Small Hyperintensities in the Area of the Perforating Arteries in Patients with Seizure.

BACKGROUND/AIM: We previously observed spotty hyperintense lesions in the region of the perforating arteries on peri-ictal diffusion-weighted imaging (DWI); however, no report has formally described these findings. The aim of this study was to investigate focal intensities on peri-ictal DWI, and to evaluate the clinical significance of these lesions. METHODS: We conducted a retrospective review of 677 consecutive patients with seizure who completed peri-ictal DWI within 24 h after seizure onset. Patients were grouped according to the presence or absence of diffusion hyperintense lesions (DHLs) in the region of the perforating arteries. We compared clinical and imaging characteristics between these 2 groups. RESULTS: Among 677 patients, 23 patients (3.4%) had DHLs. Analyses of apparent diffusion coefficient values and fluid attenuated inversion recovery images suggested that DHLs were acute or subacute ischemic lesions that had appeared prior to seizure onset. Patients with DHLs were more likely to be older in age, have atrial fibrillation, and coronary artery disease, and have more severe deep white matter hyperintensity or leukoaraiosis compared to patients without DHLs. CONCLUSION: DHLs detected on peri-ictal DWI may represent incidental acute cerebral microinfarcts in the aging brain, especially in patients with small vessel disease.

Relationship Between Infarct Volume and Prothrombin Time-International Normalized Ratio in Ischemic Stroke Patients With Nonvalvular Atrial Fibrillation.

BACKGROUND: In Japan, warfarin treatment at prothrombin time-international normalized ratio (PT-INR) of 1.60-2.60 is recommended for elderly patients with nonvalvular atrial fibrillation (NVAF). But it remains unknown whether PT-INR 1.60-1.99 has a similar effect on stroke severity as a value >2.0. The purpose of this study was to clarify the association between infarct volume and PT-INR levels.Methods and Results:The 180 patients (mean age, 76 years [SD, 10 years], 53% male) selected from 429 consecutive ischemic stroke patients admitted within 48 h of onset between 2004 and 2014 with NVAF were included. We classified them into 4 groups according to their PT-INR values on admission: no warfarin (NW), 129 patients; PT-INR <1.60 (poor control: PC), 29 patients; PT-INR 1.60-1.99 (low-intensity control: LC), 14 patients; and PT-INR ≥2.00 (high-intensity control: HC), 8 patients. Median (interquartile range: IQR) of infarct volume was 55 mL (IQR 14-175) in the NW, 42 mL (IQR 27-170) in the PC, 36 mL (IQR 6-130) in the LC, and 11 mL (IQR 0-39) in the HC groups. The infarct volume of the HC group was significantly smaller than in the other 3 groups, but no difference existed between the LC and PC groups or the LC and NW groups. CONCLUSIONS: Warfarin control at PT-INR of 1.60-1.99 is not effective for reducing the severity of ischemic stroke in NVAF patients.

Brachial-Ankle Pulse Wave Velocity as a Predictor of Silent Cerebral Embolism after Carotid Artery Stenting.

BACKGROUND: In neuroendovascular therapy, the effect of arterial stiffness on postprocedural cerebral thromboembolism is unknown. In this observational study, we examined the relationship between cerebral thromboembolism after carotid artery stenting and arterial stiffness. METHODS: From April 2015 to February 2017, we enrolled consecutive patients undergoing scheduled carotid artery stenting in our institution. In all patients, preprocedural brachial-ankle pulse wave velocity was used to assess arterial stiffness, whereas the number of new cerebral ischemic lesions on diffusion-weighted magnetic resonance imaging was assessed after treatment. We also analyzed patient data and details of procedures in patients with carotid artery stenting. RESULTS: Twenty-one patients completed the study. The mean brachial-ankle pulse wave velocity was 1879 cm/s. There was no association of cerebral thromboembolisms with age, unstable plaque, protection device, or type of stent. However, the brachial-ankle pulse wave velocity was an independent predictor of cerebral thromboembolisms (P = .0017). CONCLUSIONS: Brachial-ankle pulse wave velocity is predictive of silent cerebral embolisms on diffusion-weighted magnetic resonance imaging after carotid artery stenting.

