Effective physical therapy activities to improve the supine-to-seated transfer time in stroke patients: an observational pilot study.

[Purpose] This study aimed to examine the effective time allocation for physical therapy activities in patients with stroke. The primary outcome measure was the improvement in the time required to transition from the supine to the sitting position. [Participants and Methods] This study enrolled 19 inpatients with stroke. The activities performed during physical therapy were classified as nontherapeutic activities, minimal therapeutic activities, moderate therapeutic activities, high therapeutic activities, and other activities. We determined the relationship between the activities and the relative shortening ratio of the time required to sit up from the supine position for up to 13 weeks of physical therapy. We also considered the following background factors: patient information, functional independence measure, and Brunnstrom recovery stage. [Results] The Brunnstrom recovery stage for the lower extremity was identified as the confounding factor, and the participants were stratified into the Brunnstrom recovery stage 6 group, in which moderate therapeutic activities and other activities were significantly related to the relative shortening ratio. [Conclusion] The results suggested that other activities exerted a similar effect as moderate therapeutic activities in the Brunnstrom recovery stage 6 group and were more effective than high therapeutic activities in reducing the time required to sit up from the supine position.

Dual pathology in a patient with temporal lobe epilepsy associated with neocortical glial scar after brain abscess and end folium sclerosis/hippocampal sclerosis type 3.

End folium sclerosis or hippocampal sclerosis (HS) type 3 is often associated with another coexisting epileptogenic lesion (dual pathology); however, the pathogenesis of HS type 3 remains elusive. A 46-year-old man presented with medically intractable focal aware seizures and focal impaired awareness seizures (FIAS) with occasional focal to bilateral tonic-clonic seizures (FBTCS) two years after surgical treatment with extensive cranial reconstruction for a brain abscess in the right temporal lobe associated with intracranial extension of ipsilateral cholesteatoma. Head magnetic resonance imaging (MRI) at age 49 revealed atrophy of the right cerebral hemisphere including the hippocampus and amygdala. The patient's first epilepsy surgery was a lateral temporal lobectomy, in which the mesial temporal structures were preserved because no epileptiform discharge was detected on the intraoperative electrocorticogram. However, FIAS with FBTCS started 15 months after the operation. The second surgery, amygdalohippocampectomy, at age 52, resulted in the patient being seizure-free again for one year before seizures of the right lateral temporal origin recurred. He underwent a third surgery, resection of the Heschl's and supramarginal gyri, at age 53, but he continued to have drug-resistant epilepsy over two years after that. Histopathological examination revealed dual pathology consisting of glial scar in the lateral temporal lobe and ipsilateral HS type 3 with an unusually severe lesion in the subiculum. No significant inflammatory change was observed. The clinicopathological features in the present case indicate that HS developed secondarily in the context of neocortical epilepsy due to glial scar, suggesting a role of repetitive abnormal electrical input from neocortical epileptogenic lesions into the hippocampus finally via the perforant pathway in the pathogenesis of HS type 3. Severe hippocampal atrophy on preoperative MRI together with its silent electrocorticogram recording at initial epilepsy surgery may represent clinically pre-epileptogenic HS in a seizure-free "silent or latent period" before completion of hippocampal epileptogenesis to the extent that clinical epileptic seizures occur.

Characteristics and management of the offending veins in microvascular decompression surgery for trigeminal neuralgia.

The optimal technique of microvascular decompression (MVD) for trigeminal neuralgia (TN) caused by venous conflict remains unclear. The objectives of this study are to characterize the offending veins identified during MVD for TN and to evaluate intraoperative technique applied for their management. From 2007 till 2019, 308 MVD surgeries were performed in 288 consecutive patients with TN, and in 58 of them, pure venous conflict was identified. In 44 patients, the offending vein was interrupted, as was done for small veins arising from the cisternal trigeminal nerve (CN V) or its root entry zone (REZ) causing their stretching (19 cases), small veins on the surface of REZ (9 cases), transverse pontine vein (TPV) compressing REZ or distal CN V (12 cases), and superior petrosal vein (SPV) using flow conversion technique (4 cases). In 14 other cases, the offending vein was relocated, as was done for the SPV or the vein of cerebellopontine fissure (8 cases), TPV (3 cases), and the vein of middle cerebellar peduncle (3 cases). Complete pain relief after surgery was noted in 49 patients (84%). No one patient experienced major neurological deterioration. Postoperative facial numbness developed in 14 patients (24%), and in 8 of them, it was permanent. In 14 patients, MRI demonstrated venous infarction of the middle cerebellar peduncle, which was associated with the presence of any (P = 0.0180) and permanent (P = 0.0002) facial numbness. Ten patients experienced pain recurrence. Thus, 39 patients (67%) sustained complete pain relief at the last follow-up (median, 48 months), which was significantly associated with the presence of any (P = 0.0228) and permanent (P = 0.0427) postoperative facial numbness. In conclusion, in cases of TN, small offending veins arising from REZ and/or distal CN V and causing their stretching may be coagulated and cut. In many cases, TPV can be also interrupted safely or considered as collateral way for blood outflow. The main complication of such procedures is facial numbness, which is associated with the venous infarction of middle cerebellar peduncle and long-term complete pain relief.

