Recent advances on acute stroke therapy for patients with emergent large vessel occlusion (ELVO) using mechanical thrombectomy (MT) devices are huge. The one–year follow–up result of REVASCAT showed the consistent efficacy, and THRACE and SWIFT–PRIME revealed cost effectiveness. ASTER shoed the identical performance of aspiration device and stent retrieversients, it is now argued whether bridging therapy, i.e. intravenous thrombolysis (IVT) followed by MT, is essential for ELVO patients. One meta–analysis showed negative tendency to skip IVT in ELVO patients. The biggest impact in 2017 was the success of DAWN that employed the concept of Clinical–Imaging Mismatch, i.e. ischemic core size of ＜50cc with substantial neurological deficit. The achievement of DAWN can be translated as a big paradigm shift from “time-based” to “tissue-based” strategy.

In terms of thrmobolytic therapy, NOR–TEST used 0.4mg/kg of tenecteplase in unselected group of 1,100 patients with acute ischemic stroke. This trial showed identical efficacy and safety of tenecteplase compared to 0.9mg/kg of alteplase.

Idarucizumab is a specific agent to reverse the pharmacological activity of dabigatran. RE–VERSE AD trial proved the effect of idarucizmab is very quick, definite and sustains over 24 hours. We have now got a new option to treat ischemic stroke patients under dabigatran therapy with quick reversal using this antidote.

The concept of embolic stroke of undetermined source (ESUS) is now under investigation. For this topic, subanalysis of SOCRATES, a comparative study of ticagrelor and aspirin in non–cardioembolic ischemic stroke, presented an interesting result. Among ESUS subgroup, ticagrelor had a significant better efficacy over aspirin in patients with ＜50% stenosis of carotid artery or aortic atheroma. This fact may reveal the heterogeneity of ESUS population.

Dementia affects over 35 million people in the world with a rapidly increasing prevalence. Alzheimer's disease (AD) is the most common form of dementia. No fundamental treatment for AD has been established, and novel therapeutic strategies 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 others, and several other promising trials are currently ongoing. This review overviewed recent advances in larger clinical research in dementia.

Herein we describe recent advances in the treatment of neurological infections, as described on reports published in 2017.

Examination of a cohort of Dutch adults with community–acquired bacterial meningitis (BM) revealed that male sex and a history of alcoholism were an independent risk factors for adverse outcomes. Examinations of a Spanish cohort of patients with BM revealed that patients with meningitis and cancer had more subtle clinical manifestations than patients without cancer. Listeria monocytogenes was the predominant pathogen among patients with cancer. The ESCMID guidelines for community–acquired BM were updated, with new recommendations to start empiric treatment within one–hour of arrival for all suspected cases. Follow–up of surviving patients should include evaluations for hearing loss and pneumococcal vaccinations to prevent recurrence.

In Taiwan, the overall incidence of brain abscess (BA) was 1.88 per 100,000 person–years. Age and infectious diseases were important factors associated with in–hospital mortality.

Clinical outcomes of patients with drug–resistant tuberculous meningitis (TbM) were reported by a UK study group. Multidrug resistance was an independent predictor of death. Intensified treatments were significantly associated with improved survival in patients with isoniazid–resistant (INH–R) TBM, although INH–R was significantly associated with the combined outcome of new neurological events or death.

Outcomes of HIV–positive patients with cryptococcal meningitis (CM) in the United States were reported ; here, HIV–positive patients with CM exhibited high mortality, particularly those diagnosed after antiretroviral therapy initiation. An established multicenter retrospective cohort study out of the United States also showed that patients with coccidioidal meningitis who received adjunctive corticosteroids experienced significant reductions in secondary cerebrovascular events.

The clinical guidelines for herpes simplex virus encephalitis (HSVE) in Japan were revised, with recommendations to commence intravenous acyclovir within six–hours of arrival were added, applicable to all cases with suspected encephalitis. The revised guidelines also recommended continuation of acyclovir for at least 14 to 21 days in immunocompetent individuals if HSV–DNA was found within cerebrospinal fluid. For patients with acyclovir–resistant HSVE, a combination therapy that included acyclovir plus intravenous foscarnet or vidarabine was also recommended.

The main syndromes and clinical features of encephalitis associated with the antibodies against dipeptidyl–peptidase–like protein–6 (DPPX) gamma–aminobutyric acid type A receptor (GABAAR), and IgLON5 were reported. DPPX antibodies (predominantly IgG1 and IgG4) were associated with cognitive–mental deficits and symptoms of CNS hyperexcitability that were usually preceded by diarrhea, other gastrointestinal symptoms, and weight loss. Anti–GABAAR encephalitis was characterized by frequent seizures and distinctive multifocal cortical–subcortical MRI abnormalities, which provided important clues for diagnosis. Although the disorder is severe, most patients responded to treatment. Patients with IgLON5 antibodies, associated with the HLA–DRB1*10:01 allele, developed sleep disorder symptoms which preceded or were accompanied by bulbar symptoms, gait abnormalities, and oculomotor problems.

