Vol 18, No 2 (2024)

Cover Page

Original articles

Simultaneous dual-target magnetic resonance-guided focused ultrasound treatment for patients with tremor-dominant Parkinson’s disease

Galimova R.M., Illarioshkin S.N., Akhmadeeva G.N., Nabiullina D.I., Kashapov F.F., Safin S.M., Buzaev I.V., Teregulova D.R., Sidorova Y.A., Kachemaeva O.V.

Abstract

Introduction. Non-invasive magnetic resonance-guided focused ultrasound (MRgFUS) is a new neurosurgical treatment option for tremor-dominant Parkinson’s disease (TDPD). Outcomes of ablation with dual targeting of two subcortical nuclei to improve functional treatment results are yet to be explored.

Aim. This study aimed to evaluate the safety and efficacy of MRgFUS with simultaneous unilateral ablation of two cerebral targets in patients with TDPD.

Materials and methods. A total of 82 TDPD patients (20 women, 62 men; median age 65.0 [52.5; 70,0] years) received unilateral MRgFUS, i.e. ventrointermedial (VIM) nucleus thalamotomy and/or pallidothalamotractotomy (PTT). Motor symptoms, including tremor, were assessed using MDS-Unified Parkinson’s Disease Rating Scale Part III (MDS-UPDRS-III). VIM, PTT, and VIM + PTT ablation was received by 34, 12, and 36 patients, respectively.

Results. After surgery, MDS-UPDRS-III score improved by 40.1% (30.2; 51.7) without early or late-onset serious complications. Tremor returned in 18 patients (all after VIM thalamotomy); 9 of them successfully underwent re-treatment 9–12 months after the first procedure. Simultaneous dual-target (VIM + PPT) intervention was successfully received by 36 patients without any serious complications. A total of 89.3% and 69.7% of patients remained relapse-free in the dual-target and single-target groups, respectively (p = 0.039).

Conclusion. Simultaneous dual-target (VIM and PTT) MRgFUS showed favorable safety and efficacy profiles and can be considered a symptomatic treatment option for TDPD patients.

Annals of Clinical and Experimental Neurology. 2024;18(2):5-12
pages 5-12 views

Phenotypes of COVID-19-associated dysautonomia in patients requiring veno-venous extracorporeal membrane oxygenation

Savkov G.E., Petrikov S.S., Rybalko N.V., Khamidova L.T., Markatuk O.Y., Kiselev K.V., Lebedev D.A., Vrabiy Y.N., Altschuler N.E., Popugaev K.A.

Abstract

Background. Patients with novel coronavirus infection (COVID-19) receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO) are typically prone to hemodynamic disorders of various severity. Tachycardia, increased cardiac output, or arterial hypotension affect the effectiveness of VV-ECMO. One of the possible causes of hemodynamic disorders leading to ineffective VV-ECMO may be dysautonomia (DA), which refers to an imbalance of sympathetic and parasympathetic divisions of the autonomic nervous system (ANS). The development of DA in various critical conditions was described previously. Dysautonomia also develops in COVID-19 (COVID-19-associated DA), but it was studied only in stable non-ICU patients. The presented study focuses on COVID-19-associated DA in critical COVID-19 patients requiring VV-ECMO support.

The study was aimed at determining COVID-19-associated DA phenotypes, their impact on VV-ECMO effectiveness and disease outcomes.

Materials and methods. The study included 20 patients: 12 (60%) females, 8 (40%) males. The patients had an average age of 55 years. All the patients underwent 24-hour Holter monitoring with spectral analysis of heart rate variability (HRV) assessing low-frequency component of the spectrum (LF), the high-frequency component of the spectrum (HF), the LF/HF ratio on days 1, 3, and 5 of VV-ECMO. Diagnostic criteria for COVID-19-associated DA was a decrease in LF/HF < 2.28 or an increase in LF/HF > 6.94. The diagnostic criteria of predominant tone of sympathetic nervous system (sympathetic tone) was an increase in LF/HF > 6.94, while a decrease in LF/HF < 2.28 indicated predominant parasympathetic tone. Low sympathetic tone was determined by a decrease in LF < 15%, and an increase in LF > 40%. Low parasympathetic tone was determined by a decrease in HF < 15%, and an increase in HF > 25%. The criteria used were based on the results of previous studies.

The following parameters were registered in the study population: VV-ECMO weaning, duration of respiratory and VV-ECMO support, length of stay in the intensive care unit (ICU) and in hospital, and disease outcomes.

