Chronic Encapsulated Expanding Hematoma After Gamma Knife Thalamotomy for Essential Tremor.

There have been no previous reports of chronic encapsulated expanding hematoma after Gamma Knife thalamotomy. The present case underwent Gamma Knife thalamotomy for essential tremor at the age of 78 years. Three- and 12-month posttreatment magnetic resonance imaging (MRI) showed small T2 high-intensity lesions on the target and along with the internal capsule. Hemiparesis developed 17 months after the treatment. Twenty months post treatment, T2-MRI showed a hypointense mass across the target and internal capsule. Gradual expansion of the mass was confirmed on MRI at 26-38 months. A 54-month posttreatment MRI showed marked expansion of the mass with multiple cysts surrounded by a T2-hypointense rim. Gadolinium-enhanced T1-MRI showed partial enhancement of the mass. MRI findings suggested a radiation-induced cavernoma. Hemiparesis, dysesthesia, and pain on the right side of the body persisted even after steroid therapy for several months. Long-term careful observation is necessary after Gamma Knife thalamotomy.

Lesions of the cerebello-thalamic tract rather than the ventral intermediate nucleus determine the outcome of focused ultrasound therapy in essential tremor: A 3T and 7T MRI-study.

INTRODUCTION: The ventral intermediate nucleus of the thalamus (VIM) is an important relay station receiving cerebellar and pallidal fiber tracts. Data on structural visualization of the VIM however is limited and uncertainty prevails to what extent lesional approaches to treat tremor affect the VIM itself or passing tracts. The aim of the study was to analyze the localization of individual lesions with respect to the VIM and the cerebello-thalamic tract (CTT). METHODS: We employed ultrahigh resolution (7 Tesla) MRI to delineate the VIM and performed 3 T-DTI-imaging pre- and post-interventional in seven ET patients undergoing transcranial magnetic resonance guided focused ultrasound (tcMRgFUS). Tremor improvement was measured using a modified subscore of the Clinical Rating Scale for Tremor. RESULTS: All subjects showed substantial tremor improvement (88.5%, range 80.7%-94,8%) after tcMRgFUS. We found only a minor overlap of the lesions with the VIM (4%, range 1%-7%) but a larger overlap with the CTT (43%, range 23%-60%) in all subjects. CONCLUSIONS: Lesions within the CTT rather than the VIM seem to drive the tremorlytic response and clinical improvement in tcMRgFUS.

Relative increase in cerebellar gray matter in young onset essential tremor: Evidence from voxel-based morphometry analysis.

This study is to investigate the presence of brain gray matter abnormalities in young onset essential tremor (ET) patients with arm tremor. Thirty ET patients together with 30 healthy volunteers were taken as candidates. Magnetic resonance imaging (MRI) was performed and voxel-based morphometry was used to compare gray matter density between the patients and volunteers. Washington Heights-Inwood Genetic Study of Essential Tremor (WHIGET) rating scale was applied to assess tremor severity in the patients. Eventually Twenty-Seven ET patients and Twenty-Seven volunteers were enrolled in the study. Voxel-based morphometry showed significant expansion of the bilateral cerebellum, occipital fusiform cortices, right inferior temporal gyrus, and precentral lobes (P < 0.05, TFCE corrected). Decrease in gray matter was detected only in the left parietal lobe. Region of interest analysis showed volume enlargement in thalamus, midbrain, and precuneus (P < 0.05, TFCE corrected). Importantly, significant negative correlation was found between the lateralized index of cerebellum and the tremor score which might implicate that the altered rightward lateralization in the cerebellum is possibly a response of the tremor effects in ET patients. Cerebellar gray matter expansion in young onset ET patients with arm tremor might be the result of compensation towards decline of cerebellar function.

Connectivity profile of thalamic deep brain stimulation to effectively treat essential tremor.

