Validation of the Finnish Version of the Unified Dyskinesia Rating Scale.

INTRODUCTION: The Unified Dyskinesia Rating Scale (UDysRS) was developed to provide a comprehensive rating tool of dyskinesia in Parkinson's disease (PD). Because dyskinesia therapy trials involve multicenter studies, having a scale that is validated in multiple non-English languages is pivotal to international efforts to treat dyskinesia. The aim of the present study was to organize and perform an independent validation of the UDysRS Finnish version. METHODS: The UDysRS was translated into Finnish and then back-translated into English using 2 independent teams. Cognitive pretesting was conducted on the Finnish version and required modifications to the structure or wording of the translation. The final Finnish version was administered to 250 PD patients whose native language is Finnish. The data were analyzed to assess the confirmatory factor structure to the Spanish UDysRS (the reference standard). Secondary analyses included an exploratory factor analysis (EFA), independent of the reference standard. RESULTS: The comparative fit index (CFI), in comparison with the reference standard factor structure, was 0.963 for Finnish. In the EFA, where variability from sample to sample is expected, isolated item differences of factor structure were found between the Finnish and Reference Standard versions of the UDysRS. These subtle differences may relate to differences in sample composition or variations in disease status. CONCLUSION: The overall factor structure of the Finnish version was consistent with that of the reference standard, and it can be designated as the official version of the UDysRS for Finnish speaking populations.

Prevalence of life-supporting prolonged invasive ventilation support in Finland.

BACKGROUND: There is no comprehensive data in our country on the prevalence of life-supporting prolonged invasive ventilation support. The objective of the survey was to clarify in all hospital districts of continental Finland the prevalence of patients who were dependent on invasive ventilation support, and the disease leading to the treatment. PATIENTS AND METHODS: The KOTIVEHNO 2015 survey was carried out as population-based cross-sectional study by sending a questionnaire to all doctors in charge of prolonged invasive ventilation support. The questionnaires were used to collect data on the patients within care on 1st January, 2017. RESULTS: The prevalence of life-supporting prolonged invasive ventilation support in Finland among the population aged over 16 years or more was 2/4 patients/100,000 habitants. Altogether 107 patients were within the care. There was variation in the prevalence among the hospital districts. Of the patients, 24% were affected with a motoneuron disease, in 18% the cause was spinal cord injury, 15% suffered from Duchenne's muscular dystrophy, and the rest had some other rare neurological disease. CONCLUSIONS: Life-supporting prolonged invasive ventilation support is rare in Finland. The treatment is associated with neuromuscular diseases causing respiratory insufficiency, and with spinal cord injuries.

Etiology, diagnostics and treatment of cardiogenic stroke.

Approximately 15 to 40% of cerebral infarctions and transient ischemic attacks (TIA) are of cardiac origin. Knowledge of a significant cardiac disease arouses the suspicion of cardiogenic embolism, but its diagnosis requires identification of the source of embolism. Atrial fibrillation is the most common cause of cardiogenic embolism, and should be actively sought after an ischemic cerebrovascular attact. The detection of atrial fibrillation or an intracardiac thrombus in these patients requires initiation of permanent anticoagulant therapy. Transesophageal echocardiography (TEE) has proven to be more sensitive than transthoracic echocardiography (TTE) in detecting certain possible cardiogenic sources of embolism.

[Amyotrophic lateral sclerosis and respiratory insufficiency]. / Amyotrofinen lateraaliskleroosi ja hengitysvajaus.

Amyotrophic lateral sclerosis (ALS) is a disease causing degeneration of motor neurons, without any curative treatment. The most common cause of death is respiratory arrest due to atrophy of the respiratory musculature. ALS-associated respiratory insufficiency differs in mechanism from the more common causes of dyspnea, such as diseases of pulmonary or cardiac origin. Recognizing the respiratory insufficiency can be challenging for a clinician. It should be possible to predict the development of respiratory insufficiency in order to avoid leaving the treatment decisions concerning respiratory insufficiency to emergency services. Noninvasive ventilatory support can be used to alleviate the patient's dyspnea. It is actually recommended as the first-line treatment of ALS-associated respiratory insufficiency.

[Phenotype and incidence of Creutzfeldt-Jakob disease in Finland in 1997-2013]. / Creutzfeldt-Jakobin taudin ilmiasu ja ilmaantuvuus Suomessa vuosina 1997-2013.

INTRODUCTION: The incidence of Creutzfeldt-Jakob disease (CJD) in Finland in 1974-1989 was reported to be 0.6/1 000 000. Our aim was to compare the current incidence of CJD in Finland with the earlier incidence and also study the diagnostics of the disease. METHODS: Register study of the Finnish CJD cases from 1997 to 2012 and the clinical data of CJD patients within the Hospital District of Southwest Finland from 2007 to 2013. RESULTS: There were 119 cases. The average yearly incidence was 1.36-1.44/1 000 000. CONCLUSIONS: Compared with the previous study, the incidence in Finland appears to have increased. The change is propably due to increased awareness and improved diagnostic methods.

