R.M. Galimova 1, S.N. Illarioshkin 2, I.V. Buzaev 3, O.V. Kachemaeva 4
1 Intelligent neurosurgery clinic, Ltd
V.S. Buzaev International Medical Centre (Ufa)
2 FSBSI “Research Center of Neurology” (Moscow)
3 State Budgetary Healthcare Institution “Republican Cardiology Center” (Ufa)
4 FSBEI HE “Bashkir State Medical University” Ministry of Health of the Russian Federation (Ufa)
DOI: 10.24411/2226-079X-2020-12168
The article was published in the Bulletin of the National Society for the Study of Parkinson’s Disease and Movement Disorders No.1 2020.
For patients who have exhausted pharmacological treatment options for tremor, there are currently several important alternative methods in our country – deep brain stimulation ( deep brain stimulation, DBS), radiofrequency
and radiosurgical thalamotomy, MRI-guided focused ultrasound (MRgFUS) [1–7].
Deep brain stimulation and radiofrequency thalamotomy represent
long surgical procedures with
all their difficulties, complications, and
subsequent selection of stimulation parameters, replacement of the generator if DBS и
etc. [1, 8]. Radiosurgical thalamotomy involves a lengthy preparatory
stage, the need for multiple exposures, manifestation of results only
in a few months, as well as radiation exposure to the patient’s body [1].
At the same time, therapy using MRgFUS technology is non-invasive
a single procedure performed on a conscious patient without anesthesia, ensuring continuous feedback with the registration of any discomfort or sensation during the procedure, with timely correction of the location and size of the target brain area [2, 9, 10].
The MRgFUS method is an alternative to neurosurgical interventions for therapy
movement disorders, it is based on two proven effective technologies: focused ultrasound and magnetic resonance imaging (MRI) with
real-time thermometry function
The central nervous system (CNS) has always been the most interesting area for
applications of focused ultrasound with overcoming the bone barrier and the possibility of implementing non-invasive therapy for various pathological conditions. When performing MRgFUS using the company’s neurosurgical system INSIGHTEC controlled non-invasive tissue destruction is performed with high precision (with an average error of 0.50–0.75 mm) without the use of ionizing radiation [11].
An important feature of the system is the ability for reversible impact due to
application of sub-therapeutic levels of ultrasound intensity. This allows for the adjustment of parameters in the area of impact, taking into account the patient’s physiological response even before the start of the treatment procedure
The impact on brain tissue is performed without surgical intervention, in an outpatient setting. The procedure does not require general anesthesia, allowing for constant contact with the patient during the treatment session and, if necessary, adjusting the focus of the impact based on the response to therapy to achieve the most pronounced therapeutic effect [1, 12].
Performing the procedure without surgical intervention means minimal risk of complications and a short recovery period. The result is achieved in just one session, and its intensity is monitored during the manipulation. An additional advantage of the method is that most side effects occur directly during the procedure.
Side effects that persist immediately after treatment usually resolve on their own within a few days [2, 13].
Advantages of this method from the perspective of clinical practice are:
1) non-invasiveness of the method (without trepanation of the skull bones)
2) absence of radiation;
3) determination of the area of impact based on real-time MRI data
4) real-time brain tissue thermometry, which prevents brain damage
5) analysis of the patient’s physiological response during the procedure to minimize neurological complications;
6) precise formation of clear destruction foci from 1 mm in size
7) no need for hospitalization;
8) attracting new categories of patients to the treatment group;
9) achieving competitive advantage in the high-tech medical care market
Advantages of Using MRgFUS for Patients are:
1) therapy without the implantation of any devices
2) instant results
3) minimal risk of infectious complications
4) only 1 treatment session without general anesthesia
5) quick recovery
6) absence of hospitalization in the neurosurgery department
7) personalized treatment – precise targeting of the specific area and affecting only it
Currently, the indications for using this method in neurology and neurosurgery are the treatment of essential tremor and Parkinson’s disease with predominance
tremor, neuropathic pain [10, 14]. Clinical research is being conducted on
destructive impact on primary and metastatic brain tumors, and
also on targeted drug delivery by opening the permeability of the blood-brain barrier, sonothrombolysis, treatment of mental disorders, epilepsy, Alzheimer’s disease [9, 15–17].
