Optimizing Radiosurgery for Trigeminal Neuralgia: Impact of Radiation Dose and Anatomic Target on Patient Outcomes.

OBJECTIVE: Radiosurgery is an increasingly popular treatment for trigeminal neuralgia (TN); however, several treatment variables require further study. This meta-analysis was conducted to clarify ambiguity in the literature and optimize treatment parameters. METHODS: A random-effects proportions meta-analysis using subgroup analysis and meta-regression investigated the association of prescription dose and anatomic target on outcomes in patients with typical TN. The PRISMA guidelines were used. Radiation doses used ranged from 70 to 90 Gy and the anatomic targets were either the root entry zone or a more distal nerve location. Outcome measures were pain at last follow-up and the development of bothersome numbness. RESULTS: Increasing radiation prescription dose was associated with improved outcomes across all analyzed doses (P < 0.001). Patients treated at a distal trigeminal nerve target had better pain control compared with a root entry zone target (P < 0.001). Despite a higher median dose, a distal target was independently associated with improved pain control. There were similar rates of bothersome numbness across radiation doses and both treatment targets. CONCLUSIONS: Higher radiation dose was associated with superior pain control without increasing bothersome numbness. Independent of dose, the distal target was also associated with improved pain control. Bothersome numbness was not related to dose or target.

Simultaneous Treatment of Petroclival Meningiomas and the Trigeminal Nerve with Gamma Knife Radiosurgery for Tumor-Related Trigeminal Neuralgia.

BACKGROUND: Some petroclival meningiomas cause trigeminal nerve compression, leading to disabling trigeminal neuralgia (TN). Tumor resection and nerve decompression can offer pain relief but might not be feasible in all patients. Simultaneous stereotactic radiosurgery (SRS) to the tumor and nerve is another option. SRS is an effective means of treating meningiomas and TN separately, but data on the efficacy and outcomes of their concomitant treatment are limited. CASE DESCRIPTION: We report a series of 4 patients who presented with TN secondary to a petroclival mass causing compression of the trigeminal nerve. All patients underwent SRS to both the petroclival mass and trigeminal nerve in a single session. The average margin tumor dose was 12.25 Gy (range, 12-12.5 Gy), and the average maximum trigeminal nerve dose was 80 Gy (range, 75-85 Gy). In all patients, before intervention, the Barrow Neurologic Institute (BNI) pain intensity score was grade IV or V. At last follow-up (average, 29.8 months), all patients were pain-free (BNI I or IIIA). Two patients experienced reduced facial sensation in 1 or all 3 distributions. No brainstem edema was seen. CONCLUSIONS: This series highlights the benefits and safety of simultaneous treatment of petroclival tumors and the trigeminal nerve in a single session for patients affected by tumor-related TN.

Twelve-year results of LINAC-based radiosurgery for vestibular schwannomas.

PURPOSE: To report long-term outcomes of 53 patients with vestibular schwannomas (VS) submitted to a single high-dose LINAC-based radiosurgery (SRS) in our institution. METHODS: 48 (92%) patients were evaluable for clinical and MRI response as well as late toxicity. At a median follow-up of 12 years (range 2-16 years), local control (LC), hearing capacity, trigeminal and facial nerve function, and toxicity were assessed. Hearing capacity was classified according to the Gardner-Robertson scale, where class I-II patients had "serviceable hearing." RESULTS: Median dose of SRS was 16.5 Gy (range 13-20 Gy) and median tumor volume 1.7 cm3 (range 0.09-7.4 cm3). 35 (73%) patients were treated with SRS alone, in the remaining 13 (27%) patients, SRS was performed as salvage therapy for recurrent or progressive tumors after previous microsurgery. Before SRS, 44 patients (92%) had hearing loss and 25 (52%) had "non-serviceable" hearing. Tumor extension, classified with Koos categories, was grade I-II in 27 (56%) and grade III-IV in 21 (44%) cases. LC was 100% and hearing preservation in "serviceable hearing" patients was 91%. 4 (11%) patients developed incomplete and intermittent ipsilateral facial nerve palsy which regressed in a median time of 6 months. Trigeminal toxicity was registered in 11 (23%) patients, reversible in 6 (13%) and permanent in 5 (10%). Only Koos tumor grade III-IV significantly influenced late toxicity (p = 0.01). CONCLUSION: LC and hearing preservation after SRS were excellent. Toxicity proved acceptable. Although the median administered dose (16.5 Gy) was rather high, the only factor which significantly influenced late toxicity was Koos tumor grade III-IV.

