Clinical syndromes of thalamic stroke in the central vascular territory: a prospective hospital-based cohort study

Background. The article covers pathophysiological features and patterns of the occurrence of neurological, neuropsychological, and clinical vascular syndromes of thalamic stroke in the central vascular territory. The features of neurological clinical picture, topical, and neuroimaging diagnosis of thalamic stroke in the central vascular territory are analyzed and described in a prospective hospital-based cohort study. The purpose of this study is to determine the features of clinical vascular syndromes of acute thalamic stroke in the lower lateral and adjacent (central, posterolateral) vascular territories in a prospective hospital-based cohort study, providing a comprehensive clinical and neuroimaging analysis. Materials and methods. We have prospectively recruited 319 acute stroke patients, admitted to the Neurological Center at an academic hospital (Oleksandrivska Clinical Hospital) in Kyiv, Ukraine, within 24 hours from the onset of the stroke symptoms. Comprehensive neurological, clinical, laboratory, ultrasound, and neuroimaging examinations were performed to all study patients. Results. MRI-/CT-proven thalamic stroke was diagnosed in 34 (10.6 %) of 319 people, forming a study group. Twenty-two of 34 patients (average age 61.9 ± 10.2 years) were diagnosed with acute isolated ischemic thalamic stroke, and 12 (average age 59.0 ± 9.6 years) had acute thalamic hemorrhage. Conclusions. Specific neurological features of clinical vascular syndromes of acute thalamic stroke in the central vascular territory were analyzed, compared, and described.


Introduction
Notably, stroke is a leading cause of mortality and disability worldwide, and the economic costs of treatment and post-stroke care are substantial. Every two seconds, someone in the world has a stroke [1][2][3][4][5][6][7][8][9]. In addition, more young people are affected by stroke in low-and middle-income countries. The incidence of stroke is highest in East Asia, followed by the Eastern Europe, whereas the lowest rates were in Central America [8,[20][21][22]. As populations age, and low-and middle-income countries go through the epidemiological transition from infectious to non-communicable diseases as the predominant cause of morbidity, together with a concomitant increase in modifiable risk factors, it is expected that the burden of stroke will further increase until effective stroke prevention strategies are more widely implemented [20,21]. Thalamic strokes, both alone and in combination with strokes involving other structures, are not rare, accounting for approximately 11 to 23-25 % of all posterior circulation strokes, especially in combination with damage to other structures [23][24][25].
The thalamus, with its cortical, subcortical, and cerebellar connections, is a critical node in networks supporting cognitive and motor functions, managing our sensitiv-ity to a temperature, light, and physical touch. It controls the flow of visual, auditory, and motor information, being also involved in different aspects of learning, memory, speech, language understanding, motivation, attention and wakefulness, being in charge of our sense of balance and awareness of our arms and legs. It controls how we experience pain, and even emotional experiences, expressions, and our personalities involve the thalamus. However, currently, there are not enough published prospective hospital-based cohort studies that report and analyze pathophysiological features and patterns of the occurrence of neurological, neuropsychological, and clinical vascular syndromes of thalamic stroke in the central vascular territory, and their topical diagnosis using clinical, neurological, and neuroimaging methods in a prospective hospital-based cohort study [25][26][27][28][29][30][31]. Given all this, we performed a comprehensive clinical and neuroimaging analysis of the treatment results and assessed the outcome of the disease in 34 patients with thalamic stroke: 22 of them had isolated thalamic infarction and 12 -hemorrhage in the thalamus.
The purpose of this study is to describe and analyze the clinical and neuroimaging features of vascular syndromes of thalamic stroke in the central vascular territory in a prospective hospital-based cohort study, providing a comprehensive clinical and neuroimaging analysis.

Study setting and patients
We have conducted a prospective hospital-based cohort study of acute thalamic stroke patients. All participants were admitted to the Neurological Center of Oleksandrivska Clinical Hospital (Kyiv, Ukraine) within the first 24 h since the first stroke symptoms occurred. The Neurological Center of Oleksandrivska Clinical Hospital consists of an admission department, clinical department of neurology, department of cerebrovascular pathology with intensive care/stroke unit, and a research department of neurology. Study subjects were recruited from the hospital emergency departments, and hospital wards between 2001 and 2011. All stroke patients were reviewed by at least two board-certified neurologists with training in cerebrovascular diseases. Clinical history, 12-lead electrocardiogram, blood testing, carotid ultrasound, head computed tomography (CT) and/ or brain magnetic resonance imaging (MRI) were obtained for all participants.

Patient inclusion and exclusion
The methods of the study, inclusion and exclusion criteria have been reported in detail previously [29][30][31][46][47][48]. In brief, only acute thalamic stroke patients aged 18 years or older were included.

Study endpoints and risk factors definitions
Study endpoints of interest were acute ischemic and/ or hemorrhagic thalamic strokes. Stroke was defined according to the criteria of the World Health Organization, American Heart Association/American Stroke Association guidelines for adult stroke, and was confirmed by neuroimaging [32,33]. The etiology of stroke was classified according to the TOAST criteria [34]. The National Institutes of Health Stroke Scale, the Modified Rankin Scale, the Barthel index, and the Charlson Comorbidity Index were determined for all participants. Secondary stroke prevention was prescribed according to the American Heart Association/American Stroke Association and the European Stroke Organisation guidelines, immediately after the stroke diagnosis was made [35][36][37][38][39][40][41]. Stroke education programs were provided to all study participants [11,16,30,[42][43][44][45][46][47][48].

