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Patients with movement disorders treated by deep brain stimulation do not always achieve successful therapeutic alleviation of motor symptoms, even in cases where surgery is without complications. Magnetic resonance imaging (MRI) offers methods to investigate structural brain-related factors that may be predictive for clinical motor outcomes. This review aimed to identify features which have been associated with variability in clinical post-operative motor outcomes in patients with Parkinson’s disease, dystonia, and essential tremor from structural MRI modalities. We performed a literature search for articles published between January 01, 2000, and April 01, 2022, and identified 5197 articles. Following screening through our inclusion criteria, we identified 60 total studies (39 = Parkinson’s disease, 11 = dystonia syndromes and 10 = essential tremor). The review captured a range of structural MRI methods and analysis techniques used to identify factors related to clinical post-operative motor outcomes from deep brain stimulation. Morphometric markers, including volume and cortical thickness were commonly identified in studies focused on patients with Parkinson’s disease and dystonia syndromes. Reduced metrics in basal ganglia, sensorimotor and frontal regions showed frequent associations with reduced motor outcomes. Increased structural connectivity to subcortical nuclei, sensorimotor and frontal regions were also associated with greater motor outcomes. In patients with tremor, increased structural connectivity to the cerebellum and cortical motor regions showed high prevalence across studies for greater clinical motor outcomes. In addition, we highlight conceptual issues for studies assessing clinical response with structural MRI and discuss future approaches towards optimising individualised therapeutic benefits. Although quantitative MRI markers are in their infancy for clinical purposes in movement disorder treatments, structural features obtained from MRI offer powerful potential to identify candidates who are more likely to benefit from deep brain stimulation and provide insight into the complexity of disorder pathophysiology.

BackgroundCervical dystonia is a movement disorder, characterised by involuntary head and neck muscle contractions. Although deep brain stimulation (DBS) of the globus pallidus internus (GPi) is an effective treatment option, motor outcomes can vary even when sufficient targeting accuracy is achieved. Increasing evidence supports a role of brainstem and cerebellum dysfunction in cervical dystonia pathogenesis.ObjectiveTo determine whether morphometry of brainstem and dentate nuclei, and DBS stimulatory overlap with cerebello-thalamic tracts modelled from normative connectivity, were related to DBS clinical motor outcomes.Methods27 patients with idiopathic cervical dystonia underwent bilateral targeting of the GPi. and were separated into suboptimal and optimal motor outcome groups. Dentate nuclei and brainstem volumes were quantified in association with clinical outcomes. A brainstem shape analysis was conducted and used as a seed to assess connectivity from a normative structural connectome. Patient-specific electrodes were modelled to quantify stimulatory overlap with the GPi and proximity to cerebellothalamic tracts.ResultsGPi implantation accuracy did not significantly differ between groups. Significantly reduced dentate nuclei and brainstem volumes were observed in patients with poorer clinical outcomes. Regional surface shape change of the brainstem was also observed in patients with poorer responses. Fibre tracking from this area intersected cerebellar, pallidal and cortical motor regions. Electrode field intersection with the non-decussating dentatorubrothalamic tract in the right, and in both hemispheres were also positively associated with clinical outcome.ConclusionsVariability in cerebellar and brainstem morphometry, and stimulation of non-decussating cerebello-thalamic pathways may contribute to the mediation of DBS motor outcomes.

Background: Skin erosion is a common complication after deep brain stimulator procedures. Despite being a relatively common event, there is no standard surgical technique or a widely accepted guideline for managing this kind of complication. Methods: We describe a case of cutaneous erosion in the connector’s site of deep brain stimulation case, surgically managed with anterior displacement of the connectors and overlapping and wrapping the connections within the temporal muscle. Results: Postoperatively, the patient did well and achieved complete resolution of the skin erosion, with no signs of infection or new skin lesions. Conclusion: This technique demonstrated to be effective in this case in the long-term follow-up.

Deep Brain Stimulation (DBS) of the subthalamic nucleus (STN) is a well-recognized intervention for Parkinson’s Disease (PD). We used LEAD-DBS, a toolbox facilitating DBS electrode reconstructions and computer simulations based on postoperative MRI and CT imaging, to investigate the interaction and followed benefits of electrical field generated by STN-DBS and surrounding areas, such as caudal Zona Incerta (cZI). Thirty-two PD patients, treated with directional STN-DBS in the period 2016–2018 at the Walton Center NHS Foundation Trust, were retrospectively recruited. Their MRI and CT imaging were analyzed with LEAD-DBS to measure the volume of tissue activated (VTA). Considering the clinical outcome based on the UPDRS III score improvement of 62.65% at 6 months follow up, we found a VTA intersection of 21.5% with motor STN and 61.7% with cZI. These observations may support the contribution of cZI deep stimulation to improve clinical outcome of PD patients treated with DBS, promoting the intriguing path of dual targeting.