Time course of pain response and toxicity after whole-nerve-encompassing LINAC-based stereotactic radiosurgery for trigeminal neuralgia-a prospective observational study.

PURPOSE: To prospectively evaluate the time course of pain response and toxicity after linear accelerator-based whole-nerve-encompassing radiosurgery (LINAC-SRS) using a uniform treatment schedule for dosing and target volume definition in patients with refractory trigeminal neuralgia. METHODS: From December 2012 to December 2016, 21 patients were treated using a standardized protocol. Patients received LINAC-SRS with 70 Gy to the cisternal portion while aiming for the 90% isodose to fully envelope the nerve in one cross-sectional plane. Data on pain, analgesics, and toxicity were gathered prospectively. Four time intervals (1-6, 6-12, 12-18, and 18-24 months) were defined and compared to baseline and each other. RESULTS: The median follow-up from radiotherapy was 16 months. Freedom from pain was achieved at least once in 90.5, 81.0, and 85.7% of patients for everyday pain, rest pain, and pain peaks, respectively. At 1-6 months, pain was significantly reduced in everyday routine (mean VAS, 2.0/10 vs. 5.8/10; P = 0.004), at rest (1.5/10 vs. 4.0/10; P = 0.002), and for pain peaks (2.9/10 vs. 10/10; P < 0.001), as was the number of analgesics (mean 1.5 vs. 2.9; P < 0.001). No significant increase in pain or analgesics was observed for subsequent time intervals. At last follow-up, reduction in pain compared to baseline for everyday routine (2.1/10 vs. 5.8/10; P = 0.010) and for pain peaks (3.3/10 vs. 10/10; P < 0.001) was significant, whereas it was not for rest pain (1.8/10 vs. 3.9/10; P = 0.073). Most toxicities were related to trigeminal nerve impairment, with 42.9% reporting new-onset hypoesthesia at last follow-up. CONCLUSION: This study provides prospective data after whole nerve encompassing LINAC-SRS for trigeminal neuralgia. No significant pain relapse was observed.

Effect of Laser Photobiomodulation with Gradual or Constant Doses in the Regeneration of Rats' Mental Nerve After Lesion by Compression.

OBJECTIVE: Assess morphologically the efficacy of constant dose (CD) or gradual dose (GD) in photobiomodulation therapy (PBMT) during the regeneration process of rats' mental nerve after compression lesion. MATERIALS AND METHODS: Forty-eight male Wistar rats were used and divided into four groups (n = 12): negative control (NC): lesion by compression; positive control (PC): no lesion; GD: lesion by compression and PBMT with GD; and CD: lesion by compression and PBMT with CD. One day after the surgery, the groups GD and CD underwent PBMT daily in three equidistant points around the incision area. The parameters were wavelength of 808 nm, 100 mW, CD received treatment with 120 J/cm2, while GD underwent the protocol of application: 1st and 4th sessions: 80 J/cm2; 5th to 8th sessions: 90 J/cm2; 9th to 12th sessions: 100 J/cm2; 13th to 16th sessions: 110 J/cm2; and 17th to 20th sessions: 120 J/cm2. Euthanasias were performed at 3, 7, 14, and 21 days. Qualitative and quantitative analysis of the mental nerves were performed with ANOVA (analysis of variance) and Tukey tests (p ≤ 0.05). RESULTS: It was observed that PBMT was able to accelerate the process of nerve regeneration presenting an increase in the number of myelinated fibers starting at 14 days of treatment for groups CD and GD, and at 21 days they were similar to PC. It was observed a better lamellar organization of myelin sheath at 7 days for GD and at 14 days for CD, similar to PC. Both GD and CD presented significant differences compared to NC and PC for thickness of the myelin sheath, outer perimeter, internal area, and number of myelin fibers. CONCLUSIONS: PBMT presented positive effect on the regeneration of nerve starting at 14 days, and after 21 days there was no difference between GD and CD.

