Increased frequency of arousal parasomnias in families with nocturnal frontal lobe epilepsy: A common mechanism?

Purpose: Retrospective observations disclosed an overlap between parasomnias and nocturnal frontal lobe epilepsy (NFLE) not only in patients but also in their relatives, suggesting a possible common pathogenetic mechanism. This study aimed to verify whether relatives of patients with NFLE have a higher frequency of parasomnias, namely arousal disorders, and thereby shed light on the still unknown pathophysiologic mechanisms underlying NFLE. Methods: We undertook a case–control family study in which we recruited NFLE probands and healthy controls, matched for age, sex, education, and geographic origin. At least four relatives were included for each proband and control. Each subject underwent a standardized interview, with application of the International Classification of Sleep Disorders–Revised (ICSD‐R 2001) minimal criteria to diagnose the lifetime prevalence of the main parasomnias. Results: Four hundred fifty‐eight individuals were recruited: 33 NFLE probands, 200 relatives of probands, 31 controls, and 194 control relatives. All NFLE probands but one have sporadic NFLE. The lifetime prevalence of the following parasomnias differed in proband relatives versus control relatives: arousal disorders [odds ratio (OR) 4.7, 95% confidence interval (CI) 2.0–11.6; p < 0.001] and nightmares (OR 2.6, 95% CI 1.6–4.2; p < 0.001) were more frequent among NFLE proband relatives. In the secondary analysis comparing NFLE probands to controls, arousal disorders (OR 6.3, 95% CI 1.3–31.7; p = 0.023) and bruxism (OR 5.4, 95% CI 1.3–21.7; p = 0.017) were more frequent among NFLE probands. Discussion: The higher frequency of arousal disorders in NFLE families suggests an intrinsic link between parasomnias and NFLE and an abnormal (possibly cholinergic) arousal system as a common pathophysiologic mechanism.     

Concordance for multiple sclerosis in Danish twins: an update of a nationwide study

The occurrence of multiple sclerosis (MS) in twins has not previously been studied in complete nationwide data sets. The existence of almost complete MS and twin registries in Denmark ensures that essentially unbiased samples of MS cases among twins can be obtained. In this population-based study, virtually all Danish MS cases among twins born before 1983 with onset of MS after 1948 and diagnosis before I January 1997 were identified. Of 13 286 MS cases, 178 were twins and, of these 164 twin pairs were discordant and seven were concordant. We found significantly higher proband-wise concordance among monozygotic twins than dizygotic twins, with estimated proband-wise concordances of 24% (95% confidence interval (CI): 5-39%) for monozygotic and 3% (95% CI: 0-8%) for dizygotic twins. Thus, a monozygotic twin whose co-twin has MS has a 24% risk of developing the disease, while the corresponding risk for a dizygotic twin is only 3%. Our results largely confirm previously published concordance estimates and indicate that genetic factors are of importance in susceptibility to MS.     

Genetic predisposition to stroke in relatives of hypertensives

BACKGROUND AND PURPOSE: The genetic basis of stroke is poorly understood. We evaluated patterns of familial aggregation of hypertension and stroke to test the hypothesis that inherited susceptibility to these disorders may be determined by a common set of factors. METHODS: Genealogical and medical history information was obtained for a cohort of 354 hypertensive probands ascertained in a clinic-based setting, their 1427 first-degree relatives, and 239 of their spouses. Risks of stroke and hypertension in biological and nonbiological relatives were compared with the logistic model of the generalized estimating equations adjusted for age and sex. RESULTS: The risk of hypertension was higher for the parents and siblings of the probands than for spouses (odds ratio [OR]=2.4; 95% CI, 1.8 to 3.4; OR=2.2; 95% CI, 1.6 to 3.0, respectively). When the spouses were used as a reference group, the risk of stroke for parents of the hypertensive probands was 7.3 times higher (OR=7.3; 95% CI, 3.6 to 14.8), while a nonsignificant but slightly increased risk for siblings (OR=1.6; 95% CI, 0.8 to 3.3) was observed. Controlling for hypertension, obesity, smoking, coronary heart disease, diabetes, and cholesterol resulted in decreased estimates of the risk of stroke for parents and siblings (OR(parents)=5.4; 95% CI, 2.6 to 11.2; OR(siblings)=1.2; 95% CI, 0.6 to 2.5). The risk of stroke was significantly higher for hypertensive parents and siblings than for nonhypertensive parents (OR=5.2; 95% CI, 2.8 to 9. 7) and siblings (OR=5.8; 95% CI, 2.1 to 15.9). A history of hypertension was not associated with an increased risk for stroke in spouses (OR=0.7; 95% CI, 0.2 to 3.1). The risk of stroke in hypertensive relatives of probands with stroke was higher than that of the normotensive relatives (OR=13.4). A less elevated risk ratio was observed in the relatives of probands who did not have a stroke (OR=4.0). CONCLUSIONS: Our data showing a higher occurrence of hypertension and stroke in parents of hypertensive probands compared with spouses suggest that some of the genetic factors predisposing to these conditions may be the same. The slightly increased risk to siblings compared with spouses was not significant, suggesting that elucidation of these factors through family studies of stroke may be difficult because of secular trends toward improved treatment for hypertension. Although a history of hypertension increases the risk of stroke among parents and siblings, multivariate analyses revealed a familial component to stroke independent of hypertension.     

