A Wireless Neuroprosthesis for Patients with Drug-refractory Epilepsy:A Proof-of-Concept Study

Objective Acute or protracted cortical recording may be necessary for patients with drug-refractory epilepsy to identify the ictogenic regions before undergoing resection. Currently, these invasive recording techniques present certain limitations, one of which is the need for cables connecting the recording electrodes placed in the intracranial space with external devices displaying the recorded electrocorticographic signals. This equates to a direct connection between the sterile intracranial space with the non-sterile environment. Due to the increasing likelihood of infections with time, subdural grids are typically removed a few days after implantation, a limiting factor in localizing the epileptogenic zone if seizures are not frequent enough to be captured within this time-frame. Furthermore, patients are bound to stay in the hospital, connected by the wires to the recording device, thus increasing substantially the treatment costs. To address some of the current shortcomings of invasive monitoring, we developed a neuroprosthesis made of a subdural silicone grid connected to a wireless transmitter allowing prolonged electrocorticografic recording and direct cortical stimulation. This device consists of a silicone grid with 128-platinum/iridium contacts, connected to an implantable case providing wireless recording and stimulation. The case also houses a wirelessly rechargeable battery for chronic long-term implants. We report the results of the first human proof-of-concept trial for wireless transmission of electrocorticographic recordings using a device suited for long-term implantation in three patients with drug-refractory epilepsy. Methods Three patients with medically refractory epilepsy underwent the temporary intraoperative placement of the subdural grid connected to the wireless device for recording and transmission of electrocorticographic signals for a duration of five minutes before the conventional recording electrodes were placed or the ictal foci were resected. Results Wireless transmission of brain signals was successfully achieved. The wireless electrocorticographic signal was judged of excellent quality by a blinded neurophysiologist. Conclusions This preliminary experience reports the first successful placement of a wireless electrocorticographic recording device in humans. Long-term placement for prolonged wireless electrocorticographic recording in epilepsy patients will be the next step

Cyberknife Radiosurgery for Trigeminal Neuralgia

IntroductionImage-guided robotic radiosurgery is an emerging minimally-invasive treatment option for trigeminal neuralgia (TN). Our group has treated 560 cases up to date, and report here the clinical outcomes of 387 treatments with three years follow-up. This study represents the largest single-center experience on CyberKnife radiosurgery for the treatment of TN so far reported.MethodsCyberKnife radiosurgery treatment was offered to patients with drug-resistant TN, after the failure of other treatments or refusal of invasive procedures. A second treatment was offered to patients with a poor response after the first treatment or with recurrent pain. Treatment protocol required the non-isocentric delivery of 60 Gy prescribed to the 80% isodose to a 6 mm retrogasserian segment of the affected trigeminal nerve. Retreatments typically received 45 Gy, again prescribed to the 80% isodose. The final plan was developed accordingly to individual anatomy and dose distribution over the trigeminal nerve, gasserian ganglion, and brainstem. Clinical outcomes such as pain control and hypoesthesia/numbness have been evaluated after 6, 12, 24, and 36 months.ResultsOur group has treated 527 patients with Cyberknife radiosurgery at Centro Diagnostico Italiano (CDI), Milan, Italy, during the last decade. A minimum follow-up of six months was available on 496 patients. These patients received 560 treatments: 435 patients (87.7%) had a single treatment, 60 patients (12.1%) had two treatments, and one patient (0.2%) had five treatments (two on the right side, three on the left side). Twenty four patients had multiple sclerosis (4.8%). Four hundred and forty-three patients (84%) received the treatment without previous procedures, while 84 patients (16%) underwent radiosurgery after the failure of other treatments. A neurovascular conflict was identified in 59% of the patients. Three hundred and forty-three patients (receiving a total of 387 treatments) had a minimum of 36 months follow up. Pain relief rate at 6, 12, 18, 24, 30 and 36 months was respectively 92, 87, 87, 82, 78 and 76%. Forty-four patients out of 343 (12.8%) required a second treatment during the observed period. At 36 months post-treatment, 21 patients (6,1%) reported the presence of bothering facial hypoesthesia. Eighteen patients out of 21 (85.7%) developed this complication after a repeated treatment.ConclusionsFrameless image-guided robotic radiosurgery in experienced hands is a safe and effective procedure for the treatment of TN, providing excellent pain control rates in the absence of major neurological complications. Repeated treatments due to recurrent pain are associated with restored pain control but at the price of a higher rate of sensory complications

