Yuji Nakatsuji

A case of acute disseminated encephalomyelitis concomitant with polyneuropathy associated with anti-lactosylceramide antibody

We report a case of acute disseminated encephalomyelitis (ADEM) concomitant with polyneuropathy associated with anti-lactosylceramide antibody. A 68-year-old man was admitted to our hospital with ophthalmoparesis, bulbar palsy, tetraplegia after suffering from upper respiratory infection and headache. Subsequently, he developed respiratory failure requiring mechanical ventilation. Fluid-attenuated inversion recovery (FLAIR) MRI showed high intensities in the pons and medulla, and a nerve conduction study revealed motor-dominant axonal polyneuropathy. Although the laboratory tests revealed the presence of anti-lactosylceramide antibody in his serum, he was diagnosed with acute disseminated encephalomyelitis concomitant with polyneuropathy. Whereas the intensive treatment with corticosteroids, plasmapharesis, and high-dose intravenous immunoglobulin (IVIg) brought a moderate improvement, his tetraparesis continued to exist.

A case of neurolymphomatosis presented as cauda equine syndrome accompanied with M-proteinemia

A 63-year-old man developed a syndrome of cauda equine, with the numbness which is a left lower extremity from the left buttocks, weakness of left leg, and a dysfunction of bladder and bowel. Enhanced MRI revealed the enhancement of lower cauda equine, and a nerve conduction test revealed decreased F-wave persistency in the tibial nerve and increased F-wave latency in the peroneal nerve on the both sides. M-proteinemia was admitted and myeloma was suspected. By a biopsy of a vertebral arch, we diagnosed with diffuse large B-cell lymphoma. We treated with dexamethasone and R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, prednisone (prednisolone)), then the symptom was improved. In case of caude equine syndrome with M-proteinemia, a possibility of the malignant lymphoma should also be considered.

Cerebellar and brainstem hypoperfusion in Bickerstaff’s brainstem encephalitis: a case report

A 16-year-old healthy male experienced gastrointestinal symptoms and 9 days later developed fever, headache, numbness of the left hand, and disturbance of consciousness with rapid deterioration to a comatose state. These clinical symptoms resolved after treatment with steroid pulse, plasma exchange, and intravenous immunoglobulin. Along with the recovery, ophthalmoplegia and ataxia were observed. These symptoms and the detection of a high titer of serum anti-GQ1b immunoglobulin G autoantibodies led to the diagnosis of Bickerstaffs brainstem encephalitis (BBE). Brain 123I-IMP SPECT indicated hypoperfusion of the brainstem and bilateral cerebellar cortex during the acute phase, which increased during the recovery phase. This finding is indicative of reversible dysfunction in the cerebellar cortex and brainstem in the acute phase of BBE.

Cerebrospinal fluid mitochondrial DNA in neuromyelitis optica spectrum disorder

BackgroundNeuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease of the central nervous system. Although complement-dependent astrocyte damage mediated by anti-aquaporin 4 autoantibody (AQP4-Ab) is well acknowledged to be the core of NMOSD pathogenesis, additional inflammatory cascades may contribute to the establishment of lesion formation. Thus, in this study, we investigated the possible pathogenic role of immune-reactive mitochondrial DNA (mtDNA) in cerebrospinal fluid (CSF) of NMOSD patients.MethodsUsing quantitative polymerase chain reaction, we measured extracellular mtDNA levels in CSF of NMOSD patients positive for AQP4-Ab. Patients with multiple sclerosis or other neurological diseases were examined as controls. Pre- and post-treatment extracellular mtDNA levels were also compared in the NMOSD group. Extracellular mtDNA release from human astrocytes was analyzed in vitro utilizing NMOSD sera, and interleukin (IL)-1β production was measured in supernatants of mixed glial cells stimulated with DNA fraction of CSF derived from NMOSD patients. Furthermore, specific innate immune pathways mediating the IL-1β production by mtDNA were investigated in peripheral blood mononuclear cells with selective inhibitors of Toll-like receptor 9 (TLR9) and NOD-like receptor protein 3 (NLRP3) inflammasomes.ResultsExtracellular mtDNA level was specifically elevated in acute phase of NMOSD CSF. In vitro studies provided the evidence that mtDNA is released from human astrocytes by NMOSD sera. In addition, DNA fraction isolated from NMOSD CSF promoted secretion of IL-1β from mixed glial cells. Selective inhibition of TLR9 and NLRP3 inflammasomes revealed that mtDNA-mediated IL-1β production depends on specific innate immune pathways.ConclusionExtracellular mtDNA is specifically elevated in the CSF of patients with acute phase NMOSD, and mtDNA released by AQP4-Ab-mediated cellular damage elicits the innate immune cascades via TLR9 and NLRP3 inflammasomes pathways. Our study highlights mtDNA-mediated innate immune pathways as a novel therapeutic target for future treatment of NMOSD patients.

Effects of Transcranial Direct Current Stimulation (tDCS) Over the Frontal Polar Area on Motor and Executive Functions in Parkinson’s Disease; A Pilot Study

Parkinson’s disease (PD) is a neurodegenerative disorder with motor and non-motor symptoms due to degeneration of dopaminergic neurons. The current pharmacological treatments induce complications associated with long-term use. However, current stimulation techniques for PD treatment, such as deep brain stimulation (DBS), are too invasive. In this context, non-invasive brain stimulation including transcranial direct current stimulation (tDCS) may be a safe and effective alternative treatment for PD. We previously reported that anodal tDCS over the frontal polar area (FPA) improved motor functions in heathy subjects. Therefore, in the present study, effects of tDCS over the FPA on motor and cognitive functions of PD patients were analyzed. Nine PD patients (3 men and 6 women) participated in this cross over study with three tDCS protocols; anodal, cathodal or sham tDCS over the FPA. Each tDCS protocol was applied for 1 week (5 times/week). Before and after each protocol, motor and cognitive functions of the patients were assessed using Unified PD Rating Scale [UPDRS (part III: motor examination)], Fugl Meyer Assessment set (FMA), Simple Test for Evaluating hand Function (STEF) and Trail Making Test A (TMT-A). The results indicated that anodal stimulation significantly decreased scores of motor disability in UPDRS-III compared with sham and cathodal stimulation, and significantly increased scores of motor functions in FMA compared with sham stimulation. Furthermore, anodal stimulation significantly decreased time to complete a motor task requiring high dexterity in STEF compared with those requiring low and medium levels of dexterity. In addition, anodal stimulation significantly decreased time to complete the TMT-A task, which requires executive functions, compared with sham stimulation. To the best of our knowledge, this is the first clinical research reporting that tDCS over the FPA successfully improved the motor and non-motor functions in PD patients. These findings suggest that tDCS over the FPA might be a useful alternative for the treatment of PD patients.

What is the difference between the blood–nerve barrier and blood–brain barrier?

The blood–brain barrier and blood–nerve barrier play crucial roles in maintaining homeostasis of the central and peripheral nervous systems. Takeshita et al. reported the different molecular expression pattern in the components constituting the blood–brain barrier and blood–nerve barrier, and suggested that the blood–nerve barrier might have a distinct mechanism for T cell migration.