W. Jeffrey Elias

A Randomized Trial of Focused Ultrasound Thalamotomy for Essential Tremor

BACKGROUND Uncontrolled pilot studies have suggested the efficacy of focused ultrasound thalamotomy with magnetic resonance imaging (MRI) guidance for the treatment of essential tremor. METHODS We enrolled patients with moderate-to-severe essential tremor that had not responded to at least two trials of medical therapy and randomly assigned them in a 3:1 ratio to undergo unilateral focused ultrasound thalamotomy or a sham procedure. The Clinical Rating Scale for Tremor and the Quality of Life in Essential Tremor Questionnaire were administered at baseline and at 1, 3, 6, and 12 months. Tremor assessments were videotaped and rated by an independent group of neurologists who were unaware of the treatment assignments. The primary outcome was the between-group difference in the change from baseline to 3 months in hand tremor, rated on a 32-point scale (with higher scores indicating more severe tremor). After 3 months, patients in the sham-procedure group could cross over to active treatment (the open-label extension cohort). RESULTS Seventy-six patients were included in the analysis. Hand-tremor scores improved more after focused ultrasound thalamotomy (from 18.1 points at baseline to 9.6 at 3 months) than after the sham procedure (from 16.0 to 15.8 points); the between-group difference in the mean change was 8.3 points (95% confidence interval [CI], 5.9 to 10.7; P<0.001). The improvement in the thalamotomy group was maintained at 12 months (change from baseline, 7.2 points; 95% CI, 6.1 to 8.3). Secondary outcome measures assessing disability and quality of life also improved with active treatment (the blinded thalamotomy cohort)as compared with the sham procedure (P<0.001 for both comparisons). Adverse events in the thalamotomy group included gait disturbance in 36% of patients and paresthesias or numbness in 38%; these adverse events persisted at 12 months in 9% and 14% of patients, respectively. CONCLUSIONS MRI-guided focused ultrasound thalamotomy reduced hand tremor in patients with essential tremor. Side effects included sensory and gait disturbances. (Funded by InSightec and others; ClinicalTrials.gov number, NCT01827904.).

Incidence of symptomatic hemorrhage after stereotactic electrode placement

OBJECT Intracranial hemorrhage (ICH) is the most significant complication associated with the placement of stereotactic intracerebral electrodes. Previous reports have suggested that hypertension and the use of microelectrode recording (MER) are risk factors for cerebral hemorrhage. The authors evaluated the incidence of symptomatic ICH in a large cohort of patients with various diseases treated with stereotactic electrode placement. They examined the effect of comorbidities on the risk of ICH and independently assessed the risks associated with age, sex, use of MER, diagnosis, target location, hypertension, and previous use of anticoagulant medications. The authors also evaluated the effect of hemorrhage on length of hospital stay and discharge disposition. METHODS Between 1991 and 2005, 567 electrodes were placed by two neurosurgeons during 337 procedures in 259 patients. Deep brain stimulation (DBS) was performed in 167 procedures, radiofrequency lesioning (RFL) of subcortical structures in 74, and depth electrodes were used in 96 procedures in patients with epilepsy. Electrodes were grouped according to target, patient diagnosis, use of MER, patient history of hypertension, and patient prior use of anticoagulant medication (stopped 10 days before surgery). The Charlson Comorbidity Index (CCI) was used to evaluate the effect of comorbidities. The CCI score, patient age, length of hospital stay, and discharge status were continuous variables. Symptomatic hemorrhages were grouped as transient or leading to permanent neurological deficits. RESULTS The risk of hemorrhage leading to permanent neurological deficits in this study was 0.7%, and the risk of symptomatic hemorrhage was 1.2%. A patient history of hypertension was the most significant factor associated with hemorrhage (p = 0.007). Older age, male sex, and a diagnosis of Parkinson disease (PD) were also significantly associated with hemorrhage (p = 0.01, 0.04, 0.007, respectively). High CCI scores, specific target locations, and prior use of anticoagulant therapy were not associated with an increased risk of hemorrhage. The use of MER was not found to be correlated with an increased hemorrhage rate (p = 0.34); however, the number of hemorrhages in the patients who underwent DBS was insufficient to draw definitive conclusions. The mean length of stay for the DBS, RFL, and depth electrode patient groups was 2.9, 2.6, and 11.0 days, respectively. For patients who received DBS and RFL, the mean duration of hospitalization in cases of symptomatic hemorrhage was 8.2 days compared with 2.7 days in those without hemorrhaging (p < 0.0001). Three of the seven patients with symptomatic hemorrhages were discharged home. CONCLUSIONS The placement of stereotactic electrodes is generally safe, with a symptomatic hemorrhage rate of 1.2%, and a 0.7% rate of permanent neurological deficit. Consistent with prior reports, this study confirms that hypertension is a significant risk factor for hemorrhage. Age, male sex, and diagnosis of PD were also significant risk factors. Patients with symptomatic hemorrhage had longer hospital stays and were less likely to be discharged home.

