[Dystonia].

Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements or postures. Currently, dystonia is defined as a network disorder involving the basal ganglia, cerebellum, thalamus, and sensorimotor cortex. Considering that it is refractory to medical therapy, functional neurosurgery is indispensable in the treatment strategy for dystonia. Functional neurosurgery may improve dystonic symptoms by suppressing abnormal neuronal activity in the motor loop network. Deep brain stimulation(DBS)of the globus pallidus internus(GPi)is a useful surgical treatment for genetically defined and primary dystonia involving the axial musculature. Thalamic ventral oral(Vo)nucleus surgery is recommended for cases of peripheral dystonia, such as writer's cramp and other occupational types of dystonia. However, pallidal DBS is less effective in cases of secondary dystonia, with the exception of tardive dystonia. Recent studies have reevaluated that ablation surgery is the last-resort treatment when DBS must be discontinued for certain conditions. Magnetic resonance-guided focused ultrasound(MRgFUS), a novel, incision-free, ablation technique, is currently used for the treatment of focal hand dystonia.

Neurological adverse event profile of magnetic resonance imaging-guided focused ultrasound thalamotomy for essential tremor.

BACKGROUND: Magnetic resonance imaging-guided focused ultrasound thalamotomy is approved by the U.S. Food and Drug Administration for treatment of essential tremor. Although this incisionless technology creates an ablative lesion, it potentially avoids serious complications of open stereotactic surgery. OBJECTIVE: To determine the safety profile of magnetic resonance imaging-guided focused ultrasound unilateral thalamotomy for essential tremor, including frequency, and severity of adverse events, including serious adverse events. METHODS: Analysis of safety data for magnetic resonance imaging-guided focused ultrasound thalamotomy (186 patients, five studies). RESULTS: Procedure-related serious adverse events were very infrequent (1.6%), without intracerebral hemorrhages or infections. Adverse events were usually transient and were commonly rated as mild (79%) and rarely severe (1%). As previously reported, abnormalities in sensation and balance were the commonest thalamotomy-related adverse events. CONCLUSION: The overall safety profile of magnetic resonance imaging-guided focused ultrasound thalamotomy supports its role as a new option for patients with medically refractory essential tremor. © 2018 International Parkinson and Movement Disorder Society.

Subthalamic nucleus stimulation improves Parkinson's disease-associated camptocormia in parallel to its preoperative levodopa responsiveness.

OBJECTIVE: The aim of this work was to identify factors predictive of postoperative improvement of camptocormia in patients with Parkinson's disease (PD) treated by subthalamic nucleus (STN) stimulation. BACKGROUND: Camptocormia, one of the most disabling features of PD, often responds poorly to medical therapies. The reported effects of deep brain stimulation on PD-associated camptocormia vary, and preoperative characteristics affecting the surgical outcome remain unclear. METHODS: We evaluated 17 patients with camptocormia whose preoperative off-medication thoracolumbar angle exceeded 45°. We used photographs to measure their thoracolumbar angle preoperatively, 3 months after surgery, and at the last follow-up (mean 36.5 months postoperatively) in status on-medication and off-medication. The patient age, duration of PD and camptocormia, daily medications, Unified Parkinson's Disease Rating Scale (UPDRS) subscores and the Schwab-England activity of daily living scale (S-E) were also recorded. Univariate analysis was performed to identify factors predictive of the postoperative improvement of camptocormia. RESULTS: STN stimulation significantly improved the UPDRS subscores and S-E, and resulted in a reduction of daily medications 3 months post-treatment. The preoperative thoracolumbar angle (mean±SD) in status off-medication (84.0±29.5°) was significantly ameliorated 3 months postoperatively (49.8±29.3°) and at the last follow-up (54.8±28.3°). There was no correlation between the postoperative camptocormia improvement rate and preoperative parameters other than the duration and severity of camptocormia and the levodopa responsiveness of the thoracolumbar angle. Symptom duration negatively affected levodopa responsiveness. CONCLUSIONS: STN stimulation improves PD-associated camptocormia in parallel with preoperative levodopa responsiveness. Long symptom duration interferes with levodopa responsiveness.

Flatness of the infratentorial space associated with hemifacial spasm.

