Subarachnoid Hemorrhage

Intracranial aneurysms represent the most common etiology of nontraumatic subarachnoid hemorrhage. Management of intracranial aneurysms must be meticulous and tailor made for each patient. Various strategies in the management include main artery ligation, aneurysm neck occlusion, wrapping or coating, clipping or coiling. This article presents an overview on subarachnoid hemorrhage, patho-physiology, investigations, a management guideline and outcome in intracranial aneurysms

Stimulation-Dependent Intraspinal Microtubules and Synaptic Failure in Alzheimer's Disease: A Review

There are many microtubules in axons and dendritic shafts, but it has been thought that there were fewer microtubules in spines. Recently, there have been four reports that observed the intraspinal microtubules. Because microtubules originate from the centrosome, these four reports strongly suggest a stimulation-dependent connection between the nucleus and the stimulated postsynaptic membrane by microtubules. In contrast, several pieces of evidence suggest that spine elongation may be caused by the polymerization of intraspinal microtubules. This structural mechanism for spine elongation suggests, conversely, that the synapse loss or spine loss observed in Alzheimer's disease may be caused by the depolymerization of intraspinal microtubules. Based on this evidence, it is suggested that the impairment of intraspinal microtubules may cause spinal structural change and block the translocation of plasticity-related molecules between the stimulated postsynaptic membranes and the nucleus, resulting in the cognitive deficits of Alzheimer's disease

Neurorehabilitation in neurotrauma

Since time immemorial, neurotrauma has been recorded in various continents. The advancement in neurotraumatology ever since Denny Brown and Trussell’s landmark experimental study of concussion, has come a long way with major contributions from neuropathology, neurophysiology, neurochemistry, biomedical sciences, public policies, intensive care medicine and last but not the least, genetics. A simple introduction of lap and shoulder belt have reduced majority of serious accidents. Continuous recording of intracranial pressures, recognition of acute brain swelling with characteristics of cerebral blood flow in brain damage and development of Glasgow coma and outcome scales by a well-designed multi-centered multi-national outcome study in head injuries brought in major changes in squealae and outcome by preventing and reducing the secondary insults. Computed tomography (CT) and improvement in morbidity and mortality of acute extra axial hematomas by immediate surgery, has influenced and guided several organizations in developing research and formulating guidelines for treatment of acute neurotrauma. The recognition of the spectrum in head injury, aids in prevention of injury and measures to improve outcome by ever developing neuro-rehabilitative measures, apart from advancements in the genetic aspects of understanding the brain’s response to injury along with attention to modern principles of neuro-intensive and critical care, has manipulated neurotrauma towards achieving innovative newer frontiers. Assessment of the extent of injury and the deficits in neurotrauma is as challenging as the management itself. Several criteria including the Japanese Coma Scale and the proposition for the international coma scale have been attempted. Once the baseline characters and the psychology1 of the patient is understood along with the extent and nature of the severity of the injury, a defined patterned timescale with a schedule can be created & tailor made to every patient and all out efforts instituted to rehabilitate not only the individual but also the whole family and the society at large

Unruptured Arteriovenous Malformations of Brain: An overview

Arteriovenous malformations are congenital lesions that occur most commonly in the supratentorial region. These space-occupying vascular lesions consist of multiple arteries and veins, connecting as a fistula without an intervening normal capillary bed. Typically, AVM’s are single lesions, except when associated with hereditary hemorrhagic telangiectasia. The histology includes clusters of normal or dilated arteries and abnormal veins with calcification and occasionally some prior haemorrhage

Application of modified shrinking field radiation in RT-DeVIC chemoradiotherapy for treating localized extranodal natural killer/T-cell lymphoma

　Concurrent chemoradiotherapy (CRT) is the recommended treatment for localized extranodal natural killer/T-cell lymphoma, nasal type (ENKL). In 2009, the Japan Clinical Oncology Group first documented the safety and efficacy of a regimen involving radiotherapy (RT) plus dexamethasone, etoposide, ifosfamide, and carboplatin (DeVIC) in their phase I/II trials (JCOG0211 study). The application of this regimen has drastically improved outcomes of patients with localized ENKL. In 2013, the current guidelines were made to the cost in JCOG0211 study.　We retrospectively investigated the outcomes of three patients who received CRT for stage localized ENKL at the Kawasaki Medical School Hospital between August 2007 and March 2011. Our CRT protocol differed from that used in the JCOG0211 study as we used a different shrinking field RT method. A recent report on shrinking or extended-field RT raised questions regarding which fields are appropriate. Thus, we compared our clinical results with those of the JCOG0211 study and analyzed the effect of the differences in field size on clinical results. The median follow-up of the three patients in the present study was 9 months (range, 5-106 months), two and one of whom achieved complete and partial responses, respectively. Regarding adverse events, no severe acute side effects (e.g., mucositis) higher than Grade 4 were observed.　We reviewed cases and the JCOG0211 study which we experienced in the past about fields of the RT. The present study described our experiences with three patients receiving shrinking field RT

