The nationwide register-based prevalence of intellectual disability during childhood and adolescence.

BACKGROUND: Many studies have evaluated the prevalence of intellectual disability (ID) by focusing on different ages during childhood and adolescence. Although the prevalence of ID is higher in older age groups, how cumulative prevalence increases, and what level it reaches before adulthood, remains unclear. METHOD: We used Care Register for Health Care to retrieve information on individuals born in 1996-2007 with any of the inclusion diagnoses of ID (F7 group and/or aetiological diagnoses) for the period 1996 to 2013. The cumulative prevalence was calculated as percentages for every age based on Finnish population data. RESULTS: The registration of new diagnoses of ID continued steadily throughout the developmental years. The cumulative prevalence reached 1.19% by age 17.5 among those born in 1996. Later-born age groups appeared to receive their first ID diagnoses earlier in childhood. Those born in 1999 reached a cumulative prevalence of 1.21% already by age 14.5. Of all those with ID, 67% had an F7 diagnosis only, 42% had an aetiological diagnosis only and 9% had both diagnoses. CONCLUSIONS: Cumulative prevalence of ID by year, until the age of 18, will provide a better estimate and understanding of the prevalence of ID than a point prevalence at any one point during the developmental years.

Age-specific prevalence of intellectual disability in Finland at the beginning of new millennium--multiple register method.

BACKGROUND: In the national study of multiple registers in 2000, the average prevalence of intellectual disability (ID) was 0.70%, with marked differences by age group (range 0.38-0.96%) - what are these differences in detail, and can they be understood? METHOD: This study was based on two national health registers and six social benefit registers. Prevalence of ID was calculated by 1-year age cohorts. RESULTS: The multiple register prevalence of ID increased steadily from 0.20% in the first life year to 0.74% (male: 0.90%, female: 0.58%) at 10 years. For boys, the rate fell to 0.71% at 11 years. For both sexes, a steady increase was noted in the distribution up to 40 years (male: 0.84%, female: 0.73%), followed by a sharper increase to the maximum prevalence (male: 1.19% at 48 years, female: 1.05% at 50 years). At the pension age of 66 years, a sudden drop to 0.49% occurred for men and women. Different registers gave very different age distributions. CONCLUSIONS: By examining the data by 1-year age cohorts, and by understanding the role of each register, it could be deduced that a proportion of cases in younger age groups is lacking, and a remarkable proportion of elderly ID persons is missing from the pooled data. The findings were more difficult to interpret, if the data were grouped into bigger age groups.

Handedness in the helsinki ultrasound trial.

OBJECTIVES: To determine whether exposure to prenatal ultrasound increases non-right-handedness in boys. METHODS: The association between exposure to prenatal ultrasound and handedness was tested, using logistic regression analysis, in the Helsinki Ultrasound Trial data. We applied an intention-to-treat approach in this analysis of a subset of 4150 subjects whose parents answered a follow-up questionnaire on handedness when the children were aged 13-15 years. RESULTS: The odds ratio for non-right-handedness of children who had been exposed to prenatal ultrasound was 1.16 (0.98-1.37) for all subjects, 1.12 (0.89-1.41) for boys and 1.24 (0.97-1.58) for girls. CONCLUSIONS: We could not confirm the hypothesis that prenatal ultrasound exposure and handedness are associated. Our findings were independent of the particular definition of handedness used, whether it was considered according to the writing hand alone or defined using a laterality quotient.

Anti-myelin antibodies modulate clinical expression of childhood multiple sclerosis.

Anti-myelin basic protein (MBP) antibodies in pediatric-onset MS and controls were characterized. Serum samples were obtained from 94 children with MS and 106 controls. Paired CSF and serum were obtained from 25 children with MS at time of their initial episode of acute demyelinating syndrome (ADS). Complementary assays were applied across samples to evaluate the presence, and the physical binding properties, of anti-MBP antibodies. While the prevalence and titers of serum anti-MBP antibodies against both immature and mature forms of MBP were similar in children with MS and in controls, binding characteristics and formal Surface Plasmon Resonance (SPR) studies indicated surprisingly high binding affinities of all pediatric anti-MBP antibodies. Serum levels of anti-MBP antibodies correlated significantly with their CSF levels, and their presence in children with MS was associated with significantly increased risk of an acute disseminated encephalomyelitis-like initial clinical presentation. While antibodies to both immature and mature forms of MBP can be present as part of the normal pediatric humoral repertoire, these anti-myelin antibodies are of surprisingly high affinity, can access the CNS during inflammation, and have the capacity to modulate disease expression. Our findings identify an immune mechanism that could contribute to the observed heterogeneity in spectrum of clinical presentations in early-onset MS.

