Multi-center observational study on occurrence and related clinical factors of neurogenic heterotopic ossification in patients with disorders of consciousness.

Aims: to assess occurrence and clinical correlates of neurogenic heterotopic ossifications (NHO) in patients with prolonged disorder of consciousness (DoC).Design: multi-center cross-sectional observational study.Setting: 23 intensive neurorehabilitation units.Subjects: 287 patients with prolonged disorder of consciousness (DoC; 150 in vegetative state, VS, and 128 in minimally conscious state, MCS) of different etiology (vascular = 125, traumatic = 83, anoxic = 56, others = 14).Main Measures: clinical evidence of NHO confirmed by standard radiological and/or sonographic evaluation; Coma Recovery Scale-Revised; Disability Rating Scale (DRS); Early Rehabilitation Barthel Index; presence of ventilator support, spasticity, bone fractures and paroxysmal sympathetic hyperactivity.Results: 31 patients (11.2%) presented NHO. Univariate analyses showed that NHO was associated with VS diagnosis, traumatic etiology, high DRS category and total score, and high occurrence of limb spasticity and bone fractures. A cluster-corrected binary logistic regression model (excluding spasticity available in a subset of patients) showed that only lower DRS total score and presence of bone fractures were independently associated with NHO.Conclusions: NHO are relatively frequent in patients with DoC, and are independently associated with functional disability, bone fractures and spasticity. These findings contribute to identifying patients with DoC prone to develop NHO and requiring special interventions to improve functional recovery.

Multi-center study on overall clinical complexity of patients with prolonged disorders of consciousness of different etiologies.

Aim: to assess overall clinical complexity of patients with acquired disorders of consciousness (DoC) in vegetative state/unresponsive wakefulness syndrome (VS/UWS) vs. minimally conscious state- MCS) and in different etiologies..Design: Multi-center cross-sectional observational study.Setting: 23 intensive neurorehabilitation units.Subjects: 264 patients with DoC in the post-acute phase: VS/UWS = 141, and MCS = 123 due to vascular (n = 125), traumatic (n = 83) or anoxic (n = 56) brain injury.Main Measures: Coma Recovery Scale-Revised, and Disability Rating Scale (DRS); presence of medical devices (e.g., for eating or breathing); occurrence and severity of medical complications.Results: patients in DoC, and particularly those in VS/UWS, showed severe overall clinical complexity. Anoxic patients had higher overall clinical complexity, lower level of responsiveness/consciousness, higher functional disability, and higher needs of medical devices. Vascular patients had worse premorbid clinical comorbidities. The two etiologies showed a comparable rate of MC, higher than that observed in traumatic etiology.Conclusion: overall clinical complexity is significantly higher in VS/UWS than in MCS, and in non-traumatic vs. traumatic etiology. These findings could explain the worse clinical evolution reported in anoxic and vascular etiologies and in VS/UWS patients and contribute to plan patient-tailored care and rehabilitation programmes.

Child abuse associates with an imbalance of oligodendrocyte-lineage cells in ventromedial prefrontal white matter.

Child abuse (CA) is a major risk factor for depression, and strongly associates with suicidal behavior during adulthood. Neuroimaging studies have reported widespread changes in white matter integrity and brain connectivity in subjects with a history of CA. Although such observations could reflect changes in myelin and oligodendrocyte function, their cellular underpinnings have never been addressed. Using postmortem brain samples from depressed suicides with or without history of CA and matched controls (18 per group), we aimed to characterize the effects of CA on oligodendrocyte-lineage (OL) cells in the ventromedial prefrontal white matter. Using immunoblotting, double-labeling immunofluorescence and stereological estimates of stage-specific markers, we found that CA is associated with increased numbers of mature myelinating oligodendrocytes, accompanied by decreased numbers of more immature OL cells. This was paralleled by an increased expression of transcription factor MASH1, which is involved in the terminal differentiation of the OL, suggesting that CA may trigger an increased maturation, or bias the populations of OL cells toward a more mature phenotype. Some of these effects, which were absent in the brain of depressed suicides with no history of CA, were also found to recover with age, suggesting that changes in the balance of the OL may reflect a transient adaptive mechanism triggered by early-life adversity. In conclusion, our results indicate that CA in depressed suicides is associated with an imbalance of the OL in the ventromedial prefrontal white matter, an effect that could lead to myelin remodeling and long-term connectivity changes within the limbic network.

