Serum cholinesterase (pseudocholinesterase) in Down's syndrome: 2. Quantitative levels.

The observation elsewhere (Drew and Rundle, 1977) that increase frequencies of the C5 + variant of the serum cholinesterase in Down's syndrome may be due to a protective influence against adverse environmental factors has been investigated for such factors as age, sex, duration of institutionalisation, presence of the hepatitis -B antigen and maternal age. With the exception of the maternal age none of the factors tested appear to affect the circulating levels of cholinesterase. A maternal age effect in the Down's subjects was detected with lower levels of the enzyme being found in the subject positive for the C5 + variant born to mothers over thirty-five years when compared to the C5 + subjects born to mothers under thirty-five years. Further studies confirmed the presence of a relationship between maternal age, serum cholinesterase levels and haptoglobin phenotypes.     

Olfactory function in young adolescents with Down's syndrome.

Decreased ability to smell is present in adults with Down's syndrome, many of whom are known to have brain pathology analogous to that seen in Alzheimer's disease. Because olfactory loss is well documented in Alzheimer's disease, the question arises whether young adolescents with Down's syndrome, who have no clear Alzheimer's disease-like neuropathology, also exhibit olfactory dysfunction. To consider this issue, standardised tests of odour discrimination and identification were administered to 20 young adolescents with Down's syndrome (mean age (SD) 13.89 (1.98) years) and their test scores were compared with 20 mentally retarded and 20 non-mentally retarded control subjects matched to the patients with Down's syndrome on the basis of cognitive ability. No significant differences in olfactory function were found among the three study groups. These findings, along with those from studies of olfactory function in older patients with Down's syndrome, suggest that Down's syndrome related olfactory dysfunction occurs only at ages when Alzheimer's disease-like pathology is present.     

Acetylcholine receptor antibodies in the elderly and in Down's syndrome

Serum antibodies to the acetylcholine receptor (anti-AChR) have been reported in Japanese individuals who were elderly or had Down's syndrome at frequencies of 18% and 24%, respectively. We have measured serum anti-AChR in 3 Caucasoid groups: 53 elderly patients (aged 65-92 years) with miscellaneous (non-myasthenic) disorders, 30 individuals with Down's syndrome, and 40 elderly patients (aged 71-93 years) known to have strongly positive thyroid autoantibodies. A raised titre (greater than 0.2 nmol/l) was confined to 3 patients in the third group (7.5%). We conclude that an increased frequency of anti-AChR antibodies is not a feature of Caucasians who are elderly or have Down's syndrome, and that, even in an elderly group with a high titre of another autoantibody, the frequency of anti-AChR is lower than in elderly Japanese individuals.     

Down syndrome: immunological study in adults (author's transl)]

The immunological profile was evaluated in 12 adults affected by Down's syndrome. Our findings showed: increase of serum IgG, IgA and Gammaglobulins, decrease of IgM, presence of auto-antibodies and increased antibodies response after antigenic stimulation (typhoid vaccination). Some tests, connected with T lymphocytes functions, were also abnormal: percentage of E-active rosettes, cutaneous sensibilization with DNCB and lymphocyte stimulation index with PHA. Our findings suggest a T lymphocyte deficit, with loss of immunological surveillance and therefore of the control over antibody mediated immunological reactions. The immunological alterations observed in our adult patients with Down's syndrome were more extensive and severe than those found in young subjects. The possible relevance of these findings is discussed as well as the incidence of Alzheimer's dementia in adult patients with Down's syndrome.     

Maternal support for the Down's syndrome stereotype: the effect of direct experience of the condition

ABSTRACT. Maternal agreement with the Down's syndrome stereotype (as outlined in the literature) was investigated as a function of direct experience of the condition. Using an adjective checklist devised for this project, mothers of children aged between 3 and 9 years were asked to describe Down's children. Statistical analysis of the data collected revealed that familiarity with the condition resulted in a broader general stereotype (represented by the number of adjectives endorsed). Specifically, mothers of Down's Syndrome children attributed more personality traits to the Down's child than mothers without direct experience of the condition. Mothers of such children also claimed a wider range of personality characteristics for their own child than for Down's children in general. Implications for future research were discussed, as was the value of 'normalization' and increased contact with normal peers in the education and integration into the community of Down's children.     

The effect of context on mother's interaction style with Down's syndrome and typically developing children

Several studies suggest that difficulties with production or comprehension of language might be associated with the number of interactions initiated by parent or child, responsiveness or ability to sustain ongoing interactional sequences, or the distribution of parental interaction, control and reinforcement strategies. In this study Down's syndrome and typically developing preschool children were observed interacting with their mothers in free play and mealtime settings. We expected interaction patterns in the mothers of Down's syndrome children to be different from those in the mothers of typically developing children. Sixteen mother-child dyads (eight with Down's syndrome children and eight with typically developing children) served as subjects. Mothers of Down's syndrome children use more teacher and helper behaviors, particularly in meal time context, and less positive verbalizations than the mothers of typically developing children. Down's syndrome children also showed higher frequency of eye gazes during mealtime context. Patterns of such differences are discussed in terms of how mothers' style interactions during home activities might be differentially affected by different types of parent training interventions.     

