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Journal: Neurologia medico-chirurgica


The efficacy of hybrid assistive limb (HAL) rehabilitation in the acute phase of stroke remains unclear. The purpose of this study was to evaluate the outcomes of patients with acute intracranial hemorrhage (ICH) who were treated with or without HAL rehabilitation. Among 270 patients with acute ICH from 2009 to 2014, 91 patients with supratentorial ICH were included in this retrospective study. Of these, 14 patients (HAL group) received HAL rehabilitation at approximately 1 week after ICH occurrence, while the remaining 77 patients received usual rehabilitation without HAL (N-HAL group). We obtained various patient data from the hospitals where the patients were moved to for further rehabilitation. Statistical comparisons were performed for the characteristics of the ICH patients, and outcomes between the HAL and N-HAL groups. There were no differences in outcomes between the HAL and N-HAL groups. However, patients with right ICH in the HAL group exhibited a significant association with a functional independence measure (FIM) score of ≥ 110 compared with patients in the N-HAL group (HAL group: 81.8%, N-HAL group: 43.9%, P = 0.04). In patients with right ICH, HAL rehabilitation was associated with improved outcomes as evaluated by the FIM score. Thus, HAL rehabilitation may improve outcomes of acute ICH in appropriately selected patients.

Concepts: Patient, Hospital, Stroke, HAL 5


“Once development was ended…in the adult centers, the nerve paths are something fixed and immutable. Everything may die, nothing may be regenerated,” wrote Santiago Ramón y Cajal, a Spanish neuroanatomist and Nobel Prize winner and the father of modern neuroscience. This statement was the central dogma in neuroscience for a long time. However, in the 1960s, neural stem cells (NSCs) were discovered. Since then, our knowledge about NSCs has continued to grow. This review focuses on our current knowledge about NSCs and their surrounding microenvironment. In addition, the clinical application of NSCs for the treatment of various central nervous system diseases is also summarized.

Concepts: Central nervous system, Nervous system, DNA, Neuron, Brain, Stem cell, Neuroscience, Neurogenesis


There are considerable variations in the anatomy of the human ophthalmic artery (OphA), such as anomalous origins of the OphA and anastomoses between the OphA and the adjacent arteries. These anatomical variations seem to attribute to complex embryology of the OphA. In human embryos and fetuses, primitive dorsal and ventral ophthalmic arteries (PDOphA and PVOphA) form the ocular branches, and the supraorbital division of the stapedial artery forms the orbital branches of the OphA, and then numerous anastomoses between the internal carotid artery (ICA) and the external carotid artery (ECA) systems emerge in connection with the OphA. These developmental processes can produce anatomical variations of the OphA, and we should notice these variations for neurosurgical and neurointerventional procedures.

Concepts: Embryo, Developmental biology, Internal carotid artery, Common carotid artery, External carotid artery, Embryology, Arteries of the head and neck, Ophthalmic artery


Cerebrospinal fluid (CSF) plays an essential role in maintaining the homeostasis of the central nervous system. The functions of CSF include: (1) buoyancy of the brain, spinal cord, and nerves; (2) volume adjustment in the cranial cavity; (3) nutrient transport; (4) protein or peptide transport; (5) brain volume regulation through osmoregulation; (6) buffering effect against external forces; (7) signal transduction; (8) drug transport; (9) immune system control; (10) elimination of metabolites and unnecessary substances; and finally (11) cooling of heat generated by neural activity. For CSF to fully mediate these functions, fluid-like movement in the ventricles and subarachnoid space is necessary. Furthermore, the relationship between the behaviors of CSF and interstitial fluid in the brain and spinal cord is important. In this review, we will present classical studies on CSF circulation from its discovery over 2,000 years ago, and will subsequently introduce functions that were recently discovered such as CSF production and absorption, water molecule movement in the interstitial space, exchange between interstitial fluid and CSF, and drainage of CSF and interstitial fluid into both the venous and the lymphatic systems. Finally, we will summarize future challenges in research. This review includes articles published up to February 2016.