Designing a national combined reporting form for adverse drug reactions and medication errors.

The Maltese Medicines Authority was tasked with developing a reporting form that captures high-quality case information on adverse drug reactions (ADRs) and medication errors in order to fulfil its public-health obligations set by the European Union (EU) legislation on pharmacovigilance. This paper describes the process of introducing the first combined ADR/medication error reporting form in the EU for health-care professionals, the analysis of reports generated by it and the promotion of the system. A review of existing ADR forms was carried out and recommendations from the European Medicines Agency and World Health Organization audits integrated. A new, combined ADR/medication error reporting form was developed and pilot tested based on case studies. The Authority's quality system (ISO 9001 certified) was redesigned and a promotion strategy was deployed. The process used in Malta can be useful for countries that need to develop systems relative to ADR/medication error reporting and to improve the quality of data capture within their systems.

Italian standardization of the Apples Cancellation Test.

Hemispatial neglect due to right parieto-temporo-frontal lesions has a negative impact on the success of rehabilitation, resulting in poor functional gain. Recent research has shown that different types of neglect can impact in a different way on rehabilitation outcomes. The availability of a sensitive test, useful for distinguishing egocentric and allocentric forms of neglect, may be clinically important as all current clinical instruments fail to distinguish between these forms of disturbance, yet they differentially predict outcome. The Apples Test is a new instrument useful to evaluate both egocentric and allocentric forms of neglect. In order to establish Italian norms for this diagnostic instrument the test was administered to a sample of 412 healthy people of both genders (201 M and 211 F), aged from 20 to 80 years enrolled from 14 different rehabilitation centers in Italy. Based on the data, we established pathological performance cut-offs for the accuracy score (total omission errors), the asymmetry score for egocentric neglect (omission error difference), the asymmetry score for allocentric neglect (commission error difference) and execution time. The usefulness of the Apples Test for diagnostic purposes is illustrated by presenting three patients with different forms of neglect (egocentric, allocentric and mixed neglect).

Recommendations for clinical practice and research in severe brain injury in intensive rehabilitation: the Italian Consensus Conference.

The paper reports the final statements of the jury of a National Consensus Conference organized in November 2010 at Salsomaggiore (Parma) to draw up recommendations on the rehabilitation programs for acquired brain injury (sABI) patients in the intensive hospital phase. Because of the few clinical studies of good quality found by means of the literature research we choose a mixed approach: a systematic review of the published studies and a consensus conference in order to obtain recommendations that come from the clinical evidence and the expert opinion. The final recommendations of the jury, based on the best available evidence combined with clinical expertise and the experience of persons with disabilities and other stakeholders, cover 13 topics: 1) Management of paroxysmal manifestations (sympathetic storms); 2) management of neuroendocrine problems; 3) nutrition; 4) swallowing; 5) ventilation/respiration, 6) clinical and instrument diagnosis and prognosis of vegetative state (VS) and minimally conscious state (MCS), 7) rehabilitative and pharmacological facilitation of renewed contact with surroundings; 8) neurosurgical complications and hydrocephalus; 9) sensorimotor impairment and disability; 10) rehabilitation methods; 11) assessment and treatment of cognitive-behavioural impairment and disability; 12) methodology and organization of care; 13) involving family and caregivers in rehabilitation.

An Italian multicentre validation study of the coma recovery scale-revised.

