Overweight in Adolescence and Young Adulthood in Association With Adult Cerebrovascular Disease: The NFBC1966 Study.

BACKGROUND: Risk factors for cerebrovascular disease in adulthood are well known. However, research on individuals' risk factors throughout their life span has been limited. This prospective cohort study aims to determine the effect of body mass index (BMI) and its changes in adolescence and young adulthood on early onset cerebrovascular disease. METHODS: This study includes 10 491 people (5185 women) from the Northern Finland Birth Cohort 1966. Height, weight, and BMI were measured at ages 14 and 31 years. Sex- and age-specific BMI ranges were used to define overweight and obesity. Data on ischemic and hemorrhagic cerebrovascular diseases between ages 14 and 54 years were extracted from national hospital and death registers. Cox proportion hazard models (95% CI) were used to estimate associations between BMI or its changes and cerebrovascular disease, while adjusting for sex, smoking, educational level, BMI at the other time point, and age at menarche for women. Additionally, sex-BMI interactions were calculated. RESULTS: A total of 452 individuals (4.7%) experienced cerebrovascular disease during the follow-up. The risk of ischemic cerebrovascular disease was increased for overweight women at ages 14 years (hazard ratio [HR], 2.49 [95% CI, 1.44-4.31]) and 31 years (HR, 2.13 [95% CI, 1.14-3.97]), as well as for obese women at ages 14 years (HR, 1.87 [95% CI, 0.76-4.58) and 31 years (HR, 2.67 [95% CI, 1.26-5.65]), with normal weight as the reference. These results were independent of earlier or later BMI. Similar associations were not found among men. The risk of hemorrhagic cerebrovascular disease was increased at age 31 years both among obese women (HR, 3.49 [95% CI, 1.13-10.7) and obese men (HR, 5.75 [95% CI, 1.43-23.1). The risk of any cerebrovascular disease related to overweight at age 14 years was 2.09× higher among girls than boys (95% CI, 1.06-4.15). The risk of ischemic cerebrovascular disease related to obesity at age 31 years was 6.96× higher among women than men (95% CI, 1.36-35.7). CONCLUSIONS: Among women, being overweight in adolescence or young adulthood increases the risk of cerebrovascular disease, especially ischemic, independent of their earlier or later BMI.

XMEN disease caused by the novel MAGT1 p.(Trp136*) mutation may present with neuropsychiatric symptoms.

BACKGROUND: X-linked MAGT1 deficiency with increased susceptibility to EBV-infection and N-linked glycosylation defect (XMEN) disease is caused by MAGT1 loss-of-function (LOF) mutations. The disease commonly presents with respiratory symptoms. Although the central nervous system can be affected, the spectrum of neuropsychiatric symptoms is not completely understood. CASES: We describe a XMEN disease family presenting with atypical neuropsychiatric symptoms. The index, a previously healthy male, developed schizophrenia. Several years later, a novel hemizygous LOF MAGT1 c.407G > A, p.(Trp136X) LOF mutation and XMEN disease diagnosis was confirmed in his brother due to the burden of respiratory infections. Family screening also found the index to suffer from XMEN disease; the XMEN disease was concluded to contribute to the development of schizophrenia. CONCLUSIONS: Our case description demonstrates that the spectrum of XMEN disease clinical presentations can be variable, and the condition may also present with severe neuropsychiatric consequences. While respiratory infections are common among schizophrenia patients, the possibility of inborn errors in immunity should be considered whenever an unexplained personal or family history infection susceptibility is encountered. We recommend evaluating complete family history to exclude unusual monogenic disorders associated or presenting with psychiatric manifestations.

Quantification of Upper Limb Movements in Patients with Hereditary or Idiopathic Ataxia.