Voxel-Based Lesion Mapping of Cryptogenic Stroke in Patients with Advanced Cancer: A Detailed Magnetic Resonance Imaging Analysis of Distribution Pattern.

BACKGROUND: Ischemic stroke is one form of cancer-associated thrombosis that can greatly worsen a patient's performance status. The present investigation aimed to elucidate the characteristic distribution pattern(s) of cryptogenic stroke lesions using a voxel-based lesion-mapping technique and examine the differences in clinical manifestations between cryptogenic and conventional strokes in patients with advanced cancer. METHODS: Data from 43 patients with advanced cancer who developed acute ischemic stroke were retrospectively collected. Stroke etiology was grouped into either cryptogenic or conventional stroke etiology according to the ASCO stroke score. Clinical data were reviewed, and voxel-based lesion mapping using diffusion-weighted imaging (DWI) was performed to visualize the cross-patient spatial distribution of the lesions. RESULTS: Of the 43 patients, 25 were classified as having cryptogenic stroke etiology and 18 were classified as having conventional stroke etiology. Median survival time of patients from stroke onset was 96 days for cryptogenic stroke etiology and 570 days for conventional stroke etiology (P = .01). D-dimer of patients was significantly higher in cryptogenic stoke etiology than in conventional stroke etiology (P = .006). Voxel-based lesion mapping showed that DWI hyperintense lesions accumulated at cortical and internal watershed areas of the cerebrum and at the vascular border zone of the superior cerebellar and posterior inferior cerebellar arteries at the cerebellum. CONCLUSIONS: Voxel-based lesion mapping for cryptogenic stroke in patients with advanced cancer showed that lesions accumulated at vascular border zones within the brain both at the cerebrum and at the cerebellum, but not at perforating arterial territories.

Association of WT1 IgG antibody against WT1 peptide with prolonged survival in glioblastoma multiforme patients vaccinated with WT1 peptide.

We previously evaluated Wilms' tumor gene 1 (WT1) peptide vaccination in a large number of patients with leukemia or solid tumors and have reported that HLA-A*24:02 restricted, 9-mer WT1-235 peptide (CYTWNQMNL) vaccine induces cellular immune responses and elicits WT1-235-specific cytotoxic T lymphocytes (CTLs). However, whether this vaccine induces humoral immune responses to produce WT1 antibody remains unknown. Thus, we measured IgG antibody levels against the WT1-235 peptide (WT1-235 IgG antibody) in patients with glioblastoma multiforme (GBM) receiving the WT1 peptide vaccine. The WT1-235 IgG antibody, which was undetectable before vaccination, became detectable in 30 (50.8%) of a total of 59 patients during 3 months of WT1 peptide vaccination. The dominant WT1-235 IgG antibody subclass was Th1-type, IgG1 and IgG3 . WT1-235 IgG antibody production was significantly and positively correlated with both progression-free survival (PFS) and overall survival (OS). Importantly, the combination of WT1-235 IgG antibody production and positive delayed type-hypersensitivity (DTH) to the WT1-235 peptide was a better prognostic marker for long-term OS than either parameter alone. These results suggested that WT1-235 peptide vaccination induces not only WT1-235-specific CTLs as previously described but also WT1-235-specific humoral immune responses associated with antitumor cellular immune response. Our results indicate that the WT1 IgG antibody against the WT1 peptide may be a useful predictive marker, with better predictive performance in combination with DTH to WT1 peptide, and provide a new insight into the antitumor immune response induction in WT1 peptide vaccine-treated patients.

Respiratory Function Under Intrathecal Baclofen Therapy in Patients With Spastic Tetraplegia.

