Stroke treatment during the COVID-19 pandemic.

Studies have reported that COVID-19 is associated not only with pneumonia but also with cerebrovascular disease. Consequently, medical personnel involved in treating stroke in the emergency medicine setting have been placed in a situation that requires them to provide treatment while always remaining mindful of the possibility of COVID-19. Here, we describe the current state of stroke treatment during the COVID-19 pandemic. Four patients with stroke and concomitant COVID-19 were treated at our facility. We treated 3 patients with cerebral infarction and 1 patient with cerebral venous sinus thrombosis. All 3 patients with cerebral infarction had a poor outcome. This was attributed in part to the poor general condition of the patients due to concomitant COVID-19, as well as to the severity of the major artery occlusion and cerebral infarction. One patient with cerebral venous sinus thrombosis had a good outcome. Anticoagulant therapy was administered at our hospital and resulted in a stable clinical course. Our hospital has worked to establish an examination and treatment system that enables mechanical thrombectomy to be performed even during the COVID-19 pandemic. We devised a protocol showing the steps to be taken from initial treatment to admission to the cerebral angiography room. Our hospital was able to continue accepting requests for emergency admission thanks to the examination and treatment system we established. Up-to-date information should continue to be collected to create examination and treatment systems.

An Autopsy Report of a Case with Cerebral Infarction Complicated by Coronavirus Disease 2019 Infection.

We herein report a case of cerebral infarct in a patient with coronavirus disease 2019 (COVID-19) infection who died of aspiration pneumonia. The postmortem examination of the brain revealed embolic infarct with negative findings on quantitative reverse transcription polymerase chain reaction (qRT-PCR) as well as immunohistochemistry to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The systemic examination only revealed low copy numbers of SARS-CoV-2 in the bronchus. This is the first and so far only autopsy case of COVID-19 infection with pathologic and virologic findings of the postmortem brain in Japan.

Left Hemiplegia Possibly Due to Glucose Reperfusion Injury after Recovery of Severe Hypoglycemia in a Woman with Type 2 Diabetes Mellitus.

A 79-year-old woman with type 2 diabetes receiving insulin was rushed to our hospital due to severe hypoglycemia. Glucose was administered, and the consciousness disturbance was promptly improved. A few hours later, conjugate deviation of the eyes to the right and left hemiplegia occurred at a normal glucose level. Cerebral magnetic resonance imaging (MRI) showed hyperintensities of the right posterior limb of the internal capsule and the medial thalamus on diffusion-weighted imaging sequences. However, the changes observed using MRI disappeared completely on the third day, and her symptoms subsequently improved. This may have been a case of glucose reperfusion injury.

Cerebrospinal fluid analysis is associated with enhancement on MRI in bacterial and tuberculous meningitis: A retrospective observational study.

OBJECTIVE: Along with cerebrospinal fluid (CSF) analysis, enhancement on contrast-enhanced MRI is useful to diagnose meningitis. However, the conditions for its appearance have not been clarified. This study aimed to investigate the association between CSF parameters and enhancement on contrast-enhanced head or spinal MRI in patients with bacterial meningitis (BM) or tuberculous meningitis (TM). METHODS: A total of 12 patients with BM and 23 patients with TM who underwent both CSF analysis and contrast-enhanced MRI were included. The correlation between CSF analysis and MRI findings has been examined using receiver operating characteristic (ROC) analysis. RESULTS: Contrast enhancement was found in 7 and 10 patients with BM and TM, respectively. Both CSF analysis and MRI were useful to distinct between BM and TM, and the enhancement implied the severity of them. In patients with BM, higher CSF protein and lower CSF glucose were associated with enhancement on MRI, while not only CSF protein and glucose but also leukocyte and lymphocyte counts were associated with it in TM. CSF adenosine deaminase (ADA) did not show discriminant ability of the MRI findings. CONCLUSIONS: CSF analysis is associated with enhancement on contrast-enhanced MRI both in BM and TM. Our findings indicate the importance of CSF analysis in assessing the need to perform contrast-enhanced MRI, which may be useful in diagnosis, distinction, and estimation of prognosis in those patients.

Alanine transaminase is predominantly increased in the active phase of anti-HMGCR myopathy.