Essential tremor is the most prevalent movement disorder and is often refractory to medical treatment. Deep brain stimulation offers a therapeutic approach that can efficiently control tremor symptoms. Several deep brain stimulation targets (ventral intermediate nucleus, zona incerta, posterior subthalamic area) have been discussed for tremor treatment. Effective deep brain stimulation therapy for tremor critically involves optimal targeting to modulate the tremor network. This could potentially become more robust and precise by using state-of-the-art brain connectivity measurements. In the current study, we used two normative brain connectomes (structural and functional) to show the pattern of effective deep brain stimulation electrode connectivity in 36 patients with essential tremor. Our structural and functional connectivity models were significantly predictive of postoperative tremor improvement in out-of-sample data (P < 0.001 for both structural and functional leave-one-out cross-validation). Additionally, we segregated the somatotopic brain network based on head and hand tremor scores. These resulted in segregations that mapped onto the well-known somatotopic maps of both motor cortex and cerebellum. Crucially, this shows that slightly distinct networks need to be modulated to ameliorate head versus hand tremor and that those networks could be identified based on somatotopic zones in motor cortex and cerebellum. Finally, we propose a multi-modal connectomic deep brain stimulation sweet spot that may serve as a reference to enhance clinical care, in the future. This spot resided in the posterior subthalamic area, encroaching on the inferior borders of ventral intermediate nucleus and sensory thalamus. Our results underscore the importance of integrating brain connectivity in optimizing deep brain stimulation targeting for essential tremor.

A rapid beam simulation framework for transcranial focused ultrasound.

Transcranial focused ultrasound is a non-invasive therapeutic modality that can be used to treat essential tremor. Beams of energy are focused into a small spot in the thalamus, resulting in tissue heating and ablation. Here, we report on a rapid 3D numeric simulation framework that can be used to predict focal spot characteristics prior to the application of ultrasound. By comparing with magnetic resonance proton resonance frequency shift thermometry (MR thermometry) data acquired during treatments of essential tremor, we verified that our simulation framework can be used to predict focal spot position, and with patient-specific calibration, predict focal spot temperature rise. Preliminary data suggests that lateral smearing of the focal spot can be simulated. The framework may also be relevant for other therapeutic ultrasound applications such as blood brain barrier opening and neuromodulation.

Focused ultrasound thalamotomy location determines clinical benefits in patients with essential tremor.

Magnetic resonance guided focused ultrasound (MRgFUS) thalamotomy is a novel and minimally invasive ablative treatment for essential tremor. The size and location of therapeutic lesions producing the optimal clinical benefits while minimizing adverse effects are not known. We examined these relationships in patients with essential tremor undergoing MRgFUS. We studied 66 patients with essential tremor who underwent MRgFUS between 2012 and 2017. We assessed the Clinical Rating Scale for Tremor (CRST) scores at 3 months after the procedure and tracked the adverse effects (sensory, motor, speech, gait, and dysmetria) 1 day (acute) and 3 months after the procedure. Clinical data associated with the postoperative Day 1 lesions were used to correlate the size and location of lesions with tremor benefit and acute adverse effects. Diffusion-weighted imaging was used to assess whether acute adverse effects were related to lesions encroaching on nearby major white matter tracts (medial lemniscus, pyramidal, and dentato-rubro-thalamic). The area of optimal tremor response at 3 months after the procedure was identified at the posterior portion of the ventral intermediate nucleus. Lesions extending beyond the posterior region of the ventral intermediate nucleus and lateral to the lateral thalamic border were associated with increased risk of acute adverse sensory and motor effects, respectively. Acute adverse effects on gait and dysmetria occurred with lesions inferolateral to the thalamus. Lesions inferolateral to the thalamus or medial to the ventral intermediate nucleus were also associated with acute adverse speech effects. Diffusion-weighted imaging revealed that lesions associated with adverse sensory and gait/dysmetria effects compromised the medial lemniscus and dentato-rubro-thalamic tracts, respectively. Lesions associated with adverse motor and speech effects encroached on the pyramidal tract. Lesions larger than 170 mm3 were associated with an increased risk of acute adverse effects. Tremor improvement and acute adverse effects of MRgFUS for essential tremor are highly dependent on the location and size of lesions. These novel findings could refine current MRgFUS treatment planning and targeting, thereby improving clinical outcomes in patients.

Predicting lesion size by accumulated thermal dose in MR-guided focused ultrasound for essential tremor.

