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.

Extensive leukoencephalopathy associated with idiopathic capillary leak syndrome: report of a case with neuropathology.

INTRODUCTION: Idiopathic systemic capillary leak syndrome (ISCLS) is a rare cryptogenic disorder characterized by recurrent hemoconcentration, hypoalbuminemia, edema, and hypotension due to extravascular fluid leakage. This is the first report that details uncommon extensive leukoencephalopathy caused by ISCLS upon a neuropathological investigation. CASE REPORT: A 68-year-old female had recurrent episodes of hemoconcentration, hypoalbuminemia, and generalized edema and was diagnosed with ISCLS. After 9 years, brain magnetic resonance imaging (MRI) incidentally revealed extensive leukoencephalopathy without neurological deficits. Thorough examinations ruled out other disorders, and the cerebral involvement due to ISCLS was finally diagnosed. Three years later, she developed an acute-onset coma and status epilepticus together with hypotension and hemoconcentration, which were compatible with ISCLS recurrence. Electroencephalogram and MRI were correlated with a seizure arising from the left hemisphere. Extensive leukoencephalopathy did not show notable changes for 3 years. Although treatment for ISCLS recurrence temporally improved hemoconcentration and consciousness, consciousness worsened again by marked edema of the left hemisphere, and she died of cerebral herniation. A brain autopsy revealed straggly perivascular plasma leakage around the small vessels of the deep white matter, which supported that the leukoencephalopathy was caused by ISCLS. Widespread myelin pallor and decreased axonal density with sparse astrogliosis and microgliosis were observed in the cerebral white matter and corresponded with a chronic change in the MRI. CONCLUSION: Current radiological and pathological observations revealed that frequent perivascular leakages could cause chronic leukoencephalopathy, were linked with the development of systemic capillary leakage in ISCLS, and provided insights into the mysterious pathophysiology.

Serial Radiological Findings in Meningovascular Neurosyphilis Presenting as Acute Ischemic Stroke: A Case Report.

BACKGROUND: Meningovascular neurosyphilis, a form of early neurosyphilis, can cause infectious arteritis, which can be complicated by cerebral infarction. High-resolution vessel wall imaging (HR-VWI) is one of the techniques used to directly visualize the vessel wall. Herein, we present a rare case of meningovascular neurosyphilis, in which intracranial arterial vasculitis was evaluated using HR-VWI. CASE PRESENTATION: A 22-year-old man with no medical history of any condition was brought to the emergency room with one day history of right upper and lower extremity weakness. Diffusion-weighted magnetic resonance (MR) imaging showed a high signal from the left putamen to the corona radiata, and MR angiography showed stenosis of the right internal carotid artery (ICA) and the bilateral middle cerebral arteries (MCAs). HR-VWI showed thickening, along with smooth, intense, and concentric enhancement of the right ICA and the bilateral MCAs. The patient was diagnosed with neurosyphilis based on the findings of the blood tests and cerebrospinal fluid examination. The patient's symptoms gradually improved after treatment with intravenous penicillin G and oral antiplatelet agents. HR-VWI, performed approximately 6 months after the treatment, revealed improvement in the contrast enhancement of the vessel wall and the vascular stenosis. CONCLUSION: To the best of our knowledge, this is the first report of meningovascular neurosyphilis that evaluated the course of treatment using HR-VWI. Our report highlights the effectiveness of HR-VWI to determine the effects of treatment on meningovascular neurosyphilis.

Anti-Ma-associated paraneoplastic cerebellar degeneration in a patient with nodular lymphocyte-predominant Hodgkin lymphoma: a case report.

BACKGROUND: Paraneoplastic cerebellar degeneration (PCD) is a devastating paraneoplastic syndrome that occasionally occurs in patients with Hodgkin lymphoma (HL). Anti-Ma2 is a well-characterized onconeuronal antibody and one of the causes of PCD. There has been only one previous report of anti-Ma2-associated paraneoplastic syndrome as a complication of HL. Here we present a rare case of anti-Ma2-associated PCD in a patient with nodular lymphocyte-predominant HL (NLPHL). CASE PRESENTATION: A 77-year-old man with a 3-month history of gait instability and a 2-month history of oscillopsia was referred to our hospital for further investigation. On examination, his cognition was normal. He had nystagmus in all directions of gaze; specifically, he had horizontal and rotatory nystagmus in the primary position, downbeat nystagmus after right, left, and up gaze, and upbeat nystagmus after down gaze. Although his limb ataxia was mild, his trunk ataxia was so pronounced that he was unable to walk without support. We strongly suspected paraneoplastic syndrome and tested for neuronal autoantibodies. The anti-Ma2 antibody was strongly positive in the blood and cerebrospinal fluid but other antineuronal autoantibodies were negative. Computed tomography showed an enlarged lymph node in the right axilla but no masses. Biopsy confirmed a diagnosis of NLPHL. The NLPHL cells stained with anti-Ma-2 antibody in the cytoplasm, suggesting these abnormal cells contained protein that was cross-reactive with Ma-2. CONCLUSIONS: To the best of our knowledge, this is the first case of anti-Ma2-associated PCD in a patient with NLPHL that was confirmed using immunostaining of the lymph node tissue with anti-Ma2 antibody. Our case confirms an association between anti-Ma2-associated PCD and NLPHL.