Assessment of ataxic movements is usually based on clinical judgment. Technical devices can be employed in the quantification of ataxic movements in addition to clinical evaluation. The effect of maximal speed in upper limb movements in ataxia patients has not been quantified. The aim was to quantify upper limb movements in patients with hereditary or idiopathic ataxia and to find features of movement that are characteristic for ataxia. We examined 19 patients with degenerative ataxia and 21 healthy controls. An ad hoc system comprising a touch screen, an accelerometer, and a gyroscope was used to measure speed, angular acceleration, consistency, and accuracy of upper limb movements. The movements were quantified during finger-to-nose test that the patients were asked to perform at their own pace and as fast as possible. Disease severity was estimated by using the Scale for the Assessment and Rating of Ataxia (SARA). The mean SARA score of the patients was 13.5. Compared to the controls the performance of the patients was slow (p < 0.001) and arrhythmic (p < 0.001), but end-point accuracy on the touch screen was intact. The SARA score correlated with the standard deviation of amplitude of angular acceleration in Z-axis (F(1,17) = 15.00, p < 0.001 with R2 = 0.47). Upper limb movements of the patients with degenerative ataxia were slower and more arrhythmic than those in the controls. The patients retained spatial end-point accuracy.

Early Childhood Growth and Risk of Adult Cerebrovascular Disease: The NFBC1966.

BACKGROUND: Low birth weight is associated with an increased risk of adulthood cerebrovascular disease (CVD). Not much is known about effects of early childhood growth. We studied whether the risk of adult CVD is associated with growth or nutritional factors during early childhood. METHODS: Within the Northern Finland Birth Cohort 1966, 11 991 persons were followed from birth to 52 years of age. CVD diagnoses were extracted from national hospital and death registers with diagnostic coding based on the World Health Organization recommendations. Cox proportional hazard models were used to estimate associations of childhood growth variables, growth trajectories (by Latent Class Growth Modeling), and nutritional factors with adult CVD, for example, ischemic and hemorrhagic strokes. The analyses were adjusted for childhood socioeconomic status and birth weight. RESULTS: A total of 453 (3.8%) CVDs were recorded during follow-up. Among females, groups with low early childhood weight and height had an increased risk for adulthood ischemic CVDs, with an adjusted hazard ratio of 1.97 (95% CI, 1.21-3.20) and 2.05 (CI, 1.11-3.81), respectively. In addition, females with body mass index over 1 SD at body mass index rebound had an increased risk for ischemic CVDs (adjusted hazard ratio, 1.90 [CI, 1.19-3.04]) compared with females with body mass index -1 to +1 SD. These associations were not found among males. CONCLUSIONS: The findings suggest that timing of weight gain during childhood is of significance for development of CVD risk among females.

Molecular epidemiology of hereditary ataxia in Finland.

BACKGROUND: The genetics of cerebellar ataxia is complex. Hundreds of causative genes have been identified, but only a few cause more than single cases. The spectrum of ataxia-causing genes differs considerably between populations. The aim of the study was to investigate the molecular epidemiology of ataxia in the Finnish population. PATIENTS AND METHODS: All patients in hospital database were reviewed for the diagnosis of unspecified ataxia. Acquired ataxias and nongenetic ataxias such as those related to infection, trauma or stroke were excluded. Sixty patients with sporadic ataxia with unknown etiology and 36 patients with familial ataxia of unknown etiology were recruited in the study. Repeat expansions in the SCA genes (ATXN1, 2, 3, 7, 8/OS, CACNA1A, TBP), FXN, and RFC1 were determined. Point mutations in POLG, SPG7 and in mitochondrial DNA (mtDNA) were investigated. In addition, DNA from 8 patients was exome sequenced. RESULTS: A genetic cause of ataxia was found in 33 patients (34.4%). Seven patients had a dominantly inherited repeat expansion in ATXN8/OS. Ten patients had mitochondrial ataxia resulting from mutations in nuclear mitochondrial genes POLG or RARS2, or from a point mutation m.8561C > G or a single deletion in mtDNA. Interestingly, five patients were biallelic for the recently identified pathogenic repeat expansion in RFC1. All the five patients presented with the phenotype of cerebellar ataxia, neuropathy, and vestibular areflexia (CANVAS). Moreover, screening of 54 patients with Charcot-Marie-Tooth neuropathy revealed four additional patients with biallelic repeat expansion in RFC1, but none of them had cerebellar symptoms. CONCLUSIONS: Expansion in ATXN8/OS results in the majority of dominant ataxias in Finland, while mutations in RFC1 and POLG are the most common cause of recessive ataxias. Our results suggest that analysis of RFC1 should be included in the routine diagnostics of idiopathic ataxia and Charcot-Marie-Tooth polyneuropathy.