BACKGROUND: Whether a difference in morphology of the infratentorial space is associated with hemifacial spasm is not well understood. The aim of this study was to analyze the three-dimensional conformation of the infratentorial space and evaluate any possible contribution of morphological characteristics to the development of neurovascular compression leading to hemifacial spasm. METHODS: We enrolled 25 patients with hemifacial spasm and matched them by age and sex to controls. The extent of the three-dimensional axes and the volume of the infratentorial space were measured using image analysis software for three-dimensional MRI. We evaluated the correlation between a morphological difference in the infratentorial space and changes in vascular configuration in the brain stem. RESULTS: We found no statistical difference in volumetric analyses. The mean aspect ratio on the coronal plane (the ratio of the Z to X extent) of the infratentorial space in patients with hemifacial spasm was significantly lower (p < 0.01) than that in controls, as was the mean aspect ratio on the sagittal plane (the ratio of Z to Y extent, p < 0.01). A smaller sagittal aspect ratio was correlated (p < 0.05) with greater lateral deviation of the basilar artery. CONCLUSIONS: Our results suggest that flatness of the superior-inferior dimension of the infratentorial space is an anatomical feature that characterizes patients with hemifacial spasm. We hypothesize that this unique structural variation may exaggerate the lateral deviation of the vertebrobasilar arteries due to arteriosclerosis and exacerbate the space competition among vessels and cranial nerves.

Long disease duration interferes with therapeutic effect of globus pallidus internus pallidal stimulation in primary cervical dystonia.

OBJECTIVES: We retrospectively investigated the correlation between disease duration and the therapeutic effect of globus pallidus internus (GPi) stimulation in patients with primary cervical dystonia (CD). MATERIALS AND METHODS: Eight patients with CD unresponsive to medical treatments underwent bilateral GPi deep brain stimulation (DBS). They were followed for 63.5 ± 38.2 months (mean ± standard deviation) and were assessed before and at 1, 12, 24, and 36 months after surgery and at their final visit to our outpatient clinic using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Univariate analysis was performed to identify factors that affected their postoperative TWSTRS score. RESULTS: At last follow-up, disease severity and the degree of disability and pain on the TWSTRS were significantly improved by 70.2%, 76.1%, and 87.1%, respectively (p < 0.05, Wilcoxon signed-rank test). Neither age nor preoperative CD severity was predictive of postoperative improvement; however, the disease duration affected their reduction rate of TWSTRS severity score at each time point investigated (p < 0.05). CONCLUSIONS: Bilateral GPi-DBS is an effective long-term therapy in patients with CD. The delivery of GPi stimulation in the earlier course of CD may yield greater postoperative improvement.

Higher incidence of epilepsy in meningiomas located on the premotor cortex: a voxel-wise statistical analysis.

BACKGROUND: A substantial number of patients with brain tumors develop recurrent seizures, known as tumor-associated epilepsy. It is important to identify specific subgroups of brain tumor patients with higher incidences of epilepsy because a meta-analysis failed to certify the effectiveness of prophylactic anti-epileptic drugs (AEDs) to abort tumor-associated epilepsy as a whole. METHODS: To investigate the relationship between tumor location and incidence of epilepsy, we performed voxel-wise comparison between 3D MRI scans obtained from patients with meningioma-associated epilepsy and those from control patients using spatial normalization techniques on neuroimaging data. Variables such as age, tumor size, the degree of edema, and pathological diagnosis were also compared between the two groups. RESULTS: Our results showed the highest incidence of epilepsy when the tumor was located on the premotor cortex in the frontal lobe (Z-scores >2.0, Liebermeister's quasi-exact test). The stepwise multiple regression analysis on the clinical data revealed that the tumor diameter (p < 0.001) and the patient's age (p = 0.024) were positive and negative predictors, respectively, for the onset of epilepsy. CONCLUSIONS: The incidence of epilepsy was higher in meningiomas located on the premotor cortex than on the other cortex. Larger volume also contributed to the onset of epilepsy. We suggest that variations of epilepsy incidence dependent on tumor characteristics can be considered when treating tumor-associated epilepsy.

Hemichorea induced by a sphenoid ridge meningioma.

