Shayan Moosa’s research while affiliated with University of Virginia and other places

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Publications (51)


Temporal Summation of Pain Varies Across Body Regions: A Cutaneous Laser Stimulation Study in Healthy Controls
  • Article

May 2025

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3 Reads

Journal of Pain

Dan Wang

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Shuqi Ye

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Xiaohan Zhang

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[...]

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Chang‐Chia Liu



Safety and Efficacy of Staged, Bilateral Focused Ultrasound Thalamotomy in Essential Tremor: An Open-Label Clinical Trial

July 2024

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40 Reads

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13 Citations

Importance Unilateral magnetic resonance–guided focused ultrasound ablation of ventralis intermedius nucleus of the thalamus for essential tremor reduces tremor on 1 side, but untreated contralateral or midline symptoms remain limiting for some patients. Historically, bilateral lesioning produced unacceptable risks and was supplanted by deep brain stimulation; increasing acceptance of unilateral focused ultrasound lesioning has led to interest in a bilateral option. Objective To evaluate the safety and efficacy of staged, bilateral focused ultrasound thalamotomy. Design, Setting, and Participants This prospective, open-label, multicenter trial treated patients with essential tremor from July 2020 to October 2021, with a 12-month follow-up, at 7 US academic medical centers. Of 62 enrolled patients who had undergone unilateral focused ultrasound thalamotomy at least 9 months prior to enrollment, 11 were excluded and 51 were treated. Eligibility criteria included patient age (22 years and older), medication refractory, tremor severity (Clinical Rating Scale for Tremor [CRST] part A score ≥2 for postural or kinetic tremor), and functional disability (CRST part C score ≥2 in any category). Intervention A focused ultrasound system interfaced with magnetic resonance imaging allowed real-time alignment of thermography maps with anatomy. Subthreshold sonications allowed target interrogation for efficacy and off-target effects before creating an ablation. Main Outcomes and Measures Tremor/motor score (CRST parts A and B) at 3 months for the treated side after treatment was the primary outcome measure, and secondary assessments for efficacy and safety continued to 12 months. Results The mean (SD) population age was 73 (13.9) years, and 44 participants (86.3%) were male. The mean (SD) tremor/motor score improved from 17.4 (5.4; 95% CI, 15.9-18.9) to 6.4 (5.3; 95% CI, 4.9 to 7.9) at 3 months (66% improvement in CRST parts A and B scores; 95% CI, 59.8-72.2; P < .001). There was significant improvement in mean (SD) postural tremor (from 2.5 [0.8]; 95% CI, 2.3 to 2.7 to 0.6 [0.9]; 95% CI, 0.3 to 0.8; P < .001) and mean (SD) disability score (from 10.3 [4.7]; 95% CI, 9.0-11.6 to 2.2 [2.8]; 95% CI, 1.4-2.9; P < .001). Twelve participants developed mild (study-defined) ataxia, which persisted in 6 participants at 12 months. Adverse events (159 of 188 [85%] mild, 25 of 188 [13%] moderate, and 1 severe urinary tract infection) reported most commonly included numbness/tingling (n = 17 total; n = 8 at 12 months), dysarthria (n = 15 total; n = 7 at 12 months), ataxia (n = 12 total; n = 6 at 12 months), unsteadiness/imbalance (n = 10 total; n = 0 at 12 months), and taste disturbance (n = 7 total; n = 3 at 12 months). Speech difficulty, including phonation, articulation, and dysphagia, were generally mild (rated as not clinically significant, no participants with worsening in all 3 measures) and transient. Conclusions and Relevance Staged, bilateral focused ultrasound thalamotomy significantly reduced tremor severity and functional disability scores. Adverse events for speech, swallowing, and ataxia were mostly mild and transient. Trial Registration ClinicalTrials.gov Identifier NCT04112381 .



