The “brain-machine interface (BMI)” is a novel neurotechnology based on the artificial direct communication pathway between the brain and an external device, aiming to compensate for the defective neural function. It may be classified into two types : (1) a “motor BMI” which decodes the brain’s signals to operate external devices and (2) a “sensory BMI” which converts electric signals obtained from the external sensor device to create sensory function by stimulating the appropriate area of the brain. An example of a motor BMI under development at Osaka University is described, in which the motor intension of the ALS patient is identified by deciphering (decoding) the electrocorticogram (ECoG) to operate a cursor on a computer display or to control a robotic arm by the patient’s thoughts alone.

  This paper introduces the state of the art of current BMI research, and discusses the future of this novel neurotechnology.

  G47Δ is a third-generation oncolytic herpes simplex virus type 1 (HSV-1) that has triple mutations created in the HSV-1 genome deletions in both copies of the γ34.5 gene, an insertion of the E. coli lacZ gene in the ICP6 locus, and a deletion of the α47 gene. G47Δ shows a high efficacy for theating malignant glioma as well as for other solid cancers, because of its enhanced tumor-selective viral replication and cell killing, and efficient induction of systemic antitumor immunity. The first-in-man clinical trial in recurrent glioblastoma patients that lasted 5 years from 2009 proved the safety of G47Δ when injected into the brain tumor stereotactically twice within 2 weeks. Some patients showed a long-term efficacy that seemed to have been caused by the induction of specific antitumor immunity rather than the direct oncolytic activity of G47Δ. In the phase Ⅱ trial that started in 2015, a patient must have glioblastoma with a single residual or recurrent tumor after initial radiation therapy, and a KPS of 60% or higher. The eligible patients receive repeated stereotactic injections with G47Δ every 4 weeks, 6 injections being the maximum total. The efficacy of G47Δ will be evaluated using a one-year survival rate as the primary endpoint. We believe G47Δ will become a standard treatment for all malignant glioma in Japan in the near future.

  We conducted both a clinical trial (Phase Ⅲ : confirmatory trial) of intravenous infusion of autologous mesenchymal stem cells for cerebral infarction patients, and a clinical trial (Phase Ⅱ) using the same stem cells for spinal cord injury patients.

  The objectives of these studies were to examine the feasibility, safety, and efficacy of cell therapy using auto serum-expanded autologous mesenchymal stem cells derived from bone marrow in patients.

  Inclusion criteria for the stroke study were : 1) cerebral infarction onset within 40 days, 2) supra-tentorial cerebral infarction (NINDS-Ⅲ 1990) diagnosed by MRI (or CT), MRA (3D-CTA or DSA), ECG, chest X-ray etc., 3) classified under grade 4 or 5 on mRS (modified Rankin scale), 4) age between 20 to 80, and 5) written informed consent from the subjects and legal representative is provided.

  Inclusion criteria for the spinal cord injury trial were : 1) spinal cord injury onset within 14 days, 2) cervical spinal cord injury diagnosed by MRI (or CT), etc., 3) classified grade A, B, C on the ASIA scale, 4) age between 20 to 70, and 5) written informed consent from the subjects and legal representative is provided.

  The central nervous system has very little if any potential for regeneration. That is why cell replacement therapy is needed for functional recovery in neurodegenerative diseases. Human embryonic stem cells emerged in 1998, and induced pluripotent stem cells in 2007. Thanks to the development of these pluripotent stem cells, we are now able to manipulate the quantity and quality of donor cells for stem cell-based therapy. For Parkinson’s disease, protocols to establish induced pluripotent stem cells and to induce dopaminergic neurons have been developed up to clinical grade, and preclinical data about the efficacy and safety of these cells exist for rodent and monkey models. Based on these efforts, clinical trials against neurodegenerative disease are soon expected.

  Appropriate surgical manipulation of the mesial temporal lobe structures, as well as minimizing residual tumor for tumor control, is necessary in terms of seizure control in the surgical approach for mesial temporal glioneural tumors, which often cause chronic medical intractable epilepsy.

  It is important to plan the surgical strategy not only to remove the tumor but also to achieve seizure relief and preserve cognitive function. This study investigated neuropsychological outcomes in patients with intractable temporal lobe epilepsy due to mesial temporal lobe glioneural tumors undergoing tumor resection by the transsylvian-transcisternal & ventricular approach (TSCV).

  TSCV is a modified method of transsylvian selective amygdalohippocampectomy (TSA), which allows access to the tumor invading the amygdala, uncus, and hippocampus, both through the lateral ventricle, and through the cistern, followed by tailored resection of adjacent epileptogenic regions, such as the hippocampus and parahippocampal gyrus. Hippocampal resection was performed in all cases in which tumor invasion was suspected.

  Analysis of seizure-free rate was performed on 26 consecutive cases of mesial temporal glioneural tumors treated by TSCV with hippocampal resection. Analysis of preoperative/postoperative memory scores evaluated by WMS-R on 17 cases, and IQ scores evaluated by WAIS on 14 cases, were also performed, in which follow up data was obtained. Good seizure control (92% seizure-free rate) was achieved, and no significant postoperative memory/IQ decline was observed. Pure lesionectomy of the tumor and epileptogenic regions with preservation of lateral temporal lobe cortex is effective for memory preservation, compared to anterior temporal lobectomy, in which lateral temporal lobe cortex is resected.

  TSCV is an effective surgical strategy for mesial temporal glioneural tumors, in terms of minimizing residual tumor, seizure control, and preservation of the lateral temporal lobe cortex. This report focus on the surgical anatomy, operative procedures, and clinical outcome of TSCV.

  Venous sinus thrombosis is a relatively rare disease, and hereditary coagulopathy is a known risk factor. We report a venous sinus thrombosis that developed in the mother and child after birth and for the same period and whose etiology was subsequently diagnosed by genetic tests as congenital antithrombin deficiency. In addition to the low level of antithrombin activity, other clinical findings obtained during the course of the disease, such as family history of venous thrombosis and heparin inactivity, were important leads for the diagnosis. Although venous sinus thrombosis is relatively rare, we should look for blood coagulation abnormalities, because heparin, the standard treatment drug for thrombosis, is ineffective in patients with antithrombin deficiency.