Toxoplasmic encephalitis with high 201Tl uptake and retention mimicking malignant lymphoma in a patient with human immunodeficiency virus infection.

Various opportunistic infections develop during immunodeficiency due to human immunodeficiency virus (HIV) infection. The treatment options for malignant lymphoma (ML) and toxoplasmic encephalitis (TE) are completely different; therefore, their discrimination is critical. A 25-year-old female of foreign nationality had been experiencing headaches for several weeks and suddenly developed convulsions. Brain computed tomography revealed multiple intracranial lesions; therefore, the patient was referred to the neurosurgery department. Brain magnetic resonance imaging (MRI) revealed multiple masses with surrounding edema, accompanied by enhanced contrast. The largest mass (2 cm) in the left occipital lobe exhibited ringed contrast enhancement. Her blood test results showed a CD4 count of 40/µL, positive HIV Ag/Ab, HIV-RNA level of 56 × 104 copies/mL, positive anti-Toxoplasma IgG (63 IU/mL), and negative anti-Toxoplasma IgM. 201Tl- single photon emission computed tomography (201Tl-SPECT) revealed abnormal accumulation only in the tumor in the left occipital lobe (early T/N ratio, 3.034; delayed T/N ratio, 2.738; retention index, 0.9), which was suspected to be a ML. Both tumors, with or without high accumulation of 201Tl, were subjected to craniotomy biopsy. Pathological examination revealed infiltration of small lymphocytes with a necrotic background. The patient was diagnosed with TE based on a positive result of a tissue polymerase chain reaction test for Toxoplasma gondii. Two weeks after sulfamethoxazole and trimethoprim combination therapy, MRI imaging showed dramatic improvement in multiple brain tumors. This case is atypical because ML was ruled out despite high 201Tl-SPECT uptake and retention. Careful diagnosis through pathological examination and DNA testing is important.

Differences in amyloid-ß and tau/p-tau deposition in blood-injected mouse brains using micro-syringe to mimic traumatic brain microhemorrhages.

BACKGROUND: Cerebral microbleeds (CMBs) due to traumatic brain injuries (TBI) have been shown to lead to cognitive decline and impairment. CMBs caused by TBI may be associated with pathophysiological mechanisms involving inflammation and the accumulation of amyloid-ß (Aß), tau, and phosphorylated tau (p-tau), contributing to cognitive abnormalities. However, their relationships remain unclear. OBJECTIVES: To test our hypothesis that Aß, tau, and p-tau are accumulated and regulated separately in mice with injuries imitating CMBs from TBI, we studied. METHODS: Seven-week-old C57BL/6 male mice were injected with 15 µL of heparinized autologous blood or saline by micro-syringe into the front lobe. Expression profiles and regulation of Aß, tau, and p-tau were assessed immunohistochemically over time. RESULTS: On day 7 after blood injection, Iba-1+ and S100B+ cells in damaged cortex adjacent to the injection site were higher than saline injection group and non-injected sham. On days 3-14, Aß deposition were gradually increased but normalized by day 28. In contrast, tau/p-tau deposition gradually increased during days 14-28 and dispersed along the corticomedullary junction adjacent to hem deposits, indicating different expression profiles from Aß. Deposits of Aß, but not tau/p-tau, were phagocytosed by CD163+ macrophages increased by Gc-protein macrophage-activating factor during days 7-28, suggesting different mechanisms of deposition and regulation between Aß and tau/p-tau. CONCLUSION: Deposition and regulation differ between Aß and tau/p-tau in mice with injuries mimicking CMBs from TBI. Further clarification of relationships between the pathologies of cognitive impairment and their neurodegenerative consequences is needed.

A novel COL4A1 variant associated with recurrent epistaxis and glioblastoma.

COL4A1-related disorders are characterized by a higher incidence of cerebral hemorrhage than other hereditary cerebral small vessel diseases. Accumulating data have shown broad phenotypic variations, and extracerebral hemorrhages have been linked to these disorders. Moreover, the coexistence of neural tumors has been described. Here, we report a Japanese family with a novel COL4A1 variant, including a patient with recurrent epistaxis and glioblastoma.

Postoperative recurrence of chronic subdural hematoma is more frequent in patients with blood type A.

