Acute progression of cerebral amyloid angiopathy-related inflammation diagnosed by biopsy in an elderly patient: A case report.

Background: Cerebral amyloid angiopathy-related inflammation (CAA-I) presents with slowly progressive nonspecific neurological symptoms, such as headache, cognitive function disorder, and seizures. Pathologically, the deposition of amyloid-ß proteins at the cortical vascular wall is a characteristic and definitive finding. Differential diagnoses include infectious encephalitis, neurosarcoidosis, primary central nervous system lymphoma, and glioma. Here, we report a case of CAA-I showing acute progression, suggesting a glioma without enhancement, in which a radiological diagnosis was difficult using standard magnetic resonance imaging. Case Description: An 80-year-old woman was admitted due to transient abnormal behavior. Her initial imaging findings were similar to those of a glioma. She presented with rapid progression of the left hemiplegia and disturbance of consciousness for 6 days after admission and underwent emergent biopsy with a targeted small craniotomy under general anesthesia despite her old age. Intraoperative macroscopic findings followed by a pathological study revealed CAA-I as the definitive diagnosis. Steroid pulse therapy with methylprednisolone followed by oral prednisolone markedly improved both the clinical symptoms and imaging findings. Conclusion: Differential diagnosis between CAA-I and nonenhancing gliomas may be difficult using standard imaging studies in cases presenting with acute progression. A pathological diagnosis under minimally invasive small craniotomy may be an option, even for elderly patients.

Coexistence of RASA1 and COL4A2 variants caused pial arteriovenous fistula (AVF) in a patient with capillary malformation-arteriovenous malformation.

Pial arteriovenous fistulas (AVFs) are rare vascular lesions; their exact pathophysiology is largely unknown. Pial AVFs have been reported to develop within capillary malformation-arteriovenous malformation (CM-AVM); however, only a few cases have been reported. Variants in the RASA1 gene have been reported as a cause of CM-AVM. We report the case of an adult patient with pial AVF, who carried variants in the RASA1 and COL4A2 genes. The patient in the current report was likely to have been affected by CM-AVM and the RASA1 variant seemed to be the primary factor in the pathogenesis of pial AVF. However, COL4A2 may have also contributed to the development of pial AVF because the COL4A2 and RASA1 variants have a common pathophysiology, wherein the patient develops lesions due to collagen type IV deficiency.

Reduction of thromboembolic complications during the endovascular treatment of unruptured aneurysms by employing a tailored dual antiplatelet regimen using aspirin and prasugrel.

BACKGROUND: Thromboembolic complications (TECs) are frequent during the endovascular treatment of unruptured aneurysms. To prevent TECs, dual antiplatelet therapy using aspirin and clopidogrel is recommended for the perioperative period. In patients with a poor response, clopidogrel is a risk factor for TECs. To prevent TECs, our study assessed the stratified use of prasugrel. METHODS: Patients who underwent endovascular therapy for unruptured cerebral aneurysms from April 2017 to August 2019 were enrolled in this clinical study and given premedication with aspirin and clopidogrel for 2 weeks prior to the procedure. P2Y12 reaction units (PRU) were measured using the VerifyNow assay on the day before the procedure (tailored group). In subgroups with PRU <240, the clopidogrel dose was maintained (CPG subgroup). In subgroups with PRU ≥240, clopidogrel was changed to prasugrel (PSG subgroup). We compared the occurrence of TECs with retrospective consecutive cases from January 2015 to March 2017 without PRU assessments (non-tailored group). The frequency of TECs within 30 days was assessed as the primary endpoint. RESULTS: The tailored and non-tailored groups comprised 167 and 50 patients, respectively. TECs occurred in 11 (6.6%) and 8 (16%) patients in the tailored and non-tailored groups (P=0.048), respectively. The HR for TECs was significantly reduced in the tailored group (HR 0.3, 95% CI 0.11 to 0.81); P=0.017) compared with the non-tailored group. CONCLUSION: The results suggest that tailored dual antiplatelet therapy medication with PRU significantly reduces the frequency of TECs without increasing hemorrhagic complications.

Primary spinal intramedullary Ewing-like sarcoma harboring CIC-DUX4 translocation: a similar cytological appearance as its soft tissue counterpart but no lobulation in association with desmoplastic stroma.

