Regina S. Bower

CyberKnife radiosurgery for trigeminal neuralgia treatment: A preliminary multicenter experience

OBJECTIVERadiosurgery has gained acceptance as a treatment option for trigeminal neuralgia. We report our preliminary multicenter experience treating trigeminal neuralgia with the CyberKnife (Accuray, Inc., Sunnyvale, CA). METHODSA total of 95 patients were treated for idiopathic trigeminal neuralgia between May 2002 and October 2005. Radiosurgical dose and volume parameters were retrospectively analyzed in relation to pain response, complications, and recurrence of symptoms. Optimal treatment parameters were identified for patients who had excellent and sustained pain relief with no complications, including severe or moderate hypesthesia. RESULTSExcellent pain relief was initially experienced by 64 out of 95 patients (67%). The median time to pain relief was 14 days (range, 0.3–180 d). Posttreatment numbness occurred in 45 (47%) of the patients treated. Using higher radiation doses and treating longer segments of the nerve led to both better pain relief and a higher incidence of hypesthesia. The presence of posttreatment numbness was predictive of better pain relief. The overall rate of complications was 18%. At the mean follow-up time of 2 years, 47 of the 95 patients (50%) had sustained pain relief, all of whom were completely off pain medications. CONCLUSIONThe results of this study suggest the following optimal radiosurgical treatment parameters for treatment of idiopathic trigeminal neuralgia: a median maximal dose of 78 Gy (range, 70–85.4 Gy) and a median length of the nerve treated of 6 mm (range, 5–12 mm).

Multimodality treatment of posterior fossa arteriovenous malformations

OBJECT Posterior fossa arteriovenous malformations (AVMs) are relatively uncommon and often difficult to treat. The authors present their experience with multimodality treatment of 76 posterior fossa AVMs, with an emphasis on Spetzler-Martin Grades III-V AVMs. METHODS Seventy-six patients with posterior fossa AVMs treated with radiosurgery, surgery, and endovascular techniques were analyzed. RESULTS Between 1982 and 2006, 36 patients with cerebellar AVMs, 33 with brainstem AVMs, and 7 with combined cerebellar-brainstem AVMs were treated. Natural history data were calculated for all 76 patients. The risk of hemorrhage from presentation until initial treatment was 8.4% per year, and it was 9.6% per year after treatment and before obliteration. Forty-eight patients had Grades III-V AVMs with a mean follow-up of 4.8 years (range 0.1-18.4 years, median 3.1 years). Fifty-two percent of patients with Grades III-V AVMs had complete obliteration at the last follow-up visit. Three (21.4%) of 14 patients were cured with a single radiosurgery treatment, and 4 (28.6%) of 14 with 1 or 2 radiosurgery treatments. Twenty-one (61.8%) of 34 patients were cured with multimodality treatment. The mean Glasgow Outcome Scale (GOS) score after treatment was 3.8. Multivariate analysis performed in the 48 patients with Grades III-V AVMs showed radiosurgery alone to be a negative predictor of cure (p = 0.0047). Radiosurgery treatment alone was not a positive predictor of excellent clinical outcome (GOS Score 5; p > 0.05). Nine (18.8%) of 48 patients had major neurological complications related to treatment. CONCLUSIONS Single-treatment radiosurgery has a low cure rate for posterior fossa Spetzler-Martin Grades III-V AVMs. Multimodality therapy nearly tripled this cure rate, with an acceptable risk of complications and excellent or good clinical outcomes in 81% of patients. Radiosurgery alone should be used for intrinsic brainstem AVMs, and multimodality treatment should be considered for all other posterior fossa AVMs.

Moyamoya Disease in a Primarily White, Midwestern US Population Increased Prevalence of Autoimmune Disease

Background and Purpose— Moyamoya disease is an uncommon, cerebrovascular occlusive disease of unknown pathogenesis. Previously described Moyamoya cohorts include predominantly Asian populations or ethnically diverse North American cohorts. To gain further insight into the pathogenesis of moyamoya, we examined clinical characteristics of a primarily white, Midwestern US population Methods— Retrospective analysis of patients with angiographically confirmed moyamoya disease evaluated at our institution was performed. Prevalence of comorbidities, cerebrovascular risk factors, and autoimmune diseases were compared with the general population. Results— Ninety-four patients with moyamoya were evaluated; 72.3% were female. Ethnic composition was primarily white (85%). A significantly higher prevalence of autoimmune disease was seen, particularly type 1 diabetes mellitus (8.5% versus 0.4% in the general population) and thyroid disease (17.0% versus 8.0% in the institutional general patient population). Hyperlipidemia was also increased (27.7% versus 16.3% in the general population). Conclusions— This study of a unique, primarily white, Midwestern population of moyamoya patients demonstrates a significantly higher prevalence of autoimmune disease than in the general population. This supports a possible autoimmune component to the pathogenesis of moyamoya disease.