OBJECTIVE: Because of an aging society, the incidence of chronic subdural hematoma (CSDH) is increasing. This lesion is treated with simple burr hole irrigation, but one of the major issues is that CSDH frequently recurs. ABO blood type may be associated with a bleeding tendency and inflammation. However, its association with the recurrence of CSDH remains unknown. Therefore, the authors of the present study aimed to retrospectively investigate the association between ABO blood type and CSDH recurrence. METHODS: The authors retrospectively analyzed symptomatic CSDHs in 425 cerebral hemispheres of 376 patients who had undergone surgical treatment with irrigation of the hematoma via burr holes at their institution from January 2011 to September 2019. Among these were 366 CSDHs in 320 patients whose ABO blood type had been determined and who were included in this study. RESULTS: In the study, 307 patients with CSDHs in 350 hemispheres were followed up postoperatively until the disappearance of the CDSH or for at least 3 months. Recurrence of CSDH was observed in 37 patients (10.6%) after surgical treatment. Blood type A was found to be significantly associated with CSDH recurrence compared to non-A blood types: 24 of 153 CDSHs (15.7%) versus 13 of 197 CDSHs (6.6%) (p = 0.008). In the multivariable regression analysis, blood type A, in addition to thrombocytopenia, was a significant independent predictor of the recurrence of CSDH. CONCLUSIONS: The study results showed that blood type A is an independent risk factor for the postoperative recurrence of CSDH and that careful follow-up in these patients may be needed.

Combination Therapy Using Prothrombin Complex Concentrate and Vitamin K in Anticoagulated Patients with Traumatic Intracranial Hemorrhage Prevents Progressive Hemorrhagic Injury: A Historically Controlled Study.

Warfarin remains crucially involved in the treatment of patients at thrombotic or thromboembolic risk. However, warfarin increases the mortality rate among patients with traumatic intracranial hemorrhage (TICH) through progressive hemorrhagic injury (PHI). Therefore, a rapid anticoagulation reversal could be required in patients with TICH to prevent PHI. Differences in the warfarin reversal effect between combination therapy of prothrombin complex concentrate (PCC) with vitamin K (VK) and VK monotherapy remain unclear. However, studies have reported that PCC has greater effectiveness and safety for warfarin reversal compared with fresh frozen plasma (FFP). This retrospective study aimed to evaluate the warfarin reversal effects of combination therapy of PCC with VK and VK monotherapy on TICH. We compared the clinical outcomes between the periods before and after the PCC introduction in our hospital. There were 13 and 7 patients who received VK monotherapy and PCC with VK, respectively. PHI predictors were evaluated using univariate regression analyses. Warfarin reversal using PCC had a significant negative association with PHI (odds ratio: 0.03, 95% confidence interval: 0.00-0.41, P = 0.004). None of the patients presented with thrombotic complications. Warfarin reversal through a combination of PCC with VK could be more effective for inhibiting post-trauma PHI compared with VK monotherapy. This could be attributed to a rapid and stable warfarin reversal. PCC should be administered to patients with TICH taking warfarin for PHI prevention.

Cardiogenic cerebral embolism caused by a severe hypoglycemic attack†:†a case report.

The direct relationship between a hypoglycemic attack and cerebral infarction remains unknown. It has been reported that a hypoglycemic attack can result in takotsubo syndrome, leading to cerebral infarction. We report a case of a cardiogenic cerebral embolism caused by a hypoglycemic attack, with additional literature review. A 71-year-old woman was admitted to our hospital in a semi-comatose state due to a severe hypoglycemic attack ; she developed hemiplegia one day after admission. Magnetic resonance imaging revealed cerebral infarction in the area supplied by the left middle cerebral artery. Takotsubo syndrome was suspected based on echocardiography. We diagnosed cerebral embolism due to takotsubo syndrome, caused by the hypoglycemic attack. J. Med. Invest. 67 : 362-364, August, 2020.

Diagnosis and Operative Management of Carotid Endarterectomy in Patients with Twisted Carotid Bifurcation.

