Frovatriptan versus zolmitriptan for the acute treatment of migraine with aura: a subgroup analysis of a double-blind,randomized, multicenter,Italian study

Migraine with aura affects ~20–30 % of migraineurs and it is much less common than migraine without aura. The aim of this study was to compare the efficacy of frovatriptan 2.5 mg and zolmitriptan 2.5 mg in the treatment of migraine with aura. Analysis was carried out in a subset of 18 subjects with migraine with aura (HIS criteria) out of the 107 enrolled in a multicenter, randomized, double-blind, cross-over study. According to the study design, each patient had to treat three episodes of migraine in no more than 3 months with one drug, before switching to the other treatment. The rate of pain-free episodes at 2 h was significantly (p < 0.05) larger under frovatriptan (45.8 %) than under zolmitriptan (16.7 %). Pain free at 4 h, pain relief at 2 and 4 h and recurrent episodes were similar between the two treatments, while sustained pain-free episode was significantly (p < 0.05) more frequent during frovatriptan treatment (33.3 vs. 8.3 % zolmitriptan). Our study suggests that frovatriptan is superior to zolmitriptan in the immediate treatment of patients with migraine with aura, and it is capable of maintaining its acute analgesic effect over 48 h.     

Pure topographical disorientation in a patient with right occipito-temporal lesion

We describe a patient who presented with a pure topographical disorientation after a stroke involving the right mesial occipito-temporal cortex. He could not point to external unseen landmarks or draw a map of his city, while he could recognize landmarks, and judge the distance, and describe the route between pairs of landmarks of the same city. He underwent standardized cognitive tests, and 6 tasks were used to assess a topographical orientation route-survey. This study provides evidence that topographical disorientation can be subdivided into very specific components. The results suggest that one of these components might refer to the processing of an allocentric map separable from the representation of route knowledge.     

Schwann-like adult stem cells derived from bone marrow and adipose tissue express γ-aminobutyric acid type B receptors

γ-Aminobutyric acid type B receptors (GABA-B) are expressed in glial cells of the central and peripheral nervous systems, and recent evidence has shown their importance in modulating physiological parameters of Schwann cell (SC). SC play essential roles in peripheral nerve regeneration, but several drawbacks prevent their use for nerve repair. Adult stem cells from adipose tissue (ASC) or bone marrow (BM-MSC) can be differentiated into an SC-like phenotype and used as SC replacements. The aim of this study was to investigate GABA-B receptor functional expression in differentiated stem cells by assessing the similarity to SC. By means of RT-PCR and Western blot methodologies, BM-MSC and ASC were found to express both GABA-B1 and GABA-B2 receptor subunits. The expression levels of GABA-B1b and GABA-B2 receptors were influenced by SC-like differentiation, as shown by Western blot studies. GABA-B receptor stimulation with baclofen reduced the proliferation rate of SC and differentiated ASC (dASC) but not that of dBM-MSC. In conclusion, both of the subunits that assemble into a functional GABA-B receptor are present in differentiated stem cells. Furthermore, GABA-B receptors in dASC are functionally active, regulating a key process such as proliferation. The presence of functional GABA-B receptors on differentiated stem cells opens new opportunities for a possible pharmacological modulation of their physiology and phenotype.     

Genetic variation in the schizophrenia‐risk gene neuregulin 1 correlates with brain activation and impaired speech production in a verbal fluency task in healthy individuals

Impaired performance in verbal fluency tasks is an often replicated finding in schizophrenia. In functional neuroimaging studies, this dysfunction has been linked to signal changes in prefrontal and temporal areas. Since schizophrenia has a high heritability, it is of interest whether susceptibility genes for the disorder, such as NRG1, modulate verbal fluency performance and its neural correlates. Four hundred twenty‐nine healthy individuals performed a semantic and a lexical verbal fluency task. A subsample of 85 subjects performed an overt semantic verbal fluency task while brain activation was measured with functional magnetic resonance imaging (MRI). NRG1 (SNP8NRG221533; rs35753505) status was determined and correlated with verbal fluency performance and brain activation. For the behavioral measure, there was a linear effect of NRG1 status on semantic but not on lexical verbal fluency. Performance decreased with number of risk‐alleles. In the fMRI experiment, decreased activation in the left inferior frontal and the right middle temporal gyri as well as the anterior cingulate gyrus was correlated with the number of risk‐alleles in the semantic verbal fluency task. NRG1 genotype does influence language production on a semantic level in conjunction with the underlying neural systems. These findings are in line with results of studies in schizophrenia and may explain some of the cognitive and brain activation variation found in the disorder. More generally, NRG1 might be one of several genes that influence semantic language capacities. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Anaesthetic implications of Costello syndrome

Costello syndrome is a disorder that primarily involves ectodermal tissues and is characterized by mental and growth retardation, distinctive coarse facies, redundant skin (neck, palms and soles), and papillomata (perioral, nasal and anal). Of primary concern to anaesthesiologists are potential airway difficulties related a short neck, macroglossia, hypertrophied tonsillar and supraglottic tissues, laryngeal papillomata and choanal atresia. A significant percentage of patients also have cardiac involvement which may manifest as congenital heart defects, arrhythmias, valvular dysfunction, or hypertrophic cardiomyopathy. Central nervous system involvement includes developmental delay and seizure disorders while endocrine abnormalities have been reported including hypothalamic-pituitary dysfunction resulting in hypopituitarism, hypothyroidism, and hypoadrenalism. The authors present a 2-year old child with Costello syndrome who required anaesthesia for direct laryngoscopy, rigid bronchoscopy, bilateral pressure equalization tubes and tonsillectomy. The perioperative implications of the syndrome are discussed.     