Synchrotron-generated microbeams induce hippocampal transections in rats

Synchrotron-generated microplanar beams (microbeams) provide the most stereo-selective irradiation modality known today. This novel irradiation modality has been shown to control seizures originating from eloquent cortex causing no neurological deficit in experimental animals. To test the hypothesis that application of microbeams in the hippocampus, the most common source of refractory seizures, is safe and does not induce severe side effects, we used microbeams to induce transections to the hippocampus of healthy rats. An array of parallel microbeams carrying an incident dose of 600 Gy was delivered to the rat hippocampus. Immunohistochemistry of phosphorylated gamma-H2AX showed cell death along the microbeam irradiation paths in rats 48 hours after irradiation. No evident behavioral or neurological deficits were observed during the 3-month period of observation. MR imaging showed no signs of radio-induced edema or radionecrosis 3 months after irradiation. Histological analysis showed a very well preserved hippocampal cytoarchitecture and confirmed the presence of clear-cut microscopic transections across the hippocampus. These data support the use of synchrotron-generated microbeams as a novel tool to slice the hippocampus of living rats in a minimally invasive way, providing (i) a novel experimental model to study hippocampal function and (ii) a new treatment tool for patients affected by refractory epilepsy induced by mesial temporal sclerosis

A telerehabilitation platform for cognitive, physical and behavioural rehabilitation in elderly patients affected by dementia

Dementia is one of the main causes of disability in elderly people and its treatment becomes, year after year, an increasingly compelling priority for the public health system. In the last years, home assistance and telemedicine have paved the way to decrease the treatments’ costs and to improve the patients and caregivers quality of life quality. In this framework, the aim of ABILITY project is to design, develop and validate an integrated platform of services aimed at supporting and enhancing the rehabilitation process for patients with dementia at their homes. ABILITY platform allows the clinician to assign rehabilitation plans with a strong compliance monitoring, enabled by the technological solutions integrated, and the holistic approach to rehabilitation, as the plan includes physical, cognitive and behavioral therapies/exercises. The ABILITY platform will be assessed through a set of validation activities, involving a small group of pilot patients, and a Randomized Control Trial. In conclusion, the ABILITY project generates a series of assistive services inside a modular and flexible platform, adaptable to the single patient and his/her needs, increasing the treatment efficiency and efficacy with respect to the state of the art

Advanced neuroimaging techniques in the management of glioblastoma multiforme.

Despite the extensive research efforts over the past century, glioblastoma multiforme (GBM) remains an ominous diagnosis leading fast to progressive disability and death despite the aggressive treatment including microsurgical resection, chemotherapy, radiotherapy and stereotactic radiosurgery. Advanced neuroimaging techniques, such as volumetric acquisitions, spectroscopy, diffusion and perfusion studies added to conventional imaging, provide in selected cases a non-invasive alternative to pathological diagnosis but they are also precious tools to define the boundaries of image-guided microsurgical resection and/or radiosurgical ablation. This paper reviews the role of advanced neuroimaging techniques in the diagnosis and treatment of GBM

Image-Guided Stereotactic Radiosurgery for Optic Nerve Sheath Meningiomas

Optic nerve sheath meningiomas (ONSMs) are benign lesions primarily originating from the dural sheath of the optic nerve. Their progressive growth can lead to gradual loss of vision and exophthalmos. Treatment of these lesions is problematic and depends on the degree of visual impairment and proptosis. In patients with preserved vision and no proptosis, conservative management with frequent ophthalmologic and radiological follow-up is usually preferred. When vision begins to fail surgical intervention can be attempted, but it is often of limited success as far as preserving vision is concerned. Radiotherapy has gained an increasing role in the management of these lesions. Conventional radiotherapy has been used both pre-operatively and post-operatively for many years. More recently fractionated stereotactic radiotherapy has been employed as an alternative to surgery, and may be superior in terms of vision preservation. Care must be however exercised due to the proximity of other important radiosensitive structures. Highly conformal treatments modality, such as those provided by radiosurgery, may overcome this issue. Frame-based stereotactic radiosurgery has been rarely used because single-fraction high-dose irradiation of the optic nerve may be associated with loss of vision. New frameless radiosurgery devices, such as the robotic CyberKnife, an image-guided radiosurgery system, can provide the extremely tight conformality and submillimetric accuracy of frame-based systems combined with the possibility of delivering radiation in multiple sessions. Here, the authors review the clinical presentation and management of ONSMs, highlighting the emerging use of hypofractionated radiosurgery to treat these challenging lesions

Image-Guided Stereotactic Radiosurgery for Spinal PathologyTumors of the Central Nervous System, Volume 12

none2noRadiosurgery is the delivery, in a single or a few fractions, of a concentrated dose of radiation to diseased tissue with a steep dose fall-off outside the treatment volume. Traditionally, radiosurgery is delivered to intracranial targets using a rigid frame to immobilize the target and provide external reference points for target localization. The development of image-guided radiosurgery has allowed the principles of radiosurgery to be applied to the treatment of extracranial pathologies including spinal lesions. Image guidance is the use of imaging to locate the tumor before and during a treatment session and redirect the radiation source or reposition the patient based on these measurements. In this manner dose delivery accuracy comparable to frame-based radiosurgery can be achieved. Furthermore, frameless stereotactic radiosurgery allows treatments to be delivered in more than one fraction, which has the potential to reduce toxicity to healthy tissue and organs at risk such as the spinal cord, an organ that is among the most sensitive to radiation. Spinal radiosurgery has resulted in excellent rates of tumor control with a relatively low risk of radiation-induced myelopathy. Here we review currently available image-guided stereotactic radiosurgery devices that can be used to treat the spine, summarize clinical data showing the efficacy of these systems, and discuss dose and volume limits to avoid radiation toxicity induced by spinal radiosurgery for malignant and benign pathologies.nonePantaleo Romanelli; Alfredo ContiPantaleo Romanelli; Alfredo Cont

