Manabu Tamura

Epilepsy related to hypothalamic hamartomas: surgical management with special reference to gamma knife surgery

ObjectiveA large spectrum of surgical techniques can be proposed to young patients presenting with hypothalamic hamartomas (HH) associated with severe epilepsy. The aim of this report is to point on some clinical and anatomical parameters supposed to influence the choice of the surgical approach and to emphasize the specific role of radiosurgery.Materials and methodsWe reviewed both our experience and the recent literature based on a Pubmed search. Lateral pterional, midline frontal through the lamina terminalis, transcallosal interforniceal approaches, endoscopic treatment through the foramen of Monro, disconnecting surgery, radiofrequency ablation, brachytherapy and gamma knife surgery (GKS) were all considered. Mortality, morbidity, and efficacy of each of these techniques were compared. Specific limits, difficulties, and constraints were taken into account. Our experience of radiosurgery is based on a prospective trial which enrolled 60 patients with HH and associated severe epilepsy between October 1999 and December 2005.ResultsSeveral surgical techniques can lead to a real reversal of the epileptic encephalopathy. The main factors for the decision-making process are the age, the size of the lesion and its anatomical type (according to our original classification), the severity of the epilepsy, and the severity of the cognitive/psychiatric comorbidity. In our prospective trial (GKS), 27 patients have a follow-up superior to 3xa0years. Among those, 59.2% have an excellent result with a dramatic behavioral and cognitive improvement and are completely seizure-free (37%) or have only rare non-disabling seizures (22.2%). No permanent neurological complication has been observed so far; three patients have presented a transient poïkilothermia. GKS is clearly the safer approach for these difficult patients. Young patients with severe epilepsy and comorbidity must be operated on using a curative approach as early as possible. Very large type VI or mixed type with a large component above the floor of the third ventricle must be disconnected and then the upper remnant can be ideally treated by GKS (staged surgery). Type V (rarely epileptic) and IV are frequently operable by disconnection. Type I HH deeply embedded in the hypothalamus are operated on by GKS efficiently and safely. Type II HH can be operated on either endoscopically or transcallosally or by GKS depending on the parents’ choice and severity of epilepsy. In small type III HH, GKS is a safer procedure, due to the very close relationship to the fornix and mammillary bodies. In very large type III HH, transcallosal interforniceal approach is proposed but with significant risks especially concerning short-term memory. When the lesion is sufficiently small, GKS is globally offering the patient a rate of seizure cessation comparable to microsurgery with, however, a much lower risk (no neurological deficit reported till now).ConclusionOur first results indicate that GKS is as effective as microsurgical resection and very much safer. GKS also allows avoiding the vascular risk related to radiofrequency lesioning or stimulation. The disadvantage of radiosurgery is its delayed action. Longer follow-up is mandatory for a reliable evaluation of the role of GKS. The early effect on subclinical discharges turns out to play a major role in the dramatic improvement of sleep quality, behavior, and developmental learning acceleration at school.

HEARING PRESERVATION AFTER GAMMA KNIFE RADIOSURGERY FOR VESTIBULAR SCHWANNOMAS PRESENTING WITH HIGH-LEVEL HEARING

OBJECTIVEThe aim of this study was to evaluate long-term hearing preservation after gamma knife radiosurgery (GKS) for vestibular schwannomas in patients with initially normal or subnormal hearing (Gardner-Robertson Class 1) and to determine the predictive factors for functional hearing preservation. METHODSSince July 1992, more than 2053 vestibular schwannomas have been treated by GKS and followed at the Timone University Hospital, Marseille. A minimum of 3 years of follow-up (range, 3–11 years; median, 48 months) is available for 74 patients (without neurofibromatosis Type 2 or previous surgery) with Gardner-Robertson Class 1 hearing. RESULTSThe average age of the patients was 47.5 years (range, 17–76 years). The number of tumors in Koos Stage I was 8, the average number in Stage II was 21, the average number in Stage III was 43, and the average number in Stage IV was 2. The median number of isocenters was 8 (range, 2–45), and the median marginal dose was 12 Gy (range, 9–13 Gy). At the time of the last follow-up evaluation, 78.4% of the patients had preserved functional hearing. Tumor control was achieved in 93% of the cases. The probability of preserving functional hearing was higher in patients who had an initial symptom other than hearing decrease (91.1%), in patients younger than 50 years (83.7%), and in those treated with a dose to the cochlea of less than 4 Gy (90.9%). CONCLUSIONThis study shows that the probability of preserving functional hearing in the long term after GKS for patients presenting with unilateral vestibular schwannomas is very high. The positive predictive factors appear to be young age, an initial symptom other than hearing decrease, and a low dose to the cochlea.

