Targeting the red nucleus for cerebellar tremor.

Deep brain stimulation of the thalamus (and especially the ventral intermediate nucleus) does not significantly improve a drug-resistant, disabling cerebellar tremor. The dentato-rubro-olivary tract (Guillain-Mollaret triangle, including the red nucleus) is a subcortical loop that is critically involved in tremor genesis. We report the case of a 48-year-old female patient presenting with generalized cerebellar tremor caused by alcohol-related cerebellar degeneration. Resistance to pharmacological treatment and the severity of the symptoms prompted us to investigate the effects of bilateral deep brain stimulation of the red nucleus. Intra-operative microrecordings of the red nucleus revealed intense, irregular, tonic background activity but no rhythmic components that were synchronous with upper limb tremor. The postural component of the cerebellar tremor disappeared during insertion of the macro-electrodes and for a few minutes after stimulation, with no changes in the intentional (kinetic) component. Stimulation per se did not reduce postural or intentional tremor and was associated with dysautonomic symptoms (the voltage threshold for which was inversed related to the stimulation frequency). Our observations suggest that the red nucleus is (1) an important centre for the genesis of cerebellar tremor and thus (2) a possible target for drug-refractory tremor. Future research must determine how neuromodulation of the red nucleus can best be implemented in patients with cerebellar degeneration.

Characterization of human FCGR3B*02 (HNA-1b, NA2) cDNAs and IMGT standardized description of FCGR3B alleles.

The low-affinity Fc gamma receptor IIIb (Fc gamma RIIIb and CD16b) is constituted by a unique FCGR3B polypeptide chain that comprises two extracellular immunoglobulin-like domains, and is expressed as a glycosylphosphatidyl inositol-anchored receptor on the neutrophils. The FCGR3B chain bears allotypes that define the human neutrophil antigen-1 (HNA-1 and NA) system involved in major post-transfusional reactions. FCGR3B is highly homologous to FCGR3A, which is expressed as a transmembrane receptor on natural killer cells and monocytes/macrophages. Its transcription products were not yet fully characterized. In the present work, we sequenced FCGR3B cDNAs with complete 3' untranslated region from purified granulocytes of HNA-1b/HNA-1b (NA2/NA2) genotyped donors. We characterized two FCGR3B cDNAs of different lengths corresponding to two polyadenylation sites. This result was corroborated by data raised by serial analysis of gene expression (SAGE). FCGR3B allele polymorphisms, from this article [FCGR3B*02 (HNA-1b, NA2)] and from the literature, are described for the first time according to the IMGT standardized nomenclature and to the IMGT unique numbering for C-LIKE-DOMAIN (http://imgt.cines.fr). These rules, described in the IMGT Scientific chart, are based on the IMGT-ONTOLOGY concepts. IMGT allele alignments and IMGT Collier de Perles graphical two-dimensional representations are provided for the two Ig-like domains (or C-LIKE-DOMAINs) [D1] and [D2] of FCGR3B*02. The standardized description of FCGR3B allele polymorphisms was approved by the IMGT Nomenclature Committee (IMGT-NC) and is freely available in IMGT repertoire at IMGT, http://imgt.cines.fr.