Radiotherapy in patients with vestibular schwannoma and neurofibromatosis type 2: clinical results and review of the literature.

AIMS AND BACKGROUND: To evaluate the long-term outcome of patients with vestibular schwannoma (VS) and neurofibromatosis type 2 (NF2) treated with fractionated stereotactic radiotherapy (FSRT) or stereotactic radiosurgery (SRS). PATIENTS AND METHODS: Sixteen VS in 14 patients with NF2 were treated with FSRT (n = 14) and SRS (n = 2). Patients with tumor progression and/or progression of clinical symptoms were selected for treatment. For patients treated with FSRT a median total dose of 57.6 Gy was prescribed with a median fractionation of 5 × 1.8 Gy per week. For patients who underwent SRS a median single dose of 17 Gy was prescribed to the 80% isodose. RESULTS: FSRT and SRS were well tolerated. Local control rate was 94% for a median follow-up time of 131 months; 2- and 5-year progression-free survival were 100%. The probability of maintaining the pretreatment hearing level was 44%. Useful hearing preservation was 33%. Cranial nerve toxicity was moderate. Trigeminal nerve function worsened in 2 patients (12%) and facial nerve function in 3 patients (19%). One patient developed a new tinnitus. CONCLUSION: FSRT and SRS are both safe and effective noninvasive and minimally invasive treatment options for patients with VS in the setting of NF2. The long-term local control rates are excellent. Functional hearing preservation is worse in patients with VS and NF2 than in patients with sporadic VS.

Linear accelerator stereotactic radiosurgery for vestibular schwannomas: a UK series.

AIMS: To evaluate non-auditory toxicity and local control after linear accelerator stereotactic radiosurgery (SRS) for the treatment of vestibular schwannomas. MATERIALS AND METHODS: The institutional policy was to use SRS for radiologically progressing vestibular schwannomas. Case notes and plans were retrospectively reviewed for all patients undergoing SRS for vestibular schwannomas between September 2002 and June 2012. All patients were surgically immobilised using a BrainLab stereotactic head frame. The treatment plan was generated using BrainLab software (BrainScan 5.03). The aim was to deliver 12 Gy to the surface of the target with no margin. Patients with a minimum of 12 months of follow-up were included for toxicity and local control assessment. Radiological progression was defined as growth on imaging beyond 2 years of follow-up. Overall local control was defined in line with other series as absence of surgical salvage. RESULTS: Ninety-nine patients were identified. Two patients were lost to follow-up. After a median follow-up interval of 2.4 years, the actuarial radiological progression-free survival at 3 years was 100% and overall local control was also 100%. However, two patients progressed radiologically at 3.3 and 4.5 years, respectively. Twenty-one of 97 (22%) evaluable patients suffered trigeminal toxicity and this was persistent in 8/97 (8%). Two of 97 (2%) suffered long-term facial nerve toxicity (one with associated radiological progression causing hemi-facial spasm alone). One of 97 (1%) required intervention for obstructive hydrocephalus. No statistically significant dosimetric relationship could be shown to cause trigeminal or facial nerve toxicity. However, 7/8 patients with persistent trigeminal nerve toxicity had tumours in contact with the trigeminal nerve. CONCLUSIONS: SRS delivering 12 Gy using a linear accelerator leads to high local control rates, but only prospective evaluation will fully establish short-term toxicity. In this study, persistent trigeminal toxicity occurred almost exclusively in patients whose tumour was in contact with the trigeminal nerve.

Hearing preservation after radiotherapy for vestibular schwannomas is comparable to hearing deterioration in healthy adults and is accompanied by local tumor control and a highly preserved quality of life (QOL) as patients' self-reported outcome.