Long-term efficacy of gamma knife radiosurgery in mesial temporal lobe epilepsy

Background: Gamma knife (GK) radiosurgery has been proposed as an alternative to classic microsurgery in mesial temporal lobe epilepsy (MTLE). Short-term follow-up studies have reported encouraging results, but long-term efficacy is not known. Objective: To report the efficacy and tolerance of GK radiosurgery in MTLE after a follow-up > 5 years. Methods: Patients with a follow-up > 5 years presenting with MTLE and treated with a marginal dose of 24 Gy were included in the study. Results: Fifteen patients were included. Eight were treated on the left side, and 7 were treated on the right. The mean follow-up was 8 years (range 6–10 years). At the last follow-up, 9 of 16 patients (60%) were considered seizure free (Engel Class I) (4/16 in Class IA, 5/16 in Class IB). Seizure cessation occurred with a mean delay of 12 months (± 3) after GK radiosurgery, often preceded by a period of increasing aura or seizure occurrence (6/15 patients). The mean delay of appearance of the first neuroradiologic changes was 12 months (± 4). Nine patients (60%) experienced mild headache and were placed on corticosteroid treatment for a short period. All patients who were initially seizure free experienced a relapse of isolated aura (10/15, 66%) or complex partial seizures (10/15, 66%) during antiepileptic drug tapering. Restoration of treatment resulted in good control of seizures. Conclusion: Gamma knife radiosurgery is an effective and safe treatment for mesial temporal lobe epilepsy. Results are maintained over time with no additional side effects. Long-term results compare well with those of conventional surgery.

Radiosurgery with the world's first fully robotized leksell gamma knife perfeXion in clinical use: A 200-patient prospective, randomized, controlled comparison with the gamma knife 4C

OBJECTIVEThe worlds first Leksell Gamma Knife PerfeXion (Elekta Instrument AB, Stockholm, Sweden) for radiosurgery of the head and neck became operational at Timone University Hospital in Marseille on July 10, 2006. To allow strict evaluation of the capabilities, advantages, disadvantages, and limitations of this new technology, patients were enrolled in a prospective, randomized trial. METHODSIn 66 working days, between July 10 and December 20, 2006, 363 patients were treated by gamma knife surgery at Timone University Hospital, Marseille. Of these patients, 200 were eligible for the comparative prospective study (inclusion criteria were informed consent obtained, tumor or vascular indication, and no previous radiosurgery or radiotherapy). In accordance with the blinded randomization process, 100 patients were treated with the Leksell Gamma Knife 4C (Elekta Instrument AB) and Gamma Knife 100 (Elekta Instrument AB) with the Leksell Gamma Knife PerfeXion. Dose planning parameters, dosimetry measurements on the patients body, workflow, patient comfort, quality assurance procedure, and a series of other treatment-related parameters were systematically and prospectively evaluated in both arms of the trial. RESULTSNo technical failure of the treatment procedure was encountered. The new dose-planning system led to the use of composite shots in 39.4% of the patients. The median number of different collimator sizes used was larger with the PerfeXion than with the 4C (2 and 1, respectively). The mean number of isocenters used was lower (10.67 and 13.08, respectively). The median total treatment time was significantly shorter with the PerfeXion (40 and 60 minutes, respectively), but there was no significant difference in the median radiation time (34.02 and 33.40 minutes, respectively). The procedure was performed using only a single run in 98.99% of the PerfeXion cases and in 42% of the 4C cases. Collision risk on the 4C forced us to change the frame gamma angle for at least 1 shot in 24% of the patients and led to treatment in manual mode for at least 1 shot in 21% of the patients. Collision risk requiring technical adaptation did not occur with the PerfeXion. In 1 patient treated with the PerfeXion, the system required a direct collision check. In terms of dose to structures outside the target area, the PerfeXion delivers 8.2 times less to the vertex, 10 times less to the thyroid, 12.9 times less to the sternum, and 15 times less to the gonads. CONCLUSIONOur prospective study indicates that procedures with the PerfeXion were collision-free, even with very eccentric lesions (e.g., multiple metastases). The duration of the surgical procedure, the amount of time required for nurse, physicist, and physician intervention on the machine, and the duration of the quality assurance procedure were all shown to be dramatically reduced with the PerfeXion gamma knife. Patient protection is greatly improved with the PerfeXion. In our experience, the technological advances of the Leksell Gamma Knife PerfeXion will make a very significant contribution to future progress in head and neck radiosurgery.

