Investigation of heart rate variability in patients with vertebrobasilar stroke with focal cerebellar lesions

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Relevance: it is well known that cerebellar functions are very diverse. Habitual motor functions such as participation in the regulation of muscle tone, balance, posture maintenance, correction and coordination of slow purposeful movements, participation in programming, memorization and realization of fast unaccountable (ballistic) purposeful movements are carried out by the anterior (upper) lobe of the cerebellum. Less studied functions, such as cognitive, affective, and participation in the autonomic nervous system, are associated with the activity of the posterior lobe of the cerebellum. To study the functioning of the autonomic nervous system (ANS) in patients, many authors use the technique of heart rate variability (HRV) analysis [1], which is considered the “gold standard” in the study of ANS functioning; traditional scales and questionnaires are used to assess cognitive and affective disorders; there is also a specially developed Schmachman scale to study the cognitive-affective syndrome that develops in cerebellar lesions. Autonomic dysfunction, even expressed subclinically, can have a significant impact on the course of stroke in patients.

Purpose: to study and compare the data on heart rate variability (HRV) and non-motor neurological disorders detected by examination and using some evaluation scales in patients with acute cerebral circulatory failure (ACF) in cerebellar artery basins and infarct foci formation in one or both cerebellar hemispheres.
Materials and methods: 26 patients with ischemic stroke in VBBB with focal cerebellar lesions aged from 34 to 78 years were examined on the basis of primary neurological and neurovascular departments of BOOZ VGKBSMP №1 in Voronezh to achieve the goal set in the study. The criteria for inclusion of patients in the study were: age 18 years and older, presence of ischemic stroke (IS) in the VBB confirmed clinically and according to computed tomography (CT) of the brain. The exclusion criteria were: hemorrhagic stroke or cerebellar lesion of other etiology (tumor, posttraumatic cystic-gliosis or parasitic lesion), absence of sinus rhythm in the patient, as this disorder does not allow correct analysis of HRV indices. Six patients were excluded from the study according to the exclusion criteria. Data of 20 patients were included in the final statistical processing.

The following methods were used in the study: 1) clinical and anamnestic, including collection of anamnesis from the patient, his relatives, general clinical and neurological examination; 2) assessment of cognitive, affective disorders, sleep disorders using questionnaires and scales recognized by the medical community: Schmachman Cognitive Affective Syndrome Detection Scale, Frontal Dysfunction Test Battery; HADS Anxiety and Depression Scale, Berlin Sleep Apnea Questionnaire were used; 2) work with patients' medical histories to obtain data on additional methods of investigation: laboratory, instrumental, neuroimaging; 3) literature search by keywords heart rate variability, cerebellum, cerebellar stroke, autonomic dysfunction, non-motor symptoms and compilation of a literature review on the topic of the study using scientific databases “Pubmed”, “Medscape”, “Cyberleninka”, “Elibrary”; The criteria for inclusion in the review were compliance with the search query, age of publication not more than 10 years; 4) study and evaluation of HRV using a two-channel electrocardiographic analog-to-digital converter VNS-Micro of Neurosoft company together with the software POLISPECTR-VR, evaluation and analysis of the main HRV indices: SDNN as a measure of the power of high-, low- and ultra-low-frequency influences and the whole spectrum of neurohumoral influences (norm 30-100 ms) and its analogous spectral index TR reflecting the power of neurohumoral influences (norm 1500-4500 ms2) , RMSSD as an indicator of activity of parasympathetic nervous system (norm 20-50 ms) and similar to it indicator HF% (norm 49,4±9,4%), pNN50 - ratio of activity of parasympathetic and sympathetic parts of regulation (norm 6,3±0,8%), similar in meaning indicator LF/HF, reflecting sympativagal balance (norm 1,5-2), VLF% - indicator of activity of humoral link and suprasegmental structures in regulatory mechanisms (norm up to 30%), LF% - value reflecting the level of activity of sympathetic link in neurohumoral regulation (norm 50, 6±9,4%), SI - stress-index or stress index of regulatory systems (IN, IN=AMo/(2*dRR*Mo)), reflecting the degree of predominance of activity of central regulatory mechanisms over autonomous ones (norm 30-120).