When considering Deep Brain Stimulation (DBS) surgical treatment of dystonia syndromes, it is important to consider multiple aspects of the disease and its presentation. It is crucial to know if the dystonia is idiopathic, inherited or acquired as well as focal, segmental or generalised. Careful phenotyping of idiopathic as well as inherited dystonias and accurate diagnosis of acquired dystonias informs the decision-making process for patients and clinicians by providing them with useful predictors of outcomes of the proposed surgery. Here, we provided a review of the current literature, highlighted the areas where evidence is scarce and suggested future directions for research.

Introduction Glioblastoma treatment requires a multidisciplinary approach involving oncologists, radiotherapists and surgeons. Surgery constitutes the initial step of the therapeutic strategy and its efficacy is dependent on the extent of resection (EOR). Over the last decade, the goal of surgical treatment was the resection of the contrast enhancement on T1 MRI, defined as gross-total resection (GTR). More recently, an increasing number of studies reports a positive impact on survival parameters of a more aggressive surgical strategy aiming to resect all peri-tumoral infiltrated areas. These areas are histologically characterized by the presence of pathological cells infiltrating normal white matter and surround the neoplastic core of glioblastoma identified by gadolinium enhancement in T1-weighted MR. Intuitively, the major risk of the so called supramarginal resection is related to the possibility of resecting functionally eloquent brain tissue. Several strategies have been proposed to maximize the safety of resection and minimize the occurrence of postoperative functional deficits. The aim of this review was to focus on the clinical impact of supramarginal resection of glioblastomas, highlighting the role of image-guided surgery combined with neuromonitoring to increase surgical safety and efficacy. Evidence acquisition The MEDLINE database has been queried for the literature research. Evidence synthesis Ten studies matched the inclusion criteria, reporting a global number of 3221 patients. Conclusions The current evidence suggests a positive correlation between a more extensive resection based on FLAIR abnormal areas and overall survival.

Background Trigeminal neuralgia (TGN) is a debilitating disorder, and in patients for whom medical management is not sufficient, there are several therapeutic options. Microvascular decompression (MVD) for TGN has been shown to be highly effective; however, pain does recur after MVD in some patients. Therapeutic options for recurrent TGN are the same as those for primary TGN, including re-exploration of MVD (re-MVD). In this study we review our practice of re-MVD, comparing it with alternative options and assessing its safety and efficacy. Methods Retrospective analysis of prospectively collected data of patients undergoing re-MVD between 2007 and 2016. Results Thirty-two patients underwent re-MVD, all with a Barrow Neurosurgical Institute Pain Index (BNPI) of IV or V. Postoperatively, 87% of patients reported an improvement in their BNPI to III or better, with 50% being BNPI 1 or 2. Eleven patients without distortion or vascular conflict at the time of re-exploration underwent intraoperative neurolysis, and 90% reported improvement in their BNPI. Kaplan-Meier analysis showed a median pain-free period of 36 months after re-MVD. There were no significant complications. Conclusions Re-MVD is a safe and effective method of treating recurrent TGN. Intraoperative neurolysis is an important tool in re-exploration and should be considered when there is no ongoing compression or distortion of the trigeminal nerve.

Objective To describe the indications and outcomes of upper cervical cord stimulation in trigeminal neuropathy. Methods A consecutive single-center series of patients was retrospectively reviewed. It included 12 patients with trigeminal neuropathy treated with upper cervical spinal cord stimulation. Clinical features, complications, and outcomes were reviewed. Results All patients had a successful trial before the definitive implantation of a spinal cord stimulator at the level of the craniocervical junction. The mean follow-up period was 4.4 years (range, 0.3–21.1 years). The average coverage in the pain zone was 72% and the median baseline, trial, and postoperative numeric rating scale (NRS) was 7, 3, and 3, respectively. When compared with the baseline, the mean reduction achieved in the postoperative average numeric rating scale was 4 points, accounting for a 57.1% pain reduction. The long-term failure rate was 25%. Conclusions Despite there being enough evidence to consider upper cervical spinal cord stimulation as an effective treatment for patients with neuropathic trigeminal pain, a randomized controlled trial is needed to fully assess its indications and outcomes and compare it with other therapeutic approaches.

