Interference of New Antiseizure Agents with Hospital Transfer of Stroke Patients in Japan: A Retrospective Cohort Study.

Patients in Japan often have difficulty in screening and selecting chronic-care and rehabilitation hospitals for transfer because of the high cost and unavailability of new antiseizure medications, such as perampanel and lacosamide. To investigate whether the requirement for perampanel and lacosamide interfered with patients' hospital transfer by comparing the number of days required for hospital transfer. Data were obtained from patients 1) who were diagnosed with intracerebral hemorrhage or cerebral infarction, 2) who were treated with antiseizure medications for epilepsy, and 3) who were transferred to another hospital. The main outcome measures were the length of hospital stay and days from the last seizure to hospital transfer.Ninety-four eligible patients were divided into those treated with perampanel or lacosamide (n = 18) and those treated with other agents (n = 76). The mean length of hospital stay and days from the last seizure to hospital transfer were 52.9 and 45.4 d in the perampanel and lacosamide group, and 32.7 and 28.6 d in the other medication group (p < 0.001). The mean antiseizure medication costs and total drug costs were U.S. $4.88 and $6.85 in the perampanel/lacosamide group and U.S. $1.94 and $4.41 in the other medication group (p < 0.001, p = 0.007), respectively. Considering antiseizure medication availability and cost in the transfer destination hospital is important when choosing medications for patients requiring hospital transfer from an acute-care hospital.

Negative impact of Interhospital Transfer on Clinical Outcomes of Mechanical Thrombectomy for Fast Progressive Stroke.

OBJECTIVES: The time-dependence of the clinical outcome of mechanical thrombectomy is higher in the "fast progressor" in whom cerebral ischemia progresses rapidly. The impact of time-consuming interhospital transfer (IT) on the clinical outcome of such patients is unknown. The effect on clinical outcomes of IT of fast progressors was investigated. METHODS: Among the patients enrolled in the Tokyo/Tama REgistry of Acute endovascular Thrombectomy, fast progressor cerebral ischemia cases were retrospectively investigated. In this study, a fast progressor was defined as a case with an Alberta Stroke Program Early CT Score less than 6 and last known well (LKW) to arterial puncture within 6 h. Patients' background characteristics, treatment progress, and the modified Rankin Scale (mRS) score at 3 months were examined. RESULTS: Of a total of 1182 patients, 92 (7.8%) were included, with 76 patients in the direct transfer (DT) group, and 16 patients in the IT group. Median LKW to reperfusion was 190 min and 272 min, respectively (P<.001). The number of patients with mRS scores 0-2 at three months was 22 (28.9%) in the DT group and 1 (6.2%) in the IT group. Interhospital transfer was an independent factor associated with worse outcomes (odds ratio 0.08, 95% confidence interval 0.01-0.87, P=.038). CONCLUSION: This study showed that, among fast progressor patients, the IT group had a worse prognosis than the DT group. To provide good clinical outcomes for fast progressor patients, those who are likely to undergo mechanical thrombectomy should be sent directly to a thrombectomy-capable center.

Impact of Coronavirus Disease 2019 on Time Delay and Functional Outcome of Mechanical Thrombectomy in Tokyo, Japan.

OBJECTIVES: An association has been reported between delays in the onset-to-door (O2D) time for mechanical thrombectomy (MT) and outbreaks of coronavirus disease 2019 (COVID-19). However, the association between other MT time courses or functional outcomes and COVID-19 outbreaks remains unclear. We compared the time courses of stroke pathways or functional outcomes in 2020 (the COVID-19 era) with those in 2019 (the pre-COVID-19 era) in Tokyo, Japan. MATERIALS AND METHODS: This retrospective observational study used data from the Tokyo-tama-REgistry of Acute endovascular Thrombectomy (TREAT), a multicenter registry of MT for acute large vessel occlusion in the Tokyo Metropolitan Area. Patients who had undergone acute MT from January 2019 to December 2020 were included. Patients were classified by the year they had undergone MT (2019 or 2020). RESULTS: In total, 477 patients were analyzed. O2D time was significantly longer in 2020 (146.0 min) than in 2019 (105.0 min; p = 0.034). No significant difference in door-to-puncture time (D2P) time or modified Rankin Scale (mRS) score 0-2 at 90 days was seen between 2019 and 2020. In the subgroup analysis, O2D time was significantly longer in the first half of 2020 compared with 2019. Multivariable logistic regression analysis revealed that the year 2020 was a independent predictor of longer O2D time, but not for mRS score 0-2 at 90 days. CONCLUSIONS: Although O2D time was significantly longer in the COVID-19 compared with the pre-COVID-19 era, D2P may not be significantly delayed and functional outcomes may not be different, despite the COVID-19 pandemic.

