The results of this search were cross-referenced and combined with the known patients from our previous comprehensive study of 79 patients with SMS at the Mayo Clinic, 5 of whom had symptom onset prior to the age of 18. 3 years. including modified Rankin scale. == RESULTS == We 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 Nevanimibe hydrochloride functional movement disorder (n = 2), generalized dystonia and Nevanimibe hydrochloride 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 65IgG in all cases (median value, 754 nmol/L; range, 0. 06-3847 nmol/L; normal value, 0. 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 Nevanimibe hydrochloride 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. Historically, stiff-man syndrome (SMS)1has been an underrecognized disorder among adults and is frequently misdiagnosed as another neurological disorder or as a psychogenic disorder. 2The paucity of literature pertaining to childhood-onset SMS suggests this also may be so in child neurology practice. Patients with classic SMS (adults and children) may present with stiffness and spasms of the lumbar region and lower extremities, but some patients have a more anatomically restricted form of the disorder (SMS variants including stiff limb and stiff trunk), and rare cases present with whole-body stiffness as a component of Nevanimibe hydrochloride a severe autoimmune encephalomyelitis (known as progressive encephalomyelitis with rigidity and myoclonus [PERM]). 3-6 Patients within this SMS spectrum typically have coexisting autoimmune diseases, most commonly type 1 diabetes mellitus or thyroid dysfunction, and serological evidence IKK-gamma (phospho-Ser376) antibody of thyrogastric autoimmunity. 3An IgG specific for the 65-kDa isoform of glutamic acid decarboxylase (GAD65-IgG) is detected in 80% of SMS cases. 7, 8Other autoantibody markers aiding the diagnosis of the SMS spectrum in adults Nevanimibe hydrochloride include amphiphysin-IgG detected in patients with paraneoplastic neurological autoimmunity associated with breast adenocarcinoma or small-cell lung carcinoma, 9, 10and glycine receptor 1 subunit (GlyR1)IgG, which is usually encountered in a nonparaneoplastic context. 11, 12 Five patients in a recently reported cohort of 99 patients with SMS evaluated during a period of 25 years3had symptom onset before age 18 years; 2 of those were seropositive for both GlyR1-IgG and GAD65-IgG. 12This prompted us to interrogate our medical record index system for all pediatric patients assigned a diagnosis of SMS and to review the literature for pediatric cases. == Methods == This study was approved by the Mayo Clinic institutional review board (IRB 08-00807). We searched the Mayo Clinics computerized diagnostic index for patients with a first appointment at age 18 years or younger (January 1984-June 2012) who at.
The results of this search were cross-referenced and combined with the known patients from our previous comprehensive study of 79 patients with SMS at the Mayo Clinic, 5 of whom had symptom onset prior to the age of 18