Background High frequency stimulation (HFS) may provide pain relief without the paresthesias typical of traditional low-frequency Spinal cord stimulation (SCS). Methods A consecutive single-center series of patients was retrospectively reviewed to evaluate safety and efficacy of HF10 therapy. In this 24-month study, 62 patients with variables pathologies (44 patients with back failure surgery syndrome (FBSS), 18 patients with chronic peripheral neuropathic pain in the lower limbs (NeppL) were included to be treated with HF10. Pain outcomes were compared from preoperative baseline and at the conclusion of each study period. Clinical features, outcomes and complications were reviewed. Results 62 patients completed this study. All patients had a successful trial before the definitive implantation of a spinal cord stimulator at the low dorsal level. The mean follow-up period was 11 months, ranging from 6 to 24 months. 6 patients showed no change from baseline visual analogue scale (VAS) after permanent implant and 2 had improved during the trial but was aggravated after the permanent implant placement. At 1 month, 63% of implanted HF10 therapy subjects were responders and 77% at 6 months. The average baseline, trial and postoperative Visual Analogue Scale (VAS) was 8.1, 3.6 and 4.2 respectively. When compared to the baseline, the average reduction achieved during the VAS trial was 4.5 points, accounting for a 56% pain reduction. The long-term failure rate was 22%. Conclusions This study generated preliminary evidence showing improved VAS current pain scores in absence of paresthesias and increase patient satisfaction with HF10 spinal cord stimulation.

Objective:\ud \ud Many different gene families are currently being investigated for their potential role in epilepsy and in the response to antiepileptic drugs. A common research challenge is identifying the members of a gene family that are most significantly dysregulated within the human epileptic focus, before taking them forward for resource‐intensive functional studies. Published data about transcriptomic changes within the human epileptic focus remains incomplete. A need exists for an accurate in silico system for the prediction of dysregulated genes within the epileptic focus. We present such a bioinformatic system. We demonstrate the validity of our approach by applying it to the solute carrier (SLC) gene family. There are >400 known SLCs. SLCs have never been systematically studied in epilepsy.\ud Methods:\ud \ud Using our in silico system, we predicted the SLCs likely to be dysregulated in the epileptic focus. We validated our in silico predictions by identifying ex vivo the SLCs dysregulated in epileptic foci, and determining the overlap between our in silico and ex vivo results. For the ex vivo analysis, we used a custom oligonucleotide microarray containing exon probes for all known SLCs to analyze 24 hippocampal samples obtained from surgery for pharmacoresistant mesial temporal lobe epilepsy and 24 hippocampal samples from normal postmortem controls.\ud Results:\ud \ud There was a highly significant (p < 9.99 × 10−7) overlap between the genes identified by our in silico and ex vivo strategies. The SLCs identified were either metal ion exchangers or neurotransmitter transporters, which are likely to play a part in epilepsy by influencing neuronal excitability.\ud Significance:\ud \ud The identified SLCs are most likely to mediate pharmacoresistance in epilepsy by enhancing the intrinsic severity of epilepsy, but further functional work will be needed to fully evaluate their role. Our successful in silico strategy can be adapted in order to prioritize genes relevant to epilepsy from other gene families.

The most common primary intracranial malignancy, glioblastoma (GBM) carries an exceptionally poor prognosis. Though first line management has seen some standardisation in recent years, the approach to recurrence is more heterogenous. To determine whether resection of recurrent GBM impacts survival, cases between January 1(st) 2015 and 31(st) December 2016 were retrospectively reviewed. Eligible patients had: (i) primary GBM; (ii) undergone resection for initial tumour (iii) received treatment for recurrence that could include chemoradiotherapy, reoperation or Gliadel. Data collected included tumour location and volume, extent of resection, ECOG, time to progression and death. Univariate and multivariate analyses were then performed. 136 eligible patients were identified with a median age of 61.5 years, of whom 78 (57%) were males. Tumours were predominantly temporal and frontal (70%), with a mean volume of 34300mm(3). 36% of patients had initial gross total resection (GTR), with 81% going on to receive temozolomide and radiotherapy as part of the Stupp protocol. Median time to recurrence was 7.4 months, with 30 patients (22.1%) receiving reoperation; resulting in a significantly longer OS of 29.4 months compared to 13.5 in the non-reoperation group (P0.05). Cox regression analysis confirmed initial GTR as a significant predictor of survival, providing an OS of 20.5 months vs 16.4 months in the subtotal group (P