Increased risk of ADHD in families with ASD

Attention Deficit and Hyperactive Disorder (ADHD) and Autism Spectrum Disorders (ASD) are frequent comorbid neurodevelopmental conditions and the overlap between both disorders remains to be delineated. A more complete understanding of the shared genetic and environmental factors is needed. Using a family-based method, we evaluated the risk of ADHD in a group of relatives with an ASD proband (ASD−) and a group of relatives with an ASD and ADHD proband (ASD+). We enrolled 1245 individuals in the study: 499 probands, their 746 first-degree relatives and 140 controls. We used a multivariate generalized estimating equation (GEE) model, in which the dependent variable was the ADHD diagnosis in the relatives and the independent variable the ASD+ or ASD− in probands. We adjusted for sociodemographic factors (age, sex, IQ) and for the nature of the familial relationship with the affected proband (parent or sibling). Among the probands, there were 287 ASD− and 212 ASD+ individuals. ADHD was more frequent in relatives (19%) than in the control group (7%) (p = 0.001). The risk of ADHD was higher in the ASD+ relatives group than in the ASD− relatives group (GEE model OR 1.58 [95% CI 1.04–2.38], p = 0.032). This result was found in parents (OR 1.96 [95% CI  1.14–3.36], but not in siblings (OR 1.28 [95% CI 0.84–1.94], p = 0.434). Our study provides a representative estimate of the family distribution of ADHD in relatives of ASD probands but supports the modest effect of shared genetic and environmental factors between both disorders.

     

Risk for relatives of patients with multiple sclerosis in central Sardinia,Italy

Multiple sclerosis (MS) is a chronic, inflammatory, disabling disease of the central nervous system, known for its complex interplay between genetic and environmental factors. We used life table techniques to calculate age-adjusted recurrence risks for different categories of relatives of MS patients from Central Sardinia (Italy), a genetically homogeneous, stable population with a high degree of consanguinity. We included 313 probands and a total of 12,717 relatives in the analysis. The overall age-adjusted recurrence risk for relatives of MS probands is 1.90% [95% confidence interval (CI): 1.57-2.30]. The age-adjusted recurrence risk in parents was 1.26% (95% CI 0.60-2.63), in children 2.33% (95% CI 0.09-5.56), in sibs 4.76% (95% CI 3.57-6.32), in second-degree relatives 0.72% (95% CI 0.42-1.22), and in third-degree relatives 1.79% (95% CI 1.27-2.51). The sex of the probands (male) and of the relatives (female), and the number of affected relatives in the family significantly increase the risk of MS in relatives.     

