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This meta-analysis examines mood changes after bilateral subthalamic deep brain stimulation (STN-DBS) in patients with Parkinson's disease (PD). Deep brain stimulation improves motor outcomes in Parkinson's disease but there appears to be conflicting reports as to subsequent mood outcomes. Pubmed, PsychINFO and SCOPUS were searched for studies assessing mood outcomes in PD patients who had undergone STN-DBS published between January 2003 and the end of January 2019. Random effects meta-analyses were conducted for all outcome groups with at least two studies homogenous in design and measure. Forty-eight studies, providing data on negative moods (such as depression, anxiety, apathy, and anger) and positive moods (pleasure and euphoria) were assessed. Results of the meta-analysis suggest that post-DBS, depression and anxiety symptoms improve and there is a reduction in negative affect, an increase in apathy, and in energy level. Although there have been reported cases of mania post-DBS surgery, the meta-analysis suggested no significant changes in symptoms of mania in the broader DBS population. Considerable heterogeneity was found and partially addressed through meta-regression and qualitative assessment of the included STN-DBS controlled studies. The major strengths of this meta-analysis, include attention to outcome validity, heterogeneity, independence of samples, and clinical utility, with the potential to improve post-operative safety through comprehensive consideration of mood and psychological adjustment. It appears that STN-DBS is a relatively safe and, in the case of mood symptomatology, an advantageous treatment of Parkinson's disease.

Background and importance Obsessive-compulsive disorder (OCD) is a disabling psychiatric disorder, mainly treated with psychotherapy and pharmacotherapy. Surgical intervention may be appropriate for patients with treatment-refractory OCD. Deep brain stimulation (DBS) is an alternative for previously common ablative surgical procedures. Tractography has been proposed as a method for individualizing DBS treatment and may have the potential to improve efficacy. Clinical presentation We present a patient with treatment-refractory OCD previously treated with bilateral leucotomies, who underwent DBS surgery with targeting informed by tractography. Preoperative tractography to identify suitable DBS targets was undertaken. Structural images were also utilized for standard stereotactic surgical planning. The anteromedial globus pallidus internus (amGPi) was chosen as the target bilaterally after consideration of white matter projections to frontal cortical regions and neurosurgical approach. Bilateral amGPi DBS surgery was undertaken without adverse events. At 16-mo follow-up, there was a 48.5% reduction in OCD symptom severity as measured by the Yale-Brown Obsessive Compulsive Scale. Conclusion The amGPi can be a successful DBS target for OCD. This is the first known case to report on DBS surgery postleucotomies for OCD and highlights the utility of tractography for surgical planning in OCD.

The mirror neuron (MN) hypothesis of autism has received considerable attention, but to date has produced inconsistent findings. Using functional MRI, participants with high functioning autism or Asperger's syndrome were compared to typically developing individuals (n=12 in each group). Participants passively observed hand gestures that included waving, pointing, and grasping. Concerning the MN network, both groups activated similar regions including prefrontal, inferior parietal and superior temporal regions, with the autism group demonstrating significantly greater activation in the dorsal premotor cortex. Concerning other regions, participants with autism demonstrated increased activity in the anterior cingulate and medial frontal gyrus, and reduced activation in calcarine, cuneus, and middle temporal gyrus. These results suggest that during observation of hand gestures, frontal cortex activation is affected in autism, which we suggest may be linked to abnormal functioning of the MN system.

Background Studies are increasingly investigating the therapeutic effects of deep brain stimulation (DBS) applied to a variety of brain regions in the treatment of patients with highly treatment refractory depression. Limited research to date has investigated the therapeutic potential of DBS applied to the Bed Nucleus Of Stria Terminalis (BNST). Objective The aim of this study was to explore the therapeutic potential of DBS applied to the BNST. Method Five patients with highly treatment resistant depression underwent DBS to the BNST in an open label case series design. Results BNST DBS resulted in sustained remission of depression in two of the five patients, provided substantial therapeutic improvement two further patients, and had minimal antidepressant effect for the final patient. There were no operative complications and stimulation related side effects were limited and reversible with adjustment of stimulation. However, the time to achieve and complexity of programming required to achieve optimal therapeutic outcomes varied substantially between patients. Conclusion DBS applied to the BNST as therapeutic potential in patients with highly refractory depression and warrants exploration in larger clinical studies.