Language disturbances associated to insular and entorhinal damage: study of a patient affected by herpetic encephalitis

The herpes simplex encephalitis (HSE) patient reported in this study presented a left hemisphere lesion limited to the left insula and to the left anterior parahippocampal region. The patient was followed longitudinally, focusing on the aphasia type, the language recovery, and the integrity of semantic representations. The language deficit was of fluent type, without phonological impairment, and showed a good but incomplete recovery after four months. A semantic impairment was possible at the onset, but recovered quickly and did not present a disproportionate impairment of living categories.     

Can impairment-focused therapy change the everyday conversations of people with aphasia? A review of the literature and future directions

Background: The ultimate goal in any programme of aphasia rehabilitation is that behaviours targeted in therapy will generalise to everyday use for people with aphasia (PWA). The pervasiveness of conversation in everyday life has undoubtedly contributed to the recent interest in aphasiology regarding how we facilitate, and capture evidence of, change in conversation following therapy. Given the rich nature of conversation data, various analytical approaches have been utilised within impairment-focused therapy studies; however, much of this work has been carried out in isolation from other methodologies such as conversation analysis (CA)—a field which has historically concerned itself with conversation data. The result is a growing literature base which is dispersed in nature. For clinicians who are faced with the daily challenge of therapeutic management for a diverse population of PWA the literature on generalising therapy gains to everyday conversation may be too unwieldy to be of benefit to current clinical practice.

Aims: This paper aims to synthesise and critically review key papers from impairment-focused studies which have investigated the impact of therapy on the conversations of PWA. For the purposes of this review, conversation is defined as a dialogue between the person with aphasia and a conversation partner.

Main Contribution: First, the motivation to investigate conversation within aphasia assessment is discussed, with consideration of how conversation differs from, but ultimately complements, other forms of language assessment. Following this, five impairment therapy studies will provide a platform for discussion of methodological issues and analytical approaches relating to conversation data. Finally, consideration is given to how researchers and clinicians may build on current literature to develop the use of conversation as an outcome measure in aphasia intervention. Where appropriate, insights are drawn from interaction-focused therapy studies regarding the collection and analysis of conversation data.

Conclusions: There is emerging evidence that impairment-focused therapy can impact on the conversations of PWA. While these early findings are promising, investigations have been limited to naming therapies and the methods of data collection used have implications for ecological validity. Incorporating particular elements of interaction-focused approaches may help to inform data collection, investigations of therapy outcome, and issues of candidacy for specific treatments. Furthermore, combining therapeutic and analytical approaches is likely to be more closely akin to the clinical reality of aphasia intervention, where clinicians are likely to use all resources at their disposal in the rehabilitation of a speaker with aphasia.     

No influence of brain-derived neurotrophic factor (BDNF) polymorphisms on treatment response in a naturalistic sample of patients with major depression

The role of the brain-derived neurotrophic factor (BDNF) in the pathophysiology of major depressive disorder (MDD) remains to be elucidated. Recent post hoc analyses indicated a potential association of three polymorphisms in the BDNF gene with worse treatment outcome in patients with the subtype of melancholic depression. We aimed at replicating these findings in a German naturalistic multicenter follow-up. Three polymorphisms in the BDNF gene (rs7103411, rs6265 (Val66Met) and rs7124442) were genotyped in 324 patients with MDD and 470 healthy controls. We applied univariate tests and logistic regression models stratifying for depression subtype and gender. The three polymorphisms were not associated with MDD as diagnosis. Further, no associations were found in univariate tests. With logistic regression, we only found a tendency towards an association of the rs6265 (Val66Met) polymorphism with overall response to treatment (response rates: GG (val/val) < GA (val/met) < AA (met/met); p = 0.0129) and some gender differences for the rs6265 (Val66Met) and rs7103411 polymorphisms. Treatment outcome stratified for subtypes of depression did not differ significantly between the investigated polymorphisms or using haplotype analyses. However, results showed a tendency towards significance. At this stage, we cannot support an influence of these three polymorphisms. Further studies in larger patient samples to increase sample sizes of subgroups are warranted.     

The p.A382T TARDBP gene mutation in Sardinian patients affected by Parkinson's disease and other degenerative parkinsonisms

Based on our previous finding of the p.A382T founder mutation in ALS patients with concomitant parkinsonism in the Sardinian population, we hypothesized that the same variant may underlie Parkinson's disease (PD) and/or other forms of degenerative parkinsonism on this Mediterranean island. We screened a cohort of 611 patients with PD (544 cases) and other forms of degenerative parkinsonism (67 cases) and 604 unrelated controls for the c.1144G > A (p.A382T) missense mutation of the TARDBP gene. The p.A382T mutation was identified in nine patients with parkinsonism. Of these, five (0.9 % of PD patients) presented a typical PD (two with familiar forms), while four patients (6.0 % of all other forms of parkinsonism) presented a peculiar clinical presentation quite different from classical atypical parkinsonism with an overlap of extrapyramidal–pyramidal–cognitive clinical signs. The mutation was found in eight Sardinian controls (1.3 %) consistent with a founder mutation in the island population. Our findings suggest that the clinical presentation of the p.A382T TARDBP gene mutation may include forms of parkinsonism in which the extrapyramidal signs are the crucial core of the disease at onset. These forms can present PSP or CBD-like clinical signs, with bulbar and/or extrabulbar pyramidal signs and cognitive impairment. No evidence of association has been found between TARDBP gene mutation and typical PD.