Parkinsonin tauti ja mikrobiomi

Tutkimusmenetelmien kehittyminen on avannut elimistömme mikrobistosta tutkimuslinjoja mm. neurodegeneratiivisiin ­sairauksiin. Suomessa on tehty hiljattain ensimmäiset havainnot Parkinson-potilaiden suolistomikrobiomin poikkeavasta ­koostumuksesta

Antibiotic exposure and risk of Parkinson's disease in finland : A nationwide case-control study

Background Gut microbiota alterations have been found in prodromal and established Parkinson's disease (PD). Antibiotic exposure can have long-term effects on the composition of human intestinal microbiota, but a potential connection between antibiotic exposure and risk of PD has not been studied previously. Objective To evaluate the impact of antibiotic exposure on the risk of PD in a nationwide, register-based, case-control study. Methods We identified all patients who were diagnosed with PD in Finland during the years 1998 to 2014. Information was obtained on individual purchases of orally administered antibiotics during the years 1993 to 2014. We assessed the association between prior antibiotic exposure and PD using conditional logistic regression. Results The study population consisted of 13,976 PD cases and 40,697 controls. The strongest connection with PD risk was found for oral exposure to macrolides and lincosamides (adjusted odds ratio up to 1.416; 95% confidence interval, 1.053-1.904). After correction for multiple comparisons, exposure to antianaerobics and tetracyclines 10 to 15 years before the index date, sulfonamides and trimethoprim 1 to 5 years before the index date, and antifungal medications 1 to 5 years before the index date were positively associated with PD risk. In post hoc analyses, further positive associations were found for broad-spectrum antibiotics. Conclusions Exposure to certain types of oral antibiotics seems to be associated with an elevated risk of PD with a delay that is consistent with the proposed duration of a prodromal period. The pattern of associations supports the hypothesis that effects on gut microbiota could link antibiotics to PD, but further studies are needed to confirm this. (c) 2019 International Parkinson and Movement Disorder SocietyPeer reviewe

Suolistopatologia voi avata räätälöityjä hoitoja Parkinsonin tautiin

Merkittävällä osalla Parkinson-potilaista on suuri suolisto-oireiden kuorma

Deep brain stimulation for dystonia in Finland during 2007-2016

BackgroundDystonia is a movement disorder substantially affecting the quality of life and the ability to work. A proportion of patients does not respond to first line pharmacotherapy. Deep brain stimulation (DBS) is established as a primary operative treatment option for severe drug resistant dystonia. We studied dystonia patients treated with DBS in Finland between the years 2007-2016 to evaluate the use and outcomes of DBS treatment.MethodsWe analysed the hospital records of dystonia patients, who underwent DBS operation during 2007-2016 in Finland. The clinical and technical parameters were recorded as well as preoperative assessments and treatments. The response to DBS was evaluated retrospectively using the Global Dystonia Rating Scale (GDS).ResultsOut of 585dB implantations during the study period, 37 were done for dystonia. The clinical response improved significantly with time in the isolated focal dystonia group, and at 12months, 22 of 32 patients had over 50% alleviation of the GDS score. There was only one subclinical intracerebral haemorrhage, and four infections leading to revision. Speech impairment and limb coordination problems were common stimulation- related adverse events and were mostly resolved or relieved with the adjustment of stimulation parameters.ConclusionsDBS seems to be beneficial in dystonia. Although DBS is indicated for dystonia in Finland, the number of operations did not increase at the same rate as DBS operations in general. DBS appears to be a safe and effective treatment for focal as well as generalized dystonia.Peer reviewe

Environmental triggers of Parkinson's disease-Implications of the Braak and dual-hit hypotheses

Idiopathic Parkinson's disease (PD) may take decades to develop, during which many risk or protective factors may come into play to initiate the pathogenesis or modify its progression to clinical PD. The lack of understanding of this prodromal phase of PD and the factors involved has been a major hurdle in the study of PD etiology and preventive strategies. Although still controversial, the Braak and dual-hit hypotheses that PD may start peripherally in the olfactory structures and/or the gut provides a theoretical platform to identify the triggers and modifiers of PD prodromal development and progression. This is particularly true for the search of environmental causes of PD as the olfactory structures and gut are the major human mucosal interfaces with the environment. In this review, we lay out our personal views about how the Braak and dual-hit hypotheses may help us search for the environmental triggers and modifiers for PD, summarize available experimental and epidemiological evidence, and discuss research gaps and strategies.Peer reviewe

Hypoperfusion of an Entire Cerebral Hemisphere – Stroke or Postictal Deficit?

