Trends and Progress in Neuroendovascular Treatment in Japan: Japanese Registry of Neuroendovascular Therapy (JR-NET) 4. Main Report.

We reported the main results of the Japanese Registry of Neuroendovascular Therapy (JR-NET) 4, a nationwide surveillance of therapy (NET) in Japan from January 2015 to December 2019. JR-NET 4 registered consecutive patients who underwent NETs by Japan Society of Neuroendovascular Therapy (JSNET) -certified specialists. The primary endpoint was functional independence (mRS score of 0-2) at 30 days post-NET, with secondary endpoints focusing on technical success and major adverse events within 30 days.A total of 63,230 patients and 60,354 NET procedures from 166 participating centers were analyzed. During the study period, NET cases have consistently increased, with an increase in the proportion of elderly patients. A significant trend shift was observed in the distribution of NET procedures, with endovascular treatment for acute ischemic stroke that showed a dramatic increase in 5 years. This trend aligns with key randomized clinical trials from 2015 that presented the efficacy of this treatment. Clinical outcomes at 30 days posttreatment revealed that endovascular treatment for acute ischemic stroke and other NETs maintained safety and effectiveness despite varying prevalence of functional independence between target diseases. The study also observed a steady increase in emergency treatment cases, reflecting the increase in acute ischemic stroke, a time-sensitive medical condition.This comprehensive surveillance highlights the trend of NET practices in Japan, driven by clinical evidence and advancements in treatment devices. Although these findings were specific to Japan, they offer valuable insights into the broader trends in NETs and acute stroke care.

Successful intracranial response of lorlatinib after resistance with alectinib and brigatinib in patients with ALK-positive lung adenocarcinoma: Implications of CNS penetration rate of brigatinib.

We present the case of a 34-year-old Japanese man with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer and brain metastases. After central nervous system (CNS) disease progression with alecintib and brigatinib, treatment with lorlatinib resulted in a good intracranial response. In this case, we investigated brain penetration ratio of brigatinib using cerebrospinal fluid and paired serum samples, and the ratio was 0.012. Further, we investigated resistance mechanisms via next-generation sequencing (NGS) using lung biopsy at lung cancer diagnosis and brain biopsy sample at progressive disease of brigatinib. No apparent resistance mechanism of known ALK resistance, such as ALK mutations, amplifications, epithelial-mesenchymal transition (EMT) and bypass pathway activation were detected. Taken together, we speculate that the low CNS penetration rate of brigatinib confers CNS progression. Further studies are warranted to reveal the resistance mechanism and propose a treatment strategy for CNS progression in ALK-positive patients.

Comorbidity burden and outcomes after mechanical thrombectomy for large vessel occlusion: A retrospective analysis.

OBJECTIVES: Patients with acute ischemic stroke (AIS) often have an accumulation of pre-existing comorbidities, but its clinical impact on outcomes after mechanical thrombectomy (MT) remains unknown. Therefore, we examined whether comorbidity burden before AIS onset could predict clinical outcomes after MT. METHODS: In this retrospective cohort, we enrolled consecutive patients with community-onset AIS who underwent MT between April 2016 and December 2021. To evaluate each patient's comorbidity burden, we calculated Charlson comorbidity index (CCI), then classified the patients into the High CCI (≥ 3) and the Low CCI (< 3) groups. The primary outcome was a good neurological outcome at 90 days, defined as a modified Rankin scale 0-2 or no worse than the previous daily conditions. All-cause mortality at 90 days and hemorrhagic complications after MT were also compared between the two groups. We estimated the odds ratios and their confidence intervals using a multivariable logistic regression model. RESULTS: A total of 388 patients were enrolled, of whom 86 (22.2%) were classified into the High CCI group. Patients in the High CCI group were less likely to achieve a good neurological outcome (adjusted odds ratio of 0.26 [95% confidence interval, 0.12-0.58]). Moreover, symptomatic intracranial hemorrhage was more common in the High CCI (14.0% vs. 4.6%; adjusted odds ratio, 4.10 [95% confidence interval, 1.62-10.3]). CONCLUSIONS: Comorbidity burden assessed by CCI was associated with clinical outcomes after MT. CCI has the potential to become a simple and valuable tool for predicting neurological prognosis among patients with AIS and MT.

