Clinical syndromes of thalamic strokes in posterolateral 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 the thalamic strokes in posterolateral vascular territories. The features of the neurological clinic, topical, and neuroimaging diagnosis of thalamic strokes in posterolateral vascular territories are analyzed and described in a prospective hospital-based cohort study. We aimed to describe and analyze the clinical and neuroimaging features of vascular syndromes of thalamic strokes in posterolateral vascular territory in a prospective hospital-based cohort study. Materials and methods. We have prospectively recruited 319 acute stroke patients, admitted within 24 hours from the onset of the stroke symptoms to the Neurological Center at an academic hospital (Oleksandrivska Clinical Hospital) in Kyiv, Ukraine. Complex 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 %) out of 319 patients, forming a study group. Twenty-two out of 34 patients (average age 61.9 ± 10.2 years) were diagnosed with an acute isolated ischemic thalamic infarction, and 12 patients (average age 59.0 ± 9.6 years) were diagnosed with an acute thalamic hemorrhage. Specific neurological features of clinical vascular syndromes of acute thalamic strokes in posterolateral vascular territories were analyzed, compared, and described.

Thalamic strokes are not rare, accounting for approximately 11 to 23-25 % of cases of all posterior circulation strokes, especially in combination with damage to other structures [23][24][25]. The thalamus is involved in aspects of learning, memory, speech, language understanding, motivation, attention and wakefulness, manages our sensitivity to temperature, light, and physical touch, and is 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. 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 the thalamic stroke in posterolateral vascular territories, and their topical diagnosis using clinical, neurological, and neuroimaging methods in a prospective hospital-based cohort study [25][26][27][28][29][30].
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, among whom 22 patients were with isolated thalamic infarction and 12 had 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 posterolateral vascular territories 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 study participants were admitted to the Neurological Center of Oleksandrivska Clinical Hospital, Kyiv, Ukraine, within the first 24 h since the first stroke symptoms had 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. All stroke patients were examined 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 study participants.

Patient inclusion and exclusion
The methods of the study, inclusion and exclusion criteria have been reported in detail previously [29-31, 46, 47]. 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 stroke. Stroke was defined according to the criteria of the World Health Organization, American Heart Association/American Stroke Association (AHA/ ASA) 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 AHA/ASA and the Euro-pean 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]].

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 an acute MRI/CT-proven stroke were screened, 34 of whom were diagnosed with a thalamic stroke, forming a study group. Twenty-two (12 men, 10 women aged 50 to 84 years; average age 61.9 ± 10.2 years) out of 34 study group patients were diagnosed with an acute isolated 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 a stroke in the posterolateral thalamic vascular territory
Stroke of the posterior choroidal artery manifested itself in oculomotor disturbances, visual field deficiency, hyperkinetic syndrome, hand tremor, dystonia, and myoclonus of the fingers. Such abnormalities are referred to by the term "jerky dystonic arm" [30].
A sensitivity impairment with the development of a purely sensory syndrome that is caused by the damage to the ventrolateral nucleus is a typical manifestation of a stroke in the posterolateral vascular territory of the thalamus. Moreover, hemihypesthesia syndrome can be complete or partial with a disturbance of sensitivity in unusual combinations, such as cheiro-oral and cheiro-oral-pedal syndromes. The isolated oral syndrome is also detected in patients with a stroke in the posterior choroidal artery. This can be explained by the peculiar somatotopic organization of the thalamus as sensory projections of the face (especially lips, tongue) are somatotopically represented in the ventral posterior medial nucleus and have a particularly large representation that increases the likelihood of a damage to it with an acute stroke. Sensory projection fields from the trunk and proximal limbs are relatively small compared to the sensory projections of the face, and somatotopically represented by the ventral posterolateral nucleus, located more dorsally and therefore can selectively remain intact during the thalamic stroke [30]. Cognitive impairment manifested itself in an impaired memory and psychosensory impairment -hallucinosis.
In our cohort study, stroke in the posterolateral thalamic vascular territory was detected in 5 (22.7 %) patients. It occurred during the occlusion of thalamogenicular artery branches that vascularize ventrolateral thalamus, including the posterolateral, ventral, and medial thalamic nuclei. A typical manifestation of a stroke in posterolateral vascular territory of the thalamus was represented by sensitivity and cognitive impairments. In this case, the hemisensory syndrome was complete in two patients and incomplete in three. The complete hemisensory syndrome manifested itself in a superficial and deep sensitivity decrease, hemiataxia or a feeling of numbness of the skin by a hemitype in the absence of homonymous hemianopsia, aphasia, agnosia, and apraxia. In a case of incomplete hemisensory syndrome, sensory impairments were presented not in the entire half of the body, but only in the face, arm, or leg. In two patients, cheiro-oral syndrome was detected when sensitivity impairment occurred in the region of the angle of the mouth and palm homolaterally; in another patient, cheiro-oral-pedal syndrome was detected that manifested itself in hypoesthesia of pain and temperature sensitivity in the region of the angle of the mouth, palm and foot on the one side without any motor disorders. Three patients demonstrated moderate cognitive impairment: spatial memory impairment was detected in two patients with a right thalamus infarction, verbal memory impairment was observed in one patient with a stroke in the left posterolateral adjacent thalamus territory.
In one patient, psychosensory disorders that manifested as hallucinosis were noted. The visual hallucinations were true, specific, mainly visual, arose during a normal patient state, consisted of live scenes of colorful and non-hostile people or animals, and stereotypically repeated mainly in the evening or at night and lasted from several seconds to several hours; associated disorders were sleep disorders. It is believed that the occurrence of hallucinosis is due to a damage to the projection centers in the pulvinar of the thalamus, or the medial nuclei of the thalamus or the rostral section of the brainstem (brain peduncles). Therefore, the described disorders are known in the literature as "peduncular hallucinosis" [30].
The main risk factors for the development of thalamic stroke in the posterolateral vascular territory were arterial hypertension (in three patients), as well as diabetes mellitus and hypercholesterolemia (in two patients).

Conclusions
The development of a purely sensory syndrome (complete or in unusual combinations) or a sensorimotor syndrome, mild cognitive impairment, and psychosensory disturbances (hallucinosis) are typical manifestations of a stroke in the posterolateral 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:
Stepan M. Vinychuk -study concept and design, statistical analysis, interpretation of data, literature overview, critical revision of the manuscript for important intellectual content; Maria M. Prokopiv -study concept and design, data acquisition, statistical analysis, interpretation of data, literature overview, critical revision of the manuscript for important intellectual content; Larysa M. Trepet -study design, data acquisition, statistical analysis, interpretation of data; Olena 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.