Outcomes and Prognostic Factors of Magnetic Resonance-guided Focused Ultrasound Thalamotomy for Essential Tremor at 2-year Follow-up.

Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is an effective treatment for essential tremor (ET). However, its long-term outcomes and prognostic factors remain unclear. This study aimed to retrospectively investigate 38 patients with ET who underwent MRgFUS thalamotomy and were followed up for >2 years. The improvement in tremor was evaluated using the Clinical Rating Scale for Tremor (CRST). Adverse events were documented, and correlations with factors, such as skull density ratio (SDR), maximum mean temperature (T-max), and lesion size, were examined. Furthermore, the outcomes were compared between two groups, one that met the cutoff values, which was previously reported (preoperative CRST-B ≤ 25, T-max ≥ 52.5°C, anterior-posterior size of lesion ≥ 3.9 mm, superior-inferior [SI] size of lesion > 5.5 mm), and the other that did not. The improvement rate was 59.4% on average at the 2-year follow-up. Adverse events, such as numbness (15.8%), dysarthria (10.5%), and lower extremity weakness (2.6%), were observed even after 2 years, although these were mild. The factors correlated with tremor improvement were the T-max and SI size of the lesion (p < 0.05), whereas the SDR showed no significance. Patients who met the aforementioned cutoff values demonstrated a 69.8% improvement at the 2-year follow-up, whereas others showed a 43.6% improvement (p < 0.05). In conclusion, MRgFUS is effective even after 2 years. The higher the T-max and the larger the lesion size, the better the tremor control. Previously reported cutoff values clearly predict the 2-year prognosis, indicating the usefulness of MRgFUS.

Cerebellar and thalamic connector hubs facilitate the involvement of visual and cognitive networks in essential tremor.

INTRODUCTION: Connector hubs are specialized brain regions that connect multiple brain networks and therefore have the potential to affect the functions of multiple systems. This study aims to examine the involvement of connector hub regions in essential tremor. METHODS: We examined whole-brain functional connectivity alterations across multiple brain networks in 27 patients with essential tremor and 27 age- and sex-matched healthy controls to identify affected hub regions using a network metric called functional connectivity overlap ratio estimated from resting-state functional MRI. We also evaluated the relationships of affected hubs with cognitive and tremor scores in all patients and with motor function improvement scores in 15 patients who underwent postoperative follow-up evaluations after focused ultrasound thalamotomy. RESULTS: We have identified affected connector hubs in the cerebellum and thalamus. Specifically, the dentate nucleus in the cerebellum and the dorsomedial thalamus exhibited more extensive connections with the sensorimotor network in patients. Moreover, the connections of the thalamic pulvinar with the visual network were also significantly widespread in the patient group. The connections of these connector hub regions with cognitive networks were negatively associated (FDR q < 0.05) with cognitive, tremor, and motor function improvement scores. CONCLUSION: In patients with essential tremor, connector hub regions within the cerebellum and thalamus exhibited widespread functional connections with sensorimotor and visual networks, leading to alternative pathways outside the classical tremor axis. Their connections with cognitive networks also affect patients' cognitive function.

Boltless nylon-suture technique for stereotactic electroencephalography as a safe, effective alternative when the anchor bolt is inappropriate.

BACKGROUND: The use of anchor bolts to secure electrodes to the skull can be difficult in some clinical situations. Herein, we present the boltless technique to secure electrodes to the scalp using nylon sutures to overcome the problems associated with anchor bolts. We investigated the safety, accuracy errors, and patient-related and operative factors affecting errors in the boltless technique. METHODS: This single-institution retrospective series analyzed 103 electrodes placed in 12 patients. The target-point localization error (TPLE), entry-point localization error (EPLE), radial error (RE), and depth error (DE) of the electrodes were calculated. RESULTS: The median of the mean operative time per electrode was 9.3 min. The median TPLE, EPLE, RE, and absolute DE value were 4.1 mm, 1.6 mm, 2.7 mm, and 1.9 mm, respectively. Positive correlations were observed between the preoperative scalp thickness, mean operative time per electrode, EPLE, RE, and the absolute value of DE versus TPLE (r = .228, p = .02; r = .678, p = .015; r = .228, p = .02; r = .445, p < .01; r = .630, p < .01, respectively), and electrode approach angle versus EPLE (r = .213, p = .031). Multivariate analysis revealed that the absolute value of DE had the strongest influence on the TPLE, followed by RE and preoperative scalp thickness, respectively (ß = .938, .544, .060, respectively, p < .001). No complications related to SEEG insertion and monitoring were encountered. CONCLUSION: The boltless technique using our unique planning and technical method is a safe, effective, and low-cost alternative in cases where anchor bolts are contraindicated.