To assess HRV, 5-minute recordings of cardiorhythmogram were recorded in all patients at rest lying down (background recording), 5-minute recording in sitting (in the absence of standing ability) or standing position, i.e., orthostatic test was performed only in patients capable of these actions, there were 5 patients (25%) in our study. All recordings were performed in accordance with international standards.
The obtained data were subjected to statistical analysis using Microsoft Excel and STATISTICA 12 programs (descriptive statistics, nonparametric criteria were used: Mann-Whitney for comparison of 2 independent groups, differences were considered statistically significant at p<0.05; Spearman rank correlation coefficient (r) was calculated, the degree of relationship was considered low at 0.2 < r < 0.29; moderate at 0.3 < r < 0.49, marked at 0.5 < r < 0.69, high at 0.7 < r < 0.89 and very high at r > 0.9. Pearson's X2 test with Yeats' correction for expected frequencies less than 5 was used to compare the two empirical distributions with each other.
RESULTS: The data of 20 patients with AI in WBB with cerebellar lesions between May 2025 and February 2025 were analyzed. The age of the patients ranged from 34 to 78 years, with a median age of 66 years and 25th and 75th percentiles of 56.8 and 70 years, respectively.There were 12 males, representing 60% of the sample, median (Me) age and 25, 75 percentiles were 67 (54; 69) years; females were 8 (40% of the sample), median age 67 (63; 70) years. There were no statistically significant differences in age. All patients showed symptoms of static and dynamic ataxia (instability in the Romberg pose, slips when performing coordinator tests, adiadochokinesis, dysmetria), but in this work we tried to pay the most attention to the study of non-motor functions of the cerebellum, so most of the presented results will be devoted to them.
The right hemisphere of the cerebellum was affected in 7 patients, which amounted to 35% of the examined patients, there were 3 men and 4 women; 11 patients had the left hemisphere affected (55%), 7 of them were men and 4 women, 2 men had bilateral cerebellar lesions (10% of patients). In patients with right-sided and left-sided localization of the focus there were statistically significant differences in the level of high-density lipoproteins (HDL), their level was significantly lower in patients with right-sided foci; the severity of depressive symptoms according to the

HADS. It should be noted that only one patient's scores on this scale reached the subclinical level of depression syndrome severity, while all the others corresponded to normal values, so the obtained results can be considered only as a certain emerging trend that deserves attention and further observation.
Table 1. Medians and 25th and 75th percentiles of the indicators, statistically significantly different in patients with right-sided and left-sided localization of the foci (Mann-Whitney test, p < 0.05).
Indicator Foci on the right
(n=7) Foci on the left
(n=11)

HDL Me (25%; 75%), mmol/L 0.61 (0.58; 0.64) ↓ 1.05 (0.89; 1.25)
HADS depression
Me (25%; 75%), scores 0 (0; 2) 3 (2.5; 4.5)

Nausea and vomiting are common non-motor symptoms detected in cerebellar lesions. When dividing patients according to the presence/absence of nausea/vomiting in the clinical picture of stroke, it turned out that the majority of patients (15 out of 20, which amounted to 75%) had nausea/vomiting, only 5 patients (25%) were absent. The two groups of patients differed statistically significantly in blood sodium levels: in the group with nausea/vomiting Me (25%; 75%) were 141 (138.5; 143) mmol/l, with 2 patients having hyponatremia less than 136 mmol/l, whereas in the group without nausea and vomiting these values were 144 (142.8; 146.3), and 1 patient had hypernatremia of 150 mmol/l. Spearman correlation analysis also revealed a high level of statistically significant negative correlation between blood sodium level and severity of nausea/vomiting in patients, the correlation coefficient r was -0.71. It should be noted that according to the literature [2], the appearance of nausea and vomiting is a frequent symptom of hyponatremia, which often develops in patients with ONMK within the syndrome of inadequate secretion of antidiuretic hormone (ADH) [3].HRV analysis in patients with STEMI in the VBB with focal cerebellar lesions was performed in 17 patients; the following features were noted: the indices of total variability, which are a measure of the power of neurohumoral influences, were reduced in many patients: SDNN in 58.8% of cases, TR - in 64.7%. Deficiency of parasympathetic influences (low RMSSD level) was registered in 11 patients out of 17 (64,7%). In 16 patients out of 17 (94,1%) there was an increased level of VLF%, which indicates an increased activity of suprasegmental structures of the autonomic nervous system, and in 75% of them the level of VLF% exceeded 50%. The stress index of the regulatory systems was elevated in 70.6% of cases, and out of 12 people with elevated SI, in 5 it exceeded the value of 500 units, and in 1 it was more than 1300.
When dividing the patients into groups according to the SDNN level, which is a measure of the power of all neurohumoral influences (the first group included patients with a normal value of the index, n=7, and the second group included patients with a reduced value, n=10), differences by gender were revealed: in the group of normal SDNN values there were 2 men and 5 women, whereas in the group of low SDNN values there were 8 men and 2 women. These groups also differed in many HRV measures and in the results of the MOSA test, which is a screening test for detecting moderate cognitive impairment. The statistically significantly different scores are summarized in Table 2 below. 

Table 2. Medians and 25th and 75th percentiles of indices that were statistically significantly different between patients with normal and reduced SDNN (Mann-Whitney test, p<0.05)
Indicator
Me (25%; 75%) SDNN normal
(n=7)
SDNN decreased
(n=10)

RMSSD, ms 35 (29.5; 51) 10 (6.5; 16)
PNN50, % 8.5 (0.75; 16.35) 0.25 (0; 0.3)
TP, ms2 1929.5 (1702.5; 2474) 272 (118; 442.5)
SI 112.3 (82.9; 162.7) 502.4 (280.6; 817)
MOSA test, scores 26 (25.3; 26) 23 (20; 24)
When patients were divided into groups according to a similar TR indicator, the results of group comparison are the same.

