CD79B Y196 mutation is a potent predictive marker for favorable response to R-MPV in primary central nervous system lymphoma.

BACKGROUND: Rituximab, high-dose methotrexate (HD-MTX), procarbazine and vincristine (R-MPV), has significantly prolonged the survival of patients with primary central nervous system lymphoma (PCNSL), but predictive factors for response to R-MPV have not yet been investigated. Herein, we investigated the correlation of MYD88 L265P and CD79B Y196 mutations, which are the most frequently found molecular alterations in PCNSL, with prognosis of patients with PCNSL treated with R-MPV. METHODS: We investigated the long-term clinical course and status of MYD88 and CD79B genes in 85 patients with PCNSL treated with R-MPV or HD-MTX treatment, and the correlation of these genetic mutations with prognosis. RESULTS: R-MPV achieved an excellent tumor control rate (61.6% and 69.9% of 5-year progression-free and overall survival rates, respectively). While MYD88 L265P mutation had no significant effect on survival, patients with CD79B Y196 mutations exhibited prolonged survival (p < 0.05). However, the association of CD79B Y196 mutation with a better prognosis was not observed in the HD-MTX cohort, which indicated that CD79B Y196 mutation was a predictive marker for a favorable response to R-MPV. Furthermore, we established an all-in-one rapid genotyping system for these genetic mutations. CONCLUSIONS: In conclusion, CD79B Y196 mutation is a potent predictive marker for favorable response to R-MPV in PCNSL. The rapid identification of MYD88 L265P and CD79B Y196 mutations can be helpful not only for the accurate molecular diagnosis of PCNSL but also for the prediction of response to R-MPV.

Suicide Prevention Interventions and Their Linkages in Multilayered Approaches for Older Adults: A Review and Comparison.

Multilayered approaches to suicide prevention combine universal, selective, and indicated prevention interventions. These approaches may be more successful in reducing suicide rates among older adults if they link these layers more systematically: that is, if the programs are designed so that interventions at a lower level facilitate involvement at a higher level when appropriate. This study aimed to examine the effect on suicide rates of the structure of multilayered approaches, and in particular the types of interventions and the connections or linkages between them. We also wished to consider any different effects by sex. A literature search used PubMed and PsycINFO to identify systematic reviews of interventions in this age group. From the reference lists of these articles, we identified controlled studies assessing the impact of a multilayered program on suicide incidence among older adults. We were particularly interested in initiatives linking different kinds of prevention interventions. We found three relevant systematic reviews, and from these, we identified nine eligible studies. These included seven non-randomized controlled studies from rural areas in Japan (average eligible population: 3,087, 59% women, average duration: 8 years). We also found two cohort studies. The first was from a semi-urban area in Padua, Italy (18,600 service users, 84% women, duration: 11 years). The second was from urban Hong Kong, with 351 participants (57% women) over a 2-year follow-up period. We used a narrative synthesis of these studies to identify five different multilayered programs with different forms of connections or linkages between layers. Two studies/programs (Italy and Hong Kong) involved selective and indicated prevention interventions. One study/program (Yuri, Japan) included universal and selective prevention interventions, and the final six studies (two programs in northern Japan) involved linkages between all three layers. We also found that these linkages could be either formal or informal. Formal linkages were professional referrals between levels. Informal linkages included advice from professionals and self-referrals. Several of the studies noted that during the program, the service users developed relationships with services or providers, which may have facilitated movements between levels. All five programs were associated with reduced suicide incidence among women in the target groups or communities. Two programs were also associated with a reduction among men. The study authors speculated that women were more likely to accept services than men, and that the care provided in some studies did less to address issues that are more likely to affect men, such as suicidal impulsivity. We therefore suggest that it is important to build relationships between levels, especially between selective and indicated prevention interventions, but that these can be both formal and informal. Additionally, to reach older men, it may be important to create systematic methods to involve mental health professionals in the indicated prevention intervention. Universal interventions, especially in conjunction with systematically linked indicated and selective interventions, can help to disseminate the benefits across the community.

Two Cases of Cervical Epidural Hematoma Presenting With Left-Sided Hemiplegia and Requiring Surgical Drainage.

