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Cerebral cavernous malformations (CCMs) are congenital abnormalities of cerebral vessels. Surgical resection is rarely considered for the control of epilepsy in a first seizure patient with vascular malformation. In contrast, lesions that produce repetitive or progressive symptoms should be considered for surgical resection as treatment. Herein, we report a Japanese patient with a CCM2 mutation, c.609G>A (p.K203K) substitution, who showed drug-resistant epilepsy and dramatic improvement after surgical resection.

X-linked adrenoleukodystrophy (ALD) is a major peroxisomal disorder, in which abnormal accumulation of very long-chain fatty acids (VLCFA) caused by ABCD1 gene mutation results in damage to the peripheral and central nervous system and adrenal gland. While affected male patients with ALD present severe neurological symptoms, some female carriers slowly develop spastic gait and urinary incontinence. We report a case of a symptomatic female ALD carrier with a novel ABCD1 gene mutation. She has developed progressive gait disturbance since age 40, and her father and sister had similar symptoms. When admitted to our hospital at age 66, blood analysis showed slight increase of VLCFA, and DNA analysis of ABCD1 gene revealed a novel heterozygous missense mutation (c.1700 A>C, p.Gln567Pro). The genetic testing for ABCD1 gene can be considered in female patients over middle age presenting spastic gait, because female ALD carriers tend to be symptomatic beyond age 60.

Carnosine (β-alanyl-L-histidine) is a natural dipeptide with multiple neuroprotective properties. Previous studies have advertised that carnosine scavenges free radicals and displays anti-inflammatory activity. However, the underlying mechanism and the efficacies of its pleiotropic effect on prevention remained obscure. In this study, we aimed to investigate the anti-oxidative, anti-inflammative, and anti-pyroptotic effects of carnosine in the transient middle cerebral artery occlusion (tMCAO) mouse model. After a daily pre-treatment of saline or carnosine (1000 mg / kg / day) for 14 days, mice (n = 24) were subjected to tMCAO for 60 min and continuously treated with saline or carnosine for additional 1 and 5 days after reperfusion. The administration of carnosine significantly decreased infarct volume 5 days after the tMCAO (*p < 0.05) and effectively suppressed the expression of 4-HNE, 8-OHdG, Nitrotyrosine 5 days, and RAGE 5 days after tMCAO. Moreover, the expression of IL-1β was also significantly suppressed 5 days after tMCAO. Our present findings demonstrated that carnosine effectively relieves oxidative stress caused by ischemic stroke and significantly attenuates neuroinflammatory responses related to IL-1β, suggesting that carnosine can be a promising therapeutic strategy for ischemic stroke.

Objective: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron disease. Hypoxic stress is suspected as the pathogenesis of ALS, however, no positron emission tomography (PET...

Background Telestroke network can provide rapid access to specialized treatment and improves on‐site management of acute stroke patients through the “hub‐and‐spoke” model. In the northern part of Okayama Prefecture, there has been a regional gap of stroke care due to the shortage of stroke specialists and facilities. In addition, due to the novel coronavirus disease 2019 (COVID‐19), it is required to reduce the unnecessary contact with stroke patients from other hospitals. Aim We organized a novel cost‐free telestroke network with an image and video sharing for neurological diseases in the northern part of Okayama Prefecture to improve the stroke management in the area. Method We prepared the tablet device on which Skype® application was installed for each hospital and recruited the patients who visited or hospitalized in the spoke hospitals and were suspected to have some neurological diseases from April 2019 to May 2020. The patient's clinical data were recorded and analyzed. Results During the study period, 5 patients were recruited including the cases with the initial diagnosis of stroke or brain tumor. Among them, 2 cases were transferred to the hub hospital, 2 cases were transferred to other hospitals, and 1 case was treated on site under specialist's advice. Conclusion The new telestroke network system may be beneficial for acute stroke management and reducing the unnecessary patient's transfer in the rural area, especially under coexistence with COVID‐19.

