An increasing number of neurological conditions may be treated with high-intensity focused ultrasound (HIFU), among which is geared towards the control of tremors as seen in patients with Parkinson’s Disease (PD), X-linked Dystonia Parkinsonism (XDP), and Essential Tremor (ET). HIFU thalamotomy is a noninvasive therapy for neurological conditions with debilitating tremors despite medication. To improve treatment accuracy and patient safety, neurosurgeons, neurologists, and anesthesiologists must work together perioperatively.

A total of 30 patients detailing their demographics, symptoms, and perioperative anesthetic management in a tertiary government hospital in Metro Manila was reviewed from October 2021 to March 2024. Most of the patients were diagnosed as PD tremor dominant, followed by XDP and ET. Majority of the cases were done under minimal sedation with local infiltration on the pin site while the rest were done under monitored anesthesia care combined with local anesthesia. Specific anesthetic agents were given to provide comfort and pain relief and reduce the risk of side effects.

During sonication, an essential element of the procedure, patients were closely monitored for the anticipated effects, such as paresthesia, headache, nausea, and vomiting, and were managed accordingly. Postoperatively, these patients were reported to have decreased tremors, stable vital signs, and adequate pain control. Collaboration among healthcare providers is one of the important elements for a successful outcome. This study highlights the importance of personalized anesthetic management in enhancing patient outcomes and the need for future studies about developing anesthesia protocols and strategies.

Magnetic resonance-guided focused ultrasound (MRgFUS) is a novel and minimally invasive technology. Since the US Food and Drug Administration approved unilateral ventral intermediate nucleus-MRgFUS for medication-refractory essential tremor in 2016, studies on new indications, such as Parkinson's disease (PD), psychiatric diseases, and brain tumors, have been on the rise, and MRgFUS has become a promising method to treat such neurological diseases. Currently, as the second most common degenerative disease, PD is a research hotspot in the field of MRgFUS. The actions of MRgFUS on the brain range from thermoablation, blood-brain barrier (BBB) opening, to neuromodulation. Intensity is a key determinant of ultrasound actions. Generally, high intensity can be used to precisely thermoablate brain targets, whereas low intensity can be used as molecular therapies to modulate neuronal activity and open the BBB in conjunction with injected microbubbles. Here, we aimed to summarize advances in the application of MRgFUS for the treatment of PD, with a focus on thermal ablation, BBB opening, and neuromodulation, in the hope of informing clinicians of current applications.
Humans ; Parkinson Disease/therapy* ; Brain ; Blood-Brain Barrier ; Essential Tremor/surgery* ; Brain Neoplasms ; Magnetic Resonance Imaging/methods* ; Magnetic Resonance Spectroscopy

Essential Tremor ; Humans ; Pedigree

Essential Tremor ; diagnosis ; genetics ; Genetic Association Studies ; Genetic Predisposition to Disease ; Humans ; Polymorphism, Single Nucleotide ; genetics ; Receptors, Calcitriol ; genetics

PURPOSE: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy has become a standard treatment for medically intractable essential tremor (ET). Skull density ratio (SDR) and skull volume in patients with ET are currently considered useful indicators of the successful application of MRgFUS. We compared the clinical outcomes of MRgFUS thalamotomy with SDR above 0.4 and 0.45. We also described patterns of SDR and skull volume in Korean patients with ET who were eligible to be screened for MRgFUS. MATERIALS AND METHODS: In screening 318 ET patients, we evaluated patterns of skull density and skull volume according to age and sex. Fifty patients with ET were treated with MRgFUS. We investigated the effects of SDR and skull volume on treatment parameters and the outcomes of ET. RESULTS: The mean SDR of the 318 ET patients was 0.45±0.11, and that for skull volume was 315.74±40.95 cm³. The male patients had a higher SDR than female patients (p=0.047). Skull volume significantly decreased with aging. SDR and skull volume exhibited a linear negative relationship. Among therapeutic parameters, maximal temperature was positively related to SDR, while sonication number was not related to either SDR or skull volume. Tremor outcome was also not related to SDR or skull volume. CONCLUSION: SDR varied widely from 0.11 to 0.73, and men had a higher SDR. Therapeutic parameters and clinical outcomes were not affected by SDR or skull volume.
Aging ; Essential Tremor ; Female ; Humans ; Male ; Mass Screening ; Skull ; Sonication ; Tremor ; Ultrasonography