T and B lymphocytes in patients with Down's syndrome.

Individuals with Down's syndrome are thought to have abnormalities of immune function. Studies to quantify the number of peripheral blood T and B lymphocytes and serum immunoglobulins in 12 individuals and 12 sex and age matched control subjects were performed. Hepatitis B antigen and antihyroglobulin antibodies as markers of possible immune dysfunction were determined. The numbers of circulating T and B cells, and the level of serum immunoglobulins in children with Down's syndrome did not differ from nonretarded control children. Circulating hepatitis B antigen and antihyroglobulin antibodies were not present. These studies indicated that quantitative abnormalities of T and B cells are not present in children with Down's syndrome. The data did not exclude the existence of qualitative abnormalities.     

Verbal and nonverbal interaction of mothers with their down's syndrome and nonretarded infants.

While it appears probable that parental expectancies due to early knowledge of the condition of Down's syndrome in infants affects parent-child interactions, little data are available showing how interactions are affected. In an observational, laboratory-based study, we compared verbal and nonverbal interactions between 10 mothers and their Down's syndrome infants and 10 mothers and their nonretarded infants. Although there was no difference between the groups in mothers' language complexity, mothers of Down's syndrome children spoke at a significantly faster rate. Observational measures of infants showed that Down's syndrome babies smiled and vocalized less, but mothers in the two groups failed to differ significantly on the nonverbal interactional behavior observed. The results were discussed in relation to the conclusions of other investigators who have speculated that language delays in Down's syndrome children may be due in part to differences in the environment provided by caregivers.     

Time demands and experienced stress in Greek mothers of children with Down's syndrome

The purpose of the present study was to asses the time demands placed on mothers of children with Down's syndrome, and the possible relationship between those demands and the stress which the mothers experience. The study sample consisted of 41 mothers of children with Down's syndrome living in Northern Greece and a comparison group of 41 mothers of non-disabled children. Three instruments were used for the data collection: (1) a questionnaire for biographic information; (2) a self-report form assessing the time demands placed on the mothers; and (3) an adaptation of the Clark Questionnaire on Resources and Stress (QRS) for the evaluation of the stress experienced. The results of the present study revealed increased time demands on the mothers of children with Down's syndrome in comparison to the mothers of non-disabled children in terms of recreational/educational activities and total time demands. Furthermore, the mothers of children with Down's syndrome perceived the time they spend with their children less positively than the mothers of the comparison group. In regard to the stress experienced, it appeared that mothers of children with Down's syndrome differ significantly from-mothers of non-disabled children, not only on the level of the stress which they experience, but on the activities related to this stress as well.     

Lymphocyte surface markers and serum immunoglobulins in persons with Down's syndrome.

Distributions of the serum immunoglobulins, of T and B lymphocytes, and subpopulations of B lymphocytes were studied in children and institutionalized adults with Down's syndrome and appropriate mentally retarded controls. Noninstitutionalized Down's syndrome children, who were 2 to 6 years of age, had lower serum IgM levels, lower total white blood cell counts, lower total lymphocytes, lower B lymphocytes, and lower IgM- and IgA-producing lymphocytes than did retarded controls. Institutionalized Down's syndrome adults, 17 to 51 years of age, had significantly higher serum IgG and IgA levels than did retarded controls. Their total lymphocytes, B lymphocytes, and IgM-producing lymphocytes were in the same direction as in the Down's syndrome children but were of borderline statistical significance (between p = .09 and .11). T lymphocytes were not significantly lower for any of the Down's syndrome-retarded groups than those for controls, but the trend was in that direction.     

Hashimoto's encephalopathy in children and adolescents

Hashimoto's encephalopathy is an underdiagnosed, steroid-responsive, progressive or relapsing encephalopathy associated with high titers of serum antithyroid antibodies. Although Hashimoto's encephalopathy is well documented in adults, it is rarely observed or studied in children and adolescents. We describe the clinical and laboratory findings of four children (aged 9-15 years) with Hashimoto's encephalopathy. The clinical features of two patients at presentation included epileptic seizures and confusion. The other presenting signs included breath-holding spells, behavioral problems, psychosis, and ataxia (one patient each). During their presentation, three patients were euthyroid, and one was hyperthyroid. All patients manifested increased antithyroid antibodies, and all improved with steroid treatment. Hashimoto's encephalopathy is rarely suspected at presentation. Therefore, greater awareness of its signs by clinicians is necessary for proper diagnoses.     