OBJECTIVES: Intrathecal baclofen (ITB) therapy is an effective treatment for patients with severe spasticity. However, the effect of ITB therapy on respiratory function has not been reported in detail. In this study we quantitatively analyzed the effects of ITB on the respiratory function of patients with spastic tetraplegia. METHODS: We retrospectively reviewed 23 patients who were administrated ITB therapy from January 2009 to December 2012. Six of these 23 patients, who had spastic tetraplegia and were able to undergo spirometric testing, were included this study. The spasticity derived from cervical spinal cord injury in four patients and cerebral palsy (CP) in two patients. Patients' Ashworth Scale scores and spirometer measurements obtained before and 1-6 months after the start of ITB therapy were evaluated and compared. RESULTS: Before ITB therapy, %FVC of all six patients was below 80%, and a restrictive respiratory disorder was diagnosed in five patients and a combined respiratory disorder in one patient. Ashworth Scale scores for both the lower and upper extremities improved significantly with ITB therapy. Forced vital capacity (FVC), %FVC, and forced expiratory volume at one sec also improved significantly with ITB therapy. CONCLUSIONS: Respiratory disorders were indeed present in our SCI and CP patients with spastic tetraplegia, and the respiratory function of these patients improved with ITB therapy. Our results suggest that ITB therapy is safe and efficacious in patients with spastic tetraplegia and respiratory dysfunction.

Prediction of Malignant Middle Cerebral Artery Infarction in Elderly Patients.

BACKGROUND: We evaluated the clinical outcomes of malignant middle cerebral artery (MCA) infarction (MMI) and determined an infarcted brain volume (BV) threshold value for accurate MMI prediction in elderly patients. METHODS: We analyzed 69 consecutive patients (mean, 75.6 ± 11.7) with internal carotid artery or MCA infarction within 48 hours from onset. Diffusion-weighted high-intensity volume (DHV) and BV were measured in all patients. The percentage of DHV within BV (DHV/BV ratio) was calculated to standardize the DHV difference for each individual BV. Patients were stratified based upon their MMI status and age, compared with the following: (1) MMI versus non-MMI groups and (2) age ≥75 years group versus age <75 years group, based on DHV values, DHV/BV ratio, Glasgow Coma Scale (GCS) scores on admission, and modified Rankin Scale (mRS) scores at 3 months after onset. RESULTS: The MMI group (n = 14) showed significantly larger DHV values (P < .001), larger DHV/BV ratios (P < .001), lower GCS scores on admission (P < .01), and higher mRS scores at 3 months (P < .001) than the non-MMI group. The DHV threshold value predicting MMI was 102 cm(3) (sensitivity 85%, specificity 91%, P < .01) and DHV/BV threshold ratio was 7.8% (sensitivity 86%, specificity 87%, P < .01). Both the age ≥75 years group and the age <75 years group with MMI showed equally poor outcomes (mRS 5.7 ± .7 versus 5.3 ± 1.3). CONCLUSIONS: DHV and DHV/BV can provide reliable information for MMI prediction in elderly patients.

Wilms tumor 1 peptide vaccination combined with temozolomide against newly diagnosed glioblastoma: safety and impact on immunological response.

To investigate the safety of combined Wilms tumor 1 peptide vaccination and temozolomide treatment of glioblastoma, a phase I clinical trial was designed. Seven patients with histological diagnosis of glioblastoma underwent concurrent radiotherapy and temozolomide therapy. Patients first received Wilms tumor 1 peptide vaccination 1 week after the end of combined concurrent radio/temozolomide therapy, and administration was continued once per week for 7 weeks. Temozolomide maintenance was started and performed for up to 24 cycles, and the observation period for safety encompassed 6 weeks from the first administration of maintenance temozolomide. All patients showed good tolerability during the observation period. Skin disorders, such as grade 1/2 injection-site reactions, were observed in all seven patients. Although grade 3 lymphocytopenia potentially due to concurrent radio/temozolomide therapy was observed in five patients (71.4 %), no other grade 3/4 hematological or neurological toxicities were observed. No autoimmune reactions were observed. All patients are still alive, and six are on Wilms tumor 1 peptide vaccination without progression, yielding a progression-free survival from histological diagnosis of 5.2-49.1 months. Wilms tumor 1 peptide vaccination was stopped in one patient after 12 injections by the patient's request. The safety profile of the combined Wilms tumor 1 peptide vaccination and temozolomide therapy approach for treating glioblastoma was confirmed.