Pregnancy Risk Factors as Predictors of Offspring Cerebrovascular Disease: The Northern Finland Birth Cohort Study 1966.

[Figure: see text].

Heterozygous TLR3 Mutation in Patients with Hantavirus Encephalitis.

Puumala hantavirus (PUUV) hemorrhagic fever with renal syndrome (HFRS) is common in Northern Europe; this infection is usually self-limited and severe complications are uncommon. PUUV and other hantaviruses, however, can rarely cause encephalitis. The pathogenesis of these rare and severe events is unknown. In this study, we explored the possibility that genetic defects in innate anti-viral immunity, as analogous to Toll-like receptor 3 (TLR3) mutations seen in HSV-1 encephalitis, may explain PUUV encephalitis. We completed exome sequencing of seven adult patients with encephalitis or encephalomyelitis during acute PUUV infection. We found heterozygosity for the TLR3 p.L742F novel variant in two of the seven unrelated patients (29%, p = 0.0195). TLR3-deficient P2.1 fibrosarcoma cell line and SV40-immortalized fibroblasts (SV40-fibroblasts) from patient skin expressing mutant or wild-type TLR3 were tested functionally. The TLR3 p.L742F allele displayed low poly(I:C)-stimulated cytokine induction when expressed in P2.1 cells. SV40-fibroblasts from three healthy controls produced increasing levels of IFN-λ and IL-6 after 24 h of stimulation with increasing concentrations of poly(I:C), whereas the production of the cytokines was impaired in TLR3 L742F/WT patient SV40-fibroblasts. Heterozygous TLR3 mutation may underlie not only HSV-1 encephalitis but also PUUV hantavirus encephalitis. Such possibility should be further explored in encephalitis caused by these and other hantaviruses.

Chronic Infarcts Predict Poor Clinical Outcome in Mechanical Thrombectomy of Sexagenarian and Older Patients.

BACKGROUND: The impact of lacunar and cortical chronic ischemic lesions (CILs) on the clinical outcome of mechanical thrombectomy (MT) has been little studied. Clinical trials suggest that older patients benefit from MT. We investigated the effect of CILs on the clinical outcome of sexagenarian and older patients with acute middle cerebral artery (MCA) or distal internal carotid artery (ICA) stroke who received MT to treat large-vessel occlusion (LVO). METHODS: We prospectively collected the clinical and imaging data of 130 consecutive MT patients of which 68 met the inclusion criteria. We limited the analysis to sexagenarian and older subjects and occlusions no distal than the M2 segment. Baseline clinical, procedural and imaging variables, technical outcome, 24-hour imaging outcome, and the clinical outcome were recorded. Differences between patients with and without CILs were studied with appropriate statistical tests and binary logistic regression analysis. RESULTS: Twenty-one patients (31%) had at least 1 CIL. Thirty-eight percent of patients with CIL(s) compared with 62% without (P = .06) experienced good clinical outcome (3-month modified Rankin Scale ≤ 2). A similar nonsignificant trend was seen when lacunar lesions, lesion multiplicity, and chronic white matter lesions were examined separately. Absence of CIL increased the odds of good clinical outcome 3.7-fold (95% confidence interval 1.0-10.7, P = .05) in logistic regression modeling. CONCLUSIONS: Chronic cortical and lacunar infarcts in admission imaging are associated with poor clinical outcome in sexagenarian and older patients treated with MT for LVO of the MCA or distal ICA.

Internal Carotid Artery and the Proximal M1 Segment Are Optimal Targets for Mechanical Thrombectomy.

