Prenatal diagnosis and Down's syndrome: PART 1. Review of possible procedures

There have been many recent advances in techniques for prenatal diagnosis. The direct diagnostic procedures of amniocentesis and chorionic villus sampling, which involve analysis of foetal material, are described and indications of their risks and reliability are given. Other direct procedures are briefly mentioned. Indirect biochemical analyses that identify groups at increased risk are also considered and their individual reported relationships with Down's syndrome are discussed. Technical problems and reported acceptability of maternal serum alpha fetoprotein screening are briefly mentioned. Studies reporting the potential of ultrasonography in the prenatal detection of Down's syndrome are reviewed. Other indications of increased risk are briefly mentioned.     

No evidence of frequent human immunodeficiency virus type 1 infection in seronegative at-risk individuals

The possible existence of human immunodeficiency virus type 1 (HIV-1) infection in asymptomatic seronegative at-risk individuals was investigated in a prospective study of 55 seronegative high-risk individuals (42 homosexual men and 13 heterosexual individuals) and 32 seronegative hemophiliacs treated with factor VIII or IX concentrates before viral inactivation by heat treatment and systematic screening of blood donations. Tests used include the polymerase chain reaction assay with three primer pairs (one in the gag region and two in the pol region) and tests for serum p24 antigen, anti-nef serology (Western blot), and five biologic markers frequently altered by HIV infection (CD4 lymphocyte count, serum beta 2-microglobulin and neopterin concentration, and serum IgG and IgA concentration). Although 91 of 92 HIV-1-seropositive persons were positive in testing with at least one primer pair, no positive result was observed in seronegative at-risk individuals or in 117 seronegative low-risk controls. No nef antibody was found in seronegative at-risk individuals or seronegative controls, but 44 (47%) of 92 HIV-1-seropositive persons had nef antibodies. These findings do not support the existence of frequent HIV-1 infection in seronegative at-risk individuals.     

Early intervention programme for infants with Down's syndrome

This article describes an early intervention programme for infants with Down's syndrome (DS) implemented by a registered nurse. The purpose of this programme was to help the families cope with the realities of raising a child with DS and help the infant fulfil his/her maximum potential. Small groups of three-four families with their infants met weekly with the nurse for 2-hour sessions. Each session was divided into two parts: exercises and discussion of issues relating to DS. Implications for nursing practice, education and management are discussed.     

The preliminary evidence supports the use of spaced retrieval paired with a visual aid for teaching individuals with mild to moderate dementia to use compensatory strategies during oral intake in a controlled environment1

¹Abstracted from: Benigas, J.E. & Bourgeois, M. (2016). Using spaced retrieval with external aids to improve use of compensatory strategies during eating for persons with dementia. American Journal of Speech-Language Pathology, 25(3), 321–334.

Source of funding and disclosure of interest: Source of funding not reported. Original authors reported that there were no conflicts of interest.     

N-acetylator variability in Down's syndrome: characterization with caffeine

Little is known regarding the biotransformation of drugs in Down's syndrome. In particular, there are no published studies that examine metabolic pathways such as N-acetylation, which can exhibit genetically-determined variability. The objective of the present investigation was to compare the acetylator phenotypes of white subjects with Down's syndrome with age-matched control subjects, with use of caffeine as the pharmacologic probe. After the ingestion of caffeine-containing beverages, spot urine collections were obtained at 2 and 4 hours in 22 subjects with Down's syndrome and in 22 control subjects (age range of 4 to 49 years). The urinary excretion ratios of 5-acetylamino-6-amino-3-methyluracil (AAMU) to 1-methylxanthine (1X) determined in these 2-hour and 4-hour samples were highly correlated (r = 0.82; p less than 0.001). In addition, more extensive urinary excretion studies performed for an 8-hour period in three subjects with Down's syndrome demonstrated that the coefficient of variability for the ratio of AAMU/1X ranged from 10.1% to 14.2%, which is similar to the reproducibility previously reported for control subjects. A trimodal distribution of acetylator phenotypes was observed, with no differences in average or frequency distribution of ratio values between the subjects with Down's syndrome and the control subjects. This study demonstrates that polymorphic N-acetylator status, as assessed by caffeine metabolism, is similar in subjects with Down's syndrome and in control subjects.     

Transdisciplinary therapy model for the infant with Down's syndrome

Following a discussion of the motor deficits commonly associated with Down's syndrome, a transdisciplinary developmental therapy model is proposed for use with infants with Down's syndrome. The model includes components from various existing intervention programs for infants as well as some current therapeutic appraoches to motor intervention that have not previously been used for patients with Down's syndrome. Specific suggestions for clinical research studies designed to validate the effects of these various treatment techniques are also included.     

