A comparison of the cumulative incidence and early risk factors for psychotic disorder in young adults in the Northern Finland Birth Cohorts 1966 and 1986.

AIMS: Few studies have compared time trends for the incidence of psychosis. To date, the results have been inconsistent, showing a decline, an increase or no significant change. As far as we know, no studies explored changes in prevalence of early risk factors. The aim of this study was to investigate differences in early risk factors and cumulative incidences of psychosis by type of psychosis in two comparable birth cohorts. METHODS: The Northern Finland Birth cohorts (NFBCs) 1966 (N = 12 058) and 1986 (N = 9432) are prospective general population-based cohorts with the children followed since mother's mid-pregnancy. The data for psychoses, i.e. schizophrenia (narrow, spectrum), bipolar disorder with psychotic features, major depressive episode with psychotic features, brief psychosis and other psychoses (ICD 8-10) were collected from nationwide registers including both inpatients and outpatients. The data on early risk factors including sex and place of birth of the offspring, parental age and psychosis, maternal education at birth were prospectively collected from the population registers. The follow-up reached until the age of 27 years. RESULTS: An increase in the cumulative incidence of all psychoses was seen (1.01% in NFBC 1966 v. 1.90% in NFBC 1986; p < 0.001), which was due to an increase in diagnosed affective and other psychoses. Earlier onset of cases and relatively more psychoses in women were observed in the NFBC 1986. Changes in prevalence of potential early risk factors were identified, but only parental psychosis was a significant predictor in both cohorts (hazard ratios ≥3.0; 95% CI 1.86-4.88). The difference in psychosis incidence was not dependent on changes in prevalence of studied early risk factors. CONCLUSIONS: Surprisingly, increase in the cumulative incidence of psychosis and also changes in the types of psychoses were found between two birth cohorts 20 years apart. The observed differences could be due to real changes in incidence or they can be attributable to changes in diagnostic practices, or to early psychosis detection and treatment.

Interaction between parental psychosis and early motor development and the risk of schizophrenia in a general population birth cohort.

BACKGROUND: Delayed motor development in infancy and family history of psychosis are both associated with increased risk of schizophrenia, but their interaction is largely unstudied. AIM: To investigate the association of the age of achieving motor milestones and parental psychosis and their interaction in respect to risk of schizophrenia. METHODS: We used data from the general population-based prospective Northern Finland Birth Cohort 1966 (n=10,283). Developmental information of the cohort members was gathered during regular visits to Finnish child welfare clinics. Several registers were used to determine the diagnosis of schizophrenia among the cohort members and psychosis among the parents. Altogether 152 (1.5%) individuals had schizophrenia by the age of 46 years, with 23 (15.1%) of them having a parent with psychosis. Cox regression analysis was used in analyses. RESULTS: Parental psychosis was associated (P<0.05) with later achievement of holding the head up, grabbing an object, and walking without support. In the parental psychosis group, the risk for schizophrenia was increased if holding the head up (hazard ratio [HR]: 2.46; degrees of freedom [df]=1; 95% confidence interval [95% CI]: 1.07-5.66) and touching the thumb with the index finger (HR: 1.84; df=1; 95% CI: 1.11-3.06) was later. In the group without parental psychosis, a delay in the following milestones increased the risk of schizophrenia: standing without support and walking without support. Parental psychosis had an interaction with delayed touching thumb with index finger (HR: 1.87; df=1; 95% CI: 1.08-3.25) when risk of schizophrenia was investigated. CONCLUSIONS: Parental psychosis was associated with achieving motor milestones later in infancy, particularly the milestones that appear early in a child's life. Parental psychosis and touching the thumb with the index finger had a significant interaction on risk of schizophrenia. Genetic risk for psychosis may interact with delayed development to raise future risk of schizophrenia, or delayed development may be a marker of other risk processes that interact with genetic liability to cause later schizophrenia.

Education-corrected CERAD identifies MCI and dementia in Parkinson's disease.

OBJECTIVES: This study examined whether controlling for educational background in the CERAD cognitive screening battery would affect the likelihood of patients with Parkinson's disease to fulfill criteria for mild cognitive impairment (PD-MCI) and dementia (PDD). MATERIALS & METHODS: One-hundred seventeen patients with PD were studied. Cognitive impairment was determined as two subtest scores falling below either the standard cutoff scores or education-corrected cutoff scores. The presence of dementia was determined by clinical interview or Clinical Dementia Rating. Patients were then classified as PD-MCI and PDD according to cognitive test performance and presence/absence of dementia. RESULTS: The number of cognitively impaired patients (PD-MCI or PDD) was significantly higher when education-controlled cutoff scores were used (62.5% vs 38%). Correspondingly, the number of false negatives (demented PD patients performing normally in CERAD) was significantly lower when education-corrected cutoff scores were used (4% vs 10%). CONCLUSIONS: Controlling for education increases the sensitivity of the CERAD for PD-MCI and PDD.

