Active Finger Extension

Background and Purpose—Early prognosis of arm recovery is a major clinical issue in stroke. The aim of this study was to assess the prognostic value of 4 simple bedside tests.Methods—Forty-eight patients with arm paresis/plegia were evaluated on days 7, 14, 30, 90 and 180 after stroke. Assessment included 4 potential predictors of arm recovery (active finger extension, shoulder abduction, shoulder shrug and hand movement scales) and 3 outcome measures evaluating arm function (Nine Hole Peg Test, Fugl-Meyer arm subtest, Motricity Index arm subtest).Results—The active finger extension scale was the most powerful prognostic factor. Patients with active finger extension scores >3 had a high probability of achieving good performance as assessed by the Motricity Index.Conclusions—Active finger extension is a reliable early predictor of recovery of arm function in stroke patients

Le funzioni sensoriali nella distonia DYT1. Discriminazione temporale e rappresentazione del movimento

La distonia primaria di torsione DYT1 (PTD) \ue8 caratterizzata da contrazioni muscolari prolungate causanti movimenti torsionali e posture fisse (Bressman, 1998). Questo disordine dovuto ad una delezione di 3 paia di basi nel gene TOR1, si manifesta solamente nel 33% dei portatori della mutazione (Gambarin et al., 2006). Tipico della malattia \ue8 l\u2019esordio precoce in un arto, ingenere il piede, con rapida generalizzazione ai quattro arti (Ozelius et al. 1997). Il meccanismo sottostante la ridotta penetranza \ue8 poco conosciuto, sebbene siano stati recentemente riscontrati 3 diversi polimorfismi del DYT1 che potrebbero influenzare la penetranza in modo diverso (Risch et al., 2007). Anche se poco conosciuta, la fisiopatologia della PTD \ue8 stata correlata ad una disfunzione dei gangli della base coinvolti non solo nello sviluppo dei sintomi predominanti motori, ma anche nelle alterazioni subcliniche. Il feed back sensoriale \ue8 cruciale per la guida dell\u2019uscita motoria. Cosi\u2019, almeno ad un primo livello intuitivo, il coinvolgimento delle funzioni sensoriali pu\uf2 giocare un ruolo fondamentale nella fisiopatologia della distonia (Hallet 1995; Tinazzi 2003). Molti difetti delle funzioni sensoriali sono stati dimostrati in diverse forme di distonia. La discriminazione temporale \ue8 un aspetto base della processazione somatosensoriale, essenziale per molte altre funzioni come la cinestesia, la grafestesia, il senso vibratorio, la steregnosi. Lo studio di questa funzione si effettua attraverso la soglia di discriminazione temporale definita come il piu\u2019 breve intervallo di tempo al quale due stimoli sono percepiti come separati. Diversi lavori convergono nel definire che questa TDT \ue8 piu\u2019 alta nei pazienti con distonia generalizzata, con distonia cervicale, con distonia focale della mano, rispetto ai soggetti di controllo sani (Bara-Jimenez et al., 2000; Aglioti et al., 2003; Fiorio et al, 2003; Tinazzi et al., 2004). Questo deficit \ue8 stato attribuito alla correlazione tra la distonia e i gangli della base, implicati non solo nel controllo motorio ma anche nella processazione temporale. (Lacrutz et al., 1991; Harrington at al., 1998). Nella distonia focale della mano il deficit sensoriale \ue8 stato riscontrato non soltanto nell\u2019arto affetto, ma anche in quello non affetto (Fiorio et al., 2003). Questo fatto potrebbe suggerire che le alterazioni del sensorio avvengono prima delle manifestazioni motorie della distonia (Meunier et al., 2001; Fiorio et al., 2003). Molto poco si conosce riguardo la presenza del deficit sensoriale nelle persone portatrici del gene DYT1 siano esse affette o sane. Lo scopo della prima parte del nostro studio \ue8 stato quello di individuare se esista un deficit di alterazione somatosensoriale anche nella distonia DYT1, di capire se questa alterazione somatosensoriale possa essere riconducibile ad una alterazione del substrato genetico e di stabilire se questa alterazione somatosensoriale possa rappresentare un tratto endofenotipico della distonia. A questo scopo abbiamo applicato lo stesso paradigma di discriminazione temporale gi\ue0 utilizzato in precedenti studi (Fiorio et al., 2003) sia nei pazienti portatori del gene DYT1 affetti da distonia che nei familiari portatori della stessa mutazione ma non manifestanti