Objective Despite modern anti-epileptic drug treatment, approximately 30% of epilepsies remain medically refractory and for these patients, epilepsy surgery may be a treatment option. There have been numerous studies demonstrating good outcome of epilepsy surgery in the short to median term however, there are a limited number of studies looking at the long-term outcomes. The aim of this study was to ascertain the long-term outcome of resective epilepsy surgery in a large neurosurgery hospital in the U.K. Methods This a retrospective analysis of prospectively collected data. We used the 2001 International League Against Epilepsy (ILAE) classification system to classify seizure freedom and Kaplan-Meier survival analysis to estimate the probability of seizure freedom. Results We included 284 patients who underwent epilepsy surgery (178 anterior temporal lobe resections, 37 selective amygdalohippocampectomies, 33 temporal lesionectomies, 36 extratemporal lesionectomies), and had a prospective median follow-up of 5 years (range 1–27). Kaplan-Meier estimates showed that 47% (95% CI 40–58) remained seizure free (apart from simple partial seizures) at 5 years and 38% (95% CI 31–45) at 10 years after surgery. 74% (95% CI 69–80) had a greater than 50% seizure reduction at 5 years and 70% (95% CI 64–77) at 10 years. Patients who had an amygdalohippocampectomy were more likely to have seizure recurrence than patients who had an anterior temporal lobe resection (p = 0.006) and temporal lesionectomy (p = 0.029). There was no significant difference between extra temporal and temporal lesionectomies. Hippocampal sclerosis was associated with a good outcome but declined in relative frequency over the years. Conclusion The vast majority of patients who were not seizure free experienced at least a substantial and long-lasting reduction in seizure frequency. A positive long-term outcome after epilepsy surgery is possible for many patients and especially those with hippocampal sclerosis or those who had anterior temporal lobe resections.

ObjectivesPercutaneous balloon compression (PBC) can be offered to medically refractory patients with trigeminal neuralgia who are unsuitable for microvascular decompression. Its associated with up to 4% risk of anaesthesia dolorosa which increases with duration and severity of compression and is more common with repeat procedures. We audited our outcomes for this procedure over last 7 years.DesignRetrospective audit of prospectively collected data.SubjectsAll patients undergoing PBC at our centre.MethodsTheatre and radiology records reviewed to identify patients. Case notes and radiology reviewed for history, diagnosis, details of procedure, immediate symptom relief, complications, further procedures and last follow up. Descriptive, comparative Kaplan Meir analysis undertaken.ResultsTotal 93 patients (4 b/l), 165 procedures. Average follow up 36 months. 24 patients had MS, 17 patients had atypical pain. All except 4 patients had good immediate pain relief. No patient developed anaesthesia dolorosa, 2 patients had transient diplopia, 1 maxillary hematoma and 1 infection. 56 experienced recurrence, 43 needed further surgical intervention. 25 PBC twice, 11 thrice, 4 four times and 1 five times. Average time to first recurrence=32 months. 85% pain free at 1 year and 70% at 2 years.ConclusionsPBC is an effective procedure. With conservative approach, this procedure can be safely repeated.

Atypical meningiomas have a greater propensity to recur than benign meningiomas and the benefits of early adjuvant radiotherapy are unclear. Existing studies report conflicting results. This retrospective cohort study evaluated the role of early adjuvant radiotherapy following surgical resection of atypical meningioma. A triple center case-note review of adults with newly-diagnosed atypical meningiomas between 2001 and 2010 was performed. Pathology diagnosis was made according to the World Health Organization classification in use at the time of surgery. Patients with multiple meningiomas, neurofibromatosis type 2 and radiation-induced meningiomas were excluded. Extent of resection was defined as gross total resection (GTR; Simpson Grade I-III) or subtotal resection (STR; Simpson Grade IV-V). Survival analysis was performed using the Kaplan-Meier method. One hundred thirty-three patients were identified with a median age of 62years (range 22-86years) and median follow-up of 57.4months (range 0.1-152.2months). Tumors were mostly located in the convexity (50.4%) or falcine/parasagittal regions (27.1%). GTR (achieved in 85%) was associated with longer progression free survival (PFS) (5year PFS 81.2% versus 40.08%, log-rank=11.117, p=0.001) but not overall survival (OS) (5year OS 76.6% versus 39.7%, log-rank=3.652, p=0.056). Following GTR, early adjuvant radiotherapy was administered to 28.3% of patients and did not influence OS (5year OS 77.0% versus 75.7%, log-rank=0.075, p=0.784) or PFS (5year PFS 82.0% versus 79.3%, log-rank=0.059, p=0.808). Although extent of resection emerged as an important prognostic variable, early adjuvant radiotherapy did not influence outcome following GTR of atypical meningiomas. Prospective randomized controlled trials are planned.

Latero-posterior thalamic strokes are reported to result in delayed onset action tremor, dystonia, pseudoathetosis, chorea and myoclonus. This complex disorder is usually associated with proprioceptive sensory loss and limb ataxia. The tremor has a large amplitude postural component whichworsens on targeted movements; this with the associated sensory loss renders it incapacitating. Thalamic VIM ablation has been reported to improve this tremor. However, deep brain stimulation (DBS) has not. We report 3 cases with post-thalamic stroke tremor, 2 of which have been successfully treated with thalamic DBS; the third is being considered. The first was a 41 year old female who presented with a left sided tremor resulting from a right thalamic stroke after a vertebral artery dissection. The second was a 69 year old male with a right sided tremor resulting from an ischaemic stroke of the left thalamus and the third had bilateral arm tremor resulting from bilateral latero posterior thalamic strokes following a syringomyelia decompression surgery. The tremor in all was of the cerebellar type with joint position sense loss up to the wrist; pseudoathetosis and dystonic posturing. Thalamic DBS ameliorated the large amplitude component of the tremor improving arm function.