PURPOSE: To evaluate long-term results and patients' self-reported outcome of high-precision photon radiotherapy for the treatment of patients with vestibular schwannoma (VS). METHODS AND MATERIALS: We treated 246 patients with 248 VS with fractionated stereotactic radiotherapy (FSRT) or stereotactic radiosurgery (SRS). For FSRT, a median total dose of 57.6 Gy was prescribed in median single doses of 1.8 Gy, for SRS, a median dose of 13 Gy/80% isodose was applied. Of all patients, 51 patients died during follow-up. To evaluate long-term toxicity and QOL, we sent out a questionnaire to all living patients; of these, 81 patients (42%) sent back the questionnaire. RESULTS: Median local control was 84 months, actuarial local control rates for both groups (SRS and FSRT) were 98% after 2, 95% after 5, and 93% after 10 years; there was no statistical difference between FSRT and SRS. Hearing deterioration was significantly higher in the SRS group than the FSRT group. However, when comparing FSRT to SRS with doses ≤ 13 Gy, hearing preservation is comparable. In patients with useful hearing, hearing preservation was 89.7% at 1 year, 84.7% at 3 years, 76.5% at 5 years, and 68.6% at 10 years. After 10 years of follow-up, hearing deterioration can be observed in both subgroups. In the FSRT group, facial nerve toxicity rate was 1.6%. Trigeminal nerve toxicity was observed in 2.1% after FSRT. Overall QOL was unchanged in 47% of the patients after RT, and 31% reported an improvement in QOL during follow-up. CONCLUSION: Patients' self-reported outcome confirms good results with respect to tumor control and QOL after FSRT or SRS in patients with VS. SRS can be associated with higher side effect following a dose-dependency. In long-term follow-up, hearing deterioration is most likely attributed to normal aging, but not treatment-related.

Symptomatic outcomes in relation to tumor expansion after fractionated stereotactic radiation therapy for vestibular schwannomas: single-institutional long-term experience.

PURPOSE: The effect of transient tumor expansion after conventionally fractionated stereotactic radiation therapy (SRT) on the symptomatic outcomes is not well-known. METHODS AND MATERIALS: This study enrolled 201 consecutive patients who received SRT for vestibular schwannoma. A conventional fractionation schedule was applied in 194 patients (97%), and 142 (71%) received a total dose of 50 Gy. The median follow-up time was 72 months. RESULTS: The maximum diameter was 9 mm or less in 13 patients, 10-19 mm in 79 patients, 20-29 mm in 87 patients, and 30 mm or greater in 22 patients. At presentation, tumor size of 20 mm or greater was significantly associated with loss of serviceable hearing and trigeminal neuropathy. After SRT, tumor expansion was observed in 42 patients (21%). By tumor size, tumor expansion was observed in 0%, 11.4%, 25.6%, and 50% of patients with tumors of 9 mm or less, 10-19 mm, 20-29 mm, and 30 mm or greater, respectively, in diameter. The tumor expansion was significantly associated with an increased risk of hydrocephalus requiring shunt placement (P=.004), loss of serviceable hearing (P=.0064), and worsening of facial (P<.0001) and trigeminal nerve (P<.0001) functions. Spontaneous tumor shrinkage was observed in 29 of those 42 patients, mostly within 2 years after the expansion, and the majority of the worsened symptoms except for hearing resolved once the tumor had shrunk. As a result, salvage surgical resection for symptomatic relief was required in only 5% of patients. CONCLUSIONS: Fractionated SRT could be safely applied even for medium- to large-sized (≥20 mm) tumors. However, greater knowledge of the risks and consequences, including transient symptomatic worsening, and the time span of expansion will be required for the follow-up of patients after SRT to avoid unnecessary surgical intervention.

Fractionated stereotactic radiotherapy for acoustic neuromas: a prospective monocenter study of about 158 cases.

PURPOSE: To evaluate long-term outcomes and efficacy of fractionated stereotactic radiotherapy in the treatment of acoustic neuromas. MATERIAL AND METHODS: Between January 1996 and December 2009, 158 acoustic neuromas were treated by FSR in 155 patients. They received a dose of 50.4 Gy, with a safety margin of 1-2mm with a median tumor volume at 2.45 mL (range: 0.17-12.5 mL) and a median follow-up duration at 60 months (range: 24-192). RESULTS: FSR was well tolerated in all patients with mild sequelae consisting in radiation-induced trigeminal nerve impairments (3.2%), Grade 2 facial neuropathies (2.5%), new or aggravated tinnitus (2.1%) and VP shunting (2.5%). The treatment failed in four patients (2.5%) who had subsequent surgery respectively at 20, 38, 45 and 84 months post-FSR. The local tumor control rates were respectively 99.3%, 97.5% and 95.2% at 3, 5 and >7-year of follow-up. For initial Gardner-Robertson Grade 1 and 2 ANs, the preservation of useful hearing was possible in 54% of the cases; only Grade 1 ANs had stabilized during the course of the follow-up with 71% >7 years. However, hearing preservation was not correlated to the initial Koos Stage and to the radiation dose delivered to the cochlea. Tinnitus (70%), vertigo (59%), imbalance (46%) and ear mastoid pain (43%) had greatly improved post-FRS in most patients. Tumor control, hearing preservation and FRS toxicity were quite similar in patients with NF2, cystic acoustic neuroma, prior surgical resection and Koos Stage 4 AN. No secondary tumors were observed. CONCLUSION: FSR is a safe and effective therapeutic for acoustic neuromas and could be an alternative to microsurgery. Compared to radiosurgery, there are no contraindications for fractioned doses of stereotactic radiotherapy especially for Stage-4 tumors and patients at high risk of hearing loss.