PURPOSE: To correlate the accumulated thermal dose (ATD) with lesion size in magnetic resonance (MR)-guided focused ultrasound (MRgFUS) thalamotomy to help guide future clinical treatments. MATERIALS AND METHODS: Thirty-six patients with medication-refractory essential tremor were treated using a commercial MRgFUS brain system (ExAblate 4000, InSightec) in a 3T MR scanner (MR750, GE Healthcare). Intraoperative MR-thermometry was performed to measure the induced temperature and thermal dose distributions (thermal coefficient = -0.00909 ppm/°C). The ATD was calculated over multiple sonications with appropriate corrections for spatial-shifting artifacts. The ATD profile sizes obtained for dose values of 17, 40, 100, 200, and 240 cumulative equivalent minutes at 43°C (CEM) were correlated with the corresponding lesion sizes measured via axial T1- and T2-weighted MR images acquired 1 day post-treatment. RESULTS: Of a total of 232 included sonications, 83 required corrections for off-resonance-induced spatial-shifting artifacts (correction range = [1.1,2.2] mm). The mean lesion sizes measured on T2-weighted MR images (6.2 ± 1.3 mm, mean ± SD) were 15% larger than those measured on corresponding T1-weighted MR images (5.3 ± 1.2 mm, mean ± SD). The ATD values that provided the best correlations with the measured lesion sizes on T2- and T1-weighted MR images were 100 and 200 CEM, respectively. CONCLUSION: The ATD was correlated with lesion size measured 1 day following MRgFUS thalamotomy for essential tremor. These data provide useful information for predicting brain lesion size and determining treatment endpoints in future clinical MRgFUS procedures.

A widespread visually-sensitive functional network relates to symptoms in essential tremor.

Essential tremor is a neurological syndrome of heterogeneous pathology and aetiology that is characterized by tremor primarily in the upper extremities. This tremor is commonly hypothesized to be driven by a single or multiple neural oscillator(s) within the cerebello-thalamo-cortical pathway. Several studies have found an association of blood-oxygen level-dependent (BOLD) signal in the cerebello-thalamo-cortical pathway with essential tremor, but there is behavioural evidence that also points to the possibility that the severity of tremor could be influenced by visual feedback. Here, we directly manipulated visual feedback during a functional MRI grip force task in patients with essential tremor and control participants, and hypothesized that an increase in visual feedback would exacerbate tremor in the 4-12 Hz range in essential tremor patients. Further, we hypothesized that this exacerbation of tremor would be associated with dysfunctional changes in BOLD signal and entropy within, and beyond, the cerebello-thalamo-cortical pathway. We found that increases in visual feedback increased tremor in the 4-12 Hz range in essential tremor patients, and this increase in tremor was associated with abnormal changes in BOLD amplitude and entropy in regions within the cerebello-thalamo-motor cortical pathway, and extended to visual and parietal areas. To determine if the tremor severity was associated with single or multiple brain region(s), we conducted a birectional stepwise multiple regression analysis, and found that a widespread functional network extending beyond the cerebello-thalamo-motor cortical pathway was associated with changes in tremor severity measured during the imaging protocol. Further, this same network was associated with clinical tremor severity measured with the Fahn, Tolosa, Marin Tremor Rating Scale, suggesting this network is clinically relevant. Since increased visual feedback also reduced force error, this network was evaluated in relation to force error but the model was not significant, indicating it is associated with force tremor but not force error. This study therefore provides new evidence that a widespread functional network is associated with the severity of tremor in patients with essential tremor measured simultaneously at the hand during functional imaging, and is also associated with the clinical severity of tremor. These findings support the idea that the severity of tremor is exacerbated by increased visual feedback, suggesting that designers of new computing technologies should consider using lower visual feedback levels to reduce tremor in essential tremor.

Increased glutamate + glutamine levels in the thalamus of patients with essential tremor: A preliminary proton MR spectroscopic study.

