Tiziana Sciarma

Attention Problems in Epilepsy: Possible Significance of the Epileptogenic Focus

Summary: Investigation of the relation between epilepsy and cognition presents serious methodologic problems because several factors may contribute to impair neuropsychological performances in epileptic persons. Benign epilepsy of childhood with rolandic paroxysmal discharges (EPR) may be a very useful model of investigation in relation to opportunity to examine subjects without brain damage, therapy, and negative environmental influences. Thus, neuropsychological dysfunction in patients with EPR may support the hypothesis that epilepsy itself plays a specific role in the genesis of cognitive disturbances. We assessed the impact of the laterality of the epileptogenic focus on cognition of children with EPR. All subjects performed a figure cancellation task, a test used to evaluate mainly attention mechanisms and abilities in processing visuospatial information. Results showed that children with right‐sided (or bilateral) focus scored worse, whereas children with left‐sided focus performed as well as the control subjects. Our data agree with those of studies suggesting that focal discharges may be related to poor cognitive performance. Evidence of a concordance between neurophysiologic and neuropsy‐chologic findings may have great practical and theoretical implications in management of epileptic patients.

Modularity of music: evidence from a case of pure amusia

A case of pure amusia in a 20 year old left handed non-professional musician is reported. The patient showed an impairment of music abilities in the presence of normal processing of speech and environmental sounds. Furthermore, whereas recognition and production of melodic sequences were grossly disturbed, both the recognition and production of rhythm patterns were preserved. This selective breakdown pattern was produced by a focal lesion in the left superior temporal gyrus. This case thus suggests that not only linguistic and musical skills, but also melodic and rhythmic processing are independent of each other. This functional dissociation in the musical domain supports the hypothesis that music components have a modular organisation. Furthermore, there is the suggestion that amusia may be produced by a lesion located strictly in one hemisphere and that the superior temporal gyrus plays a crucial part in melodic processing.

Axonal injury within language network in primary progressive aphasia.

Primary progressive aphasia (PPA) is characterized by an isolated progressive impairment of word use and comprehension reflecting the distribution of pathological processes within the left hemisphere. We used proton magnetic resonance spectroscopy (1H‐MRS) to study in vivo the integrity of axonal fibers connecting perisylvian language areas in 11 patients with PPA, 11 subjects with Alzheimers disease, and 22 controls. Brain metabolites (N‐acetylaspartate, myoinositol, choline, creatine) were measured bilaterally within a volume of interest located in the central portion of the superior longitudinal fasciculus, a long associative bundle connecting Brocas area with Wernickes area, and other language regions of the temporal lobe. In the PPA group, there was an asymmetrical N‐acetylaspartate to creatine ratio reduction compared with Alzheimers disease and controls, with greater changes on the left side. The myoinositol to creatine ratio was increased in the PPA group bilaterally compared with controls. The choline to creatine ratio did not differ among the three groups. These results indicate an asymmetrical focal axonal injury within the language network in PPA. The marked difference in the distribution of N‐acetylaspartate to creatine between PPA and Alzheimers disease suggests that proton magnetic resonance spectroscopy may help to differentiate between these two conditions. Ann Neurol 2003;53:000–000

Negative evidence of difference between right- and left-handers in interhemispheric transfer of information

The present study has been designed to investigate the relationship between handedness and callosal function. Based on the previous finding of a greater anatomical connection between the hemispheres in left-handers than in right-handers and in order to test the possibility of greater functional communication, the efficiency of interhemispheric transfer of information has been measured using a finger localization task. Comparison of two groups of male right-handed and left-handed subjects shows no difference in the efficiency of interhemispheric transfer of information.

Rationale and design of an independent randomised controlled trial evaluating the effectiveness of aripiprazole or haloperidol in combination with clozapine for treatment-resistant schizophrenia

BackgroundOne third to two thirds of people with schizophrenia have persistent psychotic symptoms despite clozapine treatment. Under real-world circumstances, the need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies. In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy, despite the lack of robust evidence of its efficacy, we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematically provided and evaluated within the context of a pragmatic, multicentre, independent randomised study.Methods/DesignThe principal clinical question to be answered by the present project is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared with combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time. This project is a prospective, multicentre, randomized, parallel-group, superiority trial that follow patients over a period of 12 months. Withdrawal from allocated treatment within 3 months is the primary outcome.DiscussionThe implementation of the protocol presented here shows that it is possible to create a network of community psychiatric services that accept the idea of using their everyday clinical practice to produce randomised knowledge. The employed pragmatic attitude allowed to randomly allocate more than 100 individuals, which means that this study is the largest antipsychotic combination trial conducted so far in Western countries. We expect that the current project, by generating evidence on whether it is clinically useful to combine clozapine with aripiprazole rather than with haloperidol, provides physicians with a solid evidence base to be directly applied in the routine care of patients with schizophrenia.Trial RegistrationClincaltrials.gov Identifier: NCT00395915

Cerebral Organization for Language in Down's Syndrome Patients

Language lateralization was assessed with a dual task procedure in 10 male right-handed patients with Downs Syndrome and relatively preserved linguistic skills. Their performance was compared with that of two control groups, with and without mental retardation, matched with Downs Syndrome individuals for sex, handedness and I.Q. Results did not support the hypothesis that mental retardation is related to specific pattern of cerebral lateralization.

Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: a protocol for a randomised, independent, pragmatic, multicentre, parallel-group, superiority clinical trial.

BackgroundData on therapeutic interventions following deliberate self harm (DSH) in patients with treatment-resistant depression (TRD) are very scant and there is no unanimous consensus on the best pharmacological option for these patients. There is some evidence that lithium treatment might be effective in reducing the risk of completed suicide in adult patients with unipolar affective disorders, however no clear cut results have been found so far. The primary aim of the present study is to assess whether adding lithium to standard therapy is an effective treatment strategy to reduce the risk of suicidal behaviour in long term treatment of people with TRD and previous history of DSH.Methods/DesignWe will carry out a randomised, parallel group, assessor-blinded superiority clinical trial. Adults with a diagnosis of major depression, an episode of DSH in the previous 12 months and inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode will be allocated to add lithium to current therapy (intervention arm) or not (control arm). Following randomisation, treatment is to be taken daily for 1 year unless some clear reason to stop develops. Suicide completion and acts of DSH during the 12 months of follow-up will constitute the composite primary outcome. To preserve outcome assessor blindness, an independent adjudicating committee, blind to treatment allocation, will anonymously review all outcome events.DiscussionThe results of this study should indicate whether lithium treatment is associated with lower risk of completed suicide and DSH in adult patients with treatment resistant unipolar depression, who recently attempted suicide.Trial registrationClinicalTrials.gov identifier: NCT00927550

Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: results and lessons of an underpowered randomised clinical trial

BackgroundAs lithium treatment might be effective in reducing the risk of deliberate self-harm (DSH) in adult patients with unipolar affective disorders, we designed a pragmatic randomised trial to assess its efficacy in more than 200 patients with treatment-resistant depression. However, we randomised 56 patients only. The aim of this report is therefore twofold: first, to disseminate the results of this underpowered study which may be incorporated into future meta-analytical reviews; second, to analyse some critical aspects of the study which might explain failure to reach the target sample size.MethodsWe carried out a randomised, parallel group, assessor-blinded superiority clinical trial. Adults with a diagnosis of major depression, an episode of DSH in the previous 12 months and inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode were allocated to add lithium to usual care (intervention arm) versus usual care alone (control arm). Suicide completion and acts of DSH during the 12 months of follow-up constituted the composite primary outcome.ResultsOf 58 patients screened for inclusion, 29 were allocated to lithium plus usual care and 27 were assigned to usual care without lithium. Six patients in the lithium plus usual care group and seven in the usual care group committed acts of DSH during the follow-up phase. The survival probability did not differ between the two treatment arms (Chi2 = 0.17, p =0.676). With regard to changes in the severity of depressive symptomatology from baseline to endpoint, no significant differences were detected.ConclusionsThe present study failed to achieve the minimum sample size needed to detect a clinically meaningful difference between the two treatment arms. Consequently, the finding that lithium, in addition to usual care, did not exert a positive effect in terms of reduction of DSH after 12 months of follow-up is likely due to the lack of sufficient statistical power to detect a difference, if a difference existed. The dissemination of the results of this underpowered study will inform future meta-analytical reviews on lithium and suicide-related outcomes.Trial registrationClinicalTrials.gov identifier: NCT00927550

Selective bilateral lesion of the globus pallidus: Ten-year follow-up of memory impairment and frontal symptomatology

A case of loss of psychic self-activation (LPSA) and serious amnesia, followed for a period of ten years, is reported. MRI examination documents a selective bilateral lesion of the globus pallidus. This clinical picture, which evokes a cognitive and behavioral deficit of frontal lobe lesions, is attributed to a dysfunction of the frontal cortical area as a result of the breakdown of the frontostriatal circuits.SommarioAllo scopo di indagare il ruolo dei gangli della base nelle funzioni cognitive e comportamentali, riportiamo il caso di un paziente che presenta un quadro clinico di Perdita di Auto-Attivazione Psichica ed una grave amnesia, seguita longitudinalmente per 10 anni. La RMN mostra una lesione bilaterale del globo pallido. Il quadro clinico evoca i disturbi cognitivi e comportamentali delle lesioni del lobo frontale e pare ascrivibile ad una disconnessione di tali strutture per interruzione dei circuiti frontostriatali.