Neuropsychological outcome in refractory obsessive-compulsive disorder treated with anterior capsulotomy including repeated surgery.

AIM: Anterior capsulotomy (AC) is one of the last therapeutic options for obsessive-compulsive disorder (OCD) refractory to conservative treatments. Several forms of cognitive dysfunction have been identified after assessment of neuropsychological outcomes in OCD patients; however, few studies focused on cognitive changes in OCD patients after surgery. In the present study, we evaluated the effects of AC on cognitive performance and mood status in patients with refractory OCD. METHODS: A total of 12 patients underwent bilateral AC between 2012 and 2019 at our institution. The patients (n = 12, female : male 5:7; mean age 39.7 years; duration ≥5 years) were assessed before and 6 months after intervention. The diagnosis of treatment-refractory OCD was based on recommended criteria for surgical treatment. Patients were assessed using a neuropsychological battery and questionnaires focused on anxiety-depressive symptomatology. The Yale-Brown Obsessive Compulsive Scale was administered as a measure of severity of OCD symptoms. RESULTS: We detected a significant decrease of OCD, and anxiety and depressive symptomatology assessed by Yale-Brown Obsessive Compulsive Scale, Beck Depression Inventory, and Beck Anxiety Inventory (P < 0.05) 6 months after AC in eight patients, and a partial decrease in four patients. Four patients underwent repeated AC with more pronounced improvement achieved after the first procedure. We did not detect decline in cognitive performance in any patients, but did find better visual memory performance (P < 0.05). CONCLUSION: AC reduced OCD and anxiety-depressive symptoms, and did not appear to influence cognitive performance, even after repeated surgery.

Cerebrospinal Fluid Leak to the IPG Subcutaneous Pocket after Deep Brain Stimulation Implantation: A Case Report.

This case report presents a 54-year-old Parkinson´s disease patient who underwent a DBS implantation to the subthalamic nuclei bilaterally. Shortly after the operation, the subcutaneous pocket of the generator filled with a liquid. Repeated aspirations did not show any bacterial contamination, and an infection was not found. In the sample, a beta-trace protein was detected that proved the presence of cerebrospinal fluid. A lumbar drain was immediately placed, and a chest compression bandage was fastened for 7 days. After removing the lumbar drain and the compression bandage, no additional liquid was observed, and the wound healed without any other complication. We present an unusual adverse event related to DBS surgery and suggest an effective treatment that has led to uncomplicated healing.

Distinct populations of neurons respond to emotional valence and arousal in the human subthalamic nucleus.

Both animal studies and studies using deep brain stimulation in humans have demonstrated the involvement of the subthalamic nucleus (STN) in motivational and emotional processes; however, participation of this nucleus in processing human emotion has not been investigated directly at the single-neuron level. We analyzed the relationship between the neuronal firing from intraoperative microrecordings from the STN during affective picture presentation in patients with Parkinson's disease (PD) and the affective ratings of emotional valence and arousal performed subsequently. We observed that 17% of neurons responded to emotional valence and arousal of visual stimuli according to individual ratings. The activity of some neurons was related to emotional valence, whereas different neurons responded to arousal. In addition, 14% of neurons responded to visual stimuli. Our results suggest the existence of neurons involved in processing or transmission of visual and emotional information in the human STN, and provide evidence of separate processing of the affective dimensions of valence and arousal at the level of single neurons as well.

KMT2B rare missense variants in generalized dystonia.

BACKGROUND: Recently a novel syndrome of childhood-onset generalized dystonia originating from mutations in lysine-specific methyltransferase 2B (KMT2B) has been reported. METHODS: We sequenced the exomes of 4 generalized dystonia-affected probands recruited from a Prague movement disorders center (Czech Republic). Bioinformatics analyses were conducted to select candidate causal variants in described dystonia-mutated genes. After cosegregation testing, checklists from the American College of Medical Genetics and Genomics were adopted to judge variant pathogenicity. RESULTS: Three novel, predicted protein-damaging missense variants in KMT2B were identified (p.Glu1234Lys, p.Ala1541Val, p.Arg1779Gln). Meeting pathogenicity criteria, p.Glu1234Lys was absent from population-based controls, situated in a key protein domain, and had occurred de novo. The associated phenotype comprised adolescence-onset generalized isolated dystonia with prominent speech impairment. Although linked to a similar clinical expression, p.Ala1541Val and p.Arg1779Gln remained of uncertain significance. CONCLUSIONS: Rare missense variation in KMT2B represents an additional cause of generalized dystonia. Application of sequence interpretation standards is required before assigning pathogenicity to a KMT2B missense variant. © 2017 International Parkinson and Movement Disorder Society.

