Pericentrin expression in Down’s syndrome

Down’s syndrome (DS) is the most frequent genetic cause of intellectual disability and is a chromosomal abnormality of chromosome 21 trisomy. The pericentrin gene (PCNT) has sequenced in 21q22.3 inside of the minimal critical region for Down’s syndrome. Alterations of PCNT gene are associated with dwarfism, cardiomyopathy and other pathologies. In this study, we have evaluated the possible differential expression of PCNT mRNA, by qRT-PCR, in peripheral blood leukocytes of DS subjects compared with the normal population. In the present case–control study, PCNT gene expression was increased by 72.72 % in 16 out 22 DS samples compared with normal subjects. Our data suggest that changes in the expression levels of PCNT in DS subjects may be involved into the molecular mechanism of Down’s syndrome.     

Plasma amino acids and neopterin in healthy persons with Down’s syndrome

Summary In persons with Down’s syndrome (DS) immunological abnormalities as well as hypothyroidism and Alzheimer type dementia are frequently observed. In addition, the activity of the enzyme cystathionine beta-synthase (CBS) is over-expressed which results in an altered homocysteine metabolism. In the present study, 48 older healthy DS persons without signs of dementia, psychiatric or somatic comorbidity and free of medication were analyzed for plasma levels of amino acids, neopterin and monoaminergic metabolites. Data were compared with those obtained from age and sex matched healthy controls. It was found that the spectrum of amino acids showed widespread differences in that levels of nearly all essential amino acids were lower in DS patients as compared to healthy controls. In addition, a significantly lower methionine and higher taurine concentration were observed which is in accordance with a disturbed homocysteine metabolism. With respect to the monoamine metabolites, the concentration of 5-hydroxyindoleacetic acid was not altered whereas that of homovanillic acid was significantly increased. Finally, the concentration of the immune activation marker neopterin was increased in persons with DS. It is concluded that healthy DS persons of older age show extensive biochemical abnormalities suggesting a compromised homocysteine metabolism, an activated cell-mediated immune response and an enhanced turnover of dopamine.     

Horner’s syndrome,Pseudo-Horner’s syndrome,and simple anisocoria

This discussion reviews the common causes of Horner’s syndrome, with emphasis on case reports from the past several years. Much of the recent literature concerns the use of apraclonidine as a diagnostic test for Horner’s syndrome, possibly as an alternative for the current gold standard of cocaine eye drops. This new literature is discussed in the context of the current standards for clinical diagnosis.     

Dementia in Down’s syndrome: an MRI comparison with Alzheimer’s disease in the general population

Background

Down’s syndrome (DS) is the most common genetic cause of intellectual disability. People with DS are at an increased risk of Alzheimer’s disease (AD) compared to the general population. Neuroimaging studies of AD have focused on medial temporal structures; however, to our knowledge, no in vivo case–control study exists comparing the anatomy of dementia in DS to people with AD in the general population. We therefore compared the in vivo brain anatomy of people with DS and dementia (DS+) to those with AD in the general population.

Method

Using MRI in 192 adults, we compared the volume of whole brain matter, lateral ventricles, temporal lobes and hippocampus in DS subjects with and without dementia (DS+, DS-), to each other and to three non-DS groups. These included one group of individuals with AD and two groups of controls (each age-matched for their respective DS and general population AD cohorts).

Results

AD and DS+ subjects showed significant reductions in the volume of the whole brain, hippocampus and temporal lobes and a significant elevation in the volume of the lateral ventricle, compared to their non-demented counterparts. People with DS+ had a smaller reduction in temporal lobe volume compared to individuals with AD.

Conclusions

DS+ and AD subjects have a significant reduction in volume of the same brain regions. We found preliminary evidence that DS individuals may be more sensitive to tissue loss than others and have less ‘cognitive reserve’.     

