Mesial temporal resection following long-term ambulatory intracranial EEG monitoring with a direct brain-responsive neurostimulation system.

OBJECTIVE: To describe seizure outcomes in patients with medically refractory epilepsy who had evidence of bilateral mesial temporal lobe (MTL) seizure onsets and underwent MTL resection based on chronic ambulatory intracranial EEG (ICEEG) data from a direct brain-responsive neurostimulator (RNS) system. METHODS: We retrospectively identified all patients at 17 epilepsy centers with MTL epilepsy who were treated with the RNS System using bilateral MTL leads, and in whom an MTL resection was subsequently performed. Presumed lateralization based on routine presurgical approaches was compared to lateralization determined by RNS System chronic ambulatory ICEEG recordings. The primary outcome was frequency of disabling seizures at last 3-month follow-up after MTL resection compared to seizure frequency 3 months before MTL resection. RESULTS: We identified 157 patients treated with the RNS System with bilateral MTL leads due to presumed bitemporal epilepsy. Twenty-five patients (16%) subsequently had an MTL resection informed by chronic ambulatory ICEEG (mean = 42 months ICEEG); follow-up was available for 24 patients. After MTL resection, the median reduction in disabling seizures at last follow-up was 100% (mean: 94%; range: 50%-100%). Nine patients (38%) had exclusively unilateral electrographic seizures recorded by chronic ambulatory ICEEG and all were seizure-free at last follow-up after MTL resection; eight of nine continued RNS System treatment. Fifteen patients (62%) had bilateral MTL electrographic seizures, had an MTL resection on the more active side, continued RNS System treatment, and achieved a median clinical seizure reduction of 100% (mean: 90%; range: 50%-100%) at last follow-up, with eight of fifteen seizure-free. For those with more than 1 year of follow-up (N = 21), 15 patients (71%) were seizure-free during the most recent year, including all eight patients with unilateral onsets and 7 of 13 patients (54%) with bilateral onsets. SIGNIFICANCE: Chronic ambulatory ICEEG data provide information about lateralization of MTL seizures and can identify additional patients who may benefit from MTL resection.

Susceptibility-Weighted MRI Approximates Intraoperative Microelectrode Recording During Deep Brain Stimulation of the Subthalamic Nucleus for Parkinson's Disease.

BACKGROUND: Deep brain stimulation of the subthalamic nucleus (STN-DBS) for Parkinson's disease can be performed with intraoperative neurophysiological and radiographic guidance. Conventional T2-weighted magnetic resonance imaging sequences, however, often fail to provide definitive borders of the STN. Novel magnetic resonance imaging sequences, such as susceptibility-weighted imaging (SWI), might better localize the STN borders and facilitate radiographic targeting. We compared the radiographic location of the dorsal and ventral borders of the STN using SWI with intraoperative microelectrode recording (MER) during awake STN-DBS for Parkinson's disease. METHODS: Thirteen consecutive patients who underwent placement of 24 STN-DBS leads for Parkinson's disease were analyzed retrospectively. Preoperative targeting was performed with SWI, and MER data were obtained from intraoperative electrophysiology records. The boundaries of the STN on SWI were identified by a blinded investigator. RESULTS: The final electrode position differed significantly from the planned coordinates in depth but not in length or width, indicating that MER guided the final electrode depth. When we compared the boundaries of the STN by MER and SWI, SWI accurately predicted the entry into the STN but underestimated the length and ventral boundary of the STN by 1.2 mm. This extent of error approximates the span of a DBS contact and could affect the placement of directional contacts within the STN. CONCLUSIONS: MER might continue to have a role in STN-DBS. This could potentially be mitigated by further refinement of imaging protocols to better image the ventral boundary of the STN.

Globus Pallidus Interna and Ventral Intermediate Nucleus of the Thalamus Deep Brain Stimulation for Adductor Laryngeal Dystonia: a Case Report of Blinded Analyses of Objective Voice Outcomes in 2 Patients.