Resveratrol Derivatives Inhibit Transthyretin Fibrillization: Structural Insights into the Interactions between Resveratrol Derivatives and Transthyretin.

Hereditary ATTR amyloidosis is a disease caused by the deposition of amyloid fibrils formed by mutated transthyretin (TTR), a protein that binds to thyroid hormone in the serum, in the organs. The development of a small molecule that binds to and stabilizes TTR is a promising strategy for the treatment of ATTR amyloidosis. In the present study, we demonstrated that the resveratrol derivatives including pterostilbene available as a dietary supplement inhibit the fibrillization of V30M-TTR to the same extent as the approved drug tafamidis. Furthermore, based on a thermodynamic and X-ray crystallographic analysis, the binding of the resveratrol derivative to TTR was shown to be enthalpy-driven, with the binding enthalpy being acquired by hydrogen bonding to S117. Moreover, direct observation of hydrogen atoms by neutron crystallography provided details of the hydrogen bond network by S117 and emphasized the importance of the CH···π interaction by L110 in the ligand binding.

[Efficacy of FilmArray® ME panel for the rapid diagnosis of meningitis and encephalitis].

Microbial tests are essential for appropriate management for acute meningitis and encephalitis, but it often takes several days to identify the results of culture tests or PCR. BioFire FilmArray® meningitis/encephalitis panel (ME panel) is a rapid multiplex PCR assay that targets 14 bacteria, viruses, and yeast in 1 hour. In this single-center retrospective study, we reviewed adult patients who underwent ME panel test in parallel with conventional microbial tests from January to August 2021. Eighteen of 70 patients (26%) tested positive by ME panel, of which 8 patients (11%) were helpful in altering treatment strategy. Fifty-two patients (74%) could stop empirical treatment such as acyclovir or antibiotics due to negative results on ME panel. All results of ME panel were same as traditional assays. Use of ME panel can contribute to early diagnosis and treatment.

Impact of thrombocytopenia on hemorrhagic complications after endovascular therapy for acute large vessel occlusion: Sub-analysis of RESCUE-Japan registry 2.

BACKGROUND: Endovascular treatment (EVT) for patients with large vessel occlusion (LVO) and concurrent thrombocytopenia raises concerns about hemorrhagic complications. We examined the association between thrombocytopenia and clinical outcomes after EVT. METHODS: This is a sub-analysis of the RESCUE-Japan Registry 2, a nationwide registry that enrolled 2420 consecutive acute LVO patients. We evaluated the clinical outcomes in patients who underwent EVT according to their platelet count on admission (Moderate/Severe, < 100 × 109 /L; Mild, 100 to ≤150 × 109/L; Normal, ≥ 150 × 109/L). The outcomes included any and symptomatic intracranial hemorrhage (ICH) after EVT, and modified Rankin Scale (mRS) at 90 days. RESULTS: Of 1268 patients who underwent EVT, the Moderate/Severe and Mild groups consisted of 41 (3.2%), and 193 (15.2%) patients. Any ICH occurred in 37%, 35%, and 24% of Moderate/Severe, Mild, and Normal group patients, respectively, and the adjusted ORs (95% CIs) were 1.50 (0.71-3.18) for Moderate/Severe and 1.87 (1.28-2.73) for Mild, compared to the Normal group (p for trend = 0.004). Symptomatic ICH increased with the severity of thrombocytopenia (9.8% vs 3.6% vs 2.1%), and adjusted ORs were 4.43 (1.16-17.0) in Moderate/Severe and 1.85 (0.71-4.86) in Mild (p for trend = 0.10). Mortality was significantly associated with the severity of thrombocytopenia (p for trend = 0.005), and adjusted ORs were 3.26 (1.29-8.26) in the Moderate/Severe and 2.76 (1.58-4.84) in the Mild groups. CONCLUSIONS: Thrombocytopenia in LVO patients was not rare and associated with the incidence and manifestation of ICH after EVT.