To evaluate the impact, on morbidity and mortality, of aggressive surgical management of subdural empyema of sinus origin in children. The authors conducted a retrospective review of 20 children admitted between 2000–2007 to Alder Hay Children Hospital and The Walton centre for Neurology and Neurosurgery for subdural empyema secondary to sinus infection. Clinical presentation, duration of symptoms, radiological investigations, surgical treatment and post-operative outcome were evaluated. Outcome was favourable in 19 cases. In four cases, there were re-accumulation requiring surgical evacuation, four patients experienced post-operative seizures but were seizure-free at follow-up. There was only one mortality in the series. Subdural empyema secondary to sinus infection, although uncommon, it could be associated with a relative high morbidity and mortality rate. Early aggressive surgical and medical management with drainage of intracranial or sinus collections and antibiotics therapy lead to a low mortality or morbidity rate and good clinical outcome.

Object The aim of this study was to evaluate the efficacy of endoscopic third ventriculostomy (ETV) in patients with Chiari malformation Type I (CM-I) and hydrocephalus with or without syringomyelia. Methods The authors identified, in a prospective endoscopy database, 16 adults and children (age range 2–68 years) with CM-I and hydrocephalus that had been managed with ETV. They reviewed the clinical features and radiographic findings for all patients. Fifteen patients underwent ETV as a primary treatment, whereas 1 patient underwent the procedure at the time of shunt failure. All patients had symptomatic hydrocephalus with either aqueductal or fourth ventricular outflow obstruction. The mean duration of follow-up was 42 months. Results Fifteen patients (94%) remain shunt free following ETV for CM-I. Five (83%) of the 6 patients with a syrinx had improvement or resolution of the syrinx following ETV. Six patients (37.5%) underwent foramen magnum decompression for persistent CM-I– or syrinx-related symptoms. There was no cerebrospinal fluid leakage or intracranial pressure–related problem following foramen magnum decompression. Conclusions Endoscopic third ventriculostomy provides a durable method of treatment for hydrocephalus associated with CM-I. It is effective as a primary treatment, and the authors advocate its use as a replacement for routine ventriculoperitoneal shunt insertion in these patients. Management of the hydrocephalus alone is often sufficient and may obviate decompression, although a significant proportion of patients will still need both procedures.

Numerous diverse biological pathways are dysregulated in the epileptic focus. Which of these pathways are most critical in producing the biological abnormalities that lead to epilepsy? Answering this question is key to identifying the primary causes of epilepsy and for discovering new therapeutic strategies with greater efficacy than currently available antiepileptics (AEDs). We have performed the largest genome-wide transcriptomic analysis to date comparing epileptic with normal human hippocampi. We have identified 118 differentially expressed and, for the first time, differentially connected pathways in the epileptic focus. Using network mapping techniques, we have shown that these dysregulated pathways, though seemingly disparate, form a coherent interconnected central network. Using closeness centrality analysis, we have identified that the most influential hub pathways in this network are signalling through G protein-coupled receptors, in particular opioid receptors, and their downstream effectors PKA/CREB and DAG/IP3. Next, we have objectively demonstrated that genetic association of gene sets in independent genome-wide association studies (GWASs) can be used to identify causally relevant gene sets: we show that proven causal epilepsy genes, which cause familial Mendelian epilepsy syndromes, are associated in published sporadic epilepsy GWAS results. Using the same technique, we have shown that central pathways identified (opioid receptor and PKA/CREB and DAG/IP3 signalling pathways) are genetically associated with focal epilepsy and, hence, likely causal. Published functional studies in animal models provide evidence of a role for these pathways in epilepsy. Our work shows that these pathways play a central role in human focal epilepsy and that they are important currently unexploited antiepileptic drug targets.