SPAG5 mRNA is over-expressed in peripheral blood leukocytes of patients with Down’s syndrome and cryptorchidism

Men with Down’s syndrome (DS) have an increased risk of cryptorchidism, but the mechanisms causing its onset are not clear. Cryptorchidism causes a primary testiculopathy responsible for infertility. SPAG5 mRNA is predominantly expressed in testis in pachytene spermatocytes. This observation prompted us to evaluate the expression of SPAG5 gene in five DS men with cryptorchidism and five normal healthy men (controls) by quantitative real-time PCR in peripheral blood leukocytes. We found that SPAG5 is over expressed in the five men with DS and cryptorchidism compared with five age- and sex-matched normal controls. This finding suggests that the increased expression of this gene may play a pathogenic role durin testicular development in subjects with DS and cryptorchidism.     

Reverse relationship between β-amyloid precursor protein and β-amyloid peptide plaques in Down’s syndrome versus sporadic/familial Alzheimer’s disease

Strong genetic evidence has been accumulated in favor of a central role of β-amyloid precursor protein (APP) and β-amyloid peptide (βA4) in the pathogenesis of Alzheimer’s disease (AD). We employed four newly developed APP and βA4 antibodies and performed a comparative neuropathological study of patients with Down’s syndrome (DS), early-onset familial AD and sporadic AD to investigate the distribution of APP and βA4 plaque densities in the cerebral cortex of these disorders. Quantitative analysis of APP versus βA4 plaques revealed that brains with early-onset familial AD and sporadic AD showed significantly more βA4 plaques than brains with DS (P < 0.05). In contrast, APP plaques were more abundant in DS cerebral cortex (P < 0.02). These observations suggest that the development of pathological changes in DS brains does not parallel that observed in AD, which might be attributable to different causes in the pathogenesis of βA4 formation. A comparison of these disorders may be useful to further complement our knowledge of the mechanisms leading to plaque development. Received: 26 March 1998 / Revised: 25 May 1998 / Accepted: 30 July 1998     

Association between intracellular infectious agents and Tourette’s syndrome

The underlying pathophysiological mechanisms in Tourette’s syndrome (TS) are still unclear. Increasing evidence supports the involvement of infections, possibly on the basis of an altered immune status. Not only streptococci but also other infectious agents may be involved. This study investigates the association between the neurotrophic agents Chlamydia, Toxoplasma and TS. 32 patients with TS and 30 healthy matched controls were included. For each individual, IgA/IgG antibody titers against Chlamydia trachomatis/pneumoniae and Toxoplasma gondii were evaluated and analyzed with Fisher’s exact test. We found a significantly higher rate of TS patients with elevated antibody titers against Chlamydia trachomatis (P = 0.017) as compared to controls. A trend toward a higher prevalence in the Tourette’s group was shown for Toxoplasma (P = 0.069). In conclusion, within the TS patients a higher rate of antibody titers could be demonstrated, pointing to a possible role of Chlamydia and Toxoplasma in the pathogenesis of tic disorders. Because none of these agents has been linked with TS to date, a hypothesis is that infections could contribute to TS by triggering an immune response. It still remains unclear whether tic symptoms are partly due to the infection or to changes in the immune balance caused by an infection.     

Developmental trend of children with Down’s syndrome – How do sex and neonatal conditions influence their developmental patterns?

Objective

This study investigated factors that would influence developmental trend of children with Down’s syndrome (DS) in three different domains (motor, cognitive, language), specifically focusing on the effect of sex and neonatal conditions, including preterm birth, low birth weight, and congenital heart disease (CHD).

The neuropsychological rehabilitation of visual agnosia and Balint’s syndrome

ABSTRACT

Visual agnosia and Balint’s syndrome are complex neurological disorders of the higher visual system that can have a remarkable impact on individuals’ lives. Rehabilitation of these individuals is important to enable participation in everyday activities despite the impairment. However, the literature about the rehabilitation of these disorders is virtually silent. Therefore, the aim of this systematic review is to give an overview of available literature describing treatment approaches and their effectiveness with regard to these disorders. The search engines Psychinfo, Amed, and Medline were used, resulting in 22 articles meeting the criteria for inclusion. Only articles describing acquired disorders were considered. These articles revealed that there is some information available on the major subtypes of visual agnosia as well as on Balint’s syndrome which practising clinicians can consult for guidance. With regard to the type of rehabilitation, compensatory strategies have proven to be beneficial in most of the cases. Restorative training on the other hand has produced mixed results. Concluding, although still scarce, a scientific foundation about the rehabilitation of visual agnosia and Balint’s syndrome is evolving. The available approaches give valuable information that can be built upon in the future.     