Nonisocentric Radiosurgical Rhizotomy for Trigeminal Neuralgia.

OBJECTIVE Although stereotactic radiosurgery is an established procedure for treating trigeminal neuralgia (TN), the likelihood of a prompt and durable complete response is not assured. Moreover, the incidence of facial numbness remains a challenge. To address these limitations, a new, more anatomic radiosurgical procedure was developed that uses the CyberKnife (Accuray, Inc., Sunnyvale, CA) to lesion an elongated segment of the retrogasserian cisternal portion of the trigeminal sensory root. Because the initial experience with this approach resulted in an unacceptably high incidence of facial numbness, a gradual dose and volume de-escalation was performed over several years. In this single-institution prospective study, we evaluated clinical outcomes in a group of TN patients who underwent lesioning with seemingly optimized nonisocentric radiosurgical parameters. METHODS Forty-six patients with intractable idiopathic TN were treated between January 2005 and June 2007. Eligible patients were either poor surgical candidates or had failed previous microvascular decompression or destructive procedures. During a single radiosurgical session, a 6-mm segment of the affected nerve was treated with a mean marginal prescription dose of 58.3 Gy and a mean maximal dose of 73.5 Gy. Monthly neurosurgical follow-up was performed until the patient became pain-free. Longer-term follow-up was performed both in the clinic and over the telephone. Outcomes were graded as excellent (pain-free and off medication), good (>90% improvement while still on medication), fair (50-90% improvement), or poor (no change or worse). Facial numbness was assessed using the Barrow Neurological Institute Facial Numbness Scale score. RESULTS Symptoms disappeared completely in 39 patients (85%) after a mean latency of 5.2 weeks. In most of these patients, pain relief began within the first week. TN recurred in a single patient after a pain-free interval of 7 months; all symptoms abated after a second radiosurgical procedure. Four additional patients underwent a repeat rhizotomy after failing to respond adequately to the first operation. After a mean follow-up period of 14.7 months, patient-reported outcomes were excellent in 33 patients (72%), good in 11 patients (24%), and poor/no improvement in 2 patients (4%). Significant ipsilateral facial numbness (Grade III on the Barrow Neurological Institute Scale) was reported in 7 patients (15%). CONCLUSION Optimized nonisocentric CyberKnife parameters for TN treatment resulted in high rates of pain relief and a more acceptable incidence of facial numbness than reported previously. Longer follow-up periods will be required to establish whether or not the durability of symptom relief after lesioning an elongated segment of the trigeminal root is superior to isocentric radiosurgical rhizotomy.

Seizure outcomes after corpus callosotomy for drop attacks.

BACKGROUND Medically intractable epilepsy involving drop attacks can be difficult to manage and negatively affect quality of life. Most studies investigating the effect of corpus callosotomy (CC) on seizures have been limited, focusing on the pediatric population or drop seizures alone, with little attention to other factors influencing seizure outcome. OBJECTIVE To assess seizure outcomes after CC in adults and children. METHODS Retrospective analysis was performed on all patients who underwent CC (anterior two thirds, 1- or 2-stage complete) at our institution between 1990 and 2011. Change in frequency after CC was assessed for drop seizures and other seizure types. Multiple factors were evaluated for impact on seizure outcome. RESULTS Fifty patients met inclusion criteria. The median age was 1.5 years at seizure onset and 17 years at time of surgery. Anterior two-thirds CC was performed in 28 patients, 1-stage complete in 17, and 2-stage complete in 5. All 3 groups experienced a significant decrease in drop seizures (P < .001, P < .001, and P = .020, respectively), with 40% experiencing complete resolution, and 64% dropping at least 1 frequency category. Other seizure types significantly decreased in anterior two-thirds CC and 1-stage complete (P = .0035, P = .001, respectively). Younger age at surgery correlated with better seizure outcomes (P = .043). CONCLUSION CC for medically refractory generalizing epilepsy is effective for both drop seizures and other seizure types. CC should be considered soon after a patient has been deemed medically refractory because earlier age at surgery results in lower risk and better outcome.