Swedish parents of children with Down's syndrome

Becoming parents of a child with Down's syndrome (DS) challenges the adjustment ability in parenthood. Individuals with higher sense of coherence (SOC) are supposed to manage stressors better than those with lower SOC. The aims of this study were to investigate parental self-perceived stress, SOC, frequency of gainful employment and amount of time spent on child care in Swedish DS parents (165 parents; 86 mothers, 79 fathers) and to compare those with control parents of healthy children (169 parents; 87 mothers, 82 fathers). The mean age of the children was 4.7 years. Parents responded to questionnaires separately including Hymovich's Parent Perception Inventory as stress measurement and Antonovsky's short version of the Orientation to Life. No differences concerning total employment rate were observed, but the DS mothers were more often employed part-time than control mothers. The DS parents did not spend more time on child care than the control parents and they did not differ in mean SOC score, but the DS parents perceived greater stress. The differences in stress, particularly between the DS and control mothers, were related to time-demanding areas. Parents with high SOC scores experienced significantly less self-perceived stress.     

Dance events as a caregiver intervention for persons with dementia

The aim of the study was to illuminate the phenomenon of dance events as a caregiver intervention for persons with dementia in one nursing home as described by the caregivers. Seven caregivers were interviewed. The interviews were unstructured and conducted while the caregivers were watching a video of dance events arranged in the nursing home. The analysis was carried out using the phenomenological method developed by Giorgi. The results are presented in five consistent themes: (1) prerequisites for dance events; (2) creating and preparing different kinds of activities related to the dance events; (3) emotional arousal; (4) caregivers’ situational understanding; and (5) dance events and contextual consequences and synthesis into a general structure. The meaning of the dance events as a caregiver intervention was founded not only on the dancing itself but also encompassed the ontological state of ‘being together’.     

Neuroimaging diagnosis of Tolosa-Hunt syndrome: MRI contribution

OBJECTIVE: To present our experience in the neuroradiological diagnosis of six patients with Tolosa-Hunt syndrome. METHODS: Computerized tomograms and MRI, with and without contrast enhancement, of the cranium and orbits of patients fulfilling IHS criteria for the diagnosis of Tolosa-Hunt syndrome were analyzed. RESULTS: Standard CT scan, with and without contrast enhancement, disclosed an enlarged cavernous sinus in one patient and was normal in the remaining five. In comparison, MRI was clearly abnormal in the four patients on whom it was performed, showing a convex enlargement of the symptomatic cavernous sinus by an abnormal tissue isointense with gray matter on short TR/TE images and iso-hypointense on long TR/TE scans. This abnormal tissue markedly increased in signal intensity after contrast injection and, in two patients, extended into contiguous regions, mainly the orbital apex and subtemporal fossa ipsilaterally. One patient had follow-up studies after successful treatment with corticosteroids. Although diminished in size, the abnormal tissue was still visible on MRI after 3 months of treatment and only disappeared after 6 months of treatment. CONCLUSIONS: These MRI findings help in the differential diagnosis of the Tolosa-Hunt syndrome from conditions such as meningioma, lymphoma, and sarcoidosis, as well as confirming the similarities of the Tolosa-Hunt syndrome and orbital pseudotumor. In the presence of painful ophthalmoplegia, the finding by MRI of cavernous sinus enlargement, with the herein described signal and extension characteristics and slow resolution with corticosteroid treatment, is highly suggestive of the Tolosa-Hunt syndrome.     

Alpha-fetoprotein microheterogeneity: a potential biochemical marker for Down's syndrome

Our purpose was to examine the utility of analyzing alpha-fetoprotein (AFP) microheterogeneity assessed by lectin affinity in Down's syndrome (DS) screening. Maternal sera and amniotic fluids were collected from 18 women who were carrying DS fetuses and 70 unaffected pregnancies around 16 weeks of gestation. The percentages of AFP which reacted with Lens culinaris agglutinin (AFP-L2,3) were determined by lectin affinity electrophoresis. AFP-L2,3 levels were significantly increased (P<0.0001) in both maternal serum and amniotic fluid from DS-affected versus unaffected pregnancies. The fractional areas under the receiver operating characteristic curves were 0.835 and 0.700 (P=0.106) for AFP-L3 and AFP MoM (multiples of the median) in maternal serum. No correlation was found between AFP-L3 and AFP MoM in maternal serum (r=0.006). Our data suggest that the measurement of AFP-L3 in maternal serum is a potential biochemical marker for DS.     

