Variant Of Stiff-person Syndrome Research Articles

Progressive Encephalomyelitis with Rigidity and Myoclonus Treated with Rituximab: Case Report and Review of the Literature

A woman in her 50s presented with hyper-religiosity, auditory hallucinations, episodes of staring associated with unresponsiveness and stiffening of her entire body. A broad workup excluded autoimmune encephalitis, sarcoidosis, and prion disease. She was diagnosed with PERM (progressive encephalomyelitis with rigidity and myoclonus) syndrome which was supported by elevated cerebrospinal fluid (CSF) autoantibodies against glutamic acid decarboxylase (GAD) glutamic acid decarboxylase. She responded to treatment with corticosteroids and weekly rituximab therapy over four weeks. PERM is an autoimmune condition which is a rare variant of stiff person syndrome involving rigidity, dysautonomia and encephalopathy. PERM requires the clinician to have a high index of clinical suspicion to recognize and treat.

O-35 The Stiff Person Syndrome. Neurophysiological findings

Background Stiff Person Syndrome (SPS) an encephalomyelitis, is an immune-mediated disorder characterized by rigidity of the axial and proximal limb muscles with painful spasThis rare disease responds to immunotherapies and is frequently associated with other autoimmune diseases. More than 80% of SPS patients have autoantibodies to GAD65 and up to 15% have antibodies to glycinereceptor. Neurophysiological studies can help in the diagnosis by demonstrating the presence of continuous motor unit activity at rest, that the patient cannot voluntarily suppress. Material and methods We present a male patient 28 y/o with a history of weight loss, abdominal pain, ortostathic hypotension, ptosis and babinski sign, whith stiffness and painful spasms in both cuadriceps, tibialis anterior, gastronemius, rectus abdominis, thoracic and lumbar paraspinal muscles. Results EMG showed continuous, involuntary activity of normal motor unit potentials. Painful spasms of involuntary muscle activity, were also detected. No other abnormal spontaneus activity such as fibrilations, positive waves, miokimias, high frequency nor myotonic or neuromyotonic discharges were recorded. The SSR was absent en both hands. The Silent period was normal. ENG and SFEMG were normal. Antibodies to glycinereceptors were positive. After treatment with IvIg and plasma exchange the patient had moderate improvement and at present he is on baclofen, diazepam, methylprednisone and levetirazetam, with persistence of fluctuating stiffness and spas. Conclusions The neurophysiological studies play an important role in the differential diagnosis of the diseases associated with excess motor unit activity, leading in this patient to the diagnosis of encephalomyelitis with rigidity, variant of SPS.

F59. Spasmodic reflex myoclonus-an characteristic electrophysiological manifestation for the diagnosis of Stiff-person syndrome

Introduction Stiff person syndrome (SPS) is a rare disease entity and the pivotal clinical features contain progressive course of fluctuating stiffness of the low back and lower limbs. Progressive encephalomyelitis with rigidity and myoclonus (PERM) is one of the unique variants of stiff person syndrome, and it was characterized with rigidity, stimulus-sensitive spasms, myoclonus, autonomic disturbance, and brainstem signs. These features resemble those of hyperekplexia. The accurate diagnosis of SPS is difficult but is crucial for the in time intervention with immunotherapy for life saving. In addition to the detection of responsible antibody, clinical electrophysiological manifestation, spasmodic reflex myoclonus, would be of great help in establishing the diagnosis. Methods Multichannel surface electromyogram (sEMG) and accelerometer recordings were conducted over the lumbar paraspinalis, rectus abdominalis, quadriceps, and hamstring muscles. Stimulus sensitive phenomenon was illustrated with accelerometer tapped over the pinprick. The signals were processed and digitized with CED power1401 with Spike2. The band pass for sEMG was set from 80 Hz to 1000 Hz. Results The results demonstrated that episodes of spontaneous onset of spasm of the low trunk and legs lasted about seconds to minutes. Stimuli with nose tip tapping, would elicit vigorous jerks with dissemination of long lasting muscle spasm of the neck, paraspinal muscle, rectus abdominalis muscle, to quadriceps and hamstring muscles in a descending spreading pattern. The unique electrophysiological manifestations illustrate the characteristic feature of spasmodic reflex myoclonus. The surface EMG recording also showed the phenomena of habituation, in which a trend of amplitude decrescendo from the first toward the third EMG responses were observed during consecutive auditory stimulus. The serum levels of anti-glutamic acid decarboxylase 65 antibodies was 164 IU. Conclusion The unique EMG pattern can help identify SPS. The clinical features of spasmodic reflex myoclonus are similar to hyperekplexia. However, there are some differences between the two phenomena. Unlike hyperekplexia, the spasmodic reflex myoclonus can be habituated after repetitive stimulation in the SPS patient. Furthermore, the initial myoclonic bursts of spasmodic reflex myoclonus were not present in hyperekplexia and the EMG burst duration was much shorter of the hyperekplexia as compared with that of spasmodic reflex myoclonus. These neurophysiological features discern spasmodic reflex myoclonus from hyperekplexia and are helpful in making diagnosis of SPS.

