Illusions of Self-Motion during Magnetic Resonance-Guided Focused Ultrasound Thalamotomy for Tremor.

OBJECTIVE: Brain networks mediating vestibular perception of self-motion overlap with those mediating balance. A systematic mapping of vestibular perceptual pathways in the thalamus may reveal new brain modulation targets for improving balance in neurological conditions. METHODS: Here, we systematically report how magnetic resonance-guided focused ultrasound surgery of the nucleus ventralis intermedius of the thalamus commonly evokes transient patient-reported illusions of self-motion. In 46 consecutive patients, we linked the descriptions of self-motion to sonication power and 3-dimensional (3D) coordinates of sonication targets. Target coordinates were normalized using a standard atlas, and a 3D model of the nucleus ventralis intermedius and adjacent structures was created to link sonication target to the illusion. RESULTS: A total of 63% of patients reported illusions of self-motion, which were more likely with increased sonication power and with targets located more inferiorly along the rostrocaudal axis. Higher power and more inferiorly targeted sonications increased the likelihood of experiencing illusions of self-motion by 4 and 2 times, respectively (odds ratios = 4.03 for power, 2.098 for location). INTERPRETATION: The phenomenon of magnetic vestibular stimulation is the most plausible explanation for these illusions of self-motion. Temporary unilateral modulation of vestibular pathways (via magnetic resonance-guided focused ultrasound) unveils the central adaptation to the magnetic field-induced peripheral vestibular bias, leading to an explicable illusion of motion. Consequently, systematic mapping of vestibular perceptual pathways via magnetic resonance-guided focused ultrasound may reveal new intracerebral targets for improving balance in neurological conditions. ANN NEUROL 2024;96:121-132.

The evolution of ventral intermediate nucleus targeting in MRI-guided focused ultrasound thalamotomy for essential tremor: an international multi-center evaluation.

Background: The ventral intermediate nucleus (VIM) is the premiere target in magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy for tremor; however, there is no consensus on the optimal coordinates for ablation. This study aims to ascertain the various international VIM targeting approaches (VIM-TA) and any evolution in practice. Methods: International MRgFUS centers were invited to share VIM-TAs in 2019 and 2021. Analyses of any modification in practice and of anatomical markers and/or tractography in use were carried out. Each VIM-TA was mapped in relation to the mid-commissural point onto a 3D thalamic nucleus model created from the Schaltenbrand-Wahren atlas. Results: Of the 39 centers invited, 30 participated across the study period, providing VIM-TAs from 26 centers in 2019 and 23 in 2021. The results are reported as percentages of the number of participating centers in that year. In 2019 and 2021, respectively, 96.2% (n = 25) and 95.7% (n = 22) of centers based their targeting on anatomical landmarks rather than tractography. Increased adoption of tractography in clinical practice and/or for research was noted, changing from 34.6% to 78.3%. There was a statistically significant change in VIM-TAs in the superior-inferior plane across the study period; the percentage of VIM-TAs positioned 2 mm above the intercommissural line (ICL) increased from 16.0% in 2019 to 40.9% in 2021 (WRST, p < 0.05). This position is mapped at the center of VIM on the 3D thalamic model created based on the Schaltenbrand-Wahren atlas. In contrast, the VIM-TA medial-lateral and anterior-posterior positions remained stable. In 2022, 63.3% of participating centers provided the rationale for their VIM-TAs and key demographics. The centers were more likely to target 2 mm above the ICL if they had increased experience (more than 100 treatments) and/or if they were North American. Conclusion: Across the study period, FUS centers have evolved their VIM targeting superiorly to target the center of the VIM (2 mm above the ICL) and increased the adoption of tractography to aid VIM localization. This phenomenon is observed across autonomous international centers, suggesting that it is a more optimal site for FUS thalamotomy in tremors.

'Am I fixed, am I better now?': undergoing MR-guided focused ultrasound for essential tremor: an interpretative phenomenological analysis.

