Photomyogenic response in Niemann–Pick type C: a case report

Contains fulltext : 98214.pdf (publisher's version ) (Closed access)1 maart 201

Homozygosity for a missense mutation in the 67 kDa isoform of glutamate decarboxylase in a family with autosomal recessive spastic cerebral palsy: parallels with Stiff-Person Syndrome and other movement disorders

Background Cerebral palsy (CP) is an heterogeneous group of neurological disorders of movement and/or posture, with an estimated incidence of 1 in 1000 live births. Non-progressive forms of symmetrical, spastic CP have been identified, which show a Mendelian autosomal recessive pattern of inheritance. We recently described the mapping of a recessive spastic CP locus to a 5 cM chromosomal region located at 2q24-31.1, in rare consanguineous families. Methods Here we present data that refine this locus to a 0.5 cM region, flanked by the microsatellite markers D2S2345 and D2S326. The minimal region contains the candidate gene GAD1, which encodes a glutamate decarboxylase isoform (GAD67), involved in conversion of the amino acid and excitatory neurotransmitter glutamate to the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Results A novel amino acid mis-sense mutation in GAD67 was detected, which segregated with CP in affected individuals. Conclusions This result is interesting because auto-antibodies to GAD67 and the more widely studied GAD65 homologue encoded by the GAD2 gene, are described in patients with Stiff-Person Syndrome (SPS), epilepsy, cerebellar ataxia and Batten disease. Further investigation seems merited of the possibility that variation in the GAD1 sequence, potentially affecting glutamate/GABA ratios, may underlie this form of spastic CP, given the presence of anti-GAD antibodies in SPS and the recognised excitotoxicity of glutamate in various contexts

The synaptic vesicle-associated protein amphiphysin is the 128-kD autoantigen of stiff-man syndrome with breast cancer

Stiff-Man syndrome (SMS) is a rare disease of the central nervous system (CNS) characterized by progressive rigidity of the body musculature with superimposed painful spasms. An autoimmune origin of the disease has been proposed. In a caseload of more than 100 SMS patients, 60% were found positive for autoantibodies directed against the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD). Few patients, all women affected by breast cancer, were negative for GAD autoantibodies but positive for autoantibodies directed against a 128-kD synaptic protein. We report here that this antigen is amphiphysin. GAD and amphiphysin are nonintrinsic membrane proteins that are concentrated in nerve terminals, where a pool of both proteins is associated with the cytoplasmic surface of synaptic vesicles. GAD and amphiphysin are the only two known targets of CNS autoimmunity with this distribution. This finding suggests a possible link between autoimmunity directed against cytoplasmic proteins associated with synaptic vesicles and SMS

Growing old at home – A randomized controlled trial to investigate the effectiveness and cost-effectiveness of preventive home visits to reduce nursing home admissions: study protocol [NCT00644826]

<p>Abstract</p> <p>Background</p> <p>Regarding demographic changes in Germany it can be assumed that the number of elderly and the resulting need for long term care is increasing in the near future. It is not only an individual's interest but also of public concern to avoid a nursing home admission. Current evidence indicates that preventive home visits can be an effective way to reduce the admission rate in this way making it possible for elderly people to stay longer at home than without home visits. As the effectiveness and cost-effectiveness of preventive home visits strongly depends on existing services in the social and health system existing international results cannot be merely transferred to Germany. Therefore it is necessary to investigate the effectiveness and cost-effectiveness of such an intervention in Germany by a randomized controlled trial.</p> <p>Methods</p> <p>The trial is designed as a prospective multi-center randomized controlled trial in the cities of Halle and Leipzig. The trial includes an intervention and a control group. The control group receives usual care. The intervention group receives three additional home visits by non-physician health professionals (1) geriatric assessment, (2) consultation, (3) booster session.</p> <p>The nursing home admission rate after 18 months will be defined as the primary outcome. An absolute risk reduction from a 20% in the control-group to a 7% admission rate in the intervention group including an assumed drop out rate of 30% resulted in a required sample size of N = 320 (n = 160 vs. n = 160).</p> <p>Parallel to the clinical outcome measurement the intervention will be evaluated economically. The economic evaluation will be performed from a society perspective.</p> <p>Discussion</p> <p>To the authors' knowledge for the first time a trial will investigate the effectiveness and cost-effectiveness of preventive home visits for people aged 80 and over in Germany using the design of a randomized controlled trial. Thus, the trial will contribute to the existing evidence on preventive home visits especially in Germany.</p

Mental health in South African adolescents living with HIV: correlates of internalising and externalising symptoms