The feasibility of transcranial sonothrombolysis has been demonstrated, although little is known about the relationships between thermal or mechanical mechanisms and thrombolytic outcomes. Therefore, the present study aims to reveal the effect and safety of temperature and ultrasound through in vitro and in vivo thrombolysis models. Artificial clots in microtubes were heated in a water bath or sonicated by ultrasound irradiation, and then clots weight decrease with rising temperature and sonication time was confirmed. In the in vitro thrombotic occlusion model, based on spot heating, clot volume was reduced and clots moved to the distal side, followed by recanalization of the occlusion. In the in vivo study, the common carotid artery of rats was exposed to a spot heater or to sonication. No brain infarct or brain blood barrier disruption was shown, but endothelial junctional dysintegrity and an inflammatory response in the carotid artery were detected. The present spot heating and ultrasound irradiation models seem to be effective for disintegrating clots in vitro, but the safety of the in vivo model was not fully supported by the data. However, the data indicates that a shorter time exposure could be less invasive than a longer exposure.

Objectives: Increased attention is being paid to Asian medicine in balanced total health care. We investigated the effects of mixed exercise including yoga ('Yoga-plus') among elderly individuals. Methods: A total of 385 subjects (72 males and 313 females, 75.5 ± 8.7 years old) participated in a 12-month (M) exercise program at a health and welfare center, a day service center, and a nursing home. Cognitive, affective, and physical functions, and activities of daily living (ADL), were compared at baseline (0M), 6M and 12M of exercise intervention. Results: Mean scores on the frontal assessment battery, clock drawing test, cube copying test, letter fluency, and category fluency significantly improved after the Yoga-plus intervention, while mini-mental state examination, Hasegawa dementia score-revised, and trail-making test performance were relatively stable. Affective scores on the geriatric depression scale (GDS), apathy scale (AS) and Abe's behavioral and psychological symptoms of dementia were not significantly affected by exercise therapy, but subgroups with higher baseline GDS (GDS ≥ 5) and AS (AS ≥ 16) scores showed a significant improvement after intervention. One-leg standing time and 3-m timed up and go test performance significantly improved after 12M intervention. Discussion: Yoga-plus improved cognitive, affective, ADL, and physical functions in a local elderly population, particularly among below-baseline individuals, indicating the benefits of dementia prevention among elderly individuals.

Subacute myelo-optico neuropathy (SMON) patients typically suffer from sequelae that cause sleep disturbances. We sought to examine the prevalence of sleep problems among SMON patients. We conducted a questionnaire-based survey concerning sleep problems among 106 SMON patients, and 110 age- and gender-matched control participants. The prevalence of subjective insomnia (6 ≤ Athens Insomnia Scale score) was 89.6% among SMON patients, which was significantly higher than among control participants 54.4%. Sleep quality measured with the Pittsburgh Sleep Quality Index (PSQI) revealed that the prevalence of poor sleepers (6 ≤ PSQI score) was higher among SMON patients than control participants (75.6% vs 39.6%, respectively). Subscale analyses of rapid eye movement sleep behavior disorder screening questionnaire revealed that scores on two items (“dreams match nocturnal behavior” and “limb movements”) were significantly higher among SMON patients than control participants. In addition, daytime sleepiness scores were significantly higher among SMON patients than control participants (4 ≤ Epworth Sleepiness Scale scores: 54.0% vs 29.0%, respectively). The current study revealed that most SMON patients suffer from insomnia with dissatisfactory sleep quality, likely due to their long-term physical sequelae. Moreover, SMON patients showed higher rates of daytime sleepiness and sleep medication intake, which could be related to reduced activity during the day, as well as insomnia.