Consensus guidelines into the management of epilepsy in adults with an intellectual disability.

BACKGROUND: Epilepsy has a pervasive impact on the lives of people with intellectual disability and their carers. The delivery of high-quality care is impacted on by the complexity and diversity of epilepsy in this population. This article presents the results of a consensus clinical guideline process. RESULTS: A Delphi process identified a list of priority areas for the development of evidence-based guidelines. All guidelines were graded and consensus on scoring was achieved across the guideline group. CONCLUSION: There is a dearth of high-quality evidence from well-constructed studies on which to base guidance. However, the development of internationally derived consensus guidelines may further support the management of epilepsy in adults with an intellectual disability.

Prevalence of intellectual disability: a comprehensive study based on national registers.

BACKGROUND: Based on standard social benefit registers, the prevalence of intellectual disability (ID) in Finland is estimated to be 0.6%, while epidemiological surveys yield 1.1%. Combining several registers, our aim was to find a more reliable estimate of the prevalence of ID, especially among children and adolescents. This is important when special or inclusive general services are planned to meet the various needs of people with ID. METHOD: A survey based on eight national health and social benefit registers. RESULTS: Combining different registers yielded a mean ID prevalence of 0.70% (95% CI 0.69-0.70%), with marked differences according to sex and age group (range 0.38-0.96%). Capture-recapture analysis gave higher prevalence estimates (range 0.57-1.08%). CONCLUSIONS: When several health and social benefit registers are surveyed, the estimated prevalence of ID increases, approaching that obtained in epidemiological surveys.

Risk factors for psychiatric disturbance in children with intellectual disability.

BACKGROUND: Children with intellectual disability (ID) have a higher risk for psychiatric disturbance than their peers with normal intelligence, but research data on risk factors are insufficient and partially conflicting. METHOD: The subjects comprised 75 children with ID aged 6-13 years. Data were obtained from case files and the following four questionnaires completed by their parents or other carers: Developmental Behaviour Checklist, American Association of Mental Deficiency (AAMD) Adaptive Behavior Scale, a questionnaire on additional disabilities, and a questionnaire on family characteristics and child development. RESULTS: The risk of psychopathology was most significantly increased by moderate ID, limitations in adaptive behaviour, impaired language development, poor socialization, living with one biological parent, and low socio-economic status of the family. CONCLUSIONS: The risk of psychopathology in children with ID is increased by factors related to family characteristics and child development. Identifying these factors will help diagnose and possibly prevent psychiatric disorders in these children.

Striatal dopaminergic system in dopa-responsive dystonia: a multi-tracer PET study shows increased D2 receptors.

We investigated the integrity of striatal dopaminergic system in seven patients with dopa-responsive dystonia (DRD). Dopamine transporter function ([(11)C]CFT) and D1 ([(11)C]NNC 756) and D2 receptors ([(11)C]raclopride) were studied in same patients using positron emission tomography. Compared to age-adjusted control values the dopamine D2 receptor availability was increased in DRD. The mean age-adjusted [(11)C]raclopride uptake was 116% of the control mean in the putamen (p = 0.004) and 114% in the caudate nucleus (p = 0.007). The mean [(11)C]NNC 756 uptake was not different between DRD patients and controls, the age-adjusted uptake in DRD being 93% of mean control value in the putamen (p = 0.20) and 95% in the caudate nucleus (p = 0.40). The dopamine transporter binding was not altered. The [(11)C]CFT uptake in DRD was 96% of the control value in the putamen (p = 0.64), and 95% in the caudate nucleus (p = 0.44). In conclusion, striatal dopamine D2 receptors availability is increased in DRD whereas dopamine D1 receptors and dopamine transporter ligand binding is unchanged. The pattern of changes in striatal dopaminergic system in DRD is different from that reported in juvenile Parkinson's disease. The increased D2 receptor availability may be due to reduced competition by endogenous dopamine or a compensatory response to dopamine deficiency, or both.

