Huntington’s disease in Finland. Epidemiologic, genetic and clinical studies

Huntington’s disease (HD) is a lethal, dominantly inherited neurodegenerative disorder reported to be unusually rare in Finland. The overall HD prevalence and the proportion of late-onset cases (LOHD) are increasing in many populations. The characteristics of LOHD are nevertheless poorly understood. Information on neurological comorbidity in patients with HD is also scarce. These retrospective studies analyzed a national Finnish HD cohort in the time frame 1987-2010 by searching national registries and archives. Data was extracted from medical records. Population genotypes were obtained from the 1000 Genomes project. The prevalence of HD in Finland was found to be 2.12/100,000, or over four times more common than reported previously. Nonetheless, HD is more uncommon than in other Western European countries. The national cohort of 207 patients included 52 (25%) patients with LOHD; they had poorer motor status at the time of diagnosis than patients with mid-age onset, possibly because of the diagnostic delay. No other differences were detected between these groups. Interestingly, only one individual (0.5% of all HD patients in Finland) with juvenile-onset HD was identified. The length of the affected CAG repeat or its intergenerational stability did not differ from those reported in other populations. However, the high risk chromosome 4 haplogroup A was relatively uncommon in the Finnish general population (39.2%), possibly partly explaining the relative rarity of HD in Finland. Patients with adult-onset HD had epilepsy and strokes as often as reported in the general population. HD patients were, however, at an increased risk of suffering subdural haematomas.Huntingtonin tauti Suomessa. Epidemiologisia, perinnöllisyystieteellisiä ja kliinisiä tutkimuksia. Huntingtonin tauti (HD) on autosomaalisesti vallitsevasti periytyvä, kuolemaan johtava hermoston rappeumasairaus. Taudin on todettu olevan poikkeuksellisen harvinainen Suomessa. Monissa väestöissä HD:n esiintyvyyden sekä myöhäisiällä alkavan HD:n (LOHD) osuuden on havaittu lisääntyneen. LOHD:n ominaispiirteet tunnetaan kuitenkin huonosti. Myös HD-potilaiden neurologisesta oheissairastavuudesta on käytettävissä vain hyvin vähän tietoja. Näissä takautuvissa tutkimuksissa analysoitiin kansallinen suomalainen HD-potilaiden kohortti vuosilta 1987-2010. Potilaat tunnistettiin kansallisista rekistereistä sekä tietyistä arkistoista. Tutkimustiedot kerättiin sairauskertomuksista. Väestön genotyyppitiedot saatiin 1000 Genomes –projektista. Huntingtonin taudin vallitsevuuden (2,12/100’000) havaittiin olevan Suomessa yli nelinkertainen aiempaan tutkimustietoon nähden. Silti HD on selvästi harvinaisempi Suomessa kuin muissa läntisen Euroopan maissa. Kansallisesta 207 HD-potilaan kohortista 52 (25%) oli LOHD-potilaita ja heidän motoriset oireensa ja löydöksensä olivat diagnoosinteon hetkellä vaikeampia kuin aiemmalla aikuisiällä sairastuneiden, mikä mahdollisesti johtui diagnoosien viivästymisestä LOHD-potilailla. Muuten näiden ryhmien välillä ei havaittu eroja. Yllättäen löysimme vain yhden (0,5%) potilaan, jolla HD alkoi nuoruusiällä. Tautialleelin CAG-toistojakson pituus tai sen sukupolvien välinen vakaus eivät eronneet muissa väestöissä raportoiduista. Kromosomin 4 korkean riskin haploryhmä A:n havaittiin kuitenkin olevan suomalaisessa väestössä verrattain harvinainen (39,2%), mikä saattaa osittain selittää HD:n suhteellista harvinaisuutta Suomessa. Aikuisiällä HD-diagnoosin saaneilla potilailla oli epilepsiaa ja aivoverenkiertohäiriöitä samassa määrin kuin valtaväestöllä. Kovakalvon alaisten verenvuotojen riski havaittiin HD-potilailla suurentuneeksi.Siirretty Doriast