Autoantibodies against 3­hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and the signal recognition particle (SRP) are representative antibodies causing immune-mediated necrotizing myopathies (IMNM), called as anti-HMGCR and anti-SRP myopathies, respectively. Here, we analyzed the differences in routine blood test results between 56 anti-HMGCR and 77 anti-SRP myopathy patients. A higher alanine transaminase (ALT) level and a lower aspartate transaminase (AST)/ALT ratio were observed in anti-HMGCR myopathy patients [ALT, 265.7 ±â€¯213.3 U/L (mean ± standard deviation); AST/ALT ratio, 0.88 ±â€¯0.32] than in anti-SRP-myopathy patients (ALT, 179.3 ±â€¯111.2 U/L, p < 0.05; AST/ALT ratio, 1.28 ±â€¯0.40, p < 0.01). In the active phase, anti-HMGCR myopathy often showed ALT predominance, whereas anti-SRP myopathy often showed AST predominance. In addition, there were differences in erythrocyte sedimentation rate (ESR), total cholesterol (TChol) level, and high-density lipoprotein (HDL) level between anti-HMGCR and anti-SRP myopathies (ESR: HMGCR, 24.4 ±â€¯20.8 mm/1 h; SRP, 35.7 ±â€¯26.7 mm/1 h, p = 0.0334; TChol: HMGCR, 226.7 ±â€¯36.6 mg/dL; SRP, 207.6 ±â€¯40.8 mg/dL, p = 0.0163; HDL: HMGCR, 58.4 ±â€¯13.9 mg/dL; SRP, 46.2 ±â€¯17.3 mg/dL, p < 0.01). Additional studies on the differences in routine blood test results may further reveal the pathomechanisms of IMNM.

Status epilepticus severity score as a predictor for the length of stay at hospital for acute-phase treatment in convulsive status epilepticus.

To date, hospital length of stay (LOS) determinants for convulsive status epilepticus's (CSE) acute-phase treatment have not been sufficiently investigated, as opposed to those for status epilepticus's (SE) outcome predictors, such as status epilepticus severity score (STESS). Here, we aimed at assessing the significance of STESS in the LOS in patients with CSE. We retrospectively reviewed consecutive adult patients with CSE who were transported to the emergency department of our urban tertiary care hospital in Tokyo, Japan. The study period was from August 2010 to September 2015. The primary endpoint was the LOS of patients with CSE who were directly discharged after acute-phase treatment, and survival analysis for LOS until discharge was conducted. As a result, among 132 eligible patients with CSE admitted to our hospital, 96 (72.7%) were directly discharged with a median LOS of 10 days (IQR: 4-19 days). CSE patients with severe seizures, represented by higher STESS (≥3), had a significantly longer LOS after adjustments with multiple covariates (p = 0.016, in restricted mean survival time analysis). Additionally, prediction for the binomial longer/shorter LOS achieved better performance when STESS was incorporated into the prediction model. Our findings indicate that STESS can also be used as a rough predictor of longer LOS at index admission of patients with CSE.

Anti-myelin oligodendrocyte glycoprotein antibody-positive acute disseminated encephalomyelitis mimicking limbic encephalitis: A case report.

Anti-myelin oligodendrocyte glycoprotein antibodies (MOG-ab) have been detected in various disorders of the central nervous system including acute disseminated encephalomyelitis (ADEM), neuromyelitis optica spectrum disorders (NMOSD), optic neuritis, myelitis, and cortical encephalitis. We report an atypical case of MOG-ab-associated encephalomyelitis with part of the clinical manifestations resembling limbic encephalitis. Multifocal, hyperintense, bilateral lesions predominantly affecting the white matter on brain magnetic resonance imaging and marked response to steroid therapy were compatible with a MOG-ab-associated disease. This case illustrates that MOG-ab-associated disease should be considered in encephalomyelitis involving the bilateral limbic system.

A favorable outcome of intensive immunotherapies for new-onset refractory status epilepticus (NORSE).

BACKGROUND: New-onset refractory status epilepticus (NORSE) is a newly defined critical disease entity characterized by prolonged periods of refractory epileptic seizure with no readily identifiable cause in otherwise healthy individuals. Its etiology is uncertain, but autoimmune encephalitis is a possible candidate for the underlying cause of this condition. Immunotherapies could be considered for this condition, but its efficacy is not established. CASE PRESENTATION: A 31-year-old man with no prior history presented with refractory status epilepticus. His seizure persisted even with multiple anti-epileptic drugs and required prolonged general anesthesia under mechanical ventilation. Magnetic resonance imaging and cerebrospinal fluid did not indicate the cause of seizure, and autoantibodies related to encephalitis were not detected. It was speculated that the patient had occult autoimmune encephalopathy because of its acute-onset clinical course preceded by fever, even without definite evidence of an autoimmune mechanism. The patient received intravenous methylprednisolone, plasma exchange, and intravenous immunoglobulin in succession and manifested a favorable outcome after these treatments. CONCLUSION: Our case supports the efficacy of immunotherapies for NORSE even though it does not manifest definite evidence for autoimmune background. Clinicians should consider these immunotherapies for NORSE as early as possible, because this condition is associated with high mortality and morbidity owing to prolonged seizure activity and long-term intensive care including general anesthesia and mechanical ventilation.

