Protein tyrosine phosphatase receptor type Q in cerebrospinal fluid reflects ependymal cell dysfunction and is a potential biomarker for adult chronic hydrocephalus.

BACKGROUND AND PURPOSE: Protein tyrosine phosphatase receptor type Q (PTPRQ) was extracted from the cerebrospinal fluid (CSF) of patients with probable idiopathic normal-pressure hydrocephalus (iNPH) by proteome analysis. We aimed to assess the feasibility of using CSF PTPRQ concentrations for the additional diagnostic criterion of iNPH in Japanese and Finnish populations. METHODS: We compared PTPRQ concentrations among patients with probable iNPH and neurologically healthy individuals (normal control [NC] group), patients with normal-pressure hydrocephalus (NPH) of acquired and congenital/developmental aetiologies, patients with Alzheimer's disease and patients with Parkinson's disease in a Japanese analysis cohort. A corresponding iNPH group and NC group in a Finnish cohort was used for validation. Patients in the Finnish cohort who underwent biopsy were classified into two groups based on amyloid and/or tau deposition. We measured PTPRQ expression levels in autopsied brain specimens of iNPH patients and the NC group. RESULTS: Cerebrospinal fluid PTPRQ concentrations in the patients with NPH of idiopathic, acquired and congenital/developmental aetiologies were significantly higher than those in the NC group and those with Parkinson's disease, but iNPH showed no significant differences when compared with those in the Alzheimer's disease group. For the patients with iNPH, the area under the receiver-operating characteristic curve was 0.860 in the Japanese iNPH and 0.849 in the Finnish iNPH cohorts. Immunostaining and in situ hybridization revealed PTPRQ expression in the ependymal cells and choroid plexus. It is highly possible that the elevated PTPRQ levels in the CSF are related to ependymal dysfunction from ventricular expansion. CONCLUSIONS: Cerebrospinal fluid PTPRQ levels indicated the validity of this assay for auxiliary diagnosis of adult chronic hydrocephalus.

Antioxidant-rich foods and response to altitude training: A randomized controlled trial in elite endurance athletes.

High doses of isolated antioxidant supplements such as vitamin C and E have demonstrated the potential to blunt cellular adaptations to training. It is, however, unknown whether intake of high doses of antioxidants from foods has similar effects. Hence, the aim of the study was to investigate whether intake of antioxidant-rich foods affects adaptations to altitude training in elite athletes. In a randomized controlled trial, 31 national team endurance athletes (23 ± 5 years) ingested antioxidant-rich foods (n = 16) or eucaloric control foods (n = 15) daily during a 3-week altitude training camp (2320 m). Changes from baseline to post-altitude in hemoglobin mass (Hbmass ; optimized CO rebreathing), maximal oxygen uptake (VO2max ; n = 16) or 100 m swimming performance (n = 10), and blood parameters were compared between the groups. The antioxidant group significantly increased total intake of antioxidant-rich foods (~118%) compared to the control group during the intervention. The total study population improved VO2max by 2.5% (1.7 mL/kg/min, P = .006) and Hbmass by 4.7% (48 g, P < .001), but not 100 m swimming performance. No difference was found between the groups regarding changes in Hbmass , VO2max or swimming performance. However, hemoglobin concentration increased more in the antioxidant group (effect size = 0.7; P = .045) with a concomitantly larger decrease in plasma and blood volumes compared to control group. Changes in ferritin and erythropoietin from pre- to post-altitude did not differ between the groups. Doubling the intake of antioxidant-rich foods was well tolerated and did not negatively influence the adaptive response to altitude training in elite endurance athletes.

Health-related quality-of-life outcome in patients with idiopathic normal-pressure hydrocephalus - a 1-year follow-up study.