BACKGROUND: Multiple pathogeneses are involved in Alzheimer's disease (AD), such as amyloid-β accumulation, neuroinflammation, and oxidative stress. The pathological impact of chronic cerebral hypoperfusion on Alzheimer's disease is still poorly understood. METHODS: APP23 mice were implanted to bilateral common carotid arteries stenosis with ameroid constrictors for slowly progressive chronic cerebral hypoperfusion (CCH). The effects of the administration of Twendee X (TwX) were evaluated by behavioral analysis, immunohistochemical analysis, and immunofluorescent histochemistry. RESULTS: In the present study, chronic cerebral hypoperfusion, which is commonly found in aged Alzheimer's disease, significantly exacerbated motor dysfunction of APP23 mice from 5 months and cognitive deficit from 8 months of age, as well as neuronal loss, extracellular amyloid-β plaque and intracellular oligomer formations, and amyloid angiopathy at 12 months. Severe upregulations of oxidative markers and inflammatory markers were found in the cerebral cortex, hippocampus, and thalamus at 12 months. Twendee X treatment (20 mg/kg/d, from 4.5 to 12 months) substantially rescued the cognitive deficit and reduced the above amyloid-β pathology and neuronal loss, alleviated neuroinflammation and oxidative stress. CONCLUSIONS: The present findings suggested a potential therapeutic benefit of Twendee X for Alzheimer's disease with chronic cerebral hypoperfusion.

Here we present the first report of solitary primary peripheral nerve onset cytotoxic molecule (CM)-positive peripheral T-cell lymphoma (PTCL) diagnosed after nerve biopsy. An 84-year-old female with rheumatoid arthritis (RA) complained of asymmetric severe tenderness in her upper limbs. The biopsy pathology revealed a direct invasion of CM-positive PTCL. When RA patients complain of numbness, tenderness, or weakness, lymphomatic peripheral nerve invasion should be considered.

Ischemic stroke (IS) due to giant cell arteritis (GCA) is rare, but highly mortal. Here, we report a 72-year-old man who showed frequent IS with GCA. Initial therapy with prednisolone increased the frequency of IS, which disappeared after continuous multi-modal combination therapy with corticosteroids, immunosuppressive agents, antiplatelets, and statin. The present case was discharged with independent walk, suggesting that a multi-modal combination therapy rescued the GCA patient from frequent IS.

Due to an increasing number of dementia patients, the development of a rapid and sensitive method for cognitive assessment is awaited. Here, we examined the usefulness of a novel and short (3 min) eye tracking device to evaluate the cognitive function of normal control (NC, n = 52), mild cognitive impairment (MCI, n = 52), and Alzheimer's disease (AD, n = 70) subjects. Eye tracking total score declined significantly in MCI (**p 0.01 vs NC) and AD (**p 0.01 vs NC

Background The free radical scavenger edaravone is a proven neuroprotective drug for patients with amyotrophic lateral sclerosis (ALS). Our objective was to evaluate the therapeutic effects of edaravone for oxidative stress and anti-oxidative activity in ALS patients. Methods Twenty-two ALS patients with a disease duration of 2 years, treated by edaravone, and 25 control participants were evaluated according to their clinical scores, including ALS functional rating scale-revised (ALSFRS-R), and serum and cerebrospinal fluid (CSF) markers of oxidative stress dROM and anti-oxidative activity OXY. Results Serum and CSF markers of anti-oxidative activity OXY were significantly decreased in ALS patients at pre-treatment compared with controls (##p Conclusions The present study suggests significant correlations between anti-oxidative activity and ALS clinical severity, and the therapeutic efficacy of edaravone for decreased anti-oxidative activity in ALS.

The ubiquitin-proteasome system (UPS) and autophagy are two major pathways to degrade misfolded proteins that accumulate under pathological conditions. When UPS is overloaded, the degeneration pathway may switch to autophagy to remove excessive misfolded proteins. However, it is still unclear whether and how this switch occurs during cerebral ischemia. In the present study, transient middle cerebral artery occlusion (tMCAO) resulted in accelerated ubiquitin-positive protein aggregation from 0.5 h of reperfusion in mice brain after 10, 30 or 60 min of tMCAO. In contrast, significant reduction of p62 and induction of LC3-II were observed, peaking at 24 h of reperfusion after 30 and 60 min tMCAO. Western blot analyses showed an increase of BAG3 and HDAC6 at 1 or 24 h of reperfusion that was dependent on the ischemic period. In contract, BAG1 decreased at 24 h of reperfusion after 10, 30 or 60 min of tMCAO after double immunofluorescent colocalization of ubiquitin, HSP70, p62 and BAG3. These data suggest that a switch from UPS to autophagy occurred between 10 and 30 min of cerebral ischemia depending on the BAG1/BAG3 ratio and level of HDAC6.