The Prehospital Predictors of Tracheal Intubation for in Patients who Experience Convulsive Seizures in the Emergency Department.

Objective To identify the prehospital factors predicting the performance of tracheal intubation (TI) at the emergency department (ED) in patients with convulsive seizure or epilepsy. Methods We performed a retrospective analysis of seizure patients who underwent TI at the ED soon after arrival. The clinical variables obtained in the prehospital setting were reviewed. Patients The study population included consecutive adult patients who were transported to an urban tertiary care ED due to convulsive seizure between August 2010 and September 2015. Results Among the 822 eligible patients, 59 patients (7.2%) underwent TI at the ED. Four independent prehospital predictors were identified using multivariate analysis: age ≥50 years (+1 point), meeting the definition of convulsive status epilepticus (+4 points), and an on-scene heart rate of ≥120 bpm (+1 point) led to a higher likelihood of TI, while a higher on-scene (alert or confused) level of consciousness (-3 points) led to a lower likelihood of TI. The derived prediction rule (the sum of all points) had good predictive performance with an area under the curve of 0.88 (95% confidence interval: 0.79-0.97), a sensitivity of 0.62, a specificity of 0.91, and a positive likelihood ratio of 10.6, when the cut-off value was set to 5 points. Conclusion We constructed a simple prehospital prediction rule to help predict the need for TI in seizure patients, even in the prehospital phase. This may possibly lead to the more effective management of seizure patients in the ED.

Old Stroke as an Independent Risk Etiology for Todd's Paralysis.

BACKGROUND: Todd's paralysis (TP) is a well-known postictal paresis in which patients present with transient weakness in their limb(s) after seizures. Although recognized as a stroke mimic in clinical practice, the pathophysiological mechanism and clinical features of TP remain unknown. Furthermore, its diagnosis can be erroneous in neurological emergency practice. We aimed to illustrate the clinical features and identify factors associated with TP. METHODS: This single-center, retrospective observational study included consecutive adult patients who presented with convulsive seizure and were referred to an urban tertiary care emergency department between August 2010 and April 2016. The diagnosis of TP was set as the primary outcome measure. Clinical and laboratory variables were evaluated. RESULTS: Of 1381 eligible convulsive seizures in 1187 patients, TP was observed in 89 seizures (6.4%) in 75 patients. Patients with TP were significantly older, more likely to have convulsive status epilepticus, and had a longer duration of convulsion than patients without TP. TP was found in 19.7% (39 of 198) of convulsive seizures with remote etiologies including those due to old stroke. These etiologies were identified as independent significant risk factors for TP compared with seizures with cryptogenic etiology. The positive likelihood ratio of TP seizures was 11.2 for remote seizure etiologies. CONCLUSIONS: Our results indicated that the diagnosis of TP highly suggests premorbid or comorbid structural lesions in the central nervous system, including old stroke. This consideration in seizure etiology may help in reducing the risk of misdiagnosis of acute stroke in emergency settings and further antiepileptic treatment.

Hyperammonaemia and associated factors in unprovoked convulsive seizures: A cross-sectional study.

PURPOSE: Hyperammonaemia is frequently observed in patients who have experienced convulsive seizures. Although excessive muscle contraction is presumed to be responsible for the elevated levels of ammonia, the underlying mechanism is poorly understood. The present study aimed to identify the independent factors associated with ammonia elevation using large-scale multivariate analysis. METHODS: We conducted a cross-sectional study involving 379 adult patients who had been transported to our emergency department and treated for unprovoked convulsive seizures between August 2010 and September 2015. Elevation of venous plasma ammonia levels was set as the primary endpoint, and patients' clinical and laboratory data were obtained. Those with severe liver dysfunction, known hepatic encephalopathy, or convulsions due to cardiovascular or psychogenic causes, and those taking valproate were excluded. RESULTS: Using a cut-off value of 50µg/dL, 183 patients (48.3%) were found to have elevated levels of plasma ammonia. Four factors were identified as independent variables associated with hyperammonaemia following seizures: elevated venous lactate, lowered venous pH, sex (male), and longer duration of convulsion. CONCLUSIONS: The results of the present study revealed independent factors associated with hyperammonaemia following unprovoked convulsive seizures in a larger scale and with more plausible statistical analysis. The authors further suggest that the excessive skeletal muscle contraction and/or respiratory failure during/after convulsive seizure may be the primary mechanism of hyperammonaemia.

