This disorder is characterized by progressive muscle rigidity, stiffness, and painful spasms triggered by auditory, sensory, or emotional stimuli. Rigidity mainly involves the lower trunk and legs, but it can affect the upper extremities and neck. Sometimes improve with sleep and general anesthetics. Electrophysiologic studies demonstrate continuous motor unit activity. The associated antibodies target proteins (GAD, amphiphysin) involved in the function of inhibitory synapses using y-aminobutyric acid (GABA) or glycine as neurotransmitters. The presence of amphiphysin antibodies usually indicates a paraneoplastic etiology related to SCLC and breast cancer. By contrast, GAD antibodies may occur in some cancer patients but are much more frequently present in the nonparaneoplastic disorder. GlyR antibodies may occur in some patients with stiff-person syndrome; these antibodies are more frequently detectable in patients with PERM.
Figure: Schematic representation of an inhibitory synapse showing the main autoimmune targets (GAD, amphiphysin, GABA receptor, and glycine receptor) and the corresponding neurologic disorders. GAD antibodies predominantly occur in stiff-person syndrome (SPS), cerebellar ataxia, and epilepsy, sometimes in the setting of encephalitis. Amphiphysin antibodies are markers of paraneoplastic SPS and breast cancer, GlyR antibodies often associate with progressive encephalomyelitis with rigidity and myoclonus (PERM), and GABAa receptor antibodies occur in a form of autoimmune encephalitis that is frequently associated with refractory seizures and status epilepticus.
Optimal treatment of stiff-person syndrome requires therapy of the underlying tumor, glucocorticoids, and symptomatic use of drugs that enhance GABA-ergic transmission (diazepam, baclofen, sodium valproate, tiagabine, vigabatrin). IVIg and plasma exchange are transiently effective in some patients, and there are reports of responses to rituximab in patients who did not respond to other treatments.
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