FUS-thalamotomy in the correction of tremors in fragile X-associated tremors/ataxia syndrome (FXTAS)

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List of abbreviations

MRI — Magnetic resonance imaging

MRgFUS — Magnetic Resonance-guided Focused Ultrasound

CRST — Clinical Rating Scale for Tremor

hemi-CRST — modified version of the CRST scale for the evaluation of tremors on a single side of the body

DBS — deep brain stimulation

FXPOI — fragile X-associated primary ovarian insufficiency

FXTAS — fragile X-associated tremor/ataxia syndrome

VIM-nucleus — ventralis intermedius nucleus

MCP — middle cerebellar peduncles

BACKGROUND

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a rare neurodegenerative disease resulting from the increase in the number of cytosine-guanine-guanine (CGG) trinucleotide repeats in the FMR1 gene¹, located in the Xq27.3 area. Normally, the number of CGG trinucleotide repeats in this gene varies within the range of 5-44. This gene encodes the synthesis of FMRP protein (Fragile X Mental Retardation Protein) — the critically important regulator, providing the accuracy and the timeliness of the protein synthesis in the neurons, which form the basis of normal brain development, of learning and memory formation. The increase in the number of CGG trinucleotide repeats to the level exceeding 200 results in the “switching off” for the FMRP protein functions and this is accompanied by the development of the fragile X syndrome (FXS), or, according to the name of the authors that have first described it — the Martin-Bell syndrome. The name “fragile Х-chromosome syndrome» is related to the microscopy finding of the constriction in the long arm of the Х-chromosome, due to which the chromosome looks like it has a segment chipped off. The fragile Х-chromosome syndrome is the most common reason of hereditary mental deficiency and of the autistic spectrum disorders. An increase in the number of repeats to the level of 46–54 is considered the “grey zone”. In cases of 55–200 repeats (considered as pre-mutation), the FXTAS syndrome develops.

The FXTAS syndrome was first described by R.J. Hagerman et al. in 2001 [1]. The authors have described 5 elderly men with the pre-mutation and with similar clinical signs — intention tremor, ataxia and impaired regulatory functions. As of today, it was shown that the FXTAS syndrome can develop not only in the carriers of preliminary mutation, but also in the individuals with lesser number of repeats (“grey zone”), as well as with the complete mutation [2]. In women, the pre-mutation in the FMR1 gene can manifest with wider spectrum of clinical symptoms, including the primary ovarian insufficiency, associated with the Х-factor (fragile X-associated primary ovarian insufficiency, FXPOI), as well as the neuropsychiatric disorders (fragile X-associated neuropsychiatric disorders, FXAND) [3, 4]. The meta-analysis conducted by J. Hunter et al. in 2014 [5], has shown that the incidence of pre-mutation is about 1/300 and 1/850 among women and men, respectively. The presence of two Х-chromosomes doubles the risk of mutation carriership in women, but exactly this feature decreases the risk of clinical manifestations of FXTAS in them. According to the data from the conducted research, FXTAS manifests in 40% of men and in 16% of female carriers [6, 7]. The elderly age was associated with a significant increase in the incidence of tremors and ataxia in male carriers. The incidence rate in the age of 50–59 years is 17%, while in the age of 80–89 years — 75% [8]. Thus, the development of FXTAS in the middle and the elderly age men requires alertness in terms of this neurodegenerative disease and requires arranging the DNA tests.

The increase in the number of CGG-repeats among the pre-mutation carriers is associated with earlier age of disease onset and, probably, with more severe disease course [9, 10]. The disease is characterized by the anticipation phenomenon with the increase in the number of CGG trinucleotide repeats with each consecutive generation, increasing from pre-mutation to the fragile Х-chromosome syndrome. The most characteristic age of FXTAS debut is 55–65 years [2]. There are several reports about the patients with early onset of this disease. It is recognized that the environmental factors, such as neurotoxins, insecticides, pesticides, herbicides, environmental contamination, alcohol abuse, narcotic drugs or general anesthesia may induce the earlier onset of the disease and may aggravate the severity of its manifestations [11–13].