Thrombectomy for Stroke at 6-24 hours without Perfusion CT Software for Patient Selection.

BACKGROUND: Although, thrombectomy for stroke more than 6 hours after onset supported by automated perfusion computed tomography (CT) software (RAPID, iSchemaView) is effective, this software is not available in Japan. This study aimed to elucidate the efficacy of thrombectomy 6-24 hours after onset in our patient cohort using conventional imaging mismatch. METHODS: Of 586 ischemic stroke patients who underwent thrombectomy registered from January 2015 to December 2017, patients with occlusion of the intracranial internal carotid artery or middle cerebral artery, who had last been known to be well 6-24 hours earlier and who had a prestroke modified Rankin scale (mRS) score 0 or 1 were enrolled. Clinical outcomes were the scores of the utility-weighted (UW) mRS, which ranges from 0 (death) to 10 (no symptom or disability), and the rate of functional independence (mRS score of 0-2) at 90 days. RESULTS: This study sample included 31 patients. The median baseline National Institutes of Health Stroke Scale score was 17 (interquartile range [IQR], 13-20), and the median Diffusion-Weighted Imaging-Alberta Stroke Program Early CT Score was 7 (IQR, 5-8). The median interval between the time that the patient was last known well and revascularization was 741 (IQR, 641-818) minutes. The mean UW mRS score at 90 days was 5.3, the rate of functional independence was 32%, and the 90-day mortality rate was 13%. CONCLUSIONS: Thrombectomy 6-24 hours after onset which can be performed with conventional imaging mismatch might be secured for improving functional independence in stroke patients.

Correlation between prescription volumes of generic antiepileptic drugs and the number of clinical epileptologists across prefectural regions in Japan: A descriptive study using a national claims database.

PURPOSE: Although generic drugs are essential in reducing medical costs, their use in epilepsy therapy remains a subject of ongoing debate. In this study, we analysed prescription trends of generic drugs using data from the National Database of Health Insurance Claims and Specific Health Checkups (NDB) Open Data Japan. METHODS: The number of generic drug prescriptions from 2017-2021 was extracted from the NDB Open Data Japan, with data for each medication stratified by prefectural region, sex, and age, allowing for the analysis of the impact of each factor. We analysed the correlation between the prescription volumes of generic antiseizure medications (ASMs) and the number of clinical epileptologists registered with the Japan Epilepsy Society per 100,000 population. RESULTS: In 2021, the prescription volume of generic ASMs was 49 %, whereas that for other pharmacological agents was between 70-80 %. Notably, for children < 15 years of age, generics made up approximately 20 % of prescriptions, which was significantly less than that in other age groups. Analysis by prefecture revealed a negative correlation between prescription volumes of ASMs and the number of clinical epileptologists across prefectural regions in Japan (R = -0.47, p < 0.01). CONCLUSION: Our findings indicate that the higher the proportion of clinical epileptologists in each prefecture, the lower the number of prescribed generic ASMs. Clinical epileptologists in Japan therefore prescribe antiseizure agents in accordance with the Japanese epilepsy treatment guidelines that do not recommend the use of generic agents.

Effects of Valproic Acid Supply Shortage on Pharmacy Operations in a Region of Japan.