BACKGROUND AND PURPOSE: This prospective study explored the factors affecting the health-related quality-of-life (HRQoL) outcome in patients with idiopathic normal-pressure hydrocephalus (iNPH) 1 year after the installation of the cerebrospinal fluid shunt. METHODS: The HRQoL outcome was evaluated using a 15D instrument, in which the minimum clinically significant change/difference has been estimated to be ±0.015. The follow-up data (15D, Mini-Mental State Examination, Beck Depression Inventory, iNPH Grading Scale), frontal cortical biopsy, Charlson Age Comorbidity Index and body mass index of 145 patients diagnosed with iNPH by clinical and radiological examination were analyzed. RESULTS: At 1-year follow-up, 63 (43%) patients had experienced a clinically significant improvement in HRQoL. Multivariate binary logistic regression analysis indicated that the absence of amyloid-ß and hyperphosphorylated tau pathology in the frontal cortical biopsy (53% vs. 33%; absolute risk difference, 20%; adjusted odds ratio, 2.27; 95% confidence interval, 1.07-4.84; P < 0.05) and lower body mass index (adjusted odds ratio, 0.90, 95% confidence interval, 0.82-0.98; P < 0.05) predicted favorable HRQoL outcome 1 year after the shunting. CONCLUSIONS: Less than half of the patients with iNPH experienced clinically significant favorable HRQoL outcome, partly explained by the patient's characteristics and comorbidities. The HRQoL approach reveals aspects that are important for the patient's well-being, but may also improve the quality of the outcome assessment of cerebrospinal fluid shunting. Study results may help clinicians to estimate which patients will benefit shunt surgery.

Adipokines played a limited role in predicting temporary growth differences between very low birthweight infants with and without bronchopulmonary dysplasia.

AIMS: This study explored whether growth was poorer among very low birthweight (VLBW) infants with bronchopulmonary dysplasia (BPD) and assessed adipokine levels as predictors of early growth. METHODS: We studied 53 VLBW infants born in Tampere University Hospital up to 12 months of corrected age (CA). The median gestational age of the 21 infants with BPD and 32 infants without BPD was 29 weeks, and the median birthweights were 930 (635-1470) and 1185 (650-1470) grams. Growth parameters, macronutrients intake and plasma levels of adipokines were measured. RESULTS: Bronchopulmonary dysplasia infants were lighter than controls until 36 weeks of CA, with catch-up growth achieved by three months of CA. Adipsin levels were lower in BPD infants at 28 days of postnatal age. High leptin levels seemed protective for low weight for height at nine months of CA. The duration of ventilator therapy predicted low weight for height, length for age and body mass index and BPD predicted low length for age at 12 months of CA. CONCLUSIONS: Catch-up growth in VLBW infants with BPD was achieved by three months of CA, but adipokines played a limited role in predicting growth. Shortening ventilator therapy could help growth in VLBW infants.

Health-related quality of life in patients with idiopathic normal pressure hydrocephalus.

BACKGROUND AND PURPOSE: Factors affecting health-related quality of life (HRQoL) were explored in patients with idiopathic normal pressure hydrocephalus (iNPH). METHODS: Using the 15D instrument HRQoL was evaluated in 132 patients diagnosed with iNPH by clinical and neuroradiological examinations. The severity of iNPH symptoms was measured with the iNPH grading scale (iNPHGS), depressive symptoms with the Beck Depression Inventory (BDI-21) and cognitive impairment with the Mini-Mental State Examination. RESULTS: The mean (SD) 15D score (on a 0-1 scale) of patients with iNPH was significantly lower than that of an age- and gender-matched sample of the general population [0.718 (0.103) vs. 0.870 (0.106); P < 0.001]. The mean 15D score was lower in iNPH patients with moderate or severe depressive symptoms than in patients without depressive symptoms (P = 0.003). According to stepwise multiple linear regression analysis, a higher total iNPHGS score (b = -0.62, P < 0.001) and a higher BDI-21 total score (ß = -0.201, P = 0.025) predicted a lower 15D score; in combination, these explained 51% of the variance in the 15D score (R(2)  = 0.506, P < 0.001). CONCLUSIONS: Idiopathic normal pressure hydrocephalus impairs patients' HRQoL on multiple dimensions, similarly to other chronic diseases. Potentially treatable depressive symptoms contribute greatly to the HRQoL impairment of iNPH patients, but only if they are moderate or severe. The 15D portrayed HRQoL dimensions affected by iNPH in a similar way to broader assessment batteries and thus is a potentially useful tool for treatment evaluation and cost-utility analysis.

