouth, blurred vision, constipation, and orthostatic hypotension.2 Calcium entry into the presynaptic terminal is initially blocked, resulting in reduced release of acetylcholine and reduced muscle contraction. However, on exercise, continuous influx of calcium results in accumulation of calcium in the presynaptic nerve terminal, because its removal by mitochondria does not keep pace with its influx. This results in release of normal or near normal amounts of acetylcholine on muscle contraction for a short time, and muscle strength may seem normal initially. Indeed, grip may become more powerful over several seconds of strength testing. This is referred to as Lambert’s sign.3 For the same reason, stretch reflexes may become normal or near normal after exercising the muscles briefly.4

Many (50-70%) of these patients have associated cancer, most commonly small cell lung cancer. However, the syndrome may precede the diagnosis of cancer by two years.

2 What further investigations would you order to confirm the underlying neurological diagnosis?

Short answer

Electrophysiological testing with repetitive stimulation and antibodies to voltage gated calcium channels.

Long answer

Electrophysiological studies showed decreased amplitude of motor nerves. Repetitive nerve stimulation was normal at low frequency (1-3 Hz). At high frequency (20 Hz, 30 Hz, and 50 Hz), an incremental increase in amplitude was seen after exercise.

In Lambert-Eaton myasthenic syndrome, compound muscle action potential amplitudes are small but latencies and conduction velocities are normal. Repetitive stimulation at 2 Hz may result in a decrease in the compound muscle action potential. However, if the frequency of stimulation is increased to 30 Hz or more, the compound muscle action potential will increase by 100-200% in patients with Lambert-Eaton myasthenic syndrome, but not in those with myasthenia gravis. In our patient, repetitive low frequency nerve stimulation produced a decremental response, but higher frequency stimulation produced a marked increase in the compound muscle action potential, confirming a diagnosis of a presynaptic neuromuscular disorder—that is, Lambert-Eaton myasthenic syndrome.

Serological testing for voltage gated calcium channel antibodies is positive in 85% of patients with this syndrome. This test was not performed in our patient.

3 What is the main differential diagnosis?

Short answer

Myasthenia gravis.

Long answer

Because of similarities in clinical presentation, Lambert-Eaton myasthenic syndrome can easily be mistaken for myasthenia gravis. However, ocular and bulbar muscles are affected more prominently in myasthenia gravis than in Lambert-Eaton myasthenic syndrome. Moreover, the lower extremities are less commonly affected in patients with myasthenia gravis.5 Autonomic features may also be able to differentiate between the two conditions.

Electrophysiological studies will also differentiate Lambert-Eaton myasthenic syndrome from myasthenia gravis. Compound muscle action potential amplitudes are reduced in myasthenia gravis and are not increased after repetitive stimulation.

Patient outcome

The patient was started on prednisone 10 mg daily, increasing to 50 mg daily over the next few days, and pyridostigmine 30 mg every six hours. He did not respond to antibiotics and his condition worsened. After discussions with the family his code status was changed to palliative care. He died peacefully in his sleep.

Notes

Cite this as: BMJ 2012;344:e461

Footnotes

  • Competing interests: The author has completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declares: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Provenance and peer review: Not commissioned; externally peer reviewed.

  • Patient consent obtained.

References