Genetic and environmental effects on offspring alcoholism: new insights using an offspring-of-twins design

CONTEXT: Although there is now considerable evidence that genetic effects play a critical role in the development of alcohol dependence (AD), theoretical and methodological limitations of this literature require caution in describing the etiology and development of this disorder. OBJECTIVE: To disentangle genetic and environmental effects on AD by means of the infrequently used, yet potentially powerful, offspring-of-twins design. DESIGN: Offspring of twins. PARTICIPANTS: Male monozygotic and dizygotic twins concordant or discordant for AD and control pairs from the Vietnam Era Twin Registry were assessed, as were the offspring of these twins and the mothers of these offspring. INTERVENTIONS: Structured psychiatric interviews. MAIN OUTCOME MEASURES: Participants' psychiatric, alcohol abuse (AA), and AD histories (DSM-IV). RESULTS: Offspring of monozygotic and dizygotic twins with a history of AD were significantly more likely to exhibit AA or AD than were offspring of nonalcoholic fathers. Offspring of an alcohol-abusing monozygotic twin whose co-twin was AD were also more likely to exhibit AD than were offspring of nonalcoholic twins. In contrast, offspring of an unaffected (ie, no history of abuse or dependence) monozygotic twin whose co-twin was AD were no more likely to exhibit AA or AD than were offspring of nonalcoholic twins. CONCLUSIONS: These findings support the hypothesis that family environmental effects do make a difference in accounting for offspring outcomes, in particular, that a low-risk environment (ie, the absence of parental alcoholism) can moderate the impact of high genetic risk regarding offspring for the development of alcohol-use disorders.     

The familial sporadic classification: its power for the resolution of genetic and environmental etiologic factors

An increasingly popular research method for identifying etiologic heterogeneity in psychiatric illness has been to compare the frequency of a risk factor in affected individuals with no affected relatives (sporadic cases) and in affected individuals with one or more affected relatives (familial cases). This paper presents a power analysis of this familial vs sporadic method, assuming a multifactorial model with a normally distributed liability to illness resulting from the additive effect of polygenes and multiple environmental factors. Various parameter estimates for a risk factor that identifies a component of either the genetic or the environmental contribution to disease liability are examined. Almost without exception, large sample sizes of probands and relatives need to be studied to have a substantial probability of detecting etiologic heterogeneity. The required sample size decreases dramatically when monozygotic twins are studied. If the multifactorial model accurately depicts the etiology for psychiatric disorders, these results suggest that the familial versus sporadic design is useful only when pursued in the context of large sample nuclear family studies or studies of monozygotic twins.     

The relative role of genetic and environmental factors in migraine without aura.

OBJECTIVE: To clarify the relative role of genetic and environmental factors in the etiology of migraine without aura (MO). METHODS: The study population consisted of 5,360 twins, 1,013 monozygotic (MZ) and 1,667 same-gender dizygotic (DZ) twin pairs, from the population-based Danish Twin Registry. A total of 87% completed a simple validated questionnaire screening for migraine. All twin pairs, in whom at least one twin had self-reported migraine or severe headache with accompanying symptoms, were interviewed via telephone by a physician. Ninety percent of the eligible twins were interviewed. Probandwise concordance rates and correlations in liability were calculated, and structural equation model-fitting analyses were applied to quantitate the relative role of genetic and environmental factors in the etiology of MO. RESULTS: The probandwise concordance rate was higher in MZ than DZ twin pairs (0.43 versus 0.31; 95% CI, 0.36 to 0.49 versus 0.26 to 0.36). The correlation in liability was higher in MZ than in DZ twin pairs (0.62 versus 0.41; 95% CI, 0.50 to 0.74 versus 0.29 to 0.53). Structural equation model fitting indicated a highly significant genetic component, because a model with both genetic and environmental components fitted significantly better than a model with only environmental components. The best fitting model implied that the liability to MO resulted from additive genetic effects (61%; 95% CI, 49 to 71%)) and individual-specific environmental effects (39%; 95% CI, 29 to 51%). CONCLUSION: This study indicates that genetic factors play a role in the etiology of migraine without aura. The genetic variability is additive, with a negligible contribution of nonadditive genetic effects. The genetic contributions were similar in men and women despite a higher prevalence in women. Environmental factors are equally important and these factors are individual to the migraineurs.     