Results. COVID-19-associated DA was diagnosed in all the patients. LF/HF median value was 0.1. HRV spectrum parameters changed significantly over time: on day 5 of VV-ECMO support LF and HF values significantly decreased. The patients were divided into three groups according to the DA phenotype: group 1 (n = 4 [20%]) with normal sympathetic tone and high parasympathetic tone (nShP phenotype); group 2 (n = 14 [70%]) with low sympathetic tone and high parasympathetic tone (lShP phenotype); group 3 (n = 2 [10%]) with low sympathetic tone and normal parasympathetic tone (lSnP phenotype). The latter group was excluded from further statistical analysis due to the small sample size. In group 2, the mean HR was significantly higher compared with group 1. In group 1, VV-ECMO weaning was successful in 50% of cases, whereas in group 2 it was successful in 7.2% (p = 0.04).

Conclusions. To determine a dysautonomia phenotype, it is necessary to continuously monitor DA status in COVID-19 patients during VV-ECMO. Tachycardia in COVID-19 patients during VV-ECMO does not exclude the ANS imbalance with a significant predominance of parasympathetic tone over the sympathetic tone. It is this COVID-19-associated DA phenotype that is significantly associated with the unfavorable outcomes.

Annals of Clinical and Experimental Neurology. 2024;18(2):13-23
pages 13-23 views

Functional MRI-guided repetitive transcranial magnetic stimulation in cognitive impairment in cerebral small vessel disease

Lagoda D.Y., Bakulin I.S., Poydasheva A.G., Sinitsyn D.O., Zabirova A.K., Gadzhieva Z.S., Zabitova M.R., Shamtieva K.V., Dobrynina L.A., Suponeva N.A., Piradov M.A.

Abstract

Introduction. Cerebral small vessel disease (CSVD) is one of the leading causes of vascular and mixed cognitive impairment (CI). Treatment options for CSVD-associated CI are limited. Repetitive transcranial magnetic stimulation (rTMS) is a promising non-drug treatment option.

The aim of the study was to evaluate the effects of 10 rTMS sessions of the left dorsolateral prefrontal cortex (DLPFC) on cognitive functions in CSVD patients.

Materials and methods. The study included 30 patients with CSVD and moderate CI randomized to the active (DLPFC stimulation; n = 20) and control (vertex stimulation; n = 10) groups. Both groups received 10 sessions of high-frequency rTMS. The DLPFC target was selected based on the individual paradigm fMRI data with a focus on executive functions. Cognitive function was assessed using the Montreal Cognitive Assessment Scale (MoCA), the Trail Making Test (TMT), the Tower of London Test, and the Rey–Osterrieth Complex Figure Test before, immediately after, and 3 months after the stimulation. Adverse events were assessed using standardized questionnaires.

Results. The active group showed a significantly better effect compared to the control group according to MoCA, TMT A and B, The Tower of London Test, delayed recall on the Rey–Osterrieth Complex Figure Test immediately after the stimulation and MoCA, TMT A and B and The Tower of London 3 months after the stimulation. Adverse events in the study were mild and did not affect treatment adherence.

Conclusion. rTMS is a promising, safe, and well-tolerated treatment option for mild cognitive impairment in CSVD. However, additional research is needed to make recommendations for its clinical use.

Annals of Clinical and Experimental Neurology. 2024;18(2):24-33
pages 24-33 views

Immunomorphologic assessment of changes in functional astroglial proteins in a kainate-induced hippocampal sclerosis model

Voronkov D.N., Egorova A.V., Fedorova E.N., Stavrovskaya A.V., Potapov I.A., Pavlova A.K., Sukhorukov V.S.

Abstract

Introduction. Astrocytes are involved in mediator metabolism, neuroplasticity, energy support of neurons and neuroinflammation, and this determines their pathogenetic role in epilepsy.

Aim. This study aimed at evaluating region-specific changes in the distribution of functional astroglial proteins in reactive astrocytes in a kainate-induced model of mesial temporal lobe epilepsy.

Materials and methods. The localization and expression of functional astroglial proteins (i.e. aquaporin-4, connexin-43, EAAT1/2, and glutamine synthetase) in the hippocampus CA3 region, dentate gyrus, and stratum lucidum layer were evaluated by immunofluorescence 28 days after intra-hippocampal administration of kainic acid to animals.

Results. Changes were heterogeneous in different hyppocampus subregions. Astrocytes of the stratum lucidum associated with mossy fibers showed the highest vulnerability and decreased content and/or disturbed localization of the channels and transporters that form membrane complexes in the processes. Disturbances in homeostatic functions of astrocytes aggravated the adverse processes both on the side where the toxin was injected and in the contralateral hippocampus.

Annals of Clinical and Experimental Neurology. 2024;18(2):34-44
pages 34-44 views

Changes in contractile characteristics of rat skeletal muscles associated with P2-receptor activation after spinal cord transection

Khairullin A.E., Efimova D.V., Mukhamedyarov M.A., Baltin M.E., Baltina T.V., Grishin S.N., Ziganshin A.U.