Contact sensitizer 2,4-dinitrochlorobenzene is a highly potent human TRPA1 agonist.

2,4-Dinitrochlorobenzene (DNCB) is widely used in human clinical studies and in experimental animal studies to evoke allergic contact dermatitis. 2,4-Dinitrochlorobenzene is a potent immunogen capable of inducing contact sensitization in all humans exposed. However, the mechanism by which DNCB evokes such symptoms is presently unknown. TRPA1 is a nonselective cation channel that is expressed in peptidergic sensory neurons and fibroblasts. TRPA1 activation was recently implicated in the pathophysiology of atopic dermatitis especially in transducing cutaneous itch signals. Here, we test the hypothesis that DNCB acts as a TRPA1 agonist and thereby evokes allergic symptoms. We found that DNCB activates human TRPA1 dose dependently in FLIPR experiments with an EC50 of 167 nM, an effect that was fully blocked by selective TRPA1 antagonists Chembridge-5861528 and A-967079. Similarly, DNCB activated nonselective TRPA1 current in patch clamp studies. Neutralization of 3 critical cysteines in TRPA1 resulted in a loss of DNCB agonism.

Lost potential of kidney and liver donors amongst deceased intracerebral hemorrhage patients.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) has high acute mortality. The number of potential kidney and liver donors amongst deceased ICH patients was estimated to improve our institutional guidelines on acute care of neurocritical patients to increase organ donation. METHODS: A chart review was carried out by a multi-professional team for consecutive ICH patients admitted to the emergency department at Helsinki University Central Hospital and dying within 14 days between 2005 and 2010. RESULTS: In all, 955 patients had follow-up data, of whom 254 (27%) died within 14 days and eight ended up as organ donors. An additional 51 potentially suitable donors not different from actual donors were identified: nine suitable for kidney donation, 11 for liver and 31 for both. In 49/51 (96%) cases prognosis seemed non-existent and do-not-resuscitate orders were issued early, which led to refrainment from intensive care in 76.5%. These potential donors differed from those ICH patients surviving a whole year (n = 529) by male preponderance, more severe symptoms (median National Institutes of Health Stroke Scale 25 vs. 6 and Glasgow Coma Scale 7 vs. 15), larger hematoma volumes of 24.8 cm(3) (vs. 6.7), and frequent finding of midline shift and intraventricular rupture of the hemorrhage in admission brain CT. Based on the results, our guidelines were revised towards more active treatment including mechanical ventilation for neurocritical patients at the emergency department for at least 48 h, resulting in an increase in organ donations in 2012. CONCLUSIONS: A considerable number of ICH patients are potential organ donors if the evaluation takes place on arrival and organ donation is considered as part of usual end-of-life care.

Positron emission tomography with [18F]flutemetamol and [11C]PiB for in vivo detection of cerebral cortical amyloid in normal pressure hydrocephalus patients.

BACKGROUND AND PURPOSE: This study determined the correlation between uptake of the amyloid positron emission tomography (PET) imaging agent [(18) F]flutemetamol and amyloid-ß measured by immunohistochemical and histochemical staining in a frontal cortical biopsy. METHODS: Fifteen patients with possible normal pressure hydrocephalus (NPH) and previous brain biopsy obtained during intracranial pressure monitoring underwent [18F]flutemetamol PET. Seven of these patients also underwent [11C] Pittsburgh compound B (PiB) PET. [18F]Flutemetamol and [11C]PiB uptake was quantified using standardized uptake value ratio (SUVR) with the cerebellar cortex as a reference region. Tissue amyloid-ß was evaluated using the monoclonal antibody 4G8, Thioflavin-S and Bielschowsky silver stain. RESULTS: [18F]Flutemetamol and [11C]PiB SUVRs correlated with biopsy specimen amyloid-ß levels contralateral (r = 0.86, P < 0.0001; r = 0.96, P = 0.0008) and ipsilateral (r = 0.82, P = 0.0002; r = 0.87, P = 0.01) to the biopsy site. Association between cortical composite [(18) F]flutemetamol SUVRs and [11C]PiB SUVRs was highly significant (r = 0.97, P = 0.0003). CONCLUSIONS: [18F]Flutemetamol detects brain amyloid-ß in vivo with moderate to high sensitivity and high specificity. This agent, therefore, represents a valuable new tool to study and verify the presence of amyloid-ß pathology, both in patients with possible NPH and among the wider population.