Although declining in all other age groups, AIDS-related deaths among adolescents are increasing. In the context of HIV, mental health problems are associated with negative health outcomes, including non-adherence to life-saving ART. For effective programming it is essential to identify factors associated with psychological outcomes in this population. Adopting a socioecological perspective, we aimed to identify correlates of internalising and externalising symptoms in a large, representative sample of South African adolescents living with HIV. HIV-positive adolescents (n = 1060), who received care in public health facilities in South Africa’s Eastern Cape, completed measures of internalising and externalising symptoms. Hypothesised correlates included HIV and health-related factors (physical health, mode of infection, medication side effects, disclosure, stigma), health-service related factors (negative interactions with clinic staff, clinic support group), interpersonal factors (abuse, bullying victimisation, social support), parenting-related factors (orphanhood, positive parenting, parental monitoring, parent communication), as well as individual and demographic-related factors (self-efficacy, age, gender, urban/rural location, poverty). Correlates operating across a variety of contexts were identified. Bullying victimisation, self-efficacy, and positive parenting may be particularly salient intervention targets as they were associated with better outcomes on most or all mental health measures, can be addressed without directly targeting adolescents living with HIV (reducing the chances of accidental exposure and stigma), and are associated with better adolescent mental health in South Africa more generally.IS

Transmission in Heteronymous Spinal Pathways Is Modified after Stroke and Related to Motor Incoordination

Changes in reflex spinal pathways after stroke have been shown to affect motor activity in agonist and antagonist muscles acting at the same joint. However, only a few studies have evaluated the heteronymous reflex pathways modulating motoneuronal activity at different joints. This study investigates whether there are changes in the spinal facilitatory and inhibitory pathways linking knee to ankle extensors and if such changes may be related to motor deficits after stroke. The early facilitation and later inhibition of soleus H reflex evoked by the stimulation of femoral nerve at 2 times the motor threshold of the quadriceps were assessed in 15 healthy participants and on the paretic and the non-paretic sides of 15 stroke participants. The relationships between this reflex modulation and the levels of motor recovery, coordination and spasticity were then studied. Results show a significant (Mann-Whitney U; P<0.05) increase in both the peak amplitude (mean±SEM: 80±22% enhancement of the control H reflex) and duration (4.2±0.5 ms) of the facilitation on the paretic side of the stroke individuals compared to their non-paretic side (36±6% and 2.9±0.4 ms) and to the values of the control subjects (33±4% and 2.8±0.4 ms, respectively). Moreover, the later strong inhibition observed in all control subjects was decreased in the stroke subjects. Both the peak amplitude and the duration of the increased facilitation were inversely correlated (Spearman r = −0.65; P = 0.009 and r = −0.67; P = 0.007, respectively) with the level of coordination (LEMOCOT) of the paretic leg. Duration of this facilitation was also correlated (r = −0.58, P = 0.024) with the level of motor recovery (CMSA). These results confirm changes in transmission in heteronymous spinal pathways that are related to motor deficits after stroke

Disclosure of physical, emotional and sexual child abuse, help-seeking and access to abuse response services in two South African Provinces

Physical, emotional and sexual child abuse are major problems in South Africa. This study investigates whether children know about post-abuse services, if they disclose and seek services, and what the outcomes of help-seeking behaviour are. It also examines factors associated with request and receipt of services. Confidential self-report questionnaires were completed by adolescents in South Africa as part of a communitybased study of children aged 10-17 (n=3515) in two provinces. Child abuse, disclosure and outcomes of help-seeking were measured using internationally recognized measures. Prevalence of frequent (&gt;weekly) physical abuse was 7.4%, frequent emotional abuse 12.4%, and lifetime contact sexual abuse 9.0%. 98.6% of children could name one suitable confidante or formal service for abuse disclosure, but only 20.1% of abuse victims disclosed. Of those, 72% received help. Most common confidantes were caregivers and teachers. Of all abuse victims, 85.6% did not receive help due to non-disclosure or inactivity of services, and 14.4% received help: 4.9% from formal health or social services and 7.1% through community vigilante action. Emotional abuse, sexual abuse and female gender were associated with higher odds of help-seeking. While children in South Africa showed high knowledge of available services, access to formal services among abused children was low and not all those requesting services received them. Notably fewer children received help from formal services than through community vigilante action. Urgent action is needed to improve service access for child abuse victims

Tremor in multiple sclerosis

Tremor is estimated to occur in about 25 to 60 percent of patients with multiple sclerosis (MS). This symptom, which can be severely disabling and embarrassing for patients, is difficult to manage. Isoniazid in high doses, carbamazepine, propranolol and gluthetimide have been reported to provide some relief, but published evidence of effectiveness is very limited. Most trials were of small size and of short duration. Cannabinoids appear ineffective. Tremor reduction can be obtained with stereotactic thalamotomy or thalamic stimulation. However, the studies were small and information on long-term functional outcome is scarce. Physiotherapy, tremor reducing orthoses, and limb cooling can achieve some functional improvement. Tremor in MS remains a significant challenge and unmet need, requiring further basic and clinical research