Introduction: Essential tremor (ET) is characterised by postural and intentional tremor typically affecting the upper limbs, which can negatively impact functionality and quality of life. Magnetic Resonance-guided Focused Ultrasound (MRgFUS) is a novel and promising non-invasive treatment for ET which offers instantaneous results. Methods: Using interpretative phenomenological analysis we explored the experience of undergoing MRgFUS in six ET patients as well as their experiences pre- and post-procedure. Results: One-time, retrospective semi-structured interviews were conducted and six themes emerged: Life pre-treatment: "It's everyday tasks that get you down" and "Most people who understand, they are okay. Some people aren't"; MRgFUS: Treatment day: "Going into the unknown" and "There's no way I was going to press that button"; and Life post-treatment: "One is good. Two is better" and "Am I fixed, am I better now?." Discussion: The findings point to a significant period of adjustment associated with living with ET and the effects of undergoing ET MRgFUS treatment. As ET progressed, participants struggled to cope with increasing symptoms and had to develop coping strategies to manage life with ET. The procedure itself was perceived as strange and extraordinary and despite some immediate adverse effects participants were determined to go through with it. Post procedure, all participants reported tremor suppression which was life changing. While some participants still felt burdened by ET, others expressed it took them a while to psychologically adjust to what essentially was their new body. This study has highlighted the need for patients to be supported at all stages of their ET journey.

Effects of conventional physical therapy with and without proprioceptive neuromuscular facilitation on balance, gait, and function in patients with Parkinson's disease.

The study was conducted at University of Lahore Teaching Hospital and Sir Ganga Ram Hospital, Lahore, using non-probability convenience sampling. Thirty-eight patients of Parkinson's disease were allocated by randomisation into two groups. PNF Group (group A) performed proprioceptive neuromuscular facilitation incorporated with conservative treatment, while for the conventional therapy group (group B) only conservative treatment was followed. Berg Balance Scale, Freezing of Gait questionnaire, and Functional Independence measure were used as outcome measuring tool. Berg balance scale values were significantly improved in group A at 12th week as compared to group B. Freezing of gait and functional independence was more significantly reduced in group A at sixth and 12th week as compared to group B. Hence, it is concluded that Proprioceptive neuromuscular facilitation combined with routine treatment regime improves balance, gait, and function of Parkinson's patients more effectively as compared with routine treatment protocol only.

The cost-effectiveness of unilateral magnetic resonance-guided focused ultrasound in comparison with unilateral deep brain stimulation for the treatment of medically refractory essential tremor in England.

OBJECTIVES: This study aims to ascertain the cost-effectiveness of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment of medically refractory Essential Tremor (mrET) in England. Essential Tremor (ET) is the most common movement disorder affecting approximately 1 million in the UK causing considerable societal impact affecting patients, carers and the wider healthservice. Medical treatment has mixed efficacy, with approximately 25-55% of ET medication refractory. Deep brain stimulation (DBS) is a proven neurosurgical treatment; however, the risks of surgery and anaesthesia mean some patients are ineligible. MRgFUS is an emerging noninvasive technique that causes tremor suppression by thermal ablation of tremor-sensitive brain tissue. Several international clinical trials have demonstrated MRgFUS is safe and clinically effective; however, to-date no cost-effectiveness study has been performed in Europe. METHODS: A Markov model was used to assess two subpopulations of mrET - those eligible and those ineligible for neurosurgery - in the context specific to England and its healthcare system. For those eligible for neurosurgery, MRgFUS was compared to DBS, the current standard treatment. For those ineligible for neurosurgery, MRgFUS was compared to treatment with medication alone. The model calculated the Incremental cost-effectiveness ratio (ICER) with appropriate sensitivity and scenario analyses. RESULTS: For those eligible for neurosurgery: In the model base case, the MRgFUS was economically dominant compared to DBS; MRgFUS was less costly (£19,779 vs £62,348) and more effective generating 0.03 additional quality-adjusted life-years (QALYs) per patient (3.71 vs 3.68) over the 5-year time horizon.For those ineligible for neurosurgery: In the model base case, MRgFUS cost over £16,000 per patient more than medication alone (£19,779 vs £62,348) but yielded 0.77 additional QALYs per patient(3.71 vs 2.95), producing an incremental cost-effectiveness ratio (ICER) of £20,851 per QALY. This ICER of £20,851 per QALY falls within the National Institute for Clinical Excellence's (NICE) willingness to pay threshold (WTP) of 20,000-30,000 demonstrating the cost-effectiveness profile of MRgFUS. CONCLUSION: This study demonstrates the favourable cost-effectiveness profile of MRgFUS for the treatment of mrET in England; in both patients suitable and not suitable for neurosurgery. ADVANCES IN KNOWLEDGE: The introduction of MRgFUS as a widely available ET treatment in UK is currently undergoing the necessary stages of regulatory approval. As the first European study, these favourable cost-effectiveness outcomes (notably the model base case ICER falling within NICE's WTP) can provide a basis for future commissioning of brain MRgFUS treatments in the UK, Europe and globally.