BACKGROUND: Rate of misdiagnosis of disorders of consciousness (DoC) can be reduced by employing validated clinical diagnostic tools, such as the Coma Recovery Scale-Revised (CRS-R). An Italian version of the CRS-R has been recently developed, but its applicability across different clinical settings, and its concurrent validity and diagnostic sensitivity have not been estimated yet. AIM: To perform a multicentre validation study of the Italian version of the Coma Recovery Scale-Revised (CRS-R). DESIGN: Analysis of inter-rater reliability, concurrent validity and diagnostic sensitivity of the scale. SETTING: One Intensive Care Unit, 8 Post-acute rehabilitation centres and 2 Long-term facilities POPULATION: Twenty-seven professionals (physicians, N.=11; psychologists, N.=5; physiotherapists, N.=3; speech therapists, N.=6; nurses, N.=2) from 11 Italian Centres. METHODS: CRS-R and Disability Rating Scale (DRS) applied to 122 patients with clinical diagnosis of Vegetative State (VS) or Minimally Conscious State (MCS). RESULTS: CRS-R has good-to-excellent inter-rater reliability for all subscales, particularly for the communication subscale. The Italian version of the CRS-R showed a high sensitivity and specificity in detecting MCS with reference to clinical consensus diagnosis. The CRS-R showed good concurrent validity with the Disability Rating Scale, which had very low specificity with reference to clinical consensus diagnosis. CONCLUSIONS: The Italian version of the CRS-R is a valid scale for use from the sub-acute to chronic stages of DoC. It can be administered reliably by all members of the rehabilitation team with different specialties, levels of experience and settings. CLINICAL REHABILITATION IMPACT: The present study promote use of the Italian version of the CRS-R to improve diagnosis of DoC patients, and plan tailored rehabilitation treatment.

Designing a national combined reporting form for adverse drug reactions and medication errors

تم تكليف هيئة الأدوية المالطية بإعداد استمارة إبلاغ تلتقط معلومات عالية الجودة عن حالات التفاعات الدوائية الضارة وأخطاء المداواة لكي تفي الهيئة بالتزاماتها في مجال الصحة العامة التي حددتها تشريعات الاتحاد الأوروبي بخصوص التيقظ الدوائي. ويقدِّم هذا البحث وصفاً لعملية تقديم أول استمارة إباغ مشركة عن التفاعات الدوائية الضارة وأخطاء المداواة في الاتحاد الأوروبي للعاملن في مجال الرعاية الصحية، ولتحليل التقارير الناتجة عنها، ولتعزيز النظام الصحي. تم القيام بمراجعة الاستمارات الحالية الخاصة بالتفاعات الدوائية الضارة وإدراج التوصيات الصادرة عن عمليات التدقيق التي قامت بها وكالة الأدويةالأوروبية ومنظمة الصحة العالمية. ومن ثمّ تم إعداد استمارة جديدة مشركة للإباغ عن التفاعات الدوائية الضارة وأخطاء المداواة، وتم اختبارهاتجريبياً استناداً إلى دراسات حالات. وأعيد تصميم نظام جودة الهيئة إيزو 9001 المعتمد، ثم نظمت اسراتيجية ترويجية. إن الطريقة التي استخدمت في مالطا يمكن أن تفيد البلدان التي تحتاج إلى إعداد نظم تتعلق بالإباغ عن التفاعات الدوائية الضارة وأخطاء المداواة، وإلى تحسن جودة التقاط البيانات داخل نظمها

The Maltese Medicines Authority was tasked with developing a reporting form that captures highquality case information on adverse drug reactions (ADRs) and medication errors in order to fulfil its public-health obligations set by the European Union (EU) legislation on pharmacovigilance. This paper describes the processof introducing the first combined ADR/medication error reporting form in the EU for health-care professionals, the analysis of reports generated by it and the promotion of the system. A review of existing ADR forms was carried out and recommendations from the European Medicines Agency and World Health Organization auditsintegrated. A new, combined ADR/medication error reporting form was developed and pilot tested based on case studies. The Authority’s quality system (ISO 9001 certified) was redesigned and a promotion strategy was deployed. The process used in Malta can be useful for countries that need to develop systems relative to ADR/medication error reporting and to improve the quality of data capture within their systems.

L'Autorité maltaise pour les médicaments (Maltese Medicines Authority) a été chargée d'élaborer un formulaire de notification visant à recueillir des informations de haute qualité sur les réactions indésirables aux médicaments et les erreurs de médication afin de satisfaire à ses obligations de santé publique définies par lalégislation de l'Union européenne sur la pharmacovigilance. Le présent article décrit le processus d'introduction du premier formulaire de notification combinant les réactions indésirables aux médicaments et les erreurs de médication pour les professionnels des soins de santé dans l'Union européenne, l'analyse des rapportsissus de ce processus et la promotion de ce système. Les formulaires de notification des réactions indésirables aux médicaments existants ont été passés en revue et les recommandations de l'Agence européenne des médicaments ainsi que des audits de l'Organisation mondiale de la Santé ont été intégrés. Un nouveau formulairede notification combinant les réactions indésirables aux médicaments et les erreurs de médication a été élaboré puis soumis à un essai pilote dans des études de cas. Le système qualité de l'Autorité maltaise (certifié ISO 9001) a été remanié et une stratégie de promotion a été déployée. Le processus appliqué à Malte peut être utile à d'autres pays qui ont besoin de mettre au point des systèmes de notification des réactions indésirables aux médicaments et des erreurs de médication et souhaitent améliorer la qualité du` recueil des données au sein de leurs systèmes.