Trigeminal nerve asymmetry in classic trigeminal neuralgia - pretreatment volumetry and clinical evaluation in patients irradiated by Leksell Gamma Knife.

OBJECTIVES: The etiology of classic trigeminal neuralgia (CTN) is still under debate and, together with neurovascular compression (NVC), other anatomical abnormalities have been considered, including differences of trigeminal nerve (TN) volume. DESIGN: We evaluated the volumes of affected and non-affected nerves and the presence and type of NVC in large group of 84 CTN subjects prior to gamma knife treatment (GKS) on MR images. Correlation between affected nerve volume and NVC, treatment outcome and demographic characteristics were explored. RESULTS: NVC was detected in 71% of affected nerves, 52% of non-affected nerves, and in 31% of subjects bilaterally. Lower trigeminal nerve volume was detected on the affected side (p<0.001, affected mean 34.9 mm3 ± 14.4 SD, non-affected mean 41.9 mm3 ± 17.7 SD), however, no correlation between affected nerve volume and the presence and type NVC, treatment outcome or demographic data was detected. CONCLUSION: Our results suggest that NVC may trigger CTN in susceptible subjects but is not a reliable disease marker. Lower trigeminal nerve volume appears to manifest independently of NVC, and may represent nerve asymmetry rather than atrophy. No correlation between volumetry and clinical data was detected including treatment outcome after GKS.

Structural and microstructural predictors of cognitive decline in deep brain stimulation of subthalamic nucleus in Parkinson's disease.

BACKGROUND AND OBJECTIVES: The intricate relationship between deep brain stimulation (DBS) in Parkinson's disease (PD) and cognitive impairment has lately garnered substantial attention. The presented study evaluated pre-DBS structural and microstructural cerebral patterns as possible predictors of future cognitive decline in PD DBS patients. METHODS: Pre-DBS MRI data in 72 PD patients were combined with neuropsychological examinations and follow-up for an average of 2.3 years after DBS implantation procedure using a screening cognitive test validated for diagnosis of mild cognitive impairment in PD in a Czech population - Dementia Rating Scale 2. RESULTS: PD patients who would exhibit post-DBS cognitive decline were found to have, already at the pre-DBS stage, significantly lower cortical thickness and lower microstructural complexity than cognitively stable PD patients. Differences in the regions directly related to cognition as bilateral parietal, insular and cingulate cortices, but also occipital and sensorimotor cortex were detected. Furthermore, hippocampi, putamina, cerebellum and upper brainstem were implicated as well, all despite the absence of pre-DBS differences in cognitive performance and in the position of DBS leads or stimulation parameters between the two groups. CONCLUSIONS: Our findings indicate that the cognitive decline in the presented PD cohort was not attributable primarily to DBS of the subthalamic nucleus but was associated with a clinically silent structural and microstructural predisposition to future cognitive deterioration present already before the DBS system implantation.

Intratumoral Hemorrhage in Vestibular Schwannomas After Stereotactic Radiosurgery: Multi-Institutional Study.

BACKGROUND AND OBJECTIVES: Intratumoral hemorrhage (ITH) in vestibular schwannoma (VS) after stereotactic radiosurgery (SRS) is exceedingly rare. The aim of this study was to define its incidence and describe its management and outcomes in this subset of patients. METHODS: A retrospective multi-institutional study was conducted, screening 9565 patients with VS managed with SRS at 10 centers affiliated with the International Radiosurgery Research Foundation. RESULTS: A total of 25 patients developed ITH (cumulative incidence of 0.26%) after SRS management, with a median ITH size of 1.2 cm 3 . Most of the patients had Koos grade II-IV VS, and the median age was 62 years. After ITH development, 21 patients were observed, 2 had urgent surgical intervention, and 2 were initially observed and had late resection because of delayed hemorrhagic expansion and/or clinical deterioration. The histopathology of the resected tumors showed typical, benign VS histology without sclerosis, along with chronic inflammatory cells and multiple fragments of hemorrhage. At the last follow-up, 17 patients improved and 8 remained clinically stable. CONCLUSION: ITH after SRS for VS is extremely rare but has various clinical manifestations and severity. The management paradigm should be individualized based on patient-specific factors, rapidity of clinical and/or radiographic progression, ITH expansion, and overall patient condition.

