Masatsune Ishikawa

Proliferation of neuronal precursor cells in the dentate gyrus is accelerated after transient forebrain ischemia in mice

We investigated the proliferation of neuronal progenitor cells by labeling dividing cells by systemic application of the thymidine analog 5-bromodeoxyuridine (BrdU) during transient forebrain ischemia in mice. At 3 (n=6), 7 (n=6), 10 (n=6), and 17 days (n=6) after reperfusion, BrdU-labeled cells were detected in the dentate gyrus and paraventricle lesion. After ischemia-reperfusion, BrdU-labeled cells in the dentate gyrus significantly increased in number but not in the paraventricle lesion. These observations may help to clarify the mechanism of functional recovery after stroke.

Diagnosis of idiopathic normal pressure hydrocephalus is supported by MRI-based scheme: a prospective cohort study

BackgroundIdiopathic normal pressure hydrocephalus (iNPH) is a treatable neurological syndrome in the elderly. Although the magnetic resonance imaging (MRI) findings of tight high-convexity and medial subarachnoid spaces and the ventriculo-peritoneal (VP) shunt with programmable valve are reportedly useful for diagnosis and treatment, respectively, their clinical significance remains to be validated. We conducted a multicenter prospective study (Study of Idiopathic Normal Pressure Hydrocephalus on Neurological Improvement: SINPHONI) to evaluate the utility of the MRI-based diagnosis for determining the 1-year outcome after VP shunt with the Codman-Hakim programmable valve.MethodsTwenty-six centers in Japan were involved in this study. Patients aged between 60 and 85 years with one or more of symptoms (gait, cognitive, and urinary problems) and MRI evidence of ventriculomegaly and tight high-convexity and medial subarachnoid spaces received VP shunt using the height/weight-based valve pressure-setting scheme. The primary endpoint was a favorable outcome (improvement of one level or more on the modified Rankin Scale: mRS) at one year after surgery, and the secondary endpoints included improvement of one point or more on the total score of the iNPH grading scale. Shunt responder was defined by more than one level on mRS at any evaluation point in one year.ResultsThe full analysis set included 100 patients. A favorable outcome was achieved in 69.0% and 80.0% were shunt responders. When measured with the iNPH grading scale, the one-year improvement rate was 77.0%, and response to the surgery at any evaluation point was detected in 89.0%. Serious adverse events were recorded in 15 patients, three of which were events related to surgery or VP shunt. Subdural effusion and orthostatic headache were reported as non-serious shunt-related adverse events, which were well controlled with readjustment of pressure.ConclusionsThe MRI-based diagnostic scheme is highly useful. Tight high-convexity and medial subarachnoid spaces, and enlarged Sylvian fissures with ventriculomegaly, defined as disproportionately enlarged subarachnoid-space hydrocephalus (DESH), are worthwhile for the diagnosis of iNPH. This study is registered with ClinicalTrials.gov, number NCT00221091.

Validation of grading scale for evaluating symptoms of idiopathic normal-pressure hydrocephalus.

Background/Aims: We developed an idiopathic normal-pressure hydrocephalus grading scale (iNPHGS) to classify a triad of disorders (cognitive impairment, gait disturbance and urinary disturbance) of iNPH with a wide range of severity. The purpose of this study was to assess the reliability and validity of this scale in 38 patients with iNPH. Results: The interrater reliability of this scale was high. The iNPHGS cognitive domain score significantly correlated with the cognitive test scores, including the Mini-Mental State Examination (MMSE), the gait domain score with the Up and Go Test and Gait Status Scale scores, and the urinary domain score with the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) score. The MMSE, Gait Status Scale and ICIQ-SF scores significantly improved in patients whose iNPHGS scores improved after CSF tapping but not in those whose iNPHGS scores did not improve after CSF tapping. Fourteen of the 38 patients received shunt operations. In these 14 patients, changes in the iNPHGS cognitive and urinary domains after CSF tapping were significantly associated with the changes after the shunt operation.

Demonstration of neurovascular compression in trigeminal neuralgia and hemifacial spasm with magnetic resonance imaging: comparison with surgical findings in 60 consecutive cases.