Neurological disease patients living alone or with a single caregiver need a support system to care for their psychological symptoms. We evaluated the clinical effects of a unique telephone call system that automatically called participants at their desired times once a week for 3 months. In total, 104 neurological disease patients and caregivers were evaluated by the geriatric depression scale, apathy scale and state and trait anxiety inventories (STAI) forms X-I for depression, apathy and state anxiety, respectively. High baseline STAI scores (40≥) significantly improved in the Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and spinocerebellar degeneration (SCD) + multiple system atrophy (MSA) patients (p = 0.001, p = 0.013 and p = 0.046, respectively) after patients/caregivers used the telephone call service. The baseline (pre) STAI score significantly correlated with the score change (post-pre) in PD, ALS, SCD + MSA, Alzheimer' s disease patients (ADp), and caregivers for ADp (p < 0.0001, p = 0.001, p = 0.011, p = 0.025 and p = 0.020, respectively). The geriatric depression scale and apathy scale did not significantly improve. The present study suggests that there is a positive effect of using an automated telephone call service for anxiety in neurological disease patients and caregivers, especially in ALS, SCD + MSA and PD patients with high STAI scores (40≥).

There is a strong relationship between Alzheimer's disease (AD) and sleep problems, and a sleep condition is informative for evaluating the AD status. In the present study, we evaluated subjective sleep problems in AD and mild cognitive impairment (MCI) with self-check questionnaires and objective sleep problems with a convenient home-based portable device, WatchPAT. A total of 63 subjects with normal cognition (NC) (n = 22), MCI (n = 20), and AD (n = 21) were cross-sectionally investigated. AD patients showed a better self-check Pittsburgh sleep quality index (PSQI) score (*p 0.05) than NC and MCI patients. On the other hand, WatchPAT analysis showed a significantly reduced rapid eye movement (REM) sleep (*p 0.05) and increased light sleep in AD patients (*p 0.05) compared with NC subjects, and mildly reduced REM and increased light sleep in MCI subjects. The present study revealed a gap between the subjective self-check sleep questions and the objective WatchPAT analysis in AD patients. Thus, a home-based sleep study with WatchPAT is a useful tool to detect an objective sleep problem in AD and the risk of MCI conversion into AD.

Background Tocovid is a new combination of tocotrienols and tocopherol, both of which are neuroprotective agents for preventing cerebral infarction in mice. However, the effects of tocovid on anti-inflammation in ischemic model remain elusive. In the present study, we assessed the effects of Tocovid pretreatment on anti-inflammatory effects after transient middle cerebral occlusion (tMCAO) in mice. Materials and Methods We evaluated the therapeutic and anti-inflammatory effects of tocovid pretreatment (200 mg/kg per day, for 1 month) on mice brain under 60 minutes of tMCAO. The expressive changes of inflammatory markers were observed after tMCAO in mice. Results Tocovid pretreatment greatly improved the mice neurobehaviors, reduced infarct volumes and decreased expressions of inflammatory markers such as tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1) and ionized calcium binding adapter molecule-1 (Iba-1), and improved the damage of neurovascular units including matrix metallopeptidase 9, IgG and collagen IV after tMCAO. Conclusions Our present findings demonstrated that oral tocovid pretreatment showed obviously neuroprotective and at least in part by anti-inflammatory effects in ischemic mice brain.