Background The aims are to present a case series of Twiddler’s syndrome in spinal cord stimulators with analysis of the possible mechanism of this syndrome and discuss how this phenomenon can be prevented. Method Data were collected retrospectively between 2007 and 2013 for all patients presenting with failure of spinal cord stimulators. The diagnostic criterion for Twiddler’s syndrome is radiological evidence of twisting of wires in the presence of failure of spinal cord stimulation. Results Our unit implants on average 110 spinal cord stimulators a year. Over the 5-year study period, all consecutive cases of spinal cord stimulation failure were studied. Three patients with Twiddler’s syndrome were identified. Presentation ranged from 4 to 228 weeks after implantation. Imaging revealed repeated rotations and twisting of the wires of the spinal cord stimulators leading to hardware failure. Conclusions To the best of our knowledge this is the first reported series of Twiddler’s syndrome with implantable pulse generators (IPGs) for spinal cord stimulation. Hardware failure is not uncommon in spinal cord stimulation. Awareness and identification of Twiddler’s syndrome may help prevent its occurrence and further revisions. This may be achieved by implanting the IPG in the lumbar region subcutaneously above the belt line. Psychological intervention may have a preventative role for those who are deemed at high risk of Twiddler’s syndrome from initial psychological screening.

Glioma cells express high protein kinase C (PKC) activity, which may represent an important therapeutic target. Tamoxifen (TAM) has moderate PKC-inhibiting activity, blocking DNA synthesis and cellular proliferation in human glioma cells at concentrations that can be achieved therapeutically. Carboplatin (CBDCA), a second-generation platinum derivative, induces intra- and interstrand DNA-protein crosslinks producing inhibition of tumor-cell growth. In the present study, the effect of TAM, CBDCA, and the combination of both was evaluated against the human established U-138 glioma cell line during the exponential growth phase (48-72 h) by means of both the Biorad protein assay (BPA) method and Trypan blue exclusion study (TBES). Both TAM and CBDCA reduced the cellular growth rate, with a median 50%-inhibiting concentration (IC50) of 12.5 microM for TAM and 350 microM for CBDCA. The U-138 glioma cell line showed a moderate response to 100 microM of CBDCA, with < or = 10% reduction of the growth rate. The association of both chemotherapeutic agents induced a 98% reduction of the IC50 dose of TAM (0.1 microM), and a 71% reduction of the IC50 dose of CBDCA (100 microM). During the combinational TAM CBDCA exposure we observed a cytotoxic effect of TAM at concentrations lower than 0.1 microM, not recognized using it as a single drug. The differences observed among the IC50 doses (TAM, CBDCA, TAM-CBDCA) and among treated and untreated matched control cells were statistically significant (P < 0.01). Our results confirm previous observations about the efficacy in vitro of TAM against human glioma cell lines and show a marked enhancement of this activity by CBDCA.

Between April, 1992 and December, 1995, forty consecutive patients with a cerebral malignant glioma (WHO Grade III and IV) were enrolled in a trial consisting in surgery and post-operative administration of radiotherapy (4500-6000 cGy), carboplatin (CBDCA; dose of 450-600 mg/m2), and oral tamoxifen (TAM; at doses of 40, 80 or 120 mg/day). Two patients of the TAM group died in the postoperative period from a pulmonary embolism and myocardial infarction, respectively. The patients (all dosages combined) had a median survival time of 13 months from the time of diagnosis. The 12-month and 24-month survival rates were 52% and 32%, respectively. The median relapse-free survival time was 7 months. Patients treated with higher doses of TAM (80-120 mg/day) demonstrated a longer median survival rate (13 months both) and a longer 12-month survival result (58% and 76%, respectively). Patients who assumed TAM for a period longer than 3 months (group +3) have a higher median survival rate (16 months) and better 12-month and 24-month results (62% and 40%, respectively). Moreover, the median relapse-free survival time was 10 months (versus 6 months in group -3; p = 0.0038). However, it is not possible to exclude that patients of group +3 had a slower growing or a stable tumor and were well enough to assume TAM for a longer period. The results observed in the TAM-group have been compared with those of 40 matched controls treated with surgery, radiotherapy and CBDCA. These patients had a median survival time of 9 months (p = 0.04) and the 12-month and 24-month survival rates were 30% and 0%, respectively. The median relapse-free survival time was 4 months (p = 0.0014). These data suggest a potential role for combinational TAM-CBDCA therapy in the post-operative treatment of cerebral malignant gliomas; further clinical phase III trials, especially those with higher dosages of TAM are warranted.

The case of a patient with a right atypical trigeminal neuralgiacaused by a metastatic tumor involving the Meckel‘s cave is reported. His medical history was significant for colon-rectaladenocarcinoma. The preoperative diagnosis of Meckel‘s cave neoplasmwas made by MR. The patient underwent surgery, consisting oftotal removal of tumor and peeling of the ganglion and of the branches of the nerve, obtaining a histological diagnosis anda resolution of pain. The clinical, radiological findings and the treatment of this rare entity are discussed.

