Cerebellar Ataxia in LEMS Patients May Be Due to Calcium Channel Autoantibodies, Study Finds

Patients with Lambert-Eaton myasthenic syndrome (LEMS) and cerebellar ataxia may have autoantibodies against calcium channels, a Mayo Clinic study indicates.

The study, titled “Calcium Channel Autoimmunity: Cerebellar Ataxia and Lambert-Eaton Syndrome Coexisting,” appeared in the journal Muscle & Nerve.

Patients with LEMS typically show muscle weakness in the limbs and mild dysautonomia, which is characterized by dry eyes and mouth, and erectile dysfunction.

Over 90% of LEMS patients develop antibodies against the body’s own voltage-gated calcium channels (VGCC) of P/Q-type, a group of ion channels on the surface of cells.

These autoantibodies bind to the nerve terminal at the neuromuscular junction and block the entry of calcium into the cells, which reduces the release of the neurotransmitter acetylcholine and causes muscle weakness.

Another symptoms that may be associated with VGCC autoantibodies is cerebellar ataxia, which impairs movement, speech and swallowing. Research showed that patients with autoimmune ataxia have anti-VGCC antibodies. This correlation has also been described in case reports and in small case series.

Scientists reviewed medical records of 17 patients (53% women) with robust clinical features of both LEMS and cerebellar ataxia, and treated at the Minnesota clinic from 1977 to 2016. LEMS was diagnosed based on evidence of a neuromuscular junction defect and VGCC autoantibodies. Cerebellar ataxia was diagnosed through physical evaluation.

Findings reported that the median age at neurological symptom onset was 61 years (age range, 42–75). Patients were followed in-person for a median of seven months, and for 84 months from symptom onset; followup included communications between patients and physicians.

Muscle weakness was the initial symptom in eight patients, with cerebellar ataxia developing later, at a median of five months. In contrast, cerebellar ataxia developed first in four cases, with weakness occurring later (median of four months). Four patients had both weakness and cerebellar ataxia. One had nerve damage in the optic nerve with ataxia following one month later.

Nine patients had small-cell lung carcinoma, which is the most common cancer associated with LEMS; three patients survived for about eight years (over 100 months). The data also revealed that response to immunotherapies was best in patients without cancer and included eased ataxia and weakness. Decreased weakness was particularly evident in patients with long-term follow-up treated with Firdapse (amifampridine; 3,4-diaminopyridine), Mestinon (pyridostigmine) or both.

Nine of the 17 patients were alive at the last recorded follow‐up, which led to a median survival of 62 months. The authors considered this long-term survival notable and commented that the duration and severity of neurological disability, co-existing autoantibodies, the presence and extent of cancer, and different oncological treatment and immunotherapy may all affect survival results across studies.

“Calcium channel autoimmunity should be considered in patients with coexisting cerebellar ataxia and myasthenic weakness,” the researchers wrote.

“Affected patients may survive small-cell carcinoma or have immunotherapy-responsive neurological symptoms,” they added.