Introduction. Acute unilateral lateral medullary infarction (ULMI) may damage the respiratory central pattern generator (rCPG). Respiratory dysfunction would be therefore expected in patients with acute ULMI. However, the clinical course is usually benign and overt respiratory failure was reported in only 2–6% of such patients. Lesions of specific sites within rCPG in animal experiments and lesions of different parts of the medulla oblongata in human cases identified various pathological breathing patterns (PBPs) and sleep䀒disordered breathing (SDB). It is possible that milder forms of respiratory disturbances, which can be detected by polysomnography (PSG), actually occur more frequently in these patients but remain unrecognized. Existing studies on respiratory disturbances and their associated risk factors in ULMI are scarce despite the lesion location at the rCPG. The aim of our study was to 1) estimate the prevalence of clinical and subclinical respiratory disturbances in patients with ULMI and 2) investigate the association between the respiratory disturbances, clinical picture and morphological characteristics of ischemic lesions.
Hypotheses. This research work consists of two related sets. In the first set, we tested the following hypotheses: 1) Respiratory failure develops in ULMI patients with more severe bulbar symptoms; 2) The development of respiratory failure depends on the extent and position of the ischemic lesion in the dorsolateral medulla. The second set consists of three parts in which we tested the following hypotheses: 3) Subclinical respiratory disturbances such as PBP and SDB are frequent in ULMI patients; 4) Subclinical respiratory disturbances occur in ULMI patients with pronounced bulbar symptoms; 5) The occurrence of subclinical respiratory disturbances depends on the extent and position of the ischemic lesion in the dorsolateral medulla; 6) Subclinical respiratory disturbances and bulbar symptoms peak a few days after the onset of ULMI and improve after a few months.
Methods. We included the patients with acute ULMI with or without concomitant cerebellar infarction. Data were collected retrospectively from June 2008 to September 2015, and prospectively from October 2015 to October 2019. The first set of the study included both retro䀒 and prospectively included patients (96 patients), and the second set included 39 prospectively included patients who successfully underwent the PSG. For the comparison of the breathing patterns, we also retrospectively reviewed the PSGs from 25 healthy subjects who underwent a diagnostic PSG due to suspected sleep disorder during the study period.
Clinical bulbar dysfunction was quantified using a bulbar scale designed for this study. Ischaemic lesions were categorized based on their morphological characteristics on magnetic resonance imaging (MRI). Vertically, the lesions were categorized into four groups based on their extension (localized/extensive) and position (involvement of the closed and/or open medulla). Horizontally, the lesions were grossly categorized as large or small. The prospectively followed patients underwent up to three PSGs during the hospitalization and one PSG after 3䀒6 months.
In the first part of the study we assessed the clinical and morphological factors associated with respiratory failure. In the second part of the study we described the prevalence, types and time course of subclinical respiratory disturbances, such as SDB and irregular breathing patterns. We defined the probably pathological breathing patterns (PBP) by comparing the ULMI breathing patterns to healthy subjects. We statistically analyzed the association between PBP/SDB, bulbar dysfunction and lesion morphology, and compared the time course of bulbar dysfunction and SDB.
Results. Respiratory failure occurred in 15% of patients and was statistically significantly associated with the clinical picture (severe bulbar symptoms), lesion morphology (extensive open lesions, horizontally large lesions), and other factors such as aspiration pneumonia, large artery atherosclerosis and older age in the univariate analysis. Severe bulbar dysfunction was independently associated with respiratory failure in the multivariate analysis.
SDB, predominately central, was present in most patients during the acute period. Compared to healthy subjects, ULMI patients presented with more frequent and prolonged episodes of irregular breathing patterns, including ataxic (AB) and periodic breathing (PB), and even shallow tachypnea with sustained hypoxia, which was not observed in healthy subjects.
The presence and severity of subclinical respiratory disturbances in ULMI patients were statistically significantly associated with clinical picture (severe bulbar symptoms), lesion morphology (extensive open lesions, horizontally large lesions), and older age. AB was statistically significantly more frequent in patients with concomitant cerebellar infarction.
Bulbar symptoms often worsened a few days after the onset of stroke and later improved. Subclinical respiratory disorders peaked at different time periods not always following the dynamics of bulbar symptoms, however a trend of improvement from the acute to subacute phase was noted.
Conclusions. We found that a wide spectrum of subclinical respiratory disturbances occurs in most ULMI patients during the acute disease phase, while overt respiratory failure warranting mechanical ventilation develops in minority of them. Respiratory disturbances are most pronounced in patients with severe bulbar dysfunction and extensive lesions involving the open medulla, which may damage a significant portion of the rCPG, its contralateral connections and the inspiratory neurons in the open medulla. Overt respiratory failure may occur in the latter patients and is further associated with factors such as age, aspiration pneumonia and probably also other as yet unrecognized factors, such as the individual's tendency to respiratory instability. The observed improvement of the respiratory disturbances in the subacute phase suggests a possible functional or plastic reorganization of the respiratory network.
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