Introduction Valproic Acid (VPA) is an essential drug in epilepsy treatment, yet it has faced supply instability in Japan. The extent of the VPA shortage and the associated increase in pharmacists' workload and collaboration with healthcare organizations remains unclear. This study investigates the potential effects of these disruptions on the roles of pharmacists. Methods A questionnaire was administered to pharmacies in Hachioji City, Japan. The survey addressed inventory management, patient complaints, and the potential effects on pharmacy operations during VPA supply instability. A chi-squared test of independence was conducted to compare the most unstable VPA supply period with the current supply situation. Supply stability according to pharmacy characteristics such as the number of prescriptions received per day and primary patient age group was also evaluated. Results Of the 42 pharmacies surveyed, 76.2% reported changes in prescription processing due to VPA supply issues. The main challenges were increased workload in inventory management and patient concerns regarding medication availability and quality. Pharmacies primarily serving clinical prescriptions and pediatric patients were the most affected by the supply instability. Discussion This study highlighted the potential effects of VPA supply instability on pharmacy operations. Pharmacists are expected to provide continuous treatment to patients through effective counseling and medication guidance to alleviate anxiety and concerns related to supply shortages.

Efficacy of a new instrument for dural defect repair in anterior skull base reconstruction: a technical note.

BACKGROUND: The anterior skull base is a deep and narrow area, which makes dural repair technically challenging. The goal of this study was to demonstrate the efficacy of a new instrument for anterior skull base dural repair. METHODS: Ten patients underwent surgery via the transbasal approach, combined with either a transfacial or a transnasal endoscopic resection. The dural repair was performed prior to tumor resection, and the new instrument was used to suture the fascia lata in an underlay fashion. The repaired dural defect was then covered with a pericranial flap. RESULTS: The follow-up period ranged from 2 to 18 months, with an average follow-up time of 8.7 months. During this period, none of the patients experienced cerebrospinal fluid leakage, meningitis, tension pneumocephalus, abscess formation, or flap necrosis. CONCLUSIONS: Our findings suggest that the use of this instrument combined with the technique of suturing the fascia lata in an underlay fashion and covering it with a pericranial flap, may be an effective alternative approach to anterior skull base reconstruction.

Subacute In-Stent Occlusion 2 Weeks after CASPER Rx Stenting: A Case Report.

Objective: CASPER Rx stent (Terumo, Tokyo, Japan) is one of the dual-layer micromesh stents for carotid artery stenosis. Although it is expected to be safe and efficacious even for vulnerable plaque, we report a case of in-stent occlusion 2 weeks after stenting with CASPER Rx stent. Case Presentation: The patient was a 78-year-old man with a symptomatic, severely stenosed lesion of the cervical internal carotid artery (ICA). He had an unstable plaque and underwent carotid artery stenting with the CASPER Rx stent. There were no problems with the procedure or the patient's subsequent course, and he was discharged home 1 week after the procedure. However, on postoperative day 14, the patient had a transit ischemic attack and imaging showed acute occlusion due to thrombus in the stent and in the distal part of the ICA. Mechanical thrombectomy was performed and good recanalization was achieved, but postoperative cerebral infarction was observed and the patient was transferred to other hospital with modified Rankin Scale 2. Conclusion: We experienced a case of in-stent occlusion 2 weeks after stenting with the CASPER Rx stent.

Nonconvulsive Status Epilepticus Associated with Cerebral Hyperperfusion Syndrome after Carotid Endarterectomy: A Case Report.

We report a case of a 73-year-old man who developed nonconvulsive status epilepticus as a complication of cerebral hyperperfusion syndrome after carotid endarterectomy for carotid artery stenosis. On postoperative day 1, the patient experienced headaches and vomiting. Resting N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography showed increased cerebral blood flow to the entire right hemisphere, and the patient was diagnosed with cerebral hyperperfusion syndrome. He was treated with antihypertensive and antiseizure medications, sedated using propofol, intubated, and placed under mechanical ventilation. On postoperative day 3, computed tomography perfusion imaging showed a reduction in hyperperfusion, and propofol sedation was terminated on postoperative day 4. However, the patient exhibited prolonged impaired awareness and roving eye movements, and long-term video electroencephalographic monitoring revealed electrographic seizures. The patient was diagnosed with nonconvulsive status epilepticus. Propofol sedation was resumed, and the antiseizure medication dose was increased. Subsequently, the state of hyperperfusion in the right hemisphere diminished, and electroencephalographic findings improved, allowing sedation to be terminated on postoperative day 7. The findings from this case suggest that when clinical subtle symptoms, such as impaired awareness and roving eye movements, are observed during treatment of cerebral hyperperfusion syndrome, video electroencephalography should be performed to detect electrographic seizures.

