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Tremor in Klinefelter's syndrome is believed to be essential tremor since the publication of "Klinefelter's syndrome and essential tremor" in 1969. However, the author also stated that tremor in Klinefelter's syndrome might differ from essential tremor. A 71-year-old man with Klinefelter's syndrome who suffers from postural hand tremor is described. The electromyogram indicated lower motor neuron disturbance and chronic neurogenic change. The muscle biopsy indicated neurogenic muscle atrophy. Upon testosterone administration, the amplitude of tremor was reduced and a gradual improvement in handwriting was observed. The tremor in this patient was different from essential tremor. The foresight by Baughman in 1969 proved to be true in this patient. This case report provides new insights into the pathogenesis and treatment of tremor in Klinefelter's syndrome, which would benefit patients who suffer from the tremor.

Gene therapy for neurological diseases requires efficient gene delivery to target tissues in the central and peripheral nervous systems. Although adeno-associated virus is one of the most promising vectors for clinical use against neurological diseases, it is difficult to get it across the blood-brain barrier. A clinically practical approach to using a vector based on adeno-associated virus to decrease the expression of a specific gene in both the central and the peripheral nervous system has yet to be established. Here, we analyzed whether upper lumbar intrathecal administration of a therapeutic vector incorporating adeno-associated virus and short-hairpin RNA against superoxide dismutase-1 bypassed the blood-brain barrier to target the spinal cord and dorsal root ganglia. The therapeutic vector effectively suppressed mRNA and protein expression of endogenous superoxide dismutase-1 in the lumbar spinal cord and dorsal root ganglia. Moreover, neither neurological side effects nor toxicity due to the incorporated short-hairpin RNA occurred after the injection. We propose that this approach could be developed into novel therapies for motor neuron diseases and chronic pain conditions, such as complex regional pain syndrome, through silencing of the genes responsible for pathologies in the spinal cord and dorsal root ganglia.

authors are contributed equally to this manuscript. AbstractObjective: To characterize the CSF cytokine profile in chronic inflammatory demyelinating polyneuropathy (CIDP) patients with IgG4 anti-neurofascin 155 (NF155) antibodies (NF155 + CIDP) or those lacking anti-NF155 antibodies (NF155 À CIDP). Methods: Twenty-eight CSF cytokines/chemokines/growth factors were measured by multiplexed fluorescent immunoassay in 35 patients with NF155 + CIDP, 36 with NF155 À CIDP, and 28 with non-inflammatory neurological disease (NIND). Results: CSF CXCL8/IL-8, IL-13, TNF-a, CCL11/ eotaxin, CCL2/MCP-1, and IFN-c were significantly higher, while IL-1b, IL-1ra, and G-CSF were lower, in NF155 + CIDP than in NIND. Compared with NF155 À CIDP, CXCL8/IL-8 and IL-13 were significantly higher, and IL-1b, IL-1ra, and IL-6 were lower, in NF155 + CIDP. CXCL8/IL-8, IL-13, CCL11/eotaxin, CXCL10/IP-10, CCL3/MIP-1a, CCL4/MIP-1b, and TNF-a levels were positively correlated with markedly elevated CSF protein, while IL-13, CCL11/eotaxin, and IL-17 levels were positively correlated with increased CSF cell counts. IL-13, CXCL8/IL-8, CCL4/MIP-1b, CCL3/MIP-1a, and CCL5/RANTES were decreased by combined immunotherapies in nine NF155 + CIDP patients examined longitudinally. By contrast, NF155 À CIDP had significantly increased IFNc compared with NIND, and exhibited positive correlations of IFN-c, CXCL10/ IP-10, and CXCL8/IL-8 with CSF protein. Canonical discriminant analysis of cytokines/chemokines revealed that NF155 + and NF155 À CIDP were separable, and that IL-4, IL-10, and IL-13 were the three most significant discriminators. Interpretation: Intrathecal upregulation of type 2 helper T (Th2) cell cytokines is characteristic of IgG4 NF155 + CIDP, while type 1 helper T cell cytokines are increased in CIDP regardless of the presence or absence of anti-NF155 antibodies, suggesting that overproduction of Th2 cell cytokines is unique to NF155 + CIDP.

BackgroundThere is considerable interest in inducing RNA interference (RNAi) in neurons to study gene function and identify new targets for disease intervention. Although short interfering RNAs (siRNAs) have been used to silence genes in neurons, in vivo delivery of RNAi remains a major challenge, especially by systemic administration. We have developed a highly efficient method for in vivo gene silencing in dorsal root ganglia (DRG) by using short hairpin RNA–expressing single-stranded adeno-associated virus 9 (ssAAV9-shRNA).ResultsIntraperitoneal administration of ssAAV9-shRNA to neonatal mice resulted in highly effective and specific silencing of a target gene in DRG. We observed an approximately 80% reduction in target mRNA in the DRG, and 74.7% suppression of the protein was confirmed by Western blot analysis. There were no major side effects, and the suppression effect lasted for more than three months after the injection of ssAAV9-shRNA.ConclusionsAlthough we previously showed substantial inhibition of target gene expression in DRG via intrathecal ssAAV9-shRNA administration, here we succeeded in inhibiting target gene expression in DRG neurons via intraperitoneal injection of ssAAV9-shRNA. AAV9-mediated delivery of shRNA will pave the way for creating animal models for investigating the molecular biology of the mechanisms of pain and sensory ganglionopathies.