Spinal epidural hematoma is a rare disease that may present as motor paralysis, sensory disturbance, and a sudden radiating pain from the hematoma site. Herein, we report two cases of cervical epidural hematoma diagnosed as left hemiplegia and treated with surgery. Case 1 was a 62-year-old woman who presented to our hospital with the chief complaint of posterior neck pain and left upper and lower limb paralysis. Cervical magnetic resonance imaging (MRI) showed a cervical epidural hematoma at the C4-C6 level. Case 2 was a 67-year-old man who presented to our hospital with a history of hypertension. Both patients had left hemiparesis, numbness in the left upper and lower limbs, and hypersensitivity. They were diagnosed with idiopathic cervical epidural hematoma and underwent emergency surgery (hematoma removal + laminoplasty). In case 1, the paralysis improved immediately after the surgery. In case 2, the paralysis and hypersensitivity improved markedly after the surgery, and the manual muscle testing grade of the left upper and lower limbs improved from 3 to 5 on the second day. Both patients were subsequently discharged home unaided. In cases where the paralysis does not improve, it is important to exclude stroke, diagnose cervical epidural hematoma as soon as possible, and consider surgery aggressively.

[Primary leptomeningeal gliomatosis treated with temozolomide: a case report].

A 35-year-old man was admitted to our department for loss of consciousness. CT and MRI revealed diffuse enhancement of the subarachnoid space surrounding the brainstem and the cerebellar sulci, without any parenchymal lesions in the brain or the spinal cord. Furthermore, gadolinium-enhanced MRI revealed a nodular lesion with heterogeneous enhancement in the right prepontine cistern, at the site from which a biopsy was obtained via right lateral suboccipital craniotomy on the day following admission. Histopathological examination of the resected specimen revealed glioblastoma multiforme. Based on the radiological and histopathological findings, the patient was diagnosed with primary leptomeningeal gliomatosis (PLG). The patient received temozolomide chemotherapy with concurrent radiotherapy and showed radiological remission, 12 months after diagnosis. However, he developed local recurrence 6 months later and died 23 months after diagnosis. Autopsy findings showed tumor cell infiltration of the leptomeninges, as well as the brain and spinal parenchyma. PLG should be considered in the differential diagnosis in patients with diffuse leptomeningeal enhancement even without parenchymal lesions on radiological imaging. A surgical biopsy is recommended for prompt and accurate diagnosis in such cases.

Developing a Hypothetical Model for Suicide Progression in Older Adults With Universal, Selective, and Indicated Prevention Strategies.

Suicide prevention is an increasingly important issue, especially among older people. Recent work on improving its effectiveness has focused on developing a framework aligning interventions with key risk factors and stages of the suicide process. We have developed this further, by integrating psycho-behavioral components associated with suicide, existing guidelines for identifying critical points of intervention, and the previous preventive strategies framework. Our schematic diagram shows the relationship between the suicide process and prevention strategies, combined with initiatives for linking different types of strategies, from universal strategies at population level, through selective strategies focusing on groups at risk, to indicated strategies, aimed at specific high-risk individuals. We tested our framework using previous studies assessing the impact of suicide prevention interventions on suicide rates in older adults. It was possible to place all identified interventions within the framework. Examining effectiveness within the framework suggests that some interventions may be more successful in reducing suicide rates because they developed systematic linkages between universal, selective, and indicated prevention interventions. Other studies, however, show that interventions can be successful without these linkages, so other factors may also be important. The main weakness of our framework is a lack of evidence about critical intervention points within the suicide process, which may limit its practical application. However, the framework may help to improve the linkages between types of interventions, and support practitioners in developing a wide range of strategies across different areas and stages of the suicide process.

Long-Term Effects of a Screening Intervention for Depression on Suicide Rates among Japanese Community-Dwelling Older Adults.