Characteristics of deceased subjects transported to a postmortem imaging center due to unusual death related to epilepsy.

OBJECTIVE: Patients with epilepsy have high risk of experiencing uncommon causes of death. This study aimed to evaluate patients who underwent unusual deaths related to epilepsy and identify factors that may contribute to these deaths and may also include sudden unexpected death in epilepsy (SUDEP). METHODS: We analyzed 5291 cases in which a postmortem imaging (PMI) study was performed using plane CT, because of an unexplained death. A rapid troponin T assay was performed using peripheral blood samples. Clinical information including the cause of death suspected by the attending physician, body position, place of death, medical history, and antiseizure medications was evaluated. RESULTS: A total of 132 (2.6%) patients had an obvious history of epilepsy, while 5159 individuals had no history of epilepsy (97.4%). Cerebrovascular disease was the cause of death in 1.6% of patients in the group with epilepsy, and this was significantly lower than that in the non-epilepsy group. However, drowning was significantly higher (9.1% vs. 4.4%). Unspecified cause of death was significantly more frequent in the epilepsy group (78.0% vs. 57.8%). Furthermore, the proportion of patients who demonstrated elevation of troponin T levels without prior cardiac disease was significantly higher in the epilepsy group (37.9% vs. 31.1%). At discovery of death, prone position was dominant (30.3%), with deaths occurring most commonly in the bedroom (49.2%). No antiseizure medication had been prescribed in 12% of cases, while 29.5% of patients were taking multiple antiseizure medications. SIGNIFICANCE: The prevalence of epilepsy in individuals experiencing unusual death was higher than in the general population. Despite PMI studies, no definitive cause of death was identified in a significant proportion of cases. The high troponin T levels may be explained by long intervals between death and examination or by higher incidence of myocardial damage at the time of death. PLAIN LANGUAGE SUMMARY: This study investigated unusual deaths in epilepsy patients, analyzing 5291 postmortem imaging cases. The results showed that 132 cases (2.6%) had a clear history of epilepsy. In these cases, only 22% cases were explained after postmortem examination, which is less than in non-epilepsy group (42.2%). Cerebrovascular disease was less common in the epilepsy group, while drowning was more common. Elevated troponin T levels, which suggest possibility of myocardial damage or long intervals between death and examination, were also more frequent in the epilepsy group compared to non-epilepsy group.

Connectivity alteration in thalamic nuclei and default mode network-related area in memory processes in mesial temporal lobe epilepsy using magnetoencephalography.

This work aimed to investigate the involvement of the thalamic nuclei in mesial temporal lobe epilepsy (MTLE) and identify the influence of interictal epileptic discharges on the neural basis of memory processing by evaluating the functional connectivity (FC) between the thalamic nuclei and default mode network-related area (DMNRA) using magnetoencephalography. Preoperative datasets of nine patients with MTLE with seizure-free status after surgery and those of nine healthy controls were analyzed. The FC between the thalamic nuclei (anterior nucleus [ANT], mediodorsal nucleus [MD], intralaminar nuclei [IL]), hippocampus, and DMNRA was examined for each of the resting, pre-spike, spike, and post-spike periods in the delta to ripple bands using magnetoencephalography. The FC between the ANT, MD, hippocampus, and medial prefrontal cortex increased in the gamma to ripple bands, whereas the FC between the ANT, IL, and DMNRA decreased in the delta to beta bands, compared with that of the healthy controls at rest. Compared with the rest period, the pre-spike period had significantly decreased FC between the ANT, MD, and DMNRA in the ripple band. Different FC changes between the thalamic nuclei, hippocampus, and DMNRA of specific connections in a particular band may reflect impairment or compensation in the memory processes.

Clinical Impacts of Stereotactic Electroencephalography on Epilepsy Surgery and Associated Issues in the Current Situation in Japan.