Cortical and subcortical brain shift during stereotactic procedures

OBJECT The success of stereotactic surgery depends upon accuracy. Tissue deformation, or brain shift, can result in clinically significant errors. The authors measured cortical and subcortical brain shift during stereotactic surgery and assessed several variables that may affect it. METHODS Preoperative and postoperative magnetic resonance imaging volumes were fused and 3D vectors of deviation were calculated for the anterior commissure (AC), posterior commissure (PC), and frontal cortex. Potential preoperative (age, diagnosis, and ventricular volume), intraoperative (stereotactic target, penetration of ventricles, and duration of surgery), and postoperative (volume of pneumocephalus) variables were analyzed and correlated with cortical (frontal cortex) and subcortical (AC, PC) deviations. RESULTS Of 66 cases, nine showed a shift of the AC by more than 1.5 mm, and five by more than 2.0 mm. The largest AC shift was 5.67 mm. Deviation in the x, y, and z dimensions for each case was determined, and most of the cortical and subcortical shift occurred in the posterior direction. The mean 3D vector deviations for frontal cortex, AC, and PC were 3.5 +/- 2.0, 1.0 +/- 0.8, and 0.7 +/- 0.5 mm, respectively. The mean change in AC-PC length was -0.2 +/- -0.9 mm (range -4.28 to 1.66 mm). The volume of postoperative pneumocephalus, assumed to represent cerebrospinal fluid (CSF) loss, was significantly correlated with shift of the frontal cortex (r = 0.640, 64 degrees of freedom, p < 0.001) and even more strongly with shift of the AC (r = 0.754, p < 0.001). No other factors were significantly correlated with AC shift. Interestingly, penetration of the ventricles during electrode insertion, whether unilateral or bilateral, did not affect volume of pneumocephalus. CONCLUSIONS Cortical and subcortical brain shift occurs during stereotactic surgery as a direct function of the volume of pneumocephalus, which probably reflects the volume of CSF that is lost. Clinically significant shifts appear to be uncommon, but stereotactic surgeons should be vigilant in preventing CSF loss.

Bipolar deep brain stimulation permits routine EKG, EEG, and polysomnography

As the population of patients treated with deep brain stimulation (DBS) grows and the patients age, more will require routine or emergent electrophysiologic tests. DBS artifact may render these uninterpretable, whereas stopping DBS may release symptoms that confound evaluation. The authors find that monopolar, but not bipolar, stimulation produces significant artifact during EKG, EEG, and polysomnography.

Solitary sarcoid granuloma of the cerebellopontine angle: a case report

BACKGROUND Sarcoidosis involves the nervous system about 5% of the time and usually manifests as a granulomatous inflammation of the basal meninges and hypothalamus. Cases which are strictly isolated to the central nervous system occur infrequently; rarely, they may present as an intracranial mass. METHODS We present the case of a solitary sarcoid granuloma at the cerebellopontine angle in a 42-year-old female who presented with headache, facial numbness, and hearing loss. RESULTS A suboccipital craniectomy was performed and the lesion was noted to be grossly adherent to the lower cranial nerves and skull base. The lesion was misdiagnosed as a meningioma with preoperative magnetic resonance imaging and intraoperative histology, and perhaps additional morbidity resulted. CONCLUSION We present this case in order to demonstrate the importance of differentiating these dural-based lesions and propose that cases of neurosarcoidosis presenting as a solitary granuloma be treated with surgical debulking and immunosuppression.

The emerging role of transcranial magnetic resonance imaging–guided focused ultrasound in functional neurosurgery

To review the emerging role of transcranial MR‐guided focused ultrasound as a treatment and research modality for functional neurological disorders, we summarize recent clinical and preclinical studies. Clinical trials have investigated the safety and efficacy of thermal lesions created by transcranial, high‐intensity focused ultrasound. Preclinical work has additionally investigated the ability to disrupt the blood–brain barrier and to produce reversible neuromodulation with focused ultrasound utilizing lower intensities. We discuss ongoing trials and future avenues of investigation.