Umbilically and Peripherally Inserted Thin Central Venous Catheters Have Similar Risks of Complications in Very Low-Birth-Weight Infants.

Catheter complications can be life-threatening in very low-birth-weight (VLBW) infants. We retrospectively evaluated non-elective removals of the first thin (1-2F) umbilical vein catheters (tUVCs (n = 92)) and peripherally inserted central venous catheters (PICCs (n = 103)) among 195 VLBW infants. Catheters were removed non-electively in 78 infants (40%), typically due to suspected infection (n = 42) or catheter dislocation (n = 30). Infants with complications had lower birth weights and gestational ages than others. The frequencies and causes of catheter removal were similar in the tUVC and PICC groups. Thirty-one infants had true catheter infections. The number of infections/1000 catheter days was higher in the tUVC group than in the PICC group. In a multivariable analysis, gestational age was associated with catheter infection, but catheter type was not. The odds of catheter complications decreased with increasing gestational age, but no clear association with thin catheter type was found.

Post-mortem findings in 10 patients with presumed normal-pressure hydrocephalus and review of the literature.

AIMS: Neuropathological features of idiopathic normal-pressure hydrocephalus (iNPH) are poorly characterized. Brain biopsy during life may help in the differential diagnosis of dementia, but post-mortem validation of biopsy findings is scarce. Here we review and report brain biopsy and post-mortem neuropathological findings in patients with presumed NPH. METHODS: We evaluated 10 patients initially investigated by intraventricular pressure monitoring and a frontal cortical biopsy for histological and immunohistochemical assessment as a diagnostic procedure for presumed NPH. RESULTS: Out of the 10 patients, eight were shunted and seven benefited. Until death, six had developed severe and two mild cognitive impairment. One was cognitively unimpaired, and one was mentally retarded. Three subjects displayed amyloid-ß (Aß) aggregates in their frontal cortical biopsy obtained at the initial procedure. One of these patients developed Alzheimer's disease during a follow-up time of nearly 10 years. One patient with cognitive impairment and NPH suffered from corticobasal degeneration. In six patients various vascular lesions were seen at the final neuropathological investigation. Five of them were cognitively impaired, and in four vascular lesions were seen sufficient in extent to be considered as causative regarding their symptoms. CONCLUSIONS: The frequent finding of vascular pathology in NPH is intriguing, suggesting that vascular alterations might be causative of cognitive impairment in a notable number of patients with NPH and dementia. Brain biopsy can be used to detect Aß aggregates, but neuropathological characteristics of iNPH as a distinct disease still need to be discovered.

Rightward bias in right hemisphere infarct patients with or without thrombolytic treatment and in healthy controls.

Right hemisphere (RH) infarct patients have a tendency to begin visual scanning from the right side of a given stimulus. Our aim was to find out whether RH patients with (T+) or without (T-) thrombolytic treatment and healthy controls differ in their starting points in three cancellation tasks. Our sample comprised of 77 patients and 62 controls. Thirty-four patients received thrombolysis. Rightward orientation bias was more evident in the T- group than in the T+ group. The T+ group showed a robust tendency to start all cancellation tasks more often on the right side than the controls. Regardless of whether they had visual neglect, patients in the T+ group showed still defective rightward orienting, possibly indicating residual attentional problems. The analyses of starting points in visual cancellation tasks provide additional information on residual symptoms of attention difficulties after stroke.

Predictors of functional outcome after right hemisphere stroke in patients with or without thrombolytic treatment.