BACKGROUND: Adductor laryngeal dystonia (ADLD) is a substantially debilitating focal progressive neurological voice disorder. Current standard of care is symptomatic treatment with repeated injections of botulinum toxin into specific intrinsic laryngeal muscles with extremely variable and temporary benefits. We report the use of bilateral deep brain stimulation (DBS) of globus pallidus (GPi) for long-term improvement of ADLD voice symptoms. OBJECTIVE: To investigate the effects of bilateral DBS of the GPi and ventral intermediate nucleus (VIM) of the thalamus on vocal function in 2 patients with ADLD associated with voice and hand tremor. METHODS: Blinded objective and quantitative analyses of voice were conducted before and after treatment in 2 female patients (70 and 69 years). Paired t-tests were conducted to compare voice measurements pre-GPi and post-GPi and VIM-DBS. A 2-way analysis of variance was conducted to determine the interaction between target (GPi/VIM) and time (pre/post) for each voice measure. RESULTS: Although the follow-up period differed between patients, the GPi-DBS implanted patient had notable improvement in vowel voicing (%), extent of tremor intensity (%), and overall speech intelligibility (%), compared with preoperative status. GPi-DBS also resulted in significant improvement in cepstral peak prominence (dB). VIM-DBS resulted in a significantly greater change in the tremor rate (Hz). CONCLUSION: Changes in phonatory function provide preliminary support for the use of bilateral GPi-DBS for treatment of ADLD and bilateral VIM-DBS for vocal tremor predominant ADLD. Future studies with larger sample sizes and standardized follow-up periods are needed to better assess the role of DBS for ADLD.

A multicenter, prospective pilot study of gamma knife radiosurgery for mesial temporal lobe epilepsy: seizure response, adverse events, and verbal memory.

OBJECTIVE: The safety, efficacy, and morbidity of radiosurgery (RS) must be established before it can be offered as an alternative to open surgery for unilateral mesial temporal lobe epilepsy. We report the 3-year outcomes of a multicenter, prospective pilot study of RS. METHODS: RS was randomized to 20 or 24Gy targeting the amygdala, hippocampus, and parahippocampal gyrus. Seizure diaries evaluated the final seizure remission between months 24 and 36. Verbal memory was evaluated at baseline and 24m with the Wechsler Memory Scale-Revised (WMS-R) and California Verbal Learning Test (CVLT). Patients were classified as having "significant improvement," "no change," and "significant impairment" based on relative change indices. RESULTS: Thirteen high-dose and 17 low-dose patients were treated. Both groups showed significant reductions in seizures by 1 year after treatment. At the 36-month follow-up evaluation, 67% of patients were free of seizures for the prior 12 months (high dose: 10/13, 76.9%; low dose: 10/17, 58.8%). Use of steroids, headaches, and visual field defects did not differ by dose or seizure remission. The prevalence of verbal memory impairment was 15% (4/26 patients); none declined on more than one measure. The prevalence of significant verbal memory improvements was 12% (3/26). INTERPRETATION: RS for unilateral mesial temporal lobe epilepsy offers seizure remission rates comparable with those reported previously for open surgery. There were no major safety concerns with high-dose RS compared with low-dose RS. Additional research is required to determine whether RS may be a treatment option for some patients with mesial temporal lobe epilepsy.

Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy.

OBJECTIVE: To prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years. METHODS: Adults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory. RESULTS: Of 256 patients treated in the initial trials, 230 participated in the LTT. At 9 years, the median percent reduction in seizure frequency was 75% (p < 0.0001, Wilcoxon signed rank), responder rate was 73%, and 35% had a ≥90% reduction in seizure frequency. We found that 18.4% (47 of 256) experienced ≥1 year of seizure freedom, with 62% (29 of 47) seizure-free at the last follow-up and an average seizure-free period of 3.2 years (range 1.04-9.6 years). Overall QOL and epilepsy-targeted and cognitive domains of QOLIE-89 remained significantly improved (p < 0.05). There were no serious AEs related to stimulation, and the sudden unexplained death in epilepsy (SUDEP) rate was significantly lower than predefined comparators (p < 0.05, 1-tailed χ2). CONCLUSIONS: Adjunctive brain-responsive neurostimulation provides significant and sustained reductions in the frequency of FOS with improved QOL. Stimulation was well tolerated; implantation-related AEs were typical of other neurostimulation devices; and SUDEP rates were low. CLINICALTRIALSGOV IDENTIFIER: NCT00572195. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that brain-responsive neurostimulation significantly reduces focal seizures with acceptable safety over 9 years.

Gamma knife stereotactic radiosurgery for low-grade astrocytomas.

Patients with low-grade astrocytoma (LGA; 8 pilocytic astrocytomas, 2 subependymal giant cell astrocytomas, 2 fibrillary astrocytomas) were selected for treatment with gamma knife stereotactic radiosurgery (GKSRS) based on having a demarcated appearance on CT or MRI and the possibility of dose sparing of adjacent eloquent structures. A median dose of 13 Gy was prescribed to the 50% isodose line, which covered the gross tumor. The median patient age was 17.4 years. The median target volume was 4.4 cm(3). With a median follow-up of 48.2 months, 4-year tumor control and overall survival were 77 and 83%, respectively. Only 2 patients experienced symptomatic treatment-related toxicity. GKSRS can provide local control in cases of unresectable or recurrent LGA with a low incidence of side effects in carefully selected patients.

