Intellectual disability associated with retinal dystrophy in the Xp11.3 deletion syndrome: ZNF674 on trial. Guilty or innocent?

X-linked retinal dystrophies (XLRD) are listed among the most severe RD owing to their early onset, leading to significant visual loss before the age of 30. One-third of XLRD are accounted for by RP2 mutations at the Xp11.23 locus. Deletions of ca. 1.2 Mb in the Xp11.3-p11.23 region have been previously reported in two independent families segregating XLRD with intellectual disability (ID). Although the RD was ascribed to the deletion of RP2, the ID was suggested to be accounted for by the loss of ZNF674, which mutations were independently reported to account for isolated XLID. Here, we report deletions in the Xp11.3-p11.23 region responsible for the loss of ZNF674 in two unrelated families segregating XLRD, but no ID, identified by chromosomal microarray analysis. These findings question the responsibility of ZNF674 deletions in ID associated with X-linked retinal dystrophy.     

Prognostic Value of Early Therapeutic Alliance in Weight Recovery: A Prospective Cohort of 108 Adolescents With Anorexia Nervosa

PurposeTo determine whether patients' perception of early therapeutic alliance (TA) could predict time to achieve a target weight among adolescents undergoing treatment for anorexia nervosa.MethodTA was assessed in a prospective cohort recruited from both inpatient and outpatient settings by self-administered and validated questionnaires. Kaplan–Meier survival curves were compared by log rank test, and Cox regression was used to test whether patients' perception of early TA predicted time to achieve a target weight.ResultsIn total, 108 patients were included, and 79.6% achieved a target weight. Better patient perception of early TA increased the hazard ratio (HR) of achieving a target weight (HR = 2.7, 95% confidence interval: 1.7–4.4, p < .001) such as being in the inpatient setting by 6.7. Being very severely underweight at admission decreased the HR of achieving the target weight.ConclusionPatients' perception of early TA is a good predictor of achieving a target weight. Because TA is a modifiable construct, it could be a target for intervention.     

TARDBP mutations in motoneuron disease with frontotemporal lobar degeneration

TDP‐43 (TAR‐DNA binding protein) aggregates in neuronal inclusions in motoneuron disease (MND), as well as in frontotemporal lobar degeneration (FTLD) and FTLD associated with MND (FTLD‐MND). Mutations in TARDBP gene, coding for TDP‐43, were found in patients with pure MND. We now describe TARDBP mutations in two patients with FTLD‐MND, presenting with a behavioral variant of FTLD and semantic dementia, suggesting that TDP‐43 may also have a direct pathogenic role in FTLD disorders. Ann Neurol 2009;65:470–474     

Pulmonary thrombosis as the first manifestation of systemic lupus erythematosus in a 14-year-old boy

We describe the case of a 14-year-old boy who presented with pulmonary embolism and who was subsequently found to have nephrotic syndrome due to lupus membranous nephropathy. He had no other signs of nephrotic syndrome or of systemic lupus erythematosus, such as edema or circulating lupus anticoagulants (antiphospholipid or anticardiolipin antibodies), and no hereditary coagulopathy. This case contributes to our understanding of unusual clinical presentations of systemic lupus erythematosus in children.     

Electrical stimulation protocols for hippocampal synaptic plasticity and neuronal hyper-excitability: are they effective or relevant?

Long-term potentiation (LTP) of synaptic transmission is a widely accepted model that attempts to link synaptic plasticity with memory. LTP models are also now used in order to test how a variety of neurological disorders might affect synaptic plasticity. Interestingly, electrical stimulation protocols that induce LTP appear to display different efficiencies and importantly, some may not be as physiologically relevant as others. In spite of advancements in our understanding of these differences, many types of LTP inducing protocols are still widely used. In addition, in some cases electrical stimulation leads to normal biological phenomena, such as putative memory encoding and in other cases electrical stimulation triggers pathological phenomena, such as epileptic seizures. Kindling, a model of epileptogenesis involving repeated electrical stimulation, leads to seizure activity and has also been thought of, and studied as, a form of long-term neural plasticity and memory. Furthermore, some investigators now use electrical stimulation in order to reduce aspects of seizure activity. In this review, we compare in vitro and in vivo electrical stimulation protocols employed in the hippocampal formation that are utilized in models of synaptic plasticity or neuronal hyperexcitability. Here the effectiveness and physiological relevance of these electrical stimulation protocols are examined in situations involving memory encoding (e.g., LTP/LTD) and epileptiform activity.