Olfactory sphere cells are a cell source for γ-aminobutyric acid-producing neurons.

Olfactory sphere cells (OSCs) are stem cells generated by culturing olfactory mucosa. Adult rat OSCs express oligodendrocyte progenitor cell (OPC) markers and differentiate into mature oligodendrocytes. Although OSCs also express nestin, a marker of neural stem cells (NSCs), it remains unclear whether adult rat OSCs are multipotent and capable of giving rise to neurons as well as oligodendrocytes. Valproic acid (VPA) is a histone deacetylase inhibitor that has the contradictory capacity to induce both differentiation of NSCs and dedifferentiation of OPCs. This study investigates a potential role for VPA in inducing either differentiation or dedifferentiation of adult rat OSCs. Treatment of OSCs with VPA induced hyperacetylation of histones and decreased cell proliferation in the absence of changes in the number of nestin-positive cells. Furthermore, VPA promoted the genesis of γ-aminobutyric acid (GABA)-producing neurons identified by expression of Tuj1/GAD67/GABA while repressing oligodendrocyte production. These findings suggest that OSCs treated with VPA did not exhibit stem cell properties indicative of dedifferentiation but rather switched to a neuronal identity during their terminal differentiation. OSCs were then transplanted into the hippocampus of rats with kainic acid-induced temporal lobe epilepsy and were systemically given VPA. Although grafted OSCs expressed Tuj1 and GAD67, these cells did not sufficiently inhibit epileptic activity. These results suggest that OSCs are a transplantable cell source for GABA-producing neurons that can be modulated by VPA. However, further investigation is required to develop them for clinical applications.

Retro-odontoid synovial cyst resected via an anterolateral approach without fusion.

PURPOSE: Retro-odontoid synovial cysts are rare and attributable to degenerative changes in the atlantoaxial joints. An anterolateral approach facilitates access to lesions located anterior to the craniocervical junction without harming the atlantoaxial joints, and can also treat small lesions in the ventral mid-portion of the craniocervical junction without compression of spinal cord. METHODS: We present herein the case of a 70-year-old man with a retro-odontoid synovial cyst. A ventral midsection mass was present at the level of the atlantoaxial joint. The compressed anterior medulla led to neurological deficits. Slight atlantoaxial instability was radiologically present. An intradural cyst resection without fusion was performed via the anterolateral approach. The diagnosis of a synovial cyst was histologically confirmed. RESULTS: The patient was followed up for 3 years and exhibited improvements in the neurological deficits. There were no recurrence and postoperative deterioration of atlantoaxial instability. CONCLUSIONS: The anterolateral approach for the retro-odontoid synovial cyst had little effect on C1-2 instability and yielded neurological improvements.

Clinical and radiological features of endodermal cyst in the oculomotor nerve: A case report.

We present a 9-year-old girl with an endodermal cyst of the oculomotor nerve in the left interpeduncular cistern, who had a history of left ptosis. We suggest that a cyst localized at the exit of the oculomotor nerve from the midbrain associated with oculomotor palsy may suggest this rare entity.

Primary olfactory mucosal cells promote axonal outgrowth in a three-dimensional assay.