The rarity and the inconsistent criteria for defining atypical meningioma prior to the WHO 2007 classification made its management and prognostic factors poorly understood. Only few articles have addressed the survival rates of WHO-classified atypical meningiomas. The small number or the disproportionate representation of irradiated patients was a weakness for these articles. This study evaluated whether the extent of surgery and receiving adjuvant radiotherapy after an initial operation along with other patient characteristics influenced the recurrence and survival rates of atypical meningiomas. The clinical and surgical notes of the 79 patients with grade II atypical meningioma treated at our center over 13 years were retrospectively evaluated. The histology grading was consistent with WHO 2007 classification. The Simpson grading system was used to assess the extent of surgical resection. Kaplan Meier analysis, Cox multivariate regression analysis, and the Log-rank test were conducted using STATA® statistical package. The average age at the time of initial operation was 58 years, and 54 % were males. The mean follow-up period was 50 months. In Cox multivariate analysis, only Simpson grading was predictive of recurrence (hazard ratio = 2.22 / 1 increase in Simpson grade. p = 0.003). Simpson grade I patients had a relapse-free survival rate of 97 and 74 % at one and five years, respectively, compared with 88 and 32 % in the subtotal resection group (Simpson grades II to IV). There was no statistically significant correlation between recurrence and subjecting patients to postoperative radiotherapy. Apart from Simpson grade I patients, there was a general trend for worse outcome in irradiated patients. The most important prognostic factor in determining recurrence was Simpson grading. There was no statistically significant impact of adjuvant radiotherapy on the recurrence of atypical meningiomas. Meta-analysis for the existing literature is needed.

Tremor is an important cause of disability and poor quality of life amongst multiple sclerosis (MS) patients. We assessed the outcomes of ventral intermediate (VIM) nucleus deep brain stimulation for the treatment of multiple sclerosis (MS)–associated tremor at a single centre in a prospective fashion. Sixteen patients (9 female, 7 male) with a mean age of 41.7 years (range 24–59) underwent surgery. The median duration of MS prior to surgery was 6.5 years and median duration of tremor prior to surgery was 4 years. Case selection was by multidisciplinary assessment with carers, therapists, neurosurgeons and movement disorder neurologists. Tremor was scored pre-operatively and at 6 to 12 months post operatively using Bain and/or Fahn–Tolosa–Marin systems. The Euro-Qol 5D tool was used to assess quality of life before and after surgery. The mean tremor reduction was 39 % with a range between 0 and 87 %. Five of 16 patients achieved at least 50 % tremor reduction and 11 of 16 achieved at least 30 % tremor reduction at last follow up, mean 11.6 months (range 3–80). Tremor was significantly reduced as rated by Bain scores (Wilcoxon matched pairs, Z = 3.07, p = .002) and tended to significance as rated by Fahn scores (Wilcoxon matched pairs, Z = 1.85, p = 0.06). Sub-analysis of activities of daily living measures from the Fahn system showed post operative improvement in feeding (statistically significant), hygiene, dressing, writing and working. Mean visual analogue scores (0–100) of patient reported well-being increased from 54.6 to 57.4 post operatively with a trend to significance (Student’s t-test, t = 1.26, p = 0.2). Euro-Qol 5D utility values increased following surgery with a trend to significance which was greater in the group with at least 50 % tremor reduction than in those with none or at least 30 % tremor reduction. VIM DBS may reduce severe, disabling tremor in patients with MS. This tremor reduction tends to be associated with improved quality of life and function in those who respond. Patient reported outcome measures may not correlate with physician rated clinical outcome such as tremor scoring systems and more subtle assessment of these patients is required.

We report a series of five patients operated on for hindbrain-related syringomyelia with posterior fossa decompression and duraplasty. In all cases an early postoperative MRI was performed (24-36 h after surgery). These images have been compared with the preoperative ones and with those obtained, 1, 3 and 6 months after operation. Both before and after surgery there was not always a tight correlation between clinical and MRI pictures. In all but one patient the early postoperative MR images showed a reduction of syrinx size and were as to those obtained later. We discuss the results observed in our small series and analyze the role of early postoperative MRI studies in patients with hindbrain-related syringomyelia.

The case of a young patient with left accessory nerve paralysis is reported. He had slight tilting of the head to the right side, developed over a period of about 6 months. On neurological examination hypotrophy of the left sternocleidomastoid and trapezius muscles was observed. MRI and MR-angiography imaged the presence of a neurovascular compression between the medulla oblungata, at the level of the nerve entry zone, and a vessel loop of an elongated left vertebral artery. In spite of the absence of a surgical demonstration it is our opinion that the neurovascular conflict is the cause of the accessory nerve palsy.