胸水細胞診で形質細胞腫が疑われた血管免疫芽球性Ｔ細胞リンパ腫

血管免疫芽球性Ｔ細胞リンパ腫（angioimmunoblastic T-cell lymphoma: AITL）は新WHO分類において末梢Ｔ細胞 / NK 細胞腫瘍に分類されているＴ細胞性腫瘍である．その臨床像は，全身リンパ節腫大，肝脾腫，発熱，多クローン性高γ グロブリン血症など多様な症状を呈することが知られている．今回，我々は胸水細胞診で形質細胞腫が疑われたAITL を経験したので報告する．症例は80歳代の女性．近医にて気管支喘息治療中に，喘息症状が悪化し，全身の皮疹が出現．両側胸水貯留，CRP 高値が出現したため，精査治療目的で当院紹介となった．血液検査で貧血を認め，末梢血に形質細胞様の異型リンパ球を10％認めた．胸水には大小不同のCD138陽性形質細胞を多数認め細胞診で形質細胞腫が疑われたが，胸水セルブロックではκ・λ の軽鎖制限を認めなかった．骨髄検査では，形質細胞の増加を認めず赤芽球癆の状態であった．皮下腫瘤を生検した結果，AITL と診断した．AITL は，腫瘍細胞が直接的・間接的にサイトカインを産生し，それに起因した多彩な臨床像を呈する．そのため，AITL は反応性に形質細胞の増加を伴うことが多く，本症例は，反応性に胸水中に形質細胞の増加を伴ったと考えられた．また，AITL は赤芽球癆を合併することも報告されている．AITL では，反応性の形質細胞増多を伴う胸水貯留や赤芽球癆をきたす場合があることに注意すべきである．Angioimmunoblastic T cell lymphoma (AITL) is a T cell-related tumor that is classified as a peripheral T cell/natural killer cell tumor according to the new World Health Organization classification. AITL shows various clinical features owing to the cytokines produced directly or indirectly by tumor cells and includes a variety of symptoms, such as general lymphadenopathy, hepatosplenomegaly, fever, and polyclonal hypergammaglobulinemia. AITL is often accompanied by reactive plasmacytosis, and it has been reported that AITL can be complicated by pure red cell aplasia. Here, we report an 80-year-old woman with AITL who was suspected to have a plasma cell tumor by cytological diagnosis of hydrothorax. The patient presented with exacerbated asthmatic symptoms as well as exanthema over her entire body. Moreover, during treatment for bronchial asthma at a local doctor’s clinic, hydrothorax in both lungs and high C-reactive protein levels were observed. She was referred to our hospital for detailed examination and treatment. Blood test results revealed anemia as well as a high proportion of plasma cell-like atypical lymphocytes in the peripheral blood. Specimens of the hydrothorax also contained CD138-positive plasma cells of varying sizes; however, there was no evidence of deviation in light chain limitation. We did not notice elevated plasma cell counts, and the patient was considered to have pure red cell aplasia based on the results of the marrow examination. However, we noted a subcutaneous mass under her shoulder blade. An excisional biopsy was performed, and she was diagnosed with AITL. The patient was considered to have hydrothorax with plasmacytosis as a reaction to AITL. As seen in our case, AITL may cause pleural effusions along with reactive plasmacytosis and pure red cell aplasia

