Child Neurology: Diagnosis of Lambert-Eaton myasthenic syndrome in children

DISCUSSION

The incidence of LEMS is unknown in children. Its incidence in adults is 0.48 per million.¹ The incidence of LEMS in adults is rising, most likely related to recognition of the syndrome. The cancer most commonly associated with LEMS is small-cell lung cancer. Other malignancies associated with LEMS may have characteristics similar to small-cell lung cancer, including neuroendocrine origin.¹ In addition to our case, 3 other cases of LEMS related to neuroblastoma have been reported.^4,6 In non-tumor-associated LEMS, there may be a genetic predisposition to an autoimmune phenotype. A correlation with HLAB8 and HLADR3 and non-tumor-associated LEMS has been shown in adults.¹ No such associations have been reported in children.

There is no single confirmatory test for LEMS. Diagnosis is based on clinical signs and symptoms, electrophysiologic studies, and testing for serum P/Q-type voltage-gated calcium channels. The classic clinical triad for LEMS consists of proximal muscle weakness, hyporeflexia, and autonomic dysfunction.¹ Proximal muscle weakness is commonly seen in the lower extremities. As opposed to myasthenia gravis, weakness typically progresses in a proximal to distal and caudal to cranial fashion.¹ In contrast to Guillain-Barré syndrome, no sensory changes are present and weakness progresses proximally to distally as opposed to beginning distally and ascending.¹ It is unclear whether autonomic dysfunction was not a prominent feature or was an underrecognized feature of LEMS as reported in the pediatric literature.

One confounding factor in the diagnosis of LEMS is that postexercise facilitation may allow transient return of deep tendon reflexes and an improvement in proximal strength.¹ Nerve conduction studies characteristically show low CMAP amplitude. In addition, facilitation may not be seen initially. A low CMAP is nonspecific and may be seen clinically in combination with areflexia or hyporeflexia in polyneuropathies such as Guillain-Barré syndrome.

On repetitive nerve stimulation, a decrement in CMAP amplitude of ≥10% at low-frequency stimulation and an increment in CMAP amplitude of ≥100% at either high-frequency stimulation or postexercise testing are sensitive and specific for LEMS. Postexercise CMAP amplitude increment at high frequency of stimulation is perhaps more specific for LEMS than is repetitive nerve stimulation.¹

Testing for serum P/Q-type voltage-gated calcium channel antibodies is being done with increasing frequency in suspected cases of LEMS in adults. In adults, 85%–90% of patients with LEMS have serum P/Q-type voltage-gated calcium channel antibodies. This number is higher in cases with underlying small-cell lung cancer.¹ Antibody testing was not routinely performed in the cases of LEMS in the pediatric literature. Of the 11 cases reported, however, 4 of these had positive voltage-gated calcium channel antibodies.^2,5,7 Thus, the value of testing for P/Q-type voltage-gated calcium channel antibodies in children with suspected LEMS is unclear but may be helpful in circumstances where the diagnosis is unclear.

No uniform set of criteria exists for diagnosis of LEMS in children. Most of the reported cases used the combination of clinical signs and symptoms and electrophysiologic testing as the basis for diagnosis. However, in 2 cases, the EMG was suggestive of a myasthenic syndrome and one was normal.⁴ Another case showed normal nerve conduction.⁶ It is not stated whether repetitive nerve stimulation or exercise testing was performed in these cases. Due to the high sensitivity and specificity of the characteristic findings of LEMS in adults on electrophysiologic testing, it seems appropriate that repetitive nerve stimulation or exercise testing should be incorporated into the pediatric diagnostic algorithm for LEMS. The utility of testing for P/Q-type voltage-gated calcium channel antibodies for suspected LEMS in children is unclear due to the small number of cases reported.

The association of LEMS in children with cancer is unclear. Malignancy appears to be less common in pediatric patients with LEMS (4 of 11 cases).^3,4,6 However, due to the short follow-up in these cases (mean 13 months), one cannot exclude the possibility of later development of cancer. In a study of 100 consecutive adults diagnosed with LEMS and subsequently small-cell lung carcinoma, 96% were diagnosed with cancer within the first year of symptoms.¹¹ Current guidelines for tumor screening in paraneoplastic syndromes state that screening for 2 years postdiagnosis of LEMS in adults is sufficient.¹² There are insufficient data in the pediatric literature to make any such recommendations; however, based on adult literature, a screening period of at least 2 years for neoplasm in children with LEMS is prudent. In addition, screening for autoimmune disorders is reasonable given the adult literature on nontumor LEMS and a pediatric case report of LEMS in the setting of autoimmune disease.⁵

LEMS is an immune-mediated syndrome that rarely affects children. Diagnosis of LEMS in children should be based on the characteristic clinical presentation and on electrodiagnostic studies. The presence of serum P/Q-type calcium channel antibodies is supportive of the diagnosis of LEMS. LEMS may be associated with malignancy and autoimmune disease in children. In children without identifiable malignancy at presentation, screening for autoimmune disease and close surveillance for development of cancer for at least 2 years should be performed.