Impact of Multiple Sclerosis Subtypes on Pain Management in Patients With Trigeminal Neuralgia After Stereotactic Radiosurgery: An International Multicenter Analysis.

BACKGROUND AND OBJECTIVES: Trigeminal neuralgia affects approximately 2% of patients with multiple sclerosis (MS) and often shows higher rates of pain recurrence after treatment. Previous studies on the effectiveness of stereotactic radiosurgery (SRS) for trigeminal neuralgia did not consider the different MS subtypes, including remitting relapsing (RRMS), primary progressive (PPMS), and secondary progressive (SPMS). Our objective was to investigate how MS subtypes are related to pain control (PC) rates after SRS. METHODS: We conducted a retrospective multicenter analysis of prospectively collected databases. Pain status was assessed using the Barrow National Institute Pain Intensity Scales. Time to recurrence was estimated through the Kaplan-Meier method and compared groups using log-rank tests. Logistic regression was used to calculate the odds ratio (OR). RESULTS: Two hundred and fifty-eight patients, 135 (52.4%) RRMS, 30 (11.6%) PPMS, and 93 (36%) SPMS, were included from 14 institutions. In total, 84.6% of patients achieved initial pain relief, with a median time of 1 month; 78.7% had some degree of pain recurrence with a median time of 10.2 months for RRMS, 8 months for PPMS, 8.1 months for SPMS ( P = .424). Achieving Barrow National Institute-I after SRS was a predictor for longer periods without recurrence ( P = .028). Analyzing PC at the last available follow-up and comparing with RRMS, PPMS was less likely to have PC (OR = 0.389; 95% CI 0.153-0.986; P = .047) and SPMS was more likely (OR = 2.0; 95% CI 0.967-4.136; P = .062). A subgroup of 149 patients did not have other procedures apart from SRS. The median times to recurrence in this group were 11.1, 9.8, and 19.6 months for RRMS, PPMS, and SPMS, respectively (log-rank, P = .045). CONCLUSION: This study is the first to investigate the relationship between MS subtypes and PC after SRS, and our results provide preliminary evidence that subtypes may influence pain outcomes, with PPMS posing the greatest challenge to pain management.

The relevance of biologically effective dose for pain relief and sensory dysfunction after Gamma Knife radiosurgery for trigeminal neuralgia: an 871-patient multicenter study.

OBJECTIVE: Recent studies have suggested that biologically effective dose (BED) is an important correlate of pain relief and sensory dysfunction after Gamma Knife radiosurgery (GKRS) for trigeminal neuralgia (TN). The goal of this study was to determine if BED is superior to prescription dose in predicting outcomes in TN patients undergoing GKRS as a first procedure. METHODS: This was a retrospective study of 871 patients with type 1 TN from 13 GKRS centers. Patient demographics, pain characteristics, treatment parameters, and outcomes were reviewed. BED was compared with prescription dose and other dosimetric factors for their predictive value. RESULTS: The median age of the patients was 68 years, and 60% were female. Nearly 70% of patients experienced pain in the V2 and/or V3 dermatomes, predominantly on the right side (60%). Most patients had modified BNI Pain Intensity Scale grade IV or V pain (89.2%) and were taking 1 or 2 pain medications (74.1%). The median prescription dose was 80 Gy (range 62.5-95 Gy). The proximal trigeminal nerve was targeted in 77.9% of cases, and the median follow-up was 21 months (range 6-156 months). Initial pain relief (modified BNI Pain Intensity Scale grades I-IIIa) was noted in 81.8% of evaluable patients at a median of 30 days. Of 709 patients who achieved initial pain relief, 42.3% experienced at least one pain recurrence after GKRS at a median of 44 months, with 49.0% of these patients undergoing a second procedure. New-onset facial numbness occurred in 25.3% of patients after a median of 8 months. Age ≥ 63 years was associated with a higher probability of both initial pain relief and maintaining pain relief. A distal target location was associated with a higher probability of initial and long-term pain relief, but also a higher incidence of sensory dysfunction. BED ≥ 2100 Gy2.47 was predictive of pain relief at 30 days and 1 year for the distal target, whereas physical dose ≥ 85 Gy was significant for the proximal target, but the restricted range of BED values in this subgroup could be a confounding factor. A maximum brainstem point dose ≥ 29.5 Gy was associated with a higher probability of bothersome facial numbness. CONCLUSIONS: BED and physical dose were both predictive of pain relief and could be used as treatment planning goals for distal and proximal targets, respectively, while considering maximum brainstem point dose < 29.5 Gy as a potential constraint for bothersome numbness.