The clinical manifestations of FXTAS show significant variability. The most characteristic symptoms are the intention tremor and the cerebellar ataxia. In addition to that, neuropathy, parkinsonism and impaired regulatory and cognitive functions can be often found [14]. Besides, in patients with the pre-mutation of CGG-repeats in the FMR1 gene and without FXTAS, vegetative dysfunctions can be found [15] along with sleep disorders [16], migraine [17], vestibular dysfunction [18] and diminished hearing [19] or olfaction, as well as mental disorders [20]. Among women, the described cases include fibromyalgia [21], autoimmune disorders [22] and the dysfunction of the thyroid gland [21]. Within this context, the diagnostics of FXTAS is quite difficult and requires the differential diagnosis with a wide spectrum of diseases. The course of FXTAS varies extensively. The majority of cases are showing the slow progression with the aggravation of symptoms and with further incapacitation.

The present article provides the description of the clinical case of the diagnostics of tremors-ataxia syndrome and its correction using the focused ultrasound exposure guided by magnetic resonance imaging (MRgFUS). As far as we know, this is the first case of arranging MRgFUS in the Russian Federation for the patients with such a diagnosis.

CLINICAL CASE DESCRIPTION

Patient information

Patient R., aged 62 years, employed as a mining engineer, was admitted on a scheduled basis to the Neurology Department No. 3 of the Federal State Budgetary Institution “Federal Center of Brain Research and Neurotechnologies” under the Federal Medical-Biological Agency (FSBI FCBRN of FMBA of Russia) in November 2024 with the complaints of hand tremors, vocal jitter, head tremors and speech disorders.

Case history. According to oral information provided by the patient and according to the data from the medical documentation, he had tremors in his hands from the kindergarten age. In 90s he was diagnosed with essential tremors. Hopantenic acid was prescribed along with nicotinoyl-gamma-aminobutyric acid, Propranolol, according to oral information provided, with positive effect. Within the last 20 years, the patient was noting the gradual increase of the tremors, developing head tremors, vocal jitter and a decrease of treatment effect. Within the last 5 years, the patient is reporting a significant worsening of his symptoms expressed as the development of significant difficulties when performing his everyday activities, inability of self-care, including the progressing difficulties with taking meals or handwriting; his speech has worsened (becoming less clear). In October 2023, the therapy was supplemented with Clonazepam, however, the patient was not taking the medication. He is also reporting that after consuming alcohol, the intensity of tremors decreases.

Concomitant diseases. Hypertensive disease stage III, grade III; controlled arterial hypertension; risk of developing the cardio-vascular complications — 4 (very high; target blood pressure level — 130/80 mm. Hg.; ICD-10 I11.9). Ischemic heart disease. Post-infarction cardiosclerosis (acute myocardial infarction in 2022). Coronary artery bypass grafting in 2022 (ICD-10 I25.2).

Past medical history. Family history is compromised: tremors in mother, full sister, children (son, daughter). After the additional detailing of the past medical history, it was found that the patient’s daughter had early menopause (at the age of 35 years), while her son (aged 5 years) has a severe form of autism (Fig. 1).

 

Fig. 1. Family tree model with the FMR1 gene mutation Xq27.3.

 

Laboratory and instrumental examinations

Neurological status. No general cerebral or meningeal symptoms were found. The palpebral fissures of the right (oculus dexter) and of the left (oculus sinister) eyes are equal (OD=OS). The pupils are of medium dimensions, OD=OS; the photoreaction is intact. The patient denied diplopia. No oculomotor disorders were found, except for weakened convergence on both sides. Rapidly depleting horizontal nystagmus in the marginal lateral abductions.

The facial muscles are asymmetrical due to the flattened left nasolabial fold. The hearing is intact. The tongue is positioned along the midline. The swallowing is not impaired.

The voice is muffled. The speech articulation is abnormal: dysarthria of the scanning speech type (slowed monotonic speech, interrupted by accenting in each syllable). Vocal tremor.

The muscle strength is sufficient. The muscle tone in the axial muscles shows no signs of abnormalities; in the upper limbs: on the right side — decreased, on the left side — no changes; lower limbs: on the left side — slightly decreased, on the right side — no changes. The motor tests in the upper limbs are non-rhythmic due to tremors, worse on the right side, in the lower limbs — satisfactorily. No resting tremor was found. Tremors in the mandible, head tremor of “no-no” type. Harsh postural-kinetic tremor in the hands.

The posture is normal. No signs of general bradykinesia or hypomimia. The patient is capable of standing up without using the hands for support (first attempt). No signs of gait abnormalities. Hypocheirokinesis on the left side. The tandem gait is slightly impaired (deviating to the sides). Flank gait test — no abnormalities. Postural stability.