Stereotactic electroencephalography (SEEG) is receiving increasing attention as a safe and effective technique in the invasive evaluation for epileptogenic zone (EZ) detection. The main clinical question is whether the use of SEEG truly improves outcomes. Herein, we compared outcomes in our patients after three types of intracranial EEG (iEEG): SEEG, the subdural electrode (SDE), and a combined method using depth and strip electrodes. We present here our preliminary results from two demonstrative cases. Several international reports from large epilepsy centers found the following clinical advantages of SEEG: 1) three-dimensional analysis of structures, including bilateral and multilobar structures; 2) low rate of complications; 3) less pneumoencephalopathy and less patient burden during postoperative course, which allows the initiation of video-EEG monitoring immediately after implantation and does not require resection to be performed in the same hospitalization; and 4) a higher rate of good seizure control after resection. In other words, SEEG more accurately identified the EZ than the SDE method. We obtained similar results in our preliminary experiences under limited conditions. In Japan, as of August 2022, dedicated electrodes and SEEG accessories have not been approved and the use of the robot arm is not widespread. The Japanese medical community is hopeful that these issues will soon be resolved and that the experience with SEEG in Japan will align with that of large epilepsy centers internationally.

Relief of Central Poststroke Pain Affecting Both the Arm and Leg on One Side by Double-independent Dual-lead Spinal Cord Stimulation Using Fast-acting Subperception Therapy Stimulation: A Case Report.

Central poststroke pain is a chronic, intractable, central neuropathic pain. Spinal cord stimulation is a neuromodulation therapy for chronic neuropathic pain. The conventional stimulation method induces a sense of paresthesia. Fast-acting subperception therapy is one of the latest new stimulation methods without paresthesia. A case of achieving pain relief of central poststroke pain affecting both the arm and leg on one side by double-independent dual-lead spinal cord stimulation using fast-acting subperception therapy stimulation is presented. A 67-year-old woman had central poststroke pain due to a right thalamic hemorrhage. The numerical rating scale scores of the left arm and leg were 6 and 7, respectively. Using dual-lead stimulation at the Th 9-11 levels, a spinal cord stimulation trial was performed. Fast-acting subperception therapy stimulation achieved pain reduction in the left leg from 7 to 3. Therefore, a pulse generator was implanted, and the pain relief continued for 6 months. Then, two additional leads were implanted at the C 3-5 levels, and pain in the arm decreased from 6 to 4. Independent setting and adjustments of the dual-lead stimulation were required because the thresholds of paresthesia perception were significantly different. To achieve pain relief in both the arm and leg, double-independent dual-lead stimulation placed at cervical and thoracic levels is an effective treatment. Fast-acting subperception therapy stimulation may be effective for central poststroke pain, especially in cases where the paresthesia is perceived as uncomfortable or the conventional stimulation itself is ineffective.

Magnetic resonance-guided focused ultrasound thalamotomy restored distinctive resting-state networks in patients with essential tremor.

OBJECTIVE: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy ameliorates symptoms in patients with essential tremor (ET). How this treatment affects canonical brain networks has not been elucidated. The purpose of this study was to clarify changes of brain networks after MRgFUS thalamotomy in ET patients by analyzing resting-state networks (RSNs). METHODS: Fifteen patients with ET were included in this study. Left MRgFUS thalamotomy was performed in all cases, and MR images, including resting-state functional MRI (rsfMRI), were taken before and after surgery. MR images of 15 age- and sex-matched healthy controls (HCs) were also used for analysis. Using rsfMRI data, canonical RSNs were extracted by performing dual regression analysis, and the functional connectivity (FC) within respective networks was compared among pre-MRgFUS patients, post-MRgFUS patients, and HCs. The severity of tremor was evaluated using the Clinical Rating Scale for Tremor (CRST) score pre- and postoperatively, and its correlation with RSNs was examined. RESULTS: Preoperatively, ET patients showed a significant decrease in FC in the sensorimotor network (SMN), primary visual network (VN), and visuospatial network (VSN) compared with HCs. The decrease in FC in the SMN correlated with the severity of tremor. After MRgFUS thalamotomy, ET patients still exhibited a significant decrease in FC in a small area of the SMN, but they exhibited an increase in the cerebellar network (CN). In comparison between pre- and post-MRgFUS patients, the FC in the SMN and the VSN significantly increased after treatment. Quantitative evaluation of the FCs in these three groups showed that the SMN and VSN increased postoperatively and demonstrated a trend toward those of HCs. CONCLUSIONS: The SMN and CN, which are considered to be associated with the cerebello-thalamo-cortical loop, exhibited increased connectivity after MRgFUS thalamotomy. In addition, the FC of the visual network, which declined in ET patients compared with HCs, tended to normalize postoperatively. This could be related to the hypothesis that visual feedback is involved in tremor severity in ET patients. Overall, the analysis of the RSNs by rsfMRI reflected the pathophysiology with the intervention of MRgFUS thalamotomy in ET patients and demonstrated a possibility of a biomarker for successful treatment.