BACKGROUND: Movement disorders are rare in brain tumors. We describe a 45-year-old woman with hemichorea, a concomitant contralateral sphenoid ridge meningioma. CASE DESCRIPTION: The meningioma enlarged as her hemichorea worsened, and after meningioma resection, the hemichorea gradually subsided. N-isopropyl-p-[123I]-iodoamphetamine single-photon emission computed tomography performed preoperatively showed decreased regional cerebral blood flow (CBF) to the basal ganglia circuit ipsilateral to the tumor and, when repeated postoperatively, confirmed improved regional CBF. CONCLUSION: We propose that the enlarging sphenoid ridge meningioma had a remote effect on regional CBF and the thalamocortical motor center and that complex changes in the basal ganglia output may have caused the hemichorea.

Focused Ultrasound Thalamotomy for Refractory Essential Tremor: A Japanese Multicenter Single-Arm Study.

BACKGROUND: Several feasibility studies and a randomized, controlled, multicenter trial have demonstrated the safety and efficacy of unilateral transcranial magnetic resonance-guided focused ultrasound (FUS) lesioning of the ventral intermediate thalamic nucleus in treating essential tremor. OBJECTIVE: To evaluate the safety and efficacy of FUS thalamotomy in a Japanese patient cohort through a prospective, multicenter, single-arm confirmatory trial. METHODS: A total of 35 patients with disabling refractory essential tremor underwent unilateral FUS thalamotomy and were followed up for 12 post-treatment months. Safety was measured as the incidence and severity of treatment-related adverse events. Efficacy was measured as the tremor severity and quality of life improvements using the Clinical Rating Scale for Tremor and Questionnaire for Essential Tremor. RESULTS: The mean skull density ratio (SDR) was 0.47. There was a significant decrease in the mean postural tremor score of the treated hand from baseline to 12 mo by 56.4% (95% CI: 46.7%-66.1%; P < .001), which was maintained at last follow-up. Quality of life improved by 46.3% (mean overall Questionnaire for Essential Tremor score of 17.4 [95% CI: 12.1-22.7]) and there were no severe adverse events. The most frequent adverse event was gait disturbance and all events resolved. CONCLUSION: Unilateral FUS thalamotomy allowed significant and sustained tremor relief and improved the quality of life with an outstanding safety profile. The observed safety and efficacy of FUS thalamotomy were comparable to those reported in a previous multicenter study with a low SDR, and inclusion of the low SDR group did not affect effectiveness.

Cardiac ¹²³I-MIBG scintigraphy as an outcome-predicting tool for subthalamic nucleus stimulation in Parkinson's disease.

BACKGROUND: ¹²³I-meta-iodobenzylguanidine (MIBG) myocardial scintigraphy is a useful tool for differentiating idiopathic Parkinson's disease (PD) from other parkinsonian syndromes, but its prognostic value in PD has not been established. The objective of this study was to clarify the correlation between cardiac MIBG uptake parameters and the outcome in PD patients subjected to the subthalamic nucleus stimulation. METHOD: We enrolled 31 consecutive PD patients and calculated the heart-to-mediastinum ratio (H/M) and washout rate (WR) based on the activity measured at 15 min (early phase) and 3 h (delayed phase) after the intravenous injection of MIBG (111 MBq). Cardinal motor symptoms and activity of daily living (ADL) were assessed on the Unified Parkinson's Disease Rating Scale (UPDRS) and Schwab and England (S-E) ADL scale, before and 3 months after surgery. FINDINGS: Neither early nor delayed H/M correlated with any of the preoperative subscores on the UPDRS or S-E, nor with postoperative outcome. On the other hand, increased WR was a positive predictor for postoperative improvement rate on S-E in medication-off state (p = 0.00003). Also, WR showed a more faint but significant correlation with preoperative levodopa responsiveness on S-E (p = 0.008). CONCLUSION: Our findings suggest that ¹²³I-MIBG scintigraphy in combination with levodopa-responsiveness evaluation may represent a useful tool for prediction of outcomes in patients subjected to STN stimulation.

A positive correlation between fractional white matter volume and the response of Parkinson disease patients to subthalamic stimulation.

