Mild clinical expression of Lambert–Eaton myasthenic syndrome in a patient with HIV infection

Neuromuscular complications of HIV are related to immunodeficiency, direct cytotoxicity of the virus or side effect of the treatments. Autoimmune disorders involving the nervous system, including Guillain–Barre syndrome, myositis and vasculitis, have been described in association with HIV. Neuromuscular junction autoimmune diseases such as myasthenia gravis have been occasionally reported in patients with HIV, whereas the Lambert–Eaton myasthenic syndrome (LEMS) has never been described. We report an unusual case of paucisymptomatic LEMS in a patient with HIV infection.

Case report

A 42‐year‐old non‐smoker, HIV positive, black African male was referred to us with a 2 year history of progressive but fluctuant weakness of the lower limbs. Comorbidities included chronic inactive hepatitis B with undetectable viraemia and a history of L4–5 laminectomy for a spinal canal stenosis. Treatment with highly active antiretroviral therapy (HAART) was initiated 6 months before hospitalisation, although neither biological nor clinical signs of immunosuppression were detected.

At the time of admission, he did not complain of diplopia, speech or swallowing, but had a dry mouth as the only autonomic symptom. Examination of the cranial nerves revealed a bilateral ptosis that was not modified by Simpson's test (ie, ptosis worsened by effort). Examination of the upper limbs was normal except for symmetrical weak tendon jerks. Examination of the lower limbs revealed a paresis, which predominated on the iliopsoas muscles (grade 4 on the Medical Research Council scale). The muscle palpation and the sensory multimodal examination were normal. The findings from the remainder of his neurological and general examination were normal.

A repetitive low rate stimulation (3 Hz) test revealed a significant decrement of up to 40% in the upper limb muscle (fig 1A). High rate (50 Hz) stimulations, in contrast, induced an incremental response, from mild (+80%, fig 1B) to marked (+750%, fig 1C). Single fibre electromyography performed in the left extensor digitorum communis confirmed a severe defect of neuromuscular transmission with a marked increase in jitter and numerous blockings (fig 1D). These results were highly suggestive of LEMS.¹

Figure 1 (A) Low rate (3 Hz) repetitive stimulation test; recordings at the left hand over the abductor digiti minimi. A 40% decrement is recorded. Note the continuous decrease in M response from the first to the 10th stimulus, which is not the usual myasthenic pattern but is suggestive of Lambert–Eaton myasthenic syndrome, and the amplitude of the initial M response within the normal range (8.6 mV). (B) High rate (50 Hz) repetitive stimulation test; recordings at the left hand over the abductor digiti minimi. A mild 80% increment is recorded. (C) High rate (50 Hz) repetitive stimulation test; recordings at the left foot abductor hallucis brevis. A marked 750% increment is recorded. Note that amplitude of the initial M response is markedly reduced (0.3 mV). (D) Stimulated (10 Hz) single fibre eletromyography performed in the left extensor digitorum communis. The jitter of the marked muscle fibre potential is strongly increased at 213 μV, and there is a 51% rate of blocking.

Serum autoantibodies directed against voltage gated calcium channels (VGCC) were positive (72 PM, normal range ⩽45 PM), and their presence were confirmed 1 year after hospitalisation (107 PM). Other autoantibodies which tested as negative were antiacetylcholine receptor, antimuscle specific tyrosine kinase, antismooth muscle, antistriated muscle, antithyroglobulin, antithyroperoxidase and antinuclear antibodies.

Paraclinical investigation, including total body CT and positron emission tomography scan, prostate specific antigen, carcinoembryonic antigen, total testosterone, alpha‐fetoprotein, beta2‐microglobulin and immunoelectrophoresis of serum protein were normal. HTLV‐1 serology was negative. Total CD4⁺ cell count was >400/mm³, and viraemia was <50 copies/ml. Brain and spinal cord MRI and quadriceps surgical biopsy were also normal.

The patient received intravenous immunoglobulin G infusions (0.4 g/kg) over 5 days, associated with pyridostigmine (up to 600 mg/day), with no effect on symptoms. Introduction of 3,4‐diaminopyridine was refused by the patient. At the 1 year follow‐up, the patient was clinically stable with persistence of fluctuant weakness that was sometimes exacerbated and sometimes ameliorated by exercise. The biological, oncological and immunological screenings remained unchanged.

Discussion

LEMS is a rare disorder that can be paraneoplastic (60%) or non‐paraneoplastic (40%). In both forms autoantibodies to VGCC are implicated.¹ In our patient, LEMS was established by clinical features (weakness sometimes ameliorated by exercise, autonomic symptoms, weak tendon jerks) and suggestive electromyography findings associated with positive anti‐VGCC antibodies, known to be disease specific.²

Apart from HIV infection and HIV related treatments, we did not find any other trigger for the appearance of LEMS. The oncological screening was normal and no other concomitant autoimmune markers were detected. Interestingly, the spectrum of reported autoimmunity in HIV patients is increasing.³ In addition, HIV infection may lead to molecular mimicry, known to be a common mechanism of autoimmunity. Furthermore, HIV infection has been associated with B cell stimulation and many autoantibodies are reported in HIV patients.³ Sustained immune restoration secondary to the initiation of HAART has been associated with the appearance of autoimmune diseases, but neither significant immunosuppression nor high viraemia, or opportunistic infection, has been detected. In addition, no other neurological complication of HIV secondary to immunodeficiency or direct cytotoxicity of the virus was observed.⁴ Neuromuscular junction autoimmune disorders such as myasthenia gravis have been reported previously in HIV patients,⁵ whereas LEMS has never been described in association with HIV.

In this case report, the appearance of LEMS may have been triggered by modulation of the immune system secondary to HIV infection, although a fortuitous association cannot be excluded. Nevertheless, the mild clinical expression persisting after 1 year of follow‐up, despite the absence of treatment, remains unusual and may suggest a direct influence of the virus on autoimmunity. Interestingly, other examples of a milder phenotype of the disorders already exist in HIV infected patients, such as progressive multifocal leukoencephalopathy. In addition, improvement in myasthenia gravis symptoms in HIV infection turning into AIDS has been described.

In conclusion, this report underscores (i) the possible link between autoimmune disorders and HIV and (ii) that investigation of a HIV patient with unexplained fluctuant weakness should include exploration of LEMS.

Acknowledgements

We would like to thank Professor John Newsom‐Davis for advice and helpful comments.