Influence of nerve radiation dose in the incidence of trigeminal dysfunction after trigeminal neuralgia radiosurgery

OBJECTIVEThe authors conducted a comparative study to analyze dosimetry and results to understand the significant difference in the rate of trigeminal dysfunction after gamma knife radiosurgery for trigeminal neuralgia between two centers using the same target. METHODSThe data of 358 patients (109 patients from Brussels and 259 patients from Marseilles) were analyzed. Three different dosimetric strategies were found: treatment with less than 90 Gy and no selective beam channel blocking (Group 1; patients from Marseilles only), treatment with 90 Gy and no selective beam channel blocking (Group 2; patients from Brussels and Marseilles), or treatment with 90 Gy and use of selective beam channel blocking (Group 3; patients from Brussels only). RESULTSThe prescription dose and the use of selective beam channel blocking have been significantly associated with a higher energy received by the retrogasserian trigeminal nerve root. The different radiation dose delivered to the nerve root in these three groups of patients was significantly associated with the incidence of mild (15, 21, and 49% for Groups 1, 2, and 3, respectively) and bothersome (1.4, 2.4, and 10% for Groups 1, 2, and 3, respectively) trigeminal dysfunction. The good and excellent rates of pain relief were 81 and 66%, respectively, for Group 1, 85 and 77%, respectively, for Group 2, and 90 and 84%, respectively, for Group 3, and were also related to the amount of energy received by nerve root volume. CONCLUSIONUsing a similar target, the incidence of trigeminal dysfunction and the pain relief rate can vary according to the radiation energy received by the retrogasserian part of the trigeminal nerve root. The prescription dose and the use of beam channel blocking modify the integrated dose delivered to the nerve and may contribute to the different rates of trigeminal numbness and pain outcome. The radiobiological effect of gamma knife radiosurgery may be related to the energy delivered to nerve root volume, rather than to the maximal dose delivered.

Gamma knife surgery for facial nerve schwannomas

OBJECTIVERadical resection of facial nerve schwannomas classically implies a high risk of severe facial palsy. Owing to the rarity of facial palsy after gamma knife surgery (GKS) of vestibular schwannomas, functional evaluation after GKS seems rational in this specific group of patients. To our knowledge, no previous similar evaluation exists in the literature. METHODSOf 1783 schwannomas of the cerebellopontine angles treated by GKS at Timone University Hospital between July 1992 and May 2003, 11 were diagnosed as originating from the facial nerve. Criteria for this diagnosis were the involvement of the tympanic or mastoid segment of the facial nerve (n = 9) and/or preoperative observation of a facial nerve deficit that had occurred during previous microsurgery (two patients). The rare occurrence of facial palsy after vestibular schwannoma radiosurgery, usually within 18 months of treatment, has been considered only in the patients with more than 2 years of follow-up (n = 9). RESULTSSix of these patients experienced a previous spontaneous facial palsy on one (n = 4) or several occasions (n = 2). A normal motor facial function was observed in only three patients before GKS (House-Brackmann Grade II in six patients, Grade III in one patient, Grade IV in one patient). The median follow-up period was 39 months (range, 18–84 mo). At the time of the last follow-up examination, no patients had developed a new facial palsy or experienced deterioration of a preexisting facial palsy and three patients had improvement of a preoperative facial palsy. Ten out of the 11 tumors are stable or decreased in size; in the other, a microsurgical resection of the tumor had been recommended owing to the development of a cyst. Clinical management owing to the specificity and heterogeneity of this group of patients has required the development of an original classification of four anatomic subtypes presenting different clinical and surgical difficulties. CONCLUSIONThis first study demonstrates that radiosurgery allows treatment of these patients while preserving normal motor facial function. Such an advantage should lead to the consideration of GKS as a first treatment option for small- to medium-size facial nerve schwannomas.