Diagnostic Reliability of Headset-Type Continuous Video EEG Monitoring for Detection of ICU Patterns and NCSE in Patients with Altered Mental Status with Unknown Etiology.

BACKGROUND/OBJECTIVE: Simplified continuous electroencephalogram (cEEG) monitoring has shown improvement in detecting seizures; however, it is insufficient in detecting abnormal EEG patterns, such as periodic discharges (PDs), rhythmic delta activity (RDA), spikes and waves (SW), and continuous slow wave (CS), as well as nonconvulsive status epilepticus (NCSE). Headset-type continuous video EEG monitoring (HS-cv EEG monitoring; AE-120A EEG Headset™, Nihon Kohden, Tokyo, Japan) is a recently developed easy-to-use technology with eight channels. However, its ability to detect abnormal EEG patterns with raw EEG data has not been comprehensively evaluated. We aimed to examine the diagnostic accuracy of HS-cv EEG monitoring in detecting abnormal EEG patterns and NCSE in patients with altered mental status (AMS) with unknown etiology. We also evaluated the time required to initiate HS-cv EEG monitoring in these patients. METHODS: We prospectively observed and retrospectively examined patients who were admitted with AMS between January and December 2017 at the neurointensive care unit at Asakadai Central General Hospital, Saitama, Japan. We excluded patients whose data were missing for various reasons, such as difficulties in recording, and those whose consciousness had recovered between HS-cv EEG and conventional cEEG (C-cEEG) monitoring. For the included patients, we performed HS-cv EEG monitoring followed by C-cEEG monitoring. Definitive diagnosis was confirmed by C-cEEG monitoring with the international 10-20 system. As the primary outcome, we verified the sensitivity and specificity of HS-cv EEG monitoring in detecting abnormal EEG patterns including PDs, RDA, SW, and CS, in detecting the presence of PDs, and in detecting NCSE. As the secondary outcome, we calculated the time to initiate HS-cv EEG monitoring after making the decision. RESULTS: Fifty patients (76.9%) were included in the final analyses. The median age was 72 years, and 66% of the patients were male. The sensitivity and specificity of HS-cv EEG monitoring for detecting abnormal EEG patterns were 0.974 (0.865-0.999) and 0.909 (0.587-0.998), respectively, and for detecting PDs were 0.824 (0.566-0.926) and 0.970 (0.842-0.999), respectively. We diagnosed 13 (26%) patients with NCSE using HS-cv EEG monitoring and could detect NCSE with a sensitivity and specificity of 0.706 (0.440-0.897) and 0.970 (0.842-0.999), respectively. The median time needed to initiate HS-cv EEG was 57 min (5-142). CONCLUSIONS: HS-cv EEG monitoring is highly reliable in detecting abnormal EEG patterns, with moderate reliability for PDs and NCSE, and rapidly initiates cEEG monitoring in patients with AMS with unknown etiology.

Nonconvulsive Status Epilepticus in Acute Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Patients with acute intracerebral hemorrhages (ICHs) often develop nonconvulsive status epilepticus (NCSE). We aimed to identify determinants and the prognostic significance of NCSE among patients with acute ICH. METHODS: Consecutive patients with acute spontaneous ICH who were admitted to a comprehensive stroke center were enrolled. We diagnosed NCSE using the modified Salzburg Consensus Criteria. Factors associated with NCSE and their significance in relation to clinical outcomes were assessed using multivariate logistic regression models. RESULTS: Of 228 patients (136 men; mean age, 68±14 years), 20 (8.8%) developed NCSE during their hospital stays. In logistic regression models, the adjusted odds ratios (95% confidence intervals) for NCSE were 3.5 (1.2-10.7) for craniotomy and 7.0 (2.2-31.2) for lobar involvement. The patients with NCSE had higher modified Rankin Scale scores at discharge, but NCSE was not independently associated with poor functional outcomes (modified Rankin Scale score, 4-5) or mortality after adjusting for confounders. CONCLUSIONS: NCSE is not a rare complication of acute ICH. Craniotomy and lobar involvement are independently associated with NCSE in patients with acute ICH.

