Stiff-Person Syndrome (Stiff Man Syndrome)

A condition characterized by persistent spasms (SPASM) involving multiple muscles, primarily in the lower limbs and trunk. The illness tends to occur in the fourth to sixth decade of life, presenting with intermittent spasms that become continuous. Minor sensory stimuli, such as noise and light touch, precipitate severe spasms. Spasms do not occur during sleep and only rarely involve cranial muscles. Respiration may become impaired in advanced cases. (Adams et al., Principles of Neurology, 6th ed, p1492; Neurology 1998 Jul;51(1):85-93)

Also Known As:

Networked: 378 relevant articles (21 outcomes, 24 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Dermatomyositis (Dermatopolymyositis)
2.	Myasthenia Gravis
3.	Lambert-Eaton Myasthenic Syndrome (Lambert-Eaton Syndrome)
4.	Polyneuropathies (Polyneuropathy)
5.	Multiple Sclerosis

Experts

1.	Dalakas, Marinos C: 19 articles (02/2015 - 05/2004)
2.	Hampe, Christiane S: 10 articles (01/2015 - 12/2005)
3.	Graus, Francesc: 7 articles (08/2015 - 05/2003)
4.	Geis, Christian: 7 articles (03/2015 - 11/2010)
5.	Vincent, Angela: 7 articles (08/2014 - 06/2003)
6.	Graus, F: 7 articles (06/2012 - 07/2000)
7.	Saiz, A: 7 articles (06/2012 - 07/2000)
8.	Toyka, Klaus V: 6 articles (03/2015 - 04/2005)
9.	Weishaupt, Andreas: 6 articles (03/2015 - 04/2005)
10.	Sommer, Claudia: 6 articles (03/2015 - 04/2005)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Stiff-Person Syndrome:

1.	Intravenous Immunoglobulins (IVIG)FDA Link 12/27/2001 - "Because stiff-person syndrome is most likely immune-mediated, we evaluated the efficacy of intravenous immune globulin. " 07/01/2008 - "In a controlled study in patients with stiff person syndrome IVIg was effective, with improvements in the distribution of stiffness index and heightened sensitivity scores. " 06/01/1994 - "To evaluate the efficacy of intravenous immune globulin (IVIG) in the treatment of stiff-man syndrome (SMS). " 05/30/2002 - "High-dose intravenous immune globulin for stiff-person syndrome." 05/30/2002 - "High-dose intravenous immune globulin for stiff-person syndrome."
2.	AntibodiesIBA 06/01/2003 - "The pathogenicity of these antibodies must be in some doubt, although intravenous immunoglobulin therapy has been shown to be beneficial in stiff man syndrome, consistent with an autoimmune aetiology for the disease. " 09/01/2013 - "Progress and stiff challenges in understanding the role of GAD-antibodies in stiff-person syndrome." 01/01/2013 - "Anti-GAD antibodies (GADA) are associated with the progression of stiff person syndrome and other neurological diseases, as well as the immune-mediated (type 1) diabetes. " 01/01/2013 - "Anti-GlyR antibodies induce rare, but severe, variants of stiff person syndrome that can be of paraneoplastic origin and life threatening due to autonomic dysfunction." 09/01/2011 - "Pathological findings in a case of stiff person syndrome with anti-GAD antibodies."
3.	BaclofenFDA LinkGeneric 10/01/1995 - "We performed a double-blind, placebo-controlled trial of intrathecal baclofen (ITB) in stiff-man syndrome. " 10/01/1995 - "Intrathecal baclofen therapy in stiff-man syndrome: a double-blind, placebo-controlled trial." 05/01/2013 - "Trialing of intrathecal baclofen therapy for refractory stiff-person syndrome." 01/01/2010 - "Intrathecal baclofen pump implantation in a case of stiff person syndrome." 09/01/2008 - "From our experience, we propose that intrathecal baclofen could be a considerable alternative treatment for patients with refractory stiff-person syndrome."
4.	Immunoglobulins (Immunoglobulin)IBA 05/01/2002 - "Effect of treatment with intravenous immunoglobulin on quality of life in patients with stiff-person syndrome." 08/01/2001 - "Benefit of intravenous immunoglobulin in autoimmune stiff-person syndrome in a child." 04/01/1997 - "Successful treatment of stiff man syndrome with intravenous immunoglobulin." 09/01/1994 - "Treatment of stiff-man syndrome with intravenous immunoglobulin." 12/01/1999 - "Long-term remission of refractory stiff-man syndrome after treatment with intravenous immunoglobulin."
5.	AutoantibodiesIBA 04/01/2013 - "[Stiff-person syndrome and related autoantibodies]." 11/01/2010 - "We suggest that these findings may explain the pathophysiology of the core signs of stiff person syndrome at the molecular level and show that autoantibodies can alter the function of inhibitory synapses in vivo upon binding to an intraneuronal key protein by disturbing vesicular endocytosis." 01/01/2010 - "Long-lived plasma cells and memory B cells produce pathogenic anti-GAD65 autoantibodies in Stiff Person Syndrome." 01/01/2008 - "The two possibilities to explain the pathogenic basis of stiff-person syndrome (SPS) are intrathecal sensitization of GAD65-reactive CD4+T cells and synthesis of GAD65-specific autoantibodies within the CNS [Rakocevic et al., Arch. " 10/01/2006 - "Moreover, sera from Stiff Person Syndrome and Type I Diabetes, disorders in which GAD65 autoantibodies are present, stained with profiles that were markedly different from JNCL sera. "
6.	Glutamate Decarboxylase (Decarboxylase, Glutamate)IBA 12/01/2014 - "Glutamate decarboxylase (GAD) is an autoantigen associated with the autoimmune disorders Type-1 diabetes (T1D) and stiff-person syndrome (SPS). " 06/01/2012 - "High levels of glutamic acid decarboxylase (GAD)-ab were initially described in patients with stiff person syndrome, and have since also been observed in patients with other neurological diseases. " 12/15/2010 - "Qualitative and quantitative evidence of anti-glutamic acid decarboxylase-specific intrathecal antibody synthesis in patients with stiff person syndrome." 01/01/2010 - "Stiff person syndrome is confirmed by testing for the anti-glutamic acid decarboxylase antibody. " 02/01/2009 - "Cerebrospinal fluid T cell responses against glutamic acid decarboxylase 65 in patients with stiff person syndrome."
7.	Diazepam (Valium)FDA LinkGeneric 05/01/1981 - "Diagnosis, by appropriate electrodiagnostic studies, is important because stiff-man syndrome is easily treated with high doses of diazepam." 01/01/1986 - "Clinical history, neurologic investigations, course, EMG findings, muscle biopsy and response to diazepam treatment in two patients fulfilled criteria established by Gordon, Januszko and Kaufman for the diagnosis of the stiff-man syndrome. " 08/01/1995 - "Clues to the patient's proper diagnosis coincide with the diagnostic criteria for stiff-man syndrome: the presence of a slowly progressive stiffness of the axial muscles and proximal limb muscles, making ambulation difficult; hyperlordosis of the lumbar spine; episodic spasms precipitated by jarring or sudden movement; a normal intellectual, sensory, and motor examination when not in spasm; and a marked amelioration of symptoms with the IV administration of diazepam. " 06/01/1989 - "Analysis of 13 patients with stiff-man syndrome examined at the Mayo Clinic during the past 30 years revealed that treatment with diazepam decreased the muscle spasms. " 09/01/1980 - "A 36-year-old diabetic man with the stiff-man syndrome previously treated with diazepam improved dramatically when baclofen was added to the regimen. "
8.	Immunoglobulin M (IgM)IBA 05/01/1997 - "In other controlled or open-label trials and case reports, IVIg produced improvement in several patients with the Lambert-Eaton myasthenic syndrome and myasthenia gravis but had a variable, mild, or unsubstantiated benefit in some patients with inclusion-body myositis, paraproteinemic IgM demyelinating polyneuropathy, certain intractable childhood epilepsies, polymyositis, multiple sclerosis, optic neuritis, and the stiff-man syndrome. " 05/01/1995 - "The neurological diseases with definite or putative immune pathogenesis include myasthenia gravis; Lambert-Eaton myasthenic syndrome; IgM monoclonal anti-myelin-associated glycoprotein-associated demyelinating polyneuropathy; Guillain-Barré syndrome; chronic inflammatory demyelinating polyneuropathy; multifocal motor neuropathy with or without GM1 antibodies; multiple sclerosis; inflammatory myopathies; stiff-man syndrome; autoimmune neuromyotonia; paraneoplastic neuronopathies and cerebellar degeneration; and neurological diseases associated with systemic autoimmune conditions, vasculitis, or viral infections. " 04/01/2007 - "Recommendations for use of IVIG were made for 14 conditions, including acute disseminated encephalomyelitis, chronic inflammatory demyelinating polyneuropathy, dermatomyositis, diabetic neuropathy, Guillain-Barré syndrome, Lambert-Eaton myasthenic syndrome, multifocal motor neuropathy, multiple sclerosis, myasthenia gravis, opsoclonus-myoclonus, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, polymyositis, Rasmussen's encephalitis, and stiff person syndrome; IVIG was not recommended for 8 conditions including adrenoleukodystrophy, amyotropic lateral sclerosis, autism, critical illness polyneuropathy, inclusion body, myositis, intractable childhood epilepsy, paraproteinemic neuropathy (IgM variant), and POEMS syndrome. " 11/01/1994 - "These are; ple21 in limbic encephalitis; PCD17, CDR62, CDR34, and CZF in paraneoplastic cerebellar degeneration; one of the anion transporters band 3 in chorea-acanthocytosis; visinin-like substance in cancer-associated retinopathy (CAR syndrome); myelin basic protein (MBP) and proteolipid protein (PLP) in acute disseminated encephalomyelitis; MBP, PLP and myelin-oligodendrocyte glycoprotein (MOG) in multiple sclerosis; glutamic acid decarboxylase in stiff-man syndrome; GM1 ganglioside in amyotrophic lateral sclerosis; peripheral nerve K+ channel in Isaacs syndrome; synaptotagmin in Lambert-Eaton syndrome; acetylcholine receptor in myasthenia gravis; GM1 ganglioside in Guillain-Barré syndrome; GQ1b ganglioside in Fisher syndrome; myelin-associated glycoprotein in IgM paraproteinemic neuropathy; HuD in paraneoplastic sensory neuropathy; and tRNA and HSP65 in polymyositis."
9.	etiracetam (levetiracetam)FDA LinkGeneric 11/01/2008 - "We studied the effects of oral levetiracetam (LEV) (500 mg twice daily) in three women with stiff-person syndrome in a single-blind, placebo-controlled study. " 11/01/2008 - "Levetiracetam in stiff-person syndrome." 09/01/2008 - "Levetiracetam for stiff-person syndrome: report of 2 patients." 01/27/2004 - "Levetiracetam improves paroxysmal symptoms in a patient with stiff-person syndrome." 09/01/2008 - "We report 2 patients with stiff-person syndrome whose spasms were greatly relieved by levetiracetam (Keppra)."
10.	Antineutrophil Cytoplasmic Antibodies (ANCA)IBA 05/01/2007 - "In the absence of a defined protocol, studies have demonstrated that IVIG therapy is effective in the treatment of myasthenia gravis, dermatomyositis, stiff person syndrome, antineutrophil cytoplasmic antibody positive systemic vasculitides, Graves' ophthalmopathy, and certain forms of systemic lupus erythematosus. "