Cancer incidence among people with intellectual disability.

The aim of the present study was to address the unresolved question of the risk of neoplasms among people with intellectual disability (ID). A total of 2173 individuals with ID from a large, representative, nation-wide population study conducted in Finland in 1962 were followed-up for cancer incidence between 1967 and 1997. Standardized incidence ratios (SIRs) were defined as ratios of observed to expected numbers of cancer cases. Expected rates were based on national incidence rates. The observed number of cancers in the cohort (173) was close to what was expected [SIR = 0.9, 95% confidence interval (95% CI) = 0.8-1.0]. There was a significantly reduced risk of cancers of the prostate (SIR = 0.2, 95% CI = 0.0-0.5), urinary tract (SIR = 0.3, 95% CI = 0.1-0.7) and lung (SIR = 0.6, 95% CI = 0.4-1.0). The risk was increased in cancers of the gallbladder (SIR = 2.8, 95% CI = 1.1-5.8) and thyroid gland (SIR = 2.1, 95% CI = 1.0-4.8). The risks of lung and gallbladder cancer were lowest and highest, respectively, in those subjects with profound and severe ID, a group who also had significantly elevated SIRs for brain cancer (SIR = 3.46, 95% CI = 1.5-14.4) and testicular cancer (SIR = 9.9, 95% CI = 1.2-35.6). The incidence of cancer among people with ID was comparable with the general population, despite their low prevalence of smoking and apparently decreased diagnostic screening activity. Nevertheless, a few types of cancer carry a higher risk in the population with ID, possibly because of conditions typical among this group, such as gallstones or oesophageal reflux.

Suicide mortality in mental retardation:a 35-year follow-up study.

OBJECTIVE: We investigated suicide mortality among people with mental retardation (MR) over a period of 35 years. METHOD: The nationwide, population-based cohort of 2369 people with MR was followed-up from a representative sample of 9.4% of the population in Finland in 1962. The standardized mortality ratio of suicides was calculated and case studies of all MR suicides based on all available data were performed. RESULTS: Women with MR had an equal suicide risk to Finnish women in general, while men had only one-third of the population risk. Risk factors for suicide were similar to those in the general population. Most suicide victims had mild MR and were hospitalized for comorbid mental disorders. Suicide methods were passive and alcohol was involved in only one case. CONCLUSION: Suicide mortality in MR is significantly lowered among males. Suicide prevention in MR should be focused on people with comorbid mental disorders. Problems in adjustment to new circumstances need to be recognized. Appropriate and adequate treatment of comorbid depression is emphasized.

Cause-specific mortality of people with intellectual disability in a population-based, 35-year follow-up study.

The aim of the present study was to investigate cause-specific mortality in people with intellectual disability (ID). It was based on a 35-year follow-up study of a nation-wide population of 2369 subjects aged between 2 and 97 years. The 1095 deceased people had accumulated 64 539 person-years. The research took the form of a prospective cohort study with mortality follow-up. Observed and expected deaths were calculated as standardized mortality ratios using the Finnish general population as the reference. Cause-specific mortality ratios were calculated by the level of ID, sex and age. The three most common causes of death were cardiovascular diseases, respiratory diseases and neoplasms. Disease mortality was high up to 40 years of age, but did not increase thereafter. The difference between sexes in cause-specific mortality was smaller than in the general population. Cause-specific mortality differed significantly from the general population, with reduced mortality from neoplasms and external causes, but ageing individuals with mild ID had similar mortality patterns to the general population. The disparities in the cause-specific mortality between younger people with ID and the general population fade with advancing age, producing similar health risks. In preventative work, special attention should focus on common diseases and accidents in the community.

Neurological impairments and sleep-wake behaviour among the mentally retarded.