A proposed algorithm for the treatment of anti–LGI1 encephalitis was published, and rituximab was recommended as a second–line immunotherapy for patients who failed first–line immunotherapies, until B–cell depletion was achieved. Oral–prednisolone, in combination with immunosuppressants like azathioprine or mycophenolate mofetil, was also recommended as a maintenance therapy.

Recent advances and new findings relating to multiple sclerosis (MS) and related disorders were reviewed. We adopted the studies regarding an effective treatment for progressive MS, composite endpoints in MS clinical trials, risks for progressive multifocal leukoencephalopathy caused by fingolimod and fumarate, a clinical trial on neuromyelitis optica (NMO), and clinical spectrum of myelin oligodendrocyte glycoprotein (MOG) antibody–positive disorders.

We review reports published in 2017 providing new information on the management of Parkinson's disease (PD). Exenatide, a glucagon–like peptide–1 (GLP–1) receptor agonist, had positive effects on practically defined off–medication Unified Parkinson's Disease Rating Scale (UPDRS) part 3 scores in PD, which were sustained beyond the period of exposure. Low–dose combination of rasagiline and pramipexole (P2B001) improved total–UPDRS scores and Parkinson Disease Quality of Life Scale–39. Omega–3 fatty acids and vitamin E co–supplementation led to a significant improvement in UPDRS after 12 weeks' intervention. No evidence supporting the efficacy of preladenant, the adenosine 2a receptor antagonist, as monotherapy was observed in this phase 3 trial. Dextromethorphan/quinidine and ADS–5102 (Amantadine) Extended–Release Capsules reduced levodopa–induced dyskinesia. Off time was reduced by treatment with once–daily dose of opicapone, a catechol O–methyltransferase (COMT) inhibitor, and safinamide, which is an aminoamide derivative that acts as a highly selective, reversible monoamine oxidase B (MAO–B) inhibitor and blocks voltage dependent sodium and calcium channels and reduces neuronal glutamate release. Focused ultrasound thalamotomy for patients with tremor–dominant PD showed improvements in medication–refractory tremor. Phase 1 trial of PRX002, anti–α–synuclein monoclonal antibody demonstrates serum α–synuclein can be safely decreased after single intravenous infusions. Human induced pluripotent stem cells (iPS cells)–derived dopaminergic progenitor cells survived as midbrain dopaminergic neurons in a primate model of PD (Macaca fascicularis) treated with MPTP for two years without causing any dangerous effects in the body. The animals implanted with iPS cells showed sustained improvement after two years. Virtual house calls from a neurologist are feasible for people with PD and do not significantly change quality of life compared to in–person visits. Unilateral deep brain stimulation of the pedunculopontine nucleus was not effective in improving balance, and falls in patients with progressive supranuclear palsy.

We reviewed the recent advances in therapeutics of spinocerebellar degeneration (SCD) that were published in 2017. This article introduces the outline of therapies with antisense oligonucleotide, docosahexaenoic acid, mesenchymal stem cells, acetyl–DL–leucine, and rehabilitation using wearable devices and virtual reality. We expect that these treatments will contribute to patients with SCD.

Motor neuron diseases (MND) are neurodegenerative syndrome characterized by systemic and selective death of motor neurons. As a represetnative MND, amyotrophic lateral sclerosis (ALS) is the most rapidly progressive disease with adult–onset upper and lower motor neuron degeneration. This review provides an overview of preclinical and clinical advances in ALS research, and summarizes key literature on emerging therapeutic approaches in 2017. The topics include recently published data elucidating pathomechanisms by ALS–linked mutant SOD1, FUS, TARDBP, C9orf72, and recently reported genes. In addition, we describe novel therapeutics for MND, which refer to edaravone for ALS, leuprorelin for spinal bulbar muscular atrophy (SBMA), and nusinersen for spinal muscular atrophy (SMA).

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 2017. In addition, we introduce the promising results in clinical trials of new–targeted immunetherapies for theses diseases.

Various clinical trials for peripheral neuropathy were published in 2017. Systematic PubMed search using terms, “neuropathy”, “peripheral neuropathy”, “treatment”, “therapy”, and “clinical trials” was performed with the time lock from January 1, 2017 through December 31, 2017. Twenty–four clinical trials were detected on diabetic neuropathy (DPN), chemotherapy–induced peripheral neuropathy (CIPN), hereditary ATTR amyloidosis, POEMS syndrome, Guillain–Barre syndrome (GBS), and chronic inflammatory demyelinating polyneuropathy (CIDP). For painful DPN, pregabalin, capsaicin patch, and spinal cord electric stimulation were effective for pain relief. For CIPN, capsaicin patch and glutamine treatment showed possible beneficial effects. For ATTR amyloidosis, post–hoc analysis of the pivotal tafimidis trial revealed that the drug significantly delayed neuropathy progression, whereas a protocol paper for siRNA therapy was published. For POEMS syndrome, GBS, and CIDP, a novel treatment for each disorder finished or is on–going. These results showed sustained research activity to develop new therapies for a number of peripheral nerve disorders.