Although carotid endarterectomy (CEA) is an established procedure, technical modifications are required when anatomical features are unusual. The present study aimed to determine the characteristics of diagnostic features, surgical management, and outcomes of patients with a twisted carotid bifurcation (TCB). We assessed 108 consecutive patients by cervical carotid echography (CCE) and black-blood magnetic resonance imaging (BB-MRI) before they underwent 115 CEA procedures. We classified carotid bifurcation (CB) anatomy based on anteroposterior findings of the internal carotid artery (ICA) and external carotid artery (ECA) determined by cerebral or three-dimensional computed tomographic angiography as follows. The ICA and ECA ran laterally and medially, respectively, in Type 1, overlapped in Type 2, and the ICA and ECA ran medially and laterally, respectively, in Type 3. We also classified the patients according to whether or not they had a TCB and compared their diagnostic findings, clinical characteristics, and surgical outcomes. The numbers of patients with Types 1, 2, and 3 were 74 (64.4%), 32 (27.8%), and 9 (7.8%), respectively, and 13 (11.3%) with a TCB included four patients with Type 2 and all nine patients with Type 3. The appearance of Type 3 differed from that of the other two types on CCE and BB-MR images. After correcting the anatomical location of a TCB, surgical duration and adverse event rates did not significantly differ between patients with and without a TCB. Patients with a TCB could safely undergo CEA after correcting the ICA to the normal position.

Down-regulation of MDR1 by Ad-DKK3 via Akt/NFκB pathways augments the anti-tumor effect of temozolomide in glioblastoma cells and a murine xenograft model.

BACKGROUND: Glioblastoma multiforme (GBM) is the most malignant of brain tumors. Acquired drug resistance is a major obstacle for successful treatment. Earlier studies reported that expression of the multiple drug resistance gene (MDR1) is regulated by YB-1 or NFκB via the JNK/c-Jun or Akt pathway. Over-expression of the Dickkopf (DKK) family member DKK3 by an adenovirus vector carrying DKK3 (Ad-DKK3) exerted anti-tumor effects and led to the activation of the JNK/c-Jun pathway. We investigated whether Ad-DKK3 augments the anti-tumor effect of temozolomide (TMZ) via the regulation of MDR1. METHODS: GBM cells (U87MG and U251MG), primary TGB105 cells, and mice xenografted with U87MG cells were treated with Ad-DKK3 or TMZ alone or in combination. RESULTS: Ad-DKK3 augmentation of the anti-tumor effects of TMZ was associated with reduced MDR1 expression in both in vivo and in vitro studies. The survival of Ad-DKK3-treated U87MG cells was inhibited and the expression of MDR1 was reduced. This was associated with the inhibition of Akt/NFκB but not of YB-1 via the JNK/c-Jun- or Akt pathway. CONCLUSIONS: Our results suggest that Ad-DKK3 regulates the expression of MDR1 via Akt/NFκB pathways and that it augments the anti-tumor effects of TMZ in GBM cells.

Present epidemiology of chronic subdural hematoma in Japan: analysis of 63,358 cases recorded in a national administrative database.

OBJECTIVE Aging of the population may lead to epidemiological changes with respect to chronic subdural hematoma (CSDH). The objectives of this study were to elucidate the current epidemiology and changing trends of CSDH in Japan. The authors analyzed patient information based on reports using a Japanese administrative database associated with the diagnosis procedure combination (DPC) system. METHODS This study included patients with newly diagnosed CSDH who were treated in hospitals participating in the DPC system. The authors collected data from the administrative database on the following clinical and demographic characteristics: patient age, sex, and level of consciousness on admission; treatment procedure; and outcome at discharge. RESULTS A total of 63,358 patients with newly diagnosed CSDH and treated in 1750 DPC participation hospitals were included in this study. Analysis according to patient age showed that the most common age range for these patients was the 9th decade of life (in their 80s). More than half of patients 70 years old or older presented with some kind of disturbance of consciousness. Functional outcomes at discharge were good in 71.6% (modified Rankin Scale [mRS] score 0-2) of cases and poor in 28.4% (mRS score 3-6). The percentage of poor outcomes tended to be higher in elderly patients. Approximately 40% of patients 90 years old or older could not be discharged to home. The overall recurrence rate for CSDH was 13.1%. CONCLUSIONS This study shows a chronological change in the age distribution of CSDH among Japanese patients, which may be affecting the prognosis of this condition. In the aging population of contemporary Japan, patients in their 80s were affected more often than patients in other age categories, and approximately 30% of patients with CSDH required some help at discharge. CSDH thus may no longer have as good a prognosis as had been thought.

Utility of Indocyanine Green Video Angiography for Sylvian Fissure Dissection in Subarachnoid Hemorrhage Patients - Sylvian ICG Technique.