Therapies and Procedures

1.	Plasmapheresis 08/01/1995 - "We described a 56-year-old man with stiff-man syndrome, who was markedly improved after plasmapheresis therapy. " 10/01/1991 - "These results provide additional evidence of an autoimmune mechanism for stiff-man syndrome and indicate plasmapheresis may be beneficial in some patients." 08/01/1999 - "Plasmapheresis and immunosuppression in stiff-man syndrome with type 1 diabetes: a 2-year study." 03/01/2013 - "Treatment of stiff-person syndrome with chronic plasmapheresis." 08/01/1995 - "Plasmapheresis is one choice in the management for stiff-man syndrome."
2.	Plasma Exchange 07/01/2014 - "The efficacy of therapeutic plasma exchange (TPE) in stiff-person syndrome (SPS) is unclear. " 07/01/2014 - "Efficacy of therapeutic plasma exchange for treatment of stiff-person syndrome." 08/01/2002 - "[Successful treatment in a patient with a focal form of stiff-person syndrome using plasma exchange and intravenous immunoglobulin therapy]." 02/01/2001 - "Plasma exchange in stiff-man syndrome." 01/01/1999 - "Double filtration plasma exchange and immunoadsorption therapy in a case of stiff-man syndrome with negative anti-GAD antibody."
3.	Drug Therapy (Chemotherapy) 06/01/2013 - "Stiff person syndrome improvement with chemotherapy in a patient with cutaneous T cell lymphoma." 11/01/2015 - "The marked clinical improvement following chemotherapy for pleuropulmonary blastoma was yet more proof of the pleuropulmonary blastoma-related stiff person syndrome. " 06/01/2008 - "Treatment of stiff-person syndrome was initiated with corticosteroids followed by chemotherapy against breast cancer, which led to a remarkable improvement of her neurological symptoms. "
4.	Immunotherapy 02/01/2010 - "Effects of immunotherapy on motor cortex excitability in Stiff Person Syndrome." 10/01/2011 - "Stiff-person syndrome (SPS) is a rare condition of progressive muscular rigidity and spasm, frequently accompanied by other autoimmune conditions, an association which has been further strengthened by the discovery of anti-GAD antibodies and the response of SPS to immunotherapies. " 02/01/2010 - "A number of cortical and spinal excitability variables have been tested in a patient with Stiff Person Syndrome (SPS), before and after immunotherapy with mycophenolate mofetil, intravenous immunoglobulin and corticosteroids, which normalized plasma levels of anti-GAD antibodies and dramatically improved the clinical picture. "
5.	Aftercare (After-Treatment) 12/01/1999 - "Long-term remission of refractory stiff-man syndrome after treatment with intravenous immunoglobulin."