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) is an established treatment of acute anterior circulation stroke caused by large vessel occlusion (LVO). We compared the clinical outcome (3-month modified Rankin Scale, mRS) in hyperacute (<3h from the onset of symptoms) ischemic stroke between an MT and an intravenous thrombolysis (IVT) cohort in proximal (ICA and the proximal M1 segment of the middle cerebral artery) and distal (the distal M1 and the M2 segment) LVOs. METHODS: We prospectively reviewed 67 patients who underwent MT with newer-generation stent retrievers. The IVT cohort consisted of 98 patients who received IVT without MT. We recorded baseline clinical, procedural and imaging variables, technical outcome, 24-h imaging outcome, and the clinical outcome. Differences between the groups were studied with theoretically appropriate statistical tests and binary logistic regression analysis. RESULTS: The proportion of patients who had a proximal LVO and experienced good (mRS ≤2) or excellent (mRS ≤1) clinical outcome was significantly larger in the MT group (62 vs. 7%, p < 0.001; 47 vs. 3%, p < 0.001, respectively). In a regression model including relevant confounding variables, good clinical outcome was seen significantly more often among patients with proximal occlusions (OR = 6.0, CI 95% 1.9-18.3, p = 0.002). In a similar model, no statistically significant differences were observed in patients with more distal occlusions. CONCLUSIONS: MT is superior to IVT in achieving good clinical outcome in hyperacute anterior circulation stroke in the most proximal occlusions (ICA and proximal M1 segment). In the distal M1 and M2 segments neither of these therapies clearly outperforms the other.

A novel mutation m.8561C>G in MT-ATP6/8 causing a mitochondrial syndrome with ataxia, peripheral neuropathy, diabetes mellitus, and hypergonadotropic hypogonadism.

Defects in the respiratory chain or mitochondrial ATP synthase (complex V) result in mitochondrial dysfunction that is an important cause of inherited neurological disease. Two of the subunits of complex V are encoded by MT-ATP6 and MT-ATP8 in the mitochondrial genome. Pathogenic mutations in MT-ATP6 are associated with the Leigh syndrome, the syndrome of neuropathy, ataxia, and retinitis pigmentosa (NARP), as well as with non-classical phenotypes, while MT-ATP8 is less frequently mutated in patients with mitochondrial disease. We investigated two adult siblings presenting with features of cerebellar ataxia, peripheral neuropathy, diabetes mellitus, sensorineural hearing impairment, and hypergonadotropic hypogonadism. As the phenotype was suggestive of mitochondrial disease, mitochondrial DNA was sequenced and a novel heteroplasmic mutation m.8561C>G in the overlapping region of the MT-ATP6 and MT-ATP8 was found. The mutation changed amino acids in both subunits. Mutation heteroplasmy correlated with the disease phenotype in five family members. An additional assembly intermediate of complex V and increased amount of subcomplex F1 were observed in myoblasts of the two patients, but the total amount of complex V was unaffected. Furthermore, intracellular ATP concentration was lower in patient myoblasts indicating defective energy production. We suggest that the m.8561C>G mutation in MT-ATP6/8 is pathogenic, leads biochemically to impaired assembly and decreased ATP production of complex V, and results clinically in a phenotype with the core features of cerebellar ataxia, peripheral neuropathy, diabetes mellitus, and hypergonadotropic hypogonadism.

Collateral Circulation Predicts the Size of the Infarct Core and the Proportion of Salvageable Penumbra in Hyperacute Ischemic Stroke Patients Treated with Intravenous Thrombolysis.