Double lesion MRgFUS treatment of essential tremor targeting the thalamus and posterior sub-thalamic area: preliminary study with two year follow-up.

BACKGROUND: MR-guided focused ultrasound (MRgFUS) is an effective treatment for essential tremor (ET). However, the optimal intracranial target sites remain to be determined. OBJECTIVE: To assess MRgFUS induced sequential lesions in (anterior-VIM/VOP nuclei) the thalamus and then posterior subthalamic area (PSA) performed during the same procedure for alleviating ET. METHODS: 14 patients had unilateral MRgFUS lesions placed in anterior-VIM/VOP then PSA. Bain-Findley Spirals were collected during MRgFUS from the treated arm (BFS-TA) and throughout the study from the treated (BFS-TA) and non-treated (BFS-NTA) arms and scored by blinded assessors. Although, the primary outcome was change in the BFS-TA from baseline to 12 months we have highlighted the 24-month data. Secondary outcomes included the Clinical Rating Scale for Tremor (CRST), Quality of Life for ET (QUEST) and PHQ-9 depression scores. RESULTS: The mean improvement in the BFS-TA from baseline to 24 months was 41.1% (p < 0.001) whilst BFS-NTA worsened by 8.8% (p < 0.001). Intra-operative BFS scores from the targeted arm showed a mean 27.9% (p < 0.001) decrease after anterior-VIM/VOP ablation and an additional 30.1% (p < 0.001) reduction from post anterior-VIM/VOP to post-PSA ablation. Mean improvements at 24 month follow-up in the CRST-parts A, B and C were 60.7%, 30.4% and 65.6% respectively and 37.8% in QUEST-tremor score (all p < 0.05). Unilateral tremor severity scores decreased in the treated arm (UETTS-TA) 72.9% (p = 0.001) and non-treated arm (UETTS-NTA) 30.5% (p = 0.003). At 24 months residual adverse effects were slight unsteadiness (n = 1) and mild hemi-chorea (n = 1). CONCLUSION: Unilateral anterior-VIM/VOP and PSA MRgFUS significantly diminished contralateral arm tremor with improvements in arm function, tremor related disability and quality of life, with an acceptable adverse event profile.

Device profile of exAblate Neuro 4000, the leading system for brain magnetic resonance guided focused ultrasound technology: an overview of its safety and efficacy in the treatment of medically refractory essential tremor.