il disturbo motorio. Inoltre abbiamo testato anche familiari senza il gene alterato e quindi senza distonia e soggetti di controllo esterni. Coppie di stimoli tattili, visivi, o visuo-tattili sono state somministrati in blocchi, controbilanciati per ordine. L\u2019intervallo interstimolo aumentava da 0 a 400 ms (in steps di 10 ms). Ad ogni trial, i soggetti dovevano riportare se la percezione della coppia di stimoli era sincrona o separata. Abbiamo misurato il primo dei tre intervalli consecutivi ai quali i soggetti riconoscevano gli stimoli come separati temporalmente (TDT) e inoltre abbiamo registrato per ogni TDT l\u2019ordine di giudizio temporale (TOJ), inteso come la capacit\ue0 di stabilire quale dei due stimoli precedeva (o seguiva) l\u2019altro all\u2019interno della coppia somministrata. Abbiamo esaminato 9 pazienti manifesti del gene DYT1, 11 portatori del gene DYT1non manifesti, 9 parenti sani, 9 soggetti esterni ai soggetti di controllo. I risultati hanno dimostrato esistere un\u2019elevata soglia di TDT e di TOJ tattile e visuotattile nei portatori del gene DYT1, sia nei manifesti che nei non manifesti della malattia rispetto ai parenti sani e ai soggetti di controllo esterni (per ogni paragone P<0.039). Ci\uf2 indica che la mutazione DYT1 determina alterazioni subcliniche che possono essere evidenziate dal compito neuropsicologico. Ancora, i risultati hanno notevole implicazione sul fatto che i deficit sensoriali non sono mera conseguenza di movimenti anormali, ma che possono accadere prima delle manifestazioni cliniche della malattia, rappresentando un tratto endofenotipico subclinico nei portatori della mutazione del gene DYT1. In diverse forme di distonia \ue8 stata dimostrata la presenza anche di un altro difetto delle funzioni sensoriali: il difetto della rappresentazione del movimento di parti del corpo. Questa funzione consiste nella capacit\ue0 di prevedere la corretta sequenza dei movimenti da eseguire e la posizione finale della parte del corpo in movimento. Ci sono forti evidenze a favore del fatto che i gangli della base siano parte di una complessa rete neuronale implicata in questa funzione (Kosslyn et al., 1998; Vingerhoets et al., 2002; Wolbers et al., 2003; de Lange et al., 2005; Duncombe et al., 1994; Parson et al., 1994;1995; Bonda et al., 1995; Alvisatos et al., 1997; Ganis et al., 2000; Sirugu et al., 2001). Un utile strumento per indagare la pianificazione e la previsione del movimento \ue8 il paradigma di rotazione mentale, in cui i soggetti sono tenuti ad esprimere un giudizio sulla lateralit\ue0 di immagini di parti del corpo presentate in diverse posture e con diversi gradi di orientamento (0 \ub0, 60 \ub0, 120 \ub0, 180 \ub0, 240 \ub0, 300 \ub0) . Questo compito richiede la capacit\ue0 di immaginare un oggetto in una prospettiva diversa da quella in cui effettivamente appare, e sembra essere risolto dalla simulazione dell'effettivo movimento della stessa parte del corpo (Duncombe et al., 1994; Parson et al., 1994). Nei pazienti con altri tipi di distonia non DYT1, come la distonia focale dell\u2019adulto e la distonia cervicale, \ue8 gi\ue0 stata dimostrata la presenza di alterazioni nella rotazione mentale sia di parti del corpo affette che non affette da distonia (Fiorio et al., 2006; 2007), suggerendo la possibilit\ue0 effettiva che anche queste alterazioni di performance rappresentino un tratto endofenotipico di distonia. Cos\uec nella seconda parte dello studio abbiamo esaminato se esista un deficit della rotazione mentale anche nella distonia DYT1. Per fare questo abbiamo applicato lo stesso paradigma della rotazione mentale gi\ue0 utilizzato in precedenti studi (Fiorio et al., 2006; 2007) sia nei pazienti portatori del gene DYT1 affetti che nei familiari portatori del gene non manifesti della malattia, che nei soggetti di controllo sani. Tutti i partecipanti allo studio dovevano osservare lo schermo di un computer sul quale venivano presentate parti del corpo (mano, faccia, piede) e parti non del corpo (macchina). Gli stimoli erano presentati via via a diversi gradi di angolazione. I soggetti dovevano ruotare mentalmente gli stimoli presentati e fornire un giudizio di lateralit\ue0. Sono stati misurati il tempo di reazione e l\u2019accuratezza di risposta. Abbiamo trovato che i portatori DYT1, manifesti e non manifesti della