[A surgical fenestration of an arachnoid cyst in the cerebellomedullary cistern].

Arachnoid cysts originating from the cerebellomedullary cistern are very rare, and their indications for surgical treatment remain controversial. A 41-year-old man with a cystic lesion in the left cerebellomedullary cistern presented with sudden perspiration, palpitations, and vertigo. Subsequently, he complained of numbness of the left extremities and a dull headache. Otolaryngological evaluation revealed no abnormality. Physical examination on admission showed no neurological manifestations, except for left sensory disturbance. MRI revealed a cyst in the left cerebellomedullary cistern. Radiological examination did not reveal direct compression of the brain stem by the cyst, but the left cerebellum was compressed by the cyst. The patient underwent surgical fenestration of the arachnoid cyst via the midline suboccipital approach. The symptoms immediately disappeared after surgery. Patients with an arachnoid cyst in the cerebellomedullary cistern usually present lower cranial nerve dysfunction as a symptom. In our case, there was no cranial nerve dysfunction, but anatomically unexplainable symptoms, such as perspiration, palpitations, dizziness, and numbness of the left limbs, were observed. In conclusion, even if a patient with an arachnoid cyst in the posterior cranial fossa presents unexplainable symptoms, surgical intervention, including fenestration, is one of the therapeutic options.

Switching carbamazepine to lacosamide improves gamma-glutamyl transpeptidase levels.

Carbamazepine (CBZ) use has been limited by multiple adverse reactions. Lacosamide (LCM) is a functional amino acid anti-seizure medication (ASM), approved for focal seizure patients more than 4 years old. It is non-inferior in terms of efficacy to controlled release CBZ and was proven to have better tolerability. This study examines the effect of abruptly changing CBZ to LCM in epilepsy patients with elevated gamma-glutamyl transpeptidase (GGT). Consenting adult patients aged 18 years old and above, with controlled focal seizure disorder for more than 2 years, who were consistently taking CBZ and who had elevated GGT were included in this study. Out of 1526 patients screened, only 12 satisfied the inclusion criteria. After abruptly changing CBZ to LCM, the GGT level significantly dropped from a median of 141.5 to 63.5 IU/L (z = 3.06, p = 0.0005). Moreover, there was significantly lower proportion of patients with abnormal GGT levels after the switch in medications was done (100% vs. 66.7%, McNemar χ2 = 8, p = 0.008). Moderate to high levels of GGT in patients with focal epilepsy can be decreased by changing CBZ to LCM. Moreover, abruptly changing CBZ to LCM without cross-titration may be safe and effective in preventing seizure incidence within a 1-month period. PLAIN LANGUAGE SUMMARY: Although carbamazepine (CBZ) is the standard drug for focal seizures, its numerous side effects, especially in the liver, limits its use in a lot of patients with epilepsy. Gamma-glutamyl transferase (GGT), which is elevated in liver disease of whatever cause including intake of CBZ, is associated with increased mortality. In this study, we found that abruptly changing CBZ to Lacosamide (LCM) can significantly decrease the GGT level in 1 month without apparent increase in seizure recurrence and side effects. Therefore, we conclude that high levels of GGT may be decreased by abruptly changing CBZ to LCM.

Utility and Prognostic Value of Intraoperative Blink Reflex in Trigeminal or Facial Nerve Monitoring in Skull Base Surgeries: A Systematic Review.

