Comparison of Early Postoperative Diffusion Weighted Magnetic Resonance Imaging Findings After Resection of Gliomas and Meningiomas.

OBJECTIVE: Glioma and meningioma require vastly different surgical approaches, even if only involving a simple craniotomy procedure. Diffusion weighted imaging (DWI) is useful for the postoperative evaluation of ischemic damage. The present study evaluated the expected but unproven differences in DWI findings. METHODS: A total of 41 patients with meningiomas and 63 with gliomas met the inclusion criteria for adult cases with superficial lesions treated through simple supratentorial craniotomy. Postoperative DWI findings of DWI-positive rate, DWI-positive area type, and relationship with neurological deficits were evaluated. RESULTS: The DWI-positive rate (P = 0.01) and the proportion of rim-type lesions (P < 0.01) were significantly more common in gliomas. Patients with meningiomas and DWI-positive areas presented with higher rates of new neurological deficits (P < 0.01), and patients with meningiomas on the left side were more likely to develop new neurological deficits (P = 0.02). Patients with gliomas tended to develop new deficits with larger DWI-positive area volumes (P = 0.04). CONCLUSIONS: Postoperative early DWI-positive rate and rim-type lesions are more common after glioma resection than meningioma resection. Larger volumes of DWI-positive areas may be associated with postoperative neurological symptoms in gliomas. DWI-positive finding is less common after meningioma than glioma resection but more likely to be associated with new neurological symptoms. These differences are important for adequate postoperative DWI evaluation of common supratentorial brain tumors.

Emergent surgical evacuation of traumatic intracranial hematoma in patients with preoperative thrombocytopenia: surgical risk and early outcome.

BACKGROUND: Surgical evacuation of intracranial hematoma, including epidural, subdural, intracerebral, and intraventricular hematoma, is recommended in patients with traumatic brain injury (TBI) for prevention of cerebral herniation and possible saving of life. However, preoperative coagulopathy is a major concern for emergent surgery on patients with severe TBI. METHODS: We reviewed 65 consecutive patients with severe TBI who underwent emergency craniotomy for intracranial hematomas. RESULTS: Univariate analysis showed preoperative pupil abnormality, absence of pupil light reflex, respiratory failure, preoperative thrombocytopenia (< 100 × 109/L), increased activated partial thromboplastin time (> 36 s), low fibrinogen (< 150 mg/dL), platelet transfusion, red cell concentrate transfusion, and presence of brain contusion and traumatic subarachnoid hemorrhage (SAH) on computed tomography were correlated with poor outcome (death or vegetative state). Multivariate analysis revealed that pupil abnormality (p = 0.001; odds ratio [OR] 0.064, 95% confidence interval [CI] 0.012-0.344), preoperative thrombocytopenia (p = 0.016; OR 0.101, 95% CI 0.016-0.656), and traumatic SAH (p = 0.021; OR 0.211, 95% CI 0.057-0.791) were significant factors. Investigation of the 14 patients with preoperative thrombocytopenia found the emergency surgery was successful, with no postoperative bleeding during hospitalization. However, half of the patients died, and almost a quarter remained in the vegetative state mainly associated with severe cerebral edema. CONCLUSIONS: Emergent craniotomy for patients with severe TBI who have preoperative thrombocytopenia is often successful, but the prognosis is often poor. Emergency medical care teams and neurosurgeons should be aware of this discrepancy between successful surgery and poor prognosis in these patients. Further study may be needed on the cerebral edema regulator function of platelets.

Endoscopic Extended Transsphenoidal Approach for Sellar and Suprasellar Xanthogranuloma: Potential Implications for Surgical Strategies in Adult Craniopharyngioma.

OBJECTIVE: Differentiation of suprasellar xanthogranuloma (XG) from adult craniopharyngioma (CP) can be problematic in endoscopic extended transsphenoidal surgery. METHODS: We reviewed the clinical data, preoperative imaging, intraoperative endoscopic findings, and intraoperative frozen section pathology in newly diagnosed adult CPs (19 patients) and XGs (6 patients). RESULTS: Intracystic signal intensity was often high on T1-weighted magnetic resonance images in the XGs but low in the CPs (P = 0.015). Capsular intensity was low on T2-weighted imaging in XGs but iso to high in CPs (P < 0.001). Capsular gadolinium enhancement was often seen in CPs and not in XGs (P < 0.001). CPs often had a solid component with contrast enhancement but none in XGs (P < 0.001). Intraoperative endoscopic observations frequently found a whitish solid component in the CPs but yellow to brown fibrous granulomatous lesions in XGs (P < 0.001). The tumor capsule was dark grayish and soft in CPs, whereas it was fibrously hard in XGs (P = 0.002). Yellowish hemosiderin deposits were seen in all XGs (P = 0.003). Intraoperative pathologic diagnosis of CP was all verified whereas no evidence of tumor was found in XGs (P < 0.001). Partial removal was performed in 4 patients with XGs. No recurrence was observed in these patients during the follow-up period (1.5-8 years). CONCLUSIONS: Careful interpretation of preoperative magnetic resonance imaging, intraoperative endoscopic findings, and intraoperative frozen section diagnosis may be important for the differential diagnosis between XG and CP. In endoscopic-extended transsphenoidal surgery, intentional partial removal can be effective for XG after careful diagnosis.