Kansanvaltakriittinen – J.K. Paasikiven arvio eduskunnasta

T&auml;m&auml; tutkielma selvitt&auml;&auml; J.K. Paasikiven suhtautumista kansanvaltaan tarkastelemalla h&auml;nen my&ouml;hempi&auml; arvioitaan vuoden 1906 radikaalista eduskuntauudistuksesta ja sen my&ouml;t&auml; syntyneest&auml; eduskunnasta valtiollisena toimijana. L&auml;htein&auml; toimivat ensisijaisesti Paasikiven julkaistut p&auml;iv&auml;kirjat, puheet ja muistelmat joiden ohella tukeudutaan muihin aikalaismuistelmiin sek&auml; aiempaan tutkimuskirjallisuuteen. Paasikiven suhtautuminen eduskuntaan kehittyi 1920-luvulta M&auml;nts&auml;l&auml;n kapinaan saakka negatiivisesti yhdess&auml; yleisemm&auml;n demokratiapessimismin kanssa. Kotimaan tapahtumat ja kansainv&auml;linen kehitys saivat h&auml;net n&auml;kem&auml;&auml;n asian toisin ja tukemaan eduskuntaan kansallisen yhten&auml;isyyden tuottajana. Sotien j&auml;lkeen Paasikivi k&auml;ytti eduskuntaa my&ouml;s puolustaakseen kansallista suvereniteettia ja legitimoidakseen suomalaista yhteiskuntaj&auml;rjestyst&auml;. Ulkopoliittisen johtajuuden ja sis&auml;poliittisen huomattavan vaikutusvallan h&auml;n s&auml;ilytti arvioiden eduskunnan osaamista ja toimintakyky&auml; kriittisesti uransa loppuun saakka.</p

The H-1 and C-13 chemical shifts of 5-5 lignin model dimers : An evaluation of DFT functionals

The calculations of H-1 and C-13 NMR chemical shifts were performed on three 5-5 lignin dimers, prominent substructures in softwood lignins, to compare with experimental data. Initially, 10 DFT functionals (B3LYP, B3PW91, BPV86, CAM-B3LYP, HCTH, HSEH1PBE, mPW1PW91, PBEPBE, TPSSTPSS, and omega B97XD) combined with the gage-including atomic orbital (GIAO) method and basic set 6-31G(d,p) were tested on 3,3'-(6,6'-dihydroxy-5,5'-dimethoxy-[1,1'-biphenyl]-3,3'-diyl)dipropionic acid (1), efficiently synthesized from ferulic acid. HSEH1PBE, mPW1PW91, and omega B97XD were found to be the three best performing functionals with strong correlations (r(2) >= 0.9988) and low errors (CMAEsPeer reviewe

Anterior circulation large vessel occlusion outcomes in patients transferred from a peripheral primary stroke centre

ObjectivesTo identify predictors of functional outcome in patients with an anterior circulation large-vessel occlusion (LVO) in a setting of long transfer distances.MethodsOutcomes of LVO patients transferred for an endovascular thrombectomy (EVT) from North Karelia Central Hospital to Kuopio University Hospital between January 2018 and October 2019 were analysed using retrospective patient chart review.ResultsThree months after the stroke, modified Rankin Scale (mRS) was 0-2 in 20 of the 41 transferred patients. They were younger (66.7 vs. 74.2 years, p = 0.032) and had less severe stroke symptoms (National Institutes of Health Stroke Scale, NIHSS, 11.5 vs. 16.5, p = 0.029) than those with mRS 3-6. They also had the occlusion less often in M1 and more often in M2. EVT was performed in 32 patients (no differences between those treated with EVT and those not treated with EVT). Their median age was 73.0 years (interquartile range 65.5, 79.8; range 32-86; 25% over 80), mean NIHSS score 14.0 (standard deviation 5.9) and mRS eventually 0-2 in 44%. Only NIHSS was associated with mRS (OR = 1.16; p = 0.016) in the EVT-treated patients. mRS was 0 in 38% of all EVT-treated octogenarians but 4-6 in 83% of those with an internal carotid artery and/or M1 occlusion.DiscussionOutcomes depended on stroke severity, age and vessel of occlusion. Prognosis was worse if the occlusion included M1, especially in octogenarians. Mothership and Drip-n-ship strategies should be compared in patients from remote locations stratified by stroke severity and patient age.</p