Stroke Systems of Care During the COVID-19 Epidemic in Kobe City.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) outbreak raised concerns over healthcare systems' ability to provide suitable care to stroke patients. In the present study, we examined the provision of stroke care in Kobe City during the COVID-19 epidemic, where some major stroke centers ceased to provide emergency care. METHODS: This was a cross-sectional study. The Kobe Stroke Network surveyed the number of stroke patients admitted to all primary stroke centers (PSCs) in the city between March 1 and May 23, 2020, and between March 3 and May 25, 2019. In addition, online meetings between all PSC directors were held regularly to share information. The survey items included emergency response system characteristics, number of patients with stroke hospitalized within 7 days of onset, administered treatment types (IV rt-PA, mechanical thrombectomy, surgery, and endovascular therapy), and stroke patients with confirmed COVID-19. RESULTS: During the period of interest in 2020, the number of stroke patients hospitalized across 13 PSCs was 813, which was 15.5% lower than that during the same period of 2019 (p = 0.285). The number of patients admitted with cerebral infarction, intracerebral hemorrhage, and subarachnoid hemorrhage decreased by 15.4% (p = 0.245), 16.1% (p = 0.659), and 14.0% (p = 0.715), respectively. However, the rates of mechanical thrombectomy and surgery for intracerebral hemorrhage were slightly increased by 12.1% (p = 0.754) and 5.0% (p = 0.538), respectively. PSCs that ceased to provide emergency care reported a decrease in the number of stroke cases of 65.7% compared with the same period in 2019, while other PSCs reported an increase of 0.8%. No case of a patient with stroke and confirmed COVID-19 was reported during the study period. CONCLUSION: Kobe City was able to maintain operation of its stroke care systems thanks to close cooperation among all city PSCs and a temporal decrease in the total number of stroke cases.

Successful Reperfusion with Endovascular Therapy Has Beneficial Effects on Long-Term Outcome Beyond 90 Days.

BACKGROUND AND PURPOSE: Recent studies have demonstrated that endovascular reperfusion therapy improves clinical outcomes at 90 days after ischemic stroke. However, the effects on long-term outcomes are not well known. We hypothesized that successful reperfusion might be associated with long-term improvement beyond 90 days after endovascular therapy. To assess the long-term effects beyond 90 days, we analyzed the association of successful reperfusion with a temporal change in modified Rankin Scale (mRS) score from 90 days to 1 year after endovascular therapy. METHODS: We retrospectively analyzed a database of consecutive patients with acute ischemic stroke who received endovascular therapy between April 2006 and March 2016 at 4 centers. We compared the incidences of improvement and deterioration in patients with successful reperfusion (i.e., modified thrombolysis in cerebral infarction score of 2b or 3) with those in patients with unsuccessful reperfusion. We defined improvement and deterioration as decrease and increase on the mRS score by 1 point or more from 90 days to 1 year after endovascular therapy respectively. RESULTS: A total of 268 patients were included in the current study. The rate of patients with improvement tended to be higher in patients with successful reperfusion than in patients with unsuccessful reperfusion (20% [34/167 patients] vs. 12% [12/101], p = 0.07). The rate of patients with deterioration was lower in patients with successful reperfusion than in patients with unsuccessful reperfusion (25% [42/167] vs. 42% [42/101], p < 0.01). After adjustment for confounders, successful reperfusion was associated with improvement (adjusted OR 2.65; 95% CI 1.23-5.73; p < 0.05) and deterioration (adjusted OR 0.33; 95% CI 0.18-0.62; p < 0.01), independent of the 90-day mRS score. CONCLUSIONS: Successful reperfusion has further beneficial legacy effects on long-term outcomes beyond 90 days after stroke.