CERAD test performance and cognitive impairment in Parkinson's disease.

OBJECTIVES: Many patients with Parkinson's disease (PD) develop mild cognitive impairment (PD-MCI) and dementia (PDD). The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neurocognitive test battery was originally developed to identify early Alzheimer's disease, but it has become a widely used screening instrument also for other types of dementia. The aim of the study was to examine differences in CERAD test performances between cognitively intact and impaired PD patients. MATERIALS AND METHODS: Eighty-eight PD patients participating in a rehabilitation course were studied. The Clinical Dementia Rating (CDR) was used to assess cognitive impairment. Sixty-six patients were cognitively intact and 22 had cognitive impairment (≥1 in two or more domains or a sum of boxes score of ≥3). The Finnish CERAD test battery was used to measure cognitive functions in seven different domains (language functions, verbal learning, visuospatial functions, delayed recall, memory consolidation, recognition memory, and executive functions). RESULTS: There were significant differences between the cognitively intact and impaired patients in six CERAD subtests (wordlist learning sum, wordlist delayed recall, constructional praxis recall, clock drawing, verbal fluency and constructional praxis copy) when controlling for covariates (disease duration, motor symptoms, age, and education). No differences were observed in memory consolidation scores. CONCLUSIONS: The results indicate that mild cognitive impairment in PD is related to deficits in memory, executive functions, and visuospatial functions. The memory deficit is non-amnestic and does not entail accelerated forgetting. CERAD shows promise in identifying PD patients with cognitive impairment and increased risk of dementia.

Apathy is associated with activities of daily living ability in Parkinson's disease.

BACKGROUND: Neuropsychiatric symptoms and impairment in performing activities of daily living (ADL) in patients with Parkinson's disease (PD) are strong predictors of the overall caregiver burden and they increase the risk for nursing home admission of the patients. The purpose of the present study was to assess the association of neuropsychiatric symptoms and ADL functions in PD. METHODS: A total of 73 community-dwelling PD patients were studied. The mean age of the patient group was 65 years and the mean disease duration was 9 years. The Neuropsychiatric Inventory was used to measure neuropsychiatric symptoms, and ADL abilities were measured by the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory. RESULTS: The prevalence of neuropsychiatric symptoms in patients with PD was 73%. The most common symptoms were depression, anxiety, irritability, apathy and agitation. ADL ability correlated significantly with apathy (p < 0.002) even when adjusted for motor symptoms. CONCLUSION: Apathy was significantly associated with ADL in PD. The result indicates that more attention should be paid to identifying apathy and targeting therapeutic interventions.

Etiology of aseptic meningitis and encephalitis in an adult population.

OBJECTIVE: To investigate the etiology of aseptic meningitis and encephalitis in an adult population using modern microbiologic methods. METHODS: Consecutive patients (ages > or =16) with aseptic meningitis or encephalitis treated in Turku University Hospital, Finland, during 1999 to 2003 were included in the study. Microbiologic tests were performed, including CSF PCR tests for enteroviruses, herpes simplex virus (HSV) 1, HSV-2, and varicella zoster virus (VZV), as well as serum and CSF antibody analysis for these viruses. Antibody testing was also performed for other pathogens commonly involved in neurologic infections. Virus culture was performed on CSF, fecal, and throat swab specimens. RESULTS: Etiology was defined in 95 of 144 (66%) patients with aseptic meningitis. Enteroviruses were the major causative agents (26%), followed by HSV-2 (17% of all, 25% of females) and VZV (8%). Etiology was identified in 15 of 42 (36%) patients with encephalitis, VZV (12%), HSV-1 (9%), and tick-borne encephalitis virus (9%) being the most commonly involved pathogens. Etiologic diagnosis was achieved by PCR in 43% of the patients with meningitis and in 17% of those with encephalitis. CONCLUSIONS: Enteroviruses and HSV-2 are the leading causes of adult aseptic meningitis, and PCR is of diagnostic value. However, in most cases of encephalitis, the etiology remains undefined.