BACKGROUND: Since optimal patient selection is essential for the success of subthalamic nucleus (STN) stimulation, the identification of reliable outcome predictors is important. The purpose of this study was to identify new imaging characteristics sufficiently reliable to predict treatment results. METHOD: Using preoperative magnetic resonance imaging studies of 21 Parkinson disease (PD) patients treated by STN stimulation, we performed whole brain-based analysis of voxel-based morphometry (VBM) data. Intracranial structures segmented into the gray matter fraction (GMF), white matter fraction (WMF), and cerebrospinal fluid fraction (CSFF) were subjected to univariate and multivariate analysis of the correlation between fractional volumes and postoperative improvement rates using the Unified PD Rating Scale (UPDRS). FINDINGS: At 3 months after surgery, the WMF was significantly correlated with improvement rated on the total UPDRS (p = 0.006), UPDRS part II (activities of daily living; p = 0.008), UPDRS part III (motor; p = 0.005). In contrast, there was no significant correlation between the effect of STN stimulation and GMF or the effect of stimulation and CSFF. The WMF also showed a significant correlation with postoperative scores in the "on" drug and "on" stimulation state (total UPDRS, p = 0.027; UPDRS part II, p = 0.019; UPDRS part III, p = 0.034). CONCLUSIONS: Our data indicate that patients with a larger white matter volume benefited from STN stimulation whereas the volume of other brain structures was not correlated with its effect. We posit that preserved connectivity between components of the basal ganglia-thalamocortical circuit may be required for the effectiveness of electrical stimulation. VBM may represent a powerful tool to predict the response of patients with advanced PD to STN stimulation.

Surgical management of adverse events associated with deep brain stimulation: A single-center experience.

OBJECTIVES: Deep brain stimulation is widely used to treat movement disorders and selected neuropsychiatric disorders. Despite the fact, the surgical methods vary among centers. In this study, we aimed to evaluate our own surgical complications and how we performed surgical troubleshooting. METHODS: A retrospective chart review was performed to evaluate the clinical data of patients who underwent deep brain stimulation surgery and deep brain stimulation-related procedures at our center between October 2014 and September 2019. We reviewed surgical complications and how surgical troubleshooting was performed, regardless of where the patient underwent the initial surgery. RESULTS: A total of 92 deep brain stimulation lead implantation and 43 implantable pulse generator replacement procedures were performed. Among the 92 lead implantation procedures, there were two intracranial lead replacement surgeries and one deep brain stimulation lead implantation into the globus pallidus to add to existing deep brain stimulation leads in the bilateral subthalamic nuclei. Wound revision for superficial infection of the implantable pulse generator site was performed in four patients. There was neither intracerebral hemorrhage nor severe hardware infection in our series of procedures. An adaptor (extension cable) replacement was performed due to lead fracture resulting from a head trauma in two cases. CONCLUSION: We report our experience of surgical management of adverse events associated with deep brain stimulation therapy with clinical vignettes. Deep brain stimulation surgery is a safe and effective procedure when performed by a trained neurosurgeon. It is important for clinicians to be aware that there are troubles that are potentially manageable with optimal surgical treatment.

Predictors of Outcomes After Focused Ultrasound Thalamotomy.

BACKGROUND: Magnetic resonance-guided focused ultrasound thalamotomy (FUS-T) is an emerging treatment for essential tremor (ET). OBJECTIVE: To determine the predictors of outcomes after FUS-T. METHODS: Two treatment groups were analyzed: 75 ET patients enrolled in the pivotal trial, between 2013 and 2015; and 114 patients enrolled in the postpivotal trials, between 2015 and 2016. All patients had medication-refractory, disabling ET, and underwent unilateral FUS-T. The primary outcome (hand tremor score, 32-point scale with higher scores indicating worse tremor) and the secondary outcome variables (Clinical Rating Scale for Tremor Part C score: 32-point scale with higher scores indicating more disability) were assessed at baseline and 1, 3, 6, and 12 mo. The operative outcome variables (ie, peak temperature, number of sonications) were analyzed. The results between the 2 treatment groups, pivotal and postpivotal, were compared with repeated measures analysis of variance and adjusted for confounding variables. RESULTS: A total of 179 patients completed the 12-mo evaluation. The significant predictors of tremor outcomes were patient age, disease duration, peak temperature, and number of sonications. A greater improvement in hand tremor scores was observed in the postpivotal group at all time points, including 12 mo (61.9% ± 24.9% vs 52.1% ± 24.9%, P = .009). In the postpivotal group, higher energy was used, resulting in higher peak temperatures (56.7 ± 2.5 vs 55.6 ± 2.8°C, P = .004). After adjusting for age, years of disease, number of sonications, and maximum temperature, the treatment group was a significant predictor of outcomes (F = 7.9 [1,165], P = .005). CONCLUSION: We observed an improvement in outcomes in the postpivotal group compared to the pivotal group potentially reflecting a learning curve with FUS-T. The other associations of tremor outcomes included patient age, disease duration, peak temperature, and number of sonications.