Exclusion of Isolated Cortical Swelling Can Increase Efficacy of Baseline Alberta Stroke Program Early CT Score in the Prediction of Prognosis in Acute Ischemic Stroke Patients Treated with Thrombolysis.

BACKGROUND: The accuracy of the Alberta Stroke Program Early CT Score (ASPECTS) as a prognostic indicator in the treatment of cerebral infarction with thrombolysis remains controversial. We hypothesized that ASPECTS can more accurately predict treatment outcomes by excluding isolated cortical swelling (ICS) from ASPECTS and retrospectively tested patients treated with thrombolysis. METHODS: This retrospective cohort study included 106 patients treated with intravenous thrombolysis for cerebral infarction in our hospital. We included only patients with middle cerebral artery infarction. For the modification of ASPECTS, we removed each ICS from the ASPECTS system. We compared the correlation coefficients between the ASPECTS and modified ASPECTS with regard to treatment outcome, and performed a multivariate logistic regression analysis to evaluate the association between modified ASPECTS and outcomes. The primary outcome was a modified Rankin Scale score equal to or less than 2 on discharge and the secondary outcomes included an improvement of National Institutes of Health Stroke Scale (NIHSS) score of 4 or greater within 24 hours. RESULTS: Seventy-two patients were included in this study. The correlation coefficient of modified ASPECTS was significantly higher than that of ASPECTS in the primary outcome (r = .249 versus r = .363, P < .001) and in the improvement of NIHSS score (r = .303 versus r = .443, P < .001). Multivariate analysis revealed that a modified ASPECTS greater than 7 was significantly associated with the primary outcome (odds ratio [OR] = 1.334, 95% confidence interval [CI] = 1.071-1.661, P = .012) and the improvement of the NIHSS score (OR = 1.555, 95% CI = 1.208-2.003, P = .001). CONCLUSIONS: The present study reveals that ASPECTS may be more strongly associated with outcome by excluding ICS.

Augmenting LTP-Like Plasticity in Human Motor Cortex by Spaced Paired Associative Stimulation.

Paired associative stimulation (PASLTP) of the human primary motor cortex (M1) can induce LTP-like plasticity by increasing corticospinal excitability beyond the stimulation period. Previous studies showed that two consecutive PASLTP protocols interact by homeostatic metaplasticity, but animal experiments provided evidence that LTP can be augmented by repeated stimulation protocols spaced by ~30 min. Here we tested in twelve healthy selected PASLTP responders the possibility that LTP-like plasticity can be augmented in the human M1 by systematically varying the interval between two consecutive PASLTP protocols. The first PASLTP protocol (PAS1) induced strong LTP-like plasticity lasting for 30-60 min. The effect of a second identical PASLTP protocol (PAS2) critically depended on the time between PAS1 and PAS2. At 10 min, PAS2 prolonged the PAS1-induced LTP-like plasticity. At 30 min, PAS2 augmented the LTP-like plasticity induced by PAS1, by increasing both magnitude and duration. At 60 min and 180 min, PAS2 had no effect on corticospinal excitability. The cumulative LTP-like plasticity after PAS1 and PAS2 at 30 min exceeded significantly the effect of PAS1 alone, and the cumulative PAS1 and PAS2 effects at 60 min and 180 min. In summary, consecutive PASLTP protocols interact in human M1 in a time-dependent manner. If spaced by 30 min, two consecutive PASLTP sessions can augment LTP-like plasticity in human M1. Findings may inspire further research on optimized therapeutic applications of non-invasive brain stimulation in neurological and psychiatric diseases.

Cortical hemoglobin concentration changes underneath the coil after single-pulse transcranial magnetic stimulation: a near-infrared spectroscopy study.