OBJECTIVES: To explore the long-term impact of a universal screening intervention for depression on suicide rates among older community-dwelling adults, with gender as an effect modifier. DESIGN: Controlled cohort study reporting long-term follow-up of previous research. SETTING: Two sets of three municipalities in Japan were assigned as intervention and control regions and compared with the surrounding zone and prefecture. PARTICIPANTS: Intervention area residents aged 60 years and older (14,291) were invited to participate in a 2-year intervention (2005-2006). Four population-based dynamic cohorts of residents aged 65 years and older (1999-2010) were included as subjects, 6 years before and after the intervention started. INTERVENTION: At-risk residents within the intervention region (4,918) were invited for a two-step screening program; 2,552 participated in the program linked with care/support services for 2 years. An education program open to the public was held. MEASUREMENTS: Changes in suicide from a 6-year baseline to the 2-year intervention and a 4-year follow-up in the intervention region (11,700 adults ≥65 years) were compared with a matched control and two comparison areas using mixed-effects negative binomial regression models. Suicide rates among older adults exposed to screening were compared with those of the control region. RESULTS: Suicide rates in the intervention region decreased by 48%, which was significantly greater than in the three comparison areas. The program's benefits lasted longer for women than men. Screening exposure may be associated with decreased suicide risk over the 4-year follow-up. CONCLUSIONS: Universal screening may decrease suicide rates among older adults, with potential gender differences in treatment response.

Overview of community-based studies of depression screening interventions among the elderly population in Japan.

OBJECTIVES: In most Western and Asian countries, a higher risk of suicide is found among elderly people than those in other age groups. However, the treatment needs of elderly people who are at risk of committing suicide are not well understood. We conducted an overview of studies that assessed the impact of suicide prevention interventions on suicide rates in elderly people in Japan. We interpreted the results of these studies, as well as prominent findings associated with other successful interventions, within a framework of the suicidal process and preventive strategies. METHOD: We assessed six quasi-experimental studies of community-based interventions providing universal depression screening, subsequent care, and education to elderly people in Japan, and performed a combined analysis of outcome data. RESULTS: Screening interventions were associated with lower suicide rates. We also found a gender difference in the response to subsequent psychiatric or primary care. Two types of interventions decreased the rate of suicide among elderly people: crisis helplines and screening interventions. These interventions featured a close link between universal, selective, and indicated prevention strategies, which reflect different approaches tailored to the size and risk profile of the target individuals. CONCLUSION: Successful interventions appear to hinge on systematic links between multi-level prevention interventions. Multi-level interventions for depression screening may result in lower suicide rates among elderly individuals in communities, although primary care interventions alone appear to be insufficient in men. The benefit of linked multi-level prevention interventions may highlight the importance of the multiple steps and components of the suicidal process.

[A case of moyamoya disease with a subarachnoid hemorrhage treated with endovascular technique].

We report a case of a moyamoya disease presenting with subarachonoid hemorrhage (SAH) due to a ruptured aneurysm. A 40-year-old woman presented with sudden onset of headache and vomiting. Computed tomography (CT) showed diffuse thick SAH localized around basal cistern. 3D-CT Angiography (3D-CTA) and digital subtraction angiography (DSA) demonstrated a saccular aneurysm at the bifurcation of the left superior cerebellar artery and basilar artery. In addition, the both carotid arteries were occluded at the terminal portion and the territory of both middle cerebral arteries were perfused by abnormal moyamoya vessels. The aneurysm was completely embolized by endovascular embolization. The SAH due to a ruptured aneurysm associated with moyamoya disease is rare. We think endovascular therapy is safe and effective. However, a vasospasm of the catheter technique occurred during the operation. This fact is very important to consider when we treat diseases such as this in the future.

Effects of universal screening for depression among middle-aged adults in a community with a high suicide rate.

We examined the effect of a community-based screening program on depression in middle-aged individuals. Ten subdistricts constituting a rural township (2400 inhabitants aged 40-64 years) in northern Japan with a high suicide rate were randomly assigned to intervention (four) and control (six) groups. A 2-year depression-screening program entailing identification and subsequent care support was offered to adults aged 40 to 64 years in the intervention group, accompanied by 4-year ongoing dissemination of educational information in both groups. Change in depressive symptom prevalence was assessed through before-and-after cross-sectional surveys using the Center for Epidemiologic Studies-Depression Scale. Of the 900 targeted individuals, 49.2% participated in the screening. Comparison of data from these surveys after controlling for district-level clustering indicated a greater difference in prevalence between baseline and 5-year follow-up in the intervention group than that in the control. Universal screening and subsequent support seem effective to decrease depressive symptom prevalence among middle-aged individuals in a community setting.