A Case of Acquired Factor XIII Deficiency with Systemic Lupus Erythematosus Diagnosed after Repeated Intracerebral Hemorrhages.

We present a case of autoimmune-acquired factor XIII deficiency associated with systemic lupus erythematosus, which was diagnosed as a cause of repeated intracerebral hemorrhage. An intracerebral hemorrhage occurred in a 24-year-old female patient. Craniotomy was performed to remove the hematoma, but rebleeding occurred at the same site on days 2 and 11, respectively. Detailed blood tests revealed that factor XIII activity decreased. Although autoimmune-acquired factor XIII deficiency is a very rare disease, it can sometimes be fatal when intracerebral hemorrhage occurs. If there is repeated intracerebral hemorrhage, factor XIII activity should be confirmed.

Psychiatric disorders of the combination of levetiracetam either with lacosamide or perampanel: a retrospective cohort study.

Background The number of patients with epilepsy receiving perampanel or lacosamide as an add-on treatment following levetiracetam treatment has increased. Although levetiracetam causes psychiatric disorders, it is unclear whether they occur with the combined use of these antiepileptic drugs. Objective To determine the frequency of psychiatric disorders in patients received lacosamide or perampanel in combination with levetiracetam. Setting A single-center retrospective cohort study. Method Patients who received levetiracetam + lacosamide or levetiracetam + perampanel were selected. Medical records from the start of combination therapy contained characteristics of patients and the incidence of psychiatric disorders. Main outcome measure The frequency of psychiatric disorders, the time to onset, dose reduction or discontinuation following psychiatric disorders, and the clinical course following disorder onset. Results Forty-four patients used levetiracetam + lacosamide and 50 used levetiracetam + perampanel. The incidence of psychiatric disorders was significantly lower (p < 0.001) with levetiracetam + lacosamide (6.8%) than with levetiracetam + perampanel (44%). The incidence of affect lability was significantly higher with levetiracetam + perampanel than with levetiracetam + lacosamide (p = 0.018). The time to the onset of psychiatric disorders was within 1 month of dose initiation or increase in one case (33.3%) with levetiracetam + lacosamide and 16 cases (72.7%) with levetiracetam + perampanel. There was no significant difference in clinical characteristics and antiepileptic drug dosages owing to the presence or absence of psychiatric disorders. Conclusion As the frequency of psychiatric disorders was higher with levetiracetam + perampanel therapy, levetiracetam + lacosamide may be preferable. These disorders tended to develop within 1 month of therapy and were not dose-dependent. Antiepileptic drugs should be cautiously prescribed to avoid psychiatric disorders.

Nonocclusive Mesenteric Ischemia Is a Potentially Lethal Complication Just after Stroke Onset: Report of Six Case Studies.

Nonocclusive mesenteric ischemia (NOMI) is a rare but life-threatening post-stroke complication. This is the first case series report of NOMI after stroke, describing its characteristics and the difficulty of diagnosis. We retrospectively reviewed 367 stroke patients from April 2018 to May 2019 in our hospital. We identified six patients (1.6%) with NOMI after stroke and described their clinical presentation, including characteristics, vital signs, laboratory parameters, treatment, and outcomes. The mean interval between stroke onset and diagnosis of NOMI was 4.6 days (range, 3-10 days). Five patients had disturbance of consciousness caused by stroke, and therefore the major complaints and symptoms associated with NOMI were nonspecific, possibly resulting in delayed diagnosis and treatment. All patients had a high respiratory rate (≥22 breaths/min). C-reactive protein and lactate levels were high (mean, 21.6 mg/L and 2.4 mmol/L, respectively). All patients underwent emergent abdominal operations. Four patients were discharged with modified Rankin Scale scores ≥4, and two patients died. NOMI can be a fatal post-stroke complication and is challenging to diagnose. Further investigations should be conducted to determine the most efficient way to diagnose NOMI after stroke.

Endovascular treatment of acute basilar artery occlusion: Outcomes, influencing factors and imaging characteristics from the Tama-REgistry of acute thrombectomy (TREAT) study.

