Month of birth is associated with multiple sclerosis but not with HLA-DR15 in Finland.

BACKGROUND: Spring birth has been found to be associated with increase in the risk of MS. However, this effect is reportedly found particularly in HLA-DR15 positive patients. OBJECTIVE: Examine the month of birth (MOB) effect in Finnish MS patients and its association with HLA-DR15. METHODS: Using the national register on hospitalizations during 1979-2004 we identified 8359 MS patients. We used a χ(2)-analysis to compare the distribution of MOB in MS patients versus age-adjusted controls. Patients were subdivided into 10-year birth cohorts to analyse temporal variations in MOB. A subgroup of HLA-typed MS patients (n = 657) and a population sample of healthy donors from the Finnish Bone Marrow Donor Registry (n = 19,805) were included to analyse connections between HLA-DR15 and MOB. RESULTS: An April birth was associated with a 9.4% increased risk of MS (p = 0.008), whereas November birth was associated with an 11.1% decreased risk (p = 0.004) compared with the expected birth distribution. No temporal clustering in the MOB effect was found during 1900-1988. Both HLA-DR15 positive (34% increase, p = 0.043) and DR15 negative (48% increase, p = 0.0095) MS patients exhibited an increase in spring births (in May). HLA-DR15 in healthy subjects was not associated with MOB. CONCLUSIONS: We confirm that spring birth increases MS risk. This phenomenon was not associated with HLA-DR15 and there was no evidence of temporal clustering. The MOB effect suggests that early developmental processes may modulate MS risk.

Postoperative cognitive change after cardiac surgery predicts long-term cognitive outcome.

OBJECTIVES: Postoperative cognitive dysfunction (POCD) is a common consequence of coronary artery bypass grafting. However, domain-specific associations between postoperative changes and long-term performance are poorly known. The aim of this study was to investigate whether domain-specific cognitive changes after cardiac surgery predict long-term cognitive outcome. MATERIALS AND METHODS: We assessed 100 patients (86 men, mean age 60) before coronary artery bypass grafting, with re-examinations after one week, three months, and a mean of 6.7 years. The extensive neuropsychological test battery was organized into seven functional cognitive domains. Cognitive decline and improvement were defined with the reliable change index derived from 17 matching healthy controls. Analyses were adjusted for baseline cognitive performance, age, gender, education and cardiovascular risks factors. RESULTS: On group level, one week after surgery 71% patients showed cognitive decline and 9% improvement in any functional domain, as compared to preoperative results. Three months postsurgery, decline was observed in 47% and improvement in 25% of patients. Executive functioning was the most sensitive domain to both decline and improvement. Postoperative dysfunction predicted long-term cognitive deterioration six years after operation, particularly in the domain of executive functioning. CONCLUSIONS: POCD after coronary artery bypass grafting is an essential risk factor for long-term deterioration and an indication for neuropsychological follow-up. Assessment of change in executive functioning after coronary artery bypass grafting may help to identify patients at risk for unfavorable long-term outcome.

Hypothermia-treated cardiac arrest patients with good neurological outcome differ early in quantitative variables of EEG suppression and epileptiform activity.