malattia, si presentavano pi\uf9 lenti nelle rotazioni delle parti del corpo (ma non in quelle non del corpo), rispetto ai soggetto di controllo. Cosi\u2019 le nostre conclusioni sono state che la mutazione genica DYT1 sia associata ad una lentezza della rotazione mentale del movimento indipendentemente dalla presenza dei sintomi motori e questo ci ha portato ad ipotizzare che la rappresentazione cognitiva del movimento del corpo alterata nella distonia possa considerarsi come tratto endofenotipico della malattia. I risultati dei due lavori presentati confermano la distonia quale sindrome complessa in cui accanto al pi\uf9 evidente disturbo motorio, \ue8 possibile la contemporanea presenza di deficits subclinici delle funzioni sensoriali e percettive, e supportano l\u2019ipotesi della comune regolazione ai due sistemi, motorio e sensitivo, da parte dei gangli della base. Il fatto che sia la discriminazione temporale che la rotazione mentale siano state riscontrate alterate sia nei portatori del gene affetti dalla malattia che in quelli non affetti, suggerisce l\u2019ipotesi che il deficit sensoriale possa essere indipendente dallo sviluppo dei sintomi motori e possa costituire un tratto endofenotipico di distonia. Serviranno ulteriori studi multicentrici per stabilire se i nostri paradigmi possano costituire effettivamente un utile strumento diagnostico di diagnosi precoce di distonia.DYT1 primary torsion dystonia (PTD) is characterised by prolonged muscular contractions causing abnormal torsion movements and sustained postures (Bressman, 1998). This disorder is due to a 3bp GAG deletion in the TOR1 gene, which manifests in only 33% mutation carriers (Gambarin et al., 2006). Typical of the disease is the early-onset in a limb and rapid generalization (Ozelius et al. 1997). The mechanisms underlying reduced penetrance are poorly understood, although three DYT1 polymorphisms have been recently shown to influence penetrance (Risch et al., 2007). Albeit still largely unknown, the pathophysiology of PTD has been related to basal ganglia dysfunctions leading not only to the most prominent motor symptoms, but also to subclinical sensory deficits. Sensory feedback is crucial for driving motor outputs. Thus, although at first counterintuitive, the impairment of sensory functions may play a fundamental role in the pathophysiology of dystonia (Hallet 1995; Tinazzi 2003). Indeed, defective sensory functions have been demonstrated in several forms of dystonia. Temporal discrimination is a basic aspect of somatosensory processing, essential for a number of functions including kinaesthesia, graphesthesia, vibratory sense and stereognosis. Assessment of this function has been carried out by using temporal discrimination threshold (TDT), defined as the shortest time at witch two stimuli are perceived as separate. Studies converge to indicate that thresholds were much higher in patients with generalised, cervical and focal-hand dystonia than control subjects (Bara-Jimenez et al., 2000; Aglioti et al., 2003; Fiorio et al, 2003; Tinazzi et al., 2004). These deficits have been interpreted in light of the relation between dystonia and dysfunctions of basal ganglia that are implicated not only in motor control but also in temporal processing (Lacrutz et al., 1991; Harrington at al., 1998). Interestingly sensory deficit has been observed in the unaffected hand of patient with unilateral focal-hand dystonia (Fiorio et al., 2003). This would suggest that sensory abnormalities occur before overt manifestation of dystonia (Meunier et al., 2001; Fiorio et al., 2003). Little or no information about the presence of sensory abnormalities in DYT1 gene manifesting and non manifesting carriers is available. The main aim of the first part of our study was to reveal whether any sensory dysfunctions in DYT1 may be related to the abnormal genetic substrate and thus considered a sensory endophenotipic trait of disease. So we applied the same temporal discrimination paradigm (Fiorio et al. 2003) in manifesting and non carrier relatives and in external control subjects. Pairs of tactile, visual or visual-tactile stimuli were delivered in blocked, counter-balanced order. Interval between stimuli increased from 0 to 400 ms (in 10 ms steps). On each trial, subjects had to report whether stimuli occurred simultaneously or