Among the possible sources of autologous cells and tissues for use in spinal cord injury grafts, one promising source is the olfactory mucosa containing olfactory ensheathing cells and neural progenitor cells. Olfactory mucosa transplantation for spinal cord injury has been effective in animal models and in pilot clinical trials. However, the contributions of olfactory ensheathing cells and neurons in olfactory mucosa are unclear. For the present study, we prepared primary olfactory mucosal cells and used a cortex-Matrigel coculture assay system to examine the axonal outgrowth of olfactory mucosa. Axonal outgrowth from cortical slices was significantly enhanced in olfactory mucosal cells compared with noncell controls and respiratory mucosal cells, which have few olfactory ensheathing cells and neurons. Axonal outgrowth was severely reduced after treatment with an antineurotrophin cocktail. A conditioned medium in the olfactory mucosa-derived cell group contained neurotrophin-3. Some olfactory ensheathing cells and almost all neurons were immunopositive for neurotrophin-3. Axons originating from cortical slices targeted mainly the astrocyte-like olfactory ensheathing cells. Our findings demonstrate that the axonal outgrowth effect of olfactory mucosa is supported by both olfactory ensheathing cells and neurons in olfactory mucosa.

Gsp mutation in acromegaly and its influence on TRH-induced paradoxical GH response.

OBJECTIVE: We recently reported that paradoxical GH response to TRH administration reflects biological characteristics in patients with acromegaly. The aim of this study is to elucidate the relationship between gsp mutations and the paradoxical GH response to TRH. PATIENTS: Sixty-seven patients with acromegaly were included for analysis. Paradoxical increase in serum GH level to TRH, GH suppression by octreotide and bromocriptine, radiological profiles and histopathological findings were analysed with respect to tumour gsp-mutation status. RESULTS: Twenty-six (38·8%) gsp mutations were detected, and the number of paradoxical GH responders to TRH, defined as an increase of 100% or more in GH after TRH, was 49 (73·1%). Among the paradoxical GH responders to TRH, 21 patients (42·9%) had a gsp mutation and 28 patients (57·1%) did not. The percentage of paradoxical GH responders to TRH in gsp-positive and gsp-negative patients was not significantly different (80·8% and 68·3%, respectively). The gsp-positive group showed a significantly higher paradoxical increase in serum GH level by TRH administration (1830% vs 650% GH increase, P = 0·045) and greater GH suppression by octreotide (88·7% vs 75·4% GH decrease, P = 0·003) than the gsp-negative group. CONCLUSION: Paradoxical GH response to TRH was observed regardless of gsp mutation, although the rate of increase was significantly higher in gsp-positive patients. These results suggest that gsp mutation is not sufficient to cause the paradoxical GH response to TRH, while other unidentified factors have a strong influence on paradoxical GH response to TRH in patients with acromegaly.

Low-frequency subthalamic nucleus stimulation in Parkinson's disease: a randomized clinical trial.

BACKGROUND: Low-frequency, bilateral stimulation of the subthalamic nucleus can improve axial symptoms of advanced Parkinson's disease (PD), but it is not particularly effective for segmental symptoms. METHODS: The optimal contacts for low-frequency (60 Hz) and high-frequency (130 Hz) single monopolar stimulation were determined. Then, in a randomized, double-blind, prospective crossover manner, 60-Hz and 130-Hz stimulations via the respective optimal contacts were compared for immediate efficacy in improving the motor function of patients with PD. RESULTS: The optimal contacts for 60-Hz stimulation were situated more ventrally than those for 130-Hz stimulation (P = 0.038). Under the respective optimal, single monopolar stimulation, 60 Hz provided superior efficacy over 130 Hz in improving the total Unified Parkinson's Disease Rating Scale motor score (P < 0.001) and the akinesia (P = 0.011) and axial motor signs (P = 0.012) subscores without compromising the therapeutic effect on tremor and rigidity. CONCLUSIONS: Low-frequency stimulation via the optimal contacts is effective in improving overall motor function of patients with PD.

Regulation of motor representation by phase-amplitude coupling in the sensorimotor cortex.