Bilateral focused ultrasound medial thalamotomies for trigeminal neuropathic pain: a randomized controlled study
  • Article
  • Full-text available

December 2023

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53 Reads

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7 Citations

Journal of Neurosurgery

OBJECTIVE Medial thalamotomy has been shown to benefit patients with neuropathic pain, but widespread adoption of this procedure has been limited by reporting of clinical outcomes in studies without a control group. This study aimed to minimize confounders associated with medial thalamotomy for treating chronic pain by using modern MRI-guided stereotactic lesioning and a rigorous clinical design. METHODS This prospective, double-blinded, randomized controlled trial in 10 patients with trigeminal neuropathic pain used sham procedures as controls. Participants underwent assessments by a pain psychologist and pain management clinician, including use of the following measures: the Numeric Pain Rating Scale (NPRS); patient-reported outcome measures; and patient’s impression of improvement at baseline, 1 day, 1 week, 1 month, and 3 months postprocedure. Patients in the treated group underwent bilateral focused ultrasound (FUS) medial thalamotomy targeting the central lateral nucleus. Patients in the control group underwent sham procedures with energy output disabled. The primary efficacy outcome measure was between-group differences in pain intensity (using the NPRS) at baseline and at 3 months postprocedure. Adverse events were measured for safety and included MRI analysis. Exploratory measures of connectivity and metabolism were analyzed using diffusion tensor imaging, functional MRI, and PET, respectively. RESULTS There were no serious complications from the FUS procedures. MRI confirmed bilateral medial thalamic ablations. There was no significant improvement in pain intensity from baseline to 3 months, either for patients undergoing FUS medial thalamotomy or for sham controls; and the between-group change in NPRS score as the primary efficacy outcome measure was not significantly different. Patient-reported outcome assessments demonstrated improvement (i.e., a decrease) only in pain interference with enjoyment of life at 3 months. There was a perception of benefit at 1 week, but only for patients treated with FUS and not for the sham cohort. Advanced neuroimaging showed that these medial thalamic lesions altered structural connectivity with the postcentral gyrus and demonstrated a trend toward hypometabolism in the insula and amygdala. CONCLUSIONS This randomized controlled trial of bilateral FUS medial thalamotomy did not reduce the intensity of trigeminal neuropathic pain, although it should be noted that the ability to estimate the magnitude of treatment effects is limited by the small cohort.

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P15.17.B DYNAMIC FDG PET AS A PREDICTOR OF SURVIVAL IN PATIENTS WITH GLIOMAS

September 2023

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8 Reads

Neuro-Oncology

BACKGROUND The neuroimaging characteristics of treatment-related necrosis (TRN) induced by chemotherapy and radiotherapy mimic those of tumor progression (TPR). This can make it challenging for clinicians to deliver prognoses for patients with gliomas and subsequently optimize their treatment regimens. In this study, we evaluate the utility of dynamic FDG (dFDG) PET, which provides information about dynamic metabolic changes, for predicting survival in patients who have undergone treatment for gliomas. MATERIAL AND METHODS Clinical and radiographic information were obtained for 21 adult patients with known or suspected recurrent gliomas and had radiographic worsening reported on MRI within 6 months of completion of radiation and chemotherapy. All patients underwent dFDG PET imaging, and the prognostic significance of rate constants from the suspected tumor region were analyzed using Cox regressions. RESULTS Based on dFDG PET imaging, higher values of the k3 rate constant predicted a hazard ratio of 6.7 of death within 12 months of diagnosis. Hazard ratios of the k1 and k2 parameters were not significant in prediction of 12-month survival. CONCLUSION The k3 kinetic parameter of dFDG PET imaging, a marker for glucose uptake and metabolism, is predictive of 12-month survival in glioma patients who have questionable tumor progression. Clinicians can use this information to estimate the likelihood of TPR versus TRN in patients with gliomas and subsequently tailor their treatment plans based upon expected survival.