Cost-minimisation model of magnetic resonance-guided focussed ultrasound therapy compared to unilateral deep brain stimulation for essential tremor treatment in Japan.

OBJECTIVE: To investigate the cost differences between magnetic resonance-guided focussed ultrasound (MRgFUS) and unilateral deep brain stimulation (DBS) for the treatment of medication-refractory essential tremor (ET) in Japan using a cost-minimisation model. METHODS: A cost-minimisation model estimated total costs for MRgFUS and unilateral DBS by summing the pre-procedure, procedure, and post-procedure costs over a 12-month time horizon, using data from published sources and expert clinical opinion. The model base case considered medical costs from fee-for-service tariffs. Scenario analyses investigated the use of Diagnosis Procedure Combination tariffs, a diagnosis-related group-based fixed-payment system, and the addition of healthcare professional labour costs healthcare professionals using tariffs from the Japanese Health Insurance Federation for Surgery. One-way sensitivity analyses altered costs associated with tremor recurrence after MRgFUS, the extraction rate following unilateral DBS, the length of hospitalisation for unilateral DBS and the procedure duration for MRgFUS. The impact of uncertainty in model parameters on the model results was further explored using probabilistic sensitivity analysis. RESULTS: Compared to unilateral DBS, MRgFUS was cost saving in the base case and Diagnosis Procedure Combination cost scenario, with total savings of JPY400,380 and JPY414,691, respectively. The majority of savings were accrued at the procedural stage. Including labour costs further increased the cost differences between MRgFUS and unilateral DBS. Cost savings were maintained in each sensitivity analysis and the probabilistic sensitivity analysis, demonstrating that the model results are highly robust. CONCLUSIONS: In the Japanese healthcare setting, MRgFUS could be a cost saving option versus unilateral DBS for treating medication-refractory ET. The model results may even be conservative, as the cost of multiple follow-ups for unilateral DBS and treatment costs for adverse events associated with each procedure were not included. This model is also consistent with the results of other economic analyses of MRgFUS versus DBS in various settings worldwide.

Combining quantitative susceptibility mapping to the morphometric index in differentiating between progressive supranuclear palsy and Parkinson's disease.

PURPOSE: To determine whether the susceptibility value in the deep gray matter obtained by quantitative susceptibility mapping (QSM) provides additive value to the morphometric index for differentiating progressive supranuclear palsy (PSP) from Parkinson's disease (PD). MATERIALS AND METHODS: PSP- (n = 8) and PD patients (n = 18) and 18 age-matched healthy controls who underwent QSM and 3D magnetization-prepared rapid gradient echo (MPRAGE) sequences. The mean susceptibility values (MSVs) of the deep gray matter structures on QSM- and areas of the midbrain (morphometric index, MI) on 3D MPRAGE images were measured by two neuroradiologists. Analysis of variance, the Scheffe test and receiver operating characteristic (ROC) analysis were conducted to assess differences and discriminate among PSP, PD and controls by the MSVs and the MI. Using the MSV of a structure with the best area under the curve (AUC) and the MI, we created a decision tree to differentiate between PSP and PD. RESULTS: The MSVs of the globus pallidus (GP) and substantia nigra (SN) were significantly higher in PSP than PD and the controls (p < .05). By ROC analysis (PSP vs PD), AUC was greatest (0.903) for the GP. The MI was significantly smaller in PSP than PD and the controls (p < .05); AUC (PSP vs PD) was 0.917. The decision tree using cutoff values of 244 parts per billion for MSV of the GP and 74.0 mm2 for MI served to completely differentiate between PSP and PD. CONCLUSION: The MSV in the GP on QSM images adds value to the MI for differentiating PSP from PD.