Significant variation in mortality and functional outcome after acute ischaemic stroke between Western countries: data from the tinzaparin in acute ischaemic stroke trial (TAIST).

BACKGROUND: The medical care of patients with acute stroke varies considerably between countries. This could lead to measurable differences in mortality and functional outcome. OBJECTIVE: To compare case mix, clinical management, and functional outcome in stroke between 11 countries. METHODS: All 1484 patients from 11 countries who were enrolled into the tinzaparin in acute ischaemic stroke trial (TAIST) were included in this substudy. Information collected prospectively on demographics, risk factors, clinical features, measures of service quality (for example, admission to a stroke unit), and outcome were assessed. Outcomes were adjusted for treatment assignment, case mix, and service relative to the British Isles. RESULTS: Differences in case mix (mostly minor) and clinical service (many of prognostic relevance) were present between the countries. Significant differences in outcome were present between the countries. When assessed by geographical region, death or dependency were lower in North America (odds ratio (OR) adjusted for treatment group only = 0.52 (95% confidence interval, 0.39 to 0.71) and north west Europe (OR = 0.54 (0.37 to 0.78)) relative to the British Isles; similar reductions were found when adjustments were made for 11 case mix variables and five service quality measures. Similarly, case fatality rates were lower in North America (OR = 0.44 (0.30 to 0.66)) and Scandinavia (OR = 0.50 (0.33 to 0.74)) relative to the British Isles, whether crude or adjusted for case mix and service quality. CONCLUSIONS: Both functional outcome and case fatality vary considerably between countries, even when adjusted for prognostic case mix variables and measures of good stroke care. Differing health care systems and the management of patients with acute stroke may contribute to these findings.

Neurologic symptoms are common during gestation and puerperium in CADASIL.

Based on a structured questionnaire and medical records, the authors found that 12 of 25 mothers with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with the R133C NOTCH3 mutation had had neurologic symptoms in 17 of their 43 pregnancies, most commonly hemiparesthesia (76%), hemiparesis (36%), aphasia (65%), and visual disorders (47%). In 82% of the patients, the symptoms were the first manifestation of CADASIL. The symptoms were most common during puerperium and in patients older than age 30.

Changing incidence and outcome of infants with respiratory distress syndrome in the 1990s: a population-based survey.

AIM: To evaluate the trends in the incidence, clinical course and outcome of respiratory distress syndrome (RDS) in the newborn in the Oulu University Hospital region in northern Finland. METHODS: In the population of 58 990 infants, the incidence rates of RDS specific to gestational age and birthweight in two consecutive periods, 1990-95 and 1996-99, were calculated. Clinical course and other neonatal morbidities were reported. All surviving infants were followed up until 1 y of corrected age. RESULTS: The overall incidence of RDS did not change significantly (8.7/1000 livebirths in 1990-95 vs 7.6 in 1996-99; p = 0.15), but the gestational age-adjusted incidence decreased between the two consecutive periods (p = 0.005). The frequency of infants with gestational age below 28 wk tended to increase towards the late 1990s, while their RDS incidence remained unchanged. RDS-related neonatal mortality decreased in parallel with neonatal mortality, accounting for 15% of all neonatal deaths. The duration of oxygen therapy shortened (8.0 vs 5.5 d) and the incidence of pneumothorax decreased (9.7 vs 4.1%), whereas the rate of chronic lung disease at 36 wk of postconceptional age (16.4 vs 16.7%) and at 1 y of corrected age (9.2 vs 8.2%) remained unchanged, as did also associated neurosensory morbidity (8.8 vs 9.5%). CONCLUSION: During the 1990s, the incidence of RDS shifted towards more immature infants and the gestational-age specific incidence decreased. The course of the disease shortened and acute complications decreased. The frequency of chronic pulmonary sequelae (and associated neurosensory morbidity) at the age of 1 y did not change significantly.

Aetiological diagnosis of brain abscesses and spinal infections: application of broad range bacterial polymerase chain reaction analysis.

