Genetic abnormalities and CNS tumors: report of two cases of ependymoma associated with Klinefelter’s Syndrome (KS)

Objects Genetic syndromes associated with ependymoma are uncommon, with the exception of NF2. We describe two cases of ependymoma presenting with Klinefelter’s Syndrome (KS) as co-morbid condition. Materials and methods The first patient was diagnosed for KS during pregnancy; he also presented a thyroid agenesis and a deficit of methyltetrahydrofolate reductase (MTHFR); at 30 months of age he was operated on for a grade II ependymoma of IV ventricle; after a multiple-stage surgery, he underwent oral chemotherapy and stereotactic radiotherapy, but after 15 months he presented a local recurrence and died. The second patient was diagnosed for KS at the age of 16 months; at 10 years of age, due to back pain, he underwent an MRI, which showed a cauda equine tumor. He underwent surgery and radiotherapy. Histology was of mixopapillary ependymoma. Conclusion In a review of literature, various neoplasms have been described in association with KS. To our knowledge, these are the first two cases reported of ependymoma associated to KS. A retrospective study of 44 monoinstitutional ependymoma cases demonstrated association with genetic syndromes in 22%.     

Cabergoline compared to levodopa in the treatment of patients with severe restless legs syndrome: results from a multi-center, randomized, active controlled trial.

We report the first large-scale double-blind, randomly assigned study to compare two active dopaminergic therapies for Restless Legs Syndrome (RLS), the dopamine agonist cabergoline (CAB) and levodopa/benserazide (levodopa). Patients with idiopathic RLS were treated with fixed daily doses of 2 or 3 mg CAB or 200 or 300 mg levodopa for 30 weeks. Efficacy was assessed by changes in the IRLS (International RLS Severity Scale) and by time to discontinuation of treatment due to loss of efficacy or augmentation. 361 of 418 screened patients (age 58 +/- 12 years, 71% females) were randomly assigned and treated (CAB: n = 178; levodopa: n = 183) in 51 centers of four European countries. Baseline IRLS total score was 25.7 +/- 6.8. The baseline-adjusted mean change from baseline to week 6 in IRLS sum score was d = -16.1 in the CAB group and d = -9.5 in the levodopa group (d = -6.6, P < 0.0001). More patients in the levodopa group (24.0%) than in the CAB group (11.9%, P = 0.0029, log-rank test) discontinued because of loss of efficacy (14.2% vs. 7.9%, P = 0.0290) or augmentation (9.8% vs. 4.0%, P = 0.0412). Adverse events (AEs) occurred in 83.1% of the CAB group and in 77.6% of the levodopa group. In both groups, most frequent AEs were gastrointestinal symptoms (CAB: 55.6%, levodopa: 30.6%, P < 0.0001). This first large-scale active controlled study in RLS showed superior efficacy of cabergoline versus levodopa after a 30-week long-term therapy. Tolerability was found more favorable with levodopa than with cabergoline.     

Factors predicting mortality in midlife adults with and without Down syndrome living with family

Background Little is known about the mortality of individuals with Down syndrome who have lived at home with their families throughout their lives. The current study evaluates the predictors, causes and patterns of mortality among co‐residing individuals in midlife with Down syndrome as compared with co‐residing individuals with ID owing to other causes. Method This paper examines mortality in 169 individuals with and 292 individuals without Down syndrome from 1988 to 2007. Dates and causes of death were obtained from maternal report, the Social Security Death Index and the National Death Index. Risk factors predicting mortality, including demographic variables, transition variables, and initial and change measures of health, functional abilities and behaviour problems, were obtained from maternal report. Results Having Down syndrome is a risk factor of mortality, net of other risk factors including older age, poorer functional abilities, worsening behaviour problems, residential relocation and parental death. The causes of death among individuals with and without Down syndrome who are in midlife and co‐residing with their families are similar, and are most commonly due to cardiovascular or respiratory problems. Conclusions The findings indicate that midlife adults with Down syndrome who co‐reside with their families generally exhibit similar causes of mortality as do midlife adults with intellectual disability owing to other causes, but show an elevated risk of mortality in midlife net of other variables, such as age and changes in functional abilities and behaviour problems.     

