Do phonologic and rapid automatized naming deficits differentially affect dyslexic children with and without a history of language delay? A study of Italian dyslexic children.

OBJECTIVE: The study aims to verify whether phonologic and rapid automatized naming (RAN) deficits are present and associated in Italian dyslexic children and whether they differentially affect dyslexics with and without a history of previous language delay (LD). BACKGROUND: According to the phonologic core deficit hypothesis, dyslexia may stem from impairment of the representation and manipulation of phonemes and may be closely associated with oral language deficits. However, deficits in tasks not requiring fine-grained phonologic representations, such as RAN, have also been described in dyslexic children. METHODS: Thirty-seven children were selected on the basis of a reading deficit and were assigned to 2 groups according to whether or not they had a history of early LD as determined retrospectively by parental report. A battery of reading and writing, verbal working memory, metaphonologic, RAN, and visual search tests were administered. RESULTS: RAN deficits were shared by most dyslexics (with and without a history of LD), whereas phonologic deficits were mainly associated with a previous LD. This last condition did not result in a more profound impairment of reading and writing decoding skills. CONCLUSION: In a shallow orthography such as Italian, RAN, not phonologic deficits, may represent the main cognitive marker of developmental dyslexia.     

Psychiatric disorders in the families of schizotypal subjects.

In a study of the families of 21 schizotypal patients, we found an increased morbidity risk for schizophrenia compared with that in the families of 21 nonschizotypal patients and 42 controls. The Axis I diagnoses did not influence the distribution of the morbidity risk in the families of the schizotypal patients. If the schizotypal subjects also had other personality disorders, the morbidity risk for schizophrenia among their relatives was lower, although not significantly.     

''Gender gap'' in multiple sclerosis: magnetic resonance imaging evidence

The authors evaluated the gender difference in the magnetic resonance imaging characteristics of the lesions occurring in the brain of 413 multiple sclerosis (MS) patients. Men had fewer contrast-enhancing lesions (P = 0.01), but a higher proportion of lesions evolving into 'black holes' (P = 0.001), when compared with women. Thus, our data indicate that men with MS are prone to develop less inflammatory, but more destructive lesions than women. This study results provides support for a modulation of the MS pathological changes by gender.     

Two-year maintenance treatment with citalopram, 20 mg, in unipolar subjects with high recurrence rate

BACKGROUND: The efficacy of citalopram, 20 to 60 mg/day, in relapse prevention in major depression was demonstrated in 6-month placebo-controlled studies. The authors tested the efficacy of citalopram, 40 mg/day, in relapse prevention over a 4-month period and citalopram, 20 mg/day, in recurrence prevention over a 24-month period. METHOD: Fifty inpatients with recurrent major depressive disorder (DSM-IV criteria) who had had at least one depressive episode during the 18 months preceding the index episode were openly treated with citalopram, 40 mg/day. Thirty-six subjects had a stable response to citalopram and remained in the continuation treatment with citalopram, 40 mg/day, for 4 months as outpatients. At the time of recovery, 32 patients gave their written informed consent before entering the 24-month maintenance period with citalopram, 20 mg/day. They were evaluated monthly by trained psychiatrists on the basis of the 21-item Hamilton Rating Scale for Depression. Every 3 months, patients were given the Sheehan Disability Scale, a self-rating instrument, to assess their psychosocial adjustment. RESULTS: No relapse was observed in the 4-month continuation period. Sixteen (50%) of 32 patients who entered the 24-month maintenance period had a new recurrence. Patients with recurrence showed a persistent moderate disability on Sheehan Disability Scale score, while no further differences were highlighted in clinical and demographic characteristics between patients with and without recurrence. CONCLUSION: In agreement with previous findings, these data suggest that a full dose of antidepressant is strongly recommended in prophylactic therapy of patients with recurrent major depression. Moreover, it appears that psychosocial impairment may increase the risk of recurrence, thus conditioning a poor outcome.     

The use of magnetic resonance imaging in multiple sclerosis treatment trials: power calculations for annual lesion load measurement

Phase III definitive treatment trials of new multiple sclerosis (MS) therapies now routinely incorporate an annual magnetic resonance imaging protocol, with change in T2-weighted brain lesion load providing an important outcome measure. To date the accepted strategy has been to perform a core imaging protocol on all patients in such studies. The aim of this study was to provide power calculations based on this MRI endpoint. Serial MRI data from 128 patients with either relapsing remitting (RR) or secondary progressive (SP) MS were used to calculate sample size requirements using a repeated measures analysis of variance design. We provide sample size calculations based on various follow-up intervals and effect sizes. Sample sizes for the SPMS cohort were substantially larger than for the RRMS group, reflecting the greater variance in lesion load changes between patients in the SPMS group. With a follow-up of 3 years, we estimate that only 12 and 33 patients per arm are needed to show stabilisation of MRI lesion load in the RRMS and SPMS groups, respectively. Our results suggest that ongoing phase III treatment trials are more than adequately powered to detect even subtle treatment effects, and indicate that incorporating measurements from longer follow-up durations increases power substantially. We conclude that an annual imaging protocol provides a robust and powerful tool for assessing effects on the radiological appearance of the disease process. Received: 11 February 1999/Received in revised form: 28 July 1999/Accepted: 10 October 1999     

Prolidase enzyme is required for extracellular matrix integrity and impacts on postnatal cerebellar cortex development

The extracellular matrix is essential for brain development, lamination, and synaptogenesis. In particular, the basement membrane below the pial meninx (pBM) is required for correct cortical development. The last step in the catabolism of the most abundant protein in pBM, collagen Type IV, requires prolidase, an exopeptidase cleaving the imidodipeptides containing pro or hyp at the C-terminal end. Mutations impairing prolidase activity lead in humans to the rare disease prolidase deficiency characterized by severe skin ulcers and mental impairment. Thus, the dark-like (dal) mouse, in which the prolidase is knocked-out, was used to investigate whether the deficiency of prolidase affects the neuronal maturation during development of a brain cortex area. Focusing on the cerebellar cortex, thinner collagen fibers and disorganized pBM were found. Aberrant cortical granule cell proliferation and migration occurred, associated to defects in brain lamination, and in particular in maturation of Purkinje neurons and formation of synaptic contacts. This study deeply elucidates a link between prolidase activity and neuronal maturation shedding new light on the molecular basis of functional aspects in the prolidase deficiency.     

Real world experience with teriflunomide in multiple sclerosis: the TER-Italy study

Journal of Neurology - To identify baseline factors associated with disease activity in patients with relapsing–remitting multiple sclerosis (RRMS) under teriflunomide treatment. This was an...     

Clinical course of central nervous system demyelinating neurological adverse events associated with anti-TNF therapy

Journal of Neurology - Previous studies have reported an association between anti-tumor necrosis factor alpha (anti-TNFα) treatment and central nervous system (CNS) events. We described eight...