Thomas Flannery

Gamma Knife stereotactic radiosurgery for idiopathic trigeminal neuralgia

OBJECT Trigeminal neuralgia pain causes severe disability. Stereotactic radiosurgery is the least invasive surgical option for patients with trigeminal neuralgia. Since different medical and surgical options have different rates of pain relief and morbidity, it is important to evaluate longer-term outcomes. METHODS The authors retrospectively reviewed outcomes in 503 medically refractory patients with trigeminal neuralgia who underwent Gamma Knife surgery (GKS). The median patient age was 72 years (range 26-95 years). Prior surgery had failed in 205 patients (43%). The GKS typically was performed using MR imaging guidance, a single 4-mm isocenter, and a maximum dose of 80 Gy. RESULTS Patients were evaluated for up to 16 years after GKS; 107 patients had > 5 years of follow-up. Eighty-nine percent of patients achieved initial pain relief that was adequate or better, with or without medications (Barrow Neurological Institute [BNI] Scores I-IIIb). Significant pain relief (BNI Scores I-IIIa) was achieved in 73% at 1 year, 65% at 2 years, and 41% at 5 years. Including Score IIIb (pain adequately controlled with medication), a BNI score of I-IIIb was found in 80% at 1 year, 71% at 3 years, 46% at 5 years, and 30% at 10 years. A faster initial pain response including adequate and some pain relief was seen in patients with trigeminal neuralgia without additional symptoms, patients without prior surgery, and patients with a pain duration of < or = 3 years. One hundred ninety-three (43%) of 450 patients who achieved initial pain relief reported some recurrent pain 3-144 months after initial relief (median 50 months). Factors associated with earlier pain recurrence that failed to maintain adequate or some pain relief were trigeminal neuralgia with additional symptoms and > or = 3 prior failed surgical procedures. Fifty-three patients (10.5%) developed new or increased subjective facial paresthesias or numbness and 1 developed deafferentation pain; these symptoms resolved in 17 patients. Those who developed sensory loss had better long-term pain control (78% at 5 years). CONCLUSIONS Gamma Knife surgery proved to be safe and effective in the treatment of medically refractory trigeminal neuralgia and is of value for initial or recurrent pain management. Despite the goal of minimizing sensory loss with this procedure, some sensory loss may improve long-term outcomes. Pain relapse is amenable to additional GKS or another procedure.

Stereotactic radiosurgery for arteriovenous malformations, Part 1: management of Spetzler-Martin Grade I and II arteriovenous malformations.

OBJECT The aim of this paper was to define the outcomes and risks of stereotactic radiosurgery (SRS) for Spetzler-Martin Grade I and II arteriovenous malformations (AVMs). METHODS Between 1987 and 2006, the authors performed Gamma Knife surgery in 996 patients with brain AVMs, including 217 patients with AVMs classified as Spetzler-Martin Grade I or II. The median maximum diameter and target volumes were 1.9 cm (range 0.5-3.8 cm) and 2.3 cm(3) (range 0.1-14.1 cm(3)), respectively. The median margin dose was 22 Gy (range 15-27 Gy). RESULTS Arteriovenous malformation obliteration was confirmed by MR imaging in 148 patients and by angiography in 100 patients with a median follow-up of 64 months (range 6-247 months). The actuarial rates of total obliteration determined by angiography or MR imaging after 1 SRS procedure were 58%, 87%, 90%, and 93% at 3, 4, 5, and 10 years, respectively. The median time to complete MR imaging-determined obliteration was 30 months. Factors associated with higher AVM obliteration rates were smaller AVM target volume, smaller maximum diameter, and greater marginal dose. Thirteen patients (6%) suffered hemorrhages during the latency period, and 6 patients died. Cumulative rates of AVM hemorrhage 1, 2, 3, 5, and 10 years after SRS were 3.7%, 4.2%, 4.2%, 5.0%, and 6.1%, respectively. This corresponded to rates of annual bleeding risk of 3.7%, 0.3%, and 0.2% for Years 0-1, 1-5, and 5-10, respectively, after SRS. The presence of a coexisting aneurysm proximal to the AVM correlated with a significantly higher hemorrhage risk. Temporary symptomatic adverse radiation effects developed in 5 patients (2.3%) after SRS, and 2 patients (1%) developed delayed cysts. CONCLUSIONS Stereotactic radiosurgery is a gradually effective and relatively safe option for patients with smaller volume Spetzler-Martin Grade I or II AVMs who decline initial resection. Hemorrhage after obliteration did not occur in this series. Patients remain at risk for a bleeding event during the latency interval until obliteration occurs. Patients with aneurysms and an AVM warrant more aggressive surgical or endovascular treatment to reduce the risk of a hemorrhage in the latency period after SRS.

