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Vibhor Krishna and Dong H. Kim

Object

Studies on risk factors for subarachnoid hemorrhage (SAH) show heterogeneity. For example, hypertension has been found to be a significant risk factor in some studies but not in others. The authors hypothesized that differences in the ethnicity of the populations studied could account for these findings.

Methods

A metaanalysis was performed using 17 case-control and 10 cohort studies that met specified inclusion criteria. The authors used a random-effect model to calculate the pooled effect estimates for current smoking, hypertension, and alcohol consumption. A meta–regression analysis was performed using the ethnic composition of the study populations as a covariate. Studies were classified as multiethnic or monoethnic, and the pooled effect estimates were compared.

Results

Analysis of the cohort studies yielded a pooled effect estimate or risk ratio of 3.18 (95% confidence interval [CI] 2.37–4.26) for current smoking, 3.05 (95% CI 2.09–4.44) for hypertension, and 2.46 (95% CI 1.42–4.24) for alcohol consumption at a rate of 150 g/week or more. The results were similar for the case-control studies. For current smoking, the ethnic composition of the study population was a statistically significant predictor of heterogeneity among case-control studies (p < 0.001, even after application of the Bonferroni correction). The risk for SAH among current smokers was higher in multiethnic populations (odds ratio 3.832) than in monoethnic populations (odds ratio 2.487).

Conclusions

The results of this metaanalysis suggest that differences in susceptibility to the harmful health effects of smoking may be one cause of the observed differences in SAH incidence for different ethnic groups. The role of ethnicity in risk factors for SAH should be considered in future studies.

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Vibhor Krishna, Francesco Sammartino, Philip Yee, David Mikulis, Matthew Walker, Gavin Elias and Mojgan Hodaie

OBJECTIVE

The diagnosis of Chiari malformation Type I (CM-I) is primarily based on the degree of cerebellar tonsillar herniation even though it does not always correlate with symptoms. Neurological dysfunction in CM-I presumably results from brainstem compression. With the premise that conventional MRI does not reveal brain microstructural changes, this study examined both structural and microstructural neuroimaging metrics to distinguish patients with CM-I from age- and sex-matched healthy control subjects.

METHODS

Eight patients with CM-I and 16 controls were analyzed. Image postprocessing involved coregistration of anatomical T1-weighted with diffusion tensor images using 3D Slicer software. The structural parameters included volumes of the posterior fossa, fourth ventricle, and tentorial angle. Fractional anisotropy (FA) was calculated separately in the anterior and posterior compartments of the lower brainstem.

RESULTS

The mean age of patients in the CM-I cohort was 42.6 ± 10.4 years with mean tonsillar herniation of 12 mm (SD 0.7 mm). There were no significant differences in the posterior fossa volume (p = 0.06) or fourth ventricular volume between the 2 groups (p = 0.11). However, the FA in the anterior brainstem compartment was significantly higher in patients with CM-I preoperatively (p = 0.001). The FA values normalized after Chiari decompression except for persistently elevated FA in the posterior brainstem compartment in patients with CM-I and syrinx.

CONCLUSIONS

In this case-control study, microstructural alterations appear to be reliably associated with the diagnosis of CM-I, with a significantly elevated FA in the lower brainstem in patients with CM-I compared with controls. More importantly, the FA values normalized after decompressive surgery. These findings should be validated in future studies to determine the significance of diffusion tensor imaging–based assessment of brainstem microstructural integrity as an adjunct to the clinical assessment in patients with CM-I.

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Sunil Patel, Vibhor Krishna, Joyce Nicholas, Charles M. Welzig and Cristian Vera

Object

Pulsatile arterial compression (AC) of the ventrolateral medulla (VLM) is hypothesized to produce the hypertension in a subset of patients with essential hypertension. In animals, a network of subpial neuronal aggregates in the VLM has been shown to control cardiovascular functions. Although histochemically similar, neurons have been identified in the retro-olivary sulcus (ROS) of the human VLM, but their function is unclear.

Methods

The authors recorded cardiovascular responses to electrical stimulation at various locations along the VLM surface, including the ROS, in patients who were undergoing posterior fossa surgery for trigeminal neuralgia. This vasomotor mapping of the medullary surface was performed using a bipolar electrode, with stimulation parameters ranging from 5- to 30-second trains (20–100 Hz), constant current (1.5–5 mA), and 0.1-msec pulse durations. Heart rate (HR) and blood pressure (BP) were recorded continuously from baseline (10 seconds before the stimulus) up to 1 minute poststimulus. In 6 patients, 17 stimulation responses in BP and HR were recorded.