Impact of skull density ratio on efficacy and safety of magnetic resonance-guided focused ultrasound treatment of essential tremor.

OBJECTIVE: Skull density ratio (SDR) assesses the transparency of the skull to ultrasound. Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy in essential tremor (ET) patients with a lower SDR may be less effective, and the risk for complications may be increased. To address these questions, the authors analyzed clinical outcomes of MRgFUS thalamotomy based on SDRs. METHODS: In 189 patients, 3 outcomes were correlated with SDRs. Efficacy was based on improvement in Clinical Rating Scale for Tremor (CRST) scores 1 year after MRgFUS. Procedural efficiency was determined by the ease of achieving a peak voxel temperature of 54°C. Safety was based on the rate of the most severe procedure-related adverse event. SDRs were categorized at thresholds of 0.45 and 0.40, selected based on published criteria. RESULTS: Of 189 patients, 53 (28%) had an SDR < 0.45 and 20 (11%) had an SDR < 0.40. There was no significant difference in improvement in CRST scores between those with an SDR ≥ 0.45 (58% ± 24%), 0.40 ≤ SDR < 0.45 (i.e., SDR ≥ 0.40 but < 0.45) (63% ± 27%), and SDR < 0.40 (49% ± 28%; p = 0.0744). Target temperature was achieved more often in those with an SDR ≥ 0.45 (p < 0.001). Rates of adverse events were lower in the groups with an SDR < 0.45 (p = 0.013), with no severe adverse events in these groups. CONCLUSIONS: MRgFUS treatment of ET can be effectively and safely performed in patients with an SDR < 0.45 and an SDR < 0.40, although the procedure is more efficient when SDR ≥ 0.45.

Hemidystonia secondary to thalamic hemorrhage treated with GPi stimulation.

There have been few reports on the surgical treatment of secondary hemidystonias, most of which are due to basal ganglia stroke or trauma. We present 2 patients with hemidystonia secondary to thalamic hemorrhage whom we successfully treated with unilateral globus pallidus internus (GPi) stimulation. Case 1 is a 56-year-old man with abnormal posturing and intolerable muscle contraction pain in the left arm. Case 2 is a 73-year-old woman who developed severe abnormal posturing in the right arm and gait disturbance due to hyperextension of the right leg. The dystonic symptoms of both patients were refractory to medication. Three months after the inception of high frequency GPi stimulation, the motor scores on the Burke-Fahn-Marsden Dystonia Rating Scale were improved by 49.2% and 34.3% in Cases 1 and 2, respectively. We suggest GPi stimulation as a possible alternative to treat secondary hemidystonia.

Concurrent hemichorea and migrainous aura--a perfusion study on the basal ganglia using xenon-computed tomography.

A variety of etiologies underlie the neurophysiological imbalance resulting in chorea. We report a 57-year-old woman with a long-history of migraine who suddenly experienced concurrent scintillating scotoma and rapid involuntary movement of her neck and right extremities. Diffusion-weighted magnetic resonance imaging (MRI) failed to detect any fresh ischemic and/or hemorrhagic lesions. Xenon-computed tomography (CT) disclosed gross reduction in the cerebral blood flow (CBF) of the left occipital area. With precise mapping to the brain atlas, extreme hyperperfusion in the motor thalamus was found on the left side. Asymmetrical CBF reduction of the left subthalamic nucleus was also noted. Her symptoms gradually improved and completely disappeared within 15 days. Repeated xenon-CT 1 month post-onset demonstrated normalized CBF in the affected areas. Our study suggests that vascular event underlies the migrainous aura in this case and secondarily provokes a loss of inhibitory control of the motor thalamus resulting in the manifestation of hemichorea.

Pregabalin as a salvage preoperative treatment for refractory trigeminal neuralgia.