Endocrine response after gamma knife-based stereotactic radiosurgery for secretory pituitary adenoma.

PURPOSE: To examine treatment outcomes of Gamma Knife-based stereotactic radiosurgery (GK-based SRS) for secretory pituitary adenomas. MATERIALS AND METHODS: 25 patients were treated with GK-based SRS for secretory pituitary adenomas with >or=12 months of follow-up. RESULTS: For prolactinomas, 2 of 4 patients (50%) showed normalization of serum prolactin at a mean time of 18 months. One of 4 had a >or=50% decrease but still abnormal prolactin levels. For adrenocorticotrophic hormone-secreting tumors, 6 of 12 patients (50%) showed normalization of their endocrine levels at a median of 10 months. An additional 2 (17%) had a >or=50% decrease. For growth hormone-secreting tumors, 4 of 9 patients (44%) showed normalization of endocrine levels at a median time of 30 months. Two patients (22%) had >or=50% lower but abnormal endocrine levels. CONCLUSION: GK-based SRS provides a reasonable rate of endocrine normalization of secretory pituitary adenoma. The time to endocrine response is shorter than reported for fractionated external beam radiotherapy. There is a low risk of optic neuropathy.

Successful treatment of a skull base malignant rhabdoid tumor with surgery, chemotherapy and gamma Knife-based stereotactic radiosurgery in a young child.

Most childhood rhabdoid tumors occur in the kidney or central nervous system but they can occur in other sites and they usually run an aggressive clinical course. We report a case of an 8-month-old boy with a right temporal bone rhabdoid tumor treated with surgery, chemotherapy and Gamma Knife-based stereotactic radiosurgery. The patient remained alive after 61 months and repeat magnetic resonance imaging (MRI) of the brain showed no evidence of recurrence. There were no obvious endocrine deficits or growth abnormalities at last follow-up. Gamma Knife-based stereotactic radiosurgery may have a role in the management of very young children with skull base tumors.

Stereotactic radiosurgery and fractionated stereotactic radiotherapy in the treatment of uveal melanoma.

Uveal melanoma is the most common primary intraocular malignant tumor. Radiation therapy has now replaced enucleation as the treatment of choice, with radioactive eye plaques and proton therapy being the two most studied radiotherapy modalities. More recently, stereotactic radiosurgery and fractionated stereotactic radiotherapy have emerged as promising, non-invasive treatments for uveal melanoma. This review summarizes the available literature on these newer treatment modalities.

Stereotactic radiosurgery for pituitary tumors.

Pituitary adenomas frequently pose challenging clinical problems. Stereotactic radiosurgery (SRS) is one treatment option in selected patients. The purpose of this report is to identify the advantages and disadvantages of radiosurgery in cases of pituitary tumors to assess better its role in relation to other treatment. Methods for optimizing outcome are described. The author reviews several recent series to determine rates of growth control, endocrine response, and complications. In general, growth control is excellent, complications are very low, and reduction of excessive hormone secretion is fair. Depending on the clinical situation, SRS may be the treatment of choice in selected patients.

Long-term radiosurgery effects in the treatment of temporal lobe epilepsy.