Results

The frequency threshold for any cardiovascular response was 20 Hz; the stimulation intensity threshold ranged from 1.5 to 3 mA. In the first patient, all stimulation responses were significantly different from sham recordings (which consisted of electrodes placed without stimulations). Repeated stimulations in the lower ROS produced similar responses in 3 other patients. Two additional patients had similar responses to single stimulations in the lower ROS. Olive stimulation produced no response (control). Hypotensive and/or bradycardic responses were consistently followed by a reflex hypertensive response. Slight right/left differences were noted. No patient suffered short- or long-term effects from this stimulation.

Conclusions

This stimulation technique for vasomotor mapping of the human VLM was safe and reproducible. Neuronal aggregates near the surface of the human ROS may be important in cardiovascular regulation. This method of vasomotor mapping with measures of responses in sympathetic tone (microneurography) should yield additional data for understanding the neuronal network that controls cardiovascular functions in the human VLM. Further studies in which a concentric bipolar electrode is used to generate this type of vasomotor map should also increase understanding of the pathophysiological mechanisms of neurogenically mediated hypertension, and assist in the design of studies to prove the hypothesis that it is caused by pulsatile AC of the VLM.

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Francesco Sammartino, Dylan W. Beam, John Snell and Vibhor Krishna

Transcranial focused ultrasound (FUS) ablation is an emerging incision-less treatment for neurological disorders. The factors affecting FUS treatment efficiency are not well understood. Kranion is open-source software that allows the user to simulate the planning stages of FUS treatment and to “replay” previous treatments for off-line analysis. This study aimed to investigate the relationship between skull parameters and treatment efficiency and to create a metric to estimate temperature rise during FUS. CT images from 28 patients were analyzed to validate the use of Kranion. For stereotactic targets within each patient, individual transducer element incident angles, skull density ratio, and skull thickness measurements were recorded. A penetration metric (the “beam index”) was calculated by combining the energy loss from incident angles and the skull thickness. Kranion accurately estimated the patient’s skull and treatment parameters. The authors observed significant changes in incident angles with different targets in the brain. Using the beam index as a predictor of temperature rise in a linear-mixed-effects model, they were able to predict the average temperature rise at the focal point during ablation with < 21% error (55°C ± 3.8°C) in 75% of sonications, and with < 44% (55°C ± 7.9°C) in 97% of sonications. This research suggests that the beam index can improve the prediction of temperature rise during FUS. Additional work is required to study the relationship between temperature rise and lesion shape and clinical outcomes.

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Nicolas Kon Kam King, Vibhor Krishna, Diellor Basha, Gavin Elias, Francesco Sammartino, Mojgan Hodaie, Andres M. Lozano and William D. Hutchison

OBJECTIVE

The ventral intermediate nucleus (VIM) of the thalamus is not visible on structural MRI. Therefore, direct VIM targeting methods for stereotactic tremor surgery are desirable. The authors previously described a direct targeting method for visualizing the VIM and its structural connectivity using deterministic tractography. In this combined electrophysiology and imaging study, the authors investigated the electrophysiology within this tractography-defined VIM (T-VIM).

METHODS

Thalamic neurons were classified based on their relative location to the T-VIM: dorsal, within, and ventral to the T-VIM. The authors identified the movement-responsive cells (kinesthetic and tremor cells), performed spike analysis (firing rate and burst index), and local field potential analysis (area under the curve for 13–30 Hz). Tremor efficacy in response to microstimulation along the electrode trajectory was also assessed in relation to the T-VIM.

RESULTS

Seventy-three cells from a total of 9 microelectrode tracks were included for this analysis. Movement-responsive cells (20 kinesthetic cells and 26 tremor cells) were identified throughout the electrode trajectories. The mean firing rate and burst index of cells (n = 27) within the T-VIM are 18.8 ± 9.8 Hz and 4.5 ± 5.4, respectively. Significant local field potential beta power was identified within the T-VIM (area under the curve for 13–30 Hz = 6.6 ± 7.7) with a trend toward higher beta power in the dorsal T-VIM. The most significant reduction in tremor was also observed in the dorsal T-VIM.

CONCLUSIONS

The electrophysiological findings within the VIM thalamus defined by tractography, or T-VIM, correspond with the known microelectrode recording characteristics of the VIM in patients with tremor.

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Rosa Q. So, Vibhor Krishna, Nicolas Kon Kam King, Huijuan Yang, Zhuo Zhang, Francesco Sammartino, Andres M. Lozano, Richard A. Wennberg and Cuntai Guan

OBJECTIVE

The authors explored the feasibility of seizure detection and prediction using signals recorded from the anterior thalamic nucleus, a major target for deep brain stimulation (DBS) in the treatment of epilepsy.