Low left atrial volume is an independent predictor of persistent hypotension after carotid artery stenting.

BACKGROUND: Persistent hypotension (PH) after carotid artery stenting (CAS) is a relatively common complication; however, it is unclear which patients are more likely to experience this phenomenon. Recently, lower left atrial (LA) volume was associated with vasovagal syncope, which has a similar neurological mechanism to hypotension after CAS. This study aimed to investigate whether LA volume can predict PH after CAS. METHODS: This single center retrospective analysis used data from 316 patients who had undergone CAS between March 2013 and February 2021. After the exclusion of urgent CAS, 212 procedures (202 patients) with transthoracic echocardiograms were included. The procedures were divided among two groups according to the presence or absence of PH for more than 1 hour after CAS. RESULTS: The mean age of the patients was 73.0±7.5 years. PH was observed during 52 (24.5%) procedures. The PH group exhibited a lower LA volume index (LAVI) than the no-PH group (29.7±9.1 vs 37.7±12.5 mL/m2, respectively; p<0.001). The area under the receiver operating characteristic curve was 0.716. The optimal cut-off value was 33.5 mL/m2 (sensitivity 0.750, specificity 0.625). Multiple logistic regression analysis showed that LAVI <33.5 mL/m2 was an independent predictor for PH after CAS (OR 4.950, 95% CI 2.190 to 11.200; p<0.001). Preoperative hydration was negatively associated with PH (OR 0.235, 95% CI, 0.070 to 0.794; p=0.020). CONCLUSIONS: A lower LA volume can predict PH after CAS, and preoperative hydration may prevent PH after CAS.

Clinical Impact of Pre-Existing Autoantibodies in Patients With SCLC Treated With Immune Checkpoint Inhibitor: A Multicenter Prospective Observational Study.

Introduction: Although pretreatment autoantibodies have been associated with immune-related adverse events (irAEs) and immune checkpoint inhibitor treatment efficacy in some types of cancer, their importance has not been evaluated in patients with SCLC. Methods: A multicenter prospective observational study was conducted on a total of 52 patients with extensive-disease SCLC who received immune checkpoint inhibitors in combination with chemotherapy as the first-line treatment at either of the six participating centers in Japan. Pretreatment serum samples were collected and analyzed for autoantibodies (rheumatoid factor, antinuclear antibodies, and antithyroid). Moreover, 12 antineuronal antibodies (AMPH, CV2, PNMA2, Ri, Yo, Hu, Recoverin, SOX1, Titin, Zic4, GAD65, and Tr) were analyzed using immunoblot assays. The primary end point was the incidence of irAEs with or without autoantibodies. The secondary end points were progression-free survival (PFS) and overall survival (OS) on the basis of the presence or absence of autoantibodies. Results: PFS and OS were 4.4 and 25.3 months, respectively. Autoantibodies (rheumatoid factor, antinuclear antibodies, and antithyroid antibodies) were detected in 29 patients (56%). In total, irAEs were observed in 18 patients (35%); irAE incidence was 48% in the autoantibody-positive group and 17% in the autoantibody-negative group (p = 0.039). There was no difference in PFS or OS between patients with and without autoantibodies (4.4 mo versus 4.6 mo, p = 0.36; 15.3 mo versus 18.2 mo, p = 0.36). Antineuronal antibodies were detected in 16 patients (31%). However, the development of neurologic irAEs was not observed in both groups. Conclusions: Vigilance is required against the development of irAEs in pretreatment antibody-positive patients.

Association between anemic status on admission and clinical outcomes of acute large vessel occlusion.