High-γ amplitude (80-150 Hz) represents motor information, such as movement types, on the sensorimotor cortex. In several cortical areas, high-γ amplitudes are coupled with low-frequency phases, e.g., α and θ (phase-amplitude coupling, PAC). However, such coupling has not been studied in the sensorimotor cortex; thus, its potential functional role has yet to be explored. We investigated PAC of high-γ amplitude in the sensorimotor cortex during waiting for and the execution of movements using electrocorticographic (ECoG) recordings in humans. ECoG signals were recorded from the sensorimotor cortices of 4 epilepsy patients while they performed three different hand movements. A subset of electrodes showed high-γ activity selective to movement type around the timing of motor execution, while the same electrodes showed nonselective high-γ activity during the waiting period (>2 s before execution). Cross frequency coupling analysis revealed that the high-γ amplitude during waiting was strongly coupled with the α phase (10-14 Hz) at the electrodes with movement-selective high-γ amplitudes during execution. This coupling constituted the high-γ amplitude peaking around the trough of the α oscillation, and its strength and phase were not predictive of movement type. As the coupling attenuated toward the timing of motor execution, the high-γ amplitude appeared to be released from the α phase to build a motor representation with phase-independent activity. Our results suggest that PAC modulates motor representation in the sensorimotor cortex by holding and releasing high-γ activity in movement-selective cortical regions.

Endovascular therapy for asymptomatic unruptured intracranial aneurysms: JR-NET and JR-NET2 findings.

BACKGROUND AND PURPOSE: National registration studies (the Japanese Registry of Neuroendovascular Therapy [JR-NET] and JR-NET2) have determined the current status and outcomes of neuroendovascular therapy (neuro-EVT). We analyzed short-term outcomes of EVT for asymptomatic unruptured intracranial aneurysms (UIAs). METHODS: We extracted periprocedural information about EVT for 4767 asymptomatic UIAs from 31,968 registered procedural records of all EVT in the JR-NET and JR-NET2 databases. We assessed the features of the aneurysms and procedures, immediate radiographic findings, procedure-related complications, and clinical outcomes at 30 days after the procedures. RESULTS: We located 80.0% of UIAs in the anterior circulation, and the most frequent were paraclinoid. The diameter of 2.5%, 32.9%, 51.9%, 12.0%, and 0.7% of the UIAs was <3, 3 to 4, 5 to 9, 10 to 19, and >20 mm, respectively. EVT failed in only 2.1%. Adjunctive techniques were applied in 54.8% of procedures. Pre- and postprocedural antiplatelet agents were prescribed in 85.6% and 84.0%, respectively, of the procedures. The immediate radiographic outcomes of 57.7%, 31.9%, and 10.0% of the UIAs comprised complete occlusion, residual necks, and residual aneurysms, respectively. Complications that were associated with 9.1% of procedures comprised 2.0% hemorrhagic and 4.6% ischemic, and the 30-day morbidity and mortality rates were 2.12% and 0.31%, respectively. CONCLUSIONS: The radiographic results of EVT for asymptomatic UIAs in Japan were acceptable, with low mortality and morbidity rates.

Electrocorticographic control of a prosthetic arm in paralyzed patients.

OBJECTIVE: Paralyzed patients may benefit from restoration of movement afforded by prosthetics controlled by electrocorticography (ECoG). Although ECoG shows promising results in human volunteers, it is unclear whether ECoG signals recorded from chronically paralyzed patients provide sufficient motor information, and if they do, whether they can be applied to control a prosthetic. METHODS: We recorded ECoG signals from sensorimotor cortices of 12 patients while they executed or attempted to execute 3 to 5 simple hand and elbow movements. Sensorimotor function was severely impaired in 3 patients due to peripheral nervous system lesion or amputation, moderately impaired due to central nervous system lesions sparing the cortex in 4 patients, and normal in 5 patients. Time frequency and decoding analyses were performed with the patients' ECoG signals. RESULTS: In all patients, the high gamma power (80-150 Hz) of the ECoG signals during movements was clearly responsive to movement types and provided the best information for classifying different movement types. The classification performance was significantly better than chance in all patients, although differences between ECoG power modulations during different movement types were significantly less in patients with severely impaired motor function. In the impaired patients, cortical representations tended to overlap each other. Finally, using the classification method in real time, a moderately impaired patient and 3 nonparalyzed patients successfully controlled a prosthetic arm. INTERPRETATION: ECoG signals appear useful for prosthetic arm control and may provide clinically feasible motor restoration for patients with paralysis but no injury of the sensorimotor cortex.