These tables illustrate the fact that patients with CNMD in the VBB with cerebellar lesions with reduced activity of suprasegmental and segmental sections of the ANS demonstrate cognitive impairment in screening tests, whereas patients with a sufficient level of total variability indices and balanced activity of all sections of the ANS perform cognitive tests satisfactorily or with minimal errors.
In the foreign literature we found and translated the original Schmachman scale and instructions for its correct use aimed at detecting cerebellar cognitive-affective syndrome. In the Russian-language literature there are indications of the presence of this syndrome in patients [2], but we have not found any papers using this scale to assess the cerebellar syndrome in patients under study. The original Schmachman scale includes 120 primary (“raw”) points, which are awarded when 12 different types of tasks are performed, including the assessment of semantic, phonemic fluency, memory, switchability, and visual-spatial functions. A patient can score from 2 to 26 points for different types of tasks; if a patient fails to cope with a certain type of task, he or she is given a “penalty” point, the maximum number of “penalty” points is 10.

Normally, healthy people do not receive penalty scores and do well on all tasks. If a patient has 1 “penalty” score, it indicates possible Schmachman syndrome, if 2 - about probable, if 3 or more - about reliable. It should be noted that some types of tasks from the Schmachman scale resemble tasks from the well-known claw screening questionnaires MMSE, MOCA, and the battery of frontal dysfunction tests, but there are also original tasks. The norms and interpretations used in the Schmachman questionnaire also differ from those in the aforementioned cognitive tests.
Of our 20 patients, 18 were examined by the Schmachman questionnaire, 2 refused to participate in this test due to poor health, pronounced headache and general weakness. All 18 patients were found to have reliable Schmachman syndrome with the presence of 3 or more “penalty” scores, the sum of the “raw” scores ranging from 34 to 65% of the maximum possible score. In this regard, it would be interesting to trace the dynamics of cognitive-affective syndrome severity in patients with CNMD in the VBB on the background of treatment and rehabilitation in the acute period, as well as in the early and late recovery periods, but no such studies were conducted within the framework of this work. We would like to note that restoration of cognitive functions and control over affect is as important for restoration of the patient's quality of life as motor rehabilitation.The Spearman correlation analysis revealed statistically significant (p<0.05) positive correlations between the primary (“raw”) scores on the Shmachman scale and such HRV indices as SDNN (r=0.58), TR (r=0.62), as well as VLF (r=0.66), LF (r=0.58), HF (r=0.58), which can be interpreted in the following way: sufficient power of the whole spectrum of autonomic influences is necessary to ensure a higher level of cognitive activity and affect control; the negative correlation between Schmachman scale scores and stress index (r=-0.55) also illustrates the necessity of autonomic balance and low level of stress of body regulatory systems for more effective cognitive activity. Negative correlations were found between the primary Schmachman scale scores and the severity of general weakness (r=-0.49, p<0.05) as well as blood potassium levels (r=-0.56, p<0.05). While pronounced general weakness can be correlated with worse performance on cognitive tests, the data on the possible relationship of lower potassium levels with better performance on the Schmachman cognitive-affective scale require further investigation and study. Hypokalemia was noted in 5 patients (25%), these patients had statistically significantly more frequent and more severe headache than patients with normal blood potassium levels: in hypokalemia, 3 out of 5 patients had severe headache, and in normal potassium levels, 1 out of 15 patients had severe headache, Pearson's X2 with Yeats' correction was 3.75, p=0.0528.
Conclusion. The data presented in this work show that more than half of the patients have reduced indices of total heart rate variability, which indicates depletion of regulatory mechanisms, almost all of them have increased VLF%, and in half of the cases 2 times or more compared to the upper limit of the norm, which indicates excessive activation of suprasegmental structures of the ANS.
It was demonstrated that in patients with CNMD in the VBB with the presence of focal cerebellar lesions not only motor deficit, autonomic disturbances in the form of nausea, vomiting, changes in HRV indices are determined, but also cognitive-affective disturbances described by the Shmachman-Sherman syndrome, which was registered in all patients who agreed to be examined using the same-name scale.
A correlation between closer to normal values of HRV indices and better results on the Schmachman scale was also demonstrated.

About the authors

Anna Mikhailovna Akenteva

Voronezh State Medical University named after N. N. Burdenko; Voronezh State University.

Email: akentevaanna2@gmail.com
ORCID iD: 0009-0007-8409-0996
SPIN-code: 9258-7489
Russian Federation, 10 Studencheskaya Street, Russia, Voronezh, 394036, Voronezh Region

Olga Vasilyevna Polnyanskaya

Voronezh State Medical University named after N. N. Burdenko; Voronezh State University.

Author for correspondence.
Email: olga@polyanskaya.ru
ORCID iD: 0009-0006-9342-8226
SPIN-code: 3969-7878

Associate Professor of the Department of Neurology,
Candidate of Medical Sciences

Russian Federation, 10 Studencheskaya str., Voronezh, 394036, Russia

References

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