Sick sinus syndrome and orthostatic hypotension in Parkinson’s disease

We present a case of Parkinson's disease patient whose initial symptoms were sick sinus syndrome and orthostatic hypotension. Our case illustrates difficulties in distinguishing syncope of primary cardiac or neurological origin and highlights the importance of a diagnostic workup including neurological examination.     

The up-regulation of metabotropic glutamate receptor 5 (mGluR5) in Down’s syndrome brains

We investigated the expression of metabotropic glutamate receptor 5 (mGluR5), a subtype of group I mGluRs, in the cerebral cortex of cases with Down’s syndrome (DS), using immunohistochemistry and immunoblotting with this receptor. The up-regulation of mGluR5 was observed in DS by immunohistochemistry, and atrophic pyramidal neurons were immunolabelled in elderly DS cases. Western blotting confirmed the increased expression in DS brains. Since group I mGluR regulates the metabolism of amyloid precursor protein (APP) and accelerates its processing into non-amyloidogenic APP, the overexpression of mGluR5 may be related to the pathological state of APP metabolism in DS. Received: 9 February 1998 / Revised: 1 September 1998 / Accepted: 14 September 1998     

Accelerometer-determined physical activity and walking capacity in persons with Down syndrome,Williams syndrome and Prader–Willi syndrome

In this study we describe by use of accelerometers the total physical activity (PA), intensity pattern and walking capacity in 87 persons age 16–45 years with Down syndrome (DS), Williams syndrome (WS) and Prader–Willi syndrome (PWS). Participants were recruited from all over Norway, and lived either with their parents or in community residences with support.On average the participants generated 294 counts per minute (cpm) or 6712 steps per day, with most of the day spent in sedentary activity, 522 min/day, followed by 212 min/day in light PA, 71 min/day in lifestyle activity and 27 min/day in moderate-to-vigorous physical activity (MVPA). Inactivity was prevalent, as only 12% meet the current Nordic recommendations for PA.When compared, no differences for total physical activity or time in MVPA were observed between the three groups. However, participant with DS spent a mean of 73 min/day less and 43 min/day less in sedentary activities compared to participants with PWS and WS, respectively, (p = 0.011, 95% CI: ?10.9; ?80.1). In addition the DS-group spent a mean of 66 min/day more in light PA than the PWS-group and 41 min/day more than the WS-group, (p < 0.001, 95% CI: 29.3; 79.7). Participants with PWS spent on average 30 min/day less in lifestyle activities compared to both participants with DS and WS, (p < 0.001, 95% CI: ?14.2; ?45.4). No association between total PA and BMI were observed. Males were more active than females across all diagnoses. Males accumulated on average 85 counts per minutes more than females, (p = 0.002, 95% CI: 33.3; 136.7), 2137 more steps per day, (p = 0.002, 95% CI: 778; 3496). The mean walking capacity during six-minutes was 507 m (SD 112 m) for males and 466 m (SD 88 m) for females. Distance walked during testing decreased with 33.6 m when comparing normal or underweight participants to overweight participants, and 78.1 m when comparing overweight to obese participants (p < 0.001 95% CI: ?40.4; ?85.8). When adjusted for BMI no differences in walking capacity between the three genetic conditions were observed.     

Neurological complications of Werner’s syndrome

Abstract. Patients with Werners syndrome have the appearance of premature ageing. Neurological complications are usually regarded as uncommon. The neurological manifestations in three patients with cardinal features of Werners syndrome, including short stature, premature greying and baldness, thin arms and legs, cataracts and scleroderma-like skin changes, are presented. The neurological features included transient ischaemic attacks secondary to atherosclerosis in the common carotid arteries (one patient), sensory peripheral neuropathy (one patient) and peripheral neuropathy with a possible myelopathy (one patient). In one of these patients the diagnosis of Werners syndrome was not recognised prior to neurological referral. Although neurological disease in patients with Werners syndrome is uncommon, it may be under-recognised. Some of the neurological complications are secondary to premature cerebrovascular disease, but the pathogenesis of peripheral neuropathy and myelopathy in patients with Werners syndrome is uncertain.     