BACKGROUND: Anemia is a frequently observed condition, but its clinical impact on large vessel occlusion (LVO) remains unclear. We examined the association between anemic status on admission and clinical outcomes of LVO in a real-world setting. METHODS: We conducted a post-hoc analysis of the RESCUE-Japan Registry 2, a nationwide registry which enrolled 2408 consecutive patients with LVO who were admitted within 24 h of onset. The patients were classified into anemia (<11 g/dL) and no-anemia (≥11 g/dL) groups according to their hemoglobin level on admission. The primary outcome was defined as a modified Rankin Scale of 0-2 at day 90. RESULTS: Among the 2373 patients with available baseline hemoglobin data, 307 (13.0%) were classified in the anemia group. Anemia was associated with a lower likelihood of the primary outcome (adjusted odds ratio [OR]: 0.68; 95% confidence interval [CI]: 0.47-0.98) and higher mortality within 90 days (adjusted OR: 1.48; 95% CI: 1.01-2.17). Subgroup analyses showed that the likelihood of achieving the primary outcome between the two groups was different between men and women (P for interaction = 0.049), those with Alberta Stroke Program Early CT Score (ASPECTS) <6 and ASPECTS ≥6 (P for interaction = 0.02), and those with National Institute of Health Stroke Scale (NIHSS) ≥16 and NIHSS < 16 (P for interaction = 0.005). CONCLUSIONS: Anemic state on admission was associated with poorer clinical outcomes of LVO in real-world clinical practice. The effects of anemic status were larger in LVO patients with lower NIHSS or higher ASPECTS.

Protonation states of hen egg-white lysozyme observed using D/H contrast neutron crystallography.

Hen egg-white lysozyme (HEWL) is an enzymatic protein with two acidic amino acids, Glu35 and Asp52, in its active site. Glu35 acts as a proton donor to the substrate and Asp52 interacts with the positively charged substrate, suggesting different protonation states of these residues. However, neutron crystallographic studies thus far have not provided a consistent picture of the protonation states of these residues. Only one study succeeded in observing the active protonation states of Glu35 and Asp52 in the triclinic crystal system. However, their active states in the most widely studied tetragonal crystal system are still unknown. The application of the D/H contrast technique in neutron crystallography improves the ability to locate exchangeable D/H atoms in proteins. In the present study, D2O and H2O solvent crystals were prepared. Each neutron data set was collected for only five days by combining a time-of-flight diffractometer (iBIX) and the spallation neutron source at the Japan Proton Accelerator Research Complex. The D/H contrast map provided better visualization of the D/H atoms in HEWL than the conventional neutron scattering length density map. The neutron D/H contrast map demonstrated the alternative protonation of the OE1 and OE2 atoms in the carboxyl group of Glu35. This alternative protonation occurs in the absence of a substrate, where high selectivity of the protonation site does not occur. In this case, only the OE1-HE1 bond attacks the substrate in an equilibrium between OE1-HE1 and OE2-HE2, or the H+ ion of the OE2-HE2 bond moves to the OE1 atom just before or after substrate binding to initiate the catalytic reaction. In contrast, the carboxyl group of Asp52 is not protonated. Protonation of the carboxyl group was not observed for other Asp and Glu residues. These results are consistent with results from NMR spectroscopy and explain the protonation states at the active site in the apo form of HEWL.

The necessity of lumbar puncture in adult emergency patients with fever-associated seizures.

OBJECTIVE: Central nervous system (CNS) infections are often suspected in adult patients with fever-associated seizures. However, it is unclear whether lumbar puncture (LP) is routinely required in patients with fever-associated seizures. This study aimed to examine the prevalence of meningitis and encephalitis in adult patients with fever-associated seizures and to evaluate whether LP is routinely required. METHODS: We retrospectively studied patients aged ≥16 years who presented to the emergency department with complaints of seizures and fever above 37.5 °C who were admitted to the hospital between January 2017 and December 2019. LP was performed when the emergency physician suspected meningitis or encephalitis. Neurologists assessed patients with normal cerebrospinal fluid (CSF) findings and those admitted without LP after hospitalization. A neurologist confirmed the diagnoses of meningitis and encephalitis. RESULTS: The study included 148 patients. Ninety-seven patients (65.5%) were male, and the median age was 60 years. LP was performed in 105 patients (70.9%), and 14 (13.4%) had CSF pleocytosis. Meningitis and encephalitis were diagnosed in nine patients (6.1%), of whom four (2.8%) had CNS infections. Patients diagnosed with meningitis and encephalitis were more likely to have Glasgow Coma Scale <13 (P = 0.03) and less likely to have a history of seizures or epilepsy (P = 0.04) and had higher C-reactive protein levels than the other patients (P = 0.02). CONCLUSION: The prevalence of meningitis or encephalitis is relatively low in adult patients with fever-associated seizures. Lumbar puncture is considered unnecessary to be performed routinely, but its indication should be carefully considered with reference to the clinical course, comorbidities, and blood tests. Further validation studies with larger sample sizes are needed to confirm the findings of this study.