The tendon and the periosteal reflexes are active and symmetrical. No pathological foot signs were found. The sensorial tests were unremarkable. Coordination tests: finger-to-nose test with rough intention on both sides, more rough on the left side. Heel-to-shin test — mild intention on the left side, on the right side — satisfactorily. The functions of the pelvic organs (subjectively) are not impaired.

Hallucinations — negative (verbal information provided by the patient). No cognitive disorders: screening for cognitive disorders according to the Montreal Cognitive Assessment (МoCA) — 29 points. No hypersalivation found. The sleep (subjective data) is normal. Mood background — hypothymia.

Thus, the familiar type of tremors with its postural and symmetrical features and with developing at an early age along with the positive alcohol test have allowed for diagnosing the essential tremor (G25.0). What was slightly worrying is the patient’s ataxia and scanning speech. Due to the tremors being resistant to medication therapy, the decision drawn was to arrange a number of additional examinations for the purpose of defining the possibility of arranging the MRgFUS for the correction of tremors.

Instrumental examination. Computed tomography of the brain was conducted with determining the density of cranial bones (skull density ratio, SDR). The SDR was 0.62, signs of symmetrical hypodense areas were found in the middle cerebellar peduncles (MCP) with an involvement of the basal areas of the cerebellar hemispheres, with moderate atrophy in the cerebellum. Thus, the changes may correspond to the manifestations of the neurodegenerative disease (probably, FXTAS).

The brain MRI with magnetic field induction of 1.5 Tesla also has shown signs of symmetrical zones of abnormal superior surface of the cerebellum characteristics in the MCP and in the central areas of the cerebellar hemispheres with a background of their moderate atrophy. Besides, few small foci were found within the white matter, probably, of vascular type. Initial manifestations of cortical atrophy were found (Fig. 2).

 

Fig. 2. Magnetic resonance imaging: Т2-weighted images in the axial plane (а, b), Т1-weighted image in the sagittal plane (c). The visualized findings include symmetrical zones of high signal intensity abnormalities in the MCP (а, arrows) and in the area of the dentate nuclei of cerebellum (b, arrows); atrophy was found in the superior surface of the cerebellum (c, double arrow).

 

Genetic examination. For the purpose of the definitive confirmation of the diagnosis, the patient and his family members have received the recommendations of undergoing the genetic diagnostics of the diseases associated with an increase in the number of CGG-repeats in the FMR1 gene (Martin–Bell syndrome; FXTAS).

In March 2025, the patient (in the out-patient settings) had his sample drawn for the genetic analysis with determining the number of CGG repeats in the FMR1 gene: the findings included an increase in the number of these nucleotide repeats up to 83 in the first allele of the FMR1 gene. DNA-testing was also arranged among the close relatives of the patient: the mother had 66 repeats, the sister — 71 repeats, the sister’s son — 74 repeats and the daughter — 91 repeats. The grandson did not undergo genetic diagnostics testing.

Diagnosis

Thus, the clinical signs of disease, the results of brain MRI showing symmetrical zones of abnormal signal characteristics in the MCP and in the central areas of the cerebellar hemispheres with a background of their moderate atrophy, the results of genetic testing (83 CGG repeats in the first allele of the FMR1 gene) have allowed for setting the following diagnosis: “Neurodegenerative disease with late onset: fragile X-associated tremor/ataxia syndrome (FXTAS) (ICD-10 G11.2)”.

Treatment

In July 2025, the patient was repeatedly consulted at the FSBI FCBRN of FMBA of Russia. Due to the inefficiency of medication therapy, the recommendations included undergoing the stereotaxic thalamotomy on the left side with focused ultrasound.

Before surgical intervention, the patient underwent an evaluation of the intensity of tremors using the CRST clinical scale (Clinical Rating Scale For Tremor) [23] with a total point count of 62, also with using the hemi-CRST (modified version of scale for the evaluation of tremors on a single side of the body, parts А+В) — 20 points (Table 1).