asynchronously. We measured the first out of three consecutive interstimulus intervals at witch subjects recognised the two stimuli as temporally separated (TDT) and the first of the three consecutive intervals at witch they also reported correctly with stimulus in the pair preceded (or followed) the other temporal order judgment (TOJ). We assessed 9 DYT1 manifesting patients, 11 DYT1 non manifesting relatives, 9 non carrier relatives and 9 external control subjects. Results showed hither tactile and visuotactile TDTs and TOJs in DYT1 carriers, both manifesting and non-manifesting, compared with non carrier relatives and with external control subjects (for all comparison, P< 0.039). This finding indicates that the DYT1 mutation determines subclinical sensory alterations, with could be disclosed by a psychophysical task. Moreover the results have notable implication that sensory deficits in dystonia are not mere consequence of abnormal movements, but the may even occur before overt clinical manifestation, representing a subclinical phenotype in DYT1 mutation carriers. An other defective sensory functions, the body movement representation, have been demonstrated in several forms of dystonia. A fundamental mechanism underlying motor control is the ability to predict the correct sequence of movements to be executed and the final position of the body part. A useful tool to investigate movement prediction is the mental rotation paradigm, based on the ability to image a body part or an object in a different perspective from the one in which it actually appears. This process requires an inner simulation of real perceptual and motor performance and, when regarding body parts, it is carried out by simulating actual body movements (Parson, 1994). Cortical and subcortical networks probably underlying mental rotation of body parts and objects include posterior parietal and occipital cortices, motor, premotor and supplementary motor areas, basal ganglia, and cerebellum (Bonda et al., 1995; Pearson et al., 1995). Interestingly, patients with primary non-DYT1, late onset focal-hand and cervical dystonia showed impaired mental rotation of body parts either affected or unaffected by dystonia (Fiorio et al, 2006; 2007), raising the possibility that altered performance represents an endophenotypic trait of primary dystonia. So in the second part of our study we examined whether the mental rotation of body parts was impaired in DYT1 carriers, both manifesting and non-manifesting dystonic symptoms, as compared to normal subjects. DYT1 manifesting patients, DYT1 non manifesting carriers and control subjects were asked to fixate body (hand, foot, face) on non body (car) stimuli on a computer screen. Stimuli were presented at different degrees of orientations and subjects had to mentally rotate them, in order to give a laterality judgement. Reaction times and accuracy were collocated. We founded that DYT1 carriers, manifesting and non manifesting dystonic symptoms, were slower in mentally rotating body parts (but not cars) than control subjects and our conclusion was that DYT1 gene mutation is associated with a slowness in mental simulation of movements, independently from the presence of motor symptoms and than this suggests that the cognitive representation of body movements altered subclinically in dystonia, may be contributing to the endophenotypic trait of the disease. The advances described in the two parts of this study indicate that PTD DYT1 is a complex syndrome in witch abnormal subclinical sensory and perceptual functions may coexist with the most prominent motor symptoms. The subclinical alterations may be related to new evidence and to the concept that basal ganglia come into play only in motor but also in sensory and cognitive functions. The fact that both in temporal discrimination study and in mental rotation, non affected DYT1 gene carriers may also show similar abnormalities suggests the hypothesis that sensory deficits might be independent of motor symptoms and might even pre-exist overt clinical manifestations, constituting subclinical endophenotypic traits of disease. Whether ours paradigms might became a useful tool to diagnose the envelope of dystonia before the starting of the motor symptoms, needs further validation on a larger sample of gene carriers and control subjects

