Background Muscle cramp, twitching and stiffness are common symptoms reported by patients attending the neuromuscular clinic. In a proportion of patients, these symptoms may be due to an acquired peripheral nerve hyperexcitabilty syndrome, including benign cramp fasciculation syndrome (BCFS) and disabling neuromyotonia (NMT) or Isaac's syndrome. Antibodies to voltage–gated potassium channels (VGKC) can be detected in approximately 40% of patients with NMT. Recent literature highlights that antibodies which bind to VGKC–associated proteins may also be involved[1]. We reviewed a cohort of patients attending the muscle clinic, who had their sera tested for VGKC–antibodies based on their symptoms and examination findings.

Methods We retrospectively studied 44 patients who attended the muscle clinic during a 6–month period (April 2012–September 2012). All patients had their sera tested for VGKC–antibodies. Most (31/44; 70%) were also tested for glutamic acid decarboxylase (GAD) autoantibodies, which are usually elevated in stiff person syndrome (SPS). The majority (37/44; 84%) were further investigated with neurophysiology. Patients were diagnosed on the basis of their clinical features and investigation results. Those diagnosed with BCFS or NMT were further studied to ascertain specific diagnostic features.

Results Muscle cramp, twitching or stiffness was reported in 40 of 44 patients (91%) with cramp being the most frequently reported symptom (34/44; 77%). However, only 6 patients (14%) tested positive for VGKC–antibodies and 5 were positive for GAD–antibodies, including 2 patients who were positive for both VGKC and GAD antibodies.

Neurophysiology was carried out in 37 (84%) patients. An underlying neuropathy was present in 9 patients. EMG findings included spontaneous activity in 8 patients, myopathic changes in 3, neurogenic changes in 1 and a further patient who displayed mixed myopathic–neurogenic features on EMG.

A third of patients (15/44; 34%) were diagnosed with BFCS or NMT, 2 of these were felt to have symptoms overlapping with SPS. All patients reported cramp, twitching or muscle stiffness and 60% of them reported two of these symptoms. Five patients had raised VGKC–antibodies, including one patient who was also positive for GAD–antibodies. Another patient who was positive for both VGKC and GAD antibodies was felt to have a clinical diagnosis of SPS rather than NMT. EMG supported the diagnosis of BFCS/NMT in 4 patients who were otherwise negative for VGKC–antibodies. Another 6 patients were diagnosed with BCFS based on clinical impression despite negative EMG studies and negative VGKC–antibodies.

Conclusions Although patients' initial symptoms suggested peripheral nerve hyperexcitability, VGKC–antibodies were detected in only a small proportion of patients. It would be interesting to study how many of these patients would turn out to have antibodies to the VGKC–complexed protein, contactin–associated protein–2 (CaspR2).¹ If the yield to the latter proved high, then testing for these antibodies would be of significant diagnostic value.