Stiff person syndrome is a rare degenerative and frequently underdiagnosed immune-mediated condition of the CNS defined by progressive stiffness and painful spasms of mainly proximal and axial limb muscles.
The disease has a slow onset and gradually worsens; if left untreated, it can result in severe impairment and death.
Epidemiology
Classic SPS is estimated to impact 1 to 2 instances per million people in the total population, with females, regardless of ethnicity, being afflicted twice as frequently as males.
Most patients experience symptoms in their 30s or 40s. Only 5% of SPS instances in young adults have been documented.
Anatomy
Pathophysiology
The pathophysiology is attributed to an autoimmune inflammation caused by B-cells that damages several synaptic and inhibiting GABA neuronal components. Due to the hyperexcitability of the motor cortex, the production of autoantibodies, in contrast to antigens engaged with GABA release and synthesis within the CNS, leads to the malfunction of vital inhibitory pathways, which impairs the ability of the axial and truncal muscles to relax.
The most prevalent antigen in classic SPS is glutamic acid decarboxylase, an intracellular enzyme that converts glutamate into GABA. GAD is the main target of this disease. There are two isoforms of GAD: GAD65 and GAD67. The first isoform produces GABA when there is a greater demand, while GAD67 controls GABA synthesis at baseline.
Up to 30 percent of patients with GAD-SD, including SPS, have DM-1, and low anti-GAD antibody titers are reported in individuals with DM-1. High anti-GAD antibody titers, however, are only found in GAD-SD. Antibodies to amphiphysin or gephyrin are linked to a paraneoplastic form of SPS.
Amphiphysin is an intracellular synaptic protein that controls the production of GABA receptors at the axon membrane and is engaged in the endocytosis of the vesicle membrane. It has been shown that antibodies can decrease GABA receptor numbers against amphiphysin by lowering the endocytosis of GABA-containing vesicles. As a result, there is a reduction in the presynaptic vesicle pool, which affects GABA transmission.
Etiology
It is an autoimmune disorder characterized by high titers of autoantibodies against different inhibitory synaptic components, which impairs the function of these synapses by lowering levels of gamma-aminobutyric acid at pre- or postsynaptic neuronal junctions.
The paraneoplastic type, which makes up 5-10% of all cases, is distinguished by the presence of amphiphysin and, less commonly, gephyrin antibodies.
Breast adenocarcinoma, colonic adenocarcinoma, small-cell lung carcinoma, thyroid and thymus cancers, and Hodgkin’s lymphoma are the most frequent malignancies linked to paraneoplastic variants.
Genetics
Prognostic Factors
The clinical presentation, the severity of the symptoms, the presence of a coexisting neoplastic process, and the responsiveness to treatment are some variables that affect a patient’s prognosis for SPS.
It is critical to start therapy on time to stop or slow down development and prevent long-term consequences. With medication, most patients get better, although there are still instabilities brought on by mental and physical strain.
Despite the wide range of available treatments, some SPS patients have disease progression over time that results in impairment, irreversible orthopedic deformities, and the inability to walk.
Clinical History
Physical Examination
Age group
Associated comorbidity
Associated activity
Acuity of presentation
Differential Diagnoses
Laboratory Studies
Imaging Studies
Procedures
Histologic Findings
Staging
Treatment Paradigm
by Stage
by Modality
Chemotherapy
Radiation Therapy
Surgical Interventions
Hormone Therapy
Immunotherapy
Hyperthermia
Photodynamic Therapy
Stem Cell Transplant
Targeted Therapy
Palliative Care
Medication
Future Trends
Media Gallary
References
https://www.ncbi.nlm.nih.gov/books/NBK573078/
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Stiff person syndrome is a rare degenerative and frequently underdiagnosed immune-mediated condition of the CNS defined by progressive stiffness and painful spasms of mainly proximal and axial limb muscles.
The disease has a slow onset and gradually worsens; if left untreated, it can result in severe impairment and death.
Classic SPS is estimated to impact 1 to 2 instances per million people in the total population, with females, regardless of ethnicity, being afflicted twice as frequently as males.
Most patients experience symptoms in their 30s or 40s. Only 5% of SPS instances in young adults have been documented.
The pathophysiology is attributed to an autoimmune inflammation caused by B-cells that damages several synaptic and inhibiting GABA neuronal components. Due to the hyperexcitability of the motor cortex, the production of autoantibodies, in contrast to antigens engaged with GABA release and synthesis within the CNS, leads to the malfunction of vital inhibitory pathways, which impairs the ability of the axial and truncal muscles to relax.
The most prevalent antigen in classic SPS is glutamic acid decarboxylase, an intracellular enzyme that converts glutamate into GABA. GAD is the main target of this disease. There are two isoforms of GAD: GAD65 and GAD67. The first isoform produces GABA when there is a greater demand, while GAD67 controls GABA synthesis at baseline.