Radiosurgery for glomus jugulare tumors.

Results for treating glomus jugulare tumors with radiosurgery have been limited by short follow-up and small number of patients. We report our experience using LINAC or CyberKnife in 21 tumors with a median follow-up of 66 months (Mean follow-up of 60 months). In addition, we have a subset of eight patients that were followed out for more than 10 years. Patients were treated with doses ranging from 1400 cGy to 2700 cGy. We retrospectively assessed patients for efficacy and post treatment side effects. All patients had stable neurological symptoms, and two patients experienced transient ipsilateral tongue weakness and hearing loss, both of which subsequently resolved. One patient experienced transient ipsilateral vocal cord paresis; however, this patient received previous external beam radiotherapy. All tumors remained stable or decreased in size by MRI exam. Our results support radiosurgery as an effective and safe method of treatment for glomus jugulare tumors with low morbidity as evidenced by a larger number of patients and long term follow-up.

Surgical Outcomes and Predictors of Stroke in a North American White and African American Moyamoya Population

BACKGROUND The majority of moyamoya surgical series have been confined to Asian and pediatric populations. Few have studied demographics, risk factors, and outcomes in adult North American populations. OBJECTIVE To examine outcomes after revascularization for moyamoya in white and African American adults and to assess for predictors of recurrent stroke. METHODS A retrospective review of 75 non-Asian patients undergoing 110 procedures at the Mayo Clinic was performed. Demographics, known moyamoya associations, cerebrovascular risk factors, and autoimmune diseases were recorded. Primary outcomes for vascular events were assessed with Kaplan-Meier analysis. Fisher exact methods were used to evaluate for associations with recurrent events. RESULTS Mean age was 42 years, and mean follow-up was 47 months. Seventy-one of the 75 patients were white. The majority had bilateral disease (n = 49). Perioperative ischemic events occurred in 5 patients (4.5%). The 5- and 10-year event rates were 5.8% and 9.9%. Significant associations were found with a history of thyroid disease (P = .05) and recurrent stroke. A trend was also found between hypertension and autoimmune disease with recurrent stroke. CONCLUSION Outcomes were favorable with revascularization in this subset with moyamoya. A significant association between a history of thyroid disease and recurrent stroke was found. Additionally, high prevalences of autoimmune disease, hypertension, and thyroid disease were found in our cohort, suggesting that they may play a role in the pathophysiology and progression of moyamoya disease in this population. A new classification for moyamoya is proposed based on these data.

Intravenous Recording of Intracranial, Broadband EEG

The most direct evaluation of human brain activity has been obtained from intracranial electrodes placed either on the surface of the brain or inserted into the brain to record from deep brain structures. Currently, the placement of intracranial electrodes implies transcranial surgery, either through a burr hole or a craniotomy, but the high degree of invasiveness and potential for morbidity of such major surgical procedures limits the applicability of intracranial recording. The vascular system provides a natural avenue to reach many brain regions that currently are reached by transcranial approaches, along with deep brain structures that cannot be reached via a transcranial approach without significant risk. To determine the applicability of intravascular approaches to high-frequency intracranial monitoring, a catheter containing multiple macro- and micro-electrodes was placed into the superior sagittal sinus of anesthetized pigs in parallel with clinical, subdural electrode grids to record epileptiform activity induced by direct, cortical injection of penicillin and to record responses to electrical stimulation. Intravascular electrodes recorded epileptiform spikes with similar magnitudes and waveshapes to those obtained by surface electrodes, both for macroelectrodes and microelectrodes, including the spatiotemporal evolution of epileptiform activity, suggesting that intravascular electrodes might provide localizing information regarding seizure foci. Sinusoidal electrical stimulation showed that intravascular electrodes provide sufficient broadband fidelity to record high-frequency, physiological events that may also prove useful in localizing seizure onset zones. As intravascular techniques have transformed cardiology, so intravascular neurophysiology may transform intracranial monitoring, in general, and the treatment of epilepsy, in particular.