 

Table 1

The results of quantitative evaluation of the severity of tremors using the CRST scale and of evaluating the gait and the resistance according to the Tinetti scale before and after the left-sided thalamotomy with focused ultrasound of the VIM-nucleus

Score	FUS-thalamotomy, points		Improvement, %
	Before	In 24 h
CRST, total point	62	32	48
CRST, part А (total) • right upper limb • left upper limb • tremor of the face/ tongue/ voice/ head	16 5 6 5	10 0 7 3	37.5 100 - 40
CRST, part B (total) • handwriting • drawing spirals (right/left upper limb) • water transfusion test (right/left upper limb)	31 2 11/12 2/4	20 1 3/12 0/4	35.4 50 72.7/0 100/0
Hemi-CRST, part А+В (right/left upper limb)	20/22	4/23	80/-
CRST, part С	15	2	86.7
Tinetti score	38	38	0

 

Along with this, there was an evaluation of the neuropsychological functions and the estimation of resistance and balances using the Tinetti test [24]. According to the apathy scale, the total points count was 4 (absence of apathy) [25], according to the Beck depression inventory — 12 points (mild depression) [26], and according to the Beck anxiety inventory — 30 points (medium anxiety level) [27].

Differential diagnosis

Setting the tremors-ataxia diagnosis is a challenging clinical task and it often requires ruling out other causes for the development of these symptoms. Such a diagnosis should come across the mind in cases of developing tremors and/or ataxia in the middle or in the elderly age, especially with the familial type of disease. The presence of a grandson with autism or delayer mental development of unknown etiology, as well as the female relatives with the onset of menopause at the age under 40 years and with specific features of the mental status, such as anxiety or depression, require arranging the molecular diagnostics tests for the purpose of identifying the probable mutations in the FMR1 gene.

The diagnostic criteria for FXTAS were first established in 2003 [2] and reviewed in 2014 for the purpose of expanding the radiological and clinical criteria [28]. The diagnostic criteria include the major and the minor clinical and neuro-radiological signs (Table 2). The most significant clinical symptoms are the intention tremor and the cerebellar ataxia, the most important neuro-imaging criterion is the bilateral hyperintensity of the middle peduncles of the cerebellum and of the brainstem when using the Т2-weighted or FLAIR MRI-scans. The neuromorphological confirmation of the diagnosis is the detection of the intranuclear ubiquitin-containing inclusions in the neurons and in the astrocytes of the central nervous system. For the diagnostics of FXTAS, the molecular diagnostics of mutation in the FMR1gene is obligatory, including the “grey zone” (i.e. the increase in the number of “cytosine-guanine-guanine” trinucleotide repeats from 46 and higher).

 

Table 2

The diagnostic criteria of FXTAS (D.A. Hall et al., 2014 [28])

Signs	Major	Minor
Radiological	Lesion Foci* in the middle cerebellar peduncle. Lesion foci* in the splenium of corpus callosum	Lesion foci* within the white matter of the brain. Generalized atrophy medium/severe
Clinical	Action tremor. Cerebellar gait ataxia	Parkinsonism. Decreased short-term memory medium/severe. Impaired regulatory functions. Peripheral neuropathy
Histopathological	Pathognomonic for FXTAS eosinophilic and ubiquitin-positive intranuclear inclusions in the neurons and in the astrocytes of the central nervous system	-
FXTAS diagnosis criteria**
Credible	Probable	Possible
1 major clinical + 1 major radiological or histopathological sign	2 major clinical or 1 major radiological + 1 minor clinical sign	1 major clinical + 1 minor radiological sign

Note. * — hypointensive in Т1-weighted and hyperintensive in Т2-weighted MRI-scans; ** — obligatory presence of >45 CGG repeats in the FMR1 gene.

 

At the early stage of FXTAS, the clinical manifestations of the disease can be similar to the ones observed in cases of essential tremor [29, 30]. Due to the fact that essential tremor is often manifesting with gait ataxia and balance disorders from mild to moderate degree, they hamper the differential diagnostics, based only on the clinical symptoms. The summarized data on the differential diagnosis of FXTAS with other diseases manifesting with extrapyramidal and cognitive symptoms, are provided in the Supplement 1.

Treatment

At the moment of the discharge from the In-patient Department (November, 2024), the patient was receiving Sotahexal at a dosage of 40 mg twice daily (morning, evening); Topiramate at a dosage of 25 mg twice daily; Perindopril — 4 mg twice daily (morning, evening); Indapamide — 1.5 mg, 1 tablet in the morning; acetylsalicylic acid + magnesium hydroxide at a dosage of 75+15.2 mg, 1 tablet once daily (evening); Atorvastatin — 20 mg once daily; Clopidogrel — 75 mg once daily (morning).