Twelve-year follow-up of a large italian family with atypical phenotypes of DYT1-dystonia

Background: A heterozygous mutation in the TOR1A gene (DYT1) accounts for isolated dystonia typically presenting during childhood or adolescence, with initial involvement of one limb, spreading rapidly to other limbs and the trunk, sparing craniocervical muscles. However, atypical phenotypes, regarding age at onset, site of presentation, and spreading have been reported. Methods and Findings: In 2006, we described a large Italian family showing atypical phenotypes and intrafamilial clinical variability of DYT1-dystonia. The current article reports on a 12-year follow-up of this family, focusing on disease onset in three previously asymptomatic DYT1 mutation carriers, and the reassessment of initially affected individuals. Conclusions: The new cases confirm the intrafamilial phenotypic heterogeneity of DYT1-dystonia. Moreover, this case series highlights that symptoms in atypical phenotypes seem not to spread significantly and in the long term, rarely worsen. Prolonged follow-up of DYT1-positive pedigrees may expand the clinical spectrum of DYT1-dystonia. \ua9 2018 International Parkinson and Movement Disorder Societ

Tactile temporal discrimination in patients with blepharospasm

BACKGROUND: Blepharospasm is an adult-onset focal dystonia that causes involuntary blinking and eyelid spasms. Studies have shown the presence of sensory deficits associated to dystonia. AIM: To rule out any confounding effect of muscle spasms on sensory performance in affected and unaffected body regions of patients with blepharospasm and with hemifacial spasm. METHODS: Participants (19 patients with blepharospasm, 19 patients with hemifacial spasm and 19 control subjects) were asked to discriminate whether two stimuli were simultaneous or sequential (temporal discrimination threshold, TDT). Pairs of tactile stimuli were delivered with increasing or decreasing inter-stimulus intervals from 0 to 400 msec (in 10 msec steps) to the hands or on the skin over the orbicularis oculi muscle. RESULTS: Tactile stimuli elicited similar TDT in control subjects and patients with hemifacial spasm, but significantly higher TDT in patients with blepharospasm, regardless of whether stimuli were applied to the orbicularis muscle or the hand. CONCLUSIONS: Since TDT was abnormal in unaffected body regions of patients with blepharospasm, and patients with hemifacial spasm processed tactile stimuli normally, TDT deficits in blepharospasm depend on central rather than peripheral factors. This study further supports the link between focal dystonia and impaired temporal processing of somatosensory inputs

Active finger extension - A simple movement predicting recovery of arm function in patients with acute stroke

BACKGROUND AND PURPOSE: Early prognosis of arm recovery is a major clinical issue in stroke. The aim of this study was to assess the prognostic value of 4 simple bedside tests. METHODS: Forty-eight patients with arm paresis/plegia were evaluated on days 7, 14, 30, 90 and 180 after stroke. Assessment included 4 potential predictors of arm recovery (active finger extension, shoulder abduction, shoulder shrug and hand movement scales) and 3 outcome measures evaluating arm function (Nine Hole Peg Test, Fugl-Meyer arm subtest, Motricity Index arm subtest). RESULTS: The active finger extension scale was the most powerful prognostic factor. Patients with active finger extension scores >3 had a high probability of achieving good performance as assessed by the Motricity Index. CONCLUSIONS: Active finger extension is a reliable early predictor of recovery of arm function in stroke patients