The effects of suicide prevention measures reported through a psychoeducational video: a practice in Japan.

BACKGROUND: As the suicide rate in Japan has remained high since 1998, various suicide prevention measures have been implemented in Japanese local communities. AIMS: To report our findings on the effect of a psychoeducational video as a suicide prevention measure in a Japanese rural town. METHODS: Questionnaires were randomly mailed to 2,000 residents aged between 30 and 79 years. Within 4 weeks, volunteers in the town visited the residents individually and collected the questionnaires. The variables reported in this study are demographics, awareness of suicide prevention measures available in the town, whether the residents watched the video, help-seeking from advisers regarding suicidal ideation and financial problems and attitudes towards suicide. RESULTS: We analysed data collected from 1,118 people who reported their demographics (i.e. sex, age, and job) and whether they had watched the video. By conducting a series of logistic regression and multiple regression analyses and controlling for demographic variables, we found that watching the video had substantial psychoeducational effects. CONCLUSION: Despite conducting a cross-sectional study, our new suicide prevention measures were considered effective for psychoeducation. However, further studies using a longitudinal design are needed.

Differences in specific depressive symptoms among community-dwelling middle-aged Japanese adults before and after a universal screening intervention.

PURPOSE: This study investigated changes in depressive symptoms after the implementation of a universal screening for depression and subsequent care support. METHODS: A cluster-randomized study design used 10 subdistricts (2,400 inhabitants aged 40-64 years) in northern Japan randomly assigned in a 2:3 ratio to intervention and control conditions. All 900 residents aged 40-64 in the intervention districts were invited to participate in a 2-year depressive screening program, with a participation rate of 49.2%. A 4-year ongoing education program occurred in both intervention and control districts. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to assess depressive symptomatology. Repeated cross-sectional samples were surveyed before (n = 1,516, response rate 63.6%) and after (n = 1,596, 66.4%) intervention, and the data, clustered according to district, were analyzed at the individual level using a mixed-effects model. RESULTS: Significant changes in mean scores between baseline and 5-year follow-up in the intervention group were observed in the Depressive Affect, Somatic Symptoms, and Interpersonal Problems subscales. The difference between the changes over time in the two groups was significant for the three subscales and marginally for the CES-D total scale, but not for the Positive Affect subscale. CONCLUSIONS: Universal depression screening and subsequent support can be effective in preventing general depressive symptoms, but may not influence psychological well-being, among middle-aged adults in a community setting.

Effectiveness of a multimodal community intervention program to prevent suicide and suicide attempts: a quasi-experimental study.

BACKGROUND: Multilevel and multimodal interventions have been suggested for suicide prevention. However, few studies have reported the outcomes of such interventions for suicidal behaviours. METHODS: We examined the effectiveness of a community-based multimodal intervention for suicide prevention in rural areas with high suicide rates, compared with a parallel prevention-as-usual control group, covering a total of 631,133 persons. The effectiveness was also examined in highly populated areas near metropolitan cities (1,319,972 persons). The intervention started in July 2006, and continued for 3.5 years. The primary outcome was the incidence of composite outcome, consisting of completed suicides and suicide attempts requiring admission to an emergency ward for critical care. We compared the rate ratios (RRs) of the outcomes adjusted by sex, age group, region, period and interaction terms. Analyses were performed on an intention-to-treat basis and stratified by sex and age groups. FINDINGS: In the rural areas, the overall median adherence of the intervention was significantly higher. The RR of the composite outcome in the intervention group decreased 7% compared with that of the control group. Subgroup analyses demonstrated heterogeneous effects among subpopulations: the RR of the composite outcome in the intervention group was significantly lower in males (RR = 0.77, 95% CI 0.59-0.998, p = 0.0485) and the RR of suicide attempts was significantly lower in males (RR = 0.39, 95% CI 0.22-0.68, p = 0.001) and the elderly (RR = 0.35, 95% CI 0.17-0.71, p = 0.004). The intervention had no effect on the RR of the composite outcome in the highly populated areas. INTERPRETATION: Our findings suggest that this community-based multimodal intervention for suicide prevention could be implemented in rural areas, but not in highly populated areas. The effectiveness of the intervention was shown for males and for the elderly in rural areas. TRIAL REGISTRATION: ClinicalTrials.gov NCT00737165 UMIN Clinical Trials Registry UMIN000000460.