Gamma knife radiosurgery of brain cavernomas.

PURPOSE: Radiosurgery of cavernomas should prevent rebleeding, growth of the lesion, and deterioration of clinical symptoms. However, there is no direct diagnostic tool to verify the endpoints of treatment. At present, the positive effects of radiosurgery are identified by clinical observation and analysis of imaging changes on magnetic resonance imaging during a sufficiently long follow-up period. METHODS: Between 1992 and 2000, a total of 112 patients with brain cavernomas were treated with Gamma Knife radiosurgery at our center. In all, 59 patients experienced bleeding before radiosurgery; the remainder did not. The median age of patients was 42 years, the median volume of the cavernomas was 0.9 cm(3), and the median applied marginal dose was 16 Gy. RESULTS: After a 2-year latent interval after treatment (median follow-up 84 months), the risk of bleeding in the group of patients with bleeding before radiosurgery had decreased from 3.7 % to 0.2 %. For the patients without bleeding before radiosurgery, the annual risk of bleeding was 0.8 %. The cavernoma size decreased in 53.0 % of cases and increased in 6.4 %. Epilepsy, if present before the treatment, was alleviated in 45 % of cases. The risks of temporary or permanent morbidity caused by radiosurgery were 14.6 % and 0.9 %, respectively. CONCLUSION: Radiosurgery of cavernomas was associated with a low risk of permanent morbidity. The risk of rebleeding after the 2-year latent interval after radiosurgery had decreased. Treatment of cavernomas with no history of bleeding was halted at our center.

Quantitative MR imaging and spectroscopy of brain tumours: a step forward?

OBJECTIVES: A prospective quantitative MR study of brain tumours was performed to show the potential of combining different MR techniques to distinguish various disease processes in routine clinical practice. METHODS: Twenty-three patients with various intracranial tumours before treatment (diagnosis confirmed by a biopsy) and 59 healthy subjects were examined on a 3-T system by conventional MR imaging, 1H spectroscopic imaging, diffusion tensor imaging and T2 relaxometry. Metabolic concentrations and their ratios, T2 relaxation times and mean diffusivities were calculated and correlated on a pixel-by-pixel basis and compared to control data. RESULTS: Different tumour types and different localisations revealed specific patterns of correlations between metabolic concentrations and mean diffusivity or T2 relaxation times. The patterns distinguish given tissue states in the examined area: healthy tissue, tissue infiltrated by tumour, active tumour, oedema infiltrated by tumour, oedema, etc. This method is able to describe the complexity of a highly heterogeneous tissue in the tumour and its vicinity, and determines crucial parameters for tissue differentiation. CONCLUSIONS: A combination of different MR parameters on a pixel-by-pixel basis in individual patients enables better identification of the tumour type, direction of proliferation and assessment of the tumour extension. KEY POINTS : • Magnetic resonance offers many different methods of examining the brain. • A combination of quantitative MR parameters helps distinguish different brain lesions • Different tumour types revealed specific correlation patterns amongst different MR parameters • The correlation patterns reflect highly heterogeneous complex tissue within tumours.

Restoration of functional network state towards more physiological condition as the correlate of clinical effects of pallidal deep brain stimulation in dystonia.