Atypical phenotypes and clinical variability in a large Italian family with DYT1-primary torsion dystonia

The GAG deletion in the DYT1 gene usually causes a typical form of primary torsion dystonia (PTD) with early onset in a limb, rapid generalization, and sparing of cranial-cervical muscles, but atypical phenotypes have often been reported. Here, we describe a large DYT1 Italian family with phenotypically heterogeneous PTD that recapitulates all the atypical features associated with the DYT1 mutation, including late age at onset, focal or segmental phenotypes, onset or spreading of dystonia to the cranial-cervical muscles. Of 38 healthy family members, 15 also carried the DYT1 mutation, with an estimated penetrance of 21%. A literature review of atypical familial cases of DYT1-PTD showed that late onset, cervical involvement, and limited progression of dystonia are features frequently seen in DYT1 families. However, nearly all of these atypical patients fall within at least one of the clinical categories that best predict the DYT1 carrier status, namely, early onset, onset in a limb, and family history positive for early-onset dystonia. (C) 2006 Movement Disorder Society

Impaired body movement representation in DYT1 mutation carriers

OBJECTIVE: The only known genetic cause of early-onset primary torsion dystonia is the GAG deletion in the DYT1 gene. Due to the reduced penetrance, many mutation carriers remain clinically asymptomatic, despite the presence of subclinical abnormalities, mainly in the motor control circuitry. Our aim was to investigate whether the DYT1 mutation impairs the inner simulation of movements, a fundamental function for motor planning and execution, which relies upon cortical and subcortical systems, dysfunctional in dystonia. METHODS: DYT1 manifesting patients, DYT1 non-manifesting carriers and control subjects were asked to fixate body (hand, foot, face) or non-body (car) stimuli on a computer screen. Stimuli were presented at different degrees of orientations and subjects had to mentally rotate them, in order to give a laterality judgement. Reaction times and accuracy were collected. RESULTS: DYT1 carriers, manifesting and non-manifesting dystonic symptoms, were slower in mentally rotating body parts (but not cars) than control subjects. CONCLUSIONS: The DYT1 gene mutation is associated with a slowness in mental simulation of movements, independently from the presence of motor symptoms. SIGNIFICANCE: These findings suggest that the cognitive representation of body movements may be altered subclinically in dystonia, thus contributing to the endophenotypic trait of disease

Subclinical sensory abnormalities in unaffected PINK1 heterozygotes.

BACKGROUND : Mutations in the PINK1 gene, encoding a mitochondrial protein kinase, represent the second cause of autosomal recessive parkinsonism (ARP) after Parkin. While homozygous or compound heterozygous mutations in these genes are unequivocally causative of ARP, the role of single heterozygous mutations is still largely debated. An intriguing hypothesis suggests that these mutations could represent a risk factor to develop parkinsonism, by contributing to nigral cell degeneration. Since the substantia nigra plays an important role in temporal processing of sensory stimuli, as revealed from studies in idiopathic PD, we sought to investigate whether any subclinical sensory abnormalities could be detected in patients with PINK1- related parkinsonism and in unaffected PINK1 heterozygous carriers. METHODS : We adopted a psychophysical method, the temporal discrimination paradigm, to assess PINK1 homozygous patients, unaffected relatives who were heterozygous carriers of the same mutations and healthy control subjects. Temporal discrimination threshold (TDT) and temporal order judgement (TOJ) for pairs of tactile, visual or visuo-tactile stimuli were measured according to a standardized protocol. FINDINGS : Higher mean tactile and visuo-tactile TDTs and TOJs were detected in PINK1 mutation carriers, including not only homozygous patients but also healthy heterozygotes, compared to control subjects (for all comparisons, p < 0.001). INTERPRETATION : In clinically unaffected subjects, the mere presence of a heterozygous PINK1 mutation is sufficient to determine sensory alterations which can be disclosed by a psychophysical task. Deficits in temporal processing might be considered as subclinical signs of alteration at least in PINK1-related parkinsonism

Defective temporal processing of sensory stimuli in DYT1 mutation carriers: a new endophenotype of dystonia?