OBJECTIVE: To evaluate electroencephalogram-derived quantitative variables after out-of-hospital cardiac arrest. DESIGN: Prospective study. SETTING: University hospital intensive care unit. PATIENTS: Thirty comatose adult patients resuscitated from a witnessed out-of-hospital ventricular fibrillation cardiac arrest and treated with induced hypothermia (33 degrees C) for 24 hrs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Electroencephalography was registered from the arrival at the intensive care unit until the patient was extubated or transferred to the ward, or 5 days had elapsed from cardiac arrest. Burst-suppression ratio, response entropy, state entropy, and wavelet subband entropy were derived. Serum neuron-specific enolase and protein 100B were measured. The Pulsatility Index of Transcranial Doppler Ultrasonography was used to estimate cerebral blood flow velocity. The Glasgow-Pittsburgh Cerebral Performance Categories was used to assess the neurologic outcome during 6 mos after cardiac arrest. Twenty patients had Cerebral Performance Categories of 1 to 2, one patient had a Cerebral Performance Categories of 3, and nine patients had died (Cerebral Performance Categories of 5). Burst-suppression ratio, response entropy, and state entropy already differed between good (Cerebral Performance Categories 1-2) and poor (Cerebral Performance Categories 3-5) outcome groups (p = .011, p = .011, p = .008) during the first 24 hrs after cardiac arrest. Wavelet subband entropy was higher in the good outcome group between 24 and 48 hrs after cardiac arrest (p = .050). All patients with status epilepticus died, and their wavelet subband entropy values were lower (p = .022). Protein 100B was lower in the good outcome group on arrival at ICU (p = .010). After hypothermia treatment, neuron-specific enolase and protein 100B values were lower (p = .002 for both) in the good outcome group. The Pulsatility Index was also lower in the good outcome group (p = .004). CONCLUSIONS: Quantitative electroencephalographic variables may be used to differentiate patients with good neurologic outcomes from those with poor outcomes after out-of-hospital cardiac arrest. The predictive values need to be determined in a larger, separate group of patients.

Multiple sclerosis in G: genes and geography.

Multiple sclerosis (MS) shows uneven geographic distribution globally as well as within countries. In epidemiological studies we have previously demonstrated that there is a high-risk focus for MS in the southern Ostrobothnian region of western Finland. In genetic studies we recently identified haplotypes that associate with MS specifically in patients originating from southern Ostrobothnia suggesting a founder effect. Such haplotypes can be used as molecular tools for tracing common ancestry between patients in different geographic locations. In addition to providing clues to the historical origin, such a genetic archeological approach should help narrow the size of the shared haplotype, thus facilitating the identification of etiological variants and possibly define a superfamily of MS patients with common pathogenetic mechanisms.

Neuromyelitis optica and aquaporin-4 (AQP4) autoantibodies in consecutive optic neuritis patients in Southern Finland.

PURPOSE: To analyse the frequency of neuromyelitis optica (NMO) among consecutive optic neuritis (ON) patients in Southern Finland and the feasibility of Aquaporin-4 (AQP4) autoantibody assay in the diagnosis of NMO. METHODS: Consecutive patients with symptoms suggestive of acute ON and managed in the Helsinki University Central Hospital were evaluated critically screened for AQP4 autoantibody during a 47.5-month period. The antibodies were determined using radioimmunoprecipitation method. AQP4 index >15 was considered positive, 10-15 borderline and <10 normal. Brain magnetic resonance imaging (MRI) was performed for all patients. RESULTS: Of the 300 patients with suspected ON, 191 were eventually diagnosed as ON, and 66 (35%) of them had a previous diagnosis or were diagnosed with multiple sclerosis (MS). Of the 125 patients without MS diagnosis, 62 (50%) had demyelinative lesions in MRI, which is a risk factor for developing MS. Two patients (1.1%; 95% CI 0.3-4.5) fulfilled the criteria of NMO. Positive AQP4 antibodies were found in three patients (1.6% 95% CI 0.3-4.5), one of them had NMO, one had MS and one became diagnosed with MS a month later. Borderline autoantibody levels were found in 10 patients, 7 of whom had MS. CONCLUSIONS: NMO is rare among ON patients in the population of Southern Finland. In this small cohort, the sensitivity and positive predictive values of the AQP4 autoantibody index for NMO were low, 1/2 and 1/3 respectively, and do not support initiating routine screening.

Viral encephalitis associated with pandemic 2009 (H1N1) influenza A.

Encephalitis has been described as a rare complication of pandemic 2009 (H1N1) influenza A infection in children and adolescents. This report is on two adult patients who presented with encephalitis in relation to acute H1N1 influenza. Encephalitis is therefore also a potential complication of pandemic 2009 (H1N1) influenza infection in adults.