Reappearance of Symptoms after GPi-DBS Discontinuation in Cervical Dystonia.

BACKGROUND: Deep brain stimulation of the globus pallidus interna (GPi-DBS) is a highly efficacious treatment for cervical dystonia. Typically, the treatment response is delayed, appearing and increasing even months after implantation. However, it is not known how fast the symptoms reappear and whether there is a long-term therapeutic effect after the stimulation is discontinued. OBJECTIVES: To study symptom reappearance after switching GPi-DBS off in cervical dystonia. METHODS: Twelve patients with bilateral GPi-DBS were included in the study. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) was evaluated during the study with DBS stimulation on, after switching the stimulation off and 2 days after the stimulation was switched off. Presurgical symptom severity and best postsurgical response were extracted from the hospital records. RESULTS: At the time of the investigation, GPi-DBS was associated with 67 (SD 39)% symptom improvement of presurgical symptoms severity (P = 0.001). Symptom improvement decreased to 27 (53)% (P = 0.046) (n = 12) acutely after switching the stimulation off and was further reduced to 4 (56)% 2 days after discontinuation (P = 0.01) (n = 11), reaching the presurgical level (P = 0.42). In descriptive analyses, older age was associated with faster worsening of symptoms (P < 0.05). Presurgical symptoms severity, stimulation parameters or magnitude of treatment response did not predict symptom worsening. All but one patient tolerated 2 days DBS switched off. CONCLUSIONS: The results provide novel information about the time frame and severity of symptom worsening after discontinuing GPi-DBS in cervical dystonia. Symptoms partially reappear immediately after discontinuing GPi-DBS and full presurgical symptom severity is reached within 2 days.

Deep brain stimulation for monogenic Parkinson's disease: a systematic review.

Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD) patients with motor fluctuations and dyskinesias. The key DBS efficacy studies were performed in PD patients with unknown genotypes; however, given the estimated monogenic mutation prevalence of approximately 5-10%, most commonly LRRK2, PRKN, PINK1 and SNCA, and risk-increasing genetic factors such as GBA, proper characterization is becoming increasingly relevant. We performed a systematic review of 46 studies that reported DBS effects in 221 genetic PD patients. The results suggest that monogenic PD patients have variable DBS benefit depending on the mutated gene. Outcome appears excellent in patients with the most common LRRK2 mutation, p.G2019S, and good in patients with PRKN mutations but poor in patients with the more rare LRRK2 p.R1441G mutation. The overall benefit of DBS in SNCA, GBA and LRRK2 p.T2031S mutations may be compromised due to rapid progression of cognitive and neuropsychiatric symptoms. In the presence of other mutations, the motor changes in DBS-treated monogenic PD patients appear comparable to those of the general PD population.

Extracellular enzyme activities and nutrient availability during artificial groundwater recharge.

Natural organic matter (NOM) removal is the main objective of artificial groundwater recharge (AGR) for drinking water production and biodegradation plays a substantial role in this process. This study focused on the biodegradation of NOM and nutrient availability for microorganisms in AGR by the determination of extracellular enzyme activities (EEAs) and nutrient concentrations along a flow path in an AGR aquifer (Tuusula Water Works, Finland). Natural groundwater in the same area but outside the influence of recharge was used as a reference. Determination of the specific alpha-d-glucosidase (alpha-Glu), beta-d-glucosidase (beta-Glu), phosphomonoesterase (PME), leucine aminopeptidase (LAP) and acetate esterase (AEST) activities by fluorogenic model substrates revealed major increases in the enzymatic hydrolysis rates in the aquifer within a 10m distance from the basin. The changes in the EEAs along the flow path occurred simultaneously with decreases in nutrient concentrations. The results support the assumption that the synthesis of extracellular enzymes in aquatic environments is up and down regulated by nutrient availability. The EEAs in the basin sediment and pore water samples (down to 10cm) were in the same order of magnitude as in the basin water, suggesting similar nutritional conditions. Phosphorus was likely to be the limiting nutrient at this particular AGR site. Furthermore, the extracellular enzymes functioned in a synergistic and cooperative way.

Steroid-responsive encephalopathy with a peculiar CSF biomarker profile in an 89-year-old man.

Being treatable, steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), or Hashimoto's encephalopathy, should be distinguished from untreatable conditions. Our patient was a previously healthy 89-year-old man, who presented with cognitive and balance deterioration over several months. His cerebrospinal fluid (CSF) examination was positive for protein 14-3-3 but no other test suggested Creutzfeldt-Jacob disease. His condition improved markedly, although not fully, with intravenous corticosteroids. In control CSF sampling, protein 14-3-3 was negative but a biomarker signature consistent with Alzheimer's disease was observed. SREAT should be considered also in the very elderly in case of subacute encephalopathy.

Human Chorionic Gonadotropin Does Not Correlate with Risk for Maternal Breast Cancer: Results from the Finnish Maternity Cohort.