Objective: Deep brain stimulation can be of benefit in carefully selected patients with severe intractable obsessive-compulsive disorder. The aim of this paper is to describe the outcomes of the first seven deep brain stimulation procedures for obsessive-compulsive disorder undertaken at the Neuropsychiatry Unit, Royal Melbourne Hospital. The primary objective was to assess the response to deep brain stimulation treatment utilising the Yale-Brown Obsessive Compulsive Scale as a measure of symptom severity. Secondary objectives include assessment of depression and anxiety, as well as socio-occupational functioning. Methods: Patients with severe obsessive-compulsive disorder were referred by their treating psychiatrist for assessment of their suitability for deep brain stimulation. Following successful application to the Psychosurgery Review Board, patients proceeded to have deep brain stimulation electrodes implanted in either bilateral nucleus accumbens or bed nucleus of stria terminalis. Clinical assessment and symptom rating scales were undertaken pre- and post-operatively at 6- to 8-week intervals. Rating scales used included the Yale-Brown Obsessive Compulsive Scale, Obsessive Compulsive Inventory, Depression Anxiety Stress Scale and Social and Occupational Functioning Assessment Scale. Results: Seven patients referred from four states across Australia underwent deep brain stimulation surgery and were followed for a mean of 31 months (range, 8–54 months). The sample included four females and three males, with a mean age of 46 years (range, 37–59 years) and mean duration of obsessive-compulsive disorder of 25 years (range, 15–38 years) at the time of surgery. The time from first assessment to surgery was on average 18 months. All patients showed improvement on symptom severity rating scales. Three patients showed a full response, defined as greater than 35% improvement in Yale-Brown Obsessive Compulsive Scale score, with the remaining showing responses between 7% and 20%. Conclusion: Deep brain stimulation was an effective treatment for obsessive-compulsive disorder in these highly selected patients. The extent of the response to deep brain stimulation varied between patients, as well as during the course of treatment for each patient. The results of this series are comparable with the literature, as well as having similar efficacy to ablative psychosurgery techniques such as capsulotomy and cingulotomy. Deep brain stimulation provides advantages over lesional psychosurgery but is more expensive and requires significant multidisciplinary input at all stages, pre- and post-operatively, ideally within a specialised tertiary clinical and/or academic centre. Ongoing research is required to better understand the neurobiological basis for obsessive-compulsive disorder and how this can be manipulated with deep brain stimulation to further improve the efficacy of this emerging treatment.

Metastases to the brain and spine are common and difficult to treat. Stereotactic radiosurgery (SRS) is a non-invasive treatment option for some individuals, and may obviate the need for open surgery and/or whole brain radiotherapy. Over the past decade there has been an increased number of patients undergoing SRS for the treatment of metastatic disease, and multiple published studies show favourable results in terms of local disease control. We review the available literature pertaining to the application of SRS for the treatment of brain and spine metastases, together with its limitations and outcomes.

Deep brain stimulation (DBS) is now well established in the treatment of intractable movement disorders. Over the past decade the clinical applications have expanded into the realm of psychosurgery, including depression and obsessive compulsive disorder (OCD). The optimal targets for electrode placement in psychosurgery remain unclear, with numerous anatomical targets reported for the treatment of OCD. We present four patients with Tourette's syndrome and prominent features of OCD who underwent DBS of the anteromedial globus pallidus internus (GPi) to treat their movement disorder. Their pre-operative and post-operative OCD symptoms were compared, and responded dramatically to surgery. On the basis of these results, we propose the anteromedial (limbic) GPi as a potential surgical target for the treatment of OCD, and furnish data supporting its further investigation as a DBS target for the treatment of psychiatric conditions.

Disabling intractable tremor occurs frequently in patients with multiple sclerosis (MS). There is currently no effective medical treatment available, and the results of surgical intervention have been variable. Thalamotomy has been the mainstay of neurosurgical therapy for intractable MS tremor, however the popularisation of deep brain stimulation (DBS) has led to the adoption of chronic thalamic stimulation in an attempt to ameliorate this condition. With the goal of examining the relative efficacy and adverse effects of these two surgical strategies, we studied twenty carefully selected patients with intractable MS tremor. Thalamotomy was performed in 10 patients, with chronic DBS administered to the remaining 10. Both thalamotomy and thalamic stimulation produced improvements in postural and intention tremor. The mean improvement in postural tremor at 16.2 months following surgery was 78%, compared with a 64% improvement after thalamic stimulation (14.6 month follow-up) (P > 0.05). Intention tremor improved by 72% in the group undergoing thalamotomy, a significantly larger gain than the 36% tremor reduction following DBS (P < 0.05). Early postoperative complications were common in both groups. Permanent complications related to surgery occurred in four patients overall. Following thalamotomy, long-term adverse effects were observed in three patients (30%), and comprised hemiparesis and seizures. Only one patient in the thalamic stimulation group experienced a permanent deficit (monoparesis). We conclude that thalamotomy is a more efficacious surgical treatment for intractable MS tremor, however the higher incidence of persistent neurological deficits in patients receiving lesional surgery may support the use of DBS as the preferred surgical strategy.

The periaqueductal grey area (PAG) in the midbrain is an important area for both cardiovascular control and modulation of pain. However, the precise relationship between pain and blood pressure is unknown. We prospectively studied 16 patients undergoing deep brain stimulation of the rostral PAG for chronic pain. Pre-operatively, post-operatively, and at 1 year, pain scores were assessed using both visual analogue scores and the McGill Pain Questionnaire. Patients were tested post-operatively to determine whether electrical stimulation of the PAG would modulate blood pressure. We found that the degree of analgesia induced by deep brain stimulation of the rostral PAG in man is related to the magnitude of reduction in arterial blood pressure. We found that this relationship is linear and is related to reduced activity of the sympathetic nervous system. Thus stimulation of the PAG may partly control pain by reducing sympathetic activity as predicted by William James over a century ago.