BACKGROUND: Blink reflex (BR) is an oligosynaptic reflex that involves the ophthalmic branch of the trigeminal nerve (TN), ipsilateral main sensory and trigeminospinal nuclei, bilateral facial nuclei, and the facial nerves (FNs). Theoretically, as BR tests the function of both TN and FNs simultaneously, it is an ideal tool for monitoring the status of TN and FNs during skull base surgeries. Nevertheless, it has been used only recently in surgeries as the use of anesthesia limits its use. METHODS: For this systematic review, 2 authors input the search terms [(Blink Reflex) AND (Intraoperative Neuromonitoring OR Neuro Intraoperative Monitoring OR Intraoperative OR NIOM OR IONM) AND (skull base surgery OR Facial Nerve OR Trigeminal Nerve OR Microvascular Decompression OR Hemifacial Spasm)] in MEDLINE through its PubMed interface and other search engines. Articles that fulfilled the inclusion and exclusion criteria were obtained and scrutinized. RESULTS: Seven observational articles with a total of 437 participants were included. All 5 studies that described the use of BR in FN surgery noted that intraoperative BR is beneficial, safe, sensitive, specific, and predictive of outcomes, while 2 articles describing patients with trigeminal neuralgia recommended use of BR in microvascular decompression of TN. CONCLUSIONS: Intraoperative BR is a sensitive, specific, and safe monitoring technique that has good predictability of facial paresis and paresthesia among patients undergoing MVD for trigeminal neuralgia and primary hemifacial spasm and patients undergoing cerebellopontine angle tumor resection.

Usefulness of Robotic Stereotactic Assistance (ROSA®) Device for Stereoelectroencephalography Electrode Implantation: A Systematic Review and Meta-analysis.

The aim of this study was to systematically review and meta-analyze the efficiency and safety of using the Robotic Stereotactic Assistance (ROSA®) device (Zimmer Biomet; Warsaw, IN, USA) for stereoelectroencephalography (SEEG) electrode implantation in patients with drug-resistant epilepsy. Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a literature search was carried out. Overall, 855 nonduplicate relevant articles were determined, and 15 of them were selected for analysis. The benefits of the ROSA® device use in terms of electrode placement accuracy, as well as operative time length, perioperative complications, and seizure outcomes, were evaluated. Studies that were included reported on a total of 11,257 SEEG electrode implantations. The limited number of comparative studies hindered the comprehensive evaluation of the electrode implantation accuracy. Compared with frame-based or navigation-assisted techniques, ROSA®-assisted SEEG electrode implantation provided significant benefits for reduction of both overall operative time (mean difference [MD], -63.45 min; 95% confidence interval [CI] from -88.73 to -38.17 min; P < 0.00001) and operative time per implanted electrode (MD, -8.79 min; 95% CI from -14.37 to -3.21 min; P = 0.002). No significant differences existed in perioperative complications and seizure outcomes after the application of the ROSA® device and other techniques for electrode implantation. To conclude, the available evidence shows that the ROSA® device is an effective and safe surgical tool for trajectory-guided SEEG electrode implantation in patients with drug-resistant epilepsy, offering benefits for saving operative time and neither increasing the risk of perioperative complications nor negatively impacting seizure outcomes.

Novel technique of switching TIVA and sevoflurane during epilepsy surgery for combined intraoperative motor evoked potentials monitoring and electrocorticography: an illustrative case report.

BACKGROUND: During epilepsy surgery, it is equally important to record electrocorticography (ECoG) for detecting epileptogenic activity and guiding brain resection, and to evaluate neuromonitoring data, particularly motor evoked potentials (MEP), for avoidance of postoperative neurological complications. However, sevoflurane, which is commonly used during recording of ECoG, may attenuate the MEP response. It enforces anesthesiologists and neurosurgeons to select one anesthetic agent over another, facilitating either ECoG or MEP monitoring. CASE PRESENTATION: In the presented case of a 20-year-old man, who underwent surgery for temporal lobe epilepsy, a novel technique of neuroanesthesia was introduced, integrating initial induction of the total intravenous anesthesia (TIVA) with propofol (effect-site concentration, 2.3-3.0 µg/ml), its subsequent switching to sevoflurane (end-tidal concentration, 2.5%) for ECoG recording, and further change back to TIVA for MEP monitoring during brain resection. CONCLUSIONS: Intraoperative switch of anesthetic agents according to specific intraoperative requirements may be useful for cases of brain surgery requiring both ECoG recordings and MEP monitoring.

Chronologic Changes in Transcranial Motor Evoked Potential During Anterior Temporal Lobectomy in Patients with Temporal Lobe Epilepsy: A Single-Center Cross-Sectional Analytic Study.