Progesterone Receptor Activation Regulates Sensory Sensitivity and Migraine Susceptibility

September 2023

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53 Reads

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6 Citations

Journal of Pain

Women develop chronic pain during their reproductive years more often than men, and estrogen and progesterone regulate this susceptibility. We tested whether brain progesterone receptor (PR) signaling regulates pain susceptibility. During the estrous cycle, animals were more sensitive to mechanical stimulus during the estrus stage than in the diestrus stage, suggesting a role for reproductive hormones, estrogen, and progesterone. Progesterone treatment of ovariectomized and estrogen-primed mice caused a delayed reduction in the mechanical threshold. Segesterone, a specific agonist of PRs replicated this effect, whereas, the segesterone-induced reduction in mechanical threshold was blocked in the mice lacking PRs in the nervous system. Segesterone treatment also did not alter mechanical threshold in adult male and juvenile female mice. PR activation increased the cold sensitivity but did not affect the heat and light sensitivity. We evaluated whether PR activation altered experimental migraine. Segesterone and nitroglycerin (NTG) when administered sequentially, reduced the pain threshold but not when given separately. PRs were expressed in several components of the migraine ascending pain pathway, and their deletion blocked the painful effects of NTG. PR activation also increased the number of active neurons in the components of the migraine ascending pain pathway. These studies have uncovered a pain-regulating function of PRs. Targeting PRs may provide a novel therapeutic avenue to treat chronic pain and migraine in women. PERSPECTIVE: This article provides evidence for the role of progesterone receptors in regulating pain sensitivity and migraine susceptibility in females. Progesterone receptors may be a therapeutic target to treat chronic pain conditions more prevalent in women than men.


Citations (38)


... Staged bilateral magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomies have emerged in clinical practice, with successful results demonstrated in essential tremor (ET) patients in multiple open-label trials. [1][2][3][4][5] The procedure has recently obtained the Food and Drug Administration (FDA) approval, marking a significant milestone in managing patients with severe bilateral symptoms. 5 This achievement is expected to catalyze further studies aimed at understanding its benefits and underlying mechanisms. ...

Reference:

Bilateral Focused Ultrasound Thalamotomy for Essential Tremor: Clinical Outcomes Compared to Bilateral Deep Brain Stimulation and Probabilistic Lesion Mapping
Safety and Efficacy of Staged, Bilateral Focused Ultrasound Thalamotomy in Essential Tremor: An Open-Label Clinical Trial
  • Citing Article
  • July 2024

... Necessary spatial and temporal resolutions are dependent on the ultrasound focal size and exposure time, respectively, 21,22 and are influenced by the sequence parameters, available SNR, and clinical need. 23,24 Generally, spatial resolutions are on the order of a few millimeters 14,[25][26][27][28] and temporal resolutions are on the order of seconds 15,16,[29][30][31] dependent on application. The ultrasound focus position as well as near-and far-field regions is monitored for heating to maintain patient safety and treatment efficacy. ...

Future Directions of MR-guided Focused Ultrasound
  • Citing Article
  • April 2024

Magnetic Resonance Imaging Clinics of North America

... In addition, in most cases, spinal cord stimulation is delivered invasively, posing risk of surgical complications (Hasoon et al. 2024). Recently, high-intensity FUS has been tested as a therapeutic option for chronic neuropathic pain through ablation of thalamic pain centers (di Biase et al. 2021;Ahmed et al. 2024;Ishaque et al. 2024) or by blocking peripheral nerve conduction (Lee et al. 2015). However, it poses risks for non-reversible damage, with possible neurological consequences that are yet undetermined. ...

Bilateral focused ultrasound medial thalamotomies for trigeminal neuropathic pain: a randomized controlled study

Journal of Neurosurgery

... 68 It is possible that the neuronal damage and innate immune system response to viral infection in 69 CA1 8,10 provokes acute seizures 10,11,12,13 , while long-term changes in hippocampal circuitry 70 underlie the chronic seizures 14 marker through a 4-hydroxytamoxifen (4-OHT) dependent, Cre-inducible paradigm 15 . TRAP 75 tagging has been used to map seizure propagation in pentylenetetrazol-induced seizures 16 , 76 cobalt-induced frontal lobe seizures 17 , hypoxic-ischemic-induced seizures 18 , and status 77 epilepticus in mice 19 investigations 19,20 . 87 conditions in a random order. ...