Abstract

Introduction. Traumatic spinal cord and peripheral-nerve injury is associated with release of proinflammatory cytokines and chemokines, which may stimulate neuronal activity. Adenosine triphosphoric acid (ATP) is an important pain mediator involved in the acute and chronic neuropathic pain development. Its excessive release from primary injured tissue leads to activation of P2-receptors, which may further start secondary injury mechanisms. Although the effects of ATP on the peripheral nervous system are relatively well studied, the pathophysiological role of purinergic signaling after spinalization remains unclear.

The study was aimed at assessing the post-spinalization effects of P2-receptors on the contractile characteristics of rat skeleton muscles.

Materials and methods. The objects of the study were the soleus muscle, the extensor digitorum longus (EDL) muscle, and diaphragm in intact rats and spinalized rats. Seven days after laminectomy followed by spinal cord transection, animals were anesthetized, exsanguinated, and their muscles with nerve stumps were isolated. Contractile response parameters were recorded using mechanomyography (MMG). To study effects of ATP on ligand binding, ATP was added to a bath and mechanical responses in the rat muscles were assessed 7 min after. After washing with Krebs–Henseleit solution, the preparations were incubated with suramin solution for 20 min with subsequent ATP application. Then the mechanical responses in the muscles were again recorded. Statistical significance was assessed using Student's t-test for independent (unpaired) and paired samples.

Results. We found a significant (p < 0.05) decrease in the modulating activity of ATP, as the main endogenous signaling agent, in the cholinergic synapse of the soleus muscle from 32.4 to 5.8% and from 13.7 to 5.6% for the EDL muscle after the spinalization (spinal cord injury at the Th6–Th7 level) compared with intact animals. No such dramatic changes were observed in the diaphragm.

Conclusions. Abnormal ATP-mediated modulation of neuromuscular transmission demonstrated in this study supports the involvement of purinergic signaling in the neurotrophic control and functioning of various motor units.

Annals of Clinical and Experimental Neurology. 2024;18(2):45-51
pages 45-51 views

Reviews

Dysphagia in neurological disorders

Zaytsevskaya S.A., Lyukmanov R.K., Berdnikovich E.S., Suponeva N.A.

Abstract

Neurogenic dysphagia is a disorder with impaired swallowing, which is caused by various disorders of the central and peripheral nervous systems, neuromuscular transmission, or muscles. Dysphagia is one of the most common and at the same time the most dangerous symptoms of many neurological disorders. Patients with dysphagia often have severe disability, a higher risk of aspiration pneumonia, and significantly increased mortality rate. Despite the availability of many diagnostic screening methods, clinical scales, questionnaires, and instrumental diagnostic methods, the issue of neurogenic dysphagia is underestimated, especially in the early stages. As a result, patients do not receive timely treatment and prevention of dysphagia and associated complications. Validation of available diagnostic scales, development of international protocols and standards for the diagnosis, treatment, and prevention of dysphagia and associated complications are important to establish a unified and evidence-based approach for patients with dysphagia.

Annals of Clinical and Experimental Neurology. 2024;18(2):52-61
pages 52-61 views

Rapid eye movement sleep behavior disorder: modern concept and Parkinson’s disease correlation

Khasanova D.M., Zalyalova Z.A., Ilina G.R., Bagdanova N.I.

Abstract

This review describes the association between rapid eye movement (REM) sleep behavior disorder (RBD) and synucleinopathies, primarily Parkinson's disease. This article reviews the diagnostic criteria, the epidemiology of RBDs, their pathogenesis, and their association with early non-motor symptoms. The data are presented to assess the risk of phenoconversion of RBDs to Parkinson's disease or other synucleinopathies such as Lewy body dementia and multiple system atrophy. A prodromal period of RBDs may precede synucleinopathies years or decades before potential manifestation of motor, cognitive, or autonomic disorders, and this may be important for initiating the neuroprotective therapy. Other causes of RBDs are also reviewed.

Annals of Clinical and Experimental Neurology. 2024;18(2):62-69
pages 62-69 views

Monoclonal antibodies as analgesia of chronic low back pain: a systematic review and meta-analysis of efficacy and safety

Budiputra N., Budiputri C., Muljono M.

Abstract

Introduction. Monoclonal antibodies (mAb) emerged as a possible option in addressing the partial response to current treatment modalities in chronic low back pain (CLBP).

Objective: to evaluate the efficacy and safety of mAb for CLBP.

Materials and Methods. Randomized controlled trials on adult patients with CLBP who received mAb-therapy compared to those who did not as a control group. The result was the changes in Low Back Pain Intensity (LBPI) Numeric Rating Score and Roland–Morris Disability Questionnaire (RMDQ) indicating improved pain, disability, and the risk of adverse events. Meta-analysis, risk of bias, and confidence in the evidence for each analysis were assessed. We aimed at reviewing current treatment methods for degenerative lumbosacral spinal stenosis with an emphasis on surgical treatment methods.