INTRODUCTION: The aim of this study was to investigate the thalamic biochemical profile in patients with essential tremor (ET), using proton magnetic resonance spectroscopy (1H-MRS), and to explore the correlations between clinical and biochemical data. METHODS: Sixteen patients with ET and 14 healthy controls participated in this study. After conventional MR imaging, single-voxel 1H-MRS (TR = 2000 ms; TE = 28 ms) was performed by using a PROBE-SV system implemented on a 3-T scanner. A voxel of 10 × 10 × 15 mm involving the ventrointermediate (Vim) nucleus was acquired in each thalamus of all subjects. Peak areas of N-acetyl-aspartate + N-acetyl-aspartyl-glutamate (NAA), creatine + phosphocreatine (Cr), glycerophosphocholine + phosphocholine (Cho), and glutamate + glutamine (Glx) were calculated using a version 6.3-1 K of the fitting program LCModel for each voxel. Comparative and correlation analyses were performed on the NAA, Cr, Cho, and Glx concentrations, as well as on the values of the NAA/Cr, a neural density marker, Cho/Cr, a membrane marker, and Glx/Cr, an intracellular neurotransmitter marker. RESULTS: Patients with ET showed a significant increase in Glx concentration and Glx/Cr ratio values in both thalami, compared to healthy controls, whereas no difference inter-group was found for the other metabolites and NAA/Cr and Cho/Cr ratio values. Of note, the tremor severity was positively related to increased Glx concentrations and Glx/Cr ratio values in ET group. CONCLUSIONS: Our study shows that 1H-MRS can highlight in vivo metabolic abnormalities in the thalami of ET patients, supporting the evidence that the increase of thalamic glutamatergic transmission can play a role in developing of tremor in ET.

Role of altered cerebello-thalamo-cortical network in the neurobiology of essential tremor.

INTRODUCTION: Essential tremor (ET) is the most common movement disorder among adults. Although ET has been recognized as a mono-symptomatic benign illness, reports of non-motor symptoms and non-tremor motor symptoms have increased its clinical heterogeneity. The neural correlates of ET are not clearly understood. The aim of this study was to understand the neurobiology of ET using resting state fMRI. METHODS: Resting state functional MR images of 30 patients with ET and 30 age- and gender-matched healthy controls were obtained. The functional connectivity of the two groups was compared using whole-brain seed-to-voxel-based analysis. RESULTS: The ET group had decreased connectivity of several cortical regions especially of the primary motor cortex and the primary somatosensory cortex with several right cerebellar lobules compared to the controls. The thalamus on both hemispheres had increased connectivity with multiple posterior cerebellar lobules and vermis. Connectivity of several right cerebellar seeds with the cortical and thalamic seeds had significant correlation with an overall score of Fahn-Tolosa-Marin tremor rating scale (FTM-TRS) as well as the subscores for head tremor and limb tremor. CONCLUSION: Seed-to-voxel resting state connectivity analysis revealed significant alterations in the cerebello-thalamo-cortical network in patients with ET. These alterations correlated with the overall FTM scores as well as the subscores for limb tremor and head tremor in patients with ET. These results further support the previous evidence of cerebellar pathology in ET.

Postmortem diffusion MRI of the human brainstem and thalamus for deep brain stimulator electrode localization.

Deep brain stimulation (DBS) is an established surgical therapy for medically refractory tremor disorders including essential tremor (ET) and is currently under investigation for use in a variety of other neurologic and psychiatric disorders. There is growing evidence that the anti-tremor effects of DBS for ET are directly related to modulation of the dentatorubrothalamic tract (DRT), a white matter pathway that connects the cerebellum, red nucleus, and ventral intermediate nucleus of the thalamus. Emerging white matter targets for DBS, like the DRT, will require improved three-dimensional (3D) reference maps of deep brain anatomy and structural connectivity for accurate electrode targeting. High-resolution diffusion MRI of postmortem brain specimens can provide detailed volumetric images of important deep brain nuclei and 3D reconstructions of white matter pathways with probabilistic tractography techniques. We present a high spatial and angular resolution diffusion MRI template of the postmortem human brainstem and thalamus with 3D reconstructions of the nuclei and white matter tracts involved in ET circuitry. We demonstrate registration of these data to in vivo, clinical images from patients receiving DBS therapy, and correlate electrode proximity to tractography of the DRT with improvement of ET symptoms.

Hcn1 is a tremorgenic genetic component in a rat model of essential tremor.