Epilepsy prevalence in the developing world is many fold that found in developed countries. For individuals whose conditions failed to respond to pharmacotherapy, surgery is the only opportunity for cure. In Uganda, we developed a center for treatment of intractable temporal lobe epilepsy (iTLE) that functions within the technologic and expertise constraints of a severely low resource area. Our model relies on partnership with epilepsy professionals and training of local staff. Patients were prescreened at regional clinics for iTLE. Individuals meeting inclusion criteria were referred to the treating Ugandan hospital (CURE Children's' Hospital of Uganda, CCHU) for video-EEG (electroencephalography), computed tomography (CT) imaging, and neuropsychological evaluation. Data were transferred to epilepsy experts for analysis and treatment recommendations. Ten patients were diagnosed with iTLE and surgically treated at CCHU. Six (60%) were seizure free, and there was no neurologic morbidity or mortality. Our model for surgical treatment of pharmacoresistant TLE has functioned successfully in a true developing world low resource setting.

Deep brain stimulation (DBS) for pain was one of the earliest indications for the therapy. This study reports the outcome of DBS of the sensory thalamus and the periventricular and peri-aqueductal grey area (PVG/PAG) complex for different intractable neuropathic pain syndromes. Forty-seven patients (30 males and 17 females) were selected for surgery; they were suffering from any of the following types of pain: post-stroke neuropathic pain, phantom limb pain, post-herpetic neuralgia, anaesthesia dolorosa, brachial plexus injury and neuropathic pain secondary to neural damage from a variety of causes. Of the 47 patients selected for trial stimulation, 38 patients proceeded to permanent implantation. Patients suffering from post-stroke pain were the most likely to fail trial stimulation (33%), in contrast to individuals with phantom limb/post-brachial plexus injury pain and anaesthesia dolorosa, all of whom underwent permanent implantation. PVG stimulation alone was optimal in 17 patients (53%), whilst a combination of PVG and thalamic stimulation produced the greatest degree of analgesia in 11 patients (34%). Thalamic stimulation alone was optimal in 4 patients (13%). DBS of the PVG alone was associated with the highest degree of pain alleviation, with a mean improvement of 59% (p or =50% improvement in 66% of patients. Post-stroke pain responds in 70% of patients. We conclude that the outcomes of surgery appear to vary according to aetiology, but it would appear that the effects are best for phantom limb syndromes, head pain and anaesthesia dolorosa.

Object Resection of dysembryoplastic neuroepithelial tumor (DNET) is thought to result in favorable seizure outcome, but long-term follow-up data are scarce. The authors present a review of 18 patients who underwent surgical removal of a DNET: 12 via temporal lobectomy and six via lesionectomy. Methods The mean long-term follow up was 10.8 years (median 10.4 years, range 7.8 to 14.8 years), and results obtained during this time period were compared with previously reported short-term (mean 2.7 years) seizure outcome data. In the current study, 66.7% patients had an Engel Class I outcome and 55.6% had an Engel Class IA outcome compared with 77.8% and 55.6%, respectively. Temporal lobectomy (Engel Class I, 83.3%; Engel Class IA, 66.7%) led to a better seizure outcome than lesionectomy (Engel Classes I and IA, 33.3%). Two patients (11.1%) required repeated operation and both had an incomplete lesionectomy initially. Conclusions Results indicated that complete resection of a DNET leads to a favorable seizure outcome, with epilepsy cure in those who had experienced early postoperative seizure relief. Long-term seizure outcome after surgery is predictable based on the result of short-term follow up.

Despite the relatively high incidence of epilepsy during the first few years of life, and its documented adverse impact on development, few studies have documented the long term outcomes following epilepsy surgery in infants and young children. We report a consecutive series of 11 patients under 3 years of age who underwent excisional surgery for intractable seizures. A total of 16 resective procedures were performed, and comprised functional hemispherectomy, temporal lobectomy, and lesionectomy. The mean follow-up period was 3 years. At follow-up, 73% (8/11) were seizure-free, with over half of these patients able to cease anti-epileptic medications. Acceleration of neurodevelopment was seen in all patients in whom preoperative developmental delay was present. Quality of life was enhanced in all patients. This series confirms that excellent results can be obtained following excisional surgery in well-selected infants and young children with intractable seizures.

We have examined a hemispherectomized patient who complained of touch-evoked pricking and burning pain in her paretic hand, especially when the hand was cold. Psychophysical examination showed that for the paretic side she confused cool and warm temperatures, and confirmed that she had a robust allodynia to brush stroking that was enhanced at a cold ambient temperature. Functional magnetic resonance imaging (fMRI) showed that during brush-evoked allodynia, brain structures implicated in normal pain processing (viz. posterior part of the anterior cingulate cortex, secondary somatosensory cortex, and prefrontal cortices) were activated. The fMRI findings thus indicate that the central pain in this patient was served by brain structures implicated in normal pain processing. Possible pathophysiological mechanisms include plasticity as well as thalamic disinhibition.