The clinical differential diagnosis between ischemic stroke and postictal deficit is sometimes challenging. If the clinical presentation is inconclusive, perfusion imaging can help to identify stroke patients for thrombolysis therapy. However, also epileptic phenomena may alter cerebral perfusion. Hypoperfusion spreading beyond the borders of cerebrovascular territories is usually considered suggestive of an etiology other than stroke. We present a patient whose clinical symptoms suggested a postictal deficit rather than an acute stroke. CT perfusion imaging showed hypoperfusion of the entire left cerebral hemisphere covering all vascular territories. CT angiography revealed occlusions in the ipsilateral internal carotid artery and in the circle of Willis as the cause of the global hypoperfusion. The patient was treated with i.v. thrombolysis and recovered with moderate disability. This is the first description of hyperacute ischemia of an entire cerebral hemisphere and its treatment with thrombolysis. It demonstrates the potential of modern neuroimaging in identifying atypically presenting strokes and shows that i.v. thrombolysis can be effectively and safely used to treat such potentially fatal insults

Mikrobisto-suoli-aivoakselin merkitys Parkinsonin taudissa

Vertaisarvioitu.• Parkinsonin tautiin liittyy laaja-alaisia vaurioita keskushermostossa sekä autonomisessa ja enteerisessä hermostossa. • Taudin taustalla on alfasynukleiinin poikkeava laskostuminen ja aggregaatio. • Ummetus kuuluu taudin varhaisimpiin oireisiin. Se voi ilmaantua vuosia ennen motorisia oireita. • Osalla potilaista taudin patogeneesi saattaa saada alkunsa suolistossa ja levitä sieltä kohti keskushermostoa. • Ylemmän ruoansulatuskanavan toiminnalla on merkitystä levodopan imeytymiselle.Peer reviewe

Gut bacterial tyrosine decarboxylase associates with clinical variables in a longitudinal cohort study of Parkinsons disease

Gut microbiota influences the clinical response of a wide variety of orally administered drugs. However, the underlying mechanisms through which drug-microbiota interactions occur are still obscure. Previously, we reported that tyrosine decarboxylating (TDC) bacteria may restrict the levels of levodopa reaching circulation in patients with Parkinson's disease (PD). We observed a significant positive association between disease duration and the abundance of the bacterial tdc-gene. The question arises whether increased exposure to anti-PD medication could affect the abundance of bacterial TDC, to ultimately impact drug efficacy. To this end, we investigated the potential association between anti-PD drug exposure and bacterial tdc-gene abundance over a period of 2 years in a longitudinal cohort of PD patients and healthy controls. Our data reveal significant associations between tdc-gene abundance, several anti-PD medications, including entacapone, rasagiline, pramipexole, and ropinirole but not levodopa, and gastrointestinal symptoms, warranting further research on the effect of anti-PD medication on microbial changes and gastrointestinal function.Peer reviewe

Adaptation of cortical activity to sustained pressure stimulation on the fingertip

Background Tactile adaptation is a phenomenon of the sensory system that results in temporal desensitization after an exposure to sustained or repetitive tactile stimuli. Previous studies reported psychophysical and physiological adaptation where perceived intensity and mechanoreceptive afferent signals exponentially decreased during tactile adaptation. Along with these studies, we hypothesized that somatosensory cortical activity in the human brain also exponentially decreased during tactile adaptation. The present neuroimaging study specifically investigated temporal changes in the human cortical responses to sustained pressure stimuli mediated by slow-adapting type I afferents. Methods We applied pressure stimulation for up to 15 s to the right index fingertip in 21 healthy participants and acquired functional magnetic resonance imaging (fMRI) data using a 3T MRI system. We analyzed cortical responses in terms of the degrees of cortical activation and inter-regional connectivity during sustained pressure stimulation. Results Our results revealed that the degrees of activation in the contralateral primary and secondary somatosensory cortices exponentially decreased over time and that intra- and inter-hemispheric inter-regional functional connectivity over the regions associated with tactile perception also linearly decreased or increased over time, during pressure stimulation. Conclusion These results indicate that cortical activity dynamically adapts to sustained pressure stimulation mediated by SA-I afferents, involving changes in the degrees of activation on the cortical regions for tactile perception as well as in inter-regional functional connectivity among them. We speculate that these adaptive cortical activity may represent an efficient cortical processing of tactile information.open