doktorska disertacija
Katja Pavšič (Author), Janja Pretnar-Oblak (Mentor)

Abstract

Uvod. Akutna enostranska ishemična možganska kap (IMK) v dorzolateralni podaljšani hrbtenjači (DLPH) lahko poškoduje respiratorni centralni generator vzorcev (angl. respiratory central pattern generator, rCPG). Pri bolnikih z IMK v DLPH bi tako pričakovali pojav motenj dihanja. Klinični potek je kljub temu večinoma ugoden, o klinično pomembni dihalni odpovedi pa so poročali le pri 2?6% bolnikov. Pri bolnikih z različnimi lezijami v podaljšani hrbtenjači in živalskih modelih z lezijami v področju rCPG so bili opisani tudi primeri patoloških vzorcev dihanja (PVD) in motenj dihanja v spanju (MDS). Možno je, da se blažje oz. subklinične oblike motenj dihanja, ki jih odkrijemo s polisomnografijo (PSG), pri bolnikih z IMK v DLPH v resnici pojavljajo pogosteje, vendar ostanejo neprepoznane. Raziskave motenj dihanja in dejavnikih tveganja zanje pri IMK v DLPH so kljub lokaciji lezije v področju rCPG skope. Namen naše raziskave je bil opredeliti 1) pogostnost kliničnih in subkliničnih motenj dihanja pri bolnikih z IMK v DLPH ter 2) povezavo motenj dihanja s klinično sliko in morfološkimi značilnostmi ishemičnih lezij. Hipoteze. Raziskovalno delo je sestavljeno iz dveh povezanih sklopov. V prvem sklopu smo preverjali naslednji hipotezi: 1) Dihalna odpoved se razvije pri bolnikih z IMK v DLPH s težjo bulbarno simptomatiko; 2) Razvoj dihalne odpovedi je odvisen od obsega in položaja ishemične lezije v DLPH. V drugem sklopu smo v treh delih preverjali naslednje hipoteze: 3) Pri bolnikih z IMK v DLPH se pogosto pojavijo subklinične motnje dihanja kot so PVD in MDS; 4) Subklinične motnje dihanja pri bolnikih z IMK v DLPH se pojavijo ob izraženi bulbarni simptomatiki; 5) Pojav subkliničnih motenj dihanja je odvisen od obsega in položaja ishemične lezije v DLPH; 6) Subklinične motnje dihanja in bulbarna klinična simptomatika dosežejo vrh nekaj dni po nastanku IMK v DLPH in se po nekaj mesecih izboljšajo. Metode. V raziskavo smo vključili bolnike z akutno IMK v DLPH z ali brez sočasne IMK v malih možganih. Podatke smo od junija 2008 do septembra 2015 zbirali retrospektivno, od oktobra 2015 do oktobra 2019 pa prospektivno. V prvi sklop raziskave smo vključili tako retro? kot prospektivno zbrane bolnike (96 bolnikov), v drugi sklop pa smo vključili 39 prospektivno zbranih bolnikov, pri katerih smo uspešno opravili PSG. Za primerjavo vzorcev dihanja smo v drugi del raziskave vključili tudi retrospektivno pridobljene PSG posnetke 25 zdravih preiskovancev, ki so v istem obdobju opravili PSG zaradi suma na motnjo spanja. Klinično bulbarno prizadetost smo v obeh sklopih raziskave kvantificirali s pomočjo za namen raziskave pripravljene bulbarne lestvice. Morfološko smo ishemične lezije razvrstili v skupine na podlagi magnetnoresonančne tomografije (MRT). Navpično smo lezije razvrstili v štiri skupine glede na njihov obseg (lokalizirane/obsežne lezije) in položaj (zajemanje zaprtega in/ali odprtega dela podaljšane hrbtenjače). Vodoravno smo lezije razvrstili na velike oz. majhne. Pri prospektivno spremljanih bolnikih smo opravili tudi do tri PSG med hospitalizacijo in eno PSG snemanje po 3?6 mesecih. V prvem sklopu smo ocenili povezanost dihalne odpovedi z bulbarno prizadetostjo in morfologijo lezij. V drugem sklopu smo na podlagi analize PSG opisali pogostnost, vrsto in časovni potek subkliničnih motenj dihanja, kot so MDS in neredni vzorci dihanja. Na podlagi primerjave z zdravimi kontrolami smo opredelili, kateri vzorci dihanja so verjetno patološki. Statistično smo ocenili povezanost PVD oz. MDS z bulbarno prizadetostjo in morfologijo lezij ter primerjali časovni potek bulbarne prizadetosti in MDS. Rezultati. Dihalna odpoved je nastopila pri 15% bolnikov in je bila v univariatni analizi statistično pomembno povezana s klinično sliko (težja bulbarna simptomatika), morfologijo lezij (obsežne odprte lezije, horizontalno velike lezije), ter z drugimi dejavniki kot so aspiracijska pljučnica, ateroskleroza velikih arterij in višja starost. V multivariatni analizi je bila z dihalno odpovedjo neodvisno povezana težja bulbarna prizadetost. MDS, najpogosteje centralne, so bile v akutnem obdobju prisotne pri večini bolnikov. Bolniki z IMK v DLPH so imeli v primerjavi z zdravimi preiskovanci pogostejše in daljše epizode nerednih vzorcev dihanja kot sta ataktično (AD) in periodično dihanje (PD). Pri bolnikih z IMK v DLPH se je pojavljala tudi plitva tahipneja z vztrajno hipoksijo, ki je pri zdravih preiskovancih nismo beležili.. Prisotnost in stopnja resnosti subkliničnih motenj dihanja pri bolnikih z IMK v DLPH so bili statistično pomembno povezani s klinično sliko (težja bulbarna prizadetost), morfologijo lezij (obsežne odprte lezije, horizontalno velike lezije) in višjo starostjo. AD je bilo statistično pomembno pogostejše pri bolnikih s sočasno IMK v malih možganih. Bulbarna simptomatika se je nekaj dni po nastopu IMK pogosto pomembno poslabšala in se nato spet izboljšala. Subklinične motnje dihanja so dosegle vrh v različnih časovnih obdobjih in niso vedno sledile dinamiki bulbarne prizadetosti, nakazan pa je bil trend izboljšanja iz akutnega v subakutno obdobje. Zaključki. Ugotovili smo, da se pri večini bolnikov z IMK v DLPH v akutnem obdobju pojavijo subklinične motnje dihanja različnega spektra, pri manjšini bolnikov pa se razvije klinično pomembna dihalna odpoved s potrebo po mehanskem predihavanju. Motnje dihanja so najizrazitejše pri bolnikih s težko bulbarno prizadetostjo in obsežnimi lezijami, ki zajemajo odprto podaljšano hrbtenjačo in lahko poškudujejo velik del bulbarnega in respiratornega CPG, povezave med levim in desnim CPG ter inspiratorne nevrone v odprti podaljšani hrbtenjači. Pri slednjih bolnikih je možen tudi razvoj dihalne odpovedi, h kateri prispevajo tudi starost, aspiracijska pljučnica in verjetno tudi drugi še neprepoznani dejavniki, kot je nagnjenje posameznika k respiratorni nestabilnosti. Izboljšanje motenj dihanja v subakutnem obdobju nakazuje na možno funkcijsko ali plastično reorganizacijo respiratornega mrežja.