Genetic factors are thought to play a major role in the etiology of essential tremor (ET); however, few genetic changes that induce ET have been identified to date. In the present study, to find genes responsible for the development of ET, we employed a rat model system consisting of a tremulous mutant strain, TRM/Kyo (TRM), and its substrain TRMR/Kyo (TRMR). The TRM rat is homozygous for the tremor (tm) mutation and shows spontaneous tremors resembling human ET. The TRMR rat also carries a homozygous tm mutation but shows no tremor, leading us to hypothesize that TRM rats carry one or more genes implicated in the development of ET in addition to the tm mutation. We used a positional cloning approach and found a missense mutation (c. 1061 C>T, p. A354V) in the hyperpolarization-activated cyclic nucleotide-gated 1 channel (Hcn1) gene. The A354V HCN1 failed to conduct hyperpolarization-activated currents in vitro, implicating it as a loss-of-function mutation. Blocking HCN1 channels with ZD7288 in vivo evoked kinetic tremors in nontremulous TRMR rats. We also found neuronal activation of the inferior olive (IO) in both ZD7288-treated TRMR and non-treated TRM rats and a reduced incidence of tremor in the IO-lesioned TRM rats, suggesting a critical role of the IO in tremorgenesis. A rat strain carrying the A354V mutation alone on a genetic background identical to that of the TRM rats showed no tremor. Together, these data indicate that body tremors emerge when the two mutant loci, tm and Hcn1A354V, are combined in a rat model of ET. In this model, HCN1 channels play an important role in the tremorgenesis of ET. We propose that oligogenic, most probably digenic, inheritance is responsible for the genetic heterogeneity of ET.

Thalamic connectivity in patients with essential tremor treated with MR imaging-guided focused ultrasound: in vivo fiber tracking by using diffusion-tensor MR imaging.

PURPOSE: To use diffusion-tensor (DT) magnetic resonance (MR) imaging in patients with essential tremor who were treated with transcranial MR imaging-guided focused ultrasound lesion inducement to identify the structural connectivity of the ventralis intermedius nucleus of the thalamus and determine how DT imaging changes correlated with tremor changes after lesion inducement. MATERIALS AND METHODS: With institutional review board approval, and with prospective informed consent, 15 patients with medication-refractory essential tremor were enrolled in a HIPAA-compliant pilot study and were treated with transcranial MR imaging-guided focused ultrasound surgery targeting the ventralis intermedius nucleus of the thalamus contralateral to their dominant hand. Fourteen patients were ultimately included. DT MR imaging studies at 3.0 T were performed preoperatively and 24 hours, 1 week, 1 month, and 3 months after the procedure. Fractional anisotropy (FA) maps were calculated from the DT imaging data sets for all time points in all patients. Voxels where FA consistently decreased over time were identified, and FA change in these voxels was correlated with clinical changes in tremor over the same period by using Pearson correlation. RESULTS: Ipsilateral brain structures that showed prespecified negative correlation values of FA over time of -0.5 or less included the pre- and postcentral subcortical white matter in the hand knob area; the region of the corticospinal tract in the centrum semiovale, in the posterior limb of the internal capsule, and in the cerebral peduncle; the thalamus; the region of the red nucleus; the location of the central tegmental tract; and the region of the inferior olive. The contralateral middle cerebellar peduncle and bilateral portions of the superior vermis also showed persistent decrease in FA over time. There was strong correlation between decrease in FA and clinical improvement in hand tremor 3 months after lesion inducement (P < .001). CONCLUSION: DT MR imaging after MR imaging-guided focused ultrasound thalamotomy depicts changes in specific brain structures. The magnitude of the DT imaging changes after thalamic lesion inducement correlates with the degree of clinical improvement in essential tremor.

Structural changes in cerebellar outflow tracts after thalamotomy in essential tremor.

BACKGROUND: This study set out to determine whether structural changes are present outside the thalamus after thalamotomy in patients with essential tremor (ET), specifically in the cerebellorubrothalamic tracts. We hypothesized that diffusion tensor imaging (DTI) would detect these changes. METHODS: We collected DTI scans and analyzed differences in Fractional Anisotropy (FA) and Mean Diffusivity (MD) between the left and right superior and middle cerebellar peduncle in ET patients that have undergone unilateral, left, thalamotomy and ET patients that did not undergo thalamotomy (control group). We used classical ROI-based statistics to determine whether changes are present. RESULTS: We found decreased FA and increased MD values in the right superior cerebellar peduncle leading to the left, lesioned thalamus, only in the thalamotomy group. CONCLUSIONS: Our study suggests long-term structural changes in the cerebellorubrothalamic tract after thalamotomy. This contributes to further understanding of the biological mechanism following surgical lesions in the basal ganglia.

