Faculty Bibliography

PURPOSE: Gamma knife radiosurgery (RS) may be an alternative to open surgery for mesial temporal lobe epilepsy (MTLE), but morbidities and the anticonvulsant mechanisms of RS are unclear. Examination of visual field defects (VFDs) after RS may provide evidence of the extent of a postoperative fixed lesion. VFDs occur in 52-100% of patients following open surgery for MTLE. METHODS: This multicenter prospective trial of RS enrolled patients with unilateral hippocampal sclerosis and concordant video-electroencephalography (EEG) findings. Patients were randomized to low (20 Gy) or high (24 Gy) doses delivered to the amygdala, hippocampal head, and parahippocampal gyrus. Postoperative perimetry were obtained at 24 months after RS. Visual field defect ratios (VFDRs) were calculated to quantify the degree of VFDs. Results were contrasted with age, RS dose and 50% isodose volume, peak volume of radiation-induced change at the surgical target, quality of life measurements, and seizure remission. KEY FINDINGS: No patients reported visual changes and no patients had abnormal bedside visual field examinations. Fifteen (62.5%) of 24 patients had postoperative VFDs, all homonymous superior quadrantanopsias. None of the VFDs were consistent with injury to the optic nerve or chiasm. Clinical diagnosis of VFDs correlated significantly with VFDRs (p = 0.0005). Patients with seizure remission had smaller (more severe) VFDRs (p = 0.04). No other variables had significant correlations. SIGNIFICANCE: VFDs appeared after RS in proportions similar to historical comparisons from open surgery for MTLE. The nature of VFDs was consistent with lesions of the optic radiations. The findings support the hypothesis that the mechanism of RS involves some degree of tissue damage and is not confined entirely to functional changes in neuromodulation.

The ability to focus on and understand one talker in a noisy social environment is a critical social-cognitive capacity, whose underlying neuronal mechanisms are unclear. We investigated the manner in which speech streams are represented in brain activity and the way that selective attention governs the brain's representation of speech using a "Cocktail Party" paradigm, coupled with direct recordings from the cortical surface in surgical epilepsy patients. We find that brain activity dynamically tracks speech streams using both low-frequency phase and high-frequency amplitude fluctuations and that optimal encoding likely combines the two. In and near low-level auditory cortices, attention "modulates" the representation by enhancing cortical tracking of attended speech streams, but ignored speech remains represented. In higher-order regions, the representation appears to become more "selective," in that there is no detectable tracking of ignored speech. This selectivity itself seems to sharpen as a sentence unfolds.

An 84-year-old man underwent deep brain stimulation (DBS) for mixed rest-action tremors. One year later, he developed a keratoma where the DBS wire emerged from the insertion cap. It was suspected to be a foreign body reaction and removed by a dermatologist but returned and grew conically over the next 4 years, reaching a height of 4 cm (figure). The surrounding skin began to break down with protrusion of the adjacent extension wire. We recommended removal of the lead but due to continued efficacy and advanced age, he decided to continue with the stimulator in place under observation.

BACKGROUND: Adults with anxiety show biased categorization and avoidance of threats. Such biases may emerge through complex interplay between genetics and environments, occurring early in life. Research on threat biases in children has focuses on a restricted range of biases, with insufficient focus on genetic and environmental origins. Here, we explore differences between children with and without anxiety problems in under-studied areas of threat bias. We focused both on associations with anxious phenotype and the underlying gene-environmental correlates for two specific processes: the categorisation of threat faces and avoidance learning. METHOD: Two-hundred and fifty 10-year old MZ and DZ twin pairs (500 individuals) completed tasks assessing accuracy in the labelling of threatening facial expressions and in the acquisition of avoidant responses to a card associated with a masked threatening face. To assess whether participants met criteria for an anxiety disorder, parents of twins completed a self-guided computerized version of the Development and Well-being Assessment (DAWBA). Comparison of MZ and DZ twin correlations using model-fitting were used to compute estimates of genetic, shared and non-shared environmental effects. RESULTS: Of the 500 twins assessed, 25 (5%) met diagnostic criteria for a current anxiety disorder. Children with anxiety disorders were more accurate in their ability to recognize disgust faces than those without anxiety disorders, but were commensurate on identifying other threatening face emotions (angry, fearful, sad). Children with anxiety disorders but also more strongly avoided selecting a conditioned stimulus than non-anxious children. While recognition of socially threatening faces was moderately heritable, avoidant responses were heavily influenced by the non-shared environment. CONCLUSION: These data add to other findings on threat biases in anxious children. Specifically, we found biases in the labelling of some negative-valence faces and in the acquisition of avoidant responses. While non-shared environmental effects explained all of the variance on threat avoidance, some of this may be due to measurement error.