OBJECTIVE: Despite the benefits of anterior temporal lobectomy with amygdalohippocampectomy in patients with temporal lobe epilepsy (TLE), approximately up to 5% may have hemiparesis as its postoperative complication. This paper aims to describe which step/s of the anterior temporal lobectomy with amygdalohippocampectomy have the highest probability of having the greatest decrease in motor evoked potential (MEP) amplitude. METHODS: This study used a cross-sectional design of obtaining data from TLE patients who underwent anterior temporal lobectomy with amygdalohippocampectomy with transcranial MEP monitoring. Each of the following steps were evaluated for reduction in MEP amplitude: 1) dural opening, 2) opening the inferior horn, 2) vertical temporal lobe resection 3) subpial dissection, 4) temporal lobe stem resection, 5) lateral temporal lobe resection, 6) hippocampal resection, 7) amygdala resection, 8) uncus resection, and 9) dural closure. RESULTS: Nineteen patients were included in the study. Based on the Friedman Test, 1 or more steps had significantly different average MEP amplitude reductions (Friedman = 50.7, P = 0.0001). When compared with baseline (100%, cutoff P = 0.005), hippocampal resection (z = -3.81, P < 0.0001), T1 subpial dissection (z = -3.2, P = 0.0010), uncus resection (z = -3.48, P = 0.0002), temporal stem resection (z = -3.26, P = 0.001), lateral temporal lobe resection (z = -3.13, P = 0.002), and amygdalectomy (-z = -3.37, P = 0.0005) were significantly lower. Of these, hippocampal resection, uncus resection, and amygdalectomy were deemed highly significant. CONCLUSIONS: MEP amplitude tends to decrease during amygdala, hippocampal, and uncal resection because of surgical manipulation of anterior choroidal arteries, which can potentially cause hemiparesis. Careful attention should be paid to changes in MEP during these steps.

Subdural Hygroma After Management of Ruptured Intracranial Aneurysms: Incidence, Associated Factors, Clinical Course, and Management Options.

OBJECTIVE: To evaluate the incidence, associated factors, clinical course, and management options of subdural hygroma in patients treated for aneurysmal subarachnoid hemorrhage (aSAH). METHODS: From January 2013 until June 2022, 336 consecutive patients with aSAH underwent treatment in our center. No one patient was excluded from the study cohort. Computed tomography (CT) examinations were performed at admission, immediately after surgery and on the first postoperative day, and subsequently in case of any neurologic deterioration or, at least, once per week until discharge from the hospital. Thereafter, CT examinations were at the discretion of specialists in the rehabilitation facility, referring physicians, or neurosurgeons at the outpatient clinic. RESULTS: The length of radiologic follow-up starting from CT at admission ranged from 1 to 3286 days (mean, 673 ± 895 days; median, 150 days). Subdural hygromas developed in 84 patients (25%). An average interval until this imaging finding from the initial CT examination was 25 ± 55 days (median, 8 days; range, 0-362 days). Evaluation in the multivariate model showed that patient age ≥72 years (P < 0.0001), cerebrospinal fluid (CSF) shunting (P < 0.0001), and microsurgical clipping of ruptured intracranial aneurysm (RIA; P < 0.0001) are independently associated with the development of subdural hygroma. In 54 of 84 cases (64%), subdural hygromas required observation only. Increase of the lesion size with (5 cases) or without (10 cases) appearance of midline shift was associated with patient age <72 years (P = 0.0398), decompressive craniotomy (P = 0.0192), and CSF shunting (P = 0.0009), whereas evaluation of these factors in the multivariate model confirmed independent association of only CSF shunting (P = 0.0003). Active management of subdural hygromas included adjustment of the shunt programmable valve opening pressure, cranioplasty, external subdural drainage, or their combination. Overall, during follow-up (mean, 531 ± 824 days; median, 119 days; range, 2-3285 days) after the start of observation or applied treatment, subdural hygromas showed either decrease (50 cases) or stabilization (34 cases) of their sizes, and no one lesion showed progression again. CONCLUSIONS: The clinical course of subdural hygromas in patients treated for aSAH is generally favorable, but occasionally these lesions show progressive enlargement with or without the appearance of midline shift, which requires active management.

Early tumor-related hemorrhage after stereotactic radiosurgery of brain metastases: Systematic review of reported cases.