Stressful life events and affective illness

OBJECTIVE: To investigate the association between the occurrence of affective illnesses and the number/type of experienced negative stressful life events in a twin material. A case-control study with an unrelated twin as control to the case and a co-twin control study were both undertaken with the same material. METHOD: Postal questionnaire responses were used for confirming diagnosis and to inventory stressful life events. Risk ratios (RR) for groups of events were calculated using conditional logistic regression. RESULTS: A dose-response relationship was observed for the association between stressful life events and affective illness. The RRs for specific groups of exposures were higher in the co-twin control study and higher for dizygotic twin pairs than for monozygotic twin pairs. CONCLUSION: Individuals with a history of affective illness select themselves into high-risk environments, in part due to their genetic propensity to the disease. Thus, the association represents a classic genotype-environment correlation.     

Risk factors for motor neuron disease: a case-control study based on patients from the Scottish Motor Neuron Disease Register.

In order to identify risk factors for the subsequent development of motor neuron disease (MND) we have carried out a case-control study of incident patients in Scotland, identified using the Scottish Motor Neuron Disease Register. A standard questionnaire was given to 103 patients and the same number of community controls matched on a one to one basis using the general practitioner''s (GP) age and sex register. Recall bias was minimised by using GP records to verify the subject''s report. There was an overall lifetime excess of fractures in patients, odds ratio (OR) = 1.3 (95% confidence interval (CI), 0.7-2.5) and this was highest in the 5 years before symptom onset (OR = 15, 95% CI, 3.3-654). There was no association with non-fracture trauma but the OR for a manual occupation in patients was 2.6 (95% CI, 1.1-6.3). Both occupational exposure to lead (OR = 5.7, 95% CI, 1.6-30) and solvents/chemicals (OR = 3.3, 95% CI 1.3-10) were significantly more common in patients. No consistent association was found between MND and factors reflecting socioeconomic deprivation in childhood; childhood infections or social class. Our results identify a number of different factors which may contribute to the aetiology of MND.     

Subtypes of schizophrenia--evidence from a twin-family study

In a combined twin-family study, the concordance for subtype of schizophrenia was investigated. The sample included 31 monozygotic (MZ) and 28 dizygotic (DZ) twin probands fulfilling the criteria of DSM-III-R schizophrenia. Their co-twins and first-degree relatives were personally interviewed and diagnosed in accordance with DSM-III-R. Any twin or relative diagnosed as schizophrenic was subclassified as either paranoid or nonparanoid. Schizophrenia was more often observed in co-twins of MZ probands with nonparanoid schizophrenia than in MZ probands with paranoid schizophrenia, indicating a stronger genetic influence in nonparanoid schizophrenia. Fifteen MZ pairs were concordant for schizophrenia, and 13 of these pairs were also concordant for subtype. Such a relationship was not observed in the first-degree relatives with schizophrenia. Our results indicate a complex etiology of subtypes in schizophrenia, and to some extent the etiology of subtypes may differ from the etiology of schizophrenia.     

Comorbidity of fibromyalgia and psychiatric disorders

OBJECTIVE: To assess the co-occurrence of fibromyalgia with psychiatric disorders in participants of a fibromyalgia family study. METHOD: Patients (probands) with fibromyalgia, control probands with rheumatoid arthritis, and first-degree relatives of both groups completed a structured clinical interview and tender point examination. The co-occurrence odds ratio (OR) (the odds of a lifetime comorbid DSM-IV disorder in an individual with fibromyalgia divided by the odds of a lifetime comorbid disorder in an individual without fibromyalgia, adjusted for age and sex) was calculated; observations were weighted by the inverse probability of selection, based on the fibromyalgia status of the pro-band; and standard errors were adjusted for the correlation of observations within families. The study was conducted from September 1999 to April 2002. RESULTS: We evaluated 78 fibromyalgia pro-bands and 146 of their relatives, and 40 rheumatoid arthritis probands and 72 of their relatives. Among the relatives of both proband groups, we identified 30 cases of fibromyalgia, bringing the total number of individuals with fibromyalgia to 108, compared with 228 without fibromyalgia. The co-occurrence ORs for specific disorders in individuals with versus those without fibromyalgia were as follows: bipolar disorder: 153 (95% CI = 26 to 902, p < .001); major depressive disorder: 2.7 (95% CI = 1.2 to 6.0, p = .013); any anxiety disorder: 6.7 (95% CI = 2.3 to 20, p < .001); any eating disorder: 2.4 (95% CI = 0.36 to 17, p = .36); and any substance use disorder: 3.3 (95% CI = 1.1 to 10, p = .040). CONCLUSIONS: There is substantial lifetime psychiatric comorbidity in individuals with fibromyalgia. These results have important clinical and theoretical implications, including the possibility that fibromyalgia might share underlying pathophysiologic links with some psychiatric disorders.     