BACKGROUND Until recently, it has been impossible to demonstrate vascular compression at the root entry or exit zone (REZ) of the trigeminal nerve and facial nerve in patients with trigeminal neuralgia (TN) and hemifacial spasm (HFS) preoperatively, although surgical findings have revealed apparent neurovascular compression and its correction has resulted in a good outcome in most cases. Revealing the anatomic correlation between nerves and vessels at the REZ preoperatively would be useful to predict operative findings. METHODS To assess whether the vascular contact of the nerve at the REZ could be demonstrated preoperatively, high-resolution magnetic resonance tomographic angiography (MRTA) was performed in 21 patients with TN and 39 with HFS. Neuroradiological findings were compared with the operative findings in all patients. Contralateral asymptomatic nerves were evaluated as a control. RESULTS MRTA correctly identified offending vessels in 14 (67%) of the 21 TN and 34 (87%) of the 39 HFS patients. Failure to identify neurovascular contact was noted in the cases with compression by veins or small arteries, thickened arachnoid, or distal compression. Neurovascular contact was also observed in 15% of the asymptomatic nerves. The deformity of the nerve seemed to be a more important factor for determining operative indication. CONCLUSIONS MRTA could demonstrate offending vessels in TN and HFS at a high rate and was useful to predict operative findings. MRTA gave supportive evidence of surgical indications in patients with TN and HFS, although attention should be paid to the fact that MRTA did not necessarily detect all of the offending vessels.

Influence of comorbidities in idiopathic normal pressure hydrocephalus — research and clinical care. A report of the ISHCSF task force on comorbidities in INPH

Idiopathic normal pressure hydrocephalus (INPH) is a syndrome of ventriculomegaly, gait impairment, cognitive decline and incontinence that occurs in an elderly population prone to many types of comorbidities. Identification of the comorbidities is thus an important part of the clinical management of INPH patients. In 2011, a task force was appointed by the International Society for Hydrocephalus and Cerebrospinal Fluid Disorders (ISHCSF) with the objective to compile an evidence-based expert analysis of what we know and what we need to know regarding comorbidities in INPH. This article is the final report of the task force. The expert panel conducted a comprehensive review of the literature. After weighing the evidence, the various proposals were discussed and the final document was approved by all the task force members and represents a consensus of expert opinions. Recommendations regarding the following topics are given: I. Musculoskeletal conditions; II. Urinary problems; III. Vascular disease including risk factors, Binswanger disease, and white matter hyperintensities; IV. Mild cognitive impairment and Alzheimer disease including biopsies; V. Other dementias (frontotemporal dementia, Lewy body, Parkinson); VI. Psychiatric and behavioral disorders; VII. Brain imaging; VIII. How to investigate and quantify. The task force concluded that comorbidity can be an important predictor of prognosis and post-operative outcome in INPH. Reported differences in outcomes among various INPH cohorts may be partly explained by variation in the rate and types of comorbidities at different hydrocephalus centers. Identification of comorbidities should thus be a central part of the clinical management of INPH where a detailed history, physical examination, and targeted investigations are the basis for diagnosis and grading. Future INPH research should focus on the contribution of comorbidity to overall morbidity, mortality and long-term outcomes.

SPECT with 99mTc]-d,l-Hexamethyl-Propylene Amine Oxime (HM-PAO) Compared with Regional Cerebral Blood Flow Measured by PET: Effects of Linearization

In order to validate the use of technetium-99m–d,l-hexamethylpropyleneamine oxime (HM-PAO) as a flow tracer, a total of 21 cases were studied with single photon emission computerized tomography (SPECT), and compared to regional cerebral blood flow (rCBF) measured by position emission tomography (PET) using the oxygen-15 CO2 inhalation technique. Although HM-PAO SPECT and rCBF PET images showed a similar distribution pattern the HM-PAO SPECT image showed less contrast between high and low activity flow regions than the rCBF image and a nonlinear relationship between HM-PAO activity and rCBF was shown. Based on the assumption of flow-dependent backdiffusion of HM-PAO from the brain, we applied a “linearization algorithm” to correct the HM-PAO SPECT images. The corrected HM-PAO SPECT images revealed a good linear correlation with rCBF (r = 0.901, p < 0.001). The results indicated HM-PAO can be used as a flow tracer with SPECT after proper correction.

Lumboperitoneal shunt surgery for idiopathic normal pressure hydrocephalus (SINPHONI-2): An open-label randomised trial