BACKGROUND: We studied the impact of collateral circulation on CT perfusion (CTP) parametric maps and the amount of salvaged brain tissue, the imaging and clinical outcome at 24 h and at 3 months in a retrospective acute (<3 h) stroke cohort (105 patients) with anterior circulation thrombus treated with intravenous thrombolysis. METHODS: Baseline clinical and imaging information were collected and groups with different collateral scores (CS) were compared. Binary logistic regression analyses using good CS (CS ≥2) as the dependent variable were calculated. RESULTS: CTP Alberta Stroke Program Early CT Score (ASPECTS) was successfully assessed in 58 cases. Thirty patients displayed good CS. Poor CS were associated with more severe strokes according to National Institutes of Health Stroke Scale (NIHSS) at arrival (15 vs. 7, p = 0.005) and at 24 h (10 vs. 3, p = 0.003) after intravenous thrombolysis. Good CS were associated with a longer mean onset-to-treatment time (141 vs. 121 min, p = 0.009) and time to CTP (102 vs. 87 min, p = 0.047), better cerebral blood volume (CBV) ASPECTS (9 vs. 6, p < 0.001), better mean transit time (MTT) ASPECTS (6 vs. 3, p < 0.001), better noncontrast CT (NCCT) ASPECTS (10 vs. 8, p < 0.001) at arrival and with favorable clinical outcome at 3 months (modified Rankin Scale ≤2, p = 0.002). The fraction of penumbra that was salvageable at arrival and salvaged at 24 h was higher with better CS (p < 0.001 and p = 0.035, respectively). In multivariate analysis, time from the onset of symptoms to imaging (p = 0.037, OR 1.04 per minute, 95% CI 1.00-1.08) and CBV ASPECTS (p = 0.001, OR 2.11 per ASPECTS point, 95% CI 1.33-3.34) predicted good CS. In similar multivariable models, MTT ASPECTS (p = 0.04, OR 1.46 per ASPECTS point, 95% CI 1.02-2.10) and NCCT ASPECTS predicted good CS (p = 0.003, OR 4.38 per CT ASPECTS point, 95% CI 1.66-11.55) along with longer time from the onset of symptoms to imaging (p = 0.045, OR 1.03 per minute, 95% CI 1.00-1.06 and p = 0.02, OR 1.05 per minute, 95% CI 1.00-1.09, respectively). CBV ASPECTS had a larger area under the receiver operating characteristic curve for good CS (0.837) than NCCT ASPECTS (0.802) or MTT ASPECTS (0.752) at arrival. CONCLUSIONS: Favorable CBV ASPECTS, NCCT ASPECTS and MTT ASPECTS are associated with good CS along with more salvageable tissue and longer time from the onset of symptoms to imaging in ischemic stroke patients treated with intravenous thrombolysis.

The association of blood pressure and collateral circulation in hyperacute ischemic stroke patients treated with intravenous thrombolysis.

BACKGROUND: The integrity of collateral circulation is a major prognostic factor in ischemic stroke. Patients with good collateral status have larger penumbra and respond better to intravenous thrombolytic therapy. High systolic blood pressure is linked with worse clinical outcome in patients with acute ischemic stroke treated with intravenous thrombolytic therapy. We studied the effect of different blood pressure parameters on leptomeningeal collateral circulation in patients treated with intravenous thrombolytic therapy (<3 h) in a retrospective cohort. METHODS: Anterior circulation thrombus was detected with computed tomography angiography and blood pressure was measured prior to intravenous thrombolytic therapy in 104 patients. Baseline clinical and imaging information were collected. Group comparisons were performed; Collateral Score (CS) was assessed and entered into logistic regression analysis. RESULTS: Fifty-eight patients out of 104 displayed good collateral filling (CS ≥2). Poor CS was associated with more severe strokes according to National Institutes of Health Stroke Scale (NIHSS) at arrival (16 vs. 11, p = 0.005) and at 24 h (15 vs. 3, p < 0.001) after the treatment. Good CS was associated with higher systolic blood pressure (p = 0.03), but not with diastolic blood pressure (p = 0.26), pulse pressure (p = 0.20) or mean arterial pressure (p = 0.07). Good CS was associated with better Alberta Stroke Program Early CT Score (ASPECTS) in 24 h follow-up imaging (p < 0.001) and favorable clinical outcome at three months (mRS ≤2, p < 0.001). Median CS was the highest (CS = 3) when systolic blood pressure was between 170 and 190 mm Hg (p = 0.03). There was no significant difference in the number of patients with good (n = 11) and poor (n = 12) CS who received intravenous antihypertensive medication (p = 0.39) before or during the thrombolytic therapy. In multivariate analysis age (p = 0.02, OR 0.957 per year, 95% CI 0.92-0.99), time from the onset of symptoms to treatment (p = 0.005, OR 1.03 per minute, 95% CI 1.01-1.05), distal clot location (p = 0.02, OR 3.52, 95% CI 1.19-10.35) and systolic blood pressure (p = 0.04, OR 1.03 per unit mm Hg, 95% CI 1.00-1.05) predicted good CS. Higher systolic blood pressure (p = 0.049, OR 0.96 per unit mm Hg, 95% CI 0.93-1.00) and pulse pressure (p = 0.005, OR 0.94 per unit mm Hg, 95% CI 0.90-0.98) predicted unfavorable clinical outcome at three months in multivariate analysis. CONCLUSION: Moderately elevated systolic blood pressure is associated with good collateral circulation in patients treated with intravenous thrombolytic therapy. However, there is an inverse association of systolic blood pressure with the three-month clinical outcome. Diastolic blood pressure, mean arterial pressure and pulse pressure are not statistically and significantly associated with collateral status.