In the end of July 2025, the patient underwent the left-sided FUS-thalamotomy of the ventral intermediate nucleus (VIM-nucleus) with MRI control. During the process of surgical intervention, a total of 6 ultrasonic exposures were delivered: three calibration ones, a single verification and two therapeutic ones with achieving the average temperature of 57–60°С, and, based on the results of MR-thermometry, the mean duration of sonication was 13 seconds. The duration of treatment was 120 minutes.

Follow-up and outcomes

Right after the treatment, significant clinical improvement was achieved: the total number of points of the CRST scale after surgery has decreased by 48%, of the hemi-CRST score — by 80% (see Table 1; Fig. 3). Data from MRI-scanning: the destruction focus is sufficient (Fig. 4). A decision was drawn up on terminating the procedures.

 

Fig. 3. Spirals drawing test before (а — right hand) and in 24 hours (b) after the exposure of focused ultrasound under the magnetic resonance imaging guidance (MRgFUS).

 

Fig. 4. T2-weighted MRI in axial plane pre-procedure and 24 hours post-MRgFUS thalamotomy: hyperintense lesion in the VIM nucleus region (arrow) with perilesional edema.

 

No intraoperative adverse events or adverse events at the early post-surgery period were registered. No gait or balance abnormalities were found.

Prognosis

Our follow-up had a short-term duration. Sadly, but we did not manage to arrange the dynamic clinical follow-up, for the patient was living at the remote town and in 3 months he could not visit our center, explaining his refusal by his good general status. During telephone questioning, the patient has informed us about the persisting effect developing after surgery and expressed as the significant reduction of tremors and restoring the functional capabilities in his right hand. No adverse events were noted by the patient during the past time period. Based on the available scant literature data with the depth of observation lasting from 6 months to 3 years, it is possible to expect the persisting effect in the mentioned time period [31–35]. At the same time, it is worth noting the imminent further progression of the symptoms of the genetic diseases in future.

DISCUSSION

Our patient had a mild postural-kinetic tremor observed from the early childhood, approximately from the age of 5–7 years. The tremor was increasing in stressful situations, but in other periods it was not impairing the everyday activities, not hampering the school education and not affecting the handwriting. From the age of 43–45 years, the tremor started gradually progressing with the accompanying head tremors. The intake of beta-blockers was resulting in the decrease of tremors. During the last 5 years, the patient was reporting the rapid worsening of his health status. Tremor was increasing to such an extent that the patient could hardly eat, open a bottle of water; handwriting became practically impossible. Dysarthria and gait instability have developed. The analysis of anamnestic data has allowed for suggesting that the patient initially had an essential tremor. However, along with the age, the apparent symptoms of other neurodegenerative diseases have progressed — the tremors-ataxia syndrome, associated with the Х-chromosome. The neuro-imaging data and, above all, the genetic testing have confirmed this diagnosis. The co-existence of FXTAS with other neurodegenerative diseases was described previously: in particular, in FXTAS patients, according to the data from the pathomorphological post-mortem assessment, there were signs of Parkinson disease [36]; in other research, the findings were the combination of FXTAS and Alzheimer’s disease [37].

The interesting feature is the familial type of disease in our patient and the presence of signs of mutation among the four generations of relatives (mother, sister, daughter, daughter’s son and grandson), with this, in the patient’s daughter, the disease was manifesting with mild intention tremor and early menopause, which allows for stating the primary ovarian insufficiency associated with the Х-factor (FXPOI), and which is characteristic for female carriers of the mutation. The number of CGG trinucleotide repeats in her was the maximal in the whole family — 91. In the daughter’s son (the grandson of the patient), no genetic testing was done, but the autistic spectrum disorder was diagnosed, which, taking into consideration the phenotypical features including the elongated face with high forehead, protruding ears and hypermobility of the joints allows for stating the Х-fragile chromosome syndrome.

No therapy for FXTAS is established. As the symptomatic correction for tremors, the patients get prescribed with beta-adrenergic blockers, Primidone, Levetiracetam and Gabapentin with mild efficiency. For the correction of the cognitive dysfunctions, Memantine is recommended. There is a single randomized clinical research with a limited number of participants, showing the efficiency of using Memantine at a dosage of 10 mg in terms of verbal memory, working memory and attention [38, 39].