The CIC-DUX4 translocation is the most common genetic alteration of small round cell sarcomas without EWSR1 rearrangement. These "Ewing-like sarcomas" usually occur in peripheral soft tissues, and rare primary central nervous system (CNS) tumors have been described. We report a rare case of primary spinal intramedullary Ewing-like sarcoma harboring CIC-DUX4 translocation. A 23-year-old man presented with weakness in the extremities. Magnetic resonance imaging revealed a large intramedullary tumor spanning C3-C5 with heterogeneous enhancement following gadolinium administration. Histologically, most of the tumor displayed dense myeloid proliferation composed of medium- to slightly small-sized primitive cells. Postoperatively, he received local adjuvant radiation therapy without tumor progression for 10 months. Target RNA sequencing analysis revealed the CIC-DUX4 fusion gene. Methylation array analysis resulted in a diagnosis of "methylation class CNS Ewing sarcoma family tumor with CIC alteration". Although this tumor lacked characteristic histological features such as lobular structures in association with desmoplastic stroma, relatively uniform nuclei with prominent nucleoli and eosinophilic cytoplasm, which are often found in CIC-rearranged sarcomas of soft tissue, were identified. Recently, many CNS and soft tissue tumors require genetic analysis for precise diagnosis. To consider certain molecular testing, careful histological examination is essential.

Delayed neurological deterioration following atlantoaxial facet joint distraction and fixation in a patient with Chiari malformation type I.

Chiari malformation type I (CM-I) is typically treated with foramen magnum decompression. However, a recent study proposed a new technique for patients with CM-I, wherein only short atlantoaxial joint fusion and distraction is applied. Posterior fusion with or without atlantoaxial distraction is a potential option for patients with CM-I associated with basilar invagination or complex anomalous bony craniovertebral junction pathology, since this procedure allows clinicians to avoid using the technically demanding transoral approach in which some or all of the odontoid tip is invisible. Distraction of the atlantoaxial joint reduces ventral cervicomedullary compression, leading to neurological improvement. Here, the authors report the case of a 50-year-old woman with CM-I plus basilar invagination whose condition immediately improved but then gradually deteriorated following atlantoaxial joint distraction and fusion. Therefore, the authors performed endonasal/transoral odontoidectomy, which resulted in prolonged neurological recovery. Short atlantoaxial fusion with distraction is a smart and ideal surgical planning concept that can result in significant neurological improvement. However, this case suggests that anterior odontoidectomy is still an essential element of the intervention strategy for patients with CM-I with complex craniovertebral junction pathology.

Novel Application of Time-Spatial Labeling Inversion Pulse Magnetic Resonance Imaging for Diagnosis of External Hydrocephalus.

BACKGROUND: Although a subdural fluid collection frequently is observed, diagnostic methods that differentiate between the subdural collection caused by external hydrocephalus and that caused by subdural hygroma have not been established. Here, we report a case of external hydrocephalus caused by Gliadel-induced eosinophilic meningitis that has been previously reported in only 1 case and can be diagnosed by time-spatial labeling inversion pulse magnetic resonance imaging (time-SLIP MRI). CASE DESCRIPTION: A tumor located in the left temporal was detected incidentally in an 81-year-old man by examination of a head injury. The tumor was surgically resected and diagnosed as a high-grade glioma during the surgery; Gliadel wafers subsequently were implanted. Three weeks after the resection, the patient showed disturbed consciousness, and computed tomography revealed a subdural fluid collection. The out-flow of cerebrospinal through the resection cavity was detected by time-SLIP MRI. Cerebrospinal tests indicated high white blood cell counts and high protein levels, with more than 90% of the white blood cell count comprising eosinophils. Therefore, we suspected that the subdural fluid collection was caused by external hydrocephalus because of Gliadel-induced eosinophilic meningitis. We surgically removed the Gliadel wafers and subsequently performed a surgery to insert a ventriculoperitoneal shunt. Histologic examination indicated eosinophilic accumulation around the Gliadel wafers. The patient's symptoms improved after the insertion of a ventriculoperitoneal shunt. CONCLUSIONS: In the present case, time-SLIP MRI was a useful and noninvasive method for diagnosing external hydrocephalus which was caused by eosinophilic meningitis because of Gliadel-induced eosinophilic meningitis.

Remote intracranial recurrence of IDH mutant gliomas is associated with TP53 mutations and an 8q gain.