OBJECTIVE: To evaluate the usefulness of the broad range bacterial rDNA polymerase chain reaction (PCR) method combined with DNA sequencing in the aetiological diagnosis of intracranial or spinal infections in neurosurgical patients. METHODS: In addition to conventional methods, the broad range bacterial PCR approach was applied to examine pus or tissue specimens from cerebral or spinal lesions in patients treated in a neurosurgical unit for a clinical or neuroradiological suspicion of bacterial brain abscess or spondylitis. RESULTS: Among the 44 patients with intracranial or spinal lesions, the final diagnosis suggested bacterial disease in 25 patients, among whom the aetiological agent was identified in 17. A causative bacterial species was identified only by the rDNA PCR method in six cases, by both the PCR methodology and bacterial culture in six cases, and by bacterial culture alone in five. All samples in which a bacterial aetiology was identified only by the PCR approach were taken during antimicrobial treatment, and in three patients the method yielded the diagnosis even after >/= 12 days of parenteral treatment. One case also identified by the PCR approach alone involved a brain abscess caused by Mycoplasma hominis, which is not readily cultured by routine methods. CONCLUSIONS: In patients with brain abscesses and spinal infections, the broad range bacterial rDNA PCR approach may be the only method to provide an aetiological diagnosis when the patient is receiving antimicrobial treatment, or when the causative agent is fastidious.

Transoesophageal echocardiography in selecting patients for anticoagulation after ischaemic stroke or transient ischaemic attack.

OBJECTIVES: To investigate prospectively the role of transoesophageal echocardiography (TEE) in selecting patients for anticoagulation in an unselected stroke population. METHODS: Transthoracic echocardiography (TTE) and TEE were done in all clinically suitable hospitalised patients (n = 457) with transient ischaemic attack or ischaemic stroke in the acute phase during a two year period in Turku University Hospital. 441 patients were successfully evaluated for cardiac sources of embolism using TEE within 31 days of the event. RESULTS: A major risk factor for a cardiac source of embolism excluding atrial fibrillation, acute myocardial infarction, and prosthetic valve was detected in 10% of patients and a minor risk factor for a cardiac source of embolism in 46%. When a major risk factor of a cardiac source of embolism was detected using TTE or TEE and no contraindications were present, the patient was given anticoagulation drugs. If a minor risk factor for a cardiac source of embolism was detected, anticoagulation treatment was started after clinical assessment, if no contraindications were present. In 62 (14%) cases, the patient was given oral anticoagulation drugs or the necessity of ongoing anticoagulation treatment was confirmed on the basis of TEE. When these anticoagulation treated patients were evaluated using logistic regression analysis, they were found to have significantly more atrial fibrillation and histories of myocardial infarctions. Moreover, the patients were mainly men. When patients in sinus rhythm and without any history of cardiac disease were analysed, 8% of patients were found to have been given anticoagulation drugs on the basis of TEE data. CONCLUSION: This study suggests that TEE should be used in patients with stroke even without any clinical evidence of cardiac disease when the patients are candidates for anticoagulation.

Respiratory distress syndrome: evaluation of genetic susceptibility and protection by transmission disequilibrium test.

Based on epidemiological data and genetic association studies, neonatal respiratory distress syndrome (RDS) is a complex disease with a multigenic background. The genes coding for surfactant proteins (SP) A and B have been assigned as the most likely genes in the etiology of RDS. The major factor predisposing to RDS is prematurity, and thus the phenotype of a very premature newborn infant that does not develop the disease can be regarded as hypernormal. Altogether 107 father-mother-offspring trios were divided into two sets according to the proband's phenotype, to evaluate familial segregation of candidate gene polymorphisms by the transmission disequilibrium test. A set of 76 trios were analyzed for transmission disequilibrium from parents to affected offspring. Another set of 31 trios were studied for allele transmission from parents to hypernormal offspring born very prematurely before the gestational age of 32 weeks. SP-A1-A2 haplotype 6A(2)-1A(0) showed significant excess transmission to affected infants and SP-A1 allele 6A(2) decreased transmission to the hypernormals. The present family study provides strong support for a direct or indirect role of the SP-A alleles as genetic predisposers to RDS in premature infants. The inclusion of parent-hypernormal offspring trios in transmission disequilibrium test is a useful approach to test for genetic protection against a disease.

Tinzaparin in acute ischaemic stroke (TAIST): a randomised aspirin-controlled trial.

