Neurological Therapeutics
Online ISSN : 2189-7824
Print ISSN : 0916-8443
ISSN-L : 2189-7824
Volume 36 , Issue 5
Showing 1-20 articles out of 20 articles from the selected issue
  • Teruyuki Hirano
    2019 Volume 36 Issue 5 Pages 563-568
    Published: 2019
    Released: June 02, 2020
    JOURNALS FREE ACCESS

    In 2018, a new treatment concept of tissue–based strategy was established. The two late time window thrombectomy trials, DAWN (6–24 hours) and DEFUSE3 (6–16 hours), showed dramatical improvement of outcome in patients with emergent large vessel occlusion (LVO). Both used RAPID software to select candidates who have small core with clinical–imaging mismatch or target mismatch. Revised AHA/ASA and Japanese guidelines now recommend mechanical thrombectomy as late as 16/24 hours after onset. In addition, patients with unknown onset time or wake–up stroke are now candidates for thrombolytic therapy using alteplase if diffusion–FLAIR mismatch is confirmed.

    In patients with non–cardioembolic stroke, dual anti–platelet therapy (DAPT) using clopidogrel and aspirin is recommended up to 21 days. The POINT trial further evaluated intensive DAPT starting as early as <12 hours with higher loading dose and continued until 90 days. Though POINT disclosed better efficacy on preventing recurrence of stroke, but increased bleeding events denied clinical application of the intensive DAPT therapy.

    NAVIGATE ESUS compared the efficacy and safety of rivaroxaban and aspirin in patients with embolic stroke of undetermined source (ESUS). This study was terminated prematurely because of the increased bleeding risk assigned to rivaroxaban treatment. Although efficacy was identical between the two groups. This ESUS concept was attracting and could offer better treatment option, however, it was not a case. It is time to consider refinement of ESUS concept or treatment strategy.

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  • Atsushi Niwa, Hidekazu Tomimoto
    2019 Volume 36 Issue 5 Pages 569-572
    Published: 2019
    Released: June 02, 2020
    JOURNALS FREE ACCESS

    Dementia affects over 46 million people in the world with a rapidly increasing prevalence. No fundamental treatment for AD has been established, and novel experimental studies are under investigation. This progress has led to the development of numerous therapeutic strategies in the clinical testing. Immunotherapy against Aβ has been pursued extensively as a therapeutic approach to AD and other dementias, and several other promising trials are currently ongoing.

    In 2018, these outcomes including solanezumab, verubecestat, LMTM, idalopirdine, pimavanserin and so on have been reported. This review overviewed recent advances in these larger clinical researches in dementia.

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  • Hiroshi Kuroda
    2019 Volume 36 Issue 5 Pages 573-575
    Published: 2019
    Released: June 02, 2020
    JOURNALS FREE ACCESS

    Recent advances and new findings relating to multiple sclerosis (MS) and other inflammatory disorders in the central nervous system were reviewed. We adopted the studies regarding serum neurofilament light chain as an efficient biomarker for axonal damage in patients with MS, B cell targeted therapies for MS, the MRI technique that distinguishes MS from neuromyelitis optica spectrum disorder (NMOSD), plasma exchange as an acute–phase treatment for NMOSD, and cumulative information about myelin oligodendrocyte glycoprotein immunoglobulin G–positive disorder.

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  • Kotaro Ogaki, Nobutaka Hattori
    2019 Volume 36 Issue 5 Pages 576-579
    Published: 2019
    Released: June 02, 2020
    JOURNALS FREE ACCESS

    We review reports published in 2018 providing new information on the management of Parkinson's disease (PD) and its related disorder. Adjunct zonisamide to levodopa improved parkinsonism in dementia with Lewy body, without worsening cognitive function or psychiatric symptoms. Camicinal, a gastroprokinetic resulted in significant reduction of off–time and significant decrease in motor symptom in patients with PD, which occurred in parallel with more rapid absorption of levodopa. Subcutaneous apomorphine infusion during waking hours (16 hour a day) significantly reduced off–time. Sodium oxybate, a first–line treatment in narcolepsy, improved excessive daytime sleepiness (EDS) and Epworth Sleepiness Scale (ESS) score in patients with PD. Rasagiline also showed beneficial effects on sleep quality in patients with PD with sleep disturbances. Safinamide improved PD chronic pain in the long term (2–year). Subthalamic nucleus (STN) deep brain stimulation (DBS) slowed rest tremor progression in early PD. STN–DBS decreased restless legs syndrome symptoms in patients with PD and the improvement was sustained over a 2–year period. STN–DBS was effective in improving impulse control disorders and neuropsychiatric fluctuations in the long term. The first randomised blinded evaluation of DBS in the caudal zona incerta (cZi) showed its efficacy on PD symptoms, especially for tremor. The doses of dopaminergic medications did not decrease. PRX002 is a humanized monoclonal antibody designed to target aggregated forms of α–synuclein. Multicenter, randomized, double–blind, placebo–controlled, multiple ascending–dose trial (phase Ib) in 80 patients with PD showed that single and multiple doses of PRX002 were generally safe and well tolerated and resulted in robust binding of peripheral α–synuclein. ProSavin is a lentiviral vector–based gene therapy that delivers local and continuous dopamine. Long–term follow up of a Phase I/II Study of ProSavin showed a significant reduction of off–time in patients with PD. ProSavin continued to be safe and well tolerated.

