Stiff-man syndrome and variants: Clinical course, treatments, and outcomes

Andrew B McKeon, Maisha Robinson, Kathleen M. McEvoy, Joseph Y. Matsumoto, Vanda A Lennon, J. Eric Ahlskog, Sean J Pittock

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Abstract

Background: Little information is available about the incidence of stiff-man syndrome (SMS) (the classic form or its variants) or about long-term treatment responses and outcomes. Objective: To comprehensively describe the characteristics of a cohort of patients with SMS. Design: Observational study. Setting: Mayo Clinic, Rochester, Minnesota. Patients: Ninety-nine patients with classic SMS vs variants of the disorder, both glutamic acid decarboxylase 65 kD isoform (GAD65) antibody seropositive and seronegative. Main Outcome Measures: Neurological, autoimmune, serological, and oncological findings; treatments; and outcomes between January 1984 and December 2008. Results: The median follow-up duration was 5 years (range, 0-23 years). Seventy-nine patients (59 having classic SMS, 19 having partial SMS, and 1 having progressive encephalomyelitis with rigidity and myoclonus [PERM]) were GAD65 antibody seropositive. Sixty-seven percent (53 of 79) of them had at least 1 coexisting autoimmune disease, and 4% (3 of 79) had cancer. GAD65 antibody values at initial evaluation were significantly higher among patients with classic SMS (median value, 623 nmol/L) than among patients with partial SMS (median value, 163 nmol/L) (P<.001). The initial GAD65 antibody value was positively correlated with the last follow-up Rankin score (P=.03). Among 20 patients who were GAD65 antibody seronegative (6 with classic SMS, 12 with partial SMS, and 2 with PERM), 15% (3 of 20) had at least 1 coexisting autoimmune disease, and 25% (5 of 20) had cancer (3 with amphiphysin autoimmunity and breast carcinoma and 2 with Hodgkin lymphoma). Excluding patients with PERM, all patients but 1 had sustained improvements with at least 1 γ-aminobutyric acid agent, usually diazepam; the median dosage for patients with classic SMS was 40.0 mg/d. Additional improvements occurred among 14 of 34 patients (41%) who received immunotherapy (intravenous immune globulin, azathioprine, prednisone, mycophenolate mofetil, or cyclophosphamide). Sixteen of 25 patients (64%) with extended follow-up duration remained ambulatory. Conclusions: Recognition of classic SMS vs variants is important because appropriate therapy improves symptoms in most patients. Classification by anatomical extent and by GAD65 antibody serostatus gives important diagnostic and prognostic information.

Original languageEnglish (US)
Pages (from-to)230-238
Number of pages9
JournalArchives of Neurology
Volume69
Issue number2
DOIs
StatePublished - Feb 2012

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Stiff-Person Syndrome
Glutamate Decarboxylase
Protein Isoforms
Myoclonus
Antibodies
Syndrome
Autoimmune Diseases
Mycophenolic Acid
Aminobutyrates
Intravenous Immunoglobulins
Azathioprine
Diazepam
Prednisone
Autoimmunity
Hodgkin Disease

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

Stiff-man syndrome and variants : Clinical course, treatments, and outcomes. / McKeon, Andrew B; Robinson, Maisha; McEvoy, Kathleen M.; Matsumoto, Joseph Y.; Lennon, Vanda A; Ahlskog, J. Eric; Pittock, Sean J.

In: Archives of Neurology, Vol. 69, No. 2, 02.2012, p. 230-238.