Results. Six studies were included, with a total of 3851 participants. mAb significantly reduce LBPI and RMDQ score (weighted mean difference –1.48; 95% CI –2.63 to –0.33; p = 0.01). Tanezumab and fasinumab were significantly reduced both LBPI (weighted mean difference of –4.11; 95% CI –6.27 to –1.95; p = 0.0002 and weighted mean difference –0.24; 95% CI –0.47 to –0.02; p = 0.04 respectively) and RMDQ scores (weighted mean difference –3.72; 95% –5.48 to –1.97 and weighted mean difference –0.50; 95% –0.73 to –0.26 respectively, both p < 0.0001). The mAb have significantly greater odds of any adverse events (OR 1.23; 95% 1.06 to 1.43; p = 0.007) but no greater odds regarding serious adverse events (OR 1.00; 95% 0.69 to 1.46; p = 0.98).

Conclusion. Depending on the types of drugs used, mAb had a favorable outcome and were relatively safe in reducing LBPI and RMDQ scores.

Annals of Clinical and Experimental Neurology. 2024;18(2):70-83
pages 70-83 views

Optimization of laboratory diagnostics of neuromyelitis optica spectrum disorders: indications and algorithms

Simaniv T.O., Krasnov V.S., Lapin S.V., Bembeeva R.T., Korobko D.S., Belko E.A., Shabalina А.A.

Abstract

Neuromyelitis optica spectrum disorders are a group of autoimmune demyelinating diseases of the central nervous system characterized by severe exacerbations with development of residual neurological deficit. Anti-aquaporin-4 antibody is one of key factor in diagnosing, differentiating, and prescribing pathogenetic therapy. The paper discusses tests and methods of detecting anti-aquaporin-4 antibodies.

Annals of Clinical and Experimental Neurology. 2024;18(2):84-94
pages 84-94 views

Clinical analysis

A man who changed six spectacles: а case of Heidenhain variant of the Creutzfeldt–Jakob disease

Thiruvuru I., Hazeena P., Ramesh R., Shanmugam S., Avadhani D.

Abstract

Creutzfeldt–Jakob Disease (CJD) is a rare and rapidly progressive condition. A 54-year-old professor initially presented with insidious, progressive visual symptoms. Imaging suggested post-infectious encephalitis, but symptoms progressed to ataxia, coordination difficulties, and cognitive decline. Repeat MRI revealed findings consistent with CJD, supported by clinical and electrophysiological evidence. Though 14-3-3 protein in CSF was inconclusive, Heidenhain variant CJD was strongly suspected. Isolated visual symptoms progressing rapidly alongside ataxia and dementia prompt suspicion of this variant. Clinical examination, neuroimaging, and EEG play crucial roles in the diagnosis.

Annals of Clinical and Experimental Neurology. 2024;18(2):95-99
pages 95-99 views

Postoperative hemorrhages in vestibular schwannoma surgery pontine hemorrhage. Clinical case report

Rudenko P.G., Shnyakin P.G., Milyokhina I.E., Usatova I.S., Fayzova M.N.

Abstract

Vestibular schwannoma (acoustic neuroma) is a benign tumor that develops from Schwann cells and can be life-threatening. Nowadays, surgical treatment is the method of choice in the management of patients with this type of tumor.

We present a clinical case report of 71 y.o. patient with vestibular schwannoma (Koos grade IV, Samii grade 4B) with severe compression of the pons and the left cerebellar hemisphere. Microsurgical removal of the tumor was performed via the retrosigmoid approach. Starting from postoperative day 1, signs of respiratory distress developed. Control multislice spiral computed tomography (MSCT) of the brain revealed the area of hemorrhage in the left regions of the pons. On postoperative day 24 the patient's condition rapidly worsened progressing to coma with pronounced arterial hypotonia and cardiac arrest.

Hemorrhage in the brain stem structures is a rare and life-threatening postoperative complication in vestibular schwannoma surgery. The incidence of postoperative hemorrhage is 2–11% of cases. Vascular complications are the leading cause of mortality. The key predisposing factors are older age, large and giant size of the tumor, tumor invasion into the pia mater of the brainstem, and vascularization of the tumor stroma. Comprehensive assessment of the tumor blood supply status, the state of the brainstem, intra- and postoperative clinical and neurophysiological monitoring, careful and thorough dissection of the tumor capsule and strict control of blood pressure in the postoperative period are the basis for the prevention of these complications.

Annals of Clinical and Experimental Neurology. 2024;18(2):100-109
pages 100-109 views


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