Childhood Onset of Stiff-Man Syndrome

Abstract

IMPORTANCE Reports of pediatric-onset stiff-man syndrome (SMS) are rare. This may be an underrecognized disorder in child neurology practice.OBJECTIVE To describe patients with disorders in the SMS spectrum beginning in childhood. DESIGN, SETTING, AND PARTICIPANTSThis study was a medical record review and serological evaluation conducted at child and adult neurology clinics at the Mayo Clinic, Rochester, Minnesota. Systematic review of the literature was conducted of patients who presented from 1984-2012 with onset of symptomatic SMS occurring at age 18 years or younger. MAIN OUTCOMES AND MEASURESResponse to symptomatic and immunotherapies, patient and physician reported, including modified Rankin scale. RESULTSWe identified 8 patients with childhood-onset SMS, representing 5% of patients with SMS evaluated at Mayo Clinic during a period of 29 years (4 were girls). The median age at symptom onset was 11 years (range, 1-14 years). The diagnosis in 3 patients was not established until adulthood (median symptom duration at diagnosis, 14 years; range, 0-46 years). The phenotypes encountered were: classic SMS (n = 5, involving the low back and lower extremities), variant SMS (n = 2, limited to 1 limb [with dystonic posture] or back), and progressive encephalomyelitis with rigidity and myoclonus (n = 1). Initial misdiagnoses included functional movement disorder (n = 2), generalized dystonia and parkinsonism (n = 1), and hereditary spastic paraparesis (n = 1). Six patients had 1 or more coexisting autoimmune disorders: type 1 diabetes mellitus (n = 4), thyroid disease (n = 2), and vitiligo (n = 2). Serologic study results revealed glutamic acid decarboxylase 65-IgG in all cases (median value, 754 nmol/L; range, 0.06-3847 nmol/L; normal value, Յ0.02 nmol/L) and glycine receptor antibody in 3 cases. Improvements were noted with symptomatic therapy (diazepam, 6 of 6 patients treated, and oral baclofen, 3 of 3 treated) and immunotherapy (intravenous immune globulin, 3 of 4 treated and plasmapheresis, 3 of 4 treated). The 3 patients with glycine receptor antibody all improved with immunotherapy. At last follow-up, 4 patients had mild or no symptoms, but 4 had moderate or severe residual symptoms and required maintenance symptomatic therapy (n = 5) and immunotherapy (n = 4). Ten of 12 pediatric SMS cases identified by literature review had a severe whole-body phenotype resembling progressive encephalomyelitis with rigidity and myoclonus.CONCLUSIONS AND RELEVANCE Childhood-onset SMS is a rare but underrecognized and treatable disorder. Serological and electrophysiological testing aid diagnosis.

Utility of an immunotherapy trial in evaluating patients with presumed autoimmune epilepsy

“…Patients who responded despite having high serum levels of GAD65 antibody likely have coexisting autoantibodies targeting as yet unrecognized plasma membrane antigens, such as the glycine receptor autoantibody recently demonstrated to coexist with GAD65 antibody in some patients with stiff-man syndrome. 23,24 Similarly, one-third of patients with absent neural antibodies responded. These apparently seronegative patients may harbor as yet unidentified autoantibodies targeting plasma membrane antigens.…”

A Report of Stiff Person Syndrome in Tanzania with First Epidemiological Figures for Sub-Saharan Africa

“…Co-treatment with a course of corticosteroids did not seem to further improve the clinical condition, but the sample size is too small to draw firm conclusions from. Our patient series shows variants described elsewhere (stiff limb syndrome, likely paraneoplastic SPS and juvenile onset SPS) [1,3,4]. Laboratory tests to support the clinical diagnosis of SPS [1] are unfortunately lacking in our setting.…”

Cerebrospinal Fluid in Clinical Neurology

“…Immunotherapy with either steroids, intravenous immunoglobulin, or plasmapheresis might be benefi cial. Azathioprine and rituximab have been used with success as well (Bourke et al 2013 ;Clardy et al 2013 ;Kyskan et al 2013 ;Damasio et al 2013 ). Stiffness and spasms can be symptomatically treated with clonazepam, diazepam, baclofen, phenytoin, or gabapentin (Bourke et al 2013 ;Kyskan et al 2013 ;Mas et al 2011 ). …”

“…SPS and PERM are part of a clinical spectrum of antibody-mediated disease in both children and adults (Clardy et al 2013 ). Several antibodies have been associated with these syndromes.…”