OBJECT/OBJECTIVE:Idiopathic intracranial hypertension (IIH) may be refractory to available medical and surgical therapies. Patients with this condition may suffer from intractable headaches, experience visual deterioration, or have other symptoms related to elevated intracranial pressure. Internal cranial expansion (ICE) is a novel surgical procedure that the authors have developed for the treatment of patients with this condition. Here, they describe ICE and present their initial experience in using this surgical procedure for the treatment of patients with refractory IIH. METHODS:The authors conducted a retrospective review of 10 consecutive patients who underwent ICE for the treatment of IIH during a 5-year period. Preoperative and postoperative clinical parameters including patient symptoms, presence of papilledema, and available ICP or CSF opening pressures were compared. Procedural details and complications were noted. Intracranial volume increases were calculated using available pre- and postoperative CT scans. RESULTS:Follow-up for the 10 patients in this series ranged from 1 to 39.6 months (mean 15.5 months). Technically successful ICE was performed in all patients within the cohort. Surgical complications included a single postoperative seizure in one patient and a sagittal sinus tear with no clinical sequelae in another patient. At the time of last follow-up, 7 (70%) of 10 patients were either symptomatically improved or asymptomatic. Six (67%) of 9 patients with preoperative headaches had reduction or resolution of this symptom, and all patients (4 of 4) with preoperative papilledema had a reduction in or complete resolution of this sign. Postoperative ICP or CSF opening pressures were normal in all patients (4 of 4) tested. Postoperative intracranial volume expansion ranged between 3.8% and 12%. CONCLUSIONS:Internal cranial expansion is a safe and effective surgery for the treatment of patients with refractory IIH. This surgery expands the intracranial volume and thus promotes ICP normalization, which may lead to the reduction or complete resolution of the signs and symptoms of IIH. Internal cranial expansion may be used as part of a multidisciplinary management approach in the treatment of refractory IIH.

BACKGROUND: The effects of constant-current deep brain stimulation (DBS) have not been studied in controlled trials in patients with Parkinson's disease. We aimed to assess the safety and efficacy of bilateral constant-current DBS of the subthalamic nucleus. METHODS: This prospective, randomised, multicentre controlled trial was done between Sept 26, 2005, and Aug 13, 2010, at 15 clinical sites specialising in movement disorders in the USA. Patients were eligible if they were aged 18-80 years, had Parkinson's disease for 5 years or more, and had either 6 h or more daily off time reported in a patient diary of moderate to severe dyskinesia during waking hours. The patients received bilateral implantation in the subthalamic nucleus of a constant-current DBS device. After implantation, computer-generated randomisation was done with a block size of four, and patients were randomly assigned to the stimulation or control group (stimulation:control ratio 3:1). The control group received implantation without activation for 3 months. No blinding occurred during this study, and both patients and investigators were aware of the treatment group. The primary outcome variable was the change in on time without bothersome dyskinesia (ie, good quality on time) at 3 months as recorded in patients' diaries. Patients were followed up for 1 year. This trial is registered with ClinicalTrials.gov, number NCT00552474. FINDINGS: Of 168 patients assessed for eligibility, 136 had implantation of the constant-current device and were randomly assigned to receive immediate (101 patients) or delayed (35 patients) stimulation. Both study groups reported a mean increase of good quality on time after 3 months, and the increase was greater in the stimulation group (4.27 h vs 1.77 h, difference 2.51 [95% CI 0.87-4.16]; p=0.003). Unified Parkinson's disease rating scale motor scores in the off-medication, on-stimulation condition improved by 39% from baseline (24.8 vs 40.8). Some serious adverse events occurred after DBS implantation, including infections in five (4%) of 136 patients and intracranial haemorrhage in four (3%) patients. Stimulation of the subthalamic nucleus was associated with dysarthria, fatigue, paraesthesias, and oedema, whereas gait problems, disequilibrium, dyskinesia, and falls were reported in both groups. INTERPRETATION: Constant-current DBS of the subthalamic nucleus produced significant improvements in good quality on time when compared with a control group without stimulation. Future trials should compare the effects of constant-current DBS with those of voltage-controlled stimulation. FUNDING: St Jude Medical Neuromodulation Division

The location and trajectory of seizure activity is of great importance, yet our ability to map such activity remains primitive. Recently, the development of multi-electrode arrays for use in humans has provided new levels of temporal and spatial resolution for recording seizures. Here, we show that there is a sharp delineation between areas showing intense, hypersynchronous firing indicative of recruitment to the seizure, and adjacent territories where there is only low-level, unstructured firing. Thus, there is a core territory of recruited neurons and a surrounding 'ictal penumbra'. The defining feature of the 'ictal penumbra' is the contrast between the large amplitude EEG signals and the low-level firing there. Our human recordings bear striking similarities with animal studies of an inhibitory restraint, indicating that they can be readily understood in terms of this mechanism. These findings have important implications for how we localize seizure activity and map its spread.

Neurostimulation in epilepsy has witnessed a century-long evolution that has resulted in the use of neurostimulation to both modulate and suppress abnormal neuronal firing. The recent development of advanced responsive stimulation via a closed-loop device (the RNS System) has provided evidence that surgical epilepsy treatment continues to move toward the possibility of reducing or eliminating seizures in medically refractory patients

The mainstay of epilepsy surgery is the resection of a presumed seizure focus or disruption of seizure propagation pathways. These approaches cannot be applied to all patients with medically refractory epilepsy (MRE). Since 1997, vagus nerve stimulation has been a palliative adjunct to the care of MRE patients. Deep brain stimulation (DBS) in select locations has been reported to reduce seizure frequency in small studies over the past three decades. Recently published results from the SANTE (Stimulation of the Anterior Nuclei of Thalamus for Epilepsy) trial-the first large-scale, randomized, double-blind trial of bilateral anterior thalamus DBS for MRE-demonstrate a significant reduction in seizure frequency with programmed stimulation. Another surgical alternative is the RNS System (NeuroPace, Mountain View, CA), which uses a closed-loop system termed responsive neurostimulation to both detect apparent seizure onsets and deliver stimulation. Recently presented results from the RNS pivotal trial demonstrate a sustained reduction in seizure frequency with stimulation, although comprehensive trial results are pending