DYT1 primary torsion dystonia is an autosomal dominant movement disorder due to a 3-bp GAG deletion in the TOR1A gene, which becomes manifest in only 30-40% of mutation carriers. Investigating the factors regulating this reduced penetrance might add new insight into the mechanisms underlying the disease. The pathophysiology of dystonia has been related to basal ganglia dysfunctions that lead to the most prominent motor symptoms. However, subclinical sensory deficits have also been reported, particularly in adult-onset focal dystonia. Sensory abnormalities in different forms of sporadic dystonia have been revealed by using a psychophysical method, namely, the temporal discrimination threshold (TDT), quantified as the shortest time interval at which the two stimuli are perceived as separate. Little or no information about the presence of sensory abnormalities in DYT1 gene manifesting and non-manifesting carriers is available. With the aim of disclosing possible associations between sensory deficits and the DYT1 mutation, we assessed TDTs of DYT1 manifesting patients (n = 9); DYT1 non-manifesting relatives (n = 11); non-carrier relatives (n = 9); external control subjects (n = 11). Pairs of tactile, visual or visuo-tactile stimuli were delivered in blocked, counterbalanced order. Intervals between stimuli increased from 0 to 400 ms (in 10 ms steps). On each trial, subjects had to report whether stimuli occurred simultaneously or asynchronously. We measured the first out of three consecutive inter-stimulus intervals at which subjects recognized the two stimuli as temporally separated (TDT) and the first of three consecutive intervals at which they also reported correctly which stimulus in the pair preceded (or followed) the other temporal order judgment (TOJ). Results showed higher tactile and visuo-tactile TDTs and TOJs in DYT1 carriers, both manifesting and non-manifesting, compared with non-carrier relatives and with external control subjects (for all comparisons, P < 0.039). This finding indicates that the DYT1 mutation determines subclinical sensory alterations, which could be disclosed by a psychophysical task. Moreover, these results have the notable implication that sensory deficits in dystonia are not a mere consequence of abnormal movements, but they may even occur before overt clinical manifestations, representing a subclinical phenotype in DYT1 mutation carriers

A multi-centric observational study on heterotopic ossification in severely brain injured patients with disorders of consciousness: preliminary data

Aims: to identify occurrence of neurogenic heterotopic ossification (NHO) in patients with prolonged disorder of consciousness (DoC) and possible risk factors. Design: Multi-center observational study. Setting: twenty-three intensive neurorehabilitation units. Subjects: two hundred and seventy-eight patients with prolonged disorder of consciousness (DoC; 150 in vegetative state and 128 in minimally conscious state) of different aetiology (vascular 125, traumatic=83; anoxic=56 brain injury and other brain aetiologies=14). Main Measures: at study entry: clinical evaluation by the Coma Recovery Scale-Revised (CRS-R), Disability Rating Scale (DRS), Early Rehabilitation Barthel Index (ERBI), Clinical Feature Scale (CFS); presence of ventilator support, spasticity, bone fractures. Within 3 months after admission: clinical evidence of NHO (i.e. limited range of motion and/or joint pain and/or local inflammation) confirmed by standard radiological and/or sonographic evaluation and presence of paroxysmal sympathetic hyperactivity (PSH). Results: Thirty-one patients (11.2%) developed NHO. Presence of abnormal ossifications was significantly higher in patients in VS than in patients in MCS and in patients with traumatic brain injury. Moreover patients with NHO showed higher DRS category and total score, higher occurrence of limb spasticity and bone fractures at study entry than patients without NHO. Patients with NHO did not differ from patients without NHO for sex, age, time post-injury, CRS-R and ERBI total scores, presence of non-invasive ventilator support at study entry and presence of PSH. Conclusions: Our findings suggest a relation between development of NHO and clinical diagnosis, functional disability status and aetiology in patients with DoC. Moreover, we identified spasticity and bone fractures as possible risk factors for occurrence of NHO in patients with severe brain injury and DoC