The course of thyroid abnormalities during lithium treatment: a two-year follow-up study.

A total of 116 patients on lithium treatment were followed up for 2 years to determine the course and the clinical relevance of thyroid abnormalities. Elevated thyroid-stimulating hormone (TSH) concentrations were transitory in most patients, except those with serum antithyroid antibodies. The patients who initially had microsomal antibodies remained positive, with an increase in titre in two-thirds of cases. Three young patients of both sexes developed thyroid autoimmunity early in the treatment. The risk of developing hypothyroidism was higher in women, especially in the presence of antibodies. TSH concentrations were significantly lower when carbamazepine was combined with lithium.     

Loss of neurones from cortical and subcortical areas in Down's syndrome patients at middle age. Quantitative comparisons with younger Down's patients and patients with Alzheimer's disease

Brains were examined after autopsy from 12 patients over 53 years of age with Down's syndrome (in whose brains plaques and tangles were numerous in many areas of cortex and subcortex), 3 patients under 53 years of age with Down's syndrome (in whose brains plaques and tangles were minimal or absent), 10 patients, of age range similar to the older Down's group but with Alzheimer's disease and 5 control patients of age range similar to the younger Down's group. The number of plaques and tangles in the hippocampus and their density within the temporal cortex, the thickness of the temporal cortex, the cross-sectional area of the hippocampus and the relative number and mean nucleolar volume of nerve cells in these cortical and in some subcortical areas were estimated and compared in each of the 4 groups. The relative loss of nerve cells and the decrease in mean nucleolar volume were calculated in percentage terms for the older Down's syndrome patients by reference to data from the younger Down's syndrome patients, whereas such losses in Alzheimer's disease were calculated by reference to the younger control patients. While in qualitative terms, all areas of brain found to be damaged in Alzheimer's disease were also damaged in Down's syndrome at middle age, quantitative differences emerged with the reductions in relative nerve cell number and mean nucleolar volume being significantly less in many areas in Down's syndrome. Conversely plaques and tangles were more numerous in the hippocampus in Down's syndrome though in the temporal cortex plaques were less numerous. It seems, therefore, that although the same pathological process is likely to operate in the two conditions, additional biological and mortality differences between Down's syndrome and the general population may account for the observed quantitative variations.     

Hashimoto encephalopathy: syndrome or myth?

BACKGROUND: Hashimoto encephalopathy has been described as a syndrome of encephalopathy and high serum antithyroid antibody concentrations that is responsive to glucocorticoid therapy, but these could be chance associations. OBJECTIVE: To study a patient with Hashimoto encephalopathy and to review the literature to determine whether Hashimoto encephalopathy is an identifiable syndrome. DATA SOURCES AND EXTRACTION: We searched the MEDLINE database to June 2002 for "Hashimoto" or "autoimmune thyroiditis" and "encephalopathy" and examined all identified articles and articles referenced therein, including all languages. We included all patients with noninfectious encephalopathy (clouding of consciousness and impaired cognitive function) and high serum antithyroid antibody concentrations. We excluded patients if they did not meet these inclusion criteria or if their symptoms could be explained by another neurologic disorder. We recorded clinical features and the results of imaging, electroencephalographic, thyroid function, and cerebrospinal fluid studies. DATA SYNTHESIS: We identified 85 patients (69 women and 16 men; mean age, 44 years) with encephalopathy and high serum antithyroid antibody concentrations. Among these patients, 23 (27%) had strokelike signs, 56 (66%) had seizures, 32 (38%) had psychosis, 66 (78%) had a high cerebrospinal fluid protein concentration, and 80 (98%) of 82 had abnormal electroencephalographic findings. Thyroid function varied from overt hypothyroidism to overt hyperthyroidism; the most common abnormality was subclinical hypothyroidism (30 patients [35%]). Among patients treated with glucocorticoids, 66 (96%) improved. CONCLUSIONS: The combination of encephalopathy, high serum antithyroid antibody concentrations, and responsiveness to glucocorticoid therapy seems unlikely to be due to chance. However, there is no evidence of a pathogenic role for the antibodies, which are probably markers of some other autoimmune disorder affecting the brain.     

Calcification of the basal ganglia in Down's syndrome and Alzheimer's disease

Summary The prevalance and severity of calcification in the basal ganglia (BGC) has been examined histopathologically in 194 patients divided into ten diagnostic categories. The prevalence and severity of BGC was greater (for age) in Down's syndrome and in patients under 75 years of age with Alzheimer's disease. The severity, but not the prevalance, of BGC was greater in Down's syndrome than in patients of similar age with Alzheimer's disease. Both the prevalence and the severity of BGC in patients over 75 years of age with Alzheimer's disease were as expected for age alone. The increased prevalence and severity of BGC in Down's syndrome and in younger patients with Alzheimer's disease appeared not to be related to the presence of dementia or degenerative disease per se, nor was it affected by the presence of cerebral infarction. BGC may result from an age-related disturbance of the structure of arteries within the globus pallidus, which is accelerated (or occurs prematurely) in Down's syndrome and in younger patients with Alzheimer's disease, but probably does not form part of that spectrum of changes that constitutes the pathological basis of Alzheimer's disease.     

