Case analysis of crossed pontine-cerebellar diaschisis in acute stroke patients

Background. Stroke is the second leading global cause of death behind the heart diseases, accounting for 11.8 % of total deaths worldwide. The Monakow concept of diaschisis describes neurophysiological changes that occur distant to focal brain lesion. Diaschisis plays a significant role in the severity of acute neurological deficit and spontaneous stroke recovery. However, currently there are not enough published prospective hospital-based cohort studies that report and analyze clinical characteristics of crossed pontine-cerebellar diaschisis in acute stroke patients. The purpose of this study is to determine the features of the clinical manifestations of crossed pontinecerebellar diaschisis after acute cerebral stroke. Materials and methods. We prospectively recruited 124 acute stroke patients, who were admitted to a single department at an academic tertiary care hospital in Kyiv, Ukraine. The primary outcome was the combined incidence of stroke and diaschisis. In the secondary analyses, we evaluated pathophysiological, anatomical, and clinical features, specific to crossed pontine-cerebellar diaschisis in a cohort of acute stroke patients. Results. Among 124 selected acute stroke patients admitted to the department, 42 (33.9 %) persons were diagnosed with different forms of diaschisis. Crossed pontine-cerebellar diaschisis was detected in 5 patients. We described clinical manifestations and analyzed pathophysiological features of crossed pontine-cerebellar diaschisis in acute stroke patients. Conclusions. The main mechanism of crossed pontine-cerebellar diaschisis is an interruption of ponto-cerebellar pathway from proper nuclei of cerebellum, caused by lesion in the pons.

Purpose: to determine the features of the clinical manifestations of crossed pontine-cerebellar diaschisis after acute cerebral stroke and to improve the efficiency of its diagnosis by comparing the obtained data with the results of the magnetic resonance imaging (MRI) findings.

Materials and methods
We have previously reported in detail the materials and methods of this prospective, hospital-based, cohort study of acute ischemic stroke patients (n = 124) [20-26]. All study participants were admitted to the department of cerebrovascular diseases at the University Hospital within the first 24 hours after the stroke occurred. All stroke cases were reviewed by at least two board-certified neurologists trained in cerebrovascular diseases. Clinical history, 12-lead electrocardiogram, blood testing, carotid ultrasound, head computed tomography and brain MRI, magnetic resonance angio-

ОРИГІНАЛЬНІ ДОСЛІДЖЕННЯ
/ORIGINAL RESEARCHES/ 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.

Results and discussion
In total, 124 patients aged 28 to 84 years with acute ischemic stroke were screened. Among them, 42 patients (22 men and 20 women; mean age 60.8 years) diagnosed with the remote diaschisis were included in the study group. The localization of a primary brain lesion in this group was as follows: brain hemisphere (n = 31), pons Varolii (n = 5), cerebellar hemisphere (n = 6).
Considering the localization of primary brain lesion and secondary dysfunction of neighboring brain structures, we have described and analyzed clinical manifestations and characteristics of cerebrospinal, commissural, crossed cerebellar, and crossed cerebellar hemispheric diaschisis [21,[24][25][26]. In this article, we analyzed clinical manifestations and course of crossed pontine-cerebellar diaschisis.
The crossed pontine-cerebellar diaschisis was diagnosed in 5 of 124 screened acute stroke patients. All five patients with crossed pontine-cerebellar diaschisis had unilateral pontine infarction. Lesions, verified by MRI, were located in the upper rostral region of the pons (n = 2) and in the middle rostral region of the pons (n = 3). All these lesions were in the area of the blood supply of small paramedian arteries, departing from the main artery. Hemodynamically, significant stenosis of extra-or intracranial vessels was not detected in these patients.
Two patients had clinical features, which corresponded to the ventral infarction of the pons Varolii. Three patients demonstrated neurological deficit relevant to the ventralsegmental infarction. Corticopontine fibers and motor pathways (cortical-cerebral, cortical-nuclear), which terminate in the pontine nuclei, are located near the ventral part of the pons. At the upper and middle part of the pons, the fibers of the pyramidal path are scattered into bundles by transversely extending fibers of the ponto-cerebellar pathway. As a part of the middle cerebellar peduncles, it goes to the cortex of the opposite hemisphere of the cerebellum. Therefore, all patients with the lesion in the upper and middle pons showed mild contralateral motor hemiparesis and/or ataxic hemiparesis, facial-brachial monoparesis. However, dizziness, dysarthria, ataxia of the upper extremities with dysmetria, adiadochokinesis, and intentional tremor were prevalent. Dominant symptoms were caused by ipsilateral ischemic lesion in the superior cerebellar artery territory.
Concurrent development of pontine infarction and ischemic lesion in the cerebellar hemisphere contralateral to the pontine infarction was caused by crossed pontinecerebellar diaschisis (Fig. 1).
Pontine infarction and heterolateral diaschisis (hemispheric cerebellar diaschisis with a lesion in the superior cerebellar artery territory) can be explained as follows: interruption of impulses along the cortico-ponto-cerebellar pathway above the second neuron's cross (i.e., interruption of the ponto-cerebellar pathway from proper cerebellar nuclei) caused by lesion in the pons.
These are the characteristics of neurological manifestations and course of different forms of remote diaschisis. Diagnosis of manifestations of different types of diaschisis should be comprehensive and include dynamic clinical neurological assessment after a stroke, the sequence of occurrence/growth of neurological deficit, and the regularity of restoration of lost functions. However, it might be very dif-

Figure 1. Scheme of the afferent and efferent connections of the cerebellum and the mechanism of the development of crossed pontine-cerebellar diaschisis in patients with pontine infarction
Оригінальні дослідження /Original Researches/ ficult to diagnose cerebellar infarction based only on neurological symptoms. The gold standard of early and accurate diagnosis of cerebellar infarction includes such methods of neuroimaging as: MRI, diffusion-weighted magnetic resonance imaging, positron emission tomography, and singlephoton emission computed tomography. Those methods allow clinicians to identify circulatory-metabolic or structural disorders not only in the primary focus of the stroke, but also in the areas remote to it. MRI should be repeated in dynamics, especially during the period of growing neurological deficit. Undoubtedly, it is necessary to perform ultrasound examination of the major vessels of the head and transcranial Doppler ultrasound, electroencephalography.

Conclusions
The von Monakow concept proves that stroke is not only a focal lesion in a certain area of the brain, but is also a circulatory and neurometabolic dysfunction of the entire brain, cortical structures, subcortical formations, and remote anatomical structures that are functionally connected with the foci of brain lesion via conduction system. The clinical manifestations of cerebral stroke were often determined not only by the localization of the main stroke, but also by the phenomenon of diaschisis in the contralateral hemisphere of the brain or cerebellum. Diagnosis of diaschisis manifestations after cerebral stroke should be based on a comprehensive, dynamic assessment of neurological deficit. The sequence of occurrence and regression of this deficit should be based on electrophysiological and neuroimaging findings.

Conflicts of interests.
Authors declare no conflicts of interests that might be construed to influence the results or interpretation of their manuscript.
Author contributions: S.M. Vinychuk -study concept and design, interpretation of data, data acquisition; O.Ye. Fartushna -аrticle concept and design, literature overview, data acquisition, interpretation of data, and drafting the article.