BACKGROUND: Low-molecular-weight heparins and heparinoids are superior to unfractionated heparin in the prevention and treatment of venous thromboembolism, but their safety and efficacy in acute ischaemic stroke are inadequately defined. METHODS: This randomised, double-blind, aspirin-controlled trial tested the safety and efficacy of treatment with high-dose tinzaparin (175 anti-Xa IU/kg daily; 487 patients), medium-dose tinzaparin (100 anti-Xa IU/kg daily; 508 patients), or aspirin (300 mg daily; 491 patients) started within 48 h of acute ischaemic stroke and given for up to 10 days. Primary intracerebral haemorrhage was excluded by computed tomography. Outcome was assessed, with treatment allocation concealed, by the modified Rankin scale at 6 months (independence [scores 0-2] vs dependence or death [scores 3-6]). FINDINGS: Of 1486 randomised patients, two did not receive treatment and 46 were lost to follow-up. The proportions independent at 6 months were similar in the groups assigned high-dose tinzaparin (194/468 [41.5%]), medium-dose tinzaparin (206/486 [42.4%]), or aspirin (205/482 [42.5%]). There was no difference in effect in any predefined subgroup, including patients with presumed cardioembolic stroke. Other outcome measures were similar between the treatment groups (disability, case-fatality, and neurological deterioration rates). During the in-hospital treatment period no patient assigned high-dose tinzaparin developed a symptomatic deep-vein thrombosis compared with nine assigned aspirin. Conversely, seven patients assigned high-dose tinzaparin developed symptomatic intracerebral haemorrhage compared with one in the aspirin group. INTERPRETATION: Treatment with tinzaparin, at high or medium dose, within 48 h of acute ischaemic stroke did not improve functional outcome compared with aspirin. Although high-dose tinzaparin was superior in preventing deep-vein thrombosis, it was associated with a higher rate of symptomatic intracranial haemorrhage.

Phenotype of a homozygous CADASIL patient in comparison to 9 age-matched heterozygous patients with the same R133C Notch3 mutation.

BACKGROUND AND PURPOSE: CADASIL is an autosomal dominant arteriopathy, characterized by multiple brain infarcts, cognitive decline, and finally dementia, which is caused by mutations in Notch3 gene encoding a Notch3 receptor protein. We describe the clinical, neuropsychological, imaging, genetic, and skin biopsy findings in a CADASIL patient homozygous for the C475T mutation resulting in R133C amino acid substitution, in comparison to 9 age-matched heterozygous patients with the same mutation. METHODS: The patients were examined clinically and neuropsychologically and with MRI and positron emission tomography for assessment of cerebral blood flow. The gene defect was analyzed by sequencing the products of polymerase chain reaction of exons 3 and 4 of the Notch3 gene. Dermal arteries were analyzed electron microscopically. RESULTS: The homozygous patient had his first-ever stroke at age 28 years. This is markedly earlier than the average, but the patient's heterozygous son had his first transient ischemic attack-like episode at the same age and another heterozygous patient had his first-ever stroke when only 2 years older. He was neuropsychologically more severely deteriorated than all but 1 of the heterozygous patients. These 2 patients had the most severe (confluent grade D) white matter MRI changes. Positron emission tomography showed markedly reduced cerebral blood flow. Skin biopsy revealed profuse deposits of granular osmiophilic material. The progression of disease in the homozygous case was, however, slower than in the most severely affected heterozygous patient. CONCLUSIONS: Our homozygous patient's phenotype is within the clinical spectrum of CADASIL, although at its severe end. Thus, CADASIL may follow the classic definition of a dominant disease, according to which the heterozygous and homozygous patients are clinically indistinguishable.

Botulinum toxin in the treatment of cricopharyngeal dysphagia.

Dysphagia is a common symptom in various neurological disorders affecting pharyngeal functions. Cricopharyngeal dysfunction is one of the major findings in these patients. The most effective treatment for restoring normal swallowing function in persistent cricopharyngeal dysfunction is cricopharyngeal myotomy, especially when mechanical obstruction or a well-localized neuromuscular dysfunction, such as a cricopharyngeal muscle spasm, is present. However, when there is a more diffuse neurological disorder present the results of surgery are more disappointing. In unclear cases, or in patients with temporary problems, no good method other than swallowing training, bougienage, and tube feeding are available. During the past decade, botulinum toxin has been found to be of therapeutic value in the treatment of a variety of neurological disorders associated with inappropriate muscular contractions such as torticollis and spasmodic dysphonia. Recently, injections of botulinum toxin in patients with cricopharyngeal muscle dysfunction have been reported to result in marked relief of dysphagia. In this article we describe our experiences with botulinum toxin injections to treat four patients suffering from deglutition problems and cricopharyngeal dysphagia of different origins. Botulinum toxin was injected into the cricopharyngeus muscle that was identified by endoscopy under general anesthesia. In this study, no major side effects were observed. Three patients obtained a significant improvement of esophageal symptoms after the first injection. The treatment had limited effect in one patient who had reflux disease and only slight cricopharyngeus dysfunction.