Patients with significant debilitating tremors, resistant to medication therapy, should consider undergoing functional neurosurgery. Several cases were described with deep brain stimulation (DBS) of the VIM-nucleus of the thalamus for the treatment of refractory tremors in FXTAS patients, the results of which are controversial. When conducting the unilateral thalamic DBS, all the cases were showing a positive result [40, 41]. In patients that underwent bilateral surgery, despite the correction of tremors, the registered findings included the aggravation of ataxia, the development of dysarthria and the decrease in the cognitive functions [42, 43]. Besides, literature data describe the positive result of bilateral stimulation of the ventro-oral posterior (VOP) thalamic nucleus and of the zona incerta (ZI) using the DBS [44].

Among the destructive methods of neurosurgical treatment, which were used in patients with FXTAS, single cases were described with using the stereotaxic radiosurgery (gamma-knife) and the ultrasonic ablation (the MRgFUS method). In 2018 Polish neurosurgeons have conducted the left-sided radiosurgical thalamotomy of the VIM-nucleus in a 73-years old patient with genetically confirmed FXTAS-syndrome, which for more than 20 years had progressive tremor in the limbs, ataxia, dysarthria and mild cognitive disorders. As a result of the conducted surgery, the patient was reporting decreased tremors in the limbs, contralateral to the thalamotomy area (according to the total point count of the clinical tremors scale by 58%), and the improvement of the parameters of everyday activity. No significant effect was shown in terms of ataxia and dysarthria in the abovementioned patient after this procedure [45].

MRgFUS is a quite new surgical method, approved by the Food and Drug Administration in the US (FDA) in 2016 for the treatment of essential tremors. In 2017 this treatment method was approved by the Federal Service for Surveillance in Healthcare of the Russian Federation.

At the present moment, there is only a small worldwide experience of using MRgFUS in cases of FXTAS. In one of the first such publications, the case described was the man aged 77 years with the confirmed diagnosis of FXTAS (based on the specific MRI-signs and DNA-testing), in which, the predominant clinical signs were the incapacitating drug-resistant tremor in the limbs, severe ataxia, akinetic-rigid syndrome and decreased cognitive functions. After the conducted MRgFUS of the thalamic VIM-nucleus, the tremor in the limb contralateral to the ultrasonic exposure area has decreased by 83% when using the Fahn–Tolosa–Marin Tremor Rating Scale (FTM-TRS) — from 12/24 to 2/24. After 6 months of follow-up, the surgery effect in a patient was persisting without the worsening of the gait or speech. The neuropsychological testing of the patient in 6 months after surgery was not arranged, however, it was stated that the clinical signs of cognitive aggravation during the follow-up period were not observed [31]. Significant improvement in the tremors without the progression of ataxia 6 months after surgery was described in another case of an 82-years old patient with the confirmed FXTAS diagnosis (106 CGG trinucleotide repeats in the FMR1 gene) [32]. In 2025, an 18-months follow-up of two patients with FXTAS syndrome after unilateral MRgFUS of the thalamic VIM-nucleus was described. Both patients were showing a decrease in tremors by 70–80% after surgery. The effect was persisting in one patient for 18 months without gait aggravation. In another patient, despite the significant improvement in the disease course during the first month, to Month 6 there was a significant increase in the intention tremor. Dysarthria has also slightly increased after surgery [33].

We have found only one publication with following-up the FXTAS patient after MRgFUS for 3 years. The authors report a long-standing efficiency of surgery without the worsening of ataxia and speech disorders. Within 1 month, the improvement according to the Clinical Rating Scale for Tremor in the left limb was 88%, in 1 year — 74%, in 3 years — 60%. The patient had an improvement in the quality of his life and a decreased total points count according to the FTM-TRS incapacitation scale [34].

Our experience of treating the patient with FXTAS with drug-resistant tremors was also positive. The improvement of the tremor points in the limbs contralateral to the exposure area, 24h after surgery was 80%, the improvement of everyday activity according to the CRST scale (part С) was 87%. We did not observe any aggravation of ataxia, coordination or speech disorders.

Currently, the issue of the safest and the most effective method of surgical treatment in FXTAS patients is quite discussible. The benefit of DBS is the possibility of tremors correction in cases of the progression of the disease due to changes in the stimulation settings. MRgFUS is attractive due to its lesser invasiveness, the instantaneous effect, as well as due to the absence of implanted devices, of ionizing radiation, of the necessity for repeated presenting to the Medical Facility for adjusting the equipment and due to the lesser risk of side effects. However, the accumulated experience of using MRgFUS in patients with essential tremor and Parkinson’s disease shows the recurrence of tremors in several months in 10–20% of the patients [46, 47].