Introduction: Magnetic Resonance guided Focused UltraSound (MRgFUS) is an emerging technique that utilizes multiple high-energy low-frequency ultrasound beams generated from a multi-element transducer focused onto a single site to cause thermal ablation of the target tissue. The ExAblate Neuro 4000 system is the leading MRgFUS brain system, performing targeted thermal ablation on specific nuclei in the brain. Its precision targeting opens up new and exciting possibilities for future treatments of a wide range of neurological diseases.  Areas covered: This article aims to introduce the non-expert reader (clinician and non-clinicians) to the role of the ExAblate Neuro 4000 System in brain MRgFUS. The current clinical uses of the ExAblate system in the brain are explored with a particular focus on Essential Tremor, where internationally there is most experience, this includes reference to current literature. The safety and efficacy of MRgFUS treatments are explored and the challenges the ExAblate system must overcome to balance these juxtaposed outcomes.Expert opinion: We describe the hopes for future clinical uses of the ExAblate Neuro 4000 system to treat neurological disease and consider further advancements in MRgFUS transducer technology that may open up new exciting frontiers within the brain.

Does Right Ventricular Dysfunction Predict Mortality in Hemodynamically Stable Patients With Acute Pulmonary Embolism?

BACKGROUND: Acute pulmonary embolism (APE) is directly responsible for 100,000 deaths annually. Right ventricular dysfunction (RVD) on admission is considered a poor prognostic factor in these patients, though existing evidence of its significance in predicting mortality in hemodynamically stable patients is still unclear. We attempted to clarify this association by doing a retrospective review. METHODS: We retrospectively reviewed electronic medical records of hemodynamically stable patients older than 18 years of age with APE who were admitted to a tertiary care hospital in rural Upstate New York from July 2014 to July 2016. One hundred thirty-four patients were reviewed in two groups: patients who presented with computed tomography (CT) or echocardiographic evidence of RVD, and those without RVD. To identify differences in mortality between the two groups, the Chi-square/Fisher's exact test and t-tests were used. All variables with P < 0.2 in the initial analysis were included in a stepwise multivariable logistic regression model to predict RVD. RESULTS: No statistically significant difference was found in 30-day mortality between the groups (7.8% in RVD and 5.3% in no RVD, P = 0.563). The overall prevalence of RVD was found to be 57% (77/134). Troponin elevation (53.2% in RVD group vs. 19.3 in the no RVD group with P < 0.01) and central location of thrombus (53.1% vs. 32.1% with P = 0.016) were more prevalent in RVD group. A marginally significant difference was found in length of hospital stay among those with RVD versus no RVD (7.13 days vs. 5.46 days; P = 0.061). The multivariable analysis shows that the odds of RVD were greater for patients with elevated troponin levels (odds ratio = 7.8). CONCLUSION: There was no difference in 30-day mortality in hemodynamically stable patients with APE having RVD compared to patients with no RVD. On the basis of this study, we do not suggest the routine use of systemic fibrinolysis in hemodynamically stable patients with radiographic evidence of RVD alone.

Prognostic Significance of Elevated Cardiac Troponin in Acute Gastrointestinal Bleeding.

BACKGROUND: Acute gastrointestinal bleeding (AGIB) is responsible for over 140,000 hospitalizations annually. Cardiovascular-related deaths account for 30% of the patients surviving the initial episode of AGIB. The purpose of this study was to identify the impact of elevated troponin on short-term mortality and length of stay (LOS) of these patients. METHODS: From July 2013 to July 2016, 290 patients admitted with a diagnosis of AGIB and who had cardiac troponin I measured within 24 h of presentation were retrospectively reviewed. Clinical variables including 30-day mortality, 30-day readmission and LOS were then compared between the groups of troponin elevation and no troponin elevation. RESULTS: The overall 30-day mortality among patients with AGIB was 6.5% (19/290). Cardiac troponin was elevated in 10% of patients (29/290). Among patients with normal troponin, 5% (13/261) died within 30 days. In patients with troponin elevation, 21% died in the same period (6/29, P = 0.001). The LOS was also higher in patients with troponin elevation (6 vs. 5 days, P = 0.02). There was no difference in 30-day readmission among the two groups. Past history of coronary artery disease, congestive heart failure, hypertension, aspirin use and elevated creatinine was more common in patients with troponin elevation. On multivariate analysis, troponin elevation on presentation is associated with increased mortality (odds: 5.50, CI: 1.73 - 17.47, P = 0.004). CONCLUSION: In patients admitted to the inpatient service with AGIB, elevated troponin I on presentation is associated with high short-term mortality and longer hospital stay.