Epidemiological study of motor neuron disease in Hokkaido island--its incidence, prevalence and regional distributions--ALS Study Group]

The incidence, prevalence and regional distributions of sporadic motor neuron disease (MND) from 1980 through 1989 were evaluated in collaboration with multiple neurological institutes in Hokkaido island. Patients with sporadic MND were collected from three sources: 1) neurologist practicing in Hokkaido island, 2) sending inquiries to 620 major hospitals, 3) notification file of MND provided by Japanese Ministry of Welfare and Health. Three hundred and eighty-nine patients with sporadic MND were ascertained for this study. Of 389 patients, 238 patients were men and 151 patients were women, and the ratio of men to women was 1.6:1. The mean age of onset was 58.2 +/- 10.3 years old, 57.7 +/- 10.4 for men and 58.9 +/- 10.0 for women. Their clinical presentations were 303 patients with ALS, 52 patients were PBP and 34 patients were SPMA. The crude incidence rate for both sexes combined for 1980 through 1989 was estimated as 0.69 per 100,000 person-year. The age- and sex-adjusted incidence for men was 0.86 per 100,000 person-year (95% CI, 0.75 to 0.97) and that is higher than 0.53 per 100,000 person-year (95% CI, 0.45 to 0.61) for women. The average, crude prevalence rate from 1985 through 1989 was estimated as 2.25 per 100,000 person-year. There are no overall trends of changing the pattern in incidence and prevalence of MND in Hokkaido island, however the geographic distributions of the incidence of MND according to towns and cities disclosed the presence of some relative clustering areas.(ABSTRACT TRUNCATED AT 250 WORDS)     

Heritability of ischaemic stroke in women compared with men: a genetic epidemiological study

BACKGROUND: Ischaemic stroke is partly heritable. However, although the genetic and non-genetic factors responsible could be sex-specific, interactions between the sex of the parent affected and the sex of the proband or affected siblings are unknown. We sought to assess the relation between the sex and phenotype of affected probands and the sex of affected first-degree relatives. METHODS: We determined the prevalence of history of stroke in the mother, father, and other first-degree relatives in female and male probands with ischaemic stroke or transient ischaemic attack in the population-based Oxford Vascular Study (OXVASC). We validated our findings using unpublished individual patient data from two independent Oxford studies. FINDINGS: In OXVASC, detailed family history was available in 806 (93%) probands. Female probands were more likely than males to have at least one affected first-degree relative (146/423 vs 104/383; OR 1.4, 95% CI 1.1-2.0, p=0.02) due entirely to an excess of affected female relatives in female probands (female relative vs male relative OR=1.7, 1.3-2.4, p=0.0004; female only vs male only OR=2.1, 1.4-3.1, p=0.0001). Maternal stroke was more common than paternal stroke in female probands (OR=1.8, 1.2-2.7, p=0.001) but not in males (OR=1.1, 0.7-1.7, p=0.38), and female probands were more likely than males to have an affected sister (OR=3.1, 1.5-6.7, p=0.004) but not an affected brother (OR=1.1, 0.6-2.1, p=0.80). Ages at first stroke were also correlated within families among affected females (r=0.36, p=0.004) but not among affected males, such that the excess of affected female relatives of female probands was greatest when the difference in age at first stroke was less than 5 years (OR=3.7, 1.6-8.6, p=0.0007) and fell as the age difference increased (p for trend=0.004). These findings were independent of traditional risk factors and stroke subtype. Data from the other Oxford studies confirmed the excess maternal history of stroke in female probands (OR=2.3, 1.5-3.8, p<0.00001) and the lack in males (OR=1.0, 0.7-1.4, p=0.58). INTERPRETATION: Heritability of ischaemic stroke is greater in women than in men, with an excess of affected mothers and affected sisters in female probands independent of traditional vascular risk factors, which could be explained by sex-specific genetic, epigenetic, or non-genetic mechanisms.     