The location of human area V5 (or MT) has been correlated with the intersection of the ascending limb of the inferior temporal sulcus (ALITS) and the lateral occipital sulcus (LO). This study was undertaken to attempt a replication and quantification of these observations using functional magnetic resonance imaging. V5 was significantly activated in 19 hemispheres with alternating, low contrast, random checkerboard patterns. We confirmed the stereotaxic location of V5 and were able to describe a fairly consistent sulcal pattern in the parieto-temporo-occipital cortex. V5 was usually (95%) buried within a sulcus, most commonly within the inferior temporal sulcus (ITS) (11%), the ascending limb of the ITS (ALITS) (53%) and the posterior continuation of the ITS (26%). The average distance from V5 of two identified anatomical landmarks of V5, the junctions of the LO and the ALITS, and the ITS and ALITS, were both 1 cm. However, the LO-ALITS junction often had to be determined by interpolation (47%), and was not always present even with interpolation (21%). In contrast, the ITS-ALITS junction was always present and V5 was usually (90%) located in a sulcus intersecting with this junction, making it a more reliable landmark for localizing V5 with respect to gross morphological features on individual cortical surfaces.

Object. Changes in cortical representation in patients with cerebral lesions may alter the correlation between cortical anatomy and function. This is of potential clinical significance when the extent of cortical resection is based on surface anatomical landmarks.Methods. Fifty-one patients with supratentorial lesions were studied. Nineteen harbored noncentral lesions (no involvement of pre- or postcentral gyrus), whereas 32 had central lesions. Control studies consisted of stimulation of the hand contralateral to the unaffected hemisphere. Positron emission tomography activation studies were performed using the [15O]H2O tracer. Somatosensory stimulation of the hand or foot was performed using a mechanical vibrator. Motor activation consisted of hand clenching or foot tapping. The t-statistic volumes were generated from images showing the mean change in regional cerebral blood flow, and coregistered with a T1-weighted magnetic resonance image. At the threshold selected, exclusive contralateral primary sensorimotor cortex activation was elicited in 100% of the control studies. A different pattern of cortical activation was associated with central lesions in 35 (78%) of 45 patients, which occurred significantly more often than with noncentral lesions (eight [31%] of 26 patients). The most common difference in the pattern of activation with central lesions was activation of cortical regions outside the central area (including the supplementary sensorimotor area and the secondary somatosensory cortex). No sensorimotor activation was observed in gyri adjacent to the pre- or postcentral gyrus.Conclusions. Central lesions are more frequently associated with altered patterns in activation than lesions in noncentral locations. Characteristic patterns include activation of secondary sensorimotor areas. The absence of activation in gyri adjacent to the sensorimotor strip has clinical significance for the planning of resections in the central area.

Object. Removal or disconnection of an entire cerebral hemisphere is occasionally used to treat refractory seizures. Patients who have undergone a hemispherectomy provide useful models to study the reorganization of cortical somatosensory representation. This plasticity may be a consequence of the pathological lesion, the hemispherectomy itself, or both.Methods. Three patients who had undergone hemispherectomy were studied with functional magnetic resonance (fMR) imaging. Responses to sensory stimulation in normal hands and hands opposite the lesioned hemisphere were studied. Multislice T2*-weighted gradient-echo echoplanar images were obtained using a 1.5-tesla MR imager. The activation condition consisted of somatosensory stimulation of the index finger. A T1-weighted anatomical MR image was acquired. The fMR and anatomical MR images were coregistered, and statistically significant activation foci (p < 0.01) were identified. Stimulation of the normal hand produced activation in the primary somatosensory cortex (SI) in all patients. Stimulation of the impaired hand resulted in activation of the ipsilateral parietal operculum (second somatosensory area [SII]) and posterior parietal lobe (Brodmann's Area 7) in all cases, but no activation was elicited in the SI in any patient. In addition, other areas within the ipsilateral frontal and parietal lobes were activated in some individuals.Conclusions. Residual somatosensory function in the hand opposite the lesioned hemisphere is mediated by the SII and other cortical regions in the intact hemisphere, without involvement of the SI.

Extracranial metastasis of an intracranial meningioma is rare. We discuss the clinical, radiological and histopathological presentation of an elderly man with pulmonary metastases from a recurrent meningioma of atypical histology, and review the literature pertaining to this phenomenon.

Localization of eloquent cortical regions is an important aspect of neurosurgical practice. When lesions lie close to or within areas such as somatosensory, motor or language cortex, the goal of surgical treatment is maximal resection without causing neurological deficit. Hence precise functional mapping combined with accurate delineation of the extent of pathology is important for deciding whether surgery is feasible at all and defining the safe limit of resection and the optimal operative approach. In addition, when the electroclinical pattern of intractable seizures suggests a specific localization in sensorimotor cortex (e.g., seizures originating in the face area), functional mapping may be of use in directing the surgical treatment at the seizure focus. Activation studies using positron emission tomography (PET) and the tracer [ 15 O] labeled water ([ 15 O]H 2 O) can be used in presurgical planning and in intraoperative surgical guidance in individual patients. The use of PET technology for these purposes is critically dependent on advances in registration or alignment of images acquired using different modalities; the development of neurosurgical guidance devices; and the development of methods of statistical analysis suitable for use in single subjects.