Trigeminal Neuralgia

Trigeminal Neuralgia (TN) is the most common cranio-facial pain syndrome, with an incidence of up to 5 in 100,000. Long-term medical treatment is commonly required, with up to 10% of cases suffering adverse drug-related events. In 1951, Lars Leksell pioneered the application of stereotactic irradiation for the treatment of TN, which may now achieve up to 90% pain control at 1 year and 60% at 2 years. Pain control can remain excellent in 26% of treated patients at 10 years. Radiosurgical treatment targets either the nerve\u2019s emergence (the root entry zone) or the retrogasserian portion of the nerve. Use of the former has a greater likelihood for long-term pain control, but may lead to higher doses to the brainstem. Targeting the latter may reduce the risk of complications, but requires a higher maximum dose to obtain optimal results. Generally speaking, radiosurgical treatment achieves better results in patients receiving high doses of radiations ranging from 70 to 90 Gy. It is also recommended that the length of nerve treated is between 4 and 6 mm. Hypoesthesia and facial numbness are frequently observed after high-dose trigeminal irradiation. Mild hypoesthesia is acceptable and is considered by many an efficacy endpoint of the procedure. Bothersome facial numbness is relatively rare. Sensitive trigeminal disturbances and paresthesia after treatment have been reported to range 6%\u201354% and 0%\u201317%, respectively. The prescribed dose and brainstem-delivered dose are correlated with the subsequent rate of sensitive trigeminal disturbances. CyberKnife frameless non-isocentric radiosurgery is an emerging and thoroughly non-invasive treatment for TN that can potentially deliver homogeneous irradiation to an extended length of the trigeminal nerve. This feature makes CyberKnife radiosurgery essentially different from isocenter-based Gamma Knife treatment. By contrast, targeting an extended segment of the trigeminal nerve with Gamma Knife requires placement of a second isocenter and generates hot and cold spots along the nerve. Thus, CyberKnife can administer variable doses to discreet lengths of nerve in order to improve pain control and reduce complication rates. Currently, clinical results reported in the literature are comparable to those offered by the Gamma Knife

Somatotopy in the basal ganglia: experimental and clinical evidence for segregated sensorimotor channels

Growing experimental and clinical evidence supports the notion that the cortico-basal ganglia-thalamo-cortical loops proceed along parallel circuits linking cortical and subcortical regions subserving the processing of sensorimotor, associative and affective tasks. In particular, there is evidence that a strict topographic segregation is maintained during the processing of sensorimotor information flowing from cortical motor areas to the sensorimotor areas of the basal ganglia. The output from the basal ganglia to the motor thalamus, which projects back to neocortical motor areas, is also organized into topographically segregated channels. This high degree of topographic segregation is demonstrated by the presence of a well-defined somatotopic organization in the sensorimotor areas of the basal ganglia. The presence of body maps in the basal ganglia has become clinically relevant with the increasing use of surgical procedures, such as lesioning or deep brain stimulation, which are selectively aimed at restricted subcortical targets in the sensorimotor loop such as the subthalamic nucleus (STN) or the globus pallidus pars interna (GPi). The ability to ameliorate the motor control dysfunction without producing side effects related to interference with non-motor circuits subserving associative or affective processing requires the ability to target subcortical areas particularly involved in sensorimotor processing (currently achieved only by careful intraoperative microelectrode mapping). The goal of this article is to review current knowledge about the somatotopic segregation of basal ganglia sensorimotor areas and outline in detail what is known about their body maps. (C) 2004 Published by Elsevier B.V

Radiosurgery for movement disorders

Stereotactic radiosurgery (SRS) has been proposed as an alternative treatment modality to pharmaceutical administration and deep brain stimulation (DBS) for patients suffering from movement disorders. Advanced neuroimaging is required for the identification of the functional structures and the accurate placement of the SRS lesion within the brain. Atlas-based techniques have also been used to aid delineation of the target during treatment planning. Maximum doses greater than 120 Gy have been suggested for controlling movement disorders. These high delivered doses and the irreversible character of SRS require accurate placement of the created lesions. In this article, achievements in the field of stereotactic radiosurgery, neuroimaging, and radiosurgical dose planning are reviewed, and an overview is provided of the clinical experience obtained to date in the radiosurgical treatment of movement disorders.</