The magnetite-based receptors in the beak of birds and their role in avian navigation.

Iron-rich structures have been described in the beak of homing pigeons, chickens and several species of migratory birds and interpreted as magnetoreceptors. Here, we will briefly review findings associated with these receptors that throw light on their nature, their function and their role in avian navigation. Electrophysiological recordings from the ophthalmic nerve, behavioral studies and a ZENK-study indicate that the trigeminal system, the nerves innervating the beak, mediate information on magnetic changes, with the electrophysiological study suggesting that these are changes in intensity. Behavioral studies support the involvement of magnetite and the trigeminal system in magnetoreception, but clearly show that the inclination compass normally used by birds represents a separate system. However, if this compass is disrupted by certain light conditions, migrating birds show 'fixed direction' responses to the magnetic field, which originate in the receptors in the beak. Together, these findings point out that there are magnetite-based magnetoreceptors located in the upper beak close to the skin. Their natural function appears to be recording magnetic intensity and thus providing one component of the multi-factorial 'navigational map' of birds.

[First experience of stereotactic radiation therapy for vestibular schwannoma using CyberKnife].

Currently stereotactic radiosurgery has become the treatment of choice in small vestibular schwannomas. This paper discusses our first experience of application of CyberKnife system for stereotactic irradiation of these tumors. From April 2009 till June 2011 we treated 62 patients (35 female and 27 male) with vestibular schwannomas. Stereotactic radiosurgery using CyberKnife system was performed in 33 patients. Mean tumor volume was 2 +/- 1.4 cm3. Hypofractionated treatment was used in 30 cases (31 tumor). Mean tumor volume reached was 7 +/- 6.2 cm3 (range - 0.5-31.3 cm3). In a case of a patient with NF2 simultaneous irradiation of bilateral tumors was performed. Most frequently we applied 3 fractions 6 Gy each (17 observations of 31, or 55%) and 5 fractions with mean dose 5 Cy (10 cases, or 32%). Follow-up period varied from 1 to 26 months (mean 9 +/- 4.5 months). By the end of this study (June 30, 2011) surgical resection was required in the only case of 47-years old male patient with cystic schwannoma of left vestibular nerve 5 months after radiation treatment, due to progressive growth of the cyst and increased brainstem compression. Tumor growth control was established in 97.5% of cases. Stabilization of auditory function was achieved in 77.5% of series. Effective hearing was preserved in 75% of patients. Facial nerve palsy after stereotactic radiation treatment was observed in 2 cases (3%). Incidence of trigeminal nerve dysfunction was significantly higher: sensation disturbances occurred in 6 (10%) patients: 3% after radiosurgery and 16.7% after hypofractionation. We did not obtain significant correlations between risk of cranial nerve complications and dosimetric or demographic factors. However we observed stable tendency: larger initial volume of the tumor and presence of trigeminal nerve dysfunction before treatment were poor prognostic factors for trigeminal neuropathy. Stereotactic irradiation using CyberKnife system is effective and sufficiently safe technique for management of vestibular schwannoma. The paper demonstrates high rates of tumor stabilization, hearing preservation and minimal incidence of complications associated with trigeminal or facial nerve.

Stereotactic radiotherapy for malignancies involving the trigeminal and facial nerves.