Concepts: Central nervous system, Nervous system, Psychology, Neuron, Spinal cord, Brain, Cerebrospinal fluid, Meninges


Our aim was to clarify the nutritional status and energy intake needed for activities of daily living (ADL) improvement among convalescent stroke patients. This retrospective cohort study of stroke patients used data from the Japan Rehabilitation Nutrition Database. Mean energy intake per ideal body weight was 26 kcal/kg/day at 1 week after hospitalization. Patients were divided into two groups according to energy intake: ≥26 kcal/kg/day (high) and <26 kcal/kg/day (low). ADL was evaluated using Functional Independence Measure (FIM), and nutritional status was evaluated using the mini nutritional assessment short form score. We created an inverse probability weighted (IPW) model using propensity scoring to control and adjust for patient characteristics and confounders at the time of admission. The analysis included 290 patients aged 78.1 ± 7.8 years. There were 165 patients with high energy intake and 125 patients with low energy intake. FIM score was significantly higher in the high group compared with the low group (median 113 vs 71, P <0.001). FIM efficiency was also higher in the high group (median 0.31 vs 0.22, P <0.001). FIM efficiency was significantly higher in the high energy intake group than in the low energy intake group after adjustment by IPW (median 0.31 vs 0.25, P = 0.011). Nutritional status improvement was also higher in the high energy intake group after adjustment by IPW (60.6% vs 45.2%, P <0.001). High energy intake was associated with higher FIM efficiency and nutritional status improvement at discharge among convalescent stroke patients.


Diffuse intrinsic pontine glioma (DIPG) is a rare but uniformly fatal cancer of the brain, with peak incidence in children of 5-7 years of age. In contrast to most types of human cancer, there has been no significant improvement in treatment outcomes for patients with DIPG. Since DIPG occurs in the brainstem, a vital region of the brain, there are no surgical options for providing relief to patients, and chemotherapy as well as radiation therapy provide palliative relief at best. To date, more than 250 clinical trials evaluating radiotherapy along with conventional cytotoxic chemotherapy, as well as newer biologic agents, have failed to improve the dismal outcome when compared with palliative radiation alone. The recent discovery of somatic oncogenic histone gene mutations affecting chromatin regulation in DIPG has dramatically improved our understanding of the disease pathogenesis in DIPG, and these findings have stimulated the development of novel therapeutic approaches targeting epigenetic regulators for disease treatment. This review will discuss about the role of histone modification in chromatin machinery and epigenetic therapeutic strategies for the treatment of DIPG.

Concepts: DNA, Medicine, Cancer, Ionizing radiation, Oncology, Histone, Chemotherapy, Radiation therapy


We analyzed the cell characteristics, neuroprotective, and transplantation effects of human cranial bone-derived mesenchymal stem cells (hcMSCs) in ischemic stroke model rats compared with human iliac bone-derived mesenchymal stem cells (hiMSCs). The expressions of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF ) as neurotrophic factors were analyzed in both MSCs. hiMSCs or hcMSCs were intravenously administered into ischemic stroke model rats at 3 or 24 h after middle cerebral artery occlusion (MCAO) and neurological function was evaluated. The survival rate of neuroblastoma × glioma hybrid cells (NG108-15) after 3 or 24 h oxidative or inflammatory stress and the neuroprotective effects of hiMSCs or hcMSCs-conditioned medium (CM) on 3 or 24 h oxidative or inflammatory stress-exposed NG108-15 cells were analyzed. The expressions of BDNF and VEGF were higher in hcMSCs than in hiMSCs. hcMSCs transplantation at 3 h after MCAO resulted in significant functional recovery compared with that in the hiMSCs or control group. The survival rate of stress-exposed NG108-15 was lower after 24 h stress than after 3 h stress. The survival rates of NG108-15 cells cultured with hcMSCs-CM after 3 h oxidative or inflammatory stress were significantly higher than in the control group. Our results suggest that hcMSCs transplantation in the early stage of ischemic stroke suppresses the damage of residual nerve cells and leads to functional recovery through the strong expressions of neurotrophic factors. This is the first report demonstrating a functional recovery effect after ischemic stroke following hcMSCs transplantation.