Preoperative Magnetic Resonance Imaging Localization of the Normal Pituitary Gland in Nonfunctioning Pituitary Adenoma Patients Using the Radiological Sign of "Internal Carotid Artery Notch".

OBJECTIVE: Asymmetric features of nonfunctioning pituitary adenoma (NFPA) are poorly understood. We investigated the asymmetry in NFPA on magnetic resonance imaging. METHODS: We reviewed preoperative magnetic resonance imaging findings of patients initially treated for NFPA. The internal carotid artery (ICA) often seemed to cause an indentation in the external shape of the tumor (i.e., the ICA notch). RESULTS: Two cases with a normal pituitary gland located at the midline were excluded. The remaining 66 cases were examined. The side where the normal gland was located was defined as the normal pituitary side and the opposite side as the cavernous sinus side. The Knosp grade was significantly higher on the cavernous sinus side (P < 0.001), and the vertical distance of the ICA was significantly greater on the cavernous sinus side (P < 0.001). The ICA notch was found in 87.9% of all cases on the normal pituitary side, but in only 45.5% on the cavernous sinus side (P < 0.001). In cases with a single-side ICA notch (34 of 68), the ICA notch was found in 91.2% of cases and on the cavernous sinus side in 8.8% (P < 0.001). CONCLUSIONS: Magnetic resonance imaging of NFPA frequently shows asymmetry. The tumor does not extend laterally on the normal pituitary side but extends laterally more freely on the cavernous sinus side. The ICA notch is often found on the normal pituitary side where the position of ICA does not move. This may be useful as a preoperative sign to indicate the normal pituitary side.

Usefulness of dual isotope 123I-IMP and 201Tl SPECT for the diagnosis of primary central nervous system lymphoma and glioblastoma.

BACKGROUND: Preoperative differential diagnosis between primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM) is important because these tumors require different surgical strategies. This study investigated the usefulness of dual isotope, iodine-123-labeled N-isopropyl-p-iodo-amphetamine (123I-IMP) and thallium-201 chloride single-photon emission computed tomography (201Tl SPECT) for the differential diagnosis. METHODS: Twenty-five PCNSL patients and 27 GBM patients who underwent dual isotope imaging, 123I-IMP and 201Tl SPECT, are included. Tumor-to-normal (T/N) ratio was calculated from the ratio of maximum tracer counts in the lesion to the mean counts in the contralateral cerebral cortex. The mean and minimum apparent diffusion coefficient values (ADCmean and ADCmin, respectively) on magnetic resonance imaging were also analyzed. RESULTS: Delayed phase 123I-IMP SPECT was the most useful imaging examination for the differentiation between PCNSL and GBM compared with early phase 123I-IMP SPECT, early and delayed phase 201Tl SPECT, ADCmean, and ADCmin. However, the median T/N ratios of PCNSL and GBM were 1.32 and 0.83, respectively, in the delayed phase 123I-IMP SPECT. On the other hand, the median T/N ratios of PCNSL and GBM were 3.10 and 2.34, respectively, in the delayed phase 201Tl SPECT, with excellent tumor detection. CONCLUSION: Delayed phase 123I-IMP SPECT could differentiate between PCNSL and GBM with high accuracy, but T/N ratio was low and tumor detection was poor. 201Tl SPECT was useful for estimation of the malignancy and localization of the tumors with high T/N ratio. Dual isotope 123I-IMP and 201Tl SPECT was useful for the preoperative diagnosis of PCNSL and GBM.

A phenylphthalimide derivative, TC11, induces apoptosis by degrading MCL1 in multiple myeloma cells.

To date, the prognosis of multiple myeloma (MM) in patients harboring cytogenetic abnormalities (CA) involving t (4; 14) and deletion of chromosome 17 remains poor despite recent advances in drug development that include the use of immunomodulatory drugs (IMiDs) such as lenalidomide for MM. To address this issue, we have developed a novel phenylphthalimide derivative, TC11, that is structurally related to IMiDs. It remains unclear how TC11 induces apoptosis of MM cells with high-risk CA. Here, we show that TC11 does not induce degradation of CRBN's substrates, IKZF1/3 and CK1α, and induces apoptosis of CRBN-silenced MM; this effect was independent of the cereblon (CRBN) pathway, which is involved in the mechanism of action of IMiDs used for the treatment of MM. We also revealed that TC11, in contrast to existing IMiDs, induced degradation of MCL1 and activation of caspase-9. Furthermore, inhibition of CDK1 by CGP74514A prevented TC11-induced MCL1 degradation, caspase-9 activation, and the subsequent apoptotic cell death. We showed that ectopic MCL1 expression rescued apoptosis of MM. These observations suggest that TC11 induces apoptotic death caused by degradation of MCL1 during prolonged mitotic arrest. Therefore, our findings suggest that TC11 is a potential drug candidate for high-risk MM.