Only few studies have investigated the effectiveness of pregabalin (PGB) treatment for trigeminal neuralgia (TN). We aimed to retrospectively analyze the effectiveness of PGB treatment in refractory TN as a salvage treatment preceding surgery. Of 61 patients with TN refractory to prior treatment with carbamazepine (CBZ), we enrolled 33 patients in our study who agreed to receive PGB before they underwent surgery. The patients were divided into effective and ineffective groups depending on the patient-reported outcome. Correlations between effectiveness and clinical characteristics such as the age, sex, disease duration, initial CBZ responsiveness, the number of patients who underwent polytherapy with PGB and CBZ, final doses of CBZ and PGB at the time of evaluation, and the etiology of the neurovascular compression were statistically analyzed. Furthermore, a linear discriminant analysis was performed to predict effectiveness. TN was improved in 16 patients (48.5%) in the PGB-treatment group but none in patients without PGB-treatment. The final dose of PGB was 166.7 mg at the mean follow-up period of 5.5 months. Our results showed that age was the only factor that significantly differed between PGB-effective and ineffective groups. A logistic regression analysis also demonstrated that among all the clinical variables considered, only older age was significantly associated with effectiveness of PGB treatment. Effectiveness was correctly predicted at a threshold value of 62.7-years-old with 69.7% reliability. We suggest that PGB is useful, even at the low-dose, as a salvage preoperative treatment for patients with refractory TN, particularly for elderly patients.

Improvement of visual field defects after focal resection for occipital lobe epilepsy: case report.

Improvement of visual field defects after surgical treatment for occipital lobe epilepsy is rare. Here, the authors report on a 24-year-old man with a 15-year history of refractory epilepsy that developed after he had undergone an occipital craniotomy to remove a cerebellar astrocytoma at the age of 4. His seizures started with an elementary visual aura, followed by secondary generalized tonic-clonic convulsion. Perimetry revealed left-sided incomplete hemianopia, and MRI showed an old contusion in the right occipital lobe. After evaluation with ictal video-electroencephalography, electrocorticography, and mapping of the visual cortex with subdural electrodes, the patient underwent resection of the scarred tissue, including the epileptic focus at the occipital lobe. After surgery, he became seizure free and his visual field defect improved gradually. In addition, postoperative 123I-iomazenil (IMZ) SPECT showed partly normalized IMZ uptake in the visual cortex. This case is a practical example suggesting that neurological deficits attributable to the functional deficit zone can be remedied by successful focal resection.

Clinical significance of polyglutamylation in primary central nervous system lymphoma.

The therapeutic response to high-dose methotrexate (HD-MTX) therapy for primary central nervous system lymphoma (PCNSL) varies. Polyglutamylation is a reversible protein modification with a high occurrence rate in tumor cells. MTX incorporated into cells is polyglutamylated and strongly binds to dihydrofolate reductase without competitive inhibition by leucovorin (LV). Tumor cells with high polyglutamylation levels are selectively killed, whereas normal cells with lower polyglutamylation are rescued by LV. We hypothesized that the extent of polyglutamylation in tumor cells determines treatment resistance. Here, we investigated the therapeutic response of PCNSL to HD-MTX therapy with LV rescue based on polyglutamylation status. Among 113 consecutive PCNSL patients who underwent HD-MTX therapy in our department between 2001 and 2014, polyglutamylation was evaluated by immunostaining in 82 cases, with relationships between polyglutamylation and therapeutic response retrospectively examined. Human malignant lymphoma lines were used for in vitro experiments, and folpolyglutamate synthetase (FPGS), which induces polyglutamylation, was knocked down with short-hairpin RNA, and a stable cell line with a low rate of polyglutamylation was established. Cell viability after MTX treatment with LV rescue was evaluated using sodium butyrate (NaBu), a histone-deacetylase inhibitor that induces polyglutamylation by elevating FPGS expression. The complete response rate was significantly higher in the group with polyglutamylation than in the non-polyglutamylation group [58.1% (25/43) and 33.3% (13/39), respectively] (p < 0.05), and progression-free survival was also significantly increased in the group with polyglutamylation (p < 0.01). In vitro, the relief effect of LV after MTX administration was significantly enhanced after FPGS knockdown in al cell lines, whereas enhancement of FPGS expression by NaBu treatment significantly reduced this relief effect. These findings suggested that polyglutamylation could be a predictor of therapeutic response to HD-MTX therapy with LV rescue in PCNSL. Combination therapy with HD-MTX and polyglutamylation-inducing agents might represent a promising strategy for PCNSL treatment.