Using near-infrared spectroscopy (NIRS) and multichannel probes, we studied hemoglobin (Hb) concentration changes when single-pulse transcranial magnetic stimulation (TMS) was applied over the left hemisphere primary motor cortex (M1). Seventeen measurement probes were centered over left M1. Subjects were studied in both active and relaxed conditions, with TMS intensity set at 100%, 120%, and 140% of the active motor threshold. The magnetic coils were placed so as to induce anteromedially directed currents in the brain. Hb concentration changes were more prominent at channels over M1 and posterior to it. Importantly, Hb concentration changes at M1 after TMS differed depending on whether the target muscle was in an active or relaxed condition. In the relaxed condition, Hb concentration increased up to 3-6 s after TMS, peaking at ∼6 s, and returned to the baseline. In the active condition, a smaller increase in Hb concentrations continued up to 3-6 s after TMS (early activation), followed by a decrease in Hb concentration from 9 to 12 s after TMS (delayed deactivation). Hb concentration changes in the active condition at higher stimulus intensities were more pronounced at locations posterior to M1 than at M1. We conclude that early activation occurs when M1 is activated transsynaptically. The relatively late deactivation may result from the prolonged inhibition of the cerebral cortex after activation. The posterior-dominant activation at higher intensities in the active condition may result from an additional activation of the sensory cortex due to afferent inputs from muscle contraction evoked by the TMS.

Effective connectivity between human supplementary motor area and primary motor cortex: a paired-coil TMS study.

The supplementary motor area (SMA) is important for preparation and execution of voluntary movements and densely anatomically connected with the hand area of primary motor cortex (M1). However, little is known about the effective connectivity between SMA and ipsilateral M1 (SMA â†’ M1). Here, we used paired-coil transcranial magnetic stimulation (pcTMS) to study the SMA â†’ M1 effective connectivity in healthy human subjects. In Experiment 1, we tested the effects of different induced current directions in the SMA and M1, and different intensities of conditioning SMA stimulation. Coil placement over the SMA-proper was verified by MRI-navigation. We found a SMA â†’ M1 facilitatory effect on motor evoked potential (MEP) amplitude that occurred very specifically only with an induced conditioning current directed from the midline towards the targeted SMA, an induced test current in M1 directed antero-medially and sufficient intensity of conditioning SMA stimulation. In Experiment 2, we selected these effective parameters to explore the effects of SMA â†’ M1 on the active MEP amplitude, cortical silent period (CSP) duration, and using a triple-pulse protocol, on short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). None of these measures was affected by conditioning SMA stimulation. Our findings demonstrate that pcTMS identifies predominantly facilitatory connections from SMA-proper to the hand area of the ipsilateral M1. The successful activation of this connection depends on effective SMA-proper stimulation, is state dependent and likely mediated via excitatory interneurons in M1.

Brainstem Infarction and Panuveitis due to Sarcoidosis Successfully Treated with Steroid Pulse Therapy.

A 36-year-old man visited our hospital because of blurred vision and redness of the conjunctiva. Slit-lamp examination showed panuveitis. Two days later, he suddenly experienced dizziness, speech disturbance, paralysis of his right extremities, and gait disturbances. Neurological examinations suggested that his symptoms were caused by a left lateral medullary lesion. He also had erythema mainly on his trunk. Magnetic resonance imaging (MRI) of his brain demonstrated a small infarct on the left side of the medulla oblongata. Clinical presentation and MRI findings were consistent with the diagnosis of a Wallenberg's syndrome. He also had bilateral hilar lymphadenopathy. A skin biopsy showed granulomatous nodular dermatitis compatible with sarcoidosis. He was treated with steroid pulse therapy and his neurological and ocular symptoms immediately improved. Only seven similar cases of intracranical sarcoidosis have been reported, but none had been treated with steroid pulse therapy. We recommend that steroid pulse therapy be considered to treat patients with sarcoidosis with signs of lesions in the central nervous system.

Ambient echolalia in a patient with germinoma around the bilateral ventriculus lateralis: a case report.

Ambient echolalia is a rare condition with few reported cases. We report the case of a 20-year-old man with a germinoma around the bilateral ventriculus lateralis who exhibited ambient echolalia. Clinical features included instinctive grasp reaction and compulsive manipulation of tools in his right hand. Speech or mental deterioration has been cited as a cause of ambient echolalia, but neither dementia nor aphasia was present. We propose that ambient echolalia in our case could be interpreted as a disinhibition of pre-existing essentially intact motor subroutines due to damage of the medial frontal lobe.