Involvement of a cranial nerve caries a poor prognosis for many malignancies. Recurrent or residual disease in the trigeminal or facial nerve after primary therapy poses a challenge due to the location of the nerve in the skull base, the proximity to the brain, brainstem, cavernous sinus, and optic apparatus and the resulting complex geometry. Surgical resection caries a high risk of morbidity and is often not an option for these patients. Stereotactic radiosurgery and radiotherapy are potential treatment options for patients with cancer involving the trigeminal or facial nerve. These techniques can deliver high doses of radiation to complex volumes while sparing adjacent critical structures. In the current study, seven cases of cancer involving the trigeminal or facial nerve are presented. These patients had unresectable recurrent or residual disease after definitive local therapy. Each patient was treated with stereotactic radiation therapy using a linear accelerator based system. A multidisciplinary approach including neuroradiology and surgical oncology was used to delineate target volumes. Treatment was well tolerated with no acute grade 3 or higher toxicity. One patient who was reirradiated experienced cerebral radionecrosis with mild symptoms. Four of the seven patients treated had no evidence of disease after a median follow up of 12 months (range 2-24 months). A dosimetric analysis was performed to compare intensity modulated fractionated stereotactic radiation therapy (IM-FSRT) to a 3D conformal technique. The dose to 90% (D90) of the brainstem was lower with the IM-FSRT plan by a mean of 13.5 Gy. The D95 to the ipsilateral optic nerve was also reduced with IM-FSRT by 12.2 Gy and the D95 for the optic chiasm was lower with FSRT by 16.3 Gy. Treatment of malignancies involving a cranial nerve requires a multidisciplinary approach. Use of an IM-FSRT technique with a micro-multileaf collimator resulted in a lower dose to the brainstem, optic nerves and chiasm for each case examined.

Predicting nonauditory adverse radiation effects following radiosurgery for vestibular schwannoma: a volume and dosimetric analysis.

PURPOSE: To define clinical and dosimetric predictors of nonauditory adverse radiation effects after radiosurgery for vestibular schwannoma treated with a 12 Gy prescription dose. METHODS: We retrospectively reviewed our experience of vestibular schwannoma patients treated between September 2005 and December 2009. Two hundred patients were treated at a 12 Gy prescription dose; 80 had complete clinical and radiological follow-up for at least 24 months (median, 28.5 months). All treatment plans were reviewed for target volume and dosimetry characteristics; gradient index; homogeneity index, defined as the maximum dose in the treatment volume divided by the prescription dose; conformity index; brainstem; and trigeminal nerve dose. All adverse radiation effects (ARE) were recorded. Because the intent of our study was to focus on the nonauditory adverse effects, hearing outcome was not evaluated in this study. RESULTS: Twenty-seven (33.8%) patients developed ARE, 5 (6%) developed hydrocephalus, 10 (12.5%) reported new ataxia, 17 (21%) developed trigeminal dysfunction, 3 (3.75%) had facial weakness, and 1 patient developed hemifacial spasm. The development of edema within the pons was significantly associated with ARE (p = 0.001). On multivariate analysis, only target volume is a significant predictor of ARE (p = 0.001). There is a target volume threshold of 5 cm3, above which ARE are more likely. The treatment plan dosimetric characteristics are not associated with ARE, although the maximum dose to the 5th nerve is a significant predictor of trigeminal dysfunction, with a threshold of 9 Gy. The overall 2-year tumor control rate was 96%. CONCLUSIONS: Target volume is the most important predictor of adverse radiation effects, and we identified the significant treatment volume threshold to be 5 cm3. We also established through our series that the maximum tolerable dose to the 5th nerve is 9 Gy.

Clinical outcomes of 114 patients who underwent γ-knife radiosurgery for medically refractory idiopathic trigeminal neuralgia.