Progesterone Receptor Activation Regulates Sensory Sensitivity and Migraine Susceptibility
  • Citing Article
  • September 2023

Journal of Pain

... 68 Hence, a change in lower frequencies over temporal electrodes may not be the best candidate as a possible EEG cortical marker of TSSP. Yet, this is still premature to say since only two studies have, so far, investigated the neuro-electrophysiological correlates of temporal summation of pain, 40,69 and only one, besides the current work, has delved into its time-frequency domain. 69 Secondly, the analysis of the ERSP also indicated that TSSP alone, compared to the non-painful baseline, was accompanied by an increase in the alpha range at a frontal-central region. ...

Painful Cutaneous Laser Stimulation for Temporal Summation of Pain Assessment
  • Citing Article
  • July 2023

Journal of Pain

... Unlike NIBS, which primarily stimulates cortical areas, tFUS can non-invasively target deep brain regions with spatial resolution reaching tens to hundreds of mm 3 , depending on the signal frequency and number of transducers used [3,10,11]. This makes tFUS a promising alternative to the invasive Deep Brain Stimulation (DBS) method [12][13][14]. ...

Voice Improvement After Essential Tremor Treatment via Focused Ultrasound and Deep Brain Stimulation

... 6 More recently, three additional studies reported the outcome of unilateral MRgFUS Vim thalamotomy for patients with TdPD, outlining its overall efficacy but also warning about the risk of potential treatment failure. [7][8][9] Notably, it has been suggested that the best intrathalamic target for tremor control may differ between TdPD and ET patients. 10 Data from cohorts of patients with ET showed a positive correlation between tremor control and lesion volume. ...

Patient-Reported Outcomes After Focused Ultrasound Thalamotomy for Tremor-Predominant Parkinson's Disease
  • Citing Article
  • May 2023

Neurosurgery

... MRI-guided FUS (MRgFUS) has proven to be an effective and safe treatment for essential tremor, with up to 70% improvement in tremor and disability. 12 FUS for ablative purposes is termed high-intensity FUS (HIFU), reaching target temperatures of 55°C. However, low-intensity FUS (LIFU) differs from other ablative modalities due to its reversible neuromodulatory capacity at lower intensities. ...

High-Frequency Ultrasound Ablation in Neurosurgery
  • Citing Article
  • April 2023

Neurosurgery Clinics of North America

... This method has shown significant efficacy in improving hand and nystagmus, and has been used in the Chinese population, with postoperative follow-up demonstrating its effectiveness in relieving tremor [23]. However, studies have also found that tremor is prone to recurrence and cannot be adjusted after recurrence, requiring multiple surgical treatments, although most patients remain willing to undergo reoperation [24]. In addition, there are some limitations to the use of MRgFUS, for example, patients with a low mean skull density ratio (SDR) and patients who are unable to undergo MRI scanning are not candidates for this treatment [21]. ...

Patient-Reported Outcomes and Predictive Factors following Focused Ultrasound Thalamotomy for Essential Tremor
  • Citing Article
  • August 2022

Stereotactic and Functional Neurosurgery

... The connectivity matrix is calculated by the GRU-GC algorithm described above, and a directed graph can be constructed by binarization. The epileptic lesion localization task can then be transformed into a node classification task for the directed graph, distinguishing between lesion areas and unrelated regional nodes., Therefore, we want to extract the local features of the nodes in the directed graph for classification, and the features [28,29] selected for this topic are shown below: ...

High-Dimensional Directional Brain Network Analysis for Focal Epileptic Seizures
  • Citing Preprint
  • August 2022