Autoantibodies against glycine-associated synaptic proteins in stiff-person syndrome

Background: Autoantibodies against the postsynaptic glycine receptor were recently reported in patients with variants of stiff-person syndrome (SPS). The glycine receptor was presumed an autoantibody target because several mutations in its two subunits are associated with hereditary hyperekplexia, which in some instances resembles SPS. In a cohort of patients with SPS and related movement disorders, we report autoantibodies against two further proteins of inhibitory glycinergic synapses, glycine receptor-clustering gephyrin and presynaptic glycine transporter 2 (GlyT2/SLC6A5).

Encéphalomyélite progressive avec rigidité révélée par une douleur abdominale

IntroductionStiff-person syndrome is rare neurological disease, associating trunk rigidity and painful muscular spasms. A clinical variant of stiff person syndrome is the progressive encephalomyelitis with rigidity and myoclonus (PERM), which includes neurological cognitive disturbances. Case reportWe report a 73-year-old woman initially addressed for abdominal pain, anorexia and severe weight-loss, for whom diagnosis of PERM was made. ConclusionBecause of its various clinical presentations, sometimes without evidence for neurological disease, the diagnosis of PERM is delayed. The presence of antineuropile antibodies associated with muscular spasms at electromyogram are strong evidence for this diagnosis.

抗グリシン受容体抗体関連疾患の臨床スペクトラム

Anti-glycine receptor (anti-GlyR) antibodies were first reported in 2008 in a case of progressive encephalomyelitis with myoclonus and rigidity (PERM), which is a variant of stiff-person syndrome (SPS). After that, the antibodies have been studied extensively. At least 40 patients have been reported or presented until May 2013. We reviewed 28 patients (median age 47 years, range 1 to 75 years), whose clinical data are available. Seventeen patients (60%) were male. We classified clinical phenotype into PERM (17), classic SPS (5), variant SPS (5), and others (1: progressive optic atrophy). Nine patients (32%) had ant-GAD antibodies. Accompanied diseases included thyroiditis (5), diabetes mellitus (3), thymoma (3), and Addison's disease (2). Twenty-one patients (75%) treated with immunotherapy or thymectomy improved, but two of six patients without immunotherapy died or developed cardiac arrest. The clinical features suggested that antibody-mediated inhibition of the GlyR on the brainstem nuclei or spinal inhibitory interneurons may cause continuous firing of α motor neurons and paroxysmal excessive response to a variety of afferent impulses, leading to increased stiffness, brainstem signs, trismus, myoclonus, painful spasms or hyperekplexia. Phenotype associated with the anti-GlyR antibodies may be broader than previously thought, but among those PERM is the most common phenotype.

Central Nervous System Destruction Mediated by Glutamic Acid Decarboxylase-Specific CD4+ T Cells

High titers of autoantibodies against glutamic acid decarboxylase (GAD) 65 are commonly observed in patients suffering from type 1 diabetes as well as stiff-person syndrome (SPS), a disorder that affects the CNS, and a variant of SPS, progressive encephalomyelitis with rigidity and myoclonus. Although there is a considerable amount of data focusing on the role of GAD65-specific CD4(+) T cells in type 1 diabetes, little is known about their role in SPS. In this study, we show that mice possessing a monoclonal GAD65-specific CD4(+) T cell population (4B5, PA19.9G11, or PA17.9G7) develop a lethal encephalomyelitis-like disease in the absence of any other T cells or B cells. GAD65-reactive CD4(+) T cells were found throughout the CNS in direct concordance with GAD65 expression and activated microglia: proximal to the circumventricular organs at the interface between the brain parenchyma and the blood-brain barrier. In the presence of B cells, high titer anti-GAD65 autoantibodies were generated, but these had no effect on the incidence or severity of disease. In addition, GAD65-specific CD4(+) T cells isolated from the brain were activated and produced IFN-gamma. These findings suggest that GAD65-reactive CD4(+) T cells alone mediate a lethal encephalomyelitis-like disease that may serve as a useful model to study GAD65-mediated diseases of the CNS.

Progressive encephalomyelitis with rigidity and myoclonus preceding otherwise asymptomatic Hodgkin's lymphoma

Stiff-person syndrome (SPS), a rare neuroimmunological disorder, is characterized by symmetrical rigidity and muscle stiffness, particularly of axial and proximal limb muscles. Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a variant of SPS which includes additional clinical features (e.g. sensory symptoms, brain stem signs and pathological CSF findings). An association of both SPS and PERM with (solid) malignancies has been previously reported. Beyond this, there have been single reports of SPS in the setting of Hodgkin's lymphoma (HL). Here, we present a case of PERM associated with HL, with PERM preceding occurrence of lymphoma by more than seven months. Our observation has obvious implications for the management and, in particular, diagnostic evaluation of patients with PERM.

Glutamic acid decarboxylase antibody-positive paraneoplastic stiff limb syndrome associated with carcinoma of the breast

Stiff limb syndrome (SLS) is a rare "focal" variant of stiff person syndrome which presents with rigidity and painful spasms of a distal limb, and abnormal fixed foot or hand postures. Anti-glutamic acid decarboxylase antibodies (GAD-Ab) are variably present in most cases. Most reported cases of SLS are unassociated with cancer. We describe a patient with SLS as a paraneoplastic manifestation of breast carcinoma, in whom GAD-Ab was present. The patient responded very well to oral diazepam, baclofen and steroids.This is the third reported case of SLS as a paraneoplastic accompaniment to cancer.

Specific Clinical Features Described for Rare Variant of Stiff-Person Syndrome

Specific Clinical Features Described for Rare Variant of Stiff-Person Syndrome