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  • Yusuke Sakiyama, Hiroshi Takashima
    2019 Volume 36 Issue 5 Pages 580-583
    Published: 2019
    Released: June 02, 2020
    JOURNALS FREE ACCESS

    We reviewed the recent advances in therapeutics of spinocerebellar degeneration (SCD) that were published in 2018. This article introduces the outline of therapies with mesenchymal stem cells, cerebello–spinal tDCS, betamethasone, and cyclodextrin. We expect that these treatments will contribute to patients with cerebellar motor dysfunction and ataxia.

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  • Tetsuya Akiyama, Naoki Suzuki, Hitoshi Warita, Masashi Aoki
    2019 Volume 36 Issue 5 Pages 584-587
    Published: 2019
    Released: June 02, 2020
    JOURNALS FREE ACCESS

    Motor neuron diseases (MND) are devastating neurodegenerative disorder which primary affects motor neurons. Amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), and spinal bulbar muscular atrophy (SBMA) are representative MND. Since the advent of novel drugs of SMA (Nusinersen) and SBMA (Leuprorelin) in 2017, the treatment of MND has changed dramatically and the door of new hope has opened. This review provides an overview of preclinical and clinical advances in MND research, future issues and prospects, and summarizes selected key literature on therapeutic approaches in 2018.

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  • Yukio Takeshita, Takashi Kanda
    2019 Volume 36 Issue 5 Pages 588-590
    Published: 2019
    Released: June 02, 2020
    JOURNALS FREE ACCESS

    The treatment of brain tumors and granulomatous disease in the brain represents a serious unmet medical need in the field of neuro–oncology. Even though many effective compounds have demonstrated success in treating peripheral tumors with targeted agents, one aspect of this lack of success in the brain may be related to poor delivery of otherwise effective compounds. This review discusses some issues that are pertinent to precision medicine for glioma, brain metastases and neurosarcoidosis with some reports published in 2018. In addition, we introduce the promising results in clinical trials of new–targeted immunetherapies for these diseases.

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  • Satoshi Kuwabara
    2019 Volume 36 Issue 5 Pages 591-593
    Published: 2019
    Released: June 02, 2020
    JOURNALS FREE ACCESS

    Various clinical trials for peripheral neuropathy were published in 2018. Systematic PubMed search using terms, “neuropathy”, “peripheral neuropathy”, and “clinical trials” was performed with the time lock from January 1, 2018 through December 31, 2018. A total of 22 trials were found on diabetic neuropathy (DPN ; n=10), chemotherapy–induced peripheral neuropathy (CIPN ; n=7), hereditary ATTR amyloidosis (n=2), Guillain–Barre syndrome (GBS ; n=1), chronic inflammatory demyelinating polyneuropathy (CIDP ; n=1), and multifocal motor neuropathy (n=1). For painful DPN, exercise, pregabalin, alpha–lipoic acid, and spinal cord electric stimulation were effective for pain relief. For CIPN, exercise Calmangafodipir and Sigma–1 receptor ligand treatment showed possible beneficial effects. For ATTR amyloidosis, a tafimidis trial revealed a significantly beneficial effects on cardiomyopathy, and an anti–sense oligonucleotide, inotersen, showed improvedment in neuropathy and QOL scores. For immune–mediated neuropathies, clinical trials on eculizumab for GBS, subcutaneous immunoglobulin as a maintenance therapy for CIDP, and intravenous immunoblobulin as a maintenance therapy for multifocal motor neuropath were published. These results showed sustained research activity to develop new therapies for a number of peripheral nerve disorders.

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  • Shigeaki Suzuki
    2019 Volume 36 Issue 5 Pages 594-596
    Published: 2019
    Released: June 02, 2020
    JOURNALS FREE ACCESS

    This article reviewed the representative papers of treatment of immune–mediated muscular disorder published in 2018. We focused on molecular target drugs for treatment of myasthenia gravis and inflammatory myopathies. Eculizumab was approved by the Japanese government for the treatment of acetylcholine receptor antibodies–positive refractory MG in December 2017. Eculizumab is expected to have treatment benefits for refractory and generalized MG patients, although Eculizumab is the most expensive treatment for MG in Japan. Neuromuscular experts should keep the appropriate indication of eculizumab for refractory MG in mind. Rituximab has shown to be a remarkable effective drug for MG, especially seropositive for autoantibodies against muscle–specific kinase. Unfortunately, rituximab is not available for MG treatment. Randomized phase 2 clinical study demonstrated that belimumab did not have significant efficacy compared with placebo in generalized MG. In contrast, abatacept and infliximab were well tolerated and potentially effective for treatment of refractory polymyositis and dermatomyositis.