The optimal radiation dose and target of Gamma-knife radiosurgery (GKRS) for medically refractory idiopathic trigeminal neuralgia (TN) are contentious. We investigated the effects and trigeminal nerve deficits of GKRS using two isocenters to treat a great length of the trigeminal nerve. Between January 2005 and March 2010, 129 patients with idiopathic TN underwent GKRS at the West China Hospital of Sichuan University. A maximum central dose of 80-90 Gy was delivered to the trigeminal nerve root with two isocenters via a 4mm collimator helmet. One hundred and fourteen patients were followed-up periodically by telephone interview to determine the effects, trigeminal nerve deficits and time to the onset of pain relief. The mean follow-up duration was 29.6 months. One hundred and nine patients had complete or partial pain relief and the treatment failed in five patients. Nine patients experienced a recurrence after a mean time of 12.7 months, following an initial interval of pain relief. There were no significant differences between patients with different grades of pain relief with respect to central doses. The mean time to the onset of pain relief was 3.6 weeks. The time to the onset of complete pain relief was significantly shorter than that for partial pain relief. Forty-nine patients reported mild-to-moderate facial numbness and one patient experienced paroxysmal temporalis muscle spasms two weeks after the treatment. GKRS treatment for medically refractory idiopathic TN with two isocenters resulted in an initial pain improvement in 95.6% of patients. The early response to the treatment might suggest a good outcome but, given the high incidence of nerve deficits, GKRS for TN with two isocenters is not recommended as a routine treatment protocol.

Stereotactic fractionated radiotherapy and LINAC radiosurgery in the treatment of vestibular schwannoma-report about both stereotactic methods from a single institution.

PURPOSE: To evaluate tumor control and side effects associated with radiosurgery (RS) and stereotactic fractionated radiotherapy (SFR) for vestibular schwannomas (VSs) in a group of patients treated at the same institution. METHODS AND MATERIALS: Between May 1997 and June 2007, 115 consecutive cases of VS were treated in our department. The SFR group (47 patients), including larger tumors (maximum diameter >1.5 cm), received a total dose of 54 Gy at 1.8 Gy per fraction. The RS group (68 patients, maximum diameter <1.5 cm) received a total dose of 12 Gy at the 100% isodose. Evaluation included serial imaging tests (magnetic resonance imaging) and neurologic and functional hearing examinations. RESULTS: The tumor control rate was 97.9% in the SFR group for a mean follow-up time of 32.1 months and 98.5% in the RS group for a mean follow-up time of 30.1 months. Hearing function was preserved after RS in 85% of the patients and after SFR in 79%. Facial and trigeminal nerve function remained mostly unaffected after SFR. After RS, new trigeminal neuropathy occurred in 9 of 68 patients (13%). CONCLUSIONS: A high tumor control rate and low number of side effects are registered after SFR and RS of VS. These results confirm that considering tumor diameter, both RS and SFR are good treatment modalities for VS.

Repeat gamma knife radiosurgery for trigeminal neuralgia.

PURPOSE: Repeat gamma knife stereotactic radiosurgery (GKRS) for recurrent or persistent trigeminal neuralgia induces an additional response but at the expense of an increased incidence of facial numbness. The present series summarized the results of a repeat treatment series at Wake Forest University Baptist Medical Center, including a multivariate analysis of the data to identify the prognostic factors for treatment success and toxicity. METHODS AND MATERIALS: Between January 1999 and December 2007, 37 patients underwent a second GKRS application because of treatment failure after a first GKRS treatment. The mean initial dose in the series was 87.3 Gy (range, 80-90). The mean retreatment dose was 84.4 Gy (range, 60-90). The dosimetric variables recorded included the dorsal root entry zone dose, pons surface dose, and dose to the distal nerve. RESULTS: Of the 37 patients, 81% achieved a >50% pain relief response to repeat GKRS, and 57% experienced some form of trigeminal dysfunction after repeat GKRS. Two patients (5%) experienced clinically significant toxicity: one with bothersome numbness and one with corneal dryness requiring tarsorraphy. A dorsal root entry zone dose at repeat treatment of >26.6 Gy predicted for treatment success (61% vs. 32%, p = .0716). A cumulative dorsal root entry zone dose of >84.3 Gy (72% vs. 44%, p = .091) and a cumulative pons surface dose of >108.5 Gy (78% vs. 44%, p = .018) predicted for post-GKRS numbness. The presence of any post-GKRS numbness predicted for a >50% decrease in pain intensity (100% vs. 60%, p = .0015). CONCLUSION: Repeat GKRS is a viable treatment option for recurrent trigeminal neuralgia, although the patient assumes a greater risk of nerve dysfunction to achieve maximal pain relief.

Laser modulation of heat and capsaicin receptor TRPV1 leads to thermal antinociception.