Long-term control of petroclival meningiomas through radiosurgery

OBJECT Because of their critical location adjacent to brain, cranial nerve, and vascular structures, petroclival meningiomas remain a clinical challenge. The authors evaluated outcomes in 168 patients with petroclival meningiomas who underwent Gamma Knife surgery (GKS) during a 21-year interval. METHODS Gamma Knife surgery was used as either primary or adjuvant treatment of 168 petroclival meningiomas involving the region between the petrous apex and the upper two-thirds of the clivus. The most common presenting symptoms were trigeminal nerve dysfunction, balance problems, diplopia, and hearing loss. The median tumor volume was 6.1 cm3 (range 0.3-32.5 cm3), and the median radiation dose to the tumor margin was 13 Gy (range 9-18 Gy). RESULTS During a median follow-up of 72 months, neurological status improved in 44 patients (26%), remained stable in 98 (58%), and worsened in 26 (15%). Tumor volume decreased in 78 patients (46%), remained stable in 74 (44%), and increased in 16 (10%), all of whom were subjected to additional management strategies. Overall 5- and 10-year progression-free survival rates were 91 and 86%, respectively. Patients followed up for at least 10 years (31 patients) had tumor and symptom control rates of 97 and 94%, respectively. Eight patients had repeat radiosurgery, 4 underwent delayed resection, and 4 had fractionated radiation therapy. Cerebrospinal fluid diversion was performed in 7 patients (4%). Significant risk factors for tumor progression were a tumor volume > or = 8 cm3 (p = 0.001) and male sex (p = 0.02). CONCLUSIONS In this 21-year experience, GKS for petroclival meningiomas obviated initial or further resection in 98% of patients and was associated with a low risk of adverse radiation effects. The authors believe that radiosurgery should be considered as an initial option for patients with smaller-volume, symptomatic petroclival meningiomas.

Cathepsin S expression: An independent prognostic factor in glioblastoma tumours - A pilot Study

Cysteine proteinases have been implicated in astrocytoma invasion. We recently demonstrated that cathepsin S (CatS) expression is up‐regulated in astrocytomas and provided evidence for a potential role in astrocytoma invasion (Flannery et al., Am J Path 2003;163(1):175–82). We aimed to evaluate the significance of CatS in human astrocytoma progression and as a prognostic marker. Frozen tissue homogenates from 71 patients with astrocytomas and 3 normal brain specimens were subjected to ELISA analyses. Immunohistochemical analysis of CatS expression was performed on 126 paraffin‐embedded tumour samples. Fifty‐one astrocytoma cases were suitable for both frozen tissue and paraffin tissue analysis. ELISA revealed minimal expression of CatS in normal brain homogenates. CatS expression was increased in grade IV tumours whereas astrocytoma grades I–III exhibited lower values. Immunohistochemical analysis revealed a similar pattern of expression. Moreover, high‐CatS immunohistochemical scores in glioblastomas were associated with significantly shorter survival (10 vs. 5 months, p = 0.014). With forced inclusion of patient age, radiation dose and Karnofsky score in the Cox multivariate model, CatS score was found to be an independent predictor of survival. CatS expression in astrocytomas is associated with tumour progression and poor outcome in glioblastomas. CatS may serve as a useful prognostic indicator and potential target for anti‐invasive therapy.

Stereotactic radiosurgery for arteriovenous malformations, Part 2: management of pediatric patients

OBJECT The authors conducted a study to define the long-term outcomes and risks of stereotactic radiosurgery (SRS) for pediatric arteriovenous malformations (AVMs). METHODS Between 1987 and 2006, the authors performed Gamma Knife surgery in 996 patients with brain AVMs; 135 patients were younger than 18 years of age. The median maximum diameter and target volumes were 2.0 cm (range 0.6-5.2 cm) and 2.5 cm(3) (range 0.1-17.5 cm(3)), respectively. The median margin dose was 20 Gy (range 15-25 Gy). RESULTS The actuarial rates of total obliteration documented by angiography or MR imaging at 71.3 months (range 6-264 months) were 45%, 64%, 67%, and 72% at 3, 4, 5, and 10 years, respectively. The median time to complete angiographically documented obliteration was 48.9 months. Of 81 patients with 4 or more years of follow-up, 57 patients (70%) had total obliteration documented by angiography. Factors associated with a higher rate of documented AVM obliteration were smaller AVM target volume, smaller maximum diameter, and larger margin dose. In 8 patients (6%) a hemorrhage occurred during the latency interval, and 1 patient died. The rates of AVM hemorrhage after SRS were 0%, 1.6%, 2.4%, 5.5%, and 10.0% at 1, 2, 3, 5, and 10 years, respectively. The overall annual hemorrhage rate was 1.8%. Larger volume AVMs were associated with a significantly higher risk of hemorrhage after SRS. Permanent neurological deficits due to adverse radiation effects developed in 2 patients (1.5%) after SRS, and in 1 patient (0.7%) delayed cyst formation occurred. CONCLUSIONS Stereotactic radiosurgery is a gradually effective and relatively safe management option for pediatric patients in whom surgery is considered to pose excessive risks. Although hemorrhage after AVM obliteration did not occur in the present series, patients remain at risk during the latency interval until obliteration is complete. The best candidates for SRS are pediatric patients with smaller volume AVMs located in critical brain regions.