Asperger’s syndrome and high-functioning autism: language, motor and cognitive profiles

The objective of this study is to compare the cognitive profile, the motor and language functioning and the psychosocial adaptation of children with Asperger syndrome (AS) and with high-functioning autism (HFA). Subjects were recruited through the department Autism and Developmental Disorders of the Heckscher-Klinikum. To be included in the study, the full-scale-IQ had to be at least 80. Subjects with AS had to have a normal early language development and subjects with HFA a clear delay in language development, as reported by their parents. The sample consisted of 57 children with Asperger syndrome and 55 children with high-functioning autism. The mean age of the children was 10 years. All subjects were examined with a standardised test battery. Children with AS had a higher full-scale-IQ than children with HFA. This was due to a higher verbal-IQ. There were no significant differences in the performance-IQ. At a mean age of 10 years, subjects with AS had better language skills than subjects with HFA, but at least 30% showed clear receptive language problems. Motor problems were present in about 50% of the children with AS and HFA. The level of psychosocial adaptation was clearly reduced, but was comparable for the two groups. The differences in verbal-IQ and language skills between the two groups could be explained through the definition of the syndromes. The presence of language problems in the subjects with AS at age 10, the comparable degree of motor impairment and level of psychosocial adaptation question the validity of the distinction between AS and HFA within the category of pervasive developmental disorders.     

The spectrum of Susac’s syndrome

We report a series of four patients with Susac’s syndrome, which is characterized by the triad of visual loss due to branch retinal artery occlusions, sensorineural hearing loss due to cochlear involvement, and encephalopathy due to cerebral microangiopathy. However, as we describe in this series, the clinical triad may not be apparent for years, resulting in delays in diagnosis. We also report the variable cerebrospinal fluid and brain magnetic resonance imaging findings, and treatment using a combination of steroids and intravenous immunoglobulin, followed by mycophenolate mofetil.     

Meningioma associated with Gorlin’s syndrome

Gorlin’s syndrome or naevoid basal cell carcinoma syndrome is a rare autosominal dominant condition characterised by a variety of congenital anomalies and various malignancies. The chief manifestations include multiple basal cell naevi, mandibular cysts, plantar and palmar pits, vertebral and rib abnormalities and intracranial calcifications. We report a patient with Gorlin’s syndrome associated with meningioma treated at our institution. The clinical and radiological features together with the management strategies of this unusual disease entity are discussed.     

Functional imaging in Tourette’s syndrome

The cause or causes of Tourette's syndrome (TS) remain unknown. Functional imaging studies have evaluated several implicated neurotransmitter systems and focused predominantly on the frequency or severity of tics. The results have been inconclusive and frequently contradictory with little light shed on pathogenetic mechanisms. However, metabolic derangements have been demonstrated within regions of the basal ganglia, limbic system and sensori-motor cortex and are in keeping with the concept of TS as both a motor and behavioral disorder. TS has long been regarded an involuntary movement disorder. However, many patients have stated that without the premonitory sensation, there would be no tics. For this reason, it has been suggested that the premonitory urge may be considered the involuntary component of TS and the performance of the tic merely a voluntary response. Future studies are needed to differentiate functional changes relating to urge from those associated with the performance of tics and tic suppression.     

Dementia in idiopathic Parkinson’s syndrome

Abstract. Approximately 25% of patients with idiopathic Parkinsons disease (IPD) later developdementia, with the typical characteristics as detailed in ICD-10 and DSM-IV. Differential diagnosis has to exclude dementia due to Lewy bodies, subcortical vascular encephalopathy and subcortical dementia due to progressive supranuclear paralysis or corticobasal degeneration. Several studies showed promising results for cholinesterase inhibitors such as donepezile, rivastigmine and galantamine. The demented Parkinsonian patients then present with improvement in cognitive function while motor skills do not deteriorate.