OBJECTIVE: The effectiveness of mechanical thrombectomy (MT) for acute basilar artery occlusion (ABAO) remains unknown. We evaluated the feasibility, safety, and efficacy of endovascular treatment for ABAO. METHODS: We retrospectively investigated patients with ABAO who underwent MT using modern stent retrievers and an aspiration device between January 2015 and March 2019 at 12 comprehensive stroke centers. Functional outcomes and 90-day mortality rates were analyzed as primary outcomes. Factors influencing outcomes were analyzed as secondary outcomes. Relationships between outcome and affected area of infarction on arrival were also analyzed. RESULTS: Seventy-three patients were included. Good outcome (modified Rankin Scale (mRS) score 0-2) was achieved in 25/73 patients (34.2%) and the all-cause 90-day mortality rate was 23.3% (17/73). Successful recanalization (modified Thrombolysis In Cerebral Infarction grade 2b and 3) was achieved in 70/73 patients (95.9%). In univariate analyses, age, National Institutes of Health Stroke Scale score, and posterior circulation Alberta Stroke Program Early CT Score (pc-ASPECTS) differed significantly between good and poor functional outcome groups. Age and pc-ASPECTS were significantly associated with functional outcomes in the logistic regression model. Positive findings for the midbrain on diffusion-weighted imaging on pc-ASPECTS and brainstem score were significantly associated with poor outcomes. CONCLUSION: MT with modern devices for ABAO resulted in highly successful recanalization and good outcomes. A positive finding for the midbrain on initial imaging might predict poor outcomes. Further studies are required to confirm our results.

Surgical management of giant trigeminal schwannomas extending into the parapharyngeal space.

PURPOSE: Trigeminal schwannomas extending into the deep parapharyngeal space are relatively rare, and a surgical approach to such tumors has not been well established. We report four cases in which the tumors were completely removed by using a combination of three approaches. METHODS: Four patients with trigeminal schwannomas extending into the extracranial space were surgically treated using a combination of the transcervical approach, anterolateral retromaxillar pathway via gingivobuccal sulcus, and epi and interdural middle fossa approach. RESULTS: The maximum diameters of the tumors ranged from 4 to 7 cm. Three tumors extended beyond the lower end of the maxillary sinus. All tumors were completely excised. The Karnofsky performance scales after surgery were more than 90% in all patients. CONCLUSION: Although the tumors extending to the deep parapharyngeal space are difficult to completely remove via a single approach, a combined approach is useful in these huge extracranial extensions.

Outcomes of Endovascular Thrombectomy Performed 6-24 h after Acute Stroke from Extracranial Internal Carotid Artery Occlusion.

Thrombectomy has demonstrated clinical efficacy against acute ischemic stroke caused by intracranial occlusion of the internal carotid artery (ICA), even if performed 6-24 h after onset. This study investigated the outcomes of thrombectomy performed 6-24 h after stroke onset caused by extracranial ICA occlusion. Of 586 stroke patients receiving thrombectomy during the past 3 years and registered in the Tama Registry of Acute Endovascular Thrombectomy database, 24 were identified with ICA occlusion (14 extracranial and 10 intracranial), known to be well 6-24 h before presentation, and with pre-stroke modified Rankin Scale (mRS) score of 0 or 1. Clinical outcomes measured were the rate of functional independence at 90 days according to mRS score of 0-2 and 90 day mortality rate. Of patients with extracranial ICA occlusion, two received additional carotid stenting with thrombectomy. The median interval between the last time the patient was known to be well and hospital arrival was 601 (interquartile range, 476-729 min). Both the rate of functional independence at 90 days and 90 day mortality were comparable between patients with extracranial or intracranial ICA occlusion (36% vs. 40% and 7% vs. 10%, respectively). No symptomatic intracranial hemorrhages occurred within 24 h following treatment of extracranial ICA occlusion. Thrombectomy performed 6-24 h after extracranial ICA results in acceptable functional outcome. Further clinical study is warranted to better define the temporal window of thrombectomy for acceptable functional outcome in patients with extracranial ICA occlusion.

Emergency endovascular treatment of a ruptured external carotid artery pseudoaneurysm caused by a cervical stab wound: A case report and literature review.