Proteomic analysis of Down's syndrome patients with gout

BACKGROUND: In this study, the expression of hypoxanthine-guanine phosphoribosyl transferase (HPRT) in Down's syndrome patients with gout (DS/G) was determined, and possible underlying mechanisms of gout were characterized using proteomic tools. METHODS: Serum was obtained from DS/G, healthy controls and gout patients (without DS), recruited from the rheumatology clinic. Baseline enzyme assays were recorded and RT-PCR used to identify HPRT gene expression. 2-D electrophoresis and mass spectrometry were utilized to determine a plausible explanation concerning the mechanisms leading to increased uric acid levels in DS patients. RESULTS: Two DS patients were diagnosed with gouty arthritis. Their HPRT enzyme activity was slightly lower than that of normal controls. HPRT expression was also slightly decreased in DS/G patients compared with controls. Serum protein profiles of these two DS/G patients revealed that haptoglobin alpha chain and apolipoprotein A1 (ApoA1) were both significantly down-regulated. Protein expression was validated by immunoblot. CONCLUSION: Our results revealed that low levels of haptoglobin in the two DS/G patients were related to renal dysfunction may have affected uric acid excretion and caused gout. However, decreased ApoA1 revealed a positive correlation between defective lipid metabolism and gouty arthritis in DS/G patients.     

Counseling parents of infants with Down's syndrome.

The primary objective in counseling parents of a child with Down's syndrome is to secure realistic goals and an accepted place in the family for the child. A nurturing environment gives the child the best chance to reach full potential.     

Critical spatiotemporal gait parameters for individuals with dementia: A systematic review and meta-analysis

Instrumented gait analysis allows for the identification of walking parameters to predict cognitive decline and the worsening of dementia. The aim of this study was to perform a meta-analysis to better clarify which gait parameters are affected or modified with the progression of the dementia in a larger sample, as well as which gait assessment conditions (single-task or dual-task conditions) would be more sensitive to reflect the influence of dementia. Literature searches were conducted with the keywords “quantitative gait” OR “gait analysis” AND “dementia” AND “single-task” AND “dual-task,” and for “quantitative gait” OR “gait analysis” AND “dementia” AND “fall risk” on PubMed, EMBASE, the Cochrane Library, Scopus, and Web of Science. The results were used to perform a systematic review focussing on instrumental quantitative assessment of the walking of patients with dementia, during both single and dual tasks. The search was performed independently by two authors (C. R. and C. M.) from January 2018 to April 2020 using the PICOS criteria. Nine publications met the inclusion criteria and were included in the systematic review. Our meta-analysis showed that during a single task, most of the spatiotemporal parameters of gait discriminated best between patients with dementia and healthy controls, including speed, cadence, stride length, stride time, stride time variability, and stance time. In dual tasks, only speed, stride length, and stride time variability discriminated between the two groups. In addition, compared with spatial parameters (e.g. stride length), some temporal gait parameters were more correlated to the risk of falls during the comfortable walking in a single task, such as cadence, stride time, stride time variability, and stance time. During a dual task, only the variability of stride time was associated with the risk of falls.     

Visual spatial abilities and fall risk: an assessment tool for individuals with dementia

Risk of falling is a major concern of long-term care facilities with residents diagnosed with dementia. Use of a brief cognitive assessment focusing on visual spatial abilities could be one strategy in the prevention of falls in residents with dementia. The objective of this study was to determine if a clock test could predict a risk of falls in residents diagnosed with dementia. Three hundred sixty-four individuals with dementia participated (92 men and 272 women; ages 37 to 100, mean 80.5 years, median 83 years). Each participant was given the Reality Comprehension Clock Test (RCCT) three times, and Mini Mental-Status Examination (MMSE) two times to determine criterion-related validity, test-retest reliability, internal consistency; and to set and evaluate a risk of falls score based on the Visual Spatial Score (VSS) component produced by the RCCT. Significant findings included .72 (p < .01) correlation between the RCCT and the MMSE, .90 (p < .01) correlation between the first administration of the RCCT and the second administration of the RCCT; an alpha of .95 (p, < .001) and an F value of 7.6 (p < .001) producing a risk of falls initial VSS of 5 or lower compared to 9 or greater. Chi-square of 6.3 for 30 days (p,< .01), 11.08 for 60 days (p < .01) and 13.3 for 90 days (p < .01) indicated a significant difference in the number of falls occurring in the high risk group (VSS of 5 or lower) compared to the low/ no risk group (VSS of 9 or higher). A risk factor analysis suggested that residents in the higher risk group were three times more likely to have fallen than residents in the low risk group. Knowing a resident's visual spatial ability offers health care providers an opportunity to implement a resident-specific intervention that addresses their cognitive ability and visual spatial deficit that may reduce the resident's risk of falling.