In patients with reflex epilepsy, it is sometimes possible to evoke interictal spikes predictably, thus providing an uncommon but important experimental paradigm for examining the physiological changes produced by epileptiform discharges.To examine the changes in regional cerebral blood flow (rCBF) and glucose consumption (rCMRglc) produced by interictal spikes, we performed positron emission tomography (PET) scans with the blood-flow tracer [15O]H20 and with [18F]fluorodeoxyglucose in a patient with fixation-off epilepsy. The scans were performed in states of high and low spike frequency produced by eye closure and opening, respectively.The rCBF study revealed a focal increase in blood flow associated with the state of increased interictal spiking. The focus was in the posterior portion of the left superior parietal lobule (Talairach coordinates: x: -36, y: -71, z: 39; t = 4.5; p0.05) and corresponded to the site of maximal ictal EEG abnormality recorded with implanted electrodes. In a volume of interest of 10-mm diameter centered on the t statistic peak in the rCBF study, the mean rCMRglc was 39.1 micromol/100 g/min with eyes open and 44.1 micromol/100 g/min (13% increase) with eyes closed. An identical activation paradigm was used in six normal subjects studied with functional magnetic resonance imaging. In the normal subjects, no significant activation was observed in the parieto-occipital region, indicating that the changes observed in the patient were due to interictal spiking rather than to task performance alone.Interictal spiking produces focal increases in cerebral blood flow and glucose metabolism.

There is evidence emerging from Diffusion Tensor Imaging (DTI) research that autism spectrum disorders (ASD) are associated with greater impairment in the left hemisphere. Although this has been quantified with volumetric region of interest analyses, it has yet to be tested with white matter integrity analysis. In the present study, tract based spatial statistics was used to contrast white matter integrity of 12 participants with high-functioning autism or Aspergers syndrome (HFA/AS) with 12 typically developing individuals. Fractional Anisotropy (FA) was examined, in addition to axial, radial and mean diffusivity (AD, RD and MD). In the left hemisphere, participants with HFA/AS demonstrated significantly reduced FA in predominantly thalamic and fronto-parietal pathways and increased RD. Symmetry analyses confirmed that in the HFA/AS group, WM disturbance was significantly greater in the left compared to right hemisphere. These findings contribute to a growing body of literature suggestive of reduced FA in ASD, and provide preliminary evidence for RD impairments in the left hemisphere.

Objective: We describe 3 carriers of the FMR1 premutation with the Fragile X-associated Tremor Ataxia Syndrome (FXTAS) whose tremor was significantly improved by bilateral Deep Brain Stimulation (DBS) to Ventral Intermediate nucleus (Vim) of the thalamus. Background: FXTAS is a recently described neurodegenerative disorder caused by CGG expansions of the FMR1 gene within the premutation range (55 to 200 CGG repeats). Individuals with FXTAS typically develop an intention tremor followed by gait ataxia within two years. Vim DBS has been shown to effectively treat tremor in a variety of disorders, including Parkinson’s disease and essential tremor. Design/Methods/Results: Three men ages 62, 59 and 70 with FXTAS were treated surgically with bilateral Vim DBS. All patients experienced a significantly beneficial effect on tremor. Ataxia improved in case 1 and temporarily in case 2, but worsened in case 3. All patients experienced mild worsening of dysarthria, although the patients and their families unanimously felt there was a worthwhile benefit overall. Conclusions: These cases provided first hand evidence that bilateral Vim DBS effectively manages tremor in selected patients with FXTAS. DBS may prove to be a viable therapeutic option for treating tremor and/or ataxia with or without other medical therapeutics in patients with FXTAS.

Objectives. This is a prospective study to determine the outcomes of subthalamic nucleus (STN) vs. globus pallidus internus (GPi) deep brain stimulation (DBS) at our institution. Materials and Methods. We studied a total of 39 patients — 29 with STN and 10 with GPi DBS over a period of up to 6 years. Mean ages in the two groups were similar (59 and 60 years, respectively) and disease duration prior to implantation was similar (9.6 and 11.7 years, respectively). Unified Parkinson Disease Rating Scale (UPDRS) was recorded preoperatively and at follow-up (at least at 6-month intervals). Medications also were recorded, and each patient's levodopa equivalent units (LEU) were calculated. Results were analyzed using a paired Student's t-test. Results. LEU reduced significantly (p

Objectives. To perform a preliminary cost-utility and cost-benefit of deep brain stimulation (DBS) in the treatment of dystonia, Materials and Methods. We conducted a prospective study of 26 patients undergoing DBS for the treatment of dystonia. We performed a cost-utility analysis using the Euroquol (EQ-5D) questionnaire. A cost-benefit analysis used the willingness-to-pay principle and costs of treatment were calculated retrospectively in order to calculate the cost-benefit. Results. We found that the EQ-5D score improved from 29 to 76.2 points after surgery, an incremental utility of 0.47. There was an overall gain of 0.94 quality-adjusted life-years (QALY) with a cost of £33,980 per QALY. Conclusions. DBS for dystonia, while an expensive treatment, compares favorably to therapies that are commonly used for other conditions.