BACKGROUND: Deep brain stimulation of the internal globus pallidus (GPi DBS) is an invasive therapeutic modality intended to retune abnormal central nervous system patterns and relieve the patient of dystonic or other motor symptoms. OBJECTIVES: The aim of the presented research was to determine the neuroanatomical signature of GPi DBS modulation and its association with the clinical outcome. METHODS: This open-label fixed-order study with cross-sectional validation against healthy controls analysed the resting-state functional MRI activity changes induced by GPi DBS in 18 dystonia patients of heterogeneous aetiology, focusing on both global (full brain) and local connectivity (local signal homogeneity). RESULTS: Compared to the switched-off state, the activation of GPi DBS led to the restoration of global subcortical connectivity patterns (in both putamina, diencephalon and brainstem) towards those of healthy controls, with positive direct correlation over large-scale cortico-basal ganglia-thalamo-cortical and cerebellar networks with the clinical improvement. Nonetheless, on average, GPi DBS also seemed to bring local connectivity both in the cortical and subcortical regions farther away from the state detected in healthy controls. Interestingly, its correlation with clinical outcome showed that in better DBS responders, local connectivity defied this effect and approached healthy controls. CONCLUSIONS: All in all, the extent of restoration of both these main metrics of interest towards the levels found in healthy controls clearly correlated with the clinical improvement, indicating that the restoration of network state towards more physiological condition may be a precondition for successful GPi DBS outcome in dystonia.

The Instrumental Activities of Daily Living in Parkinson's Disease Patients Treated by Subthalamic Deep Brain Stimulation.

Background: Everyday functioning and instrumental activities of daily living (IADL) play a vital role in preserving the quality of life in patients with Parkinson's disease (PD) after deep brain stimulation of the subthalamic nucleus (STN-DBS). Objective: The main goal of the current study was to examine IADL change in pre-and post-surgery of the STN-DBS. We also analyzed the influence of the levodopa equivalent daily dose (LEDD) and global cognitive performance (Dementia Rating Scale; DRS-2) as covariates in relation to IADL. Methods: Thirty-two non-demented PD patients were administered before and after STN-DBS neurosurgery the Penn Parkinson's Daily Activities Questionnaire (PDAQ; self-report), the DRS-2 and Beck Depression Inventory (BDI-II) to assess IADL change, global cognition, and depression. Results: We found a positive effect of STN-DBS on IADL in the post-surgery phase. Moreover, lower global cognition and lower LEDD are predictive of lower IADL in both pre-surgery and post-surgery examinations. Summary/Conclusion: STN-DBS in PD is a safe method for improvement of everyday functioning and IADL. In the post-surgery phase, we show a relation of IADL to the severity of cognitive impairment in PD and to LEDD.

Subthalamic nucleus stimulation affects incentive salience attribution in Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) can induce nonmotor side effects such as behavioral and mood disturbances or body weight gain in Parkinson's disease (PD) patients. We hypothesized that some of these problems could be related to an altered attribution of incentive salience (ie, emotional relevance) to rewarding and aversive stimuli. Twenty PD patients (all men; mean age ± SD, 58.3 ± 6 years) in bilateral STN DBS switched ON and OFF conditions and 18 matched controls rated pictures selected from the International Affective Picture System according to emotional valence (unpleasantness/pleasantness) and arousal on 2 independent visual scales ranging from 1 to 9. Eighty-four pictures depicting primary rewarding (erotica and food) and aversive fearful (victims and threat) and neutral stimuli were selected for this study. In the STN DBS ON condition, the PD patients attributed lower valence scores to the aversive pictures compared with the OFF condition (P < .01) and compared with controls (P < .01). The difference between the OFF condition and controls was less pronounced (P < .05). Furthermore, postoperative weight gain correlated with arousal ratings from the food pictures in the STN DBS ON condition (P < .05 compensated for OFF condition). Our results suggest that STN DBS increases activation of the aversive motivational system so that more relevance is attributed to aversive fearful stimuli. In addition, STN DBS-related sensitivity to food reward stimuli cues might drive DBS-treated patients to higher food intake and subsequent weight gain.

Hormonal regulators of food intake and weight gain in Parkinson's disease after subthalamic nucleus stimulation.

OBJECTIVES: Weight gain has been reported in patients with Parkinson's disease (PD) treated with deep brain stimulation of the subthalamic nucleus (STN-DBS). To evaluate the influence of STN-DBS on weight changes, we studied food-related hormones. DESIGN: Anthropometric parameters and food-related hormones (leptin, adiponectin, resistin, ghrelin, cortisol, insulin, and thyroid stimulating hormone) were measured in 27 patients with STN-DBS during a 12 month period following electrode implantation. RESULTS: Besides marked motor improvements on STN-DBS, PD patients significantly gained weight. The mean weight gain at 12 months was 5.2±(SD)5.8 kg. A significant decrease in cortisol levels compared to baseline appeared at month 2 and persisted at 12 months (p<0.01, corrected), with no significant changes in other hormones tested. CONCLUSIONS: Changes in peripheral food-related hormones do not appear to cause weight gain in PD patients. Direct effects of STN-DBS on hypothalamic catabolic/anabolic peptide balance remain hypothetical and necessitate further elucidation.