Improving detection of JC virus by ultrafiltration of cerebrospinal fluid before polymerase chain reaction for the diagnosis of progressive multifocal leukoencephalopathy.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a demyelinating disorder caused by JC virus (JCV). Although detecting JCV DNA in the cerebrospinal fluid (CSF) by real-time polymerase chain reaction (PCR) is useful, diagnosis is difficult when JCV concentrations are low. We therefore aimed to lower the detection limit of real-time PCR testing by enriching JCV in the CSF via ultrafiltration. METHODS: Virus suspensions and CSF specimens from 20 untreated patients with suspected PML were collected and total DNAs were extracted. The JCV large T gene was detected by quantitative real-time PCR under condition with and without prior centrifugal ultrafiltration. RESULTS: The JCV DNA was reliably detected to a lower limit of 10 copies/mL of virus suspension by real-time PCR with ultrafiltration. When using this method, the quantity of JCV DNA per PCR reaction increased 3.2- to 8.7-fold compared with the standard procedure. Seven patients were positive for JCV when using the standard procedure, and an additional patient was positive when using ultrafiltration. All JCV-positive patients had neurological features and magnetic resonance imaging findings compatible with PML. CONCLUSIONS: The detection limit of JCV DNA by real-time PCR can be lowered by viral enrichment using ultrafiltration. Our simple protocol offers a valuable tool for PML diagnosis when extremely low copy numbers of JCV are released into the CSF or when brain biopsy is not feasible.

Clinicopathological features of adult-onset neuronal intranuclear inclusion disease.

Neuronal intranuclear inclusion disease (NIID) is a slowly progressive neurodegenerative disease characterized by eosinophilic hyaline intranuclear inclusions in the central and peripheral nervous system, and also in the visceral organs. NIID has been considered to be a heterogeneous disease because of the highly variable clinical manifestations, and ante-mortem diagnosis has been difficult. However, since we reported the usefulness of skin biopsy for the diagnosis of NIID, the number of NIID diagnoses has increased, in particular adult-onset NIID. In this study, we studied 57 cases of adult-onset NIID and described their clinical and pathological features. We analysed both NIID cases diagnosed by post-mortem dissection and by ante-mortem skin biopsy based on the presence of characteristic eosinophilic, hyaline and ubiquitin-positive intanuclear inclusion: 38 sporadic cases and 19 familial cases, from six families. In the sporadic NIID cases with onset age from 51 to 76, dementia was the most prominent initial symptom (94.7%) as designated 'dementia dominant group', followed by miosis, ataxia and unconsciousness. Muscle weakness and sensory disturbance were also observed. It was observed that, in familial NIID cases with onset age less than 40 years, muscle weakness was seen most frequently (100%), as designated 'limb weakness group', followed by sensory disturbance, miosis, bladder dysfunction, and dementia. In familial cases with more than 40 years of onset age, dementia was most prominent (100%). Elevated cerebrospinal fluid protein and abnormal nerve conduction were frequently observed in both sporadic and familial NIID cases. Head magnetic resonance imaging showed high intensity signal in corticomedullary junction in diffusion-weighted image in both sporadic and familial NIID cases, a strong clue to the diagnosis. All of the dementia dominant cases presented with this type of leukoencephalopathy on head magnetic resonance imaging. Both sporadic and familial NIID cases presented with a decline in Mini-Mental State Examination and Frontal Assessment Battery scores. Based on these clinicopathological features, we proposed a diagnosis flow chart of adult-onset NIID. Our study suggested that the prevalence rate of adult-onset NIID may be higher than previously thought, and that NIID may be underdiagnosed. We should take NIID into account for differential diagnosis of leukoencephalopathy and neuropathy.

[Cryptococcus Neoformans Var. Gattii meningoencephalitis with cryptococcoma in an immunocompetent patient successfully treated by surgical resection].

Cryptococcosis is a fungal infection, which mainly invades the lungs and central nervous system. In Japan, most cases of cryptococcosis are caused by Cryptococcus neoformans(C. neoformans). Until now, only three cases which the infectious agent was Cryptococcus neoformans var. gattii(C. gattii)have been reported. As compared with cryptococcosis caused by C. neoformans, which is often observed in immunocompromised hosts, cryptococcosis caused by C. gattii occurs predominantly in immunocompetent hosts and is resistant to antifungal drugs. Here, we report a case of refractory cerebral cryptococcoma that was successfully treated by surgical resection of the lesions. A 33-year-old man with no medical history complained of headache, hearing disturbance, and irritability. Pulmonary CT showed a nodular lesion in the left lung. Cerebrospinal fluid examination with Indian ink indicated cryptococcal meningitis, and PCR confirmed infection with C. gattii. C. gattii is usually seen in the tropics and subtropics. Since this patient imported trees and soils from abroad to feed stag beetles, parasite or fungal infection was, as such, suspected. Although he received 2 years of intravenous and intraventricular antifungal treatment, brain cryptococcomas were formed and gradually increased. Because of the refractory clinical course, the patient underwent surgical resection of the cerebral lesions. With continuation of antifungal drugs for 6 months after the surgeries, Cryptococcus could not be cultured from cerebrospinal fluid, and no lesions were seen on MR images. If cerebral cryptococcosis responds poorly to antifungal agents, surgical treatment of the cerebral lesion should be considered.

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.

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.

[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.

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.

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.

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.

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.