Magnetic resonance-guided focused ultrasound (MRgFUS) is an emerging new technology with considerable potential to treat various neurological diseases. With refinement of ultrasound transducer technology and integration with magnetic resonance imaging guidance, transcranial sonication of precise cerebral targets has become a therapeutic option. Intensity is a key determinant of ultrasound effects. High-intensity focused ultrasound can produce targeted lesions via thermal ablation of tissue. MRgFUS-mediated stereotactic ablation is non-invasive, incision-free, and confers immediate therapeutic effects. Since the US Food and Drug Administration approval of MRgFUS in 2016 for unilateral thalamotomy in medication-refractory essential tremor, studies on novel indications such as Parkinson's disease, psychiatric disease, and brain tumors are underway. MRgFUS is also used in the context of blood-brain barrier (BBB) opening at low intensities, in combination with intravenously-administered microbubbles. Preclinical studies show that MRgFUS-mediated BBB opening safely enhances the delivery of targeted chemotherapeutic agents to the brain and improves tumor control as well as survival. In addition, BBB opening has been shown to activate the innate immune system in animal models of Alzheimer’s disease. Amyloid plaque clearance and promotion of neurogenesis in these studies suggest that MRgFUS-mediated BBB opening may be a new paradigm for neurodegenerative disease treatment in the future. Here, we review the current status of preclinical and clinical trials of MRgFUS-mediated thermal ablation and BBB opening, described their mechanisms of action, and discuss future prospects.
Alzheimer Disease ; Blood-Brain Barrier ; Brain ; Brain Neoplasms ; Essential Tremor ; High-Intensity Focused Ultrasound Ablation ; Immune System ; Magnetic Resonance Imaging ; Microbubbles ; Models, Animal ; Neurodegenerative Diseases ; Neurogenesis ; Parkinson Disease ; Plaque, Amyloid ; Sonication ; Therapeutic Uses ; Transducers ; Ultrasonography ; United States Food and Drug Administration

BACKGROUND AND PURPOSE: Hand tremor is one of the most frequent symptoms in movement disorders, and differential diagnoses for hand tremor include Parkinson's disease (PD) and essential tremor (ET). However, accurately differentiating between PD and ET in clinical practice remains challenging in patients presenting with hand tremor. We investigated whether a questionnaire-based survey could be useful as a screening tool in patients with hand tremor. METHODS: A questionnaire related to hand tremor consisting of 12 items was prospectively applied to patients with PD or ET in three movement-disorder clinics. Each question was analyzed, and a query-based scoring system was evaluated for differentiating hand tremors between PD and ET. RESULTS: This study enrolled 24 patients with PD and 25 patients with ET. Nine of the 12 questions differed significantly between PD and ET: 1 about resting tremor, 4 questions about action tremor, and 4 about asymmetry. A receiver operating characteristics curve analysis revealed that the 9-item questionnaire showed a good discrimination ability, with a sensitivity of 88% and a specificity of 84%. CONCLUSIONS: The developed Hand Tremor Questionnaire might be a good screening tool for hand tremors in patients with PD and ET.
Diagnosis, Differential ; Discrimination (Psychology) ; Essential Tremor* ; Hand* ; Humans ; Mass Screening* ; Movement Disorders ; Parkinson Disease* ; Prospective Studies ; ROC Curve ; Sensitivity and Specificity ; Tremor*