Thalamic physiology of intentional essential tremor is more like cerebellar tremor than postural essential tremor.

The neuronal physiological correlates of clinical heterogeneity in human essential tremor are unknown. We now test the hypothesis that thalamic neuronal and EMG activities during intention essential tremor are similar to those of the intention tremor which is characteristic of cerebellar lesions. Thalamic neuronal firing was studied in a cerebellar relay nucleus (ventral intermediate, Vim) and in a pallidal relay nucleus (ventral oral posterior, Vop) during stereotactic surgery for the treatment of tremor. Nine patients with essential tremor were divided clinically into two categories: one with a substantial component of tremor with intention (termed intention ET) and the other without (postural ET). These types of essential tremor were compared with patients having intention tremor plus other clinical signs of cerebellar disease (cerebellar tremor). Neurons in patients with either intention ET or cerebellar tremor had lower firing rates and lower spike×EMG coherence than those in patients with postural ET. Patients with intention ET had a lower spike×EMG phase lead than those with postural ET. Overall, thalamic activity measures of intention ET were different from postural ET but not apparently different from those of cerebellar tremor. One patient with the intention ET (number 4) had a good response to a left thalamotomy and then suffered a right cerebellar hemispheric infarct five years later. After the stroke the intention ET recurred, which is consistent with our hypothesis that intention ET is similar to that of the intention tremor which is characteristic of cerebellar lesions.

Gamma Knife thalamotomy for tremor in the magnetic resonance imaging era.

OBJECT: The surgical management of disabling tremor has gained renewed vigor with the availability of deep brain stimulation. However, in the face of an aging population of patients with increasing surgical comorbidities, noninvasive approaches for tremor management are needed. The authors' purpose was to study the technique and results of stereotactic radiosurgery performed in the era of MRI targeting. METHODS: The authors evaluated outcomes in 86 patients (mean age 71 years; number of procedures 88) who underwent a unilateral Gamma Knife thalamotomy (GKT) for tremor during a 15-year period that spanned the era of MRI-based target selection (1996-2011). Symptoms were related to essential tremor in 48 patients (19 age ≥ 80 years and 3 age ≥ 90 years), Parkinson disease in 27 patients (11 age ≥ 80 years [1 patient underwent bilateral procedures]), and multiple sclerosis in 11 patients (1 patient underwent bilateral procedures). A single 4-mm isocenter was used to deliver a maximum dose of 140 Gy to the posterior-inferior region of the nucleus ventralis intermedius. The Fahn-Tolosa-Marin clinical tremor rating scale was used to grade tremor, handwriting, and ability to drink. The median follow-up was 23 months. RESULTS: The mean tremor score was 3.28 ± 0.79 before and 1.81 ± 1.15 after (p < 0.0001) GKT; the mean handwriting score was 2.78 ± 0.82 and 1.62 ± 1.04, respectively (p < 0.0001); and the mean drinking score was 3.14 ± 0.78 and 1.80 ± 1.15, respectively (p < 0.0001). After GKT, 57 patients (66%) showed improvement in all 3 scores, 11 patients (13%) in 2 scores, and 2 patients (2%) in just 1 score. In 16 patients (19%) there was a failure to improve in any score. Two patients developed a temporary contralateral hemiparesis, 1 patient noted dysphagia, and 1 sustained facial sensory loss. CONCLUSIONS: Gamma Knife thalamotomy in the MRI era was a safe and effective noninvasive surgical strategy for medically refractory tremor in the elderly or those with contraindications to deep brain stimulation or stereotactic radiofrequency (thermal) thalamotomy.

White matter connectivity of human hypothalamus.

The macroscopic extrinsic white matter connectivity and the internal structure of the hypothalamus are still incompletely defined in humans. We investigated whether in-vivo diffusion tensor imaging tractography provides evidence of systematization according to hypothalamic compartmentalization. Six defined hypothalamic macroscopic compartments, preoptic, supraoptic, anteroventral, anterodorsal, lateral and posterior, were probed, within the right and left hemispheres of 14 subjects. Important new insights into the macroscopic structure of hypothalamus and white matter connections were found; the preoptic, anteroventral, lateral and posterior compartments are strongly connected to the cortex. The anteroventral connects particularly to the prefrontal cortex while the preoptic compartment connects mainly to the deep anterior brain. The anterodorsal connects mainly to the medial thalamus and the midline gray matter. There is a rightward frontal trend of hemispheric connectivity for the preoptic, anteroventral and lateral compartments. These findings may aid new neuromodulation applications and understanding in brain connectomics.

