Chronic neurological diseases are characterized by a clinically progression and a worsening disability. The serious medical condition will be a persistent burden on patients with those diseases and their relatives all their lives, and they have to cope with the condition every day. The diseases inevitably affect their daily livings, so those patients will have to reconstruct their life style according to worsening level of the disorders. Therefore, to keep their good quality of lives, they need daily supports from various medical professions. We discuss the importance of the role of the medical professions and the team medical care for patients with chronic neurological diseases, especially focusing on multiple sclerosis.

Pharmaceuticals and Medical Devices Agency (PMDA) has been working to promote a proper drug development by academia and venture capital through consultation on R&D strategy. To promote an international harmonization in global drug development, PMDA proposed to establish a new international guideline focusing on multi–regional clinical trials and E17 guideline is currently under discussion in ICH. Recently, electronic data have been actively been utilized in review and safety assessment. Further challenges will continue for conducting appropriate review and safety measure of drugs as well as for promoting drug development.

Introduction : Parkinson's disease–associated dementia (PDD) greatly contribute to the poor prognosis of Parkinson's disease. Although cholinesterase inhibitors including donepezil are effective for the treatment of PDD, the average life–expectancy of patients who developed PDD remains considerably short. An early therapeutic intervention that can prevent the onset of PDD may enable to improve the long–term prognosis of Parkinson's disease substantially. Our previous study showed that olfactory dysfunction could be a predictive indicator of the development of PDD. In this trial, we investigated whether early administration of donepezil to patients with severe olfactory dysfunction can reduce risk for the subsequent development of PDD.

This is a multi–center, randomised, double–blind, parallel group, placebo–controlled trial in patients with Parkinson's disease, who have severe hyposmia and who have not yet developed PDD. 200 patients will be randomly allocated in a 1:1 ratio either to receive donepezil or placebo, in addition to standard therapy for Parkinson's disease. Patients will be followed up every 6 months until the onset of PDD or for a maximum of 4 years (208 weeks). Primary endpoint is the onset of PDD, which is measured by the Mini–Mental State Examination and the Clinical Dementia Rating (CDR) stage. Secondary endpoint is cognitive impairment, which is measured by the Addenbrooke's Cognitive Examination–Revised score and the CDR stage. Statistical analysis will be made to evaluate whether donepezil has a favorable effect on the risk of developing PDD. The study was approved by the ethics committees of Tohoku University Graduate School of Medicine and the National Hospital Organization, Sendai–Nishitaga Hospital and registered at UMIN Clinical Trials Registry (UMIN000009958).

Guillain–Barré syndrome (GBS) is an immune–mediated neuropathy that causes acute flaccid paralysis. Immunoglobulin and plasma exchange are established treatments for GBS ; however, a substantial number of patients, particularly those with severe disease, have poor recovery and residual deficits. Recent studies suggest that complement activation plays a pivotal role in GBS–associated axonal degeneration, and eculizumab is a humanized monoclonal antibody that specifically binds to complement component 5 and potently inhibits complement activation.

This clinical trial aims to evaluate the efficacy and safety of eculizumab for treatment of GBS.

The Japanese Eculizumab Trial for GBS (JET–GBS) is a prospective, multicenter, placebo–controlled, double–blind, randomized phase II study conducted at 13 tertiary neurology centers and is funded by the Japan Agency for Medical Research and Development. A total of 34 GBS patients unable to walk independently within 2 weeks from symptom onset (Hughes functional grade 3–5) were randomized at a 2 : 1 ratio to receive either intravenous eculizumab (900mg/day) or placebo once weekly for 4 weeks, followed by 20 weeks of follow–up. The primary endpoint for efficacy is the proportion of patients who regain their ability to walk without aid at 4 weeks after the first dose of the study treatment, while primary safety outcomes are the incidence of adverse events and serious adverse events during the trial. Enrollment for the trial began in August 2015, and follow–up of the last patient was completed in October 2016. This study is the first to investigate the efficacy and safety of eculizumab for GBS. In case of a positive result, we will plan a phase III trial to investigate this issue in a larger number of patients.

Registered with CLINICALTRIAL : UMIN Clinical Trials Registry UMIN 000018171 ; https:/upload.umin.ac.jp/cgi–open–bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&language=J&recptno=R000020978 (Archived by WebCite at http://www.webcitation.org/6lTiG8ltG). Clinical Trials.gov NCT02493725 ; https://clinicaltrials.gov/ct2/show/NCT02493725 (Archived by WebCite at http://www.webcitation.org/6lVJZXKSL).

Some infected with human T–lymphotropic virus type 1 (HTLV–1), which causes adult T cell leukemia/lymphoma (ATL), develop the neurodegenerative disease HTLV–1 associated myelopathy (HAM). Suffering from progressive spinal cord paralysis, HAM patients experience a low quality of life with high unmet needs. Thus, the prognosis for HAM patients is extremely poor, and there is a strong demand for a novel therapeutic strategy. We established a HAM national patient registration system (HAM–net) in collaboration with patient groups to gather data from and distribute information to patients on a nation–wide scale. Recently we showed that HTLV–1 mainly infects CCR4^＋ T–cells and causes functional abnormalities that are believed to drive HAM pathogenesis. We next demonstrated that anti–CCR4 antibody treatments could target infected cells of HAM patients. Finally, we began an Investigator–led clinical trial. Despite patients scattered few and far between across the nation, securing participants is going well thanks to the HAM–net registration system. This Phase I/IIa trial involves 21 HAM patients undergoing steroid maintenance therapy. With safety as the primary endpoint, we investigate the maximum tolerated dose and pharmacokinetics ; secondary endpoints include walking times and activity against infected cells. This trial is the first to evaluate a drug targeting infected cells in HAM patients, and we anticipate an imminent change in the HAM treatment paradigm. (UMIN000012655)

We report the case of a 70–year–old woman with amyotrophic lateral sclerosis treated with a sustained high dose of morphine sulfate for refractory dyspnea ; she was initially treated with high dose morphine hydrochloride for short intervals intermittently. The switch from treatment with morphine hydrochloride to treatment with morphine sulfate was performed safely and was found to be effective, especially in preventing “end-of-dose failure” dyspnea.

Additionally, we examined several different solvents and morphine sulfate injection devices for administration via enteral feeding tube. Administration of sustained morphine sulfate dissolved in Yakuruto^® by using a suspension bottle was found to be convenient and effective.

A 79–year–old man with Parkinson's disease was admitted to our hospital for drug adjustment. He had been on medication for the disease for 8 years. He showed worsening orthostatic hypotension. Droxidopa was increased from 300 to 900mg/day, and pramipexole was decreased from 2.25 to 1.5mg/day. He subsequently showed improved orthostatic hypotension. However, he developed worsening hyponatremia (126mEq/L) after drug adjustment. He received a diagnosis of syndrome of inappropriate secretion of anti–diuretic hormone (SIADH) due to the low serum osmolarity, high urine osmolarity, and high level of ADH. He showed no improvement of hyponatremia on water intake restriction. Pramipexole 1.5mg/day was changed to rotigotine 13.5mg/day because of the diagnosis of pramipexole–induced SIADH. Thereafter hyponatremia improved and did not recur. Pramipexole–induced SIADH is rare ; however, we must be careful to avoid hyponatremia when pramipexole is administered to Parkinson's disease patients.