Dynamical Behavior of Disordered Regions in Disease-Related Proteins Revealed by Quasielastic Neutron Scattering.

Background and Objectives: Intrinsically disordered proteins (IDPs) and proteins containing intrinsically disordered regions (IDRs) are known to be involved in various human diseases. Since the IDPs/IDRs are fluctuating between many structural substrates, the dynamical behavior of the disease-related IDPs/IDRs needs to be characterized to elucidate the mechanisms of the pathogenesis of the diseases. As protein motions have a hierarchy ranging from local side-chain motions, through segmental motions of loops or disordered regions, to diffusive motions of entire molecules, segmental motions, as well as local motions, need to be characterized. Materials and Methods: Combined analysis of quasielastic neutron scattering (QENS) spectra with the structural data provides information on both the segmental motions and the local motions of the IDPs/IDRs. Here, this method is applied to re-analyze the QENS spectra of the troponin core domain (Tn-CD), various mutants of which cause the pathogenesis of familial cardiomyopathy (FCM), and α-synuclein (αSyn), amyloid fibril formation of which is closely related to the pathogenesis of Parkinson's disease, collected in the previous studies. The dynamical behavior of wild-type Tn-CD, FCM-related mutant Tn-CD, and αSyn in the different propensity states for fibril formation is characterized. Results: In the Tn-CD, the behavior of the segmental motions is shown to be different between the wild type and the mutant. This difference is likely to arise from changes in the intramolecular interactions, which are suggested to be related to the functional aberration of the mutant Tn-CD. In αSyn, concerted enhancement of the segmental motions and the local motions is observed with an increased propensity for fibril formation, suggesting the importance of these motions in fibril formation. Conclusions: Characterization of the segmental motions as well as the local motions is thus useful for discussing how the changes in dynamical behavior caused by the disease-related mutations and/or environmental changes could be related to the functional and/or behavioral aberrations of these proteins.

Convulsive-like symptoms as initial indications of basilar artery occlusion: A case series study.

BACKGROUND: There is little evidence regarding relevant clinical findings for the early diagnosis of basilar artery occlusion (BAO) in the prehospital setting. We focused on "convulsive-like symptoms", including convulsive seizures and other convulsive-like movements, and examined the frequency and clinical characteristics of patients with BAO having these symptoms as an initial symptom. METHODS: In this single-center case series from 2015 to 2020, we identified patients who underwent endovascular therapy (EVT) for BAO and presented with convulsive-like symptoms between the stroke onset and initiation of emergency medical care. The clinical course and neurological findings were evaluated by reviewing the run sheets of emergency medical services and medical records. RESULTS: Among a total of 32 patients with BAO, 7 (21.9%) developed convulsive-like symptoms before EVT, of whom 6 were men and whose median age was 72 (interquartile range, 69-78) years. These 7 patients had no history of epilepsy or stroke, and the semiology of convulsive-like symptoms was generalized in 6 of them. In only 3 of the 7 cases, emergency medical services could consider the possibility of stroke on scene, and time from hospital arrival to groin puncture was longer in those who were transported without suspicion of stroke. CONCLUSIONS: 21.9% of our patients who underwent EVT for BAO experienced convulsive-like symptoms initially. We should be vigilant in the possibility of BAO when managing the first-time generalized convulsive-like symptoms occurring in older patients, which may enable to adequate triage and better management for patients with acute BAO.

Prehospital stroke notification and endovascular therapy for large vessel occlusion: a retrospective cohort study.