Hearing preservation in patients with unilateral vestibular schwannoma after gamma knife surgery

INTRODUCTIONnThe majority of patients still lose the functionality of their hearing in spite of the technical advances in microsurgery. Our aim was to evaluate the hearing preservation potential of Gamma Knife Surgery. We have reviewed our experience and the literature in order to evaluate the probability to obtain such functional preservation and the factors influencing it.nnnMETHODSnSince July 1992, 2,053 patients have been operated on by Gamma Knife Radiosurgery in Timone University Hospital. This population included 184 unilateral schwannoma patients with functional preoperative hearing (Gardner-Robertson 1 or 2) treated by first intention radiosurgery with a marginal dose lower than 13 Gy. The population included 74 patients with subnormal hearing (class 1). All have been studied with a follow-up longer than 3 years. Univariate and multivariate analyses have been carried out.nnnRESULTSnNumerous parameters greatly influence the probability of functional hearing preservation at 3 years, which is globally 60%. The main preoperative parameters of predictability are limited hearing loss that is Gardner-Robertson stage 1 (vs. 2), presence of tinnitus, young age of the patient and small size of the lesion. The functional hearing preservation at 3 years is 77.8% when the patient is initially in stage 1, 80% in patients with tinnitus as a first symptom and 95% when the patient has both. In these patients, the probability of functional preservation at 5 years is 84%. Comparison of these results with the main series of the literature confirms the reproducibility of our results. Additionally, we have demonstrated a higher chance of hearing preservation when the dose to the cochlea is lower than 4 Gy.nnnCONCLUSIONnWe report a large population of patients treated by radiosurgery with functional preoperative hearing. These results demonstrate the possibility to preserve functional hearing in a high percentage of selected patients. Radiosurgery offers them a higher chance of functional hearing preservation than microsurgery or simple follow-up.

A quantitative comparison of radiosurgical treatment parameters in vestibular schwannomas: The Leksell Gamma Knife Perfexion versus Model 4C

PurposeThe world’s first Gamma Knife Perfexion (PFX) was installed in Marseille in July 2006. The aim of this study was to investigate the impact of the PFX technology on the quality of dose planning for vestibular schwannomas (VS).MethodsWhen the PFX was first introduced, a comparative randomized prospective study of 200 patients was conducted. Seventy-eight of the 200 patients in that study had VS, of whom 38 were randomized to treatment with the Gamma Knife Model 4C (group 4C) and 40 were randomized to treatment with PFX (group P1). The authors also incorporated a matched group of 40 patients with VS consecutively treated with PFX after the initial learning curve period (group P2). Dose planning was compared and evaluated by measuring the conformity index (CI), selectivity index (SI), gradient index (GI), energy index (EI), unit isocenters (UI) and cochlear dose. Patients were also stratified into subgroups according to target volume (≥0.5xa0ml).ResultsIn the whole population, CI, EI and cochlear dose were significantly better in group P2 (CIu2009=u20090.917, EIu2009=u20091.35, cochlear doseu2009=u20093.55) than in group 4C (CIu2009=u20090.864, EIu2009=u20091.27, cochlear doseu2009=u20095.10). In the subgroup of lesions ≥0.5xa0ml, CI, GI, EI, UI and cochlear dose in group P2 (CIu2009=u20090.929, GIu2009=u20092.67, EIu2009=u20091.37, UIu2009=u200910.6, cochlear doseu2009=u20093.55) were significantly better than in group 4C (CIu2009=u20090.874, GIu2009=u20092.85, EIu2009=u20091.30, UIu2009=u200914.5, cochlear doseu2009=u20095.10).ConclusionsThe investigation of the dose planning capabilities of the PFX on a cohort of VS demonstrates a better conformity and energy distribution, with better cochlear sparing and without any particular drawback. In addition, there is an improvement in peripheral dose gradient in larger lesions. Further clinical studies will be required before drawing any conclusions about the clinical benefit achieved by these dose planning improvements.