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  • Nobuyuki Araki, Masato Asahina
    2019 Volume 36 Issue 5 Pages 597-600
    Published: 2019
    Released: June 02, 2020
    JOURNALS FREE ACCESS

    We reviewed articles on novel development of neurological treatment published in 2018. Treatment algorism of orthostatic hypotension was indicated in a JACC State–of–the–Art Review. In regard to cardiovascular autonomic dysfunction, consensus statement on the definition of neurogenic supine hypertension in autonomic failure was proposed by the American Autonomic Society (AAS) and the European Federation of Autonomic Societies (EFAS). It was reported that propranolol, bisoprolol and a combination of pyridostigmine and propranolol or bisoprolol showed effectiveness for postural tachycardia syndrome. Therapy for vasovagal syncope was also updated. For over active bladder, effectiveness of gabapentin and phytomedicine extracts were reported, and several confirmative studies were also performed. Safety and efficacy of elobixibat and linaclotide for chronic idiopathic constipation were shown by the phase 3 trials. Safety and efficacy of plecanatide (unapproved in Japan), a guanylate cyclase agonist, for irritable bowel syndrome was also shown by the phase 3 trial. A meta–analysis showed efficacy of naldemedine and naloxone for the treatment of opioid–induced constipation. Topical botulinum toxin type A liposomal cream significantly was reported to improve axillary hyperhidrosis. It was reported that a combination of topical agents and oxybutynin reduced focal hyperhidrosis. Percutaneous radiofrequency thoracic sympathectomy was reported to improve palmar hyperhidrosis.

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  • Kazutaka Horikoshi, Hisashi Ito, Shigeru Fukutake, Masaya Abe, Satoshi ...
    2019 Volume 36 Issue 5 Pages 601-605
    Published: 2019
    Released: June 02, 2020
    JOURNALS FREE ACCESS

    Herein, we present a 61–year–old female with sporadic amyotrophic lateral sclerosis (ALS), who underwent gait training with a lower limb–type Hybrid Assistive Limb (HAL®). She could walk with a quad cane and presented with anterocollis in her neck and trunk. To prevent her gait disturbance from worsening, we scheduled gait training using a HAL® for 20 minutes/day for 9 of 14 days. At the end of the 1st course, her gait speed had improved. We continued the HAL®–based gait training at intervals of >14 days. The patient's gait function gradually declined ; however, we observed temporary improvements in her gait speed. In addition, the anterocollis in her neck and trunk were transiently ameliorated. Despite its short–term efficacy, repeated gait training using a HAL® improved the gait function and resting function of an ALS patient.

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  • Kenzo Sakurai, Yu Suzuki, Yasuhiro Hasegawa
    2019 Volume 36 Issue 5 Pages 606-610
    Published: 2019
    Released: June 02, 2020
    JOURNALS FREE ACCESS

    Although telemedicine is highly convenient, many patients resist participating in a medical system that is not conventionally face–to–face. We surveyed patients for treatment of neurological disorders and investigated their awarenesses of telemedicine. We collected 215 responses to questionnaires. The ratios of patients with multiple sclerosis/neuromyelitis optica, epilepsy who responded that they could use telemedicine were 80.0%, 73.7%. Being able to use telemedicine correlated negatively with age, but not at all with gender, time to the hospital, or ADL. Telemedicine to treat neurological disorders may be easier to introduce to patients with epilepsy and multiple sclerosis, and more difficult to penetrate those with dementia.

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  • Mariko Ohara, Shuhei Okazaki, Ryoichi Imamura, Kenichi Todo, Hideki Mo ...
    2019 Volume 36 Issue 5 Pages 611-614
    Published: 2019
    Released: June 02, 2020
    JOURNALS FREE ACCESS

    We report a case of posterior reversible encephalopathy syndrome (PRES) in a 67–year–old woman with advanced renal cell carcinoma, who presented with severe hypertension, headache, and generalized seizure 1 week after the administration of axitinib, a selective inhibitor of the vascular endothelial growth factor receptor. Brain magnetic resonance imaging (MRI) on admission revealed T2–weighted hyperintense lesions in both sides of the occipital lobe and cerebellar hemisphere. Symptoms and MRI abnormalities were completely resolved after the administration of antihypertensive treatment and discontinuation of axitinib. The patient resumed axitinib treatment with strict blood pressure control 1 month later and had no recurrence of PRES. Here, we discuss the rechallenge of axitinib treatment and importance of strict blood pressure control, in addition to a literature review.

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