Predictors of Discontinuance of Oral Feeding in Patients With Advanced Alzheimer Dementia and Aspiration Pneumonia in Japan: A Single-center, Retrospective Observational Study.

BACKGROUND: Difficulty with oral feeding, the most commonly observed complication of Alzheimer disease (AD) in its final stages, occurs in 86% of AD patients and may prevent achievement of oral feeding after aspiration pneumonia. However, no reliable indicators of discontinuance of oral feeding have yet been identified. We therefore aimed to identify predictors of discontinuance of oral feeding in postaspiration pneumonia patients with AD. MATERIALS AND METHODS: Relevant clinical and laboratory data of 60 patients with AD admitted to our hospital in Japan for aspiration pneumonia were retrospectively compared between oral feeding and discontinuance groups. RESULTS: The study groups differed in interval since diagnosis of AD, CURB-65 score, pneumonia severity index score, and proportion of patients who died (higher in the discontinuance group) and body mass index (BMI), Mini Mental State Examination (MMSE) score, and functional independence measure score (lower in the discontinuance group). According to multivariate logistic regression analysis of all identified independent variables, only CURB-65 and MMSE scores and BMI are significant predictors of discontinuance of oral feeding after aspiration pneumonia in patients with advanced AD. CONCLUSIONS: In patients with advanced AD, discontinuance of oral feeding after aspiration pneumonia may be predicted by CURB-65 and MMSE scores and BMI.

Risk Factors for Hemorrhagic and Cardioembolic Complications of Intracerebral Hemorrhage Associated with Anticoagulants.

BACKGROUND: Patients with intracerebral hemorrhage taking anticoagulants are increasingly common in Japan due to the aging population. The clinical benefit of restarting anticoagulants is established, but the optimal timing of resumption is controversial. Risk factors for hemorrhagic and cardioembolic events in the acute phase are also unknown. This study investigated hemorrhagic and cardioembolic events and risk factors in intracerebral hemorrhage patients taking anticoagulants. METHODS: The clinical data of 65 consecutive intracerebral hemorrhage patients taking anticoagulants were retrospectively reviewed. Hemorrhagic and cardioembolic complications and risk factors were analyzed. RESULTS: Lobar hemorrhage was the most frequent (21 of 65 cases, 32.3%). At discharge, 31 patients (47.7%) showed severe disability or had died. Eight (18.6%) of 43 patients who restarted anticoagulants after initial treatment developed hemorrhagic events, including recurrent intracerebral hemorrhage in 3. HAS-BLED score was 2-3 in these 3 patients. Six (15.8%) of 38 patients who took anticoagulants for cardiogenic factors suffered cardioembolism. Systemic inflammatory response syndrome was significantly more common in the cardioembolic group (66.7%) compared with the noncardioembolic group (21.9%, P < .05). CHA2DS2-VASc score was paradoxically high in the noncardioembolic group (3 versus 5, P < .05). CONCLUSION: HAS-BLED score and CHA2DS2-VASc score were not useful for risk assessment for hemorrhagic events, recurrent intracerebral hemorrhage, and cardioembolism in the acute phase. Inflammatory response might be important in the occurrence of cardioembolic events.

Fibronectin on extracellular vesicles from microvascular endothelial cells is involved in the vesicle uptake into oligodendrocyte precursor cells.

We previously reported transplantation of brain microvascular endothelial cells (MVECs) into cerebral white matter infarction model improved the animal's behavioral outcome by increasing the number of oligodendrocyte precursor cells (OPCs). We also revealed extracellular vesicles (EVs) derived from MVECs promoted survival and proliferation of OPCs in vitro. In this study, we investigated the mechanism how EVs derived from MVECs contribute to OPC survival and proliferation. Protein mass spectrometry and enzyme-linked immunosorbent assay revealed fibronectin was abundant on the surface of EVs from MVECs. As fibronectin has been reported to promote OPC survival and proliferation via integrin signaling pathway, we blocked the binding between fibronectin and integrins using RGD sequence mimics. Blocking the binding, however, did not attenuate the survival and proliferation promoting effect of EVs on OPCs. Flow cytometric and imaging analyses revealed fibronectin on EVs mediates their internalization into OPCs by its binding to heparan sulfate proteoglycan on OPCs. OPC survival and proliferation promoted by EVs were attenuated by blocking the internalization of EVs into OPCs. These lines of evidence suggest that fibronectin on EVs mediates their internalization into OPCs, and the cargo of EVs promotes survival and proliferation of OPCs, independent of integrin signaling pathway.