Human chorionic gonadotropin (hCG) is necessary for the maintenance of early pregnancy and promotes normal breast cell differentiation. Administered hCG reduces risk of carcinogen-induced breast cancer in animal models, and higher circulating hCG concentrations were associated with significantly lower long-term risk of breast cancer in a prior nested case-control study. In this study, we investigated early-pregnancy hCG concentrations and subsequent breast cancer risk. We conducted a nested case-control study with 1,191 cases and 2,257 controls (matched on age and date at blood collection) in the Finnish Maternity Cohort, a cohort with serum samples from 98% of pregnancies registered in Finland since 1983. This study included women with a serum sample collected early (<140 days gestation) in their first pregnancy resulting in a live, term birth. Breast cancer cases were identified via the Finnish Cancer Registry. Age at breast cancer diagnosis ranged from 22 to 58 years (mean: 41 years). hCG was measured using a solid-phase competitive chemiluminescence assay. Odds ratios (OR) were calculated using conditional logistic regression. We observed no association between hCG and breast cancer risk, overall [Quartile 4 vs. 1, OR, 1.14; 95% confidence interval (CI), 0.94-1.39], by estrogen and progesterone receptor status, or by ages at first-term birth or diagnosis. Associations did not differ by time between pregnancy and diagnosis (e.g., <5 years, ORQ4 vs. Q1, 1.10; 95% CI, 0.64-1.89; ≥15 years, ORQ4 vs. Q1, 1.36; 95% CI, 0.86-2.13; pheterogeneity = 0.62). This large prospective study does not support an inverse relationship between early pregnancy serum hCG concentrations and breast cancer risk. Cancer Res; 77(1); 134-41. ©2016 AACR.

Recurrent paraparesis and death of a patient with 'whippet' abuse.

Nitrous oxide is increasingly used as a recreational drug that is easily and legally available worldwide. Occasional nitrous oxide use has been considered relatively safe without the development of addiction or major adverse effects. However, heavy long-term nitrous oxide abuse can be associated with severe neurological complications, and even deaths have been described. The characteristic presentation is myeloneuropathy with dorsal column degeneration and demyelinating sensory polyneuropathy related to vitamin B12 deficiency. Described is a 23-year-old male who developed recurrent paraparesis related to nitrous oxide abuse. A second, more severe, episode of paraparesis was associated with predominantly lower motor neuron damage. A partial recovery was achieved by discontinuation of nitrous oxide use and initiation of vitamin B12 supplementation. However, the patient relapsed and ultimately died while being intoxicated with several abusive substances. The case adds to the cumulative literature about the clinical phenomenology and dangers of nitrous oxide abuse.

Hypermetabolism of Olivary Nuclei in a Patient with Progressive Ataxia and Palatal Tremor.

BACKGROUND: The pathophysiology of the movement disorder progressive ataxia with palatal tremor (PAPT) is unclear. CASE REPORT: A 77-year-old male presented with dysarthria, ataxia, and 1-2 Hz palatal tremor. A diagnosis of probable sporadic PAPT was established. Brain magnetic resonance imaging was normal at the presymptomatic phase but later showed olivary hypertrophy. Brain [(18)F]-fludeoxyglucose (FDG) positron emission tomography (PET) showed bilateral hypermetabolism in the olivary nuclei. DISCUSSION: This second reported patient with PAPT and FDG-PET shows that olivary hypertrophy is paralleled with hypermetabolism. The olivary nuclei pathology also appears to be temporally associated with symptom onset.

Neutropenic infections add significant costs to palliative chemotherapy in breast cancer.

BACKGROUND: The key clinical question in treating cancer patients for palliation is balancing issues on efficacy, toxicity and cost. The costs of chemotherapy have risen substantially during recent years, yet many patients are treated even at the end of their life with unresponsive cancer. The objective of this study was to determine the additional treatment costs during six months on chemotherapy to manage toxicity. PATIENTS AND METHODS: Thirty-eight women were treated for metastatic breast cancer with an epirubicin-docetaxel regimen every three weeks. The clinical benefit was calculated for responding and stable patients maintaining the same status for at least 6 months (% of evaluable patients). Data on the use of medical resources were extracted from the hospital records. Health resources utilization analyses included the costs in Euros at year 2000 values during the six months' treatment of all additional hospitalization, drugs and blood transfusions. RESULTS: The response rate (CRIPR) was 54% (95% CI 37-71). Seventy per cent of the patients (95% CI 53-84) had objective clinical benefit. The crude cost of the treatment was 12,416 Euros per patient. The total cost of chemotherapy per patient was 14,915 Euros. The costs of hospital stays, antibiotics, granulocyte growth factors and blood transfusions when indicated added 2,499 Euros per patient, thus adding 20% to crude treatment costs. CONCLUSION: The treatment of advanced breast cancer with 3-weekly epirubicin-docetaxel combination requires additional use of health resources mainly due to infections. The clinical benefit and true cost rates should be reported with the results of novel schedules.