Computed tomography angiography source images closely reflect the integrity of collateral circulation.

BACKGROUND: We studied the interplay between collateral circulation, the location of the thrombus and infarct extent based on evaluation of CT angiography source images (CTA-SI) in predicting the clinical outcome of patients treated with intravenous thrombolytic therapy (<3h) in a retrospective cohort. METHODS: Anterior circulation occlusion was detected with CTA in 105 patients. The site of the occlusion was recorded, collaterals were assessed with Collateral Score (CS) and Alberta Stroke Program Early CT Score (ASPECTS) was evaluated from CTA-SI, and entered into logistic regression analysis to predict favorable clinical outcome (three-month modified Rankin Scale 0-2). RESULTS: CTA-SI ASPECTS was highly correlated with CS (Spearman's rho=0.63, P=0.01). Not a single patient with good collaterals (CS 2-4) had a poor CTA-SI scan (ASPECTS 0-7). The mean CTA-SI ASPECTS score became progressively lower when the status of the collateral circulation deteriorated (ANOVA P<0.001). In univariate analysis a good CTA-SI scan at the admission predicted favorable three-month outcome (P<0.001). In a multivariate model containing CTA-SI ASPECTS, CS and the site of the occlusion along with significant clinical parameters, CTA-SI ASPECTS was rendered non-significant (P=0.43) in the presence of CS. CONCLUSIONS: CTA-SI and CS convey overlapping information. CTA-SI is not a significant predictor of the clinical outcome three months after intravenous thrombolysis when the other CTA-based parameters, CS and the clot location, are considered simultaneously. CTA-SI may have a role in the assessment of the extent of irreversible ischemic changes at admission if contrast injection and image acquisition protocols are designed suitably.

Impact of atrial fibrillation and inadequate antithrombotic management on mortality in acute neurovascular syndrome.

BACKGROUND: The purpose of this study was to observe adherence to antithrombotic management guidelines among atrial fibrillation (AF) patients and to determine prognostic factors for 3-month mortality in both ischemic and hemorrhagic stroke patients with or without AF. METHODS: This was a retrospective observational single stroke center cohort study. In 2007, 380 patients with acute stroke-like symptoms were admitted to Tampere University Hospital as candidates for intravenous thrombolysis. Group comparisons (with or without AF) were performed, and binary logistic regression modeling was used to predict 3-month mortality for different clinical and imaging variables. RESULTS: The prevalence of AF in the acute neurovascular syndrome population was 33%. During hospitalization, the detection rate of previously undiagnosed paroxysmal AF was 8% (17 of 217). Only 26% (18 of 69) of known AF-related ischemic stroke patients had an International Normalized Ratio value above 1.9. National Institutes of Health Stroke Scale score and Alberta Stroke Program Early Computed Tomography Score at admission in ischemic stroke and intracerebral hemorrhage were significant prognostic factors for 3-month mortality in acute neurovascular syndrome patients with AF according to a multivariable analysis. Inadequate antithrombotic management according to at-the-time and current treatment guidelines was not a risk factor for 3-month mortality. CONCLUSIONS: Patients with AF have more severe stroke and higher mortality than stroke patients without AF. Adherence to the antithrombotic treatment guidelines for the prevention of AF-related cardioembolic strokes is suboptimal. Further studies are needed to evaluate the impact of current antithrombotic treatment guidelines on mortality.

Lambert-Eaton myasthenic syndrome following H1N1-influenza vaccination: a case report.