Most IDH mutant gliomas harbor either 1p/19q co-deletions or TP53 mutation; 1p/19q co-deleted tumors have significantly better prognoses than tumors harboring TP53 mutations. To investigate the clinical factors that contribute to differences in tumor progression of IDH mutant gliomas, we classified recurrent tumor patterns based on MRI and correlated these patterns with their genomic characterization. Accordingly, in IDH mutant gliomas (N = 66), 1p/19 co-deleted gliomas only recurred locally, whereas TP53 mutant gliomas recurred both locally and in remote intracranial regions. In addition, diffuse tensor imaging suggested that remote intracranial recurrence in the astrocytomas, IDH-mutant with TP53 mutations may occur along major fiber bundles. Remotely recurrent tumors resulted in a higher mortality and significantly harbored an 8q gain; astrocytomas with an 8q gain resulted in significantly shorter overall survival than those without an 8q gain. OncoScan® arrays and next-generation sequencing revealed specific 8q regions (i.e., between 8q22 and 8q24) show a high copy number. In conclusion, only tumors with TP53 mutations showed patterns of remote recurrence in IDH mutant gliomas. Furthermore, an 8q gain was significantly associated with remote intracranial recurrence and can be considered a poor prognostic factor in astrocytomas, IDH-mutant.

The outcomes of early aneurysm repair in World Federation of Neurosurgical Societies grade V subarachnoid haemorrhage patients with emphasis on those presenting with a Glasgow Coma Scale score of 3.

Grade V subarachnoid haemorrhage (SAH) patients may be dichotomised into those with temporary deterioration and those with irreversible injury, and only the former have a chance of favourable outcomes by aneurysm obliteration. One method of differentiating the two conditions is to wait and observe potential recovery for 12-48hours. However, early rebleeding and non-convulsive seizures may occur during this period. In our institution, grade V SAH patients receive immediate treatment (general anaesthesia induction and aneurysm obliteration within 24hours of onset) to minimise those risks. We focused on therapeutic outcomes in SAH patients presenting with a Glasgow Coma Scale score of 3 (GCS-3). Between January 2006 and December 2013, 82 GCS-3 SAH patients were admitted, among whom 51 (62%) underwent immediate aneurysm obliteration. Their outcomes 90days after onset were evaluated with the Glasgow Outcome Scale, with either good recovery or moderate disability regarded as favourable outcomes. Multivariate logistic regression analysis was performed to identify variables correlated with favourable outcomes. Among the 51 patients, 11 (22%) had favourable 90-day outcomes. Age (odds ratio [OR], 0.838; 95% confidence interval [CI], 0.733-0.959; p=0.010) and intact pupillary light reflex (OR, 21.939; 95% CI, 1.465-328.576; p=0.025) were correlated with favourable outcomes. By contrast, neither intact respiratory pattern nor isocoric pupils was correlated with favourable outcomes. The current results indicate that vigorous intervention may be worth attempting in young GCS-3 SAH patients with intact pupillary light reflex. It remains unclear, however, whether the seemingly high frequency of favourable outcomes was truly due to reduction in early rebleeding or seizures.

Therapeutic outcomes for patients with aneurysmal subarachnoid hemorrhage complicated by Takotsubo cardiomyopathy.

BACKGROUND: There are no guidelines regarding the optimal treatment of subarachnoid hemorrhage (SAH) patients complicated by Takotsubo cardiomyopathy (TCM). Although coiling has been favored as the first-line treatment, clipping may also be indicated in patients with ruptured middle cerebral artery aneurysms or in those with massive intracerebral hemorrhage. The study objective is (1) to report the feasibility/safety of clipping/coiling and (2) to identify possible prognosticators in that population. METHODS: Between January 2008 and December 2014, 371 consecutive patients with aneurysmal SAH underwent transthoracic echocardiography after admission, and 30 with TCM (7.7 %) were identified. We reviewed the incidence and type of perioperative complications among clipped (n = 11) and coiled (n = 19) patients. The 30 patients were dichotomized based on their 90-day modified Rankin scale (mRS) scores into favorable (mRS: 0-2) and unfavorable (mRS: 3-6) groups, and their demographic, laboratory and echocardiographic variables were compared. RESULTS: Neither clipped nor coiled patients developed serious perioperative cardiopulmonary complications, but coiled patients had a higher incidence of fatal procedure-related complications. Among the 30 patients, 13 (43 %) had favorable 90-day outcomes, and the favorable group was significantly younger. Age, but not the degree of cardiac dysfunction, correlated with outcomes by multivariate regression analysis. CONCLUSIONS: Clipping was shown to be a safe treatment modality in our cohort, and treatment selection may better be made on a case-by-case basis in most patients with SAH-induced TCM. The lack of correlation between the degree of cardiac dysfunction and outcomes indicates that aggressive intervention is justified in patients with severely impaired cardiac function.

Differences between Takotsubo cardiomyopathy and reverse Takotsubo cardiomyopathy associated with subarachnoid hemorrhage.