Epilepsy surgery is an effective treatment for medically resistant temporal lobe epilepsy (TLE). To minimize complication rates and potentially improve neuropsychology outcomes, stereotactic radiosurgery (SRS) has been explored as an alternative. Two pilot trials have demonstrated the effectiveness of SRS for the treatment of medically resistant TLE, with seizure-free outcomes for approximately 65% of patients at last follow-up. Despite encouraging results, no conclusive long-term outcomes are available for SRS. This article discusses a single patient who presented with recurrent seizures, worsening headaches, and persistent abnormal MRI findings 7 years and 8 months after SRS. This 29-year-old woman with a history of medically refractory complex partial seizures since childhood was referred for evaluation. Medical management had failed in this patient. The workup was compatible with left mesial temporal lobe onset, with MRI findings suggestive of mesial temporal sclerosis. In 2003, at the age of 23 years, she underwent Gamma Knife surgery (GKS) targeting the left temporal mesial area with a dose of 24 Gy at the 50% marginal isodose line. After GKS, the patient's seizures decreased in frequency over several months, but auras were persistent. Nine months after treatment, she developed worsening headaches. A follow-up MRI study demonstrated a thick, irregular, enhancing lesion in the medial part of the temporal lobe. She was placed on corticosteroids, with resolution of her headaches. Her seizures and headaches recurred in March 2010. An MRI study showed a 2.2-cm, ill-defined, enhancing cystic lesion in the left mesial temporal lobe with T2 and FLAIR hyperintensity, which was presumably radiation induced. At that time, the patient opted for left temporal lobe resection to control her seizures. Histological examination showed moderately severe, remote, longstanding sclerosis at the level of the hippocampus. A vascular lesion was identified, and it was most consistent with radiation-induced capillary hemangioma. The entorhinal region was severely damaged, with hemorrhage, necrosis, neuronal loss, astrogliosis, and hemosiderin deposition. There was evidence of radiation vasculopathy. Radiation-induced lesions after SRS for the treatment of epilepsy are not well documented. Although GKS is a promising technique for the treatment of medically resistant TLE, the ideal candidate is not yet well defined. The selection of the appropriate technical parameters to obtain a desirable functional effect without histological damage to the surrounding neural tissue remains a challenge. This case illustrates the need for long-term follow-up when radiosurgery is used for epilepsy.

Gamma knife radiosurgery in the treatment of choroidal neovascularization (wet-type macular degeneration).

We evaluated retrospectively our institutional experience in the treatment of macular degeneration with gamma knife radiosurgery (GKR). Treatment was delivered in a single shot of 12 Gy. Seven patients were treated between March of 1999 and May of 2000. The median duration of follow-up was 2.2 years. The majority of patients maintained stable visual acuity after treatment. Our series indicates that GKR may be useful as a salvage treatment for patients who have failed or are ineligible for other treatments for their macular degeneration. Further studies are needed to better define the role of GKR in the treatment of macular degeneration.

Gamma-knife-based stereotactic radiosurgery for uveal melanoma.

Nineteen patients with uveal melanoma were treated with Gamma-Knife-based stereotactic radiosurgery (SRS). The radiation dose was 40 Gy prescribed to the 50% isodose line for all patients. The median follow-up was 40 months. The 3- and 5-year overall survival rates were 86 and 55%, respectively. The 3- and 5-year tumor control rates were both 94%. Six of the 19 treated patients (32%) developed distant metastasis 31-75 months after SRS. Out of the 19 patients treated with SRS, 2 had improved, 4 had stable and 13 had worse vision in the treated eye. Gamma-Knife-based SRS appears to provide excellent local control of uveal melanoma. The risk of distant metastasis is significant. Effective systemic therapy is to be explored to improve the treatment outcome of uveal melanoma.

The role of Gamma Knife Radiosurgery in the management of unresectable gross disease or gross residual disease after surgery in ependymoma.

PURPOSE/OBJECTIVE: To evaluate the efficacy and the toxicity of Gamma Knife (GK)-based stereotactic radiosurgery (SRS) in the management of gross disease in ependymoma. MATERIALS AND METHODS: Eight patients with 13 ependymomas were treated with GK-based SRS in our institution for gross disease. Five patients were treated for recurrent disease that developed after surgery and external beam radiotherapy (EBRT), two received SRS to the gross disease after surgery and EBRT, and one received SRS alone (in a 1.3 year old child). Median EBRT dose was 54.4 Gy (range 50-55.8 Gy). Median SRS dose was 14 Gy (range 12-20 Gy). Seven of eight (87.5%) patients had SRS to a single lesion and one of eight (12.5%) patients had treatment to six tumors in three different sessions. RESULTS: The median follow up was 30.2 months (range 8-65.4 months). Out of the eight patients treated with SRS, six (75%) were alive, four (50%) were alive with no recurrence, two (25%) were alive with recurrence, and two (25%) died of recurrent disease. Both patients treated with SRS as a boost were alive and without recurrence. Out of the five patients who received SRS as salvage treatment, three (60%) were alive, two (40%) were alive without recurrence, two (40%) developed distant failure, and three (60%) had in-field control. Two patients who received SRS to their brainstem lesions developed symptoms related to radionecrosis and were successfully treated with steroid with good control of symptoms. CONCLUSIONS: GK-based SRS appears to be a feasible and safe treatment modality for patients with ependymoma with unresectable gross disease or gross residual disease after surgery. SRS provides reasonable local control but out-of-field tumor progression remains an issue. For patients who receive SRS as a boost, the local control appears to be excellent.