Intraoperative cortico-cortical evoked potentials for the evaluation of language function during brain tumor resection: initial experience with 13 cases

OBJECTIVESnThe objective in the present study was to evaluate the usefulness of cortico-cortical evoked potentials (CCEP) monitoring for the intraoperative assessment of speech function during resection of brain tumors.nnnMETHODSnIntraoperative monitoring of CCEP was applied in 13 patients (mean age 34 ± 14 years) during the removal of neoplasms located within or close to language-related structures in the dominant cerebral hemisphere. For this purpose strip electrodes were positioned above the frontal language area (FLA) and temporal language area (TLA), which were identified with direct cortical stimulation and/or preliminary mapping with the use of implanted chronic subdural grid electrodes. The CCEP response was defined as the highest observed negative peak in either direction of stimulation. In 12 cases the tumor was resected during awake craniotomy.nnnRESULTSnAn intraoperative CCEP response was not obtained in one case because of technical problems. In the other patients it was identified from the FLA during stimulation of the TLA (7 cases) and from the TLA during stimulation of the FLA (5 cases), with a mean peak latency of 83 ± 15 msec. During tumor resection the CCEP response was unchanged in 5 cases, decreased in 4, and disappeared in 3. Postoperatively, all 7 patients with a decreased or absent CCEP response after lesion removal experienced deterioration in speech function. In contrast, in 5 cases with an unchanged intraoperative CCEP response, speaking abilities after surgery were preserved at the preoperative level, except in one patient who experienced not dysphasia, but dysarthria due to pyramidal tract injury. This difference was statistically significant (p < 0.01). The time required to recover speech function was also significantly associated with the type of intraoperative change in CCEP recordings (p < 0.01) and was, on average, 1.8 ± 1.0, 5.5 ± 1.0, and 11.0 ± 3.6 months, respectively, if the response was unchanged, was decreased, or had disappeared.nnnCONCLUSIONSnMonitoring CCEP is feasible during the resection of brain tumors affecting language-related cerebral structures. In the intraoperative evaluation of speech function, it can be a helpful adjunct or can be used in its direct assessment with cortical and subcortical mapping during awake craniotomy. It can also be used to predict the prognosis of language disorders after surgery and decide on the optimal resection of a neoplasm.

Trigeminal nerve radiosurgical treatment in intractable chronic cluster headache: Unexpected high toxicity

Cluster headache (CH) is one of the most debilitating headache syndromes encountered. CH is characterized by attacks of strictly unilateral, severe pain with orbital, supraorbital, or temporal location. Attacks last 15 to 180 minutes and usually occur one or several times per day, especially at night. They are accompanied by ipsilateral conjunctival injection, lacrimation, rhinorrhea or nasal congestion, and agitation (6). CH is defined as chronic (CCH) when the attacks of paroxysmal hemicrania occur for longer than 1 year without remission or with remission lasting shorter than 1 month (6). The intractable chronic form of CH is rare, but constitutes a major clinical problem. Trigeminal activation in CH justifies surgical procedures on this nerve to relieve intractable CH cases (10). In 1998, Ford et al. (5) reported positive results after radiosurgical targeting of the trigeminal nerve. To strictly evaluate the safety efficacy of trigeminal nerve radiosurgery in CCH, we organized a bicentric prospective selfcontrolled trial and we published the preliminary results of this study in 2005 (2). The aim of this article is to report the mediumand longterm results of radiosurgery, especially in CCH.OBJECTIVEWe have previously reported short-term results of a prospective open trial designed to evaluate trigeminal nerve radiosurgical treatment in intractable chronic cluster headache (CCH). Medium- and long-term results have not yet been reported. METHODSTen patients presenting with a severe and drug-resistant CCH were enrolled (nine men, one woman). The radiosurgical treatment was performed according to the technique usually used for trigeminal neuralgia in our department. A single 4-mm shot was positioned at the level of the cisternal portion of the trigeminal nerve. The median distance between the center of the shot and the emergence of the nerve was 9.35 mm (range, 7.5–13.3 mm). The median of this maximum dose to the brainstem was 8.0 Gy (range, 4.0–11.1 Gy). Mean age was 49.8 years (range, 32–77 yr). Mean duration of the CCH was 9 years (range, 2–33 yr). The mean follow-up period was 36.3 months (range, 24–48 mo). RESULTSTwo patients had complete relief of CCH. One patient had a good result with evolution in an episodic form. Seven patients had no improvement. Nine patients developed a new trigeminal nerve disturbance: three developed paresthesia with no hypoesthesia and six developed hypoesthesia, including two patients with deafferentation pain. Only one patient had neither paresthesia nor hypoesthesia. CONCLUSIONWe confirmed, with medium- and long-term evaluation, the high rate of toxicity and failure of the technique. The high toxicity, despite a methodology identical to the one used in trigeminal neuralgia, leads us to suspect an underlying specificity of the nerve in CCH. We do not recommend radiosurgery for treatment of intractable CCH.