Up to 30 percent of patients with GAD-SD, including SPS, have DM-1, and low anti-GAD antibody titers are reported in individuals with DM-1. High anti-GAD antibody titers, however, are only found in GAD-SD. Antibodies to amphiphysin or gephyrin are linked to a paraneoplastic form of SPS.
Amphiphysin is an intracellular synaptic protein that controls the production of GABA receptors at the axon membrane and is engaged in the endocytosis of the vesicle membrane. It has been shown that antibodies can decrease GABA receptor numbers against amphiphysin by lowering the endocytosis of GABA-containing vesicles. As a result, there is a reduction in the presynaptic vesicle pool, which affects GABA transmission.
It is an autoimmune disorder characterized by high titers of autoantibodies against different inhibitory synaptic components, which impairs the function of these synapses by lowering levels of gamma-aminobutyric acid at pre- or postsynaptic neuronal junctions.
The paraneoplastic type, which makes up 5-10% of all cases, is distinguished by the presence of amphiphysin and, less commonly, gephyrin antibodies.
Breast adenocarcinoma, colonic adenocarcinoma, small-cell lung carcinoma, thyroid and thymus cancers, and Hodgkin’s lymphoma are the most frequent malignancies linked to paraneoplastic variants.
The clinical presentation, the severity of the symptoms, the presence of a coexisting neoplastic process, and the responsiveness to treatment are some variables that affect a patient’s prognosis for SPS.
It is critical to start therapy on time to stop or slow down development and prevent long-term consequences. With medication, most patients get better, although there are still instabilities brought on by mental and physical strain.
Despite the wide range of available treatments, some SPS patients have disease progression over time that results in impairment, irreversible orthopedic deformities, and the inability to walk.
https://www.ncbi.nlm.nih.gov/books/NBK573078/
medtigo
Stiff Person Syndrome
Updated :
October 3, 2022
Stiff person syndrome is a rare degenerative and frequently underdiagnosed immune-mediated condition of the CNS defined by progressive stiffness and painful spasms of mainly proximal and axial limb muscles.
The disease has a slow onset and gradually worsens; if left untreated, it can result in severe impairment and death.
Classic SPS is estimated to impact 1 to 2 instances per million people in the total population, with females, regardless of ethnicity, being afflicted twice as frequently as males.
Most patients experience symptoms in their 30s or 40s. Only 5% of SPS instances in young adults have been documented.
The pathophysiology is attributed to an autoimmune inflammation caused by B-cells that damages several synaptic and inhibiting GABA neuronal components. Due to the hyperexcitability of the motor cortex, the production of autoantibodies, in contrast to antigens engaged with GABA release and synthesis within the CNS, leads to the malfunction of vital inhibitory pathways, which impairs the ability of the axial and truncal muscles to relax.
The most prevalent antigen in classic SPS is glutamic acid decarboxylase, an intracellular enzyme that converts glutamate into GABA. GAD is the main target of this disease. There are two isoforms of GAD: GAD65 and GAD67. The first isoform produces GABA when there is a greater demand, while GAD67 controls GABA synthesis at baseline.
Up to 30 percent of patients with GAD-SD, including SPS, have DM-1, and low anti-GAD antibody titers are reported in individuals with DM-1. High anti-GAD antibody titers, however, are only found in GAD-SD. Antibodies to amphiphysin or gephyrin are linked to a paraneoplastic form of SPS.
Amphiphysin is an intracellular synaptic protein that controls the production of GABA receptors at the axon membrane and is engaged in the endocytosis of the vesicle membrane. It has been shown that antibodies can decrease GABA receptor numbers against amphiphysin by lowering the endocytosis of GABA-containing vesicles. As a result, there is a reduction in the presynaptic vesicle pool, which affects GABA transmission.
It is an autoimmune disorder characterized by high titers of autoantibodies against different inhibitory synaptic components, which impairs the function of these synapses by lowering levels of gamma-aminobutyric acid at pre- or postsynaptic neuronal junctions.
The paraneoplastic type, which makes up 5-10% of all cases, is distinguished by the presence of amphiphysin and, less commonly, gephyrin antibodies.
Breast adenocarcinoma, colonic adenocarcinoma, small-cell lung carcinoma, thyroid and thymus cancers, and Hodgkin’s lymphoma are the most frequent malignancies linked to paraneoplastic variants.
The clinical presentation, the severity of the symptoms, the presence of a coexisting neoplastic process, and the responsiveness to treatment are some variables that affect a patient’s prognosis for SPS.
It is critical to start therapy on time to stop or slow down development and prevent long-term consequences. With medication, most patients get better, although there are still instabilities brought on by mental and physical strain.
Despite the wide range of available treatments, some SPS patients have disease progression over time that results in impairment, irreversible orthopedic deformities, and the inability to walk.
https://www.ncbi.nlm.nih.gov/books/NBK573078/
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