BACKGROUND: The outbreak of influenza A (H1N1) pandemic during the year 2009 led to the development of several vaccinations against H1N1 virus. In Finland, 2.6 million citizens were vaccinated during pandemic 2009 - 2010 with adjuvanted influenza vaccine, Pandemrix(®) . CLINICAL PRESENTATION: In this case report, we describe a patient with non-paraneoplastic Lambert-Eaton myasthenic syndrome following Pandemrix(®) vaccination. CONCLUSION: Development of various autoimmune diseases in genetically predisposed subjects following exposure to certain environmental factors, including vaccinations, is a well-known entity. Clinicians should be aware of the possibility of the induction of autoimmune diseases following vaccinations and actively ask the relevant clinical history in a newly diagnosed patient with an autoimmune disorder.

Increased incidence and clinical picture of childhood narcolepsy following the 2009 H1N1 pandemic vaccination campaign in Finland.

BACKGROUND: Narcolepsy is a rare neurological sleep disorder especially in children who are younger than 10 years. In the beginning of 2010, an exceptionally large number of Finnish children suffered from an abrupt onset of excessive daytime sleepiness (EDS) and cataplexy. Therefore, we carried out a systematic analysis of the incidence of narcolepsy in Finland between the years 2002-2010. METHODS: All Finnish hospitals and sleep clinics were contacted to find out the incidence of narcolepsy in 2010. The national hospital discharge register from 2002 to 2009 was used as a reference. FINDINGS: Altogether 335 cases (all ages) of narcolepsy were diagnosed in Finland during 2002-2009 giving an annual incidence of 0.79 per 100,000 inhabitants (95% confidence interval 0.62-0.96). The average annual incidence among subjects under 17 years of age was 0.31 (0.12-0.51) per 100,000 inhabitants. In 2010, 54 children under age 17 were diagnosed with narcolepsy (5.3/100,000; 17-fold increase). Among adults ≥20 years of age the incidence rate in 2010 was 0.87/100,000, which equals that in 2002-2009. Thirty-four of the 54 children were HLA-typed, and they were all positive for narcolepsy risk allele DQB1*0602/DRB1*15. 50/54 children had received Pandemrix vaccination 0 to 242 days (median 42) before onset. All 50 had EDS with abnormal multiple sleep latency test (sleep latency <8 min and ≥2 sleep onset REM periods). The symptoms started abruptly. Forty-seven (94%) had cataplexy, which started at the same time or soon after the onset of EDS. Psychiatric symptoms were common. Otherwise the clinical picture was similar to that described in childhood narcolepsy. INTERPRETATION: A sudden increase in the incidence of abrupt childhood narcolepsy was observed in Finland in 2010. We consider it likely that Pandemrix vaccination contributed, perhaps together with other environmental factors, to this increase in genetically susceptible children.

Comparison of 64-row and 16-row multidetector CT in the perfusion CT evaluation of acute ischemic stroke patients receiving intravenous thrombolytic therapy.

INTRODUCTION: Perfusion computed tomography (PCT) is increasingly performed in multimodal CT evaluation of acute ischemic stroke. We compared the technical quality of perfusion studies performed with a 16-row and a 64-row scanner and analyzed the differences between the scanners in their ability to detect perfusion defects. METHODS: We analyzed retrospectively the clinical and imaging data of 140 consecutive acute (<3 h) stroke patients who underwent multimodal CT evaluation and received intravenous rtPA. Alberta Stroke Program Early CT Score (ASPECTS) was assigned to PCT maps. Clinical and imaging parameters were compared between the two scanners. RESULTS: There were more motion artifacts in the 16-row studies (p = 0.04), and the analysis software was able to completely correct significantly fewer of these (p < 0.001). Both ASPECTS levels were optimally covered in only 29% of the 16-row studies, whereas in the 64-row studies, both levels were invariably optimally visualized (p < 0.001). This significantly decreased the sensitivity of the 16-row scanner to detect perfusion defects in the upper ASPECTS level (p = 0.02). The 64-row scanner was able to detect more perfusion defects that were located entirely outside the ASPECTS regions (p = 0.03). There was no significant difference in the 3-month functional outcome. CONCLUSIONS: The 16-row scanner suffered from limited anatomic coverage that decreased the sensitivity to detect perfusion defects in the cranial parts of the middle cerebral artery region. The 16-row studies had poorer technical quality that was in part attributable to higher sampling frequency and smaller slice thickness making the imaging more sensitive to small-scale movement of the patient.