Autism spectrum disorders (ASDs) are developmental conditions characterized by deficits in social interaction, verbal and nonverbal communication and obsessive/stereotyped patterns of behaviour. Although there is no reliable neurophysiological marker associated with ASDs, dysfunction of the parieto-frontal mirror neuron system has been suggested as a disturbance linked to the disorder. Mirror neurons (MNs) are visuomotor neurons which discharge both when performing and observing a goal directed action. Research suggests MNs may have a role in imitation, empathy, theory of mind and language. Although the research base is small, evidence from functional MRI, transcranial magnetic stimulation, and an electroencephalographic component called the mu rhythm suggests MNs are dysfunctional in subjects with ASD. These deficits are more pronounced when ASD subjects complete tasks with social relevance, or that are emotional in nature. Promising research has identified that interventions targeting MN related functions such as imitation can improve social functioning in ASDs. Boosting the function of MNs may improve the prognosis of ASDs, and contribute to diagnostic clarity.

The past decade (1999-2009) has witnessed a dramatic increase in the use of electrical stimulation to treat chronic, intractable pain. The implantation of electrodes in close proximity to peripheral nerves, known as peripheral nerve stimulation, has been enthusiastically adopted by neurosurgeons and interventional pain specialists. The most common conditions treated with this technique are headache and complex regional pain syndromes. The potential application of peripheral neuromodulation to relatively common and frequently disabling conditions such as migraine and lower back pain represents an exciting phase in the evolution of contemporary pain surgery. We review the available evidence relating to the use of peripheral nerve stimulation for the treatment of medically refractory, chronic non-cancer pain in a variety of clinical situations, highlight the absence of randomised controlled studies, and emphasise the need for scientifically sound research in this field.

Surgery for psychiatric disorders has a controversial history. Traditionally, procedures were undertaken to physically disconnect or destroy certain areas of the brain thought to constitute critical components of the limbic pathways. The relatively recent advent of the much safer and non-destructive technique known as deep brain stimulation has coincided with a resurgence in interest in psychosurgery. Contemporary approaches to the surgical management of obsessive-compulsive disorder are discussed, together with our current understanding of its pathophysiology.

We report a 61-year-old hypertensive man who underwent deep brain stimulation of the periventricular/periaqueductal grey area for the relief of chronic neuropathic pain affecting his oral cavity and soft palate. During intraoperative stimulation, we were able to modulate his blood pressure up or down, depending on electrode location. This is the first evidence that hypertension could be effectively treated with electrical stimulation of the midbrain.

Object. The periventricular gray (PVG) zone and its continuation, the periaqueductal gray (PAG) substance, have been targets for deep brain stimulation (DBS) in the alleviation of intractable pain for longer than two decades. Nevertheless, the anatomical connectivity of this region has been fairly poorly defined. The effects of DBS in this region are probably related to the release of endogenous endorphins, but until the connectivity of this region is better understood the mechanisms will remain unclear. Methods. Diffusion tractography was used to trace the pathways of the PVG—PAG region in seven healthy human volunteers. Images were acquired with the aid of a 1.5-tesla magnetic resonance imaging system. The region of interest was located just lateral to the posterior commissure and extended caudally to the level of the superior colliculus. Probabilistic diffusion tractography was performed from each voxel in each patient's PVG—PAG region. The PVG—PAG region was found to yield descending projections to the spinal cord and cerebellum. Ascending projections to the thalamus and frontal lobes were also observed. Conclusions. These findings suggest that the PVG—PAG region may modulate pain by two mechanisms: one involving the antinociceptive system in the spinal cord and the other involving influences on the central pain network.

Deep brain stimulation (DBS) has been used to treat intractable pain for over 50 years. Variations in targets and surgical technique complicate the interpretation of many studies. To better understand its efficacy, we performed a meta-analysis of DBS for pain relief. MEDLINE (1966 to February 2003) and EMBASE (1980 to January 2003) databases were searched using key words deep brain stimulation, sensory thalamus, periventricular gray and pain. Inclusion criteria were based on patient characteristics and protocol clarity. Six studies (between 1977-1997) fitting the criteria were identified. Stimulation sites included the periventricular/periaqueductal grey matter (PVG/PAG), internal capsule (IC), and sensory thalamus (ST). The long-term pain alleviation rate was highest with DBS of the PVG/PAG (79%), or the PVG/PAG plus sensory thalamus/internal capsule (87%). Stimulation of the sensory thalamus alone was less effective (58% long-term success) (p < 0.05). DBS was more effective for nociceptive than deafferentation pain (63% vs 47% long-term success; p < 0.01). Long-term success was attained in over 80% of patients with intractable low back pain (failed back surgery) following successful trial stimulation. Trial stimulation was successful in approximately 50% of those with post-stroke pain, and 58% of patients permanently implanted achieved ongoing pain relief. Higher rates of success were seen with phantom limb pain and neuropathies. We conclude that DBS is frequently effective when used in well-selected patients. Neuroimaging and neuromodulation technology advances complicate the application of these results to modern practice. Ongoing investigations should shed further light on this complex clinical conundrum.