The impact of prehospital notification by emergency medical services (EMS) on outcomes of endovascular therapy (EVT) for large vessel occlusion (LVO) remains unclear. We therefore explored the association between prehospital notification and clinical outcomes after EVT. In this single-center retrospective study from 2016 through 2020, we identified all LVO patients who received EVT. Based on the EMS's usage of a prehospital stroke notification system, we categorized patients into two groups, Hotline and Non-hotline. The primary outcome was good neurological outcome at 90 days; other time metrics were also evaluated. Of all 312 LVO patients, the proportion of good neurological outcomes was 94/218 (43.1%) in the Hotline group and 8/34 (23.5%) in the Non-hotline group (adjusted odds ratio 2.86; 95% confidence interval 1.12 to 7.33). Time from hospital arrival to both tissue plasminogen activator and to groin puncture were shorter in the Hotline group (30 (24 to 38) min vs 48(37 to 65) min, p < 0.001; 40 (32 to 54) min vs 76 (50 to 97) min, p < 0.001), respectively. In conclusion, prehospital notification was associated with a reduction in time from hospital arrival to intervention and improved clinical outcomes in LVO patients treated with EVT.

High-dose immunoglobulin-dependent chronic demyelinating inflammatory polyneuropathy successfully managed with subcutaneous immunoglobulin using pharmacokinetic analysis.

Immunoglobulin G therapy for chronic inflammatory demyelinating polyneuropathy (CIDP) often requires individual dose adjustments because of the heterogeneity of pathogenesis and varying catabolic rates. However, currently available pharmacokinetic studies of immunoglobulin G therapy do not consider individual differences. We conducted a pharmacokinetic study of both intravenous immunoglobulin and subcutaneous immunoglobulin in a single patient with CIDP who was dependent on high-dose immunoglobulin treatment. This patient-a 77-year-old man with symmetrical limb weakness, diffuse demyelination determined by a nerve conduction study, and lacking autoantibodies-was treated with intravenous immunoglobulin and experienced severe fluctuations in symptoms. We transitioned him to subcutaneous immunoglobulin: his serum immunoglobulin G levels stabilised and he experienced symptomatic relief. Monitoring of serum immunoglobulin G concentrations revealed volatile changes following intravenous immunoglobulin administration which stabilised following subcutaneous immunoglobulin treatment. This suggests that subcutaneous immunoglobulin is a preferable long-term treatment option, especially for high-dose immunoglobulin-dependent patients with CIDP.

Impact of prior antiplatelet therapy on outcomes of endovascular therapy for acute ischemic stroke with large vessel occlusion: Sub-analysis of the RESCUE-Japan Registry 2.

BACKGROUND: The impact of prior antiplatelet therapy (APT) on clinical outcomes of endovascular therapy (EVT) for large vessel occlusion (LVO) on clinical outcomes is uncertain. We explored the associations between prior APT and in-hospital and 90-day outcomes in a real-world setting. METHODS AND RESULTS: The RESCUE-Japan Registry 2 is a physician-initiated registry of 2408 consecutive patients with acute LVO admitted to hospital within 24 h of stroke onset. We compared 1281 patients who received EVT with and without APT before stroke onset (APT group and No-APT group) in terms of intracranial hemorrhage (ICH) within 72 h after the onset, successful recanalization after EVT, and the modified Rankin Scale (mRS) score 0-2 at 90 days were also evaluated. Among the 254 patients (19.8%) in the APT group, 68 (27%) patients presented any ICH and 265 (26%) patients in the No-APT group (adjusted odds ratio [OR], 1.04; 95% confidence interval [CI], 0.71-1.53). The incidence of symptomatic ICH and successful recanalization were also similar between the APT and No-APT groups. The adjusted ORs of the APT group for mRS of 0-2 and death were 0.93 (95% CI, 0.62-1.41) and 0.59 (95% CI, 0.3-1.19), respectively. In patients with an onset to door time ≥ 180 min, any ICH tended to be more prevalent in the APT group than in their counterparts (P for interaction = 0.008). CONCLUSIONS: The risk of ICH after EVT was not different between patients with and without APT before EVT for acute LVO.

Clinical Impact of Large Vessel Occlusion Achieved First Pass Effect with Stent Retriever Alone: A Single-Center Retrospective Analysis.