The objective of the present study was to evaluate the relationship between the sleep-wake behaviour and neurological impairments among mentally retarded people. The sleep-wake behaviour of 293 mentally retarded subjects living in a rehabilitation center was studied by a standardized observation protocol carried out by trained staff members. The protocol consisted of brief check-ups of the subjects' sleep-wake status at 20-min intervals for five randomly chosen 24-h periods during 4 months. From the raw data five sleep-wake behaviour variables were formed. The data concerning the subject characteristics (age, body mass index (BMI), gender, degree of mental retardation, presence of locomotor disability, that of epilepsy, blindness or deafness and the usage of psychotropic medications) were collected from the medical records. Two main findings emerged: (1) severe locomotor disability, blindness and active epilepsy were found to be independent predictors of increased daytime sleep and increased number of wake-sleep transitions and (2) the subjects with a combination of two or all three of these impairments had a significantly more fragmented and abnormally distributed sleep than those with none or milder forms of these impairments. Age, BMI, degree of mental retardation and the studied medications played a minor role in the sleep disturbances of the study population. Finally, deafness was not found to be associated with any of the measured sleep-wake variables.

Life expectancy of people with intellectual disability: a 35-year follow-up study.

A 35-year follow-up study based on a nation-wide population study of the life expectancy of people with intellectual disability (ID) was undertaken. The study population consisted of a total of 60,969 person-years. A prospective cohort study with mortality follow-up for 35 years was used and the life expectancy of people with ID was calculated for different levels of intelligence. Proportional hazard models were used to assess the influence of level of intelligence and associated disorders on survival. People with mild ID did not have poorer life expectancy than the general population and subjects with mild ID did not have lower life expectancy in the first 3 decades of life. In cases with profound ID, the proportion of expected life lost was > 20% for almost all age groups. The female preponderance was manifested from the age of 60 years onwards, 25 years later than in the general population. Respectively, survival between sexes differed less. Epilepsy and/or hearing impairment increased the relative risk of death for all levels of ID. The prevalence of people with ID over 40 years was 0.4%. People with ID now live longer than previously expected, and the ageing of people with mild ID appears to be equal to that of the general population, posing new challenges to health care professionals.

Circulating leptin has saturable transport into intrathecal space in humans.

BACKGROUND: Leptin is an adipocyte-derived hormone that is thought to provide a negative feedback signal to control body fat mass by interacting with its hypothalamic receptor. The present study was undertaken to examine the uptake of leptin in cerebrospinal fluid (CSF) space in humans and whether the transport of leptin into CSF space is an active phenomenon or due to free access through the blood-CSF barrier. METHODS: We determined serum and CSF leptin concentrations by radioimmunoassay in 17 men [42 +/- 4 years, mean +/- SE; body mass index (BMI) 27.3 +/- 1.8 kg m-2] and 22 women (40 +/- 3 years, BMI 25.1 +/- 1.0 kg m-2). The function of the blood-CSF barrier was evaluated by determining the CSF/serum albumin ratio. RESULTS: Serum leptin concentration was lower in male (5.8 +/- 1.6 microgram L-1) than in female subjects (13.1 +/- 1.7 microgram L-1, P = 0. 001), whereas the concentrations of leptin in CSF were virtually identical in male (0.34 +/- 0.03 microgram L-1) and female (0.36 +/- 0. 03 microgram L-1) subjects. Serum leptin was correlated positively with BMI both in men (r = 0.89, P < 0.01, n = 10) and in women (r = 0.61, P < 0.05, n = 14), whereas no correlation between CSF leptin concentration and BMI was found in either group. The CSF/serum leptin ratio correlated negatively with serum leptin concentration both in men (r = -0.93, P < 0.001) and in women (r = -0.77, P < 0. 001) and with BMI both in men (r = -0.75, P = 0.02, n = 10) and in women (r = -0.64, P < 0.02, n = 14). The CSF/serum albumin ratio was not correlated with the CSF/serum leptin ratio in either group. CSF leptin concentrations and the CSF/serum leptin ratio were virtually identical in subjects with impaired and normal blood-CSF barrier function. CONCLUSION: Thus, our data support the presence of a saturable and active transporter of leptin from circulation into intrathecal space.

Multiple sclerosis: in situ evidence for antibody- and complement-mediated demyelination.