Background Dietary supplement is an attempt to reduce the risk of ischemic stroke in high-risk population. A new mixed vitamin E-Tocovid that mainly contains tocotrienols other than tocopherol, attenuated the progression of white matter lesions by oral in humans. However, the effect of Tocovid on ischemic stroke has not been examined. In the present study, we assessed the therapeutic effects of Tocovid pretreatment on transient middle cerebral artery occlusion (tMCAO) in mice. Materials and Methods After pretreatment with Tocovid (200 mg/kg/d) or vehicle for 1 month, 60-minute tMCAO was performed, and these mice were examined at 1 day, 3 days, and 7 days after reperfusion. We histologically assessed the effects of Tocovid pretreatment on the expressive changes of oxidative stress markers, cleaved caspase-3, and LC3-II after tMCAO in mice. Results We observed that Tocovid pretreatment significantly improved the rotarod time, reduced infarct volume, decreased the number of 4-HNE, nitrotyrosine, and 8-OhdG positive cells, inhibited advanced glycation end products biomarkers RAGE, CMA, and CML expressions, and increased Nrf2 and MRP1 levels with GSSG/GSH ratio decrease. Furthermore, Tocovid pretreatment greatly decreased cleaved caspase-3 and LC3-II expressions after tMCAO. Conclusions The present study obviously demonstrated that Tocovid pretreatment showed neuroprotective effects against oxidative stress and at least in part by antiapoptotic/autophagic cell death in ischemic mice brain.

An 83-year-old man developed acute ischemic stroke. Brain magnetic resonance imaging (MRI) showed ischemic stroke in the left parietal lobe gyri, but fluid-attenuated inversion recovery (FLAIR) showed hyperintensity in the contralateral right temporal-occipital lobe sulci. Follow-up FLAIR image showed the gradual disappearance of the sulcal hyperintensity in the sulci and changed to linear serpiginous structures. This is a unique stroke case showing transitioned FLAIR findings suggesting that the sulcal hyperintensity findings are more severe and an earlier ischemic condition than the linear serpiginous structures.

Vertebral artery (VA) dissection is one major cause of brain infarction in young and middle-aged adults. Risk factors for VA dissection are hypertension, diabetes mellitus, hyperlipidemia, trauma, and genetic factors. A 32-year-old man with familial Hirschsprung disease at the age of 2 presented cerebellar ischemic stroke due to bilateral VA dissections. A stroke recurred within 17 days despite oral dual antiplatelet therapy. Bilateral VA dissections and recurrent dissections are related to genetic mutations associated with connective tissue diseases. A part of familial Hirschsprung disease has genetic factors in common with cerebrovascular disease. There may be a common genetic background between his VA dissection and Hirschsprung disease.

Streptococcus pneumoniae is a major cause of bacterial meningitis usually in children or elder adults. We report a case of a 38-year-old man having pneumococcal meningoencephalitis with a small spleen (35 cm(3)), compared to seven previous patients with pneumococcal meningitis in our department. Among the eight patients, four cases were due to sinusitis, but the origin could not be identified in the other four cases, including the present case who was the youngest patient with the smallest splenic size. Of interest in the present analysis was the negative or positive correlation between splenic size and age, with or without sinusitis. This is the first report on pneumococcal meningoencephalitis that takes into consideration age, splenic size, and the origin of infection.

The primary treatment for hydrocephalus is ventricular shunt placement, and a programmable valve is widely used for ventriculoperitoneal (VP) shunt surgery to reduce over/under drainage of cerebrospinal fluid (CSF). Here, we report a rare case of a patient who developed successive VP shunt malfunction causing spastic muscle weakness in extremities associated cervical epidural venous distension and compressive myelopathy due to over-drainage of CSF through a defective VP shunt valve a decade after the initial shunt was placed. One should be aware and cognizant of this complication and carefully follow the symptoms and potentially utilize brain MRI with and without contrast to look at over drainage stigmata to avoid the development of neurological complications. Keywords: Hydrocephalus, Ventriculoperitoneal shunt, Cervical myelopathy

Alzheimer's disease (AD) is a common neurodegenerative disease that is characterized by the abnormal accumulation of intracellular and extracellular amyloid-β (Aβ) as well as disruption of the blood brain barrier (BBB). Fibrinogen plays an essential role in regulating thrombosis, wound healing, and other biological functions. In the present study, we investigated the relationship between three polypeptide chains α, β, and γ (FGA, FGB, and FGG) and Aβ deposition in the APP23 plus chronic cerebral hypoperfusion (CCH) mice model as well as the human AD brain. FGA, FGB, and FGG accumulated when Aβ was deposited in neural cells and cerebral vessels. This deposition was significantly higher in AD plus CCH mice models relative to wild-type brains, and in human AD brains compared to control brains. The present study demonstrates that FGA, FGB, and FGG are associated with AD progress, and can thus be potential targets for the diagnosis and therapy of AD.