The purpose of this study was to assess the predictors of functional outcome after right hemisphere stroke at 6-month follow up in patients with or without thrombolytic treatment. Thrombolysis did not predict functional outcome in instrumental activities of daily living (IADL). Lower acute phase basic activities of daily living (ADL) measured by the Barthel Index was a statistically significant predictor of IADL when adjusted for age and education (p = .015) and had borderline significance (p = .076) as a predictor of functional outcome when adjusted for severity of stroke at admission. When stroke severity was taken into account also higher age became a statistically significant (p = .039) predictor of functional outcome. The acute phase neuropsychological symptoms predicted the functional outcome in unadjusted analyses but when adjusted for age, education, and severity of stroke no independent association was found.

Industrial worker exposure to airborne particles during the packing of pigment and nanoscale titanium dioxide.

CONTEXT: Titanium dioxide (TiO2) factory workers' source specific exposure and dose to airborne particles was studied extensively for particles between 5 nm and 10 µm in size. OBJECTIVE: We defined TiO2 industry workers' quantitative inhalation exposure levels during the packing of pigment TiO2 (pTiO2) and nanoscale TiO2 (nTiO2) material from concentrations measured at work area. METHODS: Particle emissions from different work events were identified by linking work activity with the measured number size distributions and mass concentrations of particles. A lung deposit model was used to calculate regional inhalation dose rates in units of particles min⁻¹ and µg min⁻¹ without use of respirators. RESULTS: Workers' average exposure varied from 225 to 700 µg m⁻³ and from 1.15 × 104 to 20.1 × 104 cm⁻4. Over 90% of the particles were smaller than 100 nm. These were mainly soot and particles formed from process chemicals. Mass concentration originated primarily from the packing of pTiO2 and nTiO2 agglomerates. The nTiO2 exposure resulted in a calculated dose rate of 3.6 × 106 min⁻¹ and 32 µg min⁻¹ where 70% of the particles and 85% of the mass was deposited in head airways. CONCLUSIONS: The recommended TiO2 exposure limits in mass by NIOSH and in particle number by IFA were not exceeded. We recommend source-specific exposure assessment in order to evaluate the workers' risks. In nTiO2 packing, mass concentration best describes the workers' exposure to nTiO2 agglomerates. Minute dose rates enable the simulation of workers' risks in different exposure scenarios.

The presence of visual neglect after thrombolytic treatment in patients with right hemisphere stroke.

Visual neglect (VN) is a common consequence of right hemisphere (RH) stroke. The aims of this study were to explore the presence of VN after RH stroke in the patients with (T+) or without (T-) thrombolytic treatment, and to determine whether thrombolysis is a predictor of VN. The study group consisted of 77 RH infarct patients. VN was evaluated with six conventional subtests of the Behavioural Inattention Test (BIT). Stroke severity was assessed using the National Institute of Health Stroke Scale (NIHSS). In the neuropsychological examination, 22% of all RH stroke patients had VN. VN was present in 15% of the patients in the T+ group and in 28% of the patients in the T- group, but the difference was not statistically significant. Despite that, patients in the T- group had a higher risk of VN than patients in the T+ group. Our results suggest that thrombolysis independently predicted absence of VN.

5-Year health-related quality of life outcome in patients with idiopathic normal pressure hydrocephalus.

BACKGROUND: Health-related quality of life (HRQoL) is severely impaired in persons with idiopathic normal pressure hydrocephalus (iNPH). The HRQoL improves in a number of patients after the placement of a cerebrospinal fluid (CSF) shunt, but long-term follow-up of HRQoL is rare. METHODS: Extended follow-up (60 months) of a prospective cohort study involving 189 patients with iNPH who underwent shunt surgery. Preoperative variables were used to predict favorable HRQoL outcome (improvement or non-deterioration) measured by the 15D instrument 5 years after shunting. RESULTS: Out of the 189 initially enrolled study participants, 88 had completed 5-year HRQoL follow-up (46%), 64 had died (34%), and 37 (20%) failed to complete the HRQoL follow-up but were alive at the end of the study. After initial post-operative HRQoL improvement, HRQoL deteriorated so that 37/88 participants (42%) had a favorable HRQoL outcome 5 years after shunting. Multivariate binary logistic regression analysis indicated that younger age (adjusted OR 0.86, 95% CI 0.77-0.95; p < 0.005), lower body mass index (adjusted OR 0.87, 95% CI 0.77-0.98; p < 0.05) and better Mini-Mental State Examination performance (adjusted OR 1.16, 95% CI 1.01-1.32; p < 0.05) before surgery predicted favorable 5-year outcome. CONCLUSIONS: This extended follow-up showed that the self-evaluated HRQoL outcome is associated with iNPH patients' pre-operative cognitive status, overweight and age. The post-operative deterioration may reflect the natural progression of iNPH, but also derive from aging and comorbidities. It indicates a need for long-term follow-up.