Indocyanine green (ICG) emits fluorescence in the far-red domain under light excitation. ICG video angiography (ICG-VA) has been established as a useful method to evaluate blood flow in the operative field. We report the usefulness of ICG-VA for Sylvian fissure dissection in patients with subarachnoid hemorrhage (SAH). Subjects comprised 7 patients who underwent ICG-VA before opening the Sylvian fissure during neck clipping for ruptured cerebral aneurysm. We observed contrasted Sylvian veins before opening the Sylvian fissure using surgical microscopes. This procedure was termed "Sylvian ICG". We observed ICG fluorescence quickly in all cases. Sylvian veins that appeared unclear in the standard microscopic operative field covered with subarachnoid hemorrhage were extremely clearly depicted. These Sylvian ICG findings were helpful in identifying entry points and the dissecting course of the Sylvian fissure. At the time of clipping, no residual fluorescence from Sylvian ICG was present, and aneurysm clipping was not impeded. Sylvian ICG for SAH patients is a novel technique to facilitate dissection of the Sylvian fissure. We believe that this technique will contribute to improved safety of clipping surgery for ruptured aneurysms.

[A Case of an Orbital Angioleiomyoma].

A 70-year-old woman presented with a 4-year history of painless conjunctival congestion and proptosis of the right eye. Computed tomography and magnetic resonance imaging revealed a 48-mm lesion in the right medial orbit. As the symptoms progressed, the tumor was resected by performing fronto-orbital craniotomy. Histopathological examination revealed a vascular tumor surrounded by smooth muscle fibers and immunohistochemistry demonstrated tumor positivity for smooth muscle actin and desmin. The tumor was diagnosed as an angioleiomyoma, and no recurrence has been observed as of 5 years postoperatively. Angioleiomyomas in the orbit are extremely rare;thus, we have reported this case with reference to the literature.

Bamboo Leaf Sign as a Sensitive Magnetic Resonance Imaging Finding in Spinal Subependymoma: Case Report and Literature Review.

Background and Importance. Subependymoma occurs very rarely in the spinal cord. We report another case of spinal subependymoma along with a review of the literature and discussion of a radiological finding that is useful for preoperative diagnosis of this tumor. Clinical Presentation. A 51-year-old man presented with a 2-year history of progressive muscle weakness in the right lower extremity. Sagittal magnetic resonance imaging (MRI) showed spinal cord expansion at the Th7-12 vertebral level. Surgical resection was performed and the tumor was found to involve predominantly subpial growth. Histological diagnosis was subependymoma, classified as Grade I according to criteria of World Health Organization. We made an important discovery of what seems to be a characteristic appearance for spinal subependymoma on sagittal MRI. Swelling of the spinal cord is extremely steep, providing unusually large fusiform dilatation resembling a bamboo leaf. We have termed this characteristic MRI appearance as the "bamboo leaf sign." This characteristic was apparent in 76.2% of cases of spinal subependymoma for which MRI findings were reported. Conclusion. The bamboo leaf sign on spinal MRI is useful for differentiating between subependymoma and other intramedullary tumors. Neurosurgeons encountering the bamboo leaf sign on spinal MRI should consider the possibility of subependymoma.

Blocking of the interaction between Wnt proteins and their co-receptors contributes to the anti-tumor effects of adenovirus-mediated DKK3 in glioblastoma.

The effect of the third member of the Dickkopf family (DKK3) in the Wnt pathway in glioblastoma remains unclear. We first demonstrated the non-specific interaction of Wnt3a and Wnt5a with the receptors LRP6 and ROR2 and the up-regulation of the Wnt pathway in glioblastoma cells. We used an adenovirus vector and found that an increase in DKK3 protein attenuated the expression of Wnt3a, Wnt5a and LRP6, but not of ROR2, and their interaction, thereby affecting both canonical- and non-canonical Wnt downstream cascades. This produced anti-tumor effects in GBM xenograft models. The suppression of Wnt pathways upstream by DKK3 may have promise for the treatment of glioblastoma.

Up-regulation of endogenous PML induced by a combination of interferon-beta and temozolomide enhances p73/YAP-mediated apoptosis in glioblastoma.

Interferon-beta (IFN-ß) is reported to augment anti-tumor effects by temozolomide in glioblastoma via down-regulation of MGMT. Promyelocytic leukemia (PML), a gene induced by IFN-ß, is a tumor suppressor. Here, we report for the first time that in combination therapy, an IFN-ß-induced increase in endogenous PML contributes to anti-tumor effects in p53 wild- and mutant glioma cells in a xenograft mice model. The increased PML promoted the accumulation of p73, a structural and functional homolog of p53, to fuse the coactivator Yes-associated-protein in the PML nuclear bodies. The adjuvant therapy targeted at PML may be a promising therapeutic strategy for glioblastoma.