[Factors which affect the neurological condition in subarachnoid hemorrhage].

The factors which were related to the neurological condition were analyzed in 233 cases of subarachnoid hemorrhage. Bivariate analysis and multiple(binomial)logistic regression analysis were performed as for Hunt & Kosnik grade, modified Rankin Scale at discharge and modified Rankin Scale in the out-patient department to detect the factors which were related to the neurological condition. Hematoma-filled intraventricular hemorrhage, intracerebral hemorrhage with midline shift, acute subdural hematoma and aneurysm of the vertebrobasilar system were the representative factors which caused poor neurological condition. Hunt & Kosnik grade was poor when rebleeding occurred or hematoma was formed in the sylvian fissure. Hunt & Kosnik grade and modified Rankin Scale at discharge tended to be poor in the cases with acute hydrocephalus. The elevation of intracranial pressure was the major factor in neurological deterioration.

[Subarachnoid hemorrhage caused by dissection of the basilar artery: a case report].

We report a case of subarachnoid hemorrhage, which was caused by dissection of the basilar artery during treatment for diabetes mellitus. The patient was a 60-year-old male who consulted our hospital complaining of sudden-onset of a severe headache. Head CT scan showed subarachnoid hemorrhage around the basilar artery, but 3D-CT angiography revealed no abnormality. The basilar artery was shown to be normal during cerebral angiography on Day 1. However, in retrospect pseudolumen of the basilar artery was suspected in the proximal portion of the branching point of the anterior inferior cerebellar artery. During a second cerebral angiography on Day 17, blood pressure elevated to 185/83mmHg and 30 minutes later this patient's consciousness deteriorated to 10 points of the GCS(E4, V2, M4). The double lumen in the basilar artery was identified around the branching point of the anterior inferior cerebellar artery. Head MRI on the same day showed intramural hemorrhage of the basilar artery as a high intensity lesion. Head MRI on Day 18 revealed multiple cerebellar infarctions in the region of the bilateral anterior inferior cerebellar arteries. His consciousness recovered to almost normal by reducing the blood pressure. Transient gait disturbance also recovered thereafter. Head MRI on Day 90 indicated disappearance of the intramural hemorrhage in the basilar artery. It was important to reduce the blood pressure to prevent recurrence of the arterial dissection.

Cerebral hemorrhage and cerebral infarction in 30 cases of adult moyamoya disease: comparison between conservative therapy and superficial temporal artery-middle cerebral artery anastomosis.

To clarify the effect of surgery on the prevention cerebral hemorrhage in adult moyamoya disease, we compared postoperative courses between superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis and conservative therapy. The study subjects were 30 adults with moyamoya disease. Unilateral STA-MCA anastomosis was conducted in 7 of these 30 cases, and bilateral STA-MCA anastomosis was conducted in 8 of these 30 cases. Therefore, anastomosis was performed in a total of 23 sides. The postoperative clinical course was observed for more than 5 years after the STA-MCA anastomosis. Cerebral hemorrhage occurred after operation in 2 sides (8.7%) among the 23 sides that received STA-MCA anastomosis. On the contrary, hemorrhage occurred during conservative therapy in 5 sides (13.5%) among 37 non-operation sides (no significance in chi2 test). Cerebral infarction occurred in 3 sides (13%) among 23 sides treated with STA-MCA anastomosis. However, the infarction occurred in 2 sides (5.4%) among the 37 non-operation sides (no significance in chi2 test). Cerebral hemorrhage tended to occur less frequently after STA-MCA anastomosis, and bypass surgery was suggested to have some beneficial effect in preventing cerebral hemorrhage in adult moyamoya disease. However, it was revealed that STA-MCA anastomosis exacerbated the brain ischemia. Therefore, strict management is mandatory in the perioperative period.