Network structures and temporal stability of self- and informant-rated affective symptoms in Alzheimer's disease.

BACKGROUND: Affective symptoms in Alzheimer's disease (AD) can be rated with both informant- and self-ratings. Information from these two modalities may not converge. We estimated network structures of affective symptoms in AD with both rating modalities and assessed the longitudinal stability of the networks. METHODS: Network analyses combining self-rated and informant-rated affective symptoms were conducted in 3198 individuals with AD at two time points (mean follow-up 387 days), drawn from the NACC database. Self-rated symptoms were assessed by Geriatric Depression Scale, and informant-rated symptoms included depression, apathy and anxiety questions from Neuropsychiatric Inventory Questionnaire. RESULTS: Informant-rated symptoms were mainly connected to symptoms expressing lack of positive affect, but not to the more central symptoms of self-rated worthlessness and helplessness. Networks did not differ in structure (p = .71), or connectivity (p = .92) between visits. Symptoms formed four clinically meaningful clusters of depressive symptoms and decline, lack of positive affect, informant-rated apathy and anxiety and informant-rated depression. LIMITATIONS: The symptom dynamics in our study could have been present before AD diagnosis. The lack of positive affect cluster may represent a methodological artefact rather than a theoretically meaningful subgroup. Requiring follow-up lead to a selection of patients with less cognitive decline. CONCLUSIONS: Informant rating may only capture the more visible affective symptoms, such as not being in good spirits, instead of more central and severe symptoms, such as hopelessness and worthlessness. Future research should continue to be mindful of differences between self- and informant-rated symptoms even in earlier stages of AD.

Ongoing pain in streptozotocin model of diabetes in the rat: correlation with cutaneous cheminociception.

Streptozotocin (STZ) is commonly used to induce diabetes mellitus in experimental animal studies on peripheral diabetic neuropathy (PDN). Animals with STZ model of diabetes commonly develop changes in test stimulus-evoked pain behavior. However, it is still unclear whether rats with STZ model of diabetes have ongoing pain. Here we assessed whether STZ-induced diabetes induces ongoing pain-like behavior in male rats using conditioned place-preference (CPP) paradigm. CPP was tested in the fourth week of diabetes by pairing one chamber of the CPP device with vehicle and another chamber with either pregabalin (an established analgesic; 30 mg/kg i.p.; n = 9) or Chembridge-5861528 (a TRPA1 channel antagonist; 30 mg/kg i.p.; n = 9). After drug-pairings, the animals were allowed to choose which chamber they preferred. Mechanical sensitivity was assessed with monofilaments and chemonociception in the skin by determining mustard oil-induced pain behavior. Diabetic animals developed in two weeks mechanical hypersensitivity that changed into hyposensitivity by the fourth week. Mustard oil-induced sustained pain was reduced by the 4th week. After 4 weeks of diabetes, neither pregabalin nor the TRPA1 antagonist induced a significant overall change in the median CPP, although both drugs significantly reduced median withdrawal responses evoked by noxious mechanical stimulation. Pregabalin-induced CPP, however, had a significant positive correlation with the sustained pain behaviour induced by topical mustard oil. In conclusion, the present results suggest that the response to topical mustard oil may predict ongoing pain-like behavior in the STZ model of diabetes.

The Kuopio idiopathic normal pressure hydrocephalus protocol: initial outcome of 175 patients.