Deep brain stimulation (DBS) is an expanding field within neurosurgery. With many neurosurgeons performing relatively small numbers of these procedures, detailed descriptions of the technical aspects and nuances of DBS may be worthwhile. We describe our technique for DBS, based on over 300 procedures. This methodology continues to evolve and is refined according to our own experience, our observations of others, technological innovations, and information derived from the neurosurgical literature. The indications for DBS in our service are outlined, the anatomical targets described, and the anaesthetic and surgical aspects detailed.

Phantom limb pain is an often severe and debilitating phenomenon that has been reported in up to 85% of amputees. Its pathophysiology is poorly understood. Peripheral and spinal mechanisms are thought to play a role in pain modulation in affected individuals; however central mechanisms are also likely to be of importance. The neuromatrix theory postulates a genetically determined representation of body image, which is modified by sensory input to create a neurosignature. Persistence of the neurosignature may be responsible for painless phantom limb sensations, whereas phantom limb pain may be due to abnormal reorganisation within the neuromatrix. This study assessed the clinical outcome of deep brain stimulation of the periventricular grey matter and somatosensory thalamus for the relief of chronic neuropathic pain associated with phantom limb in three patients. These patients were assessed preoperatively and at 3 month intervals postoperatively. Self-rated visual analogue scale pain scores assessed pain intensity, and the McGill Pain Questionnaire assessed the quality of the pain. Quality of life was assessed using the EUROQOL EQ-5D scale. Periventricular gray stimulation alone was optimal in two patients, whilst a combination of periventricular gray and thalamic stimulation produced the greatest degree of relief in one patient. At follow-up (mean 13.3 months) the intensity of pain was reduced by 62% (range 55-70%). In all three patients, the burning component of the pain was completely alleviated. Opiate intake was reduced in the two patients requiring morphine sulphate pre-operatively. Quality of life measures indicated a statistically significant improvement. This data supports the role for deep brain stimulation in patients with phantom limb pain. The medical literature relating to the epidemiology, pathogenesis, and treatment of this clinical entity is reviewed in detail.

The field of movement disorder surgery is expanding rapidly. This has been accompanied by improvements in neuromodulation technology and neuroimaging, in addition to a realisation that the medical and destructive neurosurgical methods previously employed do not provide an acceptable long-term benefit for many of these patients. The contemporary treatment of Parkinson's disease, dystonia, and other tremulous disorders using deep brain chronic electrical stimulation will be reviewed, and future directions discussed.

Malignant mesothelioma is an uncommon tumour with an inevitably poor outcome. Statistics from the US National Cancer Institute reveal a steady rise in its incidence over the past 25 years. 1 It typically arises from the pleura, but can also originate in the peritoneum, pericardium, genital tracts and tunica vaginalis. 2 Previously considered a local disease with low incidence of metastasis, there is increasing evidence suggesting otherwise. Reported cases of cerebral metastasis are rare and the vast majority are postmortem findings. This report documents a patient with symptomatic cerebral metastasis from malignant mesothelioma, who underwent craniotomy and excision of two cerebral lesions. It is one of a handful of case reports in the literature in which histological confirmation has been obtained ante-mortem and where surgical treatment of the intracranial mesothelioma was undertaken.

Structural defects involving eloquent regions of the cerebral cortex may be accompanied by abnormal localisation of function. Using functional magnetic resonance imaging (fMRI), we studied the organisation of the visual cortex in a patient with callosal agenesis and colpocephaly, whose visual acuity and binocular visual fields were normal. The stimulus used was a moving grating confined to one hemifield, on a background of moving dots. In addition to activation patterns elicited by stimulation of each hemifield in the patient, the activation pattern was compared to that seen in six normal volunteers. fMRI demonstrated large scale reorganisation of visual cortical areas in the left hemisphere, and fewer activation foci were observed in both occipital lobes when compared with normal subjects.

Object. Accurate identification of eloquent cortex is important to ensure that resective surgery in the region surrounding the central sulcus is performed with minimum risk of permanent neurological deficit. Functional localization has traditionally been accomplished using intraoperative cortical stimulation (ICS). However, this technique suffers from several disadvantages that make the development and validation of noninvasive methods desirable. Functional localization accomplished by activation studies in which positron emission tomography (PET) scanning and the tracer [15O]H2O have been used has been shown to correlate well with the results of ICS. Another noninvasive method for functional localization is functional magnetic resonance (fMR) imaging. We compared the locations of activation peaks obtained in individual patients using fMR and [15O]H2O PET imaging.Methods. Twenty-six combined PET activation—fMR imaging studies were performed in 11 patients who were admitted for evaluation before undergoing surgery in the region surrounding the central sulcus. The PET scans were obtained using bolus injections of the cerebral blood flow tracer [15O]H2O (10 mCi). Multislice T2*-weighted gradient-echo echoplanar images were acquired using a 1.5-tesla MR imaging system. Activation maps were aligned with anatomical MR images and transformed into stereotactic space, after which the locations of activation peaks obtained using both modalities were compared. The average distance between activation peaks obtained using fMR imaging and those obtained using PET imaging was 7.9 ± 4.8 mm (p > 0.05), with 96% of the peaks being located on either the same or adjacent sulci and gyri. Overlapping of voxels activated by each modality occurred in 92% of the studies. Functional MR imaging failed to activate the primary sensorimotor cortex in one study and produced results that were ambiguous in the clinical setting in three cases.Conclusions. Overall, fMR imaging produced activation that correlated well with that obtained using PET scanning. Discrepancies between the sites of activation identified using these two techniques may reflect differences in their physiological bases.