BACKGROUND Lumboperitoneal shunt surgery has the potential to alleviate symptoms of normal pressure hydrocephalus but the benefits of such surgery have not been tested in a randomised trial. The aim of this trial was to determine the safety and efficacy of the lumboperitoneal shunt surgery for this disorder. METHODS For the open-label randomised SINPHONI-2 trial, eligible participants (60-85 years of age) with idiopathic normal pressure hydrocephalus, with ventriculomegaly, and tightness of the high-convexity and medial subarachnoid spaces on MRI, were recruited from 20 neurological and neurosurgical centres in Japan. Enrolled participants were randomly assigned in a 1:1 ratio according to a random code generated by the trial statistician, with a permuted block design (using a block size of 4 or 6) within each centre, to receive lumboperitoneal shunt surgery within 1 month after randomisation, or to surgery postponed for 3 months. Patients and assessors were not masked to treatment assignment. The primary endpoint was favourable outcome, defined as an improvement of one point or more on the modified Rankin scale (mRS) at 3 months after randomisation, analysed by intention to treat, and the main secondary endpoint was the same outcome 12 months after surgery, analysed per protocol. This trial is registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR), number UMIN000002730. FINDINGS Between March 1, 2010, and Oct 19, 2011, 93 patients with idiopathic normal pressure hydrocephalus were enrolled and randomly assigned to the immediate treatment group (n=49) or the postponed treatment group (n=44). More patients in the immediate treatment group than in the postponed treatment group had an improvement of one point or more on the mRS at 3 months: 32 (65%) of 49 in the immediate group vs 2 (5%) of 44 in the postponed group (difference 61% [95% CI 42-68]; p<0·0001). The number of patients who had an improvement of one point or more on the mRS at 12 months after surgery was similar between the two groups: 30 (67%) of 45 patients in the immediate group vs 22 (58%) of 38 in the postponed group (difference 9% [95% CI -14 to 31]; p=0·496). The proportions of patients with serious adverse events did not differ significantly between the groups during the 3 months post-randomisation (7 [15%] of 46 in the immediate group vs 1 [2%] of 42 in the postponed group; p=0·060). During the 12 months after surgery, 19 (22%) of 87 patients had serious adverse events, the most common of which was cerebral infarction (six patients [7%]). INTERPRETATION Our results suggest that lumboperitoneal shunt surgery might be beneficial for patients with idiopathic normal pressure hydrocephalus and, if these findings are confirmed in larger studies, could be a first-line treatment option for this disease. FUNDING Johnson & Johnson and Nihon Medi-Physics.

Activation of three types of voltage‐independent Ca2+ channel in A7r5 cells by endothelin‐1 as revealed by a novel Ca2+ channel blocker LOE 908

We have shown that in addition to voltage‐operated Ca2+ channel (VOC), endothelin‐1 (ET‐1) activates two types of Ca2+‐permeable nonselective cation channel (NSCC) in A7r5 cells: its lower concentrations (1 nM; lower [ET‐1]) activate only an SK&F 96365‐resistant channel (NSCC‐1), whereas its higher concentrations (10 nM; higher [ET‐1]) activate an SK&F 96365‐sensitive channel (NSCC‐2) as well. We now characterized the effects of a blocker ofCa2+ entry channel LOE 908 on NSCCs and store‐operatedCa2+ channel (SOCC) in A7r5 cells, and using twodrugs, clarified the involvement of these channels in the ET‐1‐inducedincrease in the intracellular free Ca2+ concentrations([Ca2+]i). Whole‐cell recordingsand [Ca2+]i monitoring withfluo‐3 were used. LOE 908 up to 10 μM had no effect on increases in [Ca2+]i induced by thapsigargin or ionomycin, but SK&F 96365 abolished them. In the cells clamped at −60 mV, both lower and higher [ET‐1] induced inward currents with linear iv relationships and the reversal potentials of −15.0 mV. Thapsigargin induced no currents. In the presence of nifedipine, lower [ET‐1] induced a sustained increase in [Ca2+]i, whereas higher [ET‐1] induced a transient peak and a sustained increase. The sustained increases by lower and higher [ET‐1] were abolished by removal of extracellular Ca2+, and they were suppressed by LOE 908 to 0 and 35%, respectively, with the LOE 908‐resistant part being abolished by SK&F 96365. These results show that LOE 908 is a blocker of NSCCs without effect on SOCC, and that the increase in [Ca2+]i at lower [ET‐1] results from Ca2+ entry through NSCC‐1 in addition to VOC, whereas the increase at higher [ET‐1] involves NSCC‐1, NSCC‐2 and SOCC in addition to VOC.

Epidural pulse waveform as an indicator of intracranial pressure dynamics

With an increase in intracranial pressure during epidural balloon inflation, epidural pulse waveform, which is polyphasic under normal conditions, becomes monotonous at about 30 mmHg. This change in waveform is considered closely related to the apparent increase in arterial driving pressure to the brain and to a disturbance of venous outflow. When cerebral vasodilatation is prominent, the waveform becomes monotonous at a significantly lower intracranial pressure. These findings correlate well with the results of spectral analysis of the pulse wave. The usefulness of change in epidural pulse waveform, which can indicate an alteration of intracranial pressure dynamics in a relatively low pressure range, is discussed with comparison to other techniques used to determine intracranial pressure dynamics.

Histochemical mapping of catecholaminergic neurons and their ascending fiber pathways in the rhesus monkey brain

Abstract A semi-stereotaxic map of CA neurons and their fiber pathways in the rhesus monkey has been constructed using the Falck-Hillarp method. The present study confirms the presence of ascending CA fiber pathways and their branches; the ventral and dorsal bundles and periventricular system in association with the well defined myelinated fasciculus by the classical neuroanatomical technique.