132 A Randomized, Sham-Controlled Trial of Transcranial Magnetic Resonance-Guided Focused Ultrasound Thalamotomy Trial for the Treatment of Tremor-Dominant, Idiopathic Parkinson Disease.

INTRODUCTION Traditional stereotactic radiofrequency thalamotomy has been used with success in medication-refractory tremor-dominant Parkinson disease (PD). Recently, transcranial magnetic resonance-guided focused ultrasound (MRgFUS) has been used to successfully perform thalamotomy for essential tremor. We designed a double-blinded, randomized controlled trial to investigate the effectiveness of MRgFUS thalamotomy in tremor-dominant PD. METHODS Patients with medication-refractory, tremor-dominant PD were enrolled in the 2-center study and randomly assigned 1:2 to receive either a sham procedure or treatment. After the 3-month blinded phase, the sham group was offered treatment. Outcome was measured with blinded Clinical Rating Scale for Tremor (CRST) and Unified Parkinsons Disease Rating Scale (UPDRS) ratings. The primary outcome compared improvement in hand tremor between the treatment and sham procedure at 3 months. Secondary outcomes were measured with UPDRS and hand tremor at 12 months. Safety was assessed with MRI, adverse events, and comprehensive neurocognitive assessment. RESULTS Twenty-seven patients were enrolled and 6 were randomly assigned to a sham procedure. For the primary outcome assessment, there was a mean 50% improvement in hand tremor from MRgFUS thalamotomy at 3 months compared with a 22% improvement from the sham procedures (P = .088). The 1-year tremor scores for all 19 patients treated with 1-year follow-up data (blinded and unblinded) showed a reduction in tremor scores of 40.6% (P = .0154) and a mean reduction in medicated UPDRS motor scores of 3.7 (32%, P = .033). Sham patients had a notable placebo effect with a mean 21.5% improvement in tremor scores at 3 months. Twenty-seven patients completed the primary analysis, 19 patients completed the 12-month assessment, 3 patients opted for deep brain stimulation, 3 were lost to follow-up, 1 patient opted for no treatment, and 1 is pending a 12-month evaluation. CONCLUSION Transcranial MRgFUS demonstrates a trend toward improvement in hand tremor, and a clinically significant reduction in mean UPDRS. A significant placebo response was noted in the randomized trial.cause of intractable epilepsy in children. Seizure freedom following resection of FCD is determined by complete resection of the dysplastic cortical tissue.However, difficulty with intraoperative identification of the FCD lesion may limit the ability to achieve the surgical objective of complete extirpation of these lesions. The use of intraoperative magnetic resonance imaging (iMRI) may aid in real-time detection of these lesions and improve seizure control outcomes compared with traditional resective surgery.

Cosmetic and functional outcomes following paramedian and anterolateral retroperitoneal access in anterior lumbar spine surgery

OBJECT In this paper, the authors review the functional and cosmetic outcomes and complications in 300 patients who underwent treatment for lumbar spine disease via either an anterior paramedian or conventional anterolateral retroperitoneal approach. METHODS Seven surgeons performed anterior lumbar surgeries in 300 patients between August 2004 and December 2006. One hundred and eighty patients were treated with an anterior paramedian approach, and 120 patients with an anterolateral retroperitoneal approach. An access surgeon was used in 220 cases (74%). Postoperative evaluation in all patients consisted of clinic visits, assessment with the modified Scoliosis Research Society-30 instrument, as well as a specific questionnaire relating to wound appearance and patient satisfaction with the wound. RESULTS At a mean follow-up of 31 months (range 12-47 months), the mean Scoliosis Research Society-30 score (out of 25) was 21.2 in the patients who had undergone the anterior paramedian approach and 19.4 in those who had undergone the anterolateral retroperitoneal approach (p = 0.005). The largest differences in quality of life measures were observed in the areas of pain control (p = 0.001), self-image (p = 0.004), and functional activity (p = 0.003), with the anterior paramedian group having higher scores in all 3 categories. Abdominal bulging in the vicinity of the surgical site was the most common wound complication observed and was reported by 22 patients in the anterolateral retroperitoneal group (18%), and 2 patients (1.1%) in the anterior paramedian group. Exposures of >or= 3 levels with the anterolateral approach were associated with abdominal bulging (p = 0.04), while 1- or 2-level exposures were not (p > 0.05). Overall satisfaction with incisional appearance was higher in patients with an anterior paramedian incision (p = 0.001) and with approaches performed by an access surgeon (p = 0.004). CONCLUSIONS Patients who undergo an anterior paramedian approach to the lumbar spine have a higher quality of life and better cosmetic outcomes than patients undergoing an anterolateral retroperitoneal approach.