Stereotactic radiosurgery for arteriovenous malformations, Part 3: outcome predictors and risks after repeat radiosurgery

OBJECT The object of this study was to evaluate the outcomes and risks of repeat stereotactic radiosurgery (SRS) for incompletely obliterated cerebral arteriovenous malformations (AVMs). METHODS Between 1987 and 2006, Gamma Knife surgery was performed in 996 patients with AVMs. During this period, repeat SRS was performed in 105 patients who had incompletely obliterated AVMs at a median of 40.9 months after initial SRS (range 27.5-139 months). The median AVM target volume was 6.4 cm(3) (range 0.2-26.3 cm(3)) at initial SRS but was reduced to 2.3 cm(3) (range 0.1-18.2 cm(3)) at the time of the second procedure. The median margin dose at both initial SRS and repeat SRS was 18 Gy. RESULTS The actuarial rate of total obliteration by angiography or MR imaging after repeat SRS was 35%, 68%, 77%, and 80% at 3, 4, 5, and 10 years, respectively. The median time to complete angiographic or MR imaging obliteration after repeat SRS was 39 months. Factors associated with a higher rate of AVM obliteration were smaller residual AVM target volume (p = 0.038) and a volume reduction of 50% or more after the initial procedure (p = 0.014). Seven patients (7%) had a hemorrhage in the interval between initial SRS and repeat SRS. Seventeen patients (16%) had hemorrhage after repeat SRS and 6 patients died. The cumulative actuarial rates of new AVM hemorrhage after repeat SRS were 1.9%, 8.1%, 10.1%, 10.1%, and 22.4% at 1, 2, 3, 5, and 10 years, respectively, which translate to annual hemorrhage rates of 4.05% and 1.79% of patients developing new post-repeat-SRS hemorrhages per year for Years 0-2 and 2-10 following repeat SRS. Factors associated with a higher risk of hemorrhage after repeat SRS were a greater number of prior hemorrhages (p = 0.008), larger AVM target volume at initial SRS (p = 0.010), larger target volume at repeat SRS (p = 0.002), initial AVM volume reduction less than 50% (p = 0.019), and a higher Pollock-Flickinger score (p = 0.010). Symptomatic adverse radiation effects developed in 5 patients (4.8%) after initial SRS and in 10 patients (9.5%) after repeat SRS. Prior embolization (p = 0.022) and a higher Spetzler-Martin grade (p = 0.004) were significantly associated with higher rates of adverse radiation effects after repeat SRS. Delayed cyst formation occurred in 5 patients (4.8%) at a median of 108 months after repeat SRS (range 47-184 months). CONCLUSIONS Repeat SRS for incompletely obliterated AVMs increases the eventual obliteration rate. Hemorrhage after obliteration did not occur in this series. The best results for patients with incompletely obliterated AVMs were seen in patients with a smaller residual nidus volume and no prior hemorrhages.

Cranioplasty: why throw the bone flap out?

Patients who undergo decompressive craniectomy for intracranial hypertension often require interval cranioplasty. Many cranioplasty agents are currently in use. The authors suggest that storage of the patients own bone flap in the subcutaneous tissue of the abdominal wall, is a safe, efficacious and cost-effective alternative to use of synthetic cranioplasty materials.

Long-term outcome of subcutaneously preserved autologous cranioplasty.