OBJECTIVE: Early (within 72 h) tumor-related hemorrhage (TRH) after stereotactic radiosurgery (SRS) of brain metastases (BM) has been reported only occasionally. Systematic review of such cases was done. METHODS: Literature search was performed through PubMed according to PRISMA guidelines using combination of the following medical subject headings: "hemorrhage," "stereotactic radiosurgery," and "brain metastasis." RESULTS: In total, 7 case reports and 8 clinical series, which noted early TRH after SRS of BM were identified. Scarce and inconsistent data precluded their precise synthesis and statistical analysis. BM of renal cell carcinoma comprised around one-third of reported cases. In 4 patients with multiple BM, TRH after SRS was noted simultaneously in several irradiated tumors. Considering 17 reported cases overall, in 3 patients TRH occurred during SRS session itself, in 4 within several minutes upon completion of treatment, in 7 within several hours thereafter, and in 3 on the third posttreatment day. Out of 11 reported cases providing detailed outcome, 6 patients died shortly after the ictus, 2 others were severely disabled at discharge, and 3 demonstrated good-to-moderate recovery. Overall, among evaluated series the median rates of early TRH after SRS for BM were 0.8% per patient (range, 0.4 - 1.9%) and 0.3% per tumor (range, 0.05 - 0.8%). CONCLUSION: Early TRH is very rare, but potentially life-threatening complication of SRS for BM; thus, its risk (while extremely low) and possible consequences should be discussed at the time of obtaining informed consent.

Nonconvulsive status epilepticus as sign of tumor recurrence.

Status epilepticus (SE) can be a sign of brain tumor progression or recurrence, but there are few reports of nonconvulsive status epilepticus (NCSE) being a sign of tumor progression or recurrence. Moreover, much remains to be elucidated about its clinical course, and outcome. This is the first report of NCSE associated with the progression of a metastatic brain tumor treated by surgical excision of the tumor. The patient was 74-year-old woman. She had a history of craniotomy for tumor resection and gamma knife treatment for multiple metastatic brain tumors originating from breast cancer. She suddenly developed dysarthria and right hemiparesis, followed by convulsive seizures in the right side of her body. Magnetic resonance imaging showed tumor recurrence in the left parietal lobe and worsening edematous changes around the tumor. Antiseizure medication was initiated, however her seizures did not improve; therefore, tumor resection was performed. Postoperatively, her consciousness, seizures, and electroencephalogram findings improved. NCSE caused by brain tumors may be refractory to treatment with antiseizure medications, and early surgical treatment may be useful for seizure control.

Efficacy and tolerability of lacosamide and controlled-release carbamazepine monotherapy in patients with newly diagnosed temporal lobe epilepsy: Post hoc analysis of a randomized, double-blind trial.

PURPOSE: Temporal lobe epilepsy (TLE) is often associated with drug-resistant seizures. We evaluated the efficacy and tolerability of lacosamide (LCM) versus controlled-release carbamazepine (CBZ-CR) monotherapy in adults with newly diagnosed TLE. METHODS: Exploratory post hoc analysis of patients with temporal focus of localization (indicated as the only localization focus) in a double-blind, noninferiority, phase 3 trial (SP0993; NCT01243177) in patients aged ≥ 16 years with newly diagnosed epilepsy randomized 1:1 to LCM or CBZ-CR monotherapy. RESULTS: Of 886 treated patients in this trial, temporal lobe focus of localization (TLE) was reported as the single focus for 287 (32.4%) patients (LCM 134, CBZ-CR 153). A similar proportion of patients with TLE on LCM (82  [61.2%]) and CBZ-CR (99  [64.7%]) completed the trial. Kaplan-Meier estimates for 6- and 12-month seizure freedom at the last evaluated dose level (stratified by number of seizures in the 3 months before screening  [≤2 or >2 seizures]) were similar with LCM and CBZ-CR (6 months overall: 88.7% and 89.7%; 12 months overall: 78.3% and 81.7%). Treatment-emergent adverse events (TEAEs) were reported by fewer patients on LCM (73.9%) than CBZ-CR (81.0%). Drug-related TEAEs (assessed by the investigator) were reported in 41.8% of patients on LCM and 52.3% of patients on CBZ-CR; 11.2% of patients on LCM and 15.0% on CBZ-CR discontinued due to TEAEs. CONCLUSION: Lacosamide was efficacious and generally well tolerated as monotherapy in patients with TLE with efficacy outcomes comparable with CBZ-CR, and fewer patients on LCM reported any TEAEs, drug-related TEAEs, or discontinued due to TEAEs.

Long-term outcomes after surgery for brainstem cavernous malformations: analysis of 46 consecutive cases.