Atherothrombotic lesion of the middle cerebral artery: report of 21 cases with stenotic and obstructive lesions.

This was a retrospective analysis of 12 consecutive cases of middle cerebral artery stenosis and 9 consecutive cases of middle cerebral artery occlusion that presented to our hospital with acute cerebral ischemia. The degree and area of the cerebral infarctions were assessed with the Alberta Stroke Program Early CT Score (ASPECTS) and ASPECTS-DWI (APSECTS with assessment of white matter lesion using diffusion-weighted image). As for cerebral infarctions in the region of the perforating artery, lesions that were more than 20 mm long in the caudal-cranial direction were diagnosed as branch atheromatous disease (BAD). Activities of daily living (ADL) were poorer in the cases with lower ASPECTS and ASPECTS-DWI. ADL tended to be worse in cases with BAD than in those without. The prognosis was significantly poorer in the group with ASPECTS< or =7 points. ASPECTS tended to be lower in cases with BAD than in those without. ADL, ASPECTS and the presence of BAD were not significantly different between the stenosis and obstruction groups. In summary, the neurological prognosis was dependent on the extent of the cerebral infarction and was related to BAD to some extent. These findings will be important when considering medical treatment at the outpatient clinic setting.

[A case with Stanford type A acute aortic dissection that presented with consciousness disturbance and hemiparesis].

The patient was a 63-year-old female who had a past history of hypertension. She suddenly complained of agonizing pain and became comatose soon thereafter. Upon admission, she was in a state of shock, with upper airway obstruction and a coma. The pupils were dilated on both sides. The laboratory data showed that D-dimer was >80µg/mL. Brain CT scan and diffusion weighted MRI of the brain showed no abnormality. On brain 2D-CT angiography, the visualization of the right internal carotid artery and the right vertebral artery was poor. She eventually was able to nod her head in response to verbal commands, but her left extremities were completely hemiplegic. Cerebral angiography showed occlusion of the right vertebral artery at the branching point from the brachiocephalic artery, and was visualized in a retrograde fashion through the left vertebral artery. The brachiocephalic artery was severely stenotic in aortography. During angiography, she became able to speak and complained of back pain. Chest CT just after angiography showed a dissection in the aortic arch. Therefore, she was directed to the cardiovascular surgeon for immediate consultation. During the operation, the aortic dissection was revealed to be Stanford type A. Laceration of the intima was found in the ascending aorta and cardiac tamponade was also found. Total arch replacement was performed. The pathological examination showed that the arterial dissection occurred in the layer of elastic fiber, and the minimum arterial thickness of the medial layer was 0.2mm. The patient improved after the operation and her neurological deficits disappeared completely 13 days after operation. Brain and spinal MRI 15 days after the operation showed no abnormality.

Visual disturbance following shunt malfunction in a patient with congenital hydrocephalus.

A 25-year-old woman presented with complaints of nausea and headache. She had been treated with a ventriculoperitoneal shunt for hydrocephalus when she was 7 months old. Her bilateral optic discs showed moderate atrophy. Right visual acuity allowed only perception of hand movement and left visual acuity was 0.02 (1.2). Computed tomography (CT) showed mild ventricular dilation but no periventricular lucency. Intracranial pressure (ICP) was not high when the shunt valve was punctured. Her visual acuity deteriorated 5 days after the consultation. She was referred again 8 days after the first consultation. The bilateral optic discs were completely pale. Both pupils were dilated on admission, and the bilateral direct light reflexes were absent. The patient could slightly detect only green light stimulus. CT showed moderate enlargement of the ventricle. ICP was 47 cmH(2)O when the shunt valve was punctured. Shuntgraphy showed obstruction of the shunt at the distal end of peritoneal catheter. Emergent total shunt revision was performed. She could detect dark stimulus and the still-dilated left pupil had recovered direct light reflex on the next day. The visual acuity was 0.01 (0.7) on the left 6 months after the operation, although she was blind in the right eye and the bilateral optic discs were completely pale. Visual loss associated with shunt failure remains a major morbidity in shunted congenital hydrocephalus. Early diagnosis and shunt revision may allow visual recovery.