Takotsubo cardiomyopathy in Guillain-Barré syndrome.

BACKGROUND AND PURPOSE: Takotsubo cardiomyopathy (TCM) is a serious autonomic complication of Guillain-Barré syndrome (GBS). However, the association between TCM and GBS has not been investigated in detail. We investigated the characteristics of GBS patients with TCM (GBS-TCM). METHODS: Clinical features and anti-ganglioside antibody between the GBS-TCM patients and 62 classical GBS patients without TCM as control patients were compared. RESULTS: Eight GBS-TCM patients were identified, in whom TCM was diagnosed at a mean of 6.5 [range 3-42] days after the onset of GBS. The age at onset of GBS was elder in the GBS-TCM patients than in the control GBS patients (76.5 [56-87] vs. 52 [20-88] years, p < 0.01). Notably, cranial nerve deficits, particularly in the lower cranial nerves, were observed in all GBS-TCM patients (100% vs. 41.9%, p < 0.01). Additionally, the GBS-TCM patients showed a higher GBS disability score at nadir (5 [4-5] vs. 4 [1-5], p < 0.01), and lower Medical Research Council sum scores at admission and nadir (37 [30-44] vs. 48 [12-60] at admission, p < 0.05, and 20 [12-44] vs. 40 [0-60] at nadir, p < 0.05, respectively). Mechanical ventilation was more frequently required in the GBS-TCM patients (62.5% vs. 11.3%, p < 0.01). Three GBS-TCM patients were positive for anti-ganglioside antibodies. CONCLUSIONS: TCM occurred at a relatively early phase of GBS. The characteristics of GBS-TCM were the elder, lower cranial nerve involvements, severe limb weakness, and respiratory failure.

Association of thyroid peroxidase antibody with the RNF213 p.R4810K variant in ischemic stroke/transient ischemic attack.

BACKGROUND AND AIMS: RNF213 is a susceptibility gene for moyamoya disease and vasospastic angina, with a second hit considered necessary for their development. Elevated thyroid peroxidase antibody (TPO-Ab) levels have been observed in both diseases, suggesting a possible role of TPO-Ab as a second hit for developing RNF213-related vasculopathy. We investigated the association of TPO-Ab levels with RNF213-related ischemic stroke (IS)/transient ischemic attack (TIA), other than moyamoya disease. METHODS: From the National Cerebral and Cardiovascular Center Genome Registry, a multicenter, prospective, observational study, we enrolled patients with IS/TIA who were admitted within 1 week of onset. Patients with IS/TIA due to definite moyamoya disease or hemorrhagic stroke were excluded. Participants underwent genotyping for RNF213 p. R4810K, and baseline characteristics and TPO-Ab levels were compared between RNF213 p. R4810K variant carriers and non-carriers. RESULTS: In total, 2090 IS/TIA patients were analyzed [733 women (35.1%); median age 74 (interquartile range, 63-81) years, baseline NIHSS score 3 (2-6)], and 85 (4.1%) of them carried the variant. Median TPO-Ab levels were significantly higher in variant carriers (8.5 IU/mL vs. 2.1 IU/mL, p < 0.01), who also showed a higher frequency of elevated TPO-Ab levels (>16 IU/mL) (27.1% vs. 4.4%). In the multivariate analysis, presence of the RNF213 p. R4810K variant (adjusted odds ratio, 12.42; 95% confidential interval, 6.23-24.75) was significantly associated with elevated TPO-Ab levels. CONCLUSIONS: Elevated TPO-Ab levels may be significantly associated with presence of the RNF213 p. R4810K variant in IS/TIA patients. Thus, TPO-Ab may inherently modify IS/TIA development in RNF213 p. R4810K variant carriers.

[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.

Successful treatment with subcutaneous ofatumumab in an adolescent patient with refractory myelin oligodendrocyte glycoprotein-immunoglobulin G-associated disease (MOGAD).

Preventing relapse of myelin oligodendrocyte glycoprotein-immunoglobulin G-associated disease (MOGAD) with steroids and immunosuppressants is sometimes difficult. There is no standard treatment for refractory cases. We present the case of a 17-year-old female patient with longitudinally extensive myelitis, asymptomatic bilateral optic neuritis, and positive serum MOG-IgG. While taking steroids and several immunosuppressants during the following 14 months, she suffered from two symptomatic relapses in the cerebrum and spinal cord, and multiple asymptomatic relapses in the cerebrum. The patient was negative for MOG-IgG at the second relapse of myelitis. Subcutaneous ofatumumab has suppressed relapse for 13 months. Ofatumumab can be considered a therapeutic option for refractory MOGAD.

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.

Circulating plasmablasts and follicular helper T-cell subsets are associated with antibody-positive autoimmune epilepsy.