Neurogenesis along the septo-temporal axis of the hippocampus: are depression and the action of antidepressants region-specific?

In recent years, both major depression and antidepressant therapy have been linked to adult hippocampal neurogenesis. The hippocampus is not a homogeneous brain area, and a converging body of evidence indicates a functional dissociation along its septo-temporal axis, the dorsal part being involved more in learning/memory and spatial navigation, while the ventral sub-region is linked more to emotional behavior and regulation of the neuroendocrine stress axis. Research has therefore been conducted in an attempt to relate effects of models of depression and of antidepressant therapies to adult neurogenesis along the septo-temporal axis of the hippocampus. The present paper reviews the current literature addressing this question and discusses the possible mechanisms involved and the functional significance of such regional effects. This review shows that animal models of depression elicit an effect restricted to the ventral hippocampus more frequently than a dorsal-specific effect. However, this is also stage specific, and concerns neurogenesis, rather than cell proliferation or survival. Surprisingly, the same does not apply regarding the effects of selective serotonin re-uptake inhibitors that act in a more uniform way on dorsal and ventral adult neurogenesis in most studies. Some recently introduced clinical compounds (e.g., agomelatine) or putative antidepressants have a specific action on the ventral sub-region, indicating that an action restricted to this part of the brain may be sufficient to achieve remission. Finally, non-pharmacological manipulations that are also endowed with antidepressant effects, such as environmental enrichment or physical exercise, also act on both subdivisions, although some studies pointed to specificity of dorsal neurogenesis. The different treatments, acting either on the dorsal or on the ventral sub-regions, could promote recovery by improving either ventral- or dorsal-related functions, both contributing in a different way to treatment efficacy.

The Italian National Registry of severe acquired brain injury: epidemiological, clinical and functional data of 1469 patients.

BACKGROUND: The lack of knowledge about epidemiological and clinical data of patients with Acquired Brain Injury (ABI) admitted to Rehabilitation facilities in Italy led to the creation, in June 2008, of a data collection on-line registry. AIM: To collect epidemiological and clinical data and to evaluate functional outcome of patients with severe traumatic and non-traumatic ABI admitted to Rehabilitation facilities in Italy between June 2008 and December 2011 and to compare data of patients with ABI of different aetiologies. DESIGN: Observational retrospective study. SETTING: The study involved 29 Italian Rehabilitation facilities. POPULATION: The study enrolled 1469 patients with severe traumatic (TBI) and non-traumatic ABI (NTBI). METHODS: Data collected included demographic (number of patients with TBI and NTBI, gender, age) and clinical characteristics (provenience, number of days elapsed between onset and rehabilitation admission, rehabilitation length of stay, discharge destination, death and vegetative state diagnosis, presence of percutaneous endoscopic gastrostomy, tracheostomy, pressure sores and paraosteoarthropathies). Functional outcome was evaluated using the Disability Rating Scale. RESULTS: Of the whole population studied, 44.31% and 55.69% patients had suffered a TBI and a NTBI, respectively. In the NTBI group 40.09% had a cerebrovascular injury, 12.04% an anoxic brain damage, 3.6% had a brain injury of other causes. The mean age was 43.67 and 56.68 for subjects with TBI and NTBI, respectively. Patients with TBI showed a lower onset-admission interval (OAI), compared with NTBI group; no difference in rehabilitation length of stay (LOS) was recorded between groups. Patients with TBI presented a lower DRS score at admission and discharge and returned home more frequently than NTBI group. CONCLUSIONS: The creation of a National registry allows the collection of data about patients with ABI in order to study the clinical course, the functional outcome and to establish a basis for comparison with other data sources. Clinical Rehabilitation Impact. Data collection could be useful in the evaluation and planning of rehabilitation pathways, and to assess the allocation of healthcare and rehabilitative resources.