The clot burden score, the Boston Acute Stroke Imaging Scale, the cerebral blood volume ASPECTS, and two novel imaging parameters in the prediction of clinical outcome of ischemic stroke patients receiving intravenous thrombolytic therapy.

INTRODUCTION: Recently two classification methods based on the location and the extent of thrombosis detected with CT angiography have been introduced: the Boston Acute Stroke Imaging Scale (BASIS) and the clot burden score (CBS). We studied the performance of BASIS and CBS in predicting good clinical outcome (mRS ≤ 2 at 90 days) in an acute (< 3 h) stroke cohort treated with intravenous thrombolytic therapy. METHODS: Eighty-three consecutive patients who underwent multimodal CT were analyzed. Binary logistic regression model was used to assess how BASIS, CBS, and cerebral blood volume (CBV) ASPECTS predict favorable clinical outcome. Diagnostic sensitivities and specificities were calculated and compared. RESULTS: Patients with low CBS and CBV ASPECTS scores and major strokes according to BASIS had significantly higher admission NIHSS scores, larger perfusion defects, and more often poor clinical outcome. In logistic regression analysis, CBV ASPECTS, CBS and BASIS were significantly associated with the clinical outcome. The performance of BASIS improved when patients with thrombosis of the M2 segment of the middle cerebral artery were classified as having minor stroke (M1-BASIS). In the anterior circulation, the sum of CBS and CBV ASPECTS (CBSV) proved to be the most robust predictor of favorable outcome. CBV ASPECTS and CBS had high sensitivity but moderate to poor specificity while BASIS was only moderately sensitive and specific. CONCLUSION: CBS, BASIS, and CBV ASPECTS are statistically robust and sensitive but unspecific predictors of good clinical outcome. Two new derived imaging parameters, CBSV and M1-BASIS, share these properties and may have increased prognostic value.

CT Perfusion ASPECTS in the Evaluation of Acute Ischemic Stroke: Thrombolytic Therapy Perspective.

BACKGROUND AND PURPOSE: Advances in the management of acute ischemic stroke and medical imaging are creating pressure to replace the rigid one-third middle cerebral artery (MCA) and non-contrast-enhanced CT (NCCT) Alberta Stroke Program Early CT Score (ASPECTS) thresholds used for the selection of patients eligible for intravenous thrombolytic therapy. The identification of potentially salvageable ischemic brain tissue lies at the core of this issue. In this study, the role of CT perfusion ASPECTS in the detection of reversible ischemia was analyzed. MATERIALS AND METHODS: We retrospectively reviewed the clinical and imaging data of 92 consecutive patients who received intravenous thrombolytic therapy for acute (duration <3 h) ischemic stroke. Most of the patients underwent admission multimodal CT, and all patients had follow-up NCCT at 24 h. ASPECTS was assigned to all modalities and correlated with clinical and imaging parameters. Receiver-operating characteristic curve analysis was performed to determine optimal thresholds for different parameters to predict clinical outcome. RESULTS: A perfusion defect could be detected in 50% of the patients. ASPECTS correlated inversely with the clinical outcome in the following order: follow-up NCCT > cerebral blood volume (CBV) > mean transit time (MTT) > admission NCCT. The follow-up NCCT and the CBV displayed a statistically significant difference from the admission NCCT, while the MTT did not reach statistical significance. The threshold that best differentiated between good and bad clinical outcome on admission was CBV ASPECTS ≥7. In patients with CT perfusion ASPECTS mismatch, MTT and CBV ASPECTS essentially provided the lower and upper limits for the follow-up NCCT ASPECTS, thus defining the spectrum of possible outcomes. Furthermore, CT perfusion ASPECTS mismatch strongly correlated (r = 0.83) with the mismatch between the tissue at risk and the final infarct, i.e. the amount of salvaged tissue. This finding suggests that the CT perfusion ASPECTS mismatch adequately identifies the amount of potentially salvageable ischemic brain tissue. CONCLUSIONS: Parameters derived from the use of CT perfusion ASPECTS can detect reversible ischemia and are correlated with clinical outcome.