A case report: Dual-lead deep brain stimulation of the posterior subthalamic area and the thalamus was effective for Holmes tremor after unsuccessful focused ultrasound thalamotomy.

Holmes tremor is a symptomatic tremor that develops secondary to central nervous system disorders. Stereotactic neuromodulation is considered when the tremors are intractable. Targeting the ventral intermediate nucleus (Vim) is common; however, the outcome is often unsatisfactory, and the posterior subthalamic area (PSA) is expected as alternative target. In this study, we report the case of a patient with intractable Holmes tremor who underwent dual-lead deep brain stimulation (DBS) to stimulate multiple locations in the PSA and thalamus. The patient was a 77-year-old female who complained of severe tremor in her left upper extremity that developed one year after her right thalamic infarction. Vim-thalamotomy using focused ultrasound therapy (FUS) was initially performed but failed to control tremor. Subsequently, we performed DBS using two leads to stimulate four different structures. Accordingly, one lead was implanted with the aim of targeting the ventral oralis nucleus (Vo)/zona incerta (Zi), and the other with the aim of targeting the Vim/prelemniscal radiation (Raprl). Electrode stimulation revealed that Raprl and Zi had obvious effects. Postoperatively, the patient achieved good tremor control without any side effects, which was maintained for two years. Considering that she demonstrated resting, postural, and intention/action tremor, and Vim-thalamotomy by FUS was insufficient for tremor control, complicated pathogenesis was presumed in her symptoms including both the cerebellothalamic and the pallidothalamic pathways. Using the dual-lead DBS technique, we have more choices to adjust the stimulation at multiple sites, where different functional networks are connected. Intractable tremors, such as Holmes tremor, may have complicated pathology, therefore, modulating multiple pathological networks is necessary. We suggest that the dual-lead DBS (Vo/Raprl and Vim/Zi) presented here is safe, technically feasible, and possibly effective for the control of Holmes tremor.

Three-Staged Surgical Strategy as a Combined Approach for Multilevel Cervical Pyogenic Spondylodiscitis.

Cervical pyogenic spondylodiscitis is rare but can lead to severe clinical problems that often require aggressive surgical treatment for neurological deterioration and life-threatening conditions. Although combined surgical procedures are often utilized to treat multilevel cervical regions, there is a clinical debate regarding the appropriate order and timing of surgeries using the anterior and posterior approaches. Here, we report a case of severe multilevel cervical pyogenic spondylodiscitis treated using a three-staged surgical strategy consisting of cervical laminectomy, posterior fixation, and anterior corpectomy and fusion with an autologous long bone graft; the outcome was quite favorable. Our report demonstrates the safety and usefulness of three-staged surgery in the multilevel cervical region, especially under urgent situations.

Phase I study of single-dose oxaliplatin in Japanese patients with malignant tumors.

BACKGROUND: Oxaliplatin, a platinum compound, has been commonly used around the world for treating advanced colorectal cancer. The generally recommended dose and schedule of oxaliplatin monotherapy is 130 mg/m(2) every 3 weeks. This trial was conducted to evaluate the safety and pharmacokinetics of oxaliplatin monotherapy in Japanese patients with solid tumors. METHODS: Oxaliplatin was administered as a 2-h intravenous infusion every 3 weeks at a dose of 90 and 130 mg/m(2). Blood was collected to determine the total platinum and the ultrafiltrate platinum concentrations in plasma in all cycles. RESULTS: Nine patients were enrolled; three were given oxaliplatin monotherapy at 90 mg/m(2) and six received 130 mg/m(2). All tumors were colorectal cancer. The major adverse reactions included myelosuppressive, neurological and gastrointestinal toxicities, although most were grades 1 and 2 at both dose levels. Peripheral sensory neuropathy of without movement disturbance (grade 1 or 2) was observed in all patients at both dose levels. The 130 mg/m(2) dose level was not found to be the maximum tolerated dose, but was judged to be the recommended dose. No objective responses were seen and five cases of no change were observed. A bi-exponential open model best described the disappearance of platinum in the plasma, and a tri-exponential open model best described the disappearance of ultrafilterable platinum in the plasma at both dose levels. No racial difference was suggested in the pharmacokinetics of oxaliplatin. CONCLUSIONS: The oxaliplatin monotherapy dose schedule of 130 mg/m(2) every 3 weeks, recommended worldwide, is acceptable for Japanese patients.