Relationship between plasma (D)-dimer level and cerebral infarction volume in patients with nonvalvular atrial fibrillation.

BACKGROUND: Plasma D-dimer level may reflect the activity of thrombus formation in the left atrium of patients with nonvalvular atrial fibrillation (NVAF). Proper anticoagulation with warfarin dramatically decreases the rate of cerebral embolism, reduces stroke severity and subsequent risk of death, as well as the level of D-dimer in NVAF patients. However, the predictive value of D-dimer level on cerebral embolism severity has not been examined. Thus, the purpose of this study was to investigate the association between plasma D-dimer level at admission and infarct size in NVAF patients. METHODS: We identified 124 patients with consecutive ischemic stroke and NVAF who were admitted within 48 h of symptom onset. We measured infarction volume from CT taken after 3 ± 1 days from the onset. Plasma D-dimer levels were measured at the time of admission. Relationships were analyzed between infarction volume and plasma D-dimer levels, cardiovascular risk factors, preadmission medications and admission conditions. We also assessed the influence of D-dimer level on functional outcome in patients with preadmission modified Rankin Scale (mRS) score of 0-1 and patients by tertile of D-dimer level (≤0.83, 0.83-2.16 and ≥2.16 µg/ml). RESULTS: Infarction volume significantly correlated with D-dimer level (r = 0.309, p < 0.001), systolic blood pressure (r = 0.201, p = 0.026), diastolic blood pressure (r = 0.283, p = 0.002), National Institutes of Health Stroke Scale (NIHSS) score on admission (r = 0.546, p < 0.001) and mRS score at discharge (r = 0.557, p < 0.001). Multivariate regression analyses showed that the D-dimer level was significantly associated with infarction volume after adjusting for age, sex, current smoker or not, prothrombin time-international normalized ratio ≥1.6, diastolic blood pressure, CHADS(2) score and NIHSS score on admission. In patients with a preadmission mRS score of 0-1 (n = 108), D-dimer level was significantly associated with NIHSS score at admission (r = 0.318, p < 0.001) and mRS score at discharge (r = 0.310, p = 0.001). Patients in the highest D-dimer tertile group showed worse outcome than those in the middle (p = 0.041) and lowest (p < 0.001) tertiles. CONCLUSIONS: Plasma D-dimer level on admission is significantly related to infarction volume and functional outcome, following cardioembolic stroke in NVAF patients.

Association between milder brain deformation before a shunt operation and improvement in cognition and gait in idiopathic normal pressure hydrocephalus.

We investigated the association between the degree of deformation of the brain before shunt operation and improvement of gait and cognitive impairment after shunt operation in 16 patients with idiopathic normal pressure hydrocephalus (iNPH). We evaluated gait and cognitive impairment and measured the cerebrospinal fluid volume in the ventricles/sylvian fissure (vVS) and the subarachnoid space at high convexity/midline areas (vHCM) using MR images with voxel-based morphometry before and 3 months after shunt operation. We used the ratio of vVS to vHCM (vVS/vHCM) as an index of the severity of brain deformation. After shunt operation, improvements were observed in gait, as shown by the Timed Up and Go (TUG) test and 10-meter reciprocating walking test (WT), and in cognitive function, as shown by the Mini-Mental State Examination, Alzheimer Disease Assessment Scale, Frontal Assessment battery (FAB), and Trail Making test A (TMT-A). The vVS/vHCM ratio was negatively correlated with improvement of the FAB, TMT-A and TUG. Preoperative vVS/vHCM was not significantly correlated with preoperative clinical assessments. The rate of change of vVS/vHCM was positively correlated with improvement in the WT. The improvements of gait and cognitive function were larger in iNPH patients with milder deformation of the brain before shunt operation.