OBJECTIVEDecompressive craniectomy for intracranial hypertension mandates later cranioplasty. Autologous cranioplasties can be preserved either by freezing or placement in a subcutaneous pocket. There are few data on the long-term follow-up of patients treated in such a fashion. METHODSA retrospective study was conducted on 100 consecutive patients who underwent decompressive craniectomy and placement of the bone flap in a subcutaneous pocket in the abdominal wall between 2000 and 2005. Initial diagnosis, Glasgow Coma Scale score on admission, complications, and Glasgow Outcome Score were recorded. RESULTSOf the 100 patients who underwent autocranioplasty, the primary diagnosis was traumatic brain injury (76%), subarachnoid hemorrhage (17%), primary intracerebral hemorrhage (3%), and tumor (4%). The mean age of the sample was 39 years (age range, 10–72 years). The mean follow-up duration was 25 months. The average Glasgow Coma Scale score on admission was 7. Eight patients died before replacement of the bone flap. The average time between craniectomy and replacement of bone flap was 42 days. The mean Glasgow Outcome Score was 4 at the time of the 1-year follow-up evaluation. Seven of the 79 patients (9%) for whom 1-year review data were available had a cosmetic result that was unacceptable and required removal of the flap (bone flap infections in 5 patients, unacceptable bone flap resorption in 2 patients) CONCLUSIONOur study indicates that storage of a cranioplasty flap in a subcutaneous pouch in the abdominal wall has a favorable long-term outcome.

Aneurysms Increase the Risk of Rebleeding After Stereotactic Radiosurgery for Hemorrhagic Arteriovenous Malformations

Background and Purpose— The purpose of this study was to define the risk of rebleeding after stereotactic radiosurgery (SRS) for hemorrhagic arteriovenous malformations with or without associated intracranial aneurysms. Methods— Between 1987 and 2006, we performed Gamma Knife SRS on 996 patients with brain arteriovenous malformations; 407 patients had sustained an arteriovenous malformation hemorrhage. Sixty-four patients (16%) underwent prior embolization and 84 (21%) underwent prior surgical resection. The median target volume was 2.3 mL (range, 0.1–20.7 mL). The median margin dose was 20 Gy (range, 13.5–27 Gy). Results— The overall rate of total obliteration defined by angiography or MRI was 56%, 77%, 80%, and 82% at 3, 4, 5, and 10 years, respectively. Before obliteration, 33 patients (8%) sustained an additional hemorrhage after SRS. The overall annual hemorrhage rate until obliteration after SRS was 1.3%. The presence of a patent aneurysm was significantly associated with an increased rehemorrhage risk after SRS (annual hemorrhage rate, 6.4%) compared with patients with a clipped or embolized aneurysm (annual hemorrhage rate, 0.8%; P=0.033). Conclusions— When an aneurysm is identified in patients with arteriovenous malformations selected for SRS, additional endovascular or surgical strategies should be considered to reduce the risk of bleeding during the latency interval.

Stereotactic radiosurgery for arteriovenous malformations, Part 4: management of basal ganglia and thalamus arteriovenous malformations.

OBJECT The authors conducted a study to define the long-term outcomes and risks of stereotactic radiosurgery (SRS) for arteriovenous malformations (AVMs) of the basal ganglia and thalamus. METHODS Between 1987 and 2006, the authors performed Gamma Knife surgery in 996 patients with brain AVMs; 56 patients had AVMs of the basal ganglia and 77 had AVMs of the thalamus. In this series, 113 (85%) of 133 patients had a prior hemorrhage. The median target volume was 2.7 cm(3) (range 0.1-20.7 cm(3)) and the median margin dose was 20 Gy (range 15-25 Gy). RESULTS Obliteration of the AVM eventually was documented on MR imaging in 78 patients and on angiography in 63 patients in a median follow-up period of 61 months (range 2-265 months). The actuarial rates documenting total obliteration after radiosurgery were 57%, 70%, 72%, and 72% at 3, 4, 5, and 10 years, respectively. Factors associated with a higher rate of AVM obliteration included AVMs located in the basal ganglia, a smaller target volume, a smaller maximum diameter, and a higher margin dose. Fifteen (11%) of 133 patients suffered a hemorrhage during the latency period and 7 patients died. The rate of post-SRS AVM hemorrhage was 4.5%, 6.2%, 9.0%, 11.2%, and 15.4% at 1, 2, 3, 5, and 10 years, respectively. The overall annual hemorrhage rate was 4.7%. When 5 patients with 7 hemorrhages occurring earlier than 6 months after SRS were removed from this analysis, the annual hemorrhage rate decreased to 2.7%. Larger volume AVMs had a higher risk of hemorrhage after SRS. Permanent neurological deficits due to adverse radiation effects (AREs) developed in 6 patients (4.5%), and in 1 patient a delayed cyst developed 56 months after SRS. No patient died of AREs. Factors associated with a higher risk of symptomatic AREs were larger target volume, larger maximum diameter, lower margin dose, and a higher Pollock-Flickinger score. CONCLUSIONS Stereotactic radiosurgery is a gradually effective and relatively safe management option for deep-seated AVMs in the basal ganglia and thalamus. Although hemorrhage after obliteration did not occur in the present series, patients remain at risk during the latency interval between SRS and obliteration. The best candidates for SRS are patients with smaller volume AVMs located in the basal ganglia.