Evaluating the cognitive and behavioral features in amyotrophic lateral sclerosis (ALS) patients is important for therapy and care. Fifty-seven ALS, 5 ALS with the behavioral variant of frontotemporal dementia (FTD) (ALS-FTD), 12 FTD patients, and 35 control subjects were evaluated by 10 different tests for cognitive and behavioral (mini-mental state examination (MMSE), Hasegawa dementia rating scale - revised (HDS-R), frontal assessment battery (FAB), Montreal cognitive assessment (MoCA), ALS-frontotemporal dementia-Questionnaire (ALS-FTD-Q), and anosognosia scale), affective (depression, apathy, and behavioral and psychological symptoms of dementia (BPSD)), and activities of daily living (ADL) assessments. The motor functions of ALS patients were evaluated by ALS functional rating scale - revised (ALSFRS-R) and modified Norris scale. ALS-FTD-Q scores showed intermediate behavioral disturbances of ALS patients between ALS-FTD and FTD patients and control subjects, but FAB, MoCA, and anosognosia scales did not. Both FAB and MoCA scores were significantly correlated with MMSE and HDS-R in ALS patients, but ALS-FTD-Q was not. ALS-FTD-Q score was significantly correlated with ALSFRS-R, apathy, BPSD, and ADL scores in ALS patients. Thus, in ALS patients, both FAB and MoCA tests were useful to assess frontal cognitive impairments, while ALS-FTD-Q was useful to detect mild behavioral and affective disturbances.

Progressive myelopathy is caused by infectious, inflammatory, autoimmune, paraneoplastic, demyelinating, vascular, hereditary, degenerative, metabolic, and toxic properties1, 4. Here we report a case of a 53-year-old woman who showed a progressive cervical and thoracic myelopathy with muscle weakness in all limbs and hypoesthesia in all limbs and trunk below the Th8 level without any evident magnetic resonance imaging (MRI) lesions. She displayed rheumatoid factor, anti-double standard DNA antibody, and hepatitis B surface antigen, as well as an elevated cerebrospinal fluid (CSF) protein level. Paraneoplastic antibodies which we examined were negative. Our treatments (plasma exchange, steroid pulse therapy, and immunoglobulin therapy) were slightly effective, but the symptoms did not improve completely. The present case suggests that the presence of a cervical and thoracic lesion without evident MRI abnormalities needs a careful follow up to discover occult lesions. This article is protected by copyright. All rights reserved.

Background and purpose Few studies have examined why some patients with dementia stop attending medical consultations. We conducted a retrospective study to investigate factors associated with discontinuous clinic attendance. Methods Participants were 988 patients with dementia from university hospital (UH) clinics and affiliated local hospital (LH) clinics. We compared continuous and discontinuous attenders on cognitive and affective functions and activities of daily living (ADL), and also compared UH and LH patients (UH: continuous, n = 176; discontinuous, n = 207; LH: continuous, n = 418; discontinuous, n = 187). Results The total annual rate of discontinuation was 8.0%, and the mean period of attendance before discontinuation was 2.2 ± 2.4 years (UH, 2.8 ± 3.0; LH, 1.5 ± 1.3, P < 0.01). Scores for the Mini-Mental State Examination, Hasegawa Dementia Scale – Revised, Geriatric Depression Scale, apathy scale, Abe's behavioral and psychological symptoms of dementia (BPSD) score, and ADL were significantly worse in the discontinuous group than the continuous group for both UH and LH patients (P < 0.01). The best predictor of discontinuation was ADL decline (UH and LH) and Abe's BPSD score (UH). The most common reason for discontinuation was returning to the family doctor (39.1% for UH), and cessation of hospital attendance at their own discretion (35.3% for LH). Conclusions We identified the main reasons for discontinuation of attendance as returning to the family doctor and cessation of hospital attendance at their own discretion. The best predictors of discontinuation were ADL decline and worsening BPSD. There were significant differences in discontinuation between UH and LH patients with dementia.