| Abstract | PB je progresivna neurodegenerativna bolest uzrokovana degeneracijom dopaminergičkih neurona substantie nigre te ima najveću prevalenciju u populaciji starijoj od 65 godina. Mehanizam nastanka uključuje unutarstaničnu agregaciju α-sinukleina što uzrokuje stvaranje eozinofilnih citoplazmatskih inkluzija (Lewyjeva tjelešca), te dovodi do posljedičnog gubitka dopaminergičkih neurona. U kliničkoj slici prevladavaju četiri motorička simptoma bolesti, a to su akinetički tremor, bradikineza, rigor te posturalna nestabilnost, a uz motoričke simptome razlikujemo i nemotoričke simptome bolesti koji obuhvaćaju poremećaje kognitivnih i autonomnih funkcija te poremećaje raspoloženja. Temelj liječenja u ranijim stadijima bolesti je medikamentozna terapija, dok se u uznapredovalim stadijima koriste napredne invazivne metode liječenja, odnosno ugradnja DBS uređaja koji se uspješno koristi u terapiji motoričkih simptoma bolesti, uz nešto slabiji učinak na nemotoričke simptome, pa čak i pogoršanje određenih kognitivnih funkcija. Stoga se postavljaju pitanja na koji način DBS utječe na kognitivne funkcije te kako individualizirati terapiju i smanjiti rizik od štetnih posljedica. Dosadašnja istraživanja ukazuju da se većina kognitivnih oštećenja uviđa u verbalnoj fluentnosti, dok su dokazi vezani uz izvršne funkcije, pamćenje, pažnju i brzinu obrade informacija i dalje neuvjerljivi. DBS ne utječe značajno na globalnu kogniciju, osobito ako se kognitivni probir provodi prije zahvata, budući da je niža početna kognicija povezana s lošijim ishodima. Stoga se rizik može ublažiti prilagođavanjem pristupa svakom pacijentu i testiranjem kognitivnih funkcija prije operativnog zahvata. Potrebna su dodatna randomizirana kontrolirana ispitivanja kako bi se povećala razina dokaza, osobito u slučaju GPi-DBS, PPN-DBS i VIM-DBS uređaja, te su nužne dugoročne studije za sve ciljne jezgre. Također, potrebna su daljnja ispitivanja u području genetike što bi moglo omogućiti individualiziraniji pristup liječenju na temelju gentskih specifičnosti. |
| Abstract (english) | PD is a progressive neurodegenerative disease caused by degeneration of dopaminergic neurons of substantia nigra and has the highest prevalence in the population over 65 years. The main pathohistological finding involves intracellular aggregation of α-synuclein, which causes the formation of eosinophilic cytoplasmic inclusions (Lewy bodies), and leads to the loss of dopaminergic neurons. PD is characterized by four main motor symptoms, those are akinetic tremor, bradykinesia, rigor and postural instability, as well as non-motor symptoms, such as sleep disorders autonomic dysfunction, behavioral changes and cognitive deficits. Medications are the cornerstone of treatment in the early stages of the disease, although more invasive therapies may be employed in advanced stages, such as implantation of DBS which is typically used for treating motor symptoms, while it is not as effective, or even aggravating, for gait, affective and cognitive symptoms. However, as the use of DBS broadens, a few questions remain. Mainly, what are the DBS effects on cognition and how to individualize therapy and reduce the risk for adverse effects. The most common form of impairment, according to current data, is verbal fluency, whereas evidence for executive function, memory, attention, and processing speed is still equivocal. Global cognition does not appear to be significantly impacted by DBS, especially if cognitive screening is performed prior to the procedure, as lower baseline cognition is associated with worse outcomes. As a result, the risk can be mitigated by tailoring the approach to each patient and testing cognitive function prior to the treatment. More randomized controlled studies are needed to raise the level of evidence, particularly for GPi-DBS, PPN-DBS, and VIM-DBS, as well as more long-term studies for all respective targets. Also, further genetics research is needed, which could enable a more individualized treatment approach based on personal genetic informations. |