Endosaccular coiling is recognized as a feasible method for treating unruptured intracranial aneurysms (UIAs). We retrospectively reviewed cases of UIAs treated by coiling in the Japanese Registry of Neuroendovascular Therapy (JR-NET) 3, a nationwide survey of NET between 2010 and 2014, the beginning period of intracranial stents in Japan. Data were extracted for 6844 UIAs (6619 procedures) from 40,169 registered records of all NETs in the JR-NET 3 databases. The features of the aneurysms and procedures, immediate radiographic findings, procedure-related complications, and clinical outcomes at 30 days after the procedures were assessed. Of 6844 UIAs, 81.8% were located in the anterior circulation. The mean patient age was 61.3 years (72.4% females). Compared with the preceding JR-NET 1 and 2, there were significant increases (P <0.05) in the rates of the following in JR-NET 3: wide-necked and small UIAs measuring <10 mm (from 56.4% to 58.8%), adjunctive techniques (54.8% to 71.8%), and stent usage (1.1% to 22.1%). Both pre- (85.6% to 96.7%) and post-procedural (84.0% to 94.6%) antiplatelet therapy were more frequently administered in JR-NET 3. Although procedure-related complication rates did not differ between the two groups, ischemic complication rates increased from 4.6% to 5.9%, leading to an increase in the 30-day morbidity (modified Rankin Scale >2) from 2.1% to 2.8%. In conclusion, introduction of neck-bridge stent was associated with an increase in cases of wide-necked aneurysms. However, the ischemic complication rate increased despite the greater use of periprocedural antiplatelet therapy.


The histone H3K27M-mutant diffuse midline glioma is often seen in children and has a very poor prognosis regardless of its histological grade. Although it can occur in adults, few studies on adult cases have been reported. We examined adult midline glioma cases for their histological grade, presence of H3K27M mutation, and expression of related factors-enhancer of zeste homolog 2 (EZH2), H3K27me3, p16, and methylthioadenosine phosphorylase. These tumor characteristics were also evaluated for their prognostic value in adult midline glioma. High histological grade, H3K27M-mutant, high EZH2 expression, and high H3K27me3 expression was detected in 12/23 (53%), 11/23 (48%), 9/23 (39%), and 12/23 (52%) cases, respectively. Histological grade and prognosis were significantly correlated (P <0.01). The high expression of EZH2 and the low expression of H3K27me3 correlated with histological malignancy (P = 0.019 and 0.009) and prognosis (P = 0.048 and 0.047). To broaden the scope of our analysis, a review of cases reported in the literature (2014-2019) was performed. In the 171 cases, H3K27M-mutant showed poor prognosis in the young adult group (P = 0.001), whereas H3K27 status had no effect on prognosis in the older age group (P = 0.141). Histological grade was correlated with prognosis in both young adults and older groups (P <0.001, P = 0.003, respectively). We demonstrate differences in prognostic factors for diffuse gliomas in the midline region for children and adults. Importantly, the H3K27M mutation significantly influences prognosis in children, but not necessarily in adults. Contrarily, histological grading and immunostaining are important prognostic tools in adults.


The long-term prophylactic effect of carotid artery stenting (CAS) remains incompletely elucidated. We evaluated outcomes of CAS at our institution to determine the safety and efficacy of CAS in real-world settings. We retrospectively analyzed 73 patients who underwent CAS from 2006 to 2013. Periprocedural results were compared between asymptomatic and symptomatic carotid stenosis groups. The primary endpoint was a composite of ipsilateral stroke, death, and carotid artery restenosis beyond 30 days and within 5 years after the first procedure. The average age was 72.2 years with a majority of male subjects (84.9%). Twenty-seven patients (37%) were asymptomatic. Incidence of periprocedural adverse events and mRS ≤2 at 30 days after CAS were not significantly different between groups (P = 0.14 and 0.07, respectively). CAS was unsuccessful in three patients and one post-procedural minor stroke occurred. Therefore, 69 patients were included in the long-term study. The rate of occurrence of the primary endpoint was 21.7%. Ipsilateral ischemic stroke occurred in one patient, which was due to cardiogenic embolus. Nine patients died, and cancer was the most frequent cause. Five in-stent restenoses were observed. All patients with restenosis underwent additional CAS without any occurrence of stroke. This study revealed the safety and long-term efficacy of CAS in a real-world setting. Routine follow-up is also important for detecting carotid artery restenosis.