We describe a case of multiple sclerosis characterized by deposition of immunoglobulin and complement in the areas of active demyelination. This was particularly evident for the C9neo antigen, which is a marker for the activated lytic complement complex and was exclusively deposited in the areas of active myelin destruction. In addition, macrophages in the lesions contained degradation products that were immunoreactive for myelin antigens, immunoglobulins, and C9neo antigen. Destruction of myelin sheaths was associated with incomplete loss of oligodendrocytes in the active areas and reappearance of oligodendrocytes with remyelination in the inactive plaque center.

Use of antiepileptic drugs in the treatment of epilepsy in people with intellectual disability.

The main principles of antiepileptic drug treatment of epilepsy in patients with intellectual disability are basically the same as for other patients with epilepsy. However, some specific issues need to be taken into account These are primarily associated with the diagnostic difficulties of epilepsy in this population. In addition, a number of other relevant issues, including the degree and location of brain lesion, the nature of the underlying disease, the higher frequency of difficult-to-treat epilepsies, the additional intellectual impairment caused by inappropriate antiepileptic medication, or by frequent and prolonged seizures, the appropriate use of monotherapy versus rational polytherapy, and the use of broad-spectrum antiepileptic drugs will be discussed in the present paper. Although the goals of treatment are to keep the patient seizure-free and alert while preventing possible mental deterioration, we have to accept compromises between these primary goals in many cases. Some people with epilepsy and intellectual disability are very vulnerable to insidious neurotoxic effects; for example, sedative effects caused by phenobarbital, or cognitive and/or cerebellar dysfunction caused by long-term phenytoin, especially together with other drugs. Because of the adverse effects of phenobarbital and phenytoin, these drugs are no longer recommended as a first-choice drugs when long-term antiepileptic medication is required. In primary generalized tonic-clonic seizures, valproate, oxcarbazepine/carbamazepine and lamotrigine are recommended in this order of preference. The corresponding recommendations are: in typical absences, valproate, ethosuximide and lamotrigine; in atypical absences, valproate and lamotrigine; in juvenile myoclonic epilepsy, valproate, lamotrigine and clobazam; in infantile spasms vigabatrin, ACTH and valproate; in Lennox-Gastaut syndrome, valproate, lamotrigine and vigabatrin; in atonic seizures, valproate and lamotrigine; in simple and complex partial seizures with or without secondary generalization, oxcarbazepine/carbamazepine, valproate/ vigabatrin and lamotrigine; and in status epilepticus lorazepam, diazepam and clonazepam together with phenytoin or fosphenytoin. In cases of poor response to the monotherapy recommended above, the following combinations may be indicated: in primary generalized tonic-clonic epilepsy, valproate and oxcarbazepine/ carbamazepine, or valproate and lamotrigine; in typical absences, valproate and lamotrigine, or valproate and ethosuximide; in juvenile myolonic epilepsy, valproate and lamotrigine, or valproate and clonazepam; and in partial epilepsies, add to the monotherapy one of the following drugs, vigabatrin, lamotrigine, gabapentin, tiagabine, topiramate, zonisamide or clobazam. So far, the order of preference of these new drugs remains undetermined. More data are needed on the efficacy and adverse effects of the new drugs based on controlled studies on patients with intellectual disability and epilepsy.

Phenytoin: effective but insidious therapy for epilepsy in people with intellectual disability.