BACKGROUND: Bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) was shown to be effective in cervical dystonia refractory to medical treatment in several small short-term and 1 long-term follow-up series. Optimal stimulation parameters and their repercussions on the cost/benefit ratio still need to be established. OBJECTIVE: To report our long-term outcome with bilateral GPi deep brain stimulation in cervical dystonia. METHODS: The Toronto Western Spasmodic Torticollis Rating Scale was evaluated in 10 consecutive patients preoperatively and at last follow-up. The relationship of improvement in postural severity and pain was analyzed and stimulation parameters noted and compared with those in a similar series in the literature. RESULTS: The mean (standard deviation) follow-up was 37.6 (16.9) months. Improvement in the total Toronto Western Spasmodic Torticollis Rating Scale score as evaluated at latest follow-up was 68.1% (95% confidence interval: 51.5-84.6). In 4 patients, there was dissociation between posture severity and pain improvement. Prevalently bipolar stimulation settings and high pulse widths and amplitudes led to excellent results at the expense of battery life. CONCLUSION: Improvement in all 3 subscale scores of the Toronto Western Spasmodic Torticollis Rating Scale with bilateral GPi deep brain stimulation seems to be the rule. Refinement of stimulation parameters might have a significant impact on the cost/ benefit ratio of the treatment. The dissociation of improvement in posture severity and pain provides tangible evidence of the complex nature of cervical dystonia and offers interesting insight into the complex functional organization of the GPi.

Optic sheath meningocele is rare; only approximately 31 cases have been reported. The term optic sheath meningocele has recently been proposed by Garrity and Forbes to describe primary CSF cysts of the optic nerve sheath, without apical mass or malformation of the cranio-orbital junction. Presenting symptoms are often related to involvement of the optic nerve, with a slow or rapid decrease of visual acuity. CT and MRI studies reveal a tubular-cystic enlargement of the optic nerve/optic sheath complex (on/onsc), with thickening of the optic nerve. Radiological differential diagnosis should include optic nerve tumors such as gliomas, meningiomas, and arachnoid cysts involving the optic nerve sheath. Up to now, it seems that early surgical management by means of optic nerve/optic nerve sheath decompression affords an improvement of visual function with minimal morbidity in patients who present a rapid decrease of visual acuity within 3-6 months. We present an additional case and discuss the clinical, radiological, and operative features of this pathological condition of the optic nerve sheath.

A case of eosinophilic granuloma of the lesser wing of the sphenoid bone is reported. The patient was a 5-year-old white male, with left temporal-frontal headache, left III cranial nerve palsy, left exophthalmos and ptosis caused by an osteolytic lesion of the anterior clinoid process extending to the left optic canal and cavernous sinus. The patient underwent surgical resection of pathologic tissue. Pathologic diagnosis was eosinophilic granuloma of the sphenoid bone. Surgical management, postoperative prognosis and differential diagnosis of eosinophilic granuloma of the skull base are discussed along with a review of the literature.

A study was performed to evaluate the efficacy of closed continuous drainage (CCD) via a lumbar subarachnoid catheter for prevention or treatment of CSF fistulas. In addition to the analysis of the physical, chemical and biological properties of the CSF obtained, the catheters themselves were tested on removal to identify any microorganisms contaminating them. Other factors taken into consideration were the symptoms reported by the patients during positioning of the catheter and while it was in place, any variations in body temperature and local inflammatory effects on the nerve roots of the cauda equine and surrounding tissues. The low percentage of systemic and local infections observed testifies to the safety of this method, regardless of the duration of treatment.

Aims and background Histiocytosis X is a condition characterized by an abnormal proliferation of histiocytes with a variable granulomatous and inflammatory component; bone involvement is almost always present. The aim of this study was to define the management of solitary eosinophilic granuloma (EG) of the calvaria in adult patients, in relation to the size and site of the lesion. Methods Fourteen patients, ranging in age from 7 to 45 years, with solitary eosinophilic granuloma of the calvaria were surgically treated by craniectomy or curettage and cranioplasty. We subgrouped the lesions into two types: A) lesions localized inside the diploë and/or compressing the cerebral parenchyma below but without dural infiltration; B) lesions with mainly intracranial growth, compressing the cerebral parenchyma and infiltrating the dura. The infiltrated dura mater in type B lesions was replaced with a dural patch. Cranioplasty was performed in lesions with a diameter of 4 cm or more and/or located in aesthetically exposed areas of the skull. Results None of the patients died during the study and no local or systemic recurrences were observed during follow-up (min. 3 yrs, max. 8 yrs). Conclusions Surgical treatment of patients with isolated EG of the calvaria not only is simple and quick but also allows histological diagnosis of the osteolytic lesion. These patients do not require further adjuvant treatment. Cranioplasty should be performed when the lesion has a diameter of 4 cm or more, when it is located in aesthetically exposed areas of the skull such as the frontal or temporal bones, or when it produces alterations of the normal skull morphology.