| A 74-year-old patient suffers from painful muscle cramps when he stands since 30 years. He has no visible tremor but 16 Hz burst activity on EMG, indicating orthostatic tremor. Previous diagnosis was hysteria, stiff person syndrome or dystonia. This shows that EMG during standing should be part of the examination of patients with stiff muscles or muscle cramps. tremor was not strictly orthostatic. It appeared in back muscles while sitting, when the patient supported a weight with outstretched arms. Phase between muscles differed between normal standing and standing on heels. Subthreshold transcranial magnetic stimulation modulated timing of the tremor bursts and inhibited them at higher intensity stimulation. ( info) |
2/87. Immune-mediated retinopathy in a patient with stiff-man syndrome. BACKGROUND: Stiff-man syndrome is a rare neurological disorder characterised by rigidity and violent spasms of the body musculature. In the majority of patients, presence of antibodies against glutamic acid decarboxylase (GAD), the enzyme synthesizing gamma-aminobutyric acid (GABA), suggests an autoimmune attack against GABA-ergic inhibitory neurons. We report a 32-year-old patient with stiff-man syndrome and anti-GAD antibodies who developed subacute progressive loss of vision in the right eye, and in the left eye 18 months thereafter. methods: Ophthalmological work-up included electro-retinogram (ERG), visual evoked potentials (VEP) and fluorescein angiography. Antiretinal antibodies were investigated using an indirect immunofluorescence technique on frozen sections of macaque retina with patients serum and FITC-conjugated goat antihuman immunoglobulin. Staining with monoclonal anti-GAD65 antibodies and with serum from three healthy normals served as controls. RESULTS: visual acuity of both eyes decreased to 0.16 within a span of 6 weeks. Perimetry revealed a central scotoma in the visual field of both eyes. VEP and flash ERG were progressively disturbed on the right eye. On the left eye, initially only pattern ERG and photopic responses were abnormal. Follow-up recordings revealed widespread pathology of photopic single and flicker responses. Immunofluorescence revealed strong reactivity of the inner plexiform layer and to a lesser extent staining of the outer plexiform layer at dilutions of 1:1000 with patients serum. The same retinal staining pattern was obtained with monoclonal anti-GAD65 antibodies. CONCLUSIONS: These findings suggest autoimmune retinopathy, mediated by anti-GAD65 autoantibodies as the underlying cause of visual loss. ( info) |
3/87. GAD65-Reactive T cells in a non-diabetic stiff-man syndrome patient. GAD65 (glutamic acid decarboxylase) is an important autoantigen in both type 1 (insulin-dependent) diabetes mellitus (IDDM) and the neurological autoimmune disease stiff-man syndrome (SMS), and is expressed in pancreatic islets as well as the nervous system. Still, only 30% of SMS patients also have type 1 diabetes. To study regulation of T cell responsiveness to GAD65, we investigated a non-diabetic SMS patient with HLA-DR3/7 (predisposing to type 1 diabetes) and high levels of type 1 diabetes-associated autoantibodies against GAD65 and islet cells, and compared the results with those of her diabetic son and two other SMS patients. T cell responses to GAD65 were repeatedly absent in primary stimulation, whereas IA-2, islet antigen and tetanus toxoid induced significant T cell proliferation. However, after in vitro restimulation, GAD65 reactive T cell lines and clones were obtained that were HLA-DR3 restricted, and cross-reactive with a homogenate of purified human pancreatic islets. These T cells produced the immunoregulatory cytokine IL-10 in combination with IFN-gamma and IL-4 (Th0). The dominant T cell epitope was mapped to the central region of GAD65. Although no primary response to whole GAD65 was detectable, the naturally processed GAD65 peptide epitope was recognized vigorously in the primary stimulation assay. The lack of detectable primary T cell responses to GAD65, together with the GAD65-specific cytokine production of restimulated T cells, suggest that GAD65-specific cellular autoimmunity in this patient is suppressed and may be related to the absence of diabetes despite humoral autoreactivity and genetic predisposition. ( info) |
4/87. Long-term remission of refractory stiff-man syndrome after treatment with intravenous immunoglobulin. The stiff-man syndrome is a rare neuromuscular disorder characterized by progressive rigidity, stiffness, and intermittent spasm of axial and extremity muscles. Its etiology is unknown. Different therapeutic regimens have been used with variable success. We present a case of refractory stiff-man syndrome, in which the symptoms were successfully controlled by the administration of intravenous immunoglobulin (IVIg). This case gives evidence that IVIg can be a safe and an efficient treatment of refractory stiff-man syndrome. The exact indication for and the cost-effectiveness of IVIg in the treatment of this rare entity remain to be determined. ( info) |