High risk of reading disability and speech sound disorder in rolandic epilepsy families: case-control study

PURPOSE: Associations between rolandic epilepsy (RE) with reading disability (RD) and speech sound disorder (SSD) have not been tested in a controlled study. We conducted a case-control study to determine whether (1) RD and SSD odds are higher in RE probands than controls and (2) an RE proband predicts a family member with RD or SSD, hence suggesting a shared genetic etiology for RE, RD, and SSD. METHODS: Unmatched case-control study with 55 stringently defined RE cases, 150 controls in the same age range lacking a primary brain disorder diagnosis, and their siblings and parents. Odds ratios (OR) were calculated by multiple logistic regression, adjusted for sex and age, and for relatives, also adjusted for comorbidity of RD and SSD in the proband. RESULTS: RD was strongly associated with RE after adjustment for sex and age: OR 5.78 (95% CI: 2.86-11.69). An RE proband predicts RD in family members: OR 2.84 (95% CI: 1.38-5.84), but not independently of the RE proband's RD status: OR 1.30 (95% CI: 0.55-12.79). SSD was also comorbid with RE: adjusted OR 2.47 (95%CI: 1.22-4.97). An RE proband predicts SSD in relatives, even after controlling for sex, age and proband SSD comorbidity: OR 4.44 (95% CI: 1.93-10.22). CONCLUSIONS: RE is strongly comorbid with RD and SSD. Both RD and SSD are likely to be genetically influenced and may contribute to the complex genetic etiology of the RE syndrome. Siblings of RE patients are at high risk of RD and SSD and both RE patients and their younger siblings should be screened early.     

Familial aggregation of early- and late-onset Parkinson's disease

The role of heredity in early- versus late-onset Parkinson's disease (PD) is controversial. We estimated the degree of increased risk of PD in first-degree relatives of 221 PD probands with age of onset 50 years or younger and 266 PD probands with age of onset older than 50 years compared with the first-degree relatives of 409 control probands. Risk of PD was similar among first-degree relatives of early-onset PD probands (risk ratio [RR], 2.9; 95% confidence interval [CI], 1.6-5.0; p = 0.0002) and late-onset PD probands (RR, 2.7; 95% CI, 1.6-4.4; p = 0.0002) when each was compared with first-degree relatives of controls. However, siblings of early-onset PD probands were at markedly increased risk of PD compared with siblings of controls (RR, 7.9; 95% CI, 2.5-25.5; p = 0.0005), whereas parents of early-onset PD probands were not at significantly increased risk compared with parents of controls (RR, 1.7; 95% CI, 0.9-3.3; p = 0.2). In late-onset families, both siblings (RR, 3.6; 95% CI, 1.3-10.3; p = 0.02) and parents (RR, 2.5; 95% CI, 1.4-4.6; p = 0.003) were at increased risk compared with control relatives. This pattern is consistent with an autosomal recessive contribution to the inheritance of early but not late-onset PD. Genetic factors are important in both early- and late-onset PD, but specific genes and mode of inheritance may differ between the two groups.     

A systematic evaluation of ADHD and comorbid psychopathology in a population-based twin sample

OBJECTIVE: Clinical and population samples demonstrate that attention-deficit/hyperactivity disorder (ADHD) occurs with other disorders. Comorbid disorder clustering within ADHD subtypes is not well studied. METHOD: Latent class analysis (LCA) examined the co-occurrence of DSM-IV ADHD, oppositional defiant disorder (ODD), conduct disorder (CD), and depression symptoms in a population twin sample. The authors fit separate models for ADHD and comorbid disorder symptoms. Twin concordance ratios (monozygotic versus dizygotic) were compared examining genetic influence on class membership. RESULTS: LCA of ADHD symptoms resulted in seven classes including inattentive, combined, and hyperactive subtypes in 1,616 subjects. The few ADHD symptoms (53.4%) and severe inattentive (12.3%) classes were most frequent. LCA of ODD, CD, and depression symptoms in 1,587 subjects revealed five classes including ODD (19.4%), depression (14.5%), and two composite classes: ODD/CD (6.9%) and ODD/CD/depression (7.2%). Internalizing and externalizing comorbid disorders were present across all ADHD subtypes. Odds ratios (ORs) for twin concordance indicate genetic influence on severe inattentive (OR = 4.18; 95% confidence interval [CI], 1.52-11.53) and combined (OR = 5.25; 95% CI, 1.32-20.78) ADHD classes and ODD (OR = 1.49; 95% CI, 0.70-3.17), ODD/CD (OR = 3.32; 95% CI, 0.57-19.28), and ODD/CD/depression (OR = 1.20; 95% CI, 0.30-4.77) classes. CONCLUSIONS: Internalizing and externalizing disorders did not cluster differentially within ADHD subtypes. LCA may provide a more precise characterization of comorbidity with ADHD.     