The shifting paradigm in the treatment of type 2 diabetes mellitus-A cardiologist's perspective.

In patients with diabetes mellitus, cardiovascular (CV) disease is the leading cause of morbidity and mortality. A multitude of contemporary antidiabetic agents presents different CV safety profiles. Metformin forms the cornerstone agent to reduce CV events. Newer agents, such as glucagon-like peptide-1 agonists and sodium-glucose cotransporter-2 inhibitors, have appealing CV benefits. Insulin, dipeptidyl peptidase-4 inhibitors, and sulfonylureas have neutral CV effects. Cardiologists should familiarize themselves with these agents to promote comprehensive CV care in patients with diabetes mellitus.

Epidemiology of Infective Endocarditis in Rural Upstate New York, 2011 - 2016.

BACKGROUND: The epidemiology of infective endocarditis (IE) depends on a number of host factors whose prevalence can vary globally. The usual patient population affected by IE is sicker and older, often with many comorbid conditions. The risk is growing in younger populations due to the emerging epidemic of intravenous (IV) drug use. We have performed a temporal trend analysis of various factors of IE in the rural counties covering a major part of central Upstate New York. METHODS: We performed a retrospective analysis of electronic medical records of patients who were admitted in a tertiary care hospital in rural Upstate New York and diagnosed with IE from January 1, 2011 to December 31, 2016. Forty-five patients were identified with definite IE and nine with possible IE. RESULTS: Total incidence of IE was 3.5 cases per 100,000 person years in the total population and 4.4 if we consider total population ≥ 18 years in the denominator. A significant (P = 0.022) increase in incidence of IE from 2011 to 2016 was seen by univariate analysis. Incidence was higher in males (P = 0.029) and for those aged 65 or older (P = 0.0003). IV drug use among cases is noted to be more prevalent in 2015 and 2016 compared to previous years. CONCLUSION: In this study of patients in a rural region of New York, an increase in the incidence of IE was seen over the study period with changes in patient characteristics and etiology over this time. We speculate that an increase in IV drug use could be a leading factor in the recent and future increased incidence of IE in the area.

Does Syncope Predict Mortality in Patients With Acute Pulmonary Embolism? A Retrospective Review.

BACKGROUND: Acute pulmonary embolism (APE) is a potentially fatal disease with high mortality. Prior studies have shown an increased frequency of central localization of the clot, right ventricular dysfunction and elevated troponin in patients who present with syncope and APE. Existing evidence regarding mortality and length of hospital stay in these patients is unclear. METHODS: We retrospectively reviewed electronic medical records of patients who were admitted in a tertiary care hospital in rural Upstate New York and diagnosed with APE from July 2014 to July 2016. Two hundred nineteen patients were reviewed in two groups: patients who presented with syncope and those without syncope. RESULTS: The prevalence of syncope was found to be 6.8% (15/219). Hypotension on admission was more common among patients with syncope compared to no syncope (26.7% and 7.4%, respectively, P = 0.03). A clinically significant difference was found in 30-day mortality among those with syncope versus no syncope (21.3% vs. 7.4%, P = 0.096). No significant difference was found in length of stay (mean 6.7 days in patients with syncope vs. 6.4 without syncope, P = 0.783), central localization (26.7% with syncope vs. 43.2% without syncope, P = 0.21) or troponin elevation (46.2% in patients with syncope vs. 27.9% without syncope, P = 0.205). On multivariable analysis, hypotension was significantly higher among those with syncope (odds ratio: 5.23, P = 0.0148). CONCLUSION: This study suggests 30-day mortality may be higher among patients with syncope. It is important to risk stratify patients on admission in order to reduce mortality and morbidity associated with lethal disease.