5/87. autoimmunity to gephyrin in Stiff-Man syndrome. Stiff-Man syndrome (SMS) is a rare disease of the central nervous system (CNS) characterized by chronic rigidity, spasms, and autoimmunity directed against synaptic antigens, most often the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD). In a subset of cases, SMS has an autoimmune paraneoplastic origin. We report here the identification of high-titer autoantibodies directed against gephyrin in a patient with clinical features of SMS and mediastinal cancer. Gephyrin is a cytosolic protein selectively concentrated at the postsynaptic membrane of inhibitory synapses, where it is associated with GABA(A) and glycine receptors. Our findings provide new evidence for a close link between autoimmunity directed against components of inhibitory synapses and neurological conditions characterized by chronic rigidity and spasms. ( info) |
6/87. Double filtration plasma exchange and immunoadsorption therapy in a case of stiff-man syndrome with negative anti-GAD antibody. We report the effects of double filtration plasma exchange and immunoadsorption therapy which were performed for a case of stiff-man syndrome even though the patient was negative for anti-glutamic acid decarboxylase (GAD) antibody. The patient underwent a course of four double filtration plasma exchanges, which resulted in marked clinical improvement. Painful muscle cramps disappeared and muscle stiffness reduced within a day after the first plasma exchange. The patient's improvement continued, but his condition declined again about ten months after plasma exchange. Immunoadsorption therapy was then performed, and this treatment was also effective. ( info) |
7/87. Motor evoked potentials in a case of stiff-man syndrome: a longitudinal study. The clinical and neurophysiological findings in a patient with a typical stiff-man syndrome and their three-year evolution are described. The patient had high titers of anti-glutamic acid decarboxylase antibodies in both serum and cerebrospinal fluid. magnetic resonance imaging (MRI) of brain and spinal cord was normal. transcranial magnetic stimulation (TMS) revealed a distinctive motor evoked potential (MEP) pattern in proximal lower limb muscles consisting of markedly increased MEP amplitudes and MEP/M ratios, reduced excitability thresholds, and absent silent period. However, MEP latencies, central and peripheral conduction times and amplitudes obtained by magnetic spinal root stimulation were normal. Treatment with benzodiazepine and baclofen normalized both the clinical picture and the MEP values. TMS may be useful both as a diagnostic tool and to monitor the response to drug treatment. ( info) |
8/87. Train of four fade in a child with stiff baby syndrome. A case is described of a child with stiff baby syndrome who underwent open reduction and femoral shortening of congenital dislocated hip under general anaesthesia. Neuromuscular function was measured electromyographically and demonstrated a great degree of train of four fade (57%) after sevoflurane inhalational induction of anaesthesia. The response to suxamethonium (2 mg x kg(-1)) was normal. The neuromuscular response to volatile anaesthetic agents and suxamethonium may be abnormal in these children with stiff baby syndrome and intraoperative neuromuscular monitoring is recommended. ( info) |
9/87. Stiff-person like syndrome in a patient with multiple pituitary hormone deficiencies. A patient with long-standing, occult pituitary insufficiency, who developed painful muscle stiffness and superimposed spasms, closely resembling stiff-person syndrome, was described. Complete resolution of neuromuscular symptoms with hormone replacement in this case, as well as in a previously reported one, led to the suggestion that a syndrome like stiff-person could represent a rare consequence of multiple pituitary hormone deficiencies. ( info) |
| stiff-person syndrome (SPS) is a disorder of motor function characterized by rigidity of axial musculature and fluctuating painful spasms, which are often induced by startle or emotional stimuli. Neurophysiological studies have demonstrated the presence of continuous motor unit activity in muscle at rest, with abnormally enhanced extereoceptive reflexes. Although criteria for the diagnosis of SPS were proposed, several variants of this syndrome have been described before. In this communication, we report the case of a patient with a focal form of SPS. A 39-year-old woman developed progressive instability in her gait, spasms and stiffness restricted to both legs. The electromyographic examination showed continuous motor unit activity of the affected muscles at rest. Moreover, high anti-GAD antibodies titers were found in CSF and serum. Clinical symptoms, electrophysiological and immunological profiles suggest a focal form of SPS. Clinical and immunological findings indicate that SPS is a heterogeneous disease, suggesting the need to redefine its diagnostic criteria. Definition of the range of clinical expression and immunological profiles could be important for the clinical management of these patients. ( info) |