Man’s ‘Diagnostic Conundrum’ Stems From Unusual Symptom Progression
The patient's symptoms were asymmetrical, confounding an obvious LEMS diagnosis
The diagnostic journey of a man in his early 30s with progressive muscle weakness that was ultimately determined to be due to Lambert-Eaton myasthenic syndrome (LEMS) was described in a recent case report.
The report, “Progressive motor quadriparesis with wasting: a diagnostic conundrum,” was published in BMJ Case Reports.
The pair of scientists in India who authored the report said they offered the case “to share their dilemmas and success in the evaluation of a young man” with unusual progression of LEMS symptoms.
The report centered on a man in his early 30s who started to notice gradual muscle weakness that at first affected only his right leg. Initially, only the upper portion of the leg was affected, but weakness spread to the lower leg over time as well.
About five months later, the man developed similar symptoms in both arms and then in his left leg. In all his limbs, the weakness spread in a proximal-to-distal pattern, initially affecting the upper part near the shoulder or hip, and then spreading down to the lower limbs.
By the time the man was evaluated by doctors — about nine months after the initial onset of symptoms — he was unable to leave his bed. In addition to limb weakness, he had profound weight loss — more than 30 kg (66 pounds) — and difficulties with speech and swallowing, as well as severe constipation.
The man had chewed tobacco for about two decades, but had no other noteworthy medical or family history. Researchers conducted a battery of clinical tests in order to deduce a diagnosis.
Based on the pattern of symptom onset, scientists at first thought he might have a motor neuron disease (MND), a group of disorders marked by the gradual dysfunction and death of the nerve cells that control body movements.
However, while tests of these nerves’ electrical activity showed some abnormalities, they were not consistent with what would be expected of a MND.
Scientists also tested for signs of nerve inflammation or damage due to infection, autoimmune disease, or exposure to heavy metals or drugs. None of these tests found a clear cause for the patient’s symptoms, however.
“When most of the clinical and investigational modalities came to nought, a rethink was required,” the researchers wrote.
Scientists then conducted physical examinations where muscle strength was tested after a brief period of exercise and found it improved slightly after exercise — a telltale sign of LEMS. Assessments of nerve activity confirmed that the strength of electrical signals increased after exercise, signaling the presence of LEMS.
Despite these clinical tests that suggested LEMS, the man tested negative for antibodies against voltage-gated calcium channels (VGCCs), the most common type of LEMS-driving antibody. Researchers also noted the muscle weakness progression was odd for LEMS, which usually affects both sides of the body symmetrically. In this case, the man’s legs were affected asymmetrically.
The man was initially treated with anti-inflammatory steroids with no improvement. He was then given muscle strengtheners — pyridostigmine (sold as Mestinon, among other brands) and 4-aminopyridine (sold as Ampyra, among other brand names) — which led to “a slight but definitive clinical improvement … in speech, neck, trunk and limb power.”
The patient’s condition improved further after a plasma exchange. At follow-up after two months, his speech had normalized, he was able to sit and stand independently, and could walk with assistance. After five months with immune-modulating therapies and muscle strengtheners, he could walk unassisted with a “waddling” gait.
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