CONCLUSION

The provided clinical case has demonstrated the efficiency and the safety of unilateral thalamotomy using MRgFUS in a FXTAS patient, especially for the phenotype with the predominance of tremors. Nevertheless, before surgery, the patients need to be informed on the progression of this neurodegenerative disease and, thus, the weakening of MRgFUS effect in future.

For the purpose of further evaluation of the efficiency and safety of using MRgFUS in the treatment of tremors, associated with the fragile Х-chromosome, there is a need for following up a larger group of such patients with longer post-operative period.

ADDITIONAL INFORMATION

Supplement 1. Differential diagnostics of FXTAS.

doi: 10.17816/clinpract692161-4390953

Author contributions: E.A. Katunina, definition of the concept, literature analysis, writing the text, editing the final version of the manuscript; N.N. Shipilova, literature analysis, working with data, visualization, writing the text; V.A. Bogomazova, literature analysis, visualization, writing the draft; R.A. Gryaznev, E.A. Malykhina, collection and processing of material; M.B. Dolgushin, S.I. Gumin, visualization; V.M. Dzhafarov, working with data, performing surgical intervention. Thereby, all authors provided approval of the version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Consent for publication: The authors obtained the patient’s written informed consent to publish personal data in a scientific journal, including its electronic version (signed January 27, 2025). The scope of the published data was agreed upon with the patient.

Funding sources: The study had no sponsorship.

Disclosure of interests: The authors declare that they have no competing interests.

Statement of originality: The authors did not use previously published information (text, illustrations, data) while conducting this work.

Data availability statement: The editorial policy regarding data sharing does not apply to this work, data can be published as open access.

Generative AI: Generative AI technologies were not used for this article creation.

 

¹ Full name of the gene: Fragile X messenger ribonucleoprotein 1. Approved HGNC-symbol of the gene: FMR1. Cytogenetic location: Xq27.3. Genomic coordinates (GRCh38): X:147,911,919-147,951,125 (from NCBI).

About the authors

Elena A. Katunina

Federal Center of Brain Research and Neurotechnologies; The Russian National Research Medical University named after N.I. Pirogov

Email: elkatunina@mail.ru
ORCID iD: 0000-0001-5805-486X

MD, PhD, Professor

Russian Federation, Moscow; Moscow

Natalia N. Shipilova

Federal Center of Brain Research and Neurotechnologies; The Russian National Research Medical University named after N.I. Pirogov

Author for correspondence.
Email: natali.33@mail.ru
ORCID iD: 0000-0002-7151-6544
SPIN-code: 8999-4537

MD, PhD

Russian Federation, Moscow; Moscow

Veronika A. Bogomazova

Federal Center of Brain Research and Neurotechnologies

Email: v.r.n.k@mail.ru
ORCID iD: 0009-0004-7073-5472

MD

Russian Federation, Moscow

Roman A. Gryaznev

Federal Center of Brain Research and Neurotechnologies

Email: partiya2009@yandex.ru
ORCID iD: 0009-0001-2365-1186

MD

Russian Federation, Moscow

Elena A. Malykhina

Federal Center of Brain Research and Neurotechnologies; The Russian National Research Medical University named after N.I. Pirogov

Email: elmalykhina@mail.ru
ORCID iD: 0000-0002-2593-5481
SPIN-code: 2980-0173

MD, PhD

Russian Federation, Moscow; Moscow

Mikhail B. Dolgushin

Federal Center of Brain Research and Neurotechnologies

Email: dolgushin.m@fccps.ru
ORCID iD: 0000-0003-3930-5998
SPIN-code: 6388-9644

MD, PhD, Professor

Russian Federation, Moscow

Ivan S. Gumin

Federal Center of Brain Research and Neurotechnologies

Email: ivangumin@mail.ru
ORCID iD: 0000-0003-2360-3261
SPIN-code: 3454-2665

MD

Russian Federation, Moscow

Vidzhai M. Dzhafarov

Federal Center of Brain Research and Neurotechnologies

Email: mvijayd@hotmail.com
ORCID iD: 0000-0002-5337-8715
SPIN-code: 1737-2522

MD

Russian Federation, Moscow

References

Supplementary files