The formation of external carotid artery (ECA) pseudoaneurysms caused by stab wounds is a rare vascular anomaly. Although the surgical exploration of the ECA segment is the standard treatment, endovascular treatment (EVT) can be considered if there is difficulty in identifying the source of bleeding in the injured regions that are difficult to operatively access. Here we treated a young patient who had hemorrhagic instability with hemorrhage-induced coagulopathy caused by a zone III cervical stab wound with a pseudoaneurysm from the main trunk of the ECA; the patient underwent EVT and successful hemostasis. A literature review based on the data available on PubMed was conducted, and 15 published reports of 82 penetrating ECA injuries treated by EVT were identified. We concluded that EVT appears to be an effective surgical alternative for patients with hemorrhage-induced coagulopathy caused by a ruptured ECA pseudoaneurysm after a cervical stab wound.

Minimally invasive space shuttle laminotomy for degenerative lumbar spinal canal stenosis.

STUDY DESIGN: Technical note. OBJECTIVES: To show microsurgical technique, considering the meticulous anatomy of the ligamentum flavum (LF). BACKGROUND: Different methods are available for treating lumbar spinal canal stenosis (LSCS). A minimally invasive surgery, namely, space shuttle laminotomy, has recently been proposed. Here, we describe the surgical method for this novel technique. To conduct this surgery accurately, surgeons must have perfect knowledge of anatomy, especially regarding the LF. MATERIALS AND METHODS AND RESULTS: We use this interlaminectomy technique for all cases of LSCS. All patients with LSCS recovered from their neurological deficits in shorter hoslital stays than regular laminectomy. CONCLUSION: Minimally invasive space shuttle laminotomy (MISSL), which involves a microsurgical technique, is a safe, complication-free procedure.

Perifascial Areolar Tissue Graft for Spinal Dural Repair with Cerebrospinal Fluid Leakage: Case Report of Novel Graft Material, Radiological Assessment Technique, and Rare Postoperative Hydrocephalus.

BACKGROUND: Incidental durotomy is a relatively common complication in spinal surgeries, and treatment of persistent cerebrospinal fluid (CSF) leakage is still challenging, especially in cases for which "watertight" suturing is inapplicable. The usefulness of a nonvascularized perifascial areolar tissue (PAT) graft recently was emphasized for plastic and skull base surgeries. Its hypervascularity allows for early engraftment and long-term survival, and its flexibility is advantageous in fixing defects of complex shapes in limited surgical spaces. CASE DESCRIPTION: The authors report a case of persistent CSF leakage after cervical spine surgery in which a PAT graft was used successfully for direct closure of the dural defect. The noninvasive, spin-labeled magnetic resonance imaging technique was used for postoperative assessment of CSF dynamics, not for CSF accumulation but for CSF leakage itself. In addition, some potential causes for the rare development of communicating hydrocephalus after cervical laminoplasty, as seen in this case, are discussed. CONCLUSIONS: PAT was used successfully as an alternative free graft material for direct spinal dural closure, and its hypervascularity seemed to assist with rapid resolution of CSF leakage in our case. Spin-labeled magnetic resonance imaging may enable assessment of spinal CSF dynamics without invasion.

Modified Goel's Methods for Basilar Impression: A Case Report with Literature.

We report the case of a 57-year-old woman who had basilar impression manifesting as severe myelopathy and occipital neuralgia and was treated by distraction and fixation performed using a modification of Goel's method. Magnetic resonance imaging (MRI) and computed tomography (CT) scans showed severe myelocompression by the dens of the axis from the ventral side and occipitalization of the atlas. After traction using a Halo vest, C1-2 facet distraction and fixation was performed in one stage using a modified Goel's method. Although Goel et al. used a custom-made spacer to distract the facet joints, we used a threaded titanium cylindrical cage that was inserted into the joint to fix the C1-2 facet joint with posterior fixation from occipital bone to C5. Postoperatively, gradual symptomatic and neurological amelioration were observed. The atlantoaxial joints were bone-fused at 3 years post-operation. Distraction and fixation performed using this modified version of Goel's method was effective for treating basilar invagination. The threaded titanium cylindrical cage provided adequate C1-2 space and strong initial fixation.