Statistical analysis
Parametric and non-parametric statistic methods were applied. The log-rank test was used for univariate comparisons of event-free survival between groups. A two-sided p < 0.05 was considered significant for all analyses. All statistical analyses were performed using IBM SPSS Statistics Version 22.

Basic characteristics of study population
In total, 319 adult patients with acute MRI-/CTproven stroke were screened, 34 of them were diagnosed with thalamic stroke, forming a study group. Twentytwo (12 men, 10 women aged 50-84 years; average age 61.9 ± 10.2 years) of 34 study group patients were diagnosed with acute isolated ischemic thalamic stroke, and in the rest 12 patients (5 men, 7 women aged 57-75 years; average age 59.0 ± 9.6 years), thalamic hemorrhage was detected.

Vascular symptoms of stroke in the central thalamic vascular territory
Stroke of the central vascular territory was detected in 2 (9.1 %) patients. This area consists of few thalamic zones that are mainly located between the paramedian, upper and lower lateral territories. These zones are the distal territories of three arterial systems: paramedian, tuberothalamic, and thalamogeniculate. Strokes of the central vascular territory were caused by arterial hypertension and accompanied by impaired consciousness, short-term verbal and visual memory, cognitive impairment, contralateral homonymous hemianopsia, emotional central paresis of facial muscles, vertical gaze palsy, hemihypesthesia, and sensitive ataxia on the side opposite to the lesion.
Isolated thalamic infarction of the central vascular territory is often manifested itself by hemianesthesia, bianesthesia associated with ataxia due to damage to the middle part of the ventral posterolateral nucleus. At the same time, a variety of neuropsychological disorders are revealed. In our study, in one patient we determined the asymmetry of the face that appears during pain, smile, and laughter, so-called emotional central paresis of the facial muscles. However, all voluntary facial movements (frowning, closing eyes, grinning) persisted. This symptom was described by the one of the most eminent research workers and clinicians in the second half of the www.mif-ua.com, http://inj.zaslavsky.com.ua Том 16, N№ 5, 2020 Оригінальні дослідження /Original Researches/ 19 th century, an Austrian physician Hermann Nothnagel. The occurrence of this particular symptom is associated with the damage to the Luys body and the psychoreflex pathway for mimic movements, the sensitive part of which is represented by the thalamus, and the motor part is represented by the extrapyramidal system. The role of the mimic center is attributed to the median nuclei of the thalamus [30]. Thalamic stroke in the central vascular territory interrupts this arc, and, as the result, emotional paresis of the facial muscles develops. Mimic disorders in this case are one-sided. Abnormal upward gaze is an expected symptom due to a pathological effect on the supranuclear pathways responsible for vertical gaze control.

Clinical and anatomical correlation of thalamic strokes
For a better understanding of the vascular syndromes that occur after thalamic stroke, we analyzed a clinical and anatomical correlation of thalamic strokes based on the detailed description of neurological symptoms and arterial localization of stroke foci, verified by the neuroimaging methods (Table 1).
Thus, isolated thalamic strokes represent a heterogeneous group of strokes that are divided to those of the anterior, paramedian, lower lateral, and posterior vascular and anatomical territories.

Conclusions
Summarizing, we would like to highlight that the loss of consciousness, contralateral hemianesthesia, hemiataxia, homonymous hemianopsia, emotional central paresis of facial muscles and cognitive impairment were detected in patients with stroke in the central vascular territory.
Conflicts of interests. Authors declare the absence of any conflicts of interests and their own financial interest that might be construed to influence the results or interpretation of their manuscript.

Author contributions
S.M. Vinychuk -study concept and design, statistical analysis, interpretation of data, literature overview, critical revision of the manuscript for important intellectual content; M.M. Prokopiv -study concept and design, data acquisition, statistical analysis, interpretation of data, literature overview, critical revision of the manuscript for important intellectual content; L.M. Trepet -study design, data acquisition, statistical analysis, interpretation of data; O.Ye. Fartushna -study concept and design, literature overview, statistical analysis, interpretation of data, article concept and design, drafting the article, critical revision of the manuscript for important intellectual content.

Vascular system
Neurological symptoms

Occlusion of some branches of the inferolateral or thalamogeniculate artery
Pure sensory syndrome -the focus of ischemia is localized in the region of the lower lateral thalamus: -complete sensory syndrome -a decrease in the superficial and/or deep sensitivity by the hemitype in the absence of hemianopsia, aphasia, agnosia and apraxia; -incomplete -decreased sensitivity on the face, arm, or leg; -cheiro-oral syndrome -impairment of pain sensitivity in the region of the angle of the mouth and in the palm heterolaterally; -cheiro-oral-pedal syndrome -hypalgesia in the area of the angle of the mouth, palm, and foot from the opposite side without a motor function impairment

Occlusion of the branches of the lower lateral or thalamogeniculate artery
Sensorimotor lacunar stroke -ischemia focus from the lateral thalamus extends to the adjacent tissue of the internal capsule: -sensitivity disturbance on the side opposite to the focus, but disorders of sensitivity can be preceded by impaired motor skills