BACKGROUND: Both Takotsubo cardiomyopathy (TTC) and reverse TTC (r-TTC) are characterized by reversible regional wall motion abnormalities of the heart unrelated to coronary artery pathology. It remains unclear whether and/or how r-TTC differs from TTC. Subarachnoid hemorrhage (SAH) is occasionally causative of TTC/r-TTC, and this study was conducted to detect possible differences between TTC and r-TTC associated with SAH. METHODS: A single-center retrospective study was conducted on 328 consecutive SAH patients. They routinely underwent transthoracic echocardiography (TTE), ECG, and measurements of plasma catecholamines and other cardiac biomarkers within 24 h of admission. Demographic, echocardiographic, electrocardiographic and neurochemical profiles were compared between patients with TTC and r-TTC. The diagnosis of TTC/r-TTC was based on the revised Mayo Clinic Criteria. RESULTS: Data of 21 SAH-induced TTC and 10 SAH-induced r-TTC patients admitted between January 2009 and December 2014 were analyzed. The patients with r-TTC were significantly younger than those with TTC (51.8 ± 10.9 vs. 63.5 ± 14.4 years, p = 0.04). The former exhibited significantly higher plasma epinephrine levels than the latter (809 ± 710 vs. 380 ± 391 pg/mL, p = 0.04). Plasma norepinephrine levels did not differ significantly (2421 ± 1374 vs. 1724 ± 1591 pg/mL, p = 0.25). No significant differences were observed in other demographic/physiologic variables, echocardiographic parameters, frequency of ECG abnormalities, and 90-day mortality. Moreover, none of the patients who underwent a follow-up TTE exhibited morphologic change from one type to the other. CONCLUSIONS: The pathomechanisms in TTC and r-TTC may not be identical: however, distinguishing the two conditions may not have great importance from the standpoint of clinical management and prognostication.

Early rebleeding in patients with subarachnoid haemorrhage under intensive blood pressure management.

The objective of this study was to report the frequency and clinical characteristics of early rebleeding in subarachnoid haemorrhage (SAH) patients who underwent intensive blood pressure (BP) management. Patients with aneurysmal SAH frequently present to the emergency department (ED) with elevated BP. Intensive BP management has been recommended to lower the risk of early rebleeding. However, few studies have reported the frequency of early rebleeding in SAH patients undergoing BP management. In our institution, SAH patients with systolic BP (SBP)>140 mmHg received continuous intravenous nicardipine to maintain their SBP within 120±20 mmHg after diagnosis. An attempt to implement intensive BP management was made on 309 consecutive SAH patients who presented to our ED within 48 hours of SAH onset. Overall, 24 (7.8%) of the 309 patients sustained early rebleeding. Fifteen patients sustained early rebleeding before the implementation of BP management, and the other nine sustained early rebleeding after the implementation of BP management. Therefore, the frequency of early rebleeding under BP management was 3.1% (9/294). When the 309 patients were dichotomised using ED SBP of 140 mmHg as a cut off (SBP>140 mmHg; n=239 versus SBP⩽140 mmHg; n=70), the latter counter-intuitively exhibited a significantly higher frequency of early rebleeding (5.9% versus 14.2%; p=0.04). This relatively low frequency of early rebleeding under BP management may be acceptable. However, early rebleeding is not eradicated even with strict BP control as factors other than elevated BP are involved. ED SBP within the target range (SBP⩽140 mmHg) does not negate the risk of early rebleeding. Other treatment options that reduce the risk should also be explored.

Spontaneous intracranial hypotension manifesting as a unilateral subdural hematoma with a marked midline shift.

Spontaneous intracranial hypotension (SIH) is a syndrome in which hypovolemia of the cerebrospinal fluid (CSF) results in various symptoms. Although its prognosis is usually benign, cases with a rapid neurologic deterioration resulting in an altered mental status have been reported. One of the characteristic radiographic findings in such cases is the presence of bilateral accumulation of subdural fluid (hematoma/hygroma). When SIH-related subdural hematoma is present only unilaterally with a concomitant midline shift, making an accurate diagnosis may be challenging, and inadvertent hematoma evacuation may result in further neurologic deterioration. We report a 58-year-old woman with an altered mental status who had visited a local hospital and in whom a brain CT showed a unilateral subdural hematoma with a marked midline shift. She was referred to our department because of her neurologic deterioration after hematoma evacuation. A CT myelography revealed a massive CSF leakage in the entire thoracic epidural space. She made a full neurologic recovery following blood patch therapy. Our case is unique and educational because the suspicion for SIH as an underlying cause of subdural hematoma is warranted in nongeriatric patients not only with bilateral but also unilateral lesions. An immediate search for CSF leakage may be important in cases with failed hematoma evacuation surgery.