BACKGROUND: The Kuopio University Hospital (KUH) idiopathic normal pressure hydrocephalus (iNPH) cerebrospinal fluid (CSF) shunting protocol is described together with the initial outcomes of 175 patients with probable iNPH treated according to this protocol from a defined population. Our secondary aim was to display the variety of differential diagnoses referred to the KUH iNPH outpatient clinic from 2010 until 2017. METHODS: Patients were divided into four groups according to the prognostic tests: tap test (positive or negative) and infusion test (positive or negative). The short-term outcome was compared between groups. The 3-month outcome following shunt surgery was assessed by measuring gait speed improvement, using a 12-point iNPH grading scale (iNPHGS) and the 15D instrument. RESULTS: From 341 patients suspected of iNPH, 88 patients were excluded from further research mostly due to deviation from the protocol's gait assessment guidelines. Hence 253 patients with suspected iNPH were included in the study, 177/253 (70%) of whom were treated with a CSF shunt. A favorable clinical outcome following surgery was observed in 79-93% of patients depending on the prognostic group. A moderate association (Cramer's V = 0.32) was found between the gait speed improvement rate and the prognostic group (X2, p = 0.003). Patients with a positive tap test had the highest gait speed improvement rate (75%). In addition, an improvement in walking speed was observed in 4/11 patients who had both a negative tap test and a negative infusion test. Other outcome measures did not differ between the prognostic groups. Conditions other than iNPH were found in 25% of the patients referred to iNPH outpatient clinic, with the most prevalent being Alzheimer's disease. CONCLUSIONS: Our results emphasize the importance of a systematic diagnostic and prognostic workup especially in cases with an atypical presentation of iNPH. Additional diagnostic testing may be required, but should not delay adequate care. Active surgical treatment is recommended in patients with a high clinical probability of iNPH. Other neurological conditions contributed to most of the non iNPH diagnoses.

Genetic study between SIRT1, PPARD, PGC-1alpha genes and Alzheimer's disease.

Single nucleotide polymorphisms (SNPs) in three diabetes-related genes (SIRT1, PPARD, PGC-1alpha) were investigated with a case-control approach. To examine the genetic association of those genes with Alzheimer's disease (AD) risk, we used the TaqMan technique to genotype five SNP sites for SIRT1, six for PPARD and eight for the PGC-1alpha gene, in 326 Finnish AD cases and 463 controls and conducted a single allele and genotypic distribution comparison as well as estimated haplotype frequencies between cases and controls. No significant differences in AD risk were found in single SNP and haplotype analyses for any of the three genes between 326 cases and 463 controls. However, in a subgroup of women older than 65 years, the frequencies of three SNPs in the SIRT1 gene were significantly different between AD and controls. We conclude that there is no real association with SNPs available in the present study between SIRT1, PPARD or PGC-1alpha genes and AD risk in the Finnish population.

Oxidative Stress in the Amygdala Contributes to Neuropathic Pain.

Earlier studies indicate that the central nucleus of the amygdala (CeA) contributes to neuropathic pain. Here we studied whether amygdaloid administration of antioxidants or antagonists of TRPA1 that is among ion channels activated by oxidative stress attenuates nociceptive or affective pain in experimental neuropathy, and whether this effect involves amygdaloid astrocytes or descending serotonergic pathways acting on the spinal 5-HT1A receptor. The experiments were performed in rats with spared nerve injury (SNI). Drugs were administered through a chronic cannula in the CeA or internal capsule (control site), and an intrathecal catheter. Nociception was assessed using monofilaments and affective pain using conditioned place-aversion. Antioxidants or TRPA1 antagonists in the CeA attenuated both nociceptive and affective pain in SNI animals but not in sham controls or in a control injection site. Drugs influencing astroglia (a gap junction decoupler or a D-amino acid oxidase inhibitor) in the CeA had no effect on SNI rats, whereas local anesthesia of the CeA attenuated nociception. Spinally administered 5-HT1A receptor antagonist at a dose that had no effect alone prevented the antinociceptive effect of amygdaloid TRPA1 blockers. The results suggest that injury-induced amygdaloid oxidative stress that drives TRPA1 promotes neuropathic pain behavior. This pronociceptive effect involves suppression of medullospinal serotonergic feedback-inhibition acting on the spinal 5-HT1A receptor. While the CeA is involved in mediating the nerve injury-induced pronociception, it may not be a critical relay for the recruitment of medullospinal feedback-inhibition.