Rehabilitation of acquired brain injuries: a multicentric prospective survey.

BACKGROUND: The rehabilitation of the persons with Severe Acquired Brain Injury (ABI) is an important concern to be approached with a comprehensive program aimed to improve the recovery of patients.The efficacy of an early and intensive rehabilitation program has been shown in large number of studies. Few studies focused on the prevalence of TBI and the data are often extrapolated in indirect ways. AIM: An analysis of the demographic characteristics of the population included in the GISCAR (Gruppo Italiano per lo Studio delle Gravi Cerebrolesioni Acquisite e Riabilitazione- Italian Group for the Study of the severe ABI) database, type and conditions associated to the index event; the treatment administered during hospitalization; and the prognosis according to outcome measures. DESIGN: The study was an observational prospective survey looking at management of ABI (both traumatic and non-traumatic). SETTING: In hospital rehabilitation. POPULATION: Patients consecutively admitted in each of the 52 GISCAR centres. METHODS: Every centre included a consecutive cohort and recorded demographic data and index event characteristics. RESULTS: In the study population were included 2626 subjects suffering of a severe ABI. The difference of length of stay (LOS) was significantly different with 67.5 days for traumatic patients compared to the 80 days of non traumatic ones. In the study population the probability of discharge at home is significantly greater for the traumatic condition (odds ratio 0,4587; CI 0.3671-0.5731). The overall benefit of the rehabilitative treatment was encountered in a net gain in all disability scores taken into account: LCF classes; DRS as well as GOS scores. At discharge the main destination for severe ABI patients was home (67.2%). CONCLUSIONS: A large number of patients admitted in Italian rehabilitative facilities for a severe ABI suffered from a TBI, more often these subjects were young male victims of road accident. The majority of subjects during the rehabilitative hospitalization demonstrated a significant recovery. CLINICAL REHABILITATION IMPACT: Considering the evidence of an early treatment benefit the delay ofthe rehabilitation program start is far from being satisfactory. The high frequency of the home discharge indicate a good compliance of national family network.

Antidepressants recruit new neurons to improve stress response regulation.

Recent research suggests an involvement of hippocampal neurogenesis in behavioral effects of antidepressants. However, the precise mechanisms through which newborn granule neurons might influence the antidepressant response remain elusive. Here, we demonstrate that unpredictable chronic mild stress in mice not only reduces hippocampal neurogenesis, but also dampens the relationship between hippocampus and the main stress hormone system, the hypothalamo-pituitary-adrenal (HPA) axis. Moreover, this relationship is restored by treatment with the antidepressant fluoxetine, in a neurogenesis-dependent manner. Specifically, chronic stress severely impairs HPA axis activity, the ability of hippocampus to modulate downstream brain areas involved in the stress response, the sensitivity of the hippocampal granule cell network to novelty/glucocorticoid effects and the hippocampus-dependent negative feedback of the HPA axis. Remarkably, we revealed that, although ablation of hippocampal neurogenesis alone does not impair HPA axis activity, the ability of fluoxetine to restore hippocampal regulation of the HPA axis under chronic stress conditions, occurs only in the presence of an intact neurogenic niche. These findings provide a mechanistic framework for understanding how adult-generated new neurons influence the response to antidepressants. We suggest that newly generated neurons may facilitate stress integration and that, during chronic stress or depression, enhancing neurogenesis enables a dysfunctional hippocampus to restore the central control on stress response systems, then allowing recovery.

Open questions in current models of antidepressant action.