OBJECTIVE: The objective of this study was to evaluate the long-term outcomes after resection of brainstem cavernous malformations (BSCMs) and to assess the usefulness of the Lawton grading system in these cases. METHODS: This retrospective study analyzed 46 consecutive patients with BSCMs operated on between July 1990 and December 2020. Outcomes at the last follow-up were defined as favorable (modified Rankin Scale [mRS] score 0-2) or unfavorable (mRS score > 2). RESULTS: The study cohort comprised 24 men (52%) and 22 women (48%), ranging in age from 8 to 78 years old (median 37 years). In 19 patients (41%), the preoperative mRS score was > 2. All patients had hemorrhagic BSCM. There were 12 (26%) mesencephalic, 19 (41%) pontine, 7 (15%) medullary, and 8 (17%) cerebellar peduncle lesions, with a maximal diameter ranging from 5 to 40 mm (median 15 mm). In total, 24 BSCMs (52%) had bilateral extension crossing the brainstem midline. Lawton grades of 0, I, II, III, IV, V, and VI were defined in 3 (7%), 2 (4%), 10 (22%), 11 (24%), 8 (17%), 7 (15%), and 5 (11%) cases, respectively. Total resection of BSCMs was attained in 43 patients (93%). There were no perioperative deaths. Excluding the 3 most recent cases, the length of follow-up ranged from 56 to 365 months. The majority of patients demonstrated good functional recovery, but regress of the preexisting oculomotor nerve deficit was usually incomplete. No new hemorrhagic events were noted after total resection of BSCMs. In 42 patients (91%), the mRS score at the time of last follow-up was ≤ 2 (favorable outcome), and in 18 (39%), it was 0 (absence of neurological symptoms). Forty-four patients (96%) demonstrated clinical improvement and 2 (4%) had no changes compared with the preoperative period. Multivariate analysis revealed that only lower Lawton grade had a statistically significant independent association (p = 0.0280) with favorable long-term outcome. The area under the receiver operating characteristic curve for prediction of favorable outcome with 7 available Lawton grades of BSCM was 0.93. CONCLUSIONS: Resection of hemorrhagic BSCMs by an experienced neurosurgeon may be performed safely and effectively, even in severely disabled patients. In the authors' experience, preexisting oculomotor nerve palsy represents the main cause of permanent postoperative neurological morbidity. The Lawton grading system effectively predicts long-term outcome after surgery.

Miliary Tuberculosis during R-MPV Therapy in an Elderly Patient with Primary Central Nerve System Lymphoma: A Case Report.

Most elderly patients with tuberculosis (TB) have previously been infected with Mycobacterium tuberculosis, which remains dormant in the body for decades and may reactivate when their immunity declines due to underlying diseases. Elderly cancer patients are at a high risk for TB, and the treatment of TB reactivation in these patients is challenging. Among cancer patients, the incidence of TB reactivation is the highest in lymphoma patients. However, the impact of chemotherapy on TB reactivation in lymphoma patients is unknown. We report the case of an immunocompetent elderly patient with primary central nervous system lymphoma (PCNSL) having no prior history of TB, who developed miliary TB during multiagent chemotherapy consisting of rituximab, high-dose methotrexate, procarbazine, and vincristine (R-MPV therapy). Retrospectively, the chest computed tomography showed calcification of the pleura, suggesting that the patient had a latent tuberculosis infection (LTBI) and developed miliary TB from the reactivation of TB triggered by the R-MPV therapy. Our case emphasizes that when chemotherapy is administered to patients with PCNSL, interferon-gamma release assay (IGRA) should be performed if there are findings on chest examination suggestive of LTBI, such as pleural calcification, and if IGRA is positive, chemotherapy should be given concurrently with LTBI treatment.

Appropriate treatment within 13 hours after onset may improve outcome in patients with high-grade aneurysmal subarachnoid hemorrhage.

OBJECTIVE: This retrospective study evaluated whether earlier timing of appropriate treatment of high-grade aneurysmal subarachnoid hemorrhage (aSAH), defined as management of ruptured intracranial aneurysm (RIA) combined with required additional surgical measures for control of increased intracranial pressure (ICP), is associated with more favorable outcomes. METHODS: The study cohort comprised 253 patients with high-grade aSAH. Modified Rankin Scale score of 0-3 at 3-month follow-up after the ictus was considered as favorable outcome. RESULTS: Appropriate treatment of aSAH was completed in 205 patients (81 %), and included clipping or coiling of RIA without (64 cases) and with (141 cases) additional surgical measures for control of increased ICP (evacuation of intracranial hematoma, decompressive craniotomy, and/or cerebrospinal fluid drainage). Favorable outcome was noted significantly more often if appropriate treatment was completed within 13 h after aSAH than between 13 and 72 h (37 % vs. 17 %; adjusted P = 0.0475), which was confirmed by evaluation in the multivariate model along with other prognostic factors. Subgroup analysis revealed that completion of the appropriate treatment within 13 h was associated with more favorable outcome in those patients, who underwent management of RIA in combination with additional surgical measures for control of increased ICP (P = 0.0023), and in those, who felt into poor outcome predicting group (P = 0.0046). CONCLUSIONS: Appropriate treatment of high-grade aSAH with management of RIA in combination with required additional surgical measures for control of increased ICP, may be associated with more favorable outcomes if completed within 13 h after the ictus.