Autoimmune epilepsy (AE) is an inflammatory disease of the central nervous system with symptoms that have seizures that are refractory to antiepileptic drugs. Since the diagnosis of AE tends to rely on a limited number of anti-neuronal antibody tests, a more comprehensive analysis of the immune background could achieve better diagnostic accuracy. This study aimed to compare the characteristics of anti-neuronal antibody-positive autoimmune epilepsy (AE/Ab(+)) and antibody-negative suspected autoimmune epilepsy (AE/Ab(-)) groups. A total of 23 patients who met the diagnostic criteria for autoimmune encephalitis with seizures and 11 healthy controls (HC) were enrolled. All patients were comprehensively analyzed for anti-neuronal antibodies; 13 patients were identified in the AE/Ab(+) group and 10 in the AE/Ab(-) group. Differences in clinical characteristics, including laboratory and imaging findings, were evaluated between the groups. In addition, the immunophenotype of peripheral blood mononuclear cells (PBMCs) and CSF mononuclear cells, particularly B cells and circulating Tfh (cTfh) subsets, and multiplex assays of serum and CSF were analyzed using flow cytometry. Patients with AE/Ab(+) did not show any differences in clinical parameters compared to patients with AE/Ab(-). However, the frequency of plasmablasts within PBMCs and CSF in patients with AE/Ab(+) was higher than that in patients with AE/Ab(-) and HC, and the frequency of cTfh17 cells and inducible T-cell co-stimulator (ICOS) expressing cTfh17 cells within cTfh subsets was higher than that in patients with AE/Ab(-). Furthermore, the frequency of ICOShighcTfh17 cells was positively correlated with that of the unswitched memory B cells. We also found that IL-12, IL-23, IL-6, IL-17A, and IFN-γ levels were elevated in the serum and IL-17A and IL-6 levels were elevated in the CSF of patients with AE/Ab(+). Our findings indicate that patients with AE/Ab(+) showed increased differentiation of B cells and cTfh subsets associated with antibody production. The elevated frequency of plasmablasts and ICOS expressing cTfh17 shift in PBMCs may be indicative of the presence of antibodies in patients with AE.

Discrepancy between distribution of alpha-synuclein oligomers and Lewy-related pathology in Parkinson's disease.

The pathological hallmarks of Parkinson's disease (PD) are α-synuclein (αSYN)-positive inclusions referred to as Lewy bodies and Lewy neurites, collectively referred to as Lewy-related pathology (LRP). LRP is thought to propagate in an ascending manner throughout the brain as the disease progresses. LRP is visible with histologic methods and is thought to represent a later stage of the disease process, while αSYN oligomers, which are not visible with routine histologic methods, are considered earlier. There is increasing evidence to suggest that αSYN oligomers may be more toxic than visible LRP. Detecting αSYN oligomers requires special techniques, and their distribution and association with clinical features are important research objectives. In this report, we describe the distribution of αSYN oligomers in multiple cortical and subcortical regions of PD using a proximity ligation assay (PLA). We observe widespread distribution of αSYN oligomers with PLA and more restricted distribution of LRP with αSYN immunohistochemistry. The distribution of αSYN oligomers differed from LRP in that αSYN oligomer burden was significantly greater in the neocortex, while LRP was greater in vulnerable subcortical regions, including the brainstem. We also found that cognitive impairment was associated with αSYN oligomers in the hippocampus. These results suggest that αSYN oligomers may be widely distributed in PD early in the disease process and that they may contribute to cognitive impairment in PD.

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.

Cervical cord lesions in Wernicke's encephalopathy.

A 30-year-old woman suffering from an eating disorder and alcoholism presented with a progressively worsening gait disturbance lasting 2 weeks. Her neurological findings included impaired ocular motility and trunk ataxia. Fluid-attenuated inversion recovery imaging of the brain showed hyperintensity in the dorsal brainstem, aqueduct, thalamus, and cerebral cortex. A long hyperintense segment on T2-weighted imaging was visible in the central gray matter of the cervical spinal cord. No restricted diffusion was observed; thus, T2 elongation in the spine was suggested to be due to vasogenic edema. We diagnosed the patient with Wernicke's encephalopathy and initiated vitamin supplementation. Thereafter, her symptoms rapidly improved; magnetic resonance imaging on the 11th day of hospitalization showed normalization of the signals in her brain and spinal cord. As our case demonstrates, Wernicke's encephalopathy can induce vasogenic edema of the spinal cord, which can rapidly improve with early therapeutic intervention.

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 Seizure Recurrence on 1-Year Functional Outcome and Mortality in Patients With Poststroke Epilepsy.

BACKGROUND AND OBJECTIVES: The functional outcome and mortality of patients with poststroke epilepsy (PSE) have not been assessed in a prospective study. Previous reports have suggested that patients with PSE may suffer from prolonged functional deterioration after a seizure. In this study, we prospectively investigated the functional outcome and mortality of patients with PSE and analyzed the effect of seizure recurrence on the outcomes. METHODS: This is part of the Prognosis of Post-Stroke Epilepsy study, a multicenter, prospective observational cohort study, where 392 patients with PSE (at least 1 unprovoked seizure more than 7 days after the onset of the last symptomatic stroke) were followed for at least 1 year at 8 hospitals in Japan. This study included only PSE patients with a first-ever seizure and assessed their functional decline and mortality at 1 year. Functional decline was defined as an increase in modified Rankin Scale (mRS) score at 1 year compared with baseline, excluding death. The associations between the seizure recurrence and the outcomes were analyzed statistically. RESULTS: A total of 211 patients (median age of 75 years; median mRS score of 3) were identified. At 1 year, 50 patients (23.7%) experienced seizure recurrence. Regarding outcomes, 25 patients (11.8%) demonstrated functional decline and 20 (9.5%) had died. Most patients died of pneumonia or cardiac disease (7 patients each), and no known causes of death were directly related to recurrent seizures. Seizure recurrence was significantly associated with functional decline (odds ratio [OR] 2.96, 95% CI 1.25-7.03, p = 0.01), even after adjusting for potential confounders (adjusted OR 3.26, 95% CI 1.27-8.36, p = 0.01), but not with mortality (OR 0.79, 95% CI 0.25-2.48, p = 0.68). Moreover, there was a significant trend where patients with more recurrent seizures were more likely to have functional decline (8.7%, 20.6%, and 28.6% in none, 1, and 2 or more recurrent seizures, respectively; p = 0.006). DISCUSSION: One-year functional outcome and mortality of patients with PSE were poor. Seizure recurrence was significantly associated with functional outcome, but not with mortality. Further studies are needed to ascertain whether early and adequate antiseizure treatment can prevent the functional deterioration of patients with PSE.

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.