Gamma knife thalamotomy for disabling tremor: a blinded evaluation.

BACKGROUND: Gamma knife thalamotomy (GKT) has been used as a therapeutic option for patients with disabling tremor refractory to medications. Impressive improvement of tremor has been reported in the neurosurgical literature, but the reliability of such data has been questioned. OBJECTIVE: To prospectively evaluate clinical outcomes after GKT for disabling tremor with blinded assessments. DESIGN: Prospective study with blinded independent neurologic evaluations. SETTING: University hospital. PATIENTS: Consecutive patients who underwent unilateral GKT for essential tremor and Parkinson disease tremor at our center. These patients were unwilling or deemed unsuitable candidates for deep brain stimulation or other surgical procedures. INTERVENTIONS: Unilateral GKT and regular follow-up evaluations for up to 30 months, with blinded video evaluations by a movement disorders neurologist. MAIN OUTCOME MEASURES: Clinical outcomes, as measured by the Fahn-Tolosa-Marin Tremor Rating Scale and activities of daily living scores, and incidence of adverse events. RESULTS: From September 1, 2006, to November 30, 2008, 18 patients underwent unilateral GKT for essential tremor and Parkinson disease tremor at our center. Videos for 14 patients (11 with essential tremor, 3 with Parkinson disease tremor) with at least 6 months' postoperative follow-up were available for analysis (mean [SD] follow-up duration, 19.2 [7.3] months; range, 7-30 months). The Fahn-Tolosa-Marin Tremor Rating Scale activities of daily living scores improved significantly after GKT (P = .03; median and mean change scores, 2.5 and 2.7 points, respectively [range of scale was 0-27]), but there was no significant improvement in other Fahn-Tolosa-Marin Tremor Rating Scale items (P = .53 for resting tremor, P = .24 for postural tremor, P = .62 for action tremor, P = .40 for drawing, P > .99 for pouring water, P = .89 for head tremor). Handwriting and Unified Parkinson's Disease Rating Scale activities of daily living scores tended to improve (P = .07 and .11, respectively). Three patients developed delayed neurologic adverse events. CONCLUSIONS: Overall, we found that GKT provided only modest antitremor efficacy. Of the 2 patients with essential tremor who experienced marked improvement in tremor, 1 subsequently experienced a serious adverse event. Further prospective studies with careful neurologic evaluation of outcomes are necessary before GKT can be recommended for disabling tremor on a routine clinical basis.

Brain structural changes in essential tremor: voxel-based morphometry at 3-Tesla.

BACKGROUND: Abnormalities in cerebello-thalamo-cortical pathways have been suggested as a basis for essential tremor (ET). Two voxel-based morphometry (VBM) studies, each using a 1.5-T magnet, evaluated ET patients, leading to contradictory results. Using a 3-T magnet, we assessed whether white or gray matter changes occurred in ET patients vs. controls. METHODS: We recruited 19 ET patients (mean age 69.8+/-9.4 years) and 20 age and gender-matched controls. 3-T MRI data were analyzed using the Statistical Parametric Mapping (SPM) 5 package. RESULTS: In case-control comparisons, white matter changes were seen in several areas (right cerebellum, left medulla, right parietal lobe, and right limbic lobe); gray matter changes were seen in several areas as well (bilateral cerebellum, bilateral parietal lobes, right frontal lobe, and right insula) (p<0.001, uncorrected at a voxel level). Compared with controls, ET patients with severe tremor had white matter changes in the midbrain, both occipital lobes, and right frontal lobe, and gray matter changes bilaterally in the cerebellum (p<0.001, uncorrected at a voxel level). CONCLUSIONS: Structural white and gray abnormalities may be detected in ET patients using VBM and a high-field MRI scanner. Such changes may be related to the pathological substrates associated with this disease.