Intravenous perampanel as an alternative to the oral formulations in Japanese patients with epilepsy.

OBJECTIVE: Perampanel is an oral anti-seizure medication, which is approved in Japan for focal-onset seizures, with/without focal to bilateral tonic-clonic seizures, as monotherapy/adjunctive therapy in patients aged 4 years and older. Treatment for generalized tonic-clonic seizures as adjunctive therapy in patients aged 12 years and older is approved as well. We evaluated the feasibility of intravenous (IV) administration of perampanel as an alternative to oral administration. METHODS: Study 240 (NCT03754582) was an uncontrolled, open-label study of IV perampanel, conducted in 21 Japanese patients with epilepsy who received a stable dose of 8-12 mg/day of oral perampanel. Patients received 30-minute IV infusions at equivalent daily doses of oral perampanel for 4 days, then were switched back to oral perampanel. Safety, tolerability, plasma concentration, and maintenance of efficacy throughout the transition between IV and oral dosing of perampanel were assessed. As supportive data, a subgroup analysis was also conducted using data from healthy Japanese subjects (n = 18) who were enrolled in Study 050 (NCT03376997) investigating the pharmacokinetics and safety of IV perampanel in healthy subjects who received an IV infusion (30-, 60-, or 90-minute) of perampanel 12 mg and a single oral administration of perampanel 12-mg tablet. RESULTS: In Study 240, the transition between 30-minute IV and oral perampanel dosing was associated with a ≤1.4-fold increase in the mean change in maximum observed concentration of perampanel. Seizure outcomes demonstrated no considerable changes in efficacy before, during, or after 30-minute IV dosing of perampanel. The safety profiles were similar between IV and oral formulations. In Study 050, the pharmacokinetics of 30- or 60-minute IV infusion of perampanel further support the interchangeability between oral and IV formulations in the Japanese subjects. SIGNIFICANCE: These results support that 30-minute IV perampanel may be a potential short-term alternative to oral formulations for patients with epilepsy.

Adult-onset angiocentric glioma of epithelioid cell-predominant type of the mesial temporal lobe suggestive of a rare but distinct clinicopathological subset within a spectrum of angiocentric cortical ependymal tumors.

Angiocentric glioma (AG) is defined as an epilepsy-associated stable or slowly growing cerebral tumor primarily affecting children and young adults, histologically consisting mainly of monomorphic, bipolar spindle-shaped cells and occasional round to monopolar columnar epithelioid cells, showing angiocentric growth pattern and features of ependymal differentiation. We describe two clinicopathologically unusual cases of AG. Case 1 is a 54-year-old woman with a 10-year history of complex partial seizures. MRI revealed non-enhancing T1-low, T2/fluid-attenuated inversion recovery (FLAIR)-high intensity signal change in the left hippocampus and amygdala. After selective amygdalohippocampectomy, she had rare non-disabling seizures on medication for over 50 months (Engel's class I). Case 2 is a 37-year-old man with a 3-year history of complex partial seizures. MRI revealed non-enhancing T1-low, T2/FLAIR-high intensity signal change in the left uncus and amygdala. After combined amygdalohippocampectomy and anterior temporal lobectomy, he has been seizure-free for over 11 months. Histologically the tumors in both cases consisted mainly of infiltrating epithelioid cells (GFAP- ∼±, S-100-) with perinuclear epithelial membrane antigen (EMA)-positive dots and rings, showing conspicuous single- and multi-layered angiocentric arrangements. Occasional tumor cells showed spindle-shaped morphology (GFAP+, S-100+) with rare EMA-positive dots aligned radially and longitudinally along parenchymal blood vessels. Focal solid areas showed a Schwannoma-like fascicular arrangement with rare EMA-positive dots and/or sheets of epithelioid cells with abundant EMA dots. Electron microscopic investigation demonstrated features of ependymal differentiation. These cases, together with a few similar cases previously reported, appear to represent a rare but distinct clinicopathological subset of AG characterized by adult-onset, mesial temporal lobe localization and epithelioid cell-predominant histology.