METHODS

Using data from 5 patients (13 seizures in total), the authors performed a feasibility study and analyzed the performance of a seizure prediction and detection algorithm applied to simultaneously acquired scalp and thalamic electroencephalography (EEG). The thalamic signal was obtained from DBS electrodes. The applied algorithm used the similarity index as a nonlinear measure for seizure identification, with patient-specific channel and threshold selection. Receiver operating characteristic (ROC) curves were calculated using data from all patients and channels to compare the performance between DBS and EEG recordings.

RESULTS

Thalamic DBS recordings were associated with a mean prediction rate of 84%, detection rate of 97%, and false-alarm rate of 0.79/hr. In comparison, scalp EEG recordings were associated with a mean prediction rate of 71%, detection rate of 100%, and false-alarm rate of 1.01/hr. From the ROC curves, when considering all channels, DBS outperformed EEG for both detection and prediction of seizures.

CONCLUSIONS

This is the first study to compare automated seizure detection and prediction from simultaneous thalamic and scalp EEG recordings. The authors have demonstrated that signals recorded from DBS leads are more robust than EEG recordings and can be used to predict and detect seizures. These results indicate feasibility for future designs of closed-loop anterior nucleus DBS systems for the treatment of epilepsy.

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Francesco Sammartino, Vibhor Krishna, Tejas Sankar, Jason Fisico, Suneil K. Kalia, Mojgan Hodaie, Walter Kucharczyk, David J. Mikulis, Adrian Crawley and Andres M. Lozano

OBJECTIVE

The aim of this study was to evaluate the safety of 3-T MRI in patients with implanted deep brain stimulation (DBS) systems.

METHODS

This study was performed in 2 phases. In an initial phantom study, a Lucite phantom filled with tissue-mimicking gel was assembled. The system was equipped with a single DBS electrode connected to an internal pulse generator. The tip of the electrode was coupled to a fiber optic thermometer with a temperature resolution of 0.1°C. Both anatomical (T1- and T2-weighted) and functional MRI sequences were tested. A temperature change within 2°C from baseline was considered safe. After findings from the phantom study suggested safety, 10 patients with implanted DBS systems targeting various brain areas provided informed consent and underwent 3-T MRI using the same imaging sequences. Detailed neurological evaluations and internal pulse generator interrogations were performed before and after imaging.

RESULTS

During phantom testing, the maximum temperature increase was registered using the T2-weighted sequence. The maximal temperature changes at the tip of the DBS electrode were < 1°C for all sequences tested. In all patients, adequate images were obtained with structural imaging, although a significant artifact from lead connectors interfered with functional imaging quality. No heating, warmth, or adverse neurological effects were observed.

CONCLUSIONS

To the authors' knowledge, this was the first study to assess the clinical safety of 3-T MRI in patients with a fully implanted DBS system (electrodes, extensions, and pulse generator). It provided preliminary data that will allow further examination and assessment of the safety of 3-T imaging studies in patients with implanted DBS systems. The authors cannot advocate widespread use of this type of imaging in patients with DBS implants until more safety data are obtained.

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Michael L. Schwartz, Robert Yeung, Yuexi Huang, Nir Lipsman, Vibhor Krishna, Jennifer D. Jain, Martin G. Chapman, Andres M. Lozano and Kullervo Hynynen

OBJECTIVE

One patient for whom an MR-guided focused ultrasound (MRgFUS) pallidotomy was attempted was discovered to have multiple new skull lesions with the appearance of infarcts on the MRI scan 3 months after his attempted treatment. The authors conducted a retrospective review of the first 30 patients treated with MRgFUS to determine the incidence of skull lesions in patients undergoing these procedures and to consider possible causes.

METHODS

A retrospective review of the MRI scans of the first 30 patients, 1 attempted pallidotomy and 29 ventral intermediate nucleus thalamotomies, was conducted. The correlation of the mean skull density ratio (SDR) and the maximum energy applied in the production or attempted production of a brain lesion was examined.

RESULTS

Of 30 patients treated with MRgFUS for movement disorders, 7 were found to have new skull lesions that were not present prior to treatment and not visible on the posttreatment day 1 MRI scan. Discomfort was reported at the time of treatment by some patients with and without skull lesions. All patients with skull lesions were completely asymptomatic. There was no correlation between the mean SDR and the presence or absence of skull lesions, but the maximum energy applied with the Exablate system was significantly greater in patients with skull lesions than in those without.

CONCLUSIONS

It is known that local skull density, thickness, and SDR vary from location to location. Sufficient energy transfer resulting in local heating sufficient to produce a bone lesion may occur in regions of low SDR. A correlation of lesion location and local skull properties should be made in future studies.