[Deep brain stimulation in movement disorders: a Prague-center experience]. / Hluboká mozková stimulace u extrapyramidových poruch pohybu - praiská zkusenost.

Deep brain stimulation (DBS) in the basal ganglia plays an irreplaceable role in the treatment of Parkinson's disease (PD), essential tremor (ET), and some types of dystonia. Electrodes are typically inserted into the subthalamic nucleus (STN), the internal globus pallidus (GPi) and the ventral intermediate nucleus of the thalamus (VIM). Stimulation of the STN is the main objective in PD, GPi in the treatment of dystonia and PD, and VIM stimulation is effective against tremor. In patients indicated for DBS treatment, stimulation eliminates or reduces rigidity (PD), hypokinesia (PD), tremor (ET, PD) and dyskinesias (dystonia, PD). At the Center for Movement Disorders in Prague, DBS has been performed in 127 patients: in 86 patients for PD, 19 patients for dystonia (11 primary generalized dystonia, 5 primary cervical dystonia, 1 segmental craniocervical dystonia), and in 22 patients for tremor (20 ET, 2 other types of tremor). Intraoperatively we have succeeded in eliminating rigidity in 95% of cases of PD, and tremor in 93% of cases of ET. The positive effect of stimulation on dystonia appeared in 95% with a latency of weeks. Transitory intraoperative morbidity occurred in 8%, intracranial hemorrhage in 1%, infectious complications in 6%, and problems with hardware in 7%.

[Significance of radiosurgery for the treatment of meningiomas]. / Význam radiochirurgie v lécbe meningiomu.

Treatment of intracranial meningiomas in the light of their benignity (90%) should ensure minimal risk of recurrence, avoid new neurological deficit and preserve quality of life. Stereotactic radiosurgery has proved its long-term effectiveness and safety with a low complication rate. It can be applied as a method of choice for meningiomas in locations that are too risky for microsurgical removal, meningiomas that usually do not exceed 3 cm in diameter and in patients, who are not candidates for microsurgery because of associated disease. It is a part of multimodal treatment for recurrence after operative resection or after partial removal of large meningiomas, where radical surgery represents a high risk of postoperative morbidity and mortality. Indication of radiosurgical treatment of intracranial meningiomas should be considered for each patient individually in order to choose methods or their combination with the lowest risk of complications.

Large vestibular schwannomas: long-term outcomes after stereotactic radiosurgery.

OBJECTIVES: Stereotactic radiosurgery (SRS) is an established treatment option of small/medium-sized vestibular schwannomas (VSs). Concerning management of the large VSs, primary SRS remains a controversial option. Our retrospective study analyzes long-term radiological and clinical outcomes of SRS in large VSs. MATERIAL AND METHODS: We retrospectively analyzed 73 patients with single large VS, treated with SRS. Inclusion criteria were: tumor volume >4 cm3, follow-up >2 years, radiological (3D-volumetric studies) and clinical follow-up. SRS was either primary (94.5%) or secondary (5.5%) treatment. The median marginal dose (50%-isodose line) was 12Gy (11.5-12Gy). Fisher exact test, t-test, ANOVA, Kaplan-Meier and Cox regression models were performed when appropriate RESULTS: The median follow-up was 5.5 years. The median VS volume at SRS was 6.5 cm3 (range 4-14.2 cm3). The tumor control rates assessed from Kaplan-Meier curve were 88.3%, 82.4% and 74.7% 5.8 and 10 years after SRS, respectively. Tumor shrinkage was observed in 83.6% of patients (n=61), unchanged volume in 4.1% patients (n=3) and progression in 12.3% (n=9). The median tumor volume significantly decreased to 4.0 cm3, measured at 5-year follow-up (p<0.0001). Large cystic VSs responded better to SRS then homogeneous. Pre-SRS serviceable hearing was present in 37% of patients; 55% of these had hearing preserved after treatment. After SRS, new facial palsy (House-Brackmann gr. III-VI) appeared in 4.1% of patients; 9.6% of patients had transient brainstem/cranial nerves edema. For tumor progression, 8.2% of patients underwent resection, 2.8% of patients repeated SRS. CONCLUSION: Our results are showing that SRS might be safe and effective primary treatment even in large VSs. However, long-term tumor control rates are lower in comparison with small/medium-sized VSs. Thus, closer follow-up should be applied.