臍帯血移植後発症した early lesion of PTLD の剖検例

移植後リンパ増殖性疾患（post-transplant lymphoproliferative disorders, PTLD）は，同種造血幹細胞移植後の生命を脅かす予後不良な合併症の一つである．臨床症状は非特異的であるが，PTLD を疑った場合はPCR 法による血中EB（Epstein-Barr）ウイルス-DNA 量を測定し，高値を示した場合はPTLD と判断する必要がある．今回，造血幹細胞移植後に高EB ウイルス血症を認め，急激な病状の悪化により死亡した症例を経験したため剖検所見を含め報告する．症例は，40歳代男性でフィラデルフィア染色体陽性急性リンパ性白血病を発症し，治療にて寛解を得た後に臍帯血移植を施行した．移植後280日に高熱が出現し，胸部CT 検査から細菌性肺炎と診断し入院．抗菌薬治療を開始するも効果不良であり，呼吸状態の悪化と，意識障害が出現した．血液，肺胞洗浄液と髄液から，EB ウイルス-DNA 異常高値が検出された．PTLD と判断したが，急激に呼吸状態が悪化し死亡した．剖検では，肺胞内出血を認め，急激に悪化した原因と考えられた．そして，肺門部リンパ節や肺にはEBER（EBV-encoded small RNA）陽性細胞を多数認め，一部では大型多核細胞も散見され，early lesion of PTLD と判断された．Early lesion of PTLD であっても，本症例のように肺病変を認めた場合，出血による呼吸状態の悪化から急激な経過をたどることがあり，早期の対応が必要と考えられた．Post-transplant lymphoproliferative disorder (PTLD), a life-threatening condition with poor prognosis, can arise after allogeneic hematopoietic stem cell transplantation. The clinical symptoms are non-specific, but if PTLD is suspected, the blood levels of Epstein-Barr (EB) virus DNA are measured using PCR. Here, we report our experience with a patient who showed high levels of EB virus DNA in the blood and a rapidly worsening condition resulting in death, after undergoing hematopoietic stem cell transplantation. The patient was male and in his 40s; he had developed Philadelphia chromosome-positive acute lymphoid leukemia and achieved remission with treatment, and he later underwent umbilical cord blood transplantation. A high fever appeared 280 days after transplantation, and he was hospitalized and diagnosed with bacterial pneumonia following a thoracic CT examination. He was initiated on antimicrobial therapy, but responded poorly, exhibiting a worsening respiratory condition and disturbance of consciousness. Abnormally high EB virus DNA levels were detected in his blood, bronchoalveolar lavage fluid, and cerebrospinal fluid. He was diagnosed with PTLD, but his respiratory condition deteriorated rapidly and he died. The autopsy revealed alveolar hemorrhage, which was thought to be the cause of the rapid deterioration. A large number of EBER (EBV-encoded small RNA)- positive cells were also found in hilar lymph nodes and lungs, which were deemed to be early lesions of PTLD. Therefore, timely action is crucial if lesions are presents as even early PTLD lesions can progress rapidly owing to bleeding that can result in the deterioration of the respiratory condition

クリプトコッカス髄膜炎を発症したCD4リンパ球減少症の２例

　クリプトコッカス感染症はCryptococcus neoformans による真菌感染症であり，免疫不全患者に発症しやすい．今回，我々はCD4リンパ球減少を認め，クリプトコッカス髄膜炎を発症した２例を経験したので報告する．症例１は，40歳代男性で不明熱のため受診した．血液検査でリンパ球930/μL，髄膜刺激症状はなかったが，髄液検査にてクリプトコッカス菌体が検出され，血液培養からも検出された．CD4 72.5/μL と低値であり，HIV 抗体陽性であった．クリプトコッカス髄膜炎を発症したAIDS 患者と診断した．症例２は，20歳代女性で不明熱のため受診した．血液検査でリンパ球510/μL，髄膜刺激症状はなかったが，髄液検査にてクリプトコッカス菌体が検出され，血液培養からも検出された．CD4 19.4/μL と低値であったが，HIV 抗体陰性で原発性免疫不全症や他の免疫不全となる原因は認められなかった．Idiopathic CD4 lymphocytopenia（ICL）に発症したクリプトコッカス髄膜炎と診断した．AIDS とICL がそれぞれ原因となったクリプトコッカス髄膜炎であった．前者での本症併発は2.4 %，後者での併発は19.7 % と報告されている．HIV非感染のクリプトコッカス髄膜炎をみた際にはICL によるCD4リンパ球減少症を考える必要がある．死に至ることもまれではないクリプトコッカス髄膜炎であるが，治療が奏効し１年以上経過しているため報告する．　Cryptococcal infections are fungal infections caused by Cryptococcus neoformans. This infection develops more commonly in immunocompromised patients. We report two cases of cryptococcal meningitis that developed as a result of CD4 lymphocytopenia. Case 1 was a man in his 40s who presented with a fever of unknown origin. A blood test revealed a lymphocyte count of 930/μL, with no meningeal irritation; however, examination of his cerebrospinal fluid detected cryptococcal bodies, which was also confirmed by blood culture. In addition, the patient had a low CD4 count of 72.5/μL, and was HIV antibodypositive. We thus diagnosed him as an AIDS patient who developed cryptococcal meningitis. Case 2 was a woman in her 20s who also presented with a fever of unknown origin. A blood test revealed a lymphocyte count of 510/μL, with no meningeal irritation; however, examination of her cerebrospinal fluid detected cryptococcal bodies, which was confirmed by blood culture. Despite the patient having a low CD4 count of 19.4/μL, she was HIV antibody-negative, and there was no evidence of primary immunodeficiency or any other causes of immune deficiency. Accordingly, we diagnosed this patient as cryptococcal meningitis that developed as a result of idiopathic CD4 lymphocytopenia (ICL). In the above cases, cryptococcal meningitis developed as a result of AIDS and ICL, respectively. The incidence rates of this complication are reported as 2.4% for the former and 19.7% for the latter. When cryptococcal meningitis without HIV infection is observed, it is necessary to consider the possibility of CD4 lymphocytopenia due to ICL. Although cryptococcal meningitis can be fatal, treatment was successful in both cases, and more than one year has elapsed since their initial presentation