Research on depression and antidepressant drugs is necessary, as many patients display poor response to therapy. Different symptomatic and pathophysiological features have been proposed as end points of the depressive phenotype and of the antidepressant action, including anhedonia, depressed mood, alterations in morphology and activity of some brain areas (amygdala, nucleus accumbens, hippocampus, prefrontal cortex and cingulate cortex), modifications in the connectivity between brain structures, changes in neurotransmitters (serotonin, noradrenaline, glutamate and neuropeptides), brain plasticity (neurogenesis, neurotrophins) and abnormal function of the hypothalamic-pituitary adrenal axis. However, few models have been proposed to describe how these end points could induce the depressive phenotype and are involved in the mechanism of action of antidepressants. Here we propose a connectionist-inspired network of depression and antidepressant action, in which the different aetiological factors participating in the release of a depressive episode are represented by input nodes, the different symptomatic as well as pathophysiological end points are represented by an intermediate layer, and the onset of depression or of comorbid disease is represented by the output node. The occurrence of depression and the mechanism of the antidepressant action thus depend upon the weight of the interactions between the different end points, none of them being per se crucial to the onset of a depressive phenotype or to the antidepressant action. This model is heuristic to draw future lines of research concerning new antidepressant therapies, designing new animal models of depression and for a better understanding of the depressive pathology and of its comorbid pathology such as anxiety disorders.

The effects of traumatic brain injury on patients and their families. A follow-up study.

AIM: With this study we wanted to verify whether the same uneasiness elements as those described by numerous previous studies also existed in an Italian sample of traumatic brain-injured (TBI) patients. METHODS: A follow-up investigation was conducted on a sample of 16 subjects who had suffered severe TBI 5 to 10 years earlier. Based on series of neuropsychological tests, the patients' levels of remaining autonomous function were assessed. For each patient, a family reference person was identified with a semistructured interview to define how they dealt with the consequences of the trauma within the familial nucleus, what motivated their choices, the social outcome of the familial nucleus, the behavioral outcome, and the social- and work-related outcomes of the patient. The caregiver's current emotions were also analyzed. RESULTS: The study results confirmed that the family felt isolated from the social groups it used to belong to, and that few patients had fully achieved reinsertion into their social and/or work environments. Only 50% of subjects had returned to their job, most of them finding work at a lower level. The closest relatives reported experiencing a state of hardship. Many (70%) care-givers expressed by a steady feeling of worry but had devised effective compensatory strategies over the course of the study period to deal with depression. Such compensation appeared to be the result of the care-givers' awareness of the need to cope with situations where the patients very often depended on them. The hardship level the patient's familial nucleus experienced was not correlated with the patient's social- and work-related outcome, and elements of difficulty were evident among the relatives of patients who had returned to a productive life and those who were close to the family. The presence of severe cognitive and/or behavioral disability was a major factor in generating concern and worry about the future. In cases where the patient was severely disabled, the happiness level perceived by the patient's relatives, as expressed on a 5-point Likert scale, was 2.1, whilst in cases where disability was absent the level was 3.5. CONCLUSIONS: Our observations confirm evidence from previous studies that even many years after a severe trauma incident, a state of disability and/or hardship involving the entire familial nucleus persists.

Sensory stimulation for brain injured individuals in coma or vegetative state.

BACKGROUND: Coma and vegetative state follow traumatic brain injury in about one out of eight patients, and in patients with non traumatic injury the prognosis is worse. The use of sensory stimulation for coma and vegetative state has gained popularity during the 1980's but beliefs and opinions about its effectiveness vary substantially among health professionals. OBJECTIVES: To assess the effectiveness of sensory stimulation programmes in patients in coma or vegetative state. SEARCH STRATEGY: We searched the Injuries Group specialised register, the Cochrane Controlled trials register, EMBASE, MEDLINE, CINAHL and PSYCHLIT from 1966 to January 2002, without language restriction. Reference lists of articles were scanned and we contacted experts in the area to find other relevant studies. SELECTION CRITERIA: Randomised or controlled trials that compared sensory stimulation programmes with standard rehabilitation in patients in coma or vegetative state. DATA COLLECTION AND ANALYSIS: Abstracts and papers found were screened by one reviewer. Three reviewers independently identified relevant studies, extracted data and assessed study quality resolving disagreement by consensus. MAIN RESULTS: Three studies were identified with 68 patients in total. The overall methodological quality was poor and studies differed widely in terms of outcomes measures, study design and conduct. We therefore did not carry out any quantitative synthesis but reviewed results of available studies qualitatively. REVIEWER'S CONCLUSIONS: This systematic review indicates that there is no reliable evidence to support, or rule out, the effectiveness of multisensory programmes in patients in coma or vegetative state.