This article reviews the representative papers of treatment of muscular disorder published in 2017. There are many excellent works, which can provide a framework for the treatment of myasthenia gravis (MG). The mainstays of MG treatment are acetylcholinesterase inhibitors, and immunosuppressive and immunomodulatory therapies. MG presents many challenges for establishing treatment efficacy through clinical trials. Among these are the rarity and heterogeneity of the disease, spontaneous fluctuations, prolonged latency to effect for many immunosuppressive drugs, and the uncertain generalizability of results from randomized controlled trials. Prospective observational study designs may overcome some of these limitations, but attention is required for management for MG. In addition, we also present both basic and clinical investigation of inflammatory myopathies, Duchenne muscular dystrophy, and Pompe disease.

Article on novel development of neurological treatment published in 2017 were reviewed.

Neurogenic orthostatic hypotension (OH) and postprandial hypotension (PH) : According to the Grading of Recommendations Assessment, Development and Evaluation (GRADE), abdominal binder, midodrine and droxidopa were assessed as strong recommendation for OH, and acarbose as strong recommendation for PH.

Postural tachycardia syndrome (PoTS) : Ivabradine showed a possibility of effectiveness for PoTS, but.droxidopa did not improve significantly.

Vasovagal syncope : Fluoxetine improved vasovagal syncope in patients with anxiety. Dual–Chamber pacing significantly reduced the recurrence of vasovagal syncope.

Urinary disturbance : Solifenacine increased maximum cystometric capacity, and injection of onabotulinum toxin A reduced frequency of urinary incontinence.

Chronic constipation : Lubiprostone increased spontaneous bowel movements in diabetic patients with constipation. Low dose linaclotide improved chronic idiopathic constipation. The phase II trial suggest that a clinically optimal dose of elobixibat is 10mg/day for Japanese patients with chronic constipation. Naldemedine significantly increased spontaneous bowel movements in patients with opioid–induced constipation.

Anhidrosis : Degranulation and shrinkage of dark cells in eccrine glands and elevated serum carcinoembryonic antigen were seen in patients with acquired idiopathic generalized anhidrosis (AIGA). The Japanese guideline of AIGA was revised in 2017.

Hyperhidrosis : Percutaneous and oral oxybutynin administration improved hyperhidrosis.

Introduction :

The purpose of this study was to evaluate the effectiveness of a 4–week intensive balance training program and to assess the retention effects during follow–up in patients with spinocerebellar degeneration (SCD) using the Balance Evaluation Systems Test (BESTest).

Methods :

The study included 16 SCD patients. We considered the patients with a Scale for the Assessment and Rating of Ataxia (SARA) score of ＜3 points for inclusion. Our program included five 1–hour training sessions per week with one–on–one instructions and five 1–hour self–balance training sessions per week for 4 weeks. Additionally, occupational or speech–language–hearing therapies were performed for 1 hour a day. We assessed the SARA score and BESTest findings 4 weeks before the intervention (E1), immediately before the first training (E2), immediately after the last training (E3), and 1 month after the last training (E4).

Results :

The SARA score was not significantly different between E2 and E3. The section III (anticipatory postural adjustment), section IV (postural response), and section VI (gait stability) subcategories of the BESTest were significantly different between E2 and E3. Additionally, the section III subcategory of the BESTest showed significant improvement at E4 than at E2.

Conclusion :

It is possible to identify the balance elements that are considered weak using the BESTest in ambulatory SCD patients. We could identify the weak points and balance elements associated with weakness by performing an evaluation using the BESTest protocol. Furthermore, it suggested that the intervention has effects on the total score and the sections III, IV, and VI subcategories of the BESTest, and these tend to sensitively capture the changes associated with the intervention.

We report two cases in which patients with Parkinson's disease underwent unilateral magnetic resonance imaging–guided focused ultrasound (MRgFUS) thalamotomy for medication–refractory tremors. Both patients were males in their 70s, and their resting tremors disappeared immediately during the procedure ; however, severe bradykinesia and gait disturbance persisted. The administration of corticosteroids for severe edema around the targeted lesions ameliorated the bradykinesia and gait disturbance. In addition to the Unified Parkinson's Disease Rating Scale, serial examinations of gait function, including the timed up & go test and the comfortable gait speed in 10–m walking test, were useful for evaluating the patients' motor functions.

A 61–year–old female with advanced Parkinson disease underwent implantation of a deep brain stimulator into the subthalamic nucleus with directional lead and multiple current control technology. The patient's motor fluctuation was abolished by conventional monopolar stimulation with a cylindrical cathode ; however, she complained of dysarthria and postural instability one week after discharge. An investigation of current thresholds and adverse effects identified the responsible contacts―the anteroventral contact for dysarthria, the posteroventrolateral contact for hemibody dysesthesia, and the posteroventral contact for eyelid dullness. Using directional current steering, four different stimulation programs were tested to resolve the dysarthria by steering the current towards the dorsal and posterior directions. After several repetitive adjustments and trials, the patient finally selected the program that featured current distribution of 30% in the dorsal direction and 60% in the posterolateral direction. Based on a subjective assessment, this program was optimal, helping to resolve the dysarthria and dysesthesia, and producing minimal postural instability and best motor performance. Our findings suggest that directional current steering provides optimal therapeutic efficacy with minimal adverse effects.