CyberKnife radiosurgical rhizotomy for the treatment of atypical trigeminal nerve pain.

OBJECT Patients with atypical trigeminal neuralgia (TN) have unilateral pain in the trigeminal distribution that is dull, aching, or burning in nature and is constant or nearly constant. Studies of most radiosurgical and surgical series have shown lower response rates in patients with atypical TN. This study represents the first report of the treatment of atypical TN with frameless CyberKnife stereotactic radiosurgery (SRS). METHODS Between 2002 and 2007, 7 patients that satisfied the criteria for atypical TN and underwent SRS were included in our study. A 6-8-mm segment of the trigeminal nerve was targeted, excluding the proximal 3 mm at the brainstem. All patients were treated in a single session with a median maximum dose of 78 Gy and a median marginal dose of 64 Gy. RESULTS Outcomes in 7 patients with a mean age of 61.6 years and a median follow-up of 20 months are reported. Following SRS, 4 patients had complete pain relief, 2 had minimal pain relief with some decrease in the intensity of their pain, and 1 patient experienced no pain relief. Pain relief was reported within 1 week of SRS in 4 patients and at 4 months in 2 patients. After a median follow-up of 28 months, pain did not recur in any of the 4 patients who had reported complete pain relief. Complications after SRS included bothersome numbness in 3 patients and significant dysesthesias in 1 patient. CONCLUSIONS The authors have previously reported a 90% rate of excellent pain relief in patients with classic TN treated with CyberKnife SRS. Compared with patients with classic TN, patients with atypical TN have a lower rate of pain relief. Nevertheless, the nearly 60% rate of success after SRS achieved in this study is still comparable to or better than results achieved with any other treatment modality for atypical TN.

Paroxysmal Sympathetic Hyperactivity After Traumatic Brain Injury

A 35-year-old male was the unrestrained driver in a rollover motor vehicle accident from which he was ejected. He was initially comatose, with anisocoria and bilaterally unreactive pupils, absent oculocephalic, corneal, cough and gag reflexes, and no motor response to painful stimulus, but initiating respirations on his own (GCS 3T, FOUR score E0 M0 B0 R1 [1]). Shortly after admission, he developed extensor posturing, elevating his exam to GCS 4T, FOUR score E0 M1 B0 R1. However, his exam did not improve further. Head CT demonstrated small petechial hemorrhages at the gray/white junction, corpus callosum, basal ganglia, and in the interpeduncular cistern, consistent with diffuse axonal injury (Fig. 1). An intracranial pressure monitor was placed, and intracranial pressures were wellcontrolled over the next several days without requiring any interventions. Three days after the accident, the patient developed intermittent episodes of tachycardia with tachypnea, hypertension, fever, profuse sweating, and brisk extensor posturing, consistent with paroxysmal sympathetic hyperactivity [2, 3] (Video in Supplementary material). Paroxysmal sympathetic hyperactivity (PSH) can occur following traumatic brain injury with axonal shear injury, due to disinhibition of subcortical sympathoexcitatory structures [3]. This may have an early and late onset, and is most frequently seen in younger patients. The classic features of these episodes include at least four of the following: profuse sweating, tachycardia, hypertension, tachypnea, fever and extensor posturing, and occur transiently without any other cause [4]. PSH has been previously called diencephalic seizures, but EEGs in these patients have always been normal. The typical clinical features were present in our patient, and were never associated with twitches or decrease in responsiveness that may indicate seizures. PSH typically responds most effectively to a combination of opiate agonist and nonselective beta blockade [4, 5]. Bromocriptine and clonidine may also be used, but with less consistent results [4, 5], and gabapentin is gaining more widespread use for long term effectiveness. In our patient, the episodes were initially treated with beta blockade with propranolol, but did not respond. A combination of clonidine and morphine given during acute episodes was most effective in halting them. Gabapentin was started two days later for longer-term control. However, his neurologic exam failed to improve, care was withdrawn at the strong request of the family and he expired soon after extubation. Paroxysmal sympathetic hyperactivity is a common occurrence in catastrophic neurologic injuries leading to persistent vegetative state. These manifestations are often mistaken for rigors or convulsions and are commonly inadequately treated. Electronic supplementary material The online version of this article (doi:10.1007/s12028-010-9381-y) contains supplementary material, which is available to authorized users.