Fifteen-year follow-up of 92 hospitalized adults with Down's syndrome: incidence of cognitive decline, its relationship to age and neuropathology

Background The clinical and neuropathological features associated with dementia in Down’s syndrome (DS) are not well established. Aims To examine clinico‐pathological correlations and the incidence of cognitive decline in a cohort of adults with DS. Method A total of 92 hospitalized persons with DS were followed up from 1985 to December 2000. At outset, 87 participants were dementia‐free, with a median age of 38 years. Assessments included the Prudhoe Cognitive Function Test (PCFT) and the Adaptive Behavior Scale (ABS), to measure cognitive and behavioural deterioration. Dementia was diagnosed from case records and caregivers’ reports. Results Eighteen (21%) patients developed dementia during follow‐up, with a median age of onset 55.5 years (range 45–74). The PCFT demonstrated cognitive decline among those with a less severe intellectual disability (mild and moderate) but not among the profoundly disabled people (severe and profound). Clinical dementia was associated with neuropathological features of Alzheimer’s disease, and correlated with neocortical neurofibrillary tangle densities. At the age of 60 years and above, a little more than 50% of patients still alive had clinical evidence of dementia. Conclusions Clinical dementia associated with measurable cognitive and functional decline is frequent in people with DS after middle age, and can be readily diagnosed among less severely intellectually disabled persons using measures of cognitive function such as the PCFT and behavioural scales such as the ABS. In the more profoundly disabled people, the diagnosis of dementia is facilitated by the use of behavioural and neurological criteria. In this study, the largest prospective DS series including neuropathology on deceased patients, the density of neurofibrillary tangles related more closely to the dementia of DS than senile plaques. In people with DS surviving to middle and old age, the development of dementia of Alzheimer type is frequent but not inevitable, and some people with DS reach old age without clinical features of dementia.     

Natural history of extensive Mongolian spots in mucopolysaccharidosis type II (Hunter syndrome): a survey among 52 Japanese patients

BACKGROUND: Recent reports have shown a correlation between extensive Mongolian spots and mucopolysaccharidosis type II (Hunter syndrome). However, a statistical survey of the incidence and natural history of extensive Mongolian spots among the patients with Hunter syndrome is lacking. OBJECTIVES: To determine the prevalence of extensive Mongolian spots, to determine the natural course of the spots according to age in Japanese patients with Hunter syndrome, and to compare them with the results obtained from the patients' brothers who did not have Hunter syndrome. PATIENTS/METHODS: Fifty-two males with Hunter syndrome aged 3 to 40 years were studied. Twenty-five patients were examined in two clinics to determine the existence and characteristics of the spots. We interviewed their families about the spots in their neonates and the natural course of the spots according to their ages. The same survey was done among another 27 patients using a mailed questionnaire to their families. As control, we investigated 21 brothers of the patients by a mailed questionnaire to their families. RESULTS: The extensive Mongolian spots are identified in almost all the infants with Hunter syndrome and disappear extremely later in their life. The lesions had a high incidence of deep-blue hyperpigmentation. Regardless of age, the overall incidence was 78%. All of the brothers who did not have Hunter syndrome had common-type Mongolian spots in neonates, which regressed during their childhood. CONCLUSION: Our results confirm a strong correlation between extensive Mongolian spots and Hunter syndrome for the Japanese population. The presence of extensive Mongolian blue spots should alert the physician to the possibility of Hunter syndrome.     

Hydrops Fetalis Caused by Fetal Kasabach-Merritt Syndrome

There have been only 2 previous reports of nonimmunologic hydrops fetalis (NIHF) caused by fetal Kasabach-Merritt syndrome, both of which were pathological studies. This is the first clinical case report of NIHF due to fetal Kasabach-Merritt syndrome that was prenatally diagnosed by sonography, computerized tomography, and percutaneous umbilical blood sampling.     

Bullous systemic lupus erythematosus with antiphospholipid syndrome

We report the case of a 44-year-old male with a 10-year history of manifestations of the rare form of bullous systemic lupus erythematosus (SLE) with coexisting antiphospholipid syndrome (APS) that remained undiagnosed until thrombotic-embolic episodes appeared and high titres of anticardiolipin (ACL) antibodies were detected. The patient fulfilled the criteria for SLE and the atypical cutaneous manifestations together with histopathological changes and a favourable response to sulphones were the grounds for the diagnosis of the bullous variety of SLE. Treatment with prednisolone, acenocoumarol and dapsone resulted in marked clinical improvement, reduction in antinuclear antibodies (ANAs) and normalization of ACL antibody titres.     

Sural nerve biopsies in Guillain-Barre syndrome: axonal degeneration and macrophage-associated demyelination and absence of cytomegalovirus genome.

T-cell infiltration was detected by immunohistochemistry in only 2 of 10 sural nerve biopsies from patients with Guillain-Barré syndrome (GBS). The number of endoneurial macrophages, identified by the monoclonal antibody MAC 387, was increased, compared with the number in 10 cases of axonal neuropathy. Macrophage-associated demyelination was identified in 7 and axonal degeneration in 8 cases. Cytomegalovirus (CMV) genome was not detected with the polymerase chain reaction.