Objective: The first pass effect (FPE), which means the achievement of complete or near-complete reperfusion of large vessel occlusion (LVO) in the first pass, is one of the goals of mechanical thrombectomy (MT). However, the impact of FPE on the prognosis has not been assessed for Japanese patients with various degrees of independence before the onset of LVO. The purpose of this study was to investigate the prognostic effects of FPE in a comprehensive stroke center in Japan, which includes patients in a variety of self-independence states with different comorbidities before stroke onset. Methods: Between April 2017 and March 2020, 151 patients who underwent MT with a stent retriever (SR) alone as initial strategy for anterior circulation (internal carotid artery terminal, M1, M2) LVO at our hospital and finally achieved modified treatment in cerebral infarction (mTICI) 2b-3 were analyzed. Forty-eight patients in whom first pass mTICI 2c-3 was achieved were classified into the FPE+ group, and the other 103 patients were classified into the FPE- group. We compared the characteristics and clinical outcomes between patients with and without FPE, and estimated the odds ratio for outcomes after adjusting for confounders. Results: The puncture-reperfusion time was shorter (20 vs. 35 minutes; p <0.01), and cardiogenic embolism was more common (81.3 vs. 60.2%; p = 0.01) in the FPE+ group. The FPE was significantly associated with good neurological outcome after 3 months (p <0.01; adjusted odds ratio [aOR], 3.87; 95% confidence interval [CI], 1.69-9.38), reduction in all intracranial hemorrhage (p <0.01; aOR, 0.24; 95% CI, 0.10-0.54), and symptomatic intracranial hemorrhage (p = 0.04; aOR, 0.16; 95% CI, 0.01-0.98). Conclusion: The FPE with an SR alone improved the neurological prognosis in a Japanese patient group.

Post COVID-19 Bilateral Facial Nerve Palsy.

Coronavirus disease 2019 (COVID-19) patients have been increasingly reported to develop various neurological manifestations. We herein present a rare case of bilateral facial nerve palsy in a patient that occurred 5 weeks after the onset of COVID-19. The patient had no motor or sensory deficits in his extremities, and there were no other diseases that may have resulted in bilateral facial palsy. Based on these findings, we concluded that the facial palsy in this case may have been triggered by COVID-19.

[Biopsy-proven autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy with characteristic image findings: a case report].

A 53-year-old woman was admitted to the hospital because she developed headache and malaise 3 months prior to her arrival, followed by gait disturbance, abnormal behavior, and hallucinations. On admission, she was stupor and showed left hemispatial neglect, and brain MRI showed extensive FLAIR high-signal lesions with contrast enhancement in the bilateral periventricular white matter, and CSF examination showed pleocytosis and elevated protein. A stereotactic brain biopsy was performed from the right temporal lobe lesion, and pathological findings demonstrated a perivascular inflammatory cell infiltrate. After the administration of intravenous methylprednisolone followed by oral prednisolone, she recovered almost completely within three months and the abnormal MRI findings disappeared. Anti-glial fibrillary acidic protein (GFAP) antibody in the cerebrospinal fluid turned out to be positive, then the diagnosis of autoimmune GFAP astrocytopathy was made. Reports of this disease are still rare, and we report this case because of its slowly progressive course and pathological evaluation by brain biopsy.

Isolated progression of miliary brain metastasis in a patient with stable lung adenocarcinoma successfully treated with whole-brain radiotherapy: A case report.

Miliary brain metastasis is a rare form of metastasis commonly associated with advanced stages of cancer. In this article, we report a case of a 38-year-old male with solitary progression of miliary brain metastasis originating from stage 4 EML-ALK-positive lung adenocarcinoma. Multiple brain lesions were first detected upon the patient's inclusion in a brigatinib clinical trial. The brain lesions dissipated, and the lung and bone lesions decreased in size after starting the brigatinib therapy; however, the brain lesions later increased in number. A biopsy revealed miliary brain metastasis of lung adenocarcinoma. The patient was successfully treated with whole brain therapy, in addition to brigatinib. This case suggests that it is possible for an isolated miliary brain metastasis to occur during the effective suppression of systemic cancer progression. Whole brain radiotherapy while continuing effective systemic therapy is a good strategy for such patients.