Small cell lung carcinoma causing epidural hematoma: case report.

BACKGROUND Epidural hematoma usually stems from trauma, yet it may occur from other etiologies, including neoplasms. We present a case of small cell lung carcinoma with focal hemorrhagic central nervous system metastasis producing an epidural hematoma, and review the associated literature. CLINICAL PRESENTATION A 67-year-old man was undergoing chemotherapy for small cell carcinoma of the lung. Acute neurologic deterioration resulted from a large parietal epidural hematoma of non-traumatic origin. INTERVENTION The clot was evacuated via craniotomy with marked improvement in his clinical state. Metastatic tumor was present in the scalp, muscle, bone, and dura. No gross brain invasion was apparent. CONCLUSIONS This case illustrates the wisdom of including metastatic disease in the differential diagnosis of intracranial hemorrhage. Even epidural hematoma may result from metastatic cancer. The prevalence of lung carcinoma and the aging of the population may produce an increased appearance of this phenomenon. Appropriate evaluation and rapid intervention will aid the patient in both the acute and long-term phases, and should improve the quality of survival.

Safety and Efficacy of Focused Ultrasound Thalamotomy for Patients With Medication-Refractory, Tremor-Dominant Parkinson Disease: A Randomized Clinical Trial

Importance Clinical trials have confirmed the efficacy of focused ultrasound (FUS) thalamotomy in essential tremor, but its effectiveness and safety for managing tremor-dominant Parkinson disease (TDPD) is unknown. Objective To assess safety and efficacy at 12-month follow-up, accounting for placebo response, of unilateral FUS thalamotomy for patients with TDPD. Design, Setting, and Participants Of the 326 patients identified from an in-house database, 53 patients consented to be screened. Twenty-six were ineligible, and 27 were randomized (2:1) to FUS thalamotomy or a sham procedure at 2 centers from October18, 2012, to January 8, 2015. The most common reasons for disqualification were withdrawal (8 persons [31%]), and not being medication refractory (8 persons [31%]). Data were analyzed using intention-to-treat analysis, and assessments were double-blinded through the primary outcome. Interventions Twenty patients were randomized to unilateral FUS thalamotomy, and 7 to sham procedure. The sham group was offered open-label treatment after unblinding. Main Outcomes and Measures The predefined primary outcomes were safety and difference in improvement between groups at 3 months in the on-medication treated hand tremor subscore from the Clinical Rating Scale for Tremor (CRST). Secondary outcomes included descriptive results of Unified Parkinson’s Disease Rating Scale (UPDRS) scores and quality of life measures. Results Of the 27 patients, 26 (96%) were male and the median age was 67.8 years (interquartile range [IQR], 62.1-73.8 years). On-medication median tremor scores improved 62% (IQR, 22%-79%) from a baseline of 17 points (IQR, 10.5-27.5) following FUS thalamotomy and 22% (IQR, −11% to 29%) from a baseline of 23 points (IQR, 14.0-27.0) after sham procedures; the between-group difference was significant (Wilcoxon P = .04). On-medication median UPDRS motor scores improved 8 points (IQR, 0.5-11.0) from a baseline of 23 points (IQR, 15.5-34.0) following FUS thalamotomy and 1 point (IQR, −5.0 to 9.0) from a baseline of 25 points (IQR, 15.0-33.0) after sham procedures. Early in the study, heating of the internal capsule resulted in 2 cases (8%) of mild hemiparesis, which improved and prompted monitoring of an additional axis during magnetic resonance thermometry. Other persistent adverse events were orofacial paresthesia (4 events [20%]), finger paresthesia (1 event [5%]), and ataxia (1 event [5%]). Conclusions and Relevance Focused ultrasound thalamotomy for patients with TDPD demonstrated improvements in medication-refractory tremor by CRST assessments, even in the setting of a placebo response. Trial Registration ClinicalTrials.gov identifier NCT01772693