We used functional magnetic resonance imaging (fMRI) to investigate the neural substrates mediating residual vision in the ‘‘blind’’ hemifield of hemispherectomized patients. The visual stimuli were semicircular gratings moving in opposite directions on a dynamic random-dot background. They were specifically constructed to eliminate intra- and extraocular light scatter and optimize the activation of extrastriate cortical areas and their subcortical relays. Multislice T2*weighted gradient echo (GE) echoplanar imaging (EPI) images (TR/TE 5 4 s/45 ms, flip angle 90°) were acquired during activation and baseline visual stimulation. An activation minus baseline subtraction was performed, and the acquired t statistic map transformed into the stereotaxic coordinate space of Talairach and Tournoux. In seven normal control subjects, right hemifield stimulation produced significant activation foci in contralateral V1/V2, V3/V3A, VP, and V5 (MT). Significant activation was also produced in homologous regions of the right occipital lobe with left hemifield stimulation. Stimulation of the intact hemifield in hemispherectomized patients resulted in activation of similar areas exclusively within the contralateral hemisphere. Stimulation of the anopic hemifield produced statistically significant activation in the ipsilateral occipital lobe (putative area V5 or MT) and areas V3/V3A in the only subject with blindsight. We conclude that the remaining hemisphere may contribute to residual visual functions in the blind hemifield of hemispherectomized patients, possibly through the collicular‐pulvinar route since the activated areas are known to receive their afferents from these subcortical nuclei. r 1999 Academic Press

Object. To investigate the utility of [15O]H2O positron emission tomography (PET) activation studies in the presurgical mapping of primary somatosensory cortex, the authors compared the magnitude and location of activation foci obtained using PET scanning with the results of intraoperative cortical stimulation (ICS).Methods. The authors used PET scanning and vibrotactile stimulation (of the face, hand, or foot) to localize the primary somatosensory cortex before surgical resection of mass lesions or epileptogenic foci affecting the central area in 20 patients. With the aid of image-guided surgical systems, the locations of significant activation foci on PET scanning were compared with those of positive ICS performed at craniotomy after the patient had received a local anesthetic agent. In addition, the relationship between the magnitude and statistical significance of blood flow changes and the presence of positive ICS was examined.In 22 (95.6%) of 23 statistically significant (p < 0.05) PET activation foci, spatially concordant sites on ICS were also observed. Intraoperative cortical stimulation was positive in 40% of the PET activation studies that did not result in statistically significant activation. In the patients showing these results, there was a clearly identifiable t-statistic peak that was spatially concordant with the site of positive ICS in the sensorimotor area. All PET activation foci with a t statistic greater than 4.75 were associated with spatially concordant sites of positive ICS. All PET activation foci with a t statistic less than 3.2 were associated with negative ICS.Conclusions. Positron emission tomography is an accurate method for mapping the primary somatosensory cortex before surgery. The need for ICS, which requires local anesthesia, may be eliminated when PET foci with high (> 4.75) or low (< 3.20) t-statistic peaks are elicited by vibrotactile stimulation.

McClelland et al. have produced a methodical, albeit small and retrospective, study that suggests a degree of clinical tolerance compensating for variations in lead location within the subthalamic nucleus (STN). They did not analyse electrode position in relation to the STN itself, but rather in relation to its intended position. Their series of operations was performed at least 8 years to 9 years ago, and significant improvements in the quality of imaging of the STN have occurred since. The technique of indirect targeting, as was used in the study by McClelland et al., is now less commonly used. A recognition of individual variation in anatomy, together with vastly improved anatomical delineation of the STN with modern MRI, have resulted in most centres adopting direct targeting (with or without intraoperative neurophysiology). 1 Rather than the position of the STN being inferred, it is seen relatively clearly on preoperative MRI scanning. A further limitation of this study is the lack of discussion of whether intraoperative macrostimulation was used to determine clinical efficacy and to guide final electrode placement. It appears to have been used only to determine side effects. In addition, two different electrode types were used in this study, introducing a potential confounder. If the goal of surgery is to ameliorate Parkinsonian symptoms, it would make sense that intraoperative stimulation should be used to determine not only the likely side effects, but also the potential benefits. In other words, intraoperative stimulation may provide valuable information with respect to a ‘‘therapeutic window”. This study does support the notion that indirect targeting, combined with microelectrode recording and limited macrostimulation, can produce consistent results in terms of motor benefits. Importantly, it did not examine whether variations in electrode placement had a significant impact on neuropsychological outcomes, an area of increasing concern in this burgeoning field.