Research output: Contribution to journalArticle

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abstract = "Background: Little information is available about the incidence of stiff-man syndrome (SMS) (the classic form or its variants) or about long-term treatment responses and outcomes. Objective: To comprehensively describe the characteristics of a cohort of patients with SMS. Design: Observational study. Setting: Mayo Clinic, Rochester, Minnesota. Patients: Ninety-nine patients with classic SMS vs variants of the disorder, both glutamic acid decarboxylase 65 kD isoform (GAD65) antibody seropositive and seronegative. Main Outcome Measures: Neurological, autoimmune, serological, and oncological findings; treatments; and outcomes between January 1984 and December 2008. Results: The median follow-up duration was 5 years (range, 0-23 years). Seventy-nine patients (59 having classic SMS, 19 having partial SMS, and 1 having progressive encephalomyelitis with rigidity and myoclonus [PERM]) were GAD65 antibody seropositive. Sixty-seven percent (53 of 79) of them had at least 1 coexisting autoimmune disease, and 4{\%} (3 of 79) had cancer. GAD65 antibody values at initial evaluation were significantly higher among patients with classic SMS (median value, 623 nmol/L) than among patients with partial SMS (median value, 163 nmol/L) (P<.001). The initial GAD65 antibody value was positively correlated with the last follow-up Rankin score (P=.03). Among 20 patients who were GAD65 antibody seronegative (6 with classic SMS, 12 with partial SMS, and 2 with PERM), 15{\%} (3 of 20) had at least 1 coexisting autoimmune disease, and 25{\%} (5 of 20) had cancer (3 with amphiphysin autoimmunity and breast carcinoma and 2 with Hodgkin lymphoma). Excluding patients with PERM, all patients but 1 had sustained improvements with at least 1 γ-aminobutyric acid agent, usually diazepam; the median dosage for patients with classic SMS was 40.0 mg/d. Additional improvements occurred among 14 of 34 patients (41{\%}) who received immunotherapy (intravenous immune globulin, azathioprine, prednisone, mycophenolate mofetil, or cyclophosphamide). Sixteen of 25 patients (64{\%}) with extended follow-up duration remained ambulatory. Conclusions: Recognition of classic SMS vs variants is important because appropriate therapy improves symptoms in most patients. Classification by anatomical extent and by GAD65 antibody serostatus gives important diagnostic and prognostic information.",
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AU - Ahlskog, J. Eric

AU - Pittock, Sean J

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N2 - Background: Little information is available about the incidence of stiff-man syndrome (SMS) (the classic form or its variants) or about long-term treatment responses and outcomes. Objective: To comprehensively describe the characteristics of a cohort of patients with SMS. Design: Observational study. Setting: Mayo Clinic, Rochester, Minnesota. Patients: Ninety-nine patients with classic SMS vs variants of the disorder, both glutamic acid decarboxylase 65 kD isoform (GAD65) antibody seropositive and seronegative. Main Outcome Measures: Neurological, autoimmune, serological, and oncological findings; treatments; and outcomes between January 1984 and December 2008. Results: The median follow-up duration was 5 years (range, 0-23 years). Seventy-nine patients (59 having classic SMS, 19 having partial SMS, and 1 having progressive encephalomyelitis with rigidity and myoclonus [PERM]) were GAD65 antibody seropositive. Sixty-seven percent (53 of 79) of them had at least 1 coexisting autoimmune disease, and 4% (3 of 79) had cancer. GAD65 antibody values at initial evaluation were significantly higher among patients with classic SMS (median value, 623 nmol/L) than among patients with partial SMS (median value, 163 nmol/L) (P<.001). The initial GAD65 antibody value was positively correlated with the last follow-up Rankin score (P=.03). Among 20 patients who were GAD65 antibody seronegative (6 with classic SMS, 12 with partial SMS, and 2 with PERM), 15% (3 of 20) had at least 1 coexisting autoimmune disease, and 25% (5 of 20) had cancer (3 with amphiphysin autoimmunity and breast carcinoma and 2 with Hodgkin lymphoma). Excluding patients with PERM, all patients but 1 had sustained improvements with at least 1 γ-aminobutyric acid agent, usually diazepam; the median dosage for patients with classic SMS was 40.0 mg/d. Additional improvements occurred among 14 of 34 patients (41%) who received immunotherapy (intravenous immune globulin, azathioprine, prednisone, mycophenolate mofetil, or cyclophosphamide). Sixteen of 25 patients (64%) with extended follow-up duration remained ambulatory. Conclusions: Recognition of classic SMS vs variants is important because appropriate therapy improves symptoms in most patients. Classification by anatomical extent and by GAD65 antibody serostatus gives important diagnostic and prognostic information.

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