Magnetic resonance-guided focused ultrasound (MRgFUS) is a new emerging neurosurgical procedure applied in a wide range of clinical fields. It can generate high-intensity energy at the focal zone in deep body areas without requiring incision of soft tissues. Although the effectiveness of the focused ultrasound technique had not been recognized because of the skull being a main barrier in the transmission of acoustic energy, the development of hemispheric distribution of ultrasound transducer phased arrays has solved this issue and enabled the performance of true transcranial procedures. Advanced imaging technologies such as magnetic resonance thermometry could enhance the safety of MRgFUS. The current clinical applications of MRgFUS in neurosurgery involve stereotactic ablative treatments for patients with essential tremor, Parkinson's disease, obsessive-compulsive disorder, major depressive disorder, or neuropathic pain. Other potential treatment candidates being examined in ongoing clinical trials include brain tumors, Alzheimer's disease, and epilepsy, based on MRgFUS abilities of thermal ablation and opening the blood-brain barrier. With the development of ultrasound technology to overcome the limitations, MRgFUS is gradually expanding the therapeutic field for intractable neurological disorders and serving as a trail for a promising future in noninvasive and safe neurosurgical care.
Acoustics ; Alzheimer Disease ; Blood-Brain Barrier ; Brain Neoplasms ; Depressive Disorder, Major ; Epilepsy ; Essential Tremor ; High-Intensity Focused Ultrasound Ablation ; Humans ; Magnetic Resonance Imaging ; Nervous System Diseases ; Neuralgia ; Neurosurgery* ; Neurosurgical Procedures ; Obsessive-Compulsive Disorder ; Parkinson Disease ; Skull ; Thermometry ; Transducers ; Ultrasonography*

Essential tremor (ET) is one of the most common movement disorders. Its clinical manifestations not only include typical kinetic and/or postural tremors, but also other non-motor symptoms such as cognitive dysfunction, sleep disturbance, and dysosmia. The exact etiology and pathogenesis of ET is still unknown. Approximately 60% of ET patients have a family history, and genetic factor plays an important role in the onset of the disease. Researchers have so far identified 3 genetic loci (ETM 1-3) through family studies, and proposed additional causative genes such as FUS, HTRA2, TENM4, NOS3 and susceptibility genes such as LINGO, SLC1A2, and GABA. This review focuses on the progress made in genetic research on ET.
Essential Tremor ; etiology ; genetics ; Genetic Predisposition to Disease ; Genetic Research ; High-Temperature Requirement A Serine Peptidase 2 ; genetics ; Humans ; Membrane Proteins ; genetics ; Nerve Tissue Proteins ; genetics ; RNA-Binding Protein FUS ; genetics

The concept of focused ultrasound (FUS) and its application in the field of medicine have been suggested since the mid-20th century. However, the clinical applications of this technique in central nervous system (CNS) diseases have been extremely limited because the skull inhibits efficient energy transmission. Therefore, early application of FUS treatment was only performed in patients who had already undergone invasive procedures including craniectomy and burr hole trephination. In the 1990s, the phased array technique was developed and this enabled the focus of ultrasonic energy through the skull, and in conjunction with another technique, magnetic resonance thermal monitoring, the possibility of applying FUS in the CNS was further strengthened. The first clinical trial using FUS treatment for CNS diseases was performed in the early 21(st) century in patients with glioblastoma, which consists of highly malignant primary brain tumors. However, this trial resulted in a failure to make lesions in the tumors. Various causes were suggested for this outcome including different acoustic impedances across heterogeneous intracranial tissue (not only brain tissue, but also fibrous or tumor tissue). To avoid the influence of this factor, the targets for FUS treatment were shifted to functional diseases such as essential tremor, Parkinson's disease, and psychiatric disease, which usually occur in normal brain structures. The first trial for functional diseases was started in 2010, and the results were successful as accurate lesions were made in the target area. Nowadays, the indication of FUS treatment for functional CNS diseases is gradually widening, and many trials using the FUS technique are reporting good results. In addition to the lesioning technique using high intensity FUS treatment, the possibility of clinical application of low intensity FUS to CNS disease treatment has been investigated at a preclinical level, and it is expected that FUS treatment will become one of the most important novel techniques for the treatment of CNS diseases in the near future.
Acoustics ; Brain ; Brain Neoplasms ; Central Nervous System Diseases ; Central Nervous System* ; Essential Tremor ; Glioblastoma ; Humans ; Parkinson Disease ; Skull ; Trephining ; Ultrasonics ; Ultrasonography*