Review of clinical outcomes of MRgFUS in patients with medication-resistant tremor has allowed for the identification of clear indications and contraindications, with the development of corresponding clinical guidelines for neurologists, neurosurgeons, and other specialists (Table 1, 2)
Table 1. Indications for the use of MRgFUS in the treatment of patients with essential tremor and
Parkinson’s disease with predominant tremor [11].
| Essential tremor | Parkinson’s Disease |
| Age over 22 years | Age over 30 years |
| Confirmed diagnosis of essential tremor and refractoriness to drug therapy (propranolol or primidone) | Confirmed diagnosis of tremor (Tremor-rigid form of Parkinson’s disease. The tremor persists despite medication therapy. Tremor is the main factor of disability. |
| Absence of contraindications for performing a CT scan of the skull before therapy to determine bone density |
| Absence of contraindications for MRI. No pathological changes in the projection of the thalamus and subthalamic nucleus on brain MRI. |
| The patient’s ability to undergo a therapy session without sedation or with minimal sedation. |
| The patient’s ability to understand and perform movement tests during the procedure and activate the button to stop sonication ( Stop Sonication). |
Table 2. Contraindications for the Use of MRgFUS in the Treatment of Patients with Essential Tremor and Parkinson’s Disease with Tremor Dominance [11]
| Contraindications | Explanations and clarifications |
| Inability to perform MRI | Implanted metal devices, incompatible with MRI (see below); weight limitations; allergy contrast agent; severe claustrophobia that cannot be overcome |
| Presence of implants in the brain or on the skull bones | Shunting systems, electrodes, plates, artificial dura mater, clips |
| Presence of areas in the brain brain, bones, and skin that have increased ультразвуковой абсорбционной ability in projection proposed routes ultrasound waves | Residual changes in the projection of the removed shunt systems, scars on the skin surface, etc. |
| Presence of other diseases from the CNS | Brain tumors, aneurysms, etc. |
| Presence in medical history for previous year defined diseases | Acute Ischemic Cerebrovascular Accidents or hemorrhagic nature; seizure episodes |
| Taking certain medications | Anticoagulants in the previous 2 weeks or medications, increasing the risk of bleeding, within 1 month after the procedure |
| Unstable diseases cardiovascular system and severe arterial hypertension | Unstable angina, regardless of medication intake documented myocardial infarction in the previous 6 months congestive heart failure with ejection fraction left ventricle <40%; unstable ventricular arrhythmia; uncontrolled atrial arrhythmia; severe arterial hypertension (diastolic BP >100 mmHg during intake лекарств) |
| Chronic kidney Kidney failure and undergoing dialysis treatment | Severe renal impairment with an estimated glomerular filtration rate <30 mL/min/1.73 m²; patient on dialysis |
| Infectious disease | Acute period, remission of chronic disease |
| Presence of certain conditions in medical history pathological conditions | Abnormal bleeding; hemorrhages; coagulopathies |
| Pregnancy | At any stage |
| Alcohol abuse and other psychoactive substances | Taking medications that affect the CNS in the previous 6 months |
| Contrast agent administration in the previous 24 hours | Diagnostic studies (MRI, CT, ultrasound, radiological examination) using contrast agents |
| Critical values skull density ratio | Value of the coefficient ≤0.45 (±0.05) according to CT data |
| Personal Characteristics patient | The patient cannot or does not wish to undergo the required procedure stationary position during treatment (approximately 2 hours), cannot independently communicate with staff during therapy |
Table 3 . Differential Diagnostic Features of Essential Tremor and Disease
Parkinson’s with predominant tremor.