Outcomes after stereotactic radiosurgery for schwannomas of the oculomotor, trochlear, and abducens nerves.

OBJECTIVE: Cranial nerve (CN) schwannomas are intracranial tumors that are commonly managed by stereotactic radiosurgery (SRS). There is a large body of literature supporting the use of SRS for vestibular schwannomas. Schwannomas of the oculomotor nerves (CNs III, IV, and VI) are rare skull base tumors, occurring close to the brainstem and often involving the cavernous sinus. Resection can cause significant morbidity, including loss of nerve function. As for other schwannomas, SRS can be used to manage these tumors, but only a handful of cases have been published so far, often among reports of other uncommon schwannoma locations. METHODS: The goal of this study was to collect retrospective multicenter data on tumor control, clinical evolution, and morbidity after SRS. This study was performed through the International Radiosurgery Research Foundation. Patients managed with single-session SRS for an oculomotor cranial nerve schwannoma (CN III, IV, or VI) were included. The diagnosis was based on diplopia or ptosis as the main presenting symptom and anatomical location on the trajectory of the presumed cranial nerve of origin, or prior resection confirming diagnosis. Demographic, SRS dose planning, clinical, and imaging data were collected from chart review of the treated patients. Chi-square and Kaplan-Meier analyses were performed. RESULTS: Seven institutions submitted data for a total of 25 patients. The median follow-up time was 41 months. The median age at the time of treatment was 52 years. There were 11 CN III schwannomas, 11 CN IV schwannomas, and 3 CN VI schwannomas. The median target volume was 0.74 cm3, and the median marginal dose delivered was 12.5 Gy. After SRS, only 2 patients (including the only patient with neurofibromatosis type 2) had continued tumor growth. Crude local control was 92% (23/25), and the 10-year actuarial control was 86%. Diplopia improved in the majority of patients (11/21), and only 3 had worsening following SRS, 2 of whom also had worsened ptosis, both in the context of tumor progression. CONCLUSIONS: SRS for schwannomas of the oculomotor, trochlear, and abducens nerves is effective and provides tumor control rates similar to those for other cranial nerve schwannomas. SRS allows improvement of diplopia in the majority of patients. SRS should therefore be considered as a first-line treatment option for oculomotor nerve schwannomas.

Widespread and sustained target engagement in Huntington's disease minipigs upon intrastriatal microRNA-based gene therapy.

Huntingtin (HTT)-lowering therapies hold promise to slow down neurodegeneration in Huntington's disease (HD). Here, we assessed the translatability and long-term durability of recombinant adeno-associated viral vector serotype 5 expressing a microRNA targeting human HTT (rAAV5-miHTT) administered by magnetic resonance imaging-guided convention-enhanced delivery in transgenic HD minipigs. rAAV5-miHTT (1.2 × 1013 vector genome (VG) copies per brain) was successfully administered into the striatum (bilaterally in caudate and putamen), using age-matched untreated animals as controls. Widespread brain biodistribution of vector DNA was observed, with the highest concentration in target (striatal) regions, thalamus, and cortical regions. Vector DNA presence and transgene expression were similar at 6 and 12 months after administration. Expression of miHTT strongly correlated with vector DNA, with a corresponding reduction of mutant HTT (mHTT) protein of more than 75% in injected areas, and 30 to 50% lowering in distal regions. Translational pharmacokinetic and pharmacodynamic measures in cerebrospinal fluid (CSF) were largely in line with the effects observed in the brain. CSF miHTT expression was detected up to 12 months, with CSF mHTT protein lowering of 25 to 30% at 6 and 12 months after dosing. This study demonstrates widespread biodistribution, strong and durable efficiency of rAAV5-miHTT in disease-relevant regions in a large brain, and the potential of using CSF analysis to determine vector expression and efficacy in the clinic.