Er,Cr:YSGG lasers are used clinically in dentistry. The advantages of laser therapy include minimal thermal damage and the alleviation of pain. This study examined whether the Er,Cr:YSGG laser has in vivo and in vitro antinociceptive effects in itself. In capsaicin-evoked acute licking/shaking tests and Hargreaves tests, laser irradiation with an aerated water spray suppressed nociceptive behavior in mice. Laser irradiation attenuated TRPV1 activation by capsaicin in Ca(2+) imaging experiments with TRPV1-overexpressing cells and cultured trigeminal neurons. Therefore, the laser-induced behavioral changes are probably due to the loss of TRPV1 activity. TRPV4 activity was also attenuated, but limited mechanical antinociception by the laser was observed. The laser failed to alter the other receptor functions, which indicates that the antinociceptive effect of the laser is dependent on TRPV1. These results suggest that the Er,Cr:YSGG laser has analgesic effects via TRPV1 inhibition. Such mechanistic approaches may help define the laser-sensitive pain modality and increase its beneficial uses.

Bright light activates a trigeminal nociceptive pathway.

Bright light can cause ocular discomfort and/or pain; however, the mechanism linking luminance to trigeminal nerve activity is not known. In this study we identify a novel reflex circuit necessary for bright light to excite nociceptive neurons in superficial laminae of trigeminal subnucleus caudalis (Vc/C1). Vc/C1 neurons encoded light intensity and displayed a long delay (>10s) for activation. Microinjection of lidocaine into the eye or trigeminal root ganglion (TRG) inhibited light responses completely, whereas topical application onto the ocular surface had no effect. These findings indicated that light-evoked Vc/C1 activity was mediated by an intraocular mechanism and transmission through the TRG. Disrupting local vasomotor activity by intraocular microinjection of the vasoconstrictive agents, norepinephrine or phenylephrine, blocked light-evoked neural activity, whereas ocular surface or intra-TRG microinjection of norepinephrine had no effect. Pupillary muscle activity did not contribute since light-evoked responses were not altered by atropine. Microinjection of lidocaine into the superior salivatory nucleus diminished light-evoked Vc/C1 activity and lacrimation suggesting that increased parasympathetic outflow was critical for light-evoked responses. The reflex circuit also required input through accessory visual pathways since both Vc/C1 activity and lacrimation were prevented by local blockade of the olivary pretectal nucleus. These findings support the hypothesis that bright light activates trigeminal nerve activity through an intraocular mechanism driven by a luminance-responsive circuit and increased parasympathetic outflow to the eye.

Differences in clinical results after LINAC-based single-dose radiosurgery versus fractionated stereotactic radiotherapy for patients with vestibular schwannomas.

PURPOSE: To evaluate the outcomes of patients with vestibular schwannoma (VS) treated with fractionated stereotactic radiotherapy (FSRT) vs. those treated with stereotactic radiosurgery (SRS). METHODS AND MATERIALS: This study is based on an analysis of 200 patients with 202 VSs treated with FSRT (n = 172) or SRS (n = 30). Patients with tumor progression and/or progression of clinical symptoms were selected for treatment. In 165 out of 202 VSs (82%), RT was performed as the primary treatment for VS, and for 37 VSs (18%), RT was conducted for tumor progression after neurosurgical intervention. For patients receiving FSRT, a median total dose of 57.6 Gy was prescribed, with a median fractionation of 5 x 1.8 Gy per week. For patients who underwent SRS, a median single dose of 13 Gy was prescribed to the 80% isodose. RESULTS: FSRT and SRS were well tolerated. Median follow-up time was 75 months. Local control was not statistically different for both groups. The probability of maintaining the pretreatment hearing level after SRS with doses of < or =13 Gy was comparable to that of FSRT. The radiation dose for the SRS group (< or =13 Gy vs. >13 Gy) significantly influenced hearing preservation rates (p = 0.03). In the group of patients treated with SRS doses of < or =13 Gy, cranial nerve toxicity was comparable to that of the FSRT group. CONCLUSIONS: FSRT and SRS are both safe and effective alternatives for the treatment of VS. Local control rates are comparable in both groups. SRS with doses of < or =13 Gy is a safe alternative to FSRT. While FSRT can be applied safely for the treatment of VSs of all sizes, SRS should be reserved for smaller lesions.