Age Is Only a Number Also in Hyperacute Stroke Care-But Not an Irrelevant One

“It is difficult to make predictions, especially about the future [...

Tapaturmaisten aivovammojen epidemiologia muutoksessa – katse vanhempiin ikäluokkiin

Vanhusten tapaturmaisten aivovammojen lisääntyminen on kansanterveyden kannalta merkittävä trendi, joka näkyy myös meillä. Iäkkäiden naisten kuolleisuus aivovammoihin ja neuro­kirurgisia leikkauksia vaativien aivovammojen määrä ovat ­maassamme kasvussa. Vanhusten tapaturmat ovat usein ­kaatumisia, ja alkoholilla voi heilläkin olla osuutta asiaan.</p

Adult onset epilepsy incidence in Finland over 34 years: A nationwide registry study

Background and purposeThe incidence of epilepsy is decreasing among the working-aged in high-income countries, but previous studies have reported conflicting results in Finland.MethodsA nationwide population-based cross-sectional analysis was made of annual epilepsy drug reimbursement rights frequency data from the Social Insurance Institution of Finland, the national authority, between 1986 and 2019. All persons at least 20 years of age living in Finland during the study period were included.ResultsBased on the analysis of 77,939 new reimbursement rights, crude incidence was 57.4/100,000 (95% confidence interval [CI] = 57.0-57.8) person-years, and age-standardized (to the European Standard Population 2013) incidence was 51.6/100,000 person-years. Both crude (r = 0.62, p = 0.00009) and standardized (r = 0.65, p = 0.00003) incidence increased over time. Incidence increased in both men (from 66.4 to 71.6/100,000, r = 0.51, p = 0.002) and women (from 51.5 to 55.3/100,000, r = 0.68, p r = -0.47, p = 0.006). Incidence decreased in those 20-59 years old but increased in all older age groups. This development was similar between sexes. Conclusions The incidence of adult onset epilepsy in Finland increased in people older than 60 years and decreased in the 20-59-year age group during the study period. These trends were similar between sexes. Therefore, etiological epilepsy trends in the elderly need to be studied further to plan public health measures to prevent epilepsy in this age group.</p

Comorbidities in patients with Unverricht-Lundborg disease (EPM1) COMMENT

Background: Unverricht-Lundborg disease (EPM1) typically leads to accumulating disability. Disability may also be caused by comorbidities but there are no data available on these.Aims of the study: To investigate the frequency of comorbidities in EPM1.Methods: Comorbidity data of a previously described cohort of 135 Finnish patients with EPM1 were retrieved from neurological, surgical (including subspecialities), internal medicine (including subspecialities) and intensive care patient charts of the treating hospitals.Results: Mean follow-up time was 31.4 years (SD 12.4 years, range 6.8-57.8 years), during which at least one comorbidity was observed in 107 patients (79%) and three or more in 53 (39%). The most common diagnostic categories were external injuries, mental and behavioural disorders and endocrine, nutritional and metabolic diseases. The most common single comorbid diagnosis was a fracture of the ankle (in 19% of all patients). The second most common single comorbid diagnosis in the cohort was diabetes (in 13% of all patients), and the third was depression, recorded for 13% of the cohort. Malignancies and cardiovascular end-organ damage were rare, whereas phimosis/paraphimosis appeared more common than in general population.Conclusions: Patients with EPM1 often have comorbidities. Trauma and mental health risks should be especially followed and acted upon. Further studies are needed to more accurately comorbidity risks, characteristics and patient needs.</p