| Essential tremor | Tremor in Parkinson’s Disease |
| Tremor – primary, main symptom Diseases. Possible gait issues (tandem walking) and maintaining body balance, but these impairments are usually minimal | Symptoms include bradykinesia, muscle rigidity, resting tremor, and (in a more advanced stage) postural control disorders, freezing, falls, propulsion and retropulsion, etc. |
| High frequency of tremor (8–10 Hz), can decrease as the disease progresses | Low tremor frequency (4–6 Hz) |
| Tremor is postural-kinetic in nature. Resting tremor may be observed, more often in more severe patients with a long course of the disease | Rest tremor. In some patients it may postural tremor observed |
| Handwriting is large and shaky | Handwriting is small, the writing process becomes slow |
| The amplitude of kinetic tremor is greater than the amplitude of postural tremor | Kinetic tremor is rare |
| Family history of the disease in more than 50% patients | Family history of the disease is rare |
| Usually, both sides of the body are involved in the tremor (bilateral tremor), with the shaking possibly being unequal in identical parts of the body | Usually, tremor and other manifestations Parkinsonism symptoms appear on one side of the body and only later spread to the other side |
| The disease can begin at any age (most often – on average) | The disease usually begins at the 6th–7th Decade of life |
| Tremor involves the hands, head, and voice, less often the legs | The tremor involves the hands, legs, chin, and lower jaw, rarely the head and voice |
Patient selection should be conducted by an interdisciplinary team experienced in tremor therapy, including physicians
who have undergone special training in movement disorders. At the preparatory stage, it is necessary to accurately establish the diagnosis and cause of the tremor development.
Characteristic differential diagnostic features of the two most common diseases accompanied by tremor hyperkinesis are presented in Table 3.
Patients and caregivers must understand that currently
the duration of the MRgFUS procedure for treating tremor is initially conducted on one (dominant) side of the body, with a possible subsequent intervention on the contralateral side after 3 months or more (as needed). Before performing MRgFUS, it is mandatory to conduct a computed tomography (CT) scan of the skull bones to determine the overall bone density and identify areas of calcification in the brain. Results
CT scans conducted during the preparatory stage are uploaded to the workstation to determine bone thickness and density for calculating the necessary phasing of the ultrasound wave and ensuring precise focus through the cranial vault bones. Patients with an overall bone density coefficient ≤0.45 (±0.05) according to CT data cannot be admitted for therapy [11].
The results of previous brain MRIs can also help in treatment planning. MRI neuroimaging data is uploaded to the workstation and together with
CT results are used to identify areas to avoid
(for example, areas of calcification)
Based on the analysis of the economic component, a statistically
reliable effectiveness of MRgFUS technology compared to DBS
(p < 0,001) and stereotactic radiosurgery ( p < 0,001) [18]. Projected costs
for therapy using MRgFUS is significantly less than for the procedure DBS
(p < 0,001), what is achieved by the absence of the need for hospitalization, the use of anesthesia, the absence of significant complications, the implantation of a device and its subsequent replacement, the need for repeated visits to adjust the generator parameters. It is precisely due to economic feasibility combined with high efficiency and safety that this method has become the standard of treatment in many countries [5, 19].
MRI-guided focused ultrasound is an effective non-invasive personalized method for treating movement disorders
violations and meets all modern requirements for patient-centered medical care: it is performed quickly, safely, without surgery, without hospitalization, and without the need for general anesthesia.
Patients who have experienced tremor for years and were completely dependent on caregivers for simple daily routines, after a single procedure, easily perform them and become socially adapted individuals.
Today, there are more than 60 medical centers worldwide where
assistance is provided using MRgFUS. In the Russian Federation, the first
the device will be launched in March 2020 at the Intelligent Neurosurgery Clinic, Ltd, V.S. Buzaev International Medical Centre in Ufa. The next step
on the path to expanding the use of MRgFUS in neurology beyond tremor therapy will become
providing assistance to patients with neuropathic pain, depression, obsessive-compulsive disorders, epilepsy, brain tumors, hydrocephalus
and others [9, 15–17]. Given the current data on ongoing research and developments worldwide, it can be concluded that the application of MRgFUS in neurology holds tremendous potential.
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