Manganese-containing superoxide dismutase signal sequence polymorphism associated with sporadic motor neuron disease

An alanin-9valin (Ala-9Val) polymorphism in the mitochondrial targeting sequence of manganese-containing superoxide dismutase (Mn-SOD) has recently been described. We studied this polymorphism in 72 Swedish patients with sporadic motor neuron diseases (MND) and controls using an oligonucleotide ligation assay. There were significant differences in genotype between MND patients and controls (P = 0.025), and between male and female MND patients (P = 0.009). Individuals homozygous for the Ala allele had a higher risk for MND [odds ratio, 2.9; 95% confidence interval (CI), 1.3-6.6], which was increased when including only females in the analysis (odds ratio, 5.0; 95% CI, 1.8-14.0). In classical amyotrophic lateral sclerosis, the odds ratio was 3.8 (95% CI, 1.3-10.0), and 5. 5 (95% CI, 1.5-19.9) when including only females. The results suggest that mutations influencing the cellular allocation of Mn-SOD may be a risk factor in MND, especially in females, and that MND may be a disease of misdistribution of the superoxide dismutase enzymes.     

Genetic susceptibility to multiple sclerosis. A co-twin study of a nationwide series

The problems of differentiation between environmental and genetic influences on the development of multiple sclerosis are well known. Twin studies may provide valuable information on this question. However, most published twin series are selected and no through clinical twin studies based on epidemiologic series have been carried out. In this study, all available same-sex twin pairs with clinically definite multiple sclerosis derived from the Finnish Twin Cohort of 15815 pairs were studied by clinical evaluation, magnetic resonance imaging, and visual and auditory evoked responses. The mean length of follow-up of the pairs after the onset of symptoms of multiple sclerosis was 20 years. Two of the seven monozygotic pairs were concordant; one was definitely so, and in the other, the co-twin of the index case had, in addition to clinical findings, white matter changes suggestive of multiple sclerosis in magnetic resonance imaging and abnormal visual evoked responses. All six dizygotic pairs were discordant. The frequency of the HLA antigen DR2 in probands (69%) was significantly increased, but the distribution among the healthy subjects and patients showed nonsignificant differences. The results indicate a genetic influence on the susceptibility to multiple sclerosis, although still unknown genetic determinants are possible involved.     

Increased risk of migraine with typical aura in probands with familial hemiplegic migraine and their relatives

We investigated the occurrence of migraine without aura (MO) and migraine with typical aura (MA) amongst probands with familial hemiplegic migraine (FHM) and their first degree relatives in order to evaluate the relations between these syndromes. A total of 44 FHM probands and 240 first degree relatives were identified in the Danish population. The pattern of familial aggregation was assessed by population relative risk (PRR) calculations. Amongst FHM probands the PRR of MO was 1.5 (95% CI: 0.8-2.2), whereas the PRR of MA was 7.1 (95% CI: 5.0-9.2). Thus, compared with the general population, FHM probands had no increased risk of MO but a significantly increased risk of MA. A similar pattern was seen amongst their first degree relatives, who had no increased risk of MO, whereas the risk of MA was significantly increased; 7.6 times in FHM-affected first degree relatives and 2.4-times in non-FHM-affected first degree relatives. These results are contrary to a sharing of genetic mechanisms between FHM and MO. Furthermore, they suggest that the genetic abnormality causing FHM may also cause attacks with the symptomatology of MA.