Several variants have recently been characterised according to the relative distribution of clinical signs. “Encephalomyelitis with rigidity” is characterised by a subacute course leading to death within three years; “jerking stiff person syndrome” presents a predominant brainstem involvement ad “stiff limb syndrome” is a focal form with predominant involvement of the spinal cord.

A paraneoplastic variant has been described in association with breast cancer in women harbouring anti-amphiphysin antibodies. In those patients the onset of stiffness in upper limbs is suggestive of a paraneoplastic aetiology. Autoimmunity to gephyrin, a cytosolic protein at post-synaptic inhibitory synapses, has been described in association with undifferentiated mediastinal tumour. SPS has also been reported in association with neoplasia of the colon and lung, Hodgkin’s disease, thymoma.

Associated antibodies

Anti-GAD antibodies (figure1) are present in 60% of patients and stain the axon hillocks of Purkinje cells and diffuse nerve terminals in the molecular and granular layers of cerebellum. In addition, antibodies to pancreatic islet cells, gastric parietal cells, thyroid microsomes, and thyroglobulin are frequently found in patients positive for anti-GAD antibodies. The relationship of autoantibodies to the pathogenesis of the disease remains to be determined. Anti-GAD antibodies are also present in patients with insulin dependent diabetes mellitus and autoimmune polyendocrine syndrome but the anti-GAD level in these syndromes is usually much lower than in SPS.

Figure 1. Immunohistochemistry on frozen sections of rat cerebellum. Anti-GAD antibodies positive sera recognise the axon hillocks of Purkinje cells and diffuse nerve terminals in the molecular and granular layer of cerebellum.

Anti-amphiphysin antibodies: (figure 2) are directed to a 128 kd neuronal protein concentrated in nerve terminals. Rare paraneoplastic SPS present anti-GAD antibodies alone or associated with anti-amphiphysin antibodies.

Figure 2. Immunohistochemistry on paraffin-section of rat cerebellum. Anti-amphiphysin antibodies positive sera stain diffusely the synaptic terminals in molecular layer and granular glomeruli. In addition they recognise the membrane of Purkinje cells.

Treatment
Benzodiazepines are an effective therapy for SPS because they modulate the levels and activity of GABA. A similar mode of action has been proposed for baclofen, which can be administered orally or via an intrathecal route. Sodium valproate and vigabatrin are found to be effective therapies for a few patients; the mechanism of action may be to potentiate GABAergic synaptic transmission.
Immunosuppressive agents such as steroids, azathioprine; plasmapheresis and intravenous immunoglobulin are also effective.

30-10-2006 om 12:07 geschreven door kristof the stiffman