Keywords

nevrologija;cerebrovaskularne bolezni;enostranska ishemična možganska kap;podaljšani hrbtni mozeg;podaljšana hrbtenjača GLEJ: podaljšani hrbtni mozeg;dihalne motnje;respiratorni centralni generator vzorcev;dihalna odpoved;subklinične dihalne motnje;ishemične lezije;Bolezni dihal;Disertacije;Dihanje;Težave;Zapleti;Možganska kap;Bolezni živčevja;Možgani;Posledice;

Data

Language: Slovenian
Year of publishing:
Typology: 2.08 - Doctoral Dissertation
Organization: UL MF - Faculty of Medicine
Publisher: [K. Pavšič]
UDC: 616.831-005.1-06(043.3)
COBISS: 60892419 Link will open in a new window
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Other data

Secondary language: English
Secondary title: Breathing disorders in patients with acute unilateral dorsolateral medullary ischaemic infarction
Secondary abstract: 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.
Secondary keywords: Dihanje;Možganska kap;Ishemična možganska kap;Disertacije;Komplikacije;Motnje;Lateral medullary syndrome;Respiration;Physiology;Respiration disorders;Sleep wake disorders;Stroke;Etiology;Polysomnography;Spinal cord;Spinal cord injuries;Patients;Data interpretation, statistical;Methods;Retrospective studies;Prospective studies;Lateralni medularni sindrom;Fiziologija;Motnje dihanja;Motnje spanja in zbujajnja;Etiologija;Polisomnografija;Hrbtenjača;Poškodbe hrbtenjače;Bolniki;Statistična interpretacija podatkov;Metode;Retrospektivne študije;Prospektivne študije;
Type (COBISS): Dissertation
Study programme: 0
Embargo end date (OpenAIRE): 1970-01-01
Thesis comment: Univ. v Ljubljani, Medicinska fak.
Pages: 112 str.
ID: 12216172