Phenytoin (5,5-diphenylhydantoin), which has been in use for 60 years, is still an important antiepileptic drug. Its primary mechanism of action is modulation of the sustained repetitive firing of neurones by direct inhibition and blockage of voltage-gated sodium channels in the neuronal cell membrane, and by delay of cellular reactivation. The plasma protein binding of phenytoin is normally between 90% and 95%. The drug is rapidly distributed from the blood to the tissues and is almost completely metabolized in the liver. The plasma phenytoin concentration normally reaches the steady-state level within 1-2 weeks. The half-life of phenytoin is less than 20 h in low doses, but is prolonged in high doses, newborn infants and elderly people. The half-life is shortened when phenytoin is given concomitantly with an enzyme-inducing drug, such as phenobarbital or carbamazepine. Phenytoin is effective for treating generalized tonic-clonic seizures, partial seizures with or without generalization, and convulsive status epilepticus. Over the years, many new, and even serious, adverse effects of phenytoin have been recognized. Phenytoin encephalopathy, manifesting as cognitive impairment and a cerebellar syndrome, is an important adverse neurological effect, the development of which depends on the saturation kinetics of phenytoin, individual differences in phenytoin metabolism, an inhibitory effect of certain drugs on phenytoin metabolism, or the ability of certain drugs to displace phenytoin from plasma proteins, leading to an increase in the plasma level of unbound phenytoin. Because of its potentially adverse effects, phenytoin is not recommended as the first choice for treating epileptic seizures, except as a co-drug for managing convulsive status epilepticus. In patients with epilepsy who also have intellectual disability, and are susceptible to balance disturbances and cognitive dysfunction, it is wise to replace phenytoin with another drug, such as carbamazepine or oxcarbazepine. The long-term use of phenytoin is not recommended for patients with loss of locomotion, marked cognitive impairment, or symptoms and signs of cerebellar disease. The prevention of phenytoin intoxication, with the subsequent development of phenytoin-induced encephalopathy, depends on careful observation of the patients and frequent monitoring of plasma levels of phenytoin and other concomitantly administered antiepileptic drugs.

Subcortical type cognitive impairment in herpes zoster encephalitis.

Nine immunocompetent patients with acute herpes zoster encephalitis (HZE) were studied with the help of neurological investigations. All patients were treated with acyclovir. Neuropsychological performance was compared with that of a group of 16 healthy controls. Computed tomography of the head showed infarct-like hypodense lesions in two patients, involving the internal capsule in one case and the temporoparietal cortex and white matter in another. Hypoperfusion shown by single photon emission computed tomography, mostly involving the frontal areas bilaterally, was seen in six of the seven patients examined. Hyperperfusion as seen in herpes simplex encephalitis was not encountered. One patient remained mildly demented, but all the other patients recovered relatively well. Neuropsychological examination after acyclovir treatment showed a decline in memory and speed of cognitive processes, without circumscribed neuropsychological deficits. Six of the nine patients showed behavioural disinhibition, and mood changes were also observed. Memory impairment in HZE was not as global or as severe as is described after encephalitis due to herpes simplex virus. In HZE both the brain perfusion pattern and the neuropsychological test profile showed features compatible with subcortical dysfunction.

Cognitive impairment after acute encephalitis: comparison of herpes simplex and other aetiologies.

OBJECTIVE: To compare the cognitive defects after acute acyclovir treated herpes simplex encephalitis with those after other types of acute encephalitis. METHODS: Seventy seven consecutive patients between 1985 and 1995 and 29 normal controls were studied. Of the 77 patients without concomitant neurological conditions, 17 had herpes simplex, one virus encephalitis (HSVE group), 27 had some other identified aetiology (non-HSVE group), and in 33 patients the cause was unknown. Acyclovir treatment was started less than four days after the first mental symptoms in 12 of 17 patients with HSVE. A thorough neuropsychological assessment was carried out about one month after the onset. RESULTS: The HSVE group had deficits in verbal memory, verbal-semantic functions, and visuoperceptual functions more often than the non-HSVE group. The risk for cognitive defects was twofold to four-fold in the patients with HSVE compared with the non-HSVE patients. Two (12%) of the patients with HSVE and 12 (44%) of the non-HSVE patients were cognitively intact. Six patients with HSVE (46%) and 17 (89%) non-HSVE patients later returned to work. The lesions on CT or MRI were bilateral only in one patient with HSVE. The defects in the three patients with adenovirus infection were severe and resembled the amnesia after HSVE. Cognitive impairment, not previously reported, was found in encephalitis after rotavirus infection and epidemic nephropathy. CONCLUSION: The recovery in the HSVE group was better than expected based on the medical literature. On the other hand there were surprisingly severe cognitive defects in encephalitis after other viruses. With early acyclovir treatment patients with the least severe HSVE were equivalent to those with non-HSV encephalitis with good outcome whereas those with the most severe non-HSV encephalitis were equivalent to those with HSVE with poor outcome.