Mental retardation and stress on the parents: a contrast between Down's syndrome and childhood autism.

Mothers of autistic, Down's syndrome, and outpatient psychiatric clinic children completed a questionnaire about their attitudes toward the identified child and the effects of the child on themselves and their families. A canonical correlation between the 15 questionnaire scales and three groups revealed a general retardation/social dependency factor separating the mothers of the two retarded groups from the clinic sample. The autism group was differentiated from the Down's syndrome group by scales measuring severity of the child's handicap and family integration problems more than by scales measuring stress on the mother. The hypothesis that mothers of autistic children would report more problems than both other groups was supported; the hypothesis that mothers of Down's syndrome children would report more problems than mothers of outpatient clinic children was not.     

Down's syndrome: intellectual and behavioural functioning during adulthood

ABSTRACT. Previous cross–sectional studies of Down's syndrome have suggested thatdeficits in cognitive and neurological functioning after the age of 35 years are symptomatic of Alzheimer's disease. It has been claimed that this pattern corresponds to post-mortem neuropathological findings of Alzheimer's disease in all Down's syndrome patients who die aged over 35 years. In the present study of Down's syndrome patients aged between 19 and 49 years, results showed that, for those over 35 years, intellectual deterioration had occurred in less than a third. No relationship was found between chronological age and the level of self care skills or the presence of disturbed behaviour. Results are discussed in terms of the interpretation of the existing neuropathological literature, the methodology of future studies and clinicaldecisions regarding hospitalized patients with Down's syndrome.     

Somatomedin C (insulin-like growth factor 1) in adults with Down's syndrome

ABSTRACT. In a Norwegian institution for the mentally retarded, 29 adults with chromosomally verified Down's syndrome were compared to other mentally retarded patients with respect to serum somatomedin C (SmC) (insulin-like growth factor 1 [IGF-1]). Contrary to what has been observed in children, no shortage of SmC could be demonstrated in the adults with Down's syndrome. The results were within the normal range, and there was no difference between those with Down's syndrome and the other mentally retarded patients. Human growth hormone (HGH) and body height were studied in a previous work. Some correlations with these data are, nevertheless, included herein because they are of relevance. SmC correlated with body height in Down's syndrome, while there was no correlation between SmC and HGH or between HGH and body height.     

Comparative coherence studies in healthy volunteers and Down's syndrome patients from childhood to adult age.

Within the scope of the Munich Pediatric Longitudinal Study, EEG coherence was studied in 212 Down's syndrome patients and 342 healthy controls aged from 6 months up to 30 years. The digitalized EEG records were subjected to spectral analysis. Frequency band-related coherences were calculated to reveal age-specific differences in the functional relationship between two brain areas in Down's syndrome patients and controls. The results show that in the "eyes-open" state the intra-hemispheric coherence in the alpha band was significantly lower (P less than 0.05) in the Down's syndrome patients than in the controls whereas that in the delta bands it was generally higher. The intra-hemispheric coherence in the "eyes-closed" state was generally higher in the Down's syndrome groups than in the controls; however, significant differences could be detected only in some age groups. The age-specific development of coherence in the inter-hemispheric parieto-occipital region was almost identical in Down's syndrome children as in controls, both with open and closed eyes. The most distinct differences were found in the fronto-central inter-hemispheric coherence (P less than 0.01), while the coherence deficiencies in the Down's syndrome group became more prominent with increasing age from school age onwards. These electrophysiological results are compared with the results of neuropathological and neurophysiological studies of other authors. It can be suggested that there are correlations with a significantly small number of dendritic spines in Down's syndrome patients, which was determined in neuropathological examinations. A neuronal model of interpretation is presented which explains the increasing developmental deficit with age in Down's syndrome children.     

Dopaminergic neurotransmitter systems in Alzheimer''s disease and in Down''s syndrome at middle age.

In 15 patients with Alzheimer's disease and in 10 with Down's syndrome at middle age, there was severe atrophy, neurofibrillary degeneration and loss of pigmented dopaminergic nerve cells from ventral tegmental area (A10) whereas nerve cells in neighbouring substantia nigra (A9) were much less affected in all three respects. It is suggested that these findings may represent different patterns of damage within the two systems in these conditions which may relate to the presence of Alzheimer type changes (senile plaques) within their respective projection fields.