Wisconsin card sorting test: a new global score, with Italian norms, and its relationship with the Weigl sorting test.

The Wisconsin card sorting test and the Weigl test are two neuropsychological tools widely used in clinical practice to assess frontal lobe functions. In this study we present norms useful for Italian subjects aged from 15 to 85 years, with 5-17 years of education. Concerning the Wisconsin card sorting test, a new measure of global efficiency (global score) is proposed as well as norms for some well known qualitative aspects of the performance, i.e. perseverative responses, failure to maintain the set and non-perseverative errors. In setting normative values, we followed a statistical methodology (equivalent scores) employed in Italy for other neuropsychological tests, in order to favour the possibility of comparison among these tests. A correlation study between the global score of the Wisconsin card sorting test and the score on the Weigl test was carried out and it emerges that some cognitive aspects are not overlapping in these two measures.

Unilateral neglect and disambiguation of the Necker cube.

Three groups of patients (right brain-damaged patients with or without left neglect, and left brain-damaged patients) and a group of healthy subjects, matched for age and educational level to the three groups of patients, were asked to report which of the two frontal surfaces of Necker cubes oriented in four different ways looked, at first sight, nearer to the viewer. The extent to which, and the way in which, disambiguation of the apparent perspective of Necker cubes occurred was found to vary across the four orientations and to be different in left-neglect patients compared with subjects of the other three groups. With normal subjects, the disambiguating factor is suggested to be a disposition to perceive the upper surface, which is nearly orthogonal to the frontal plane, as external to the cube. This would result from a navigation of the observer's spatial attention towards its target along a particular path that is altered in patients suffering from left neglect. It is suggested that comparison of the paths followed by the attentional vectors of normal subjects and left-neglect patients is potentially fruitful for a better understanding of the brain's normal mechanisms of spatial attention and of unresolved issues concerning the perception of the Necker cube.

Writing disorders in Italian aphasic patients. A multiple single-case study of dysgraphia in a language with shallow orthography.

We report results of a writing task given to 53 mildly to moderately aphasic Italian subjects. The task was designed to test the writing performance along the subword-level routine for the spelling of regular words and non-words, and along the lexical routine for the spelling of irregular words. The aim of the study was to identify the incidence of different dysgraphic subtypes in Italian, a language that is considered to have shallow orthography. Its spelling, however, is not completely free of ambiguity. A five-part writing task was used: (i) words with regular one-sound-to-one-grapheme conversion; (ii) words with regular syllabic conversion; (iii) words with ambiguous transcription; (iv) loan-words; and (v) non-words. For regular words, the effects of word length and word frequency, and of the variables determining the complexity of the acoustic-to-phonological conversion (continuant versus plosive phones; consonant-vowel sequence versus doubled consonants or consonant clusters) were also considered. Patients' performances were classified according to the presence of a dissociation between (i) regular words and non-words, (ii) regular words and words with unpredictable spellings, and (iii) one-to-one and syllabic conversions. The 53 aphasic patients span the whole spectrum of dysgraphic taxonomy. Thirty-nine patients, in particular, manifested a dissociated pattern of performance. Eighteen patients showed a prevalent surface dysgraphic pattern and seven a phonological one, while 11 patients showed a mixed pattern (i.e. a better performance for regular words than for ambiguous words or regular non-words). Three patients showed a specific deficit for regular syllabic conversion rules only. A high rate of 'mixed dysgraphia' suggests either a mutual interaction of the two impaired routines when regular words are written, or two separate functional lesions: one at the level of the auditory-to-phonological conversion procedure, the other at the level of the orthographic output lexicon.

Different patterns of dissociation in unilateral spatial neglect.

The aim of this paper is to discuss the issue of dissociations found in unilateral spatial neglect according to the modality of space exploration and the nature of the task. For this purpose we present a reanalysis of the data from a recent paper of Gentilini et al. (1989) comparing visual and blindfolded exploration of a computer keyboard and discuss the performance of a left-brain-damaged patient with right visuospatial neglect and left-sided neglect dyslexia. We conclude that unilateral spatial neglect cannot be interpreted as a disruption of a single attentional mechanism, but rather it reflects impaired attentional mechanisms at several levels of cognitive processing.