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.

Active ankle dorsiflexion and the Mingazzini manoeuvre: two clinical bedside tests related to prognosis of postural transferring, standing and walking ability in patients with stroke.

BACKGROUND: Lower limb paresis is one of the main determinants of postural transferring, standing and walking disability in patients with stroke. Early prognosis of recovery of lower limb function and of related functional disability is an important issue in neurorehabilitation clinical practice. AIM: Aim of this study was to assess the relationship between active ankle dorsiflexion and the Mingazzini manoeuvre with the prognosis of lower limb function and of postural transferring, standing and walking ability in patients with stroke. DESIGN: This was a longitudinal study with prospectively collected data. SETTING: University hospital. POPULATION: The study included 53 patients with first unilateral brain ischemic stroke. METHODS: Patients were evaluated initially (mean 4.02 days) and approximately at six months (mean 178.6 days) after stroke. Initial assessment included active ankle dorsiflexion and the Mingazzini manoeuvre. The assessment after six months included three outcome measures evaluating the rate of improvement of lower limb function and of postural transferring, standing and walking ability (Postural Assessment Scale for Stroke patients, Functional Ambulation Category, Motricity Index leg subtest). RESULTS: The active ankle dorsiflexion showed to be related with the prognosis of lower limb function and of walking ability, while the Mingazzini manoeuvre was related with the improvement of postural transferring and standing ability. CONCLUSION: Active ankle dorsiflexion and the Mingazzini manoeuvre are related with the prognosis of lower limb function and of postural transferring, standing and walking ability in patients with stroke. CLINICAL REHABILITATION IMPACT: These simple bedside tests give a picture of improvement potential of motor activities connected to lower limb function in patients with acute stroke.

Corticospinal excitability during action observation in task-specific dystonia: a transcranial magnetic stimulation study.

Observation of actions performed by other individuals activates the onlooker's motor system in a way similar to real movement execution. The functioning of this mechanism in the pathological domain is not clear yet. The aim of this study was to explore whether action observation activates the motor system of patients affected by a task-specific form of dystonia, such as writer's cramp. Transcranial magnetic stimulation was applied over the primary motor cortex and motor evoked potentials were recorded from hand (FDI and ADM) and forearm (FCR) muscles at baseline and during observation of actions (grasping and writing) or images. Writing actions could be performed with healthy or dystonic movement patterns. Results showed a highly specific and reversed pattern of activation in the FDI muscle of the two groups. Differences between the two writing conditions were significantly opposite in the two groups: control subjects had higher activation during observation of the dystonic compared to the healthy action, whereas in patients observation of the healthy writing led to higher activation than the dystonic writing. This opposite corticospinal modulation might be explained by a different self-attribution of the observed actions in the two groups.

Expression profiling in peripheral blood reveals signature for penetrance in DYT1 dystonia.

DYT1 dystonia is an autosomal-dominantly inherited movement disorder, which is usually caused by a GAG deletion in the TOR1A gene. Due to the reduced penetrance of approximately 30-40%, the determination of the mutation in a subject is of limited use with regard to actual manifestation of symptoms. In the present study, we used Affymetrix oligonucleotide microarrays to analyze global gene expression in blood samples of 15 manifesting and 15 non-manifesting mutation carriers in order to identify a susceptibility profile beyond the GAG deletion which is associated with the manifestation of symptoms in DYT1 dystonia. We identified a genetic signature which distinguished between asymptomatic mutation carriers and symptomatic DYT1 patients with 86.7% sensitivity and 100% specificity. This genetic signature could correctly predict the disease state in an independent test set with a sensitivity of 87.5% and a specificity of 85.7%. Conclusively, this genetic signature might provide a possibility to distinguish DYT1 patients from asymptomatic mutation carriers.

Genotype-phenotype interactions in primary dystonias revealed by differential changes in brain structure.

Our understanding of how genotype determines phenotype in primary dystonia is limited. Familial young-onset primary dystonia is commonly due to the DYT1 gene mutation. A critical question, given the 30% penetrance of clinical symptoms in DYT1 mutation carriers, is why the same genotype leads to differential clinical expression and whether non-DYT1 adult-onset primary dystonia, with and without family history share pathophysiological mechanisms with DYT1 dystonia. This study examines the relationship between dystonic phenotype and the DYT1 gene mutation by monitoring whole-brain structure using voxel-based morphometry. We acquired magnetic resonance imaging data of symptomatic and asymptomatic DYT1 mutation carriers, of non-DYT1 primary dystonia patients, with and without family history and control subjects with normal DYT1 alleles. By crossing the factors genotype and phenotype we demonstrate a significant interaction in terms of brain anatomy confined to the basal ganglia bilaterally. The explanation for this effect differs according to both gene and dystonia status: non-DYT1 adult-onset dystonia patients and asymptomatic DYT1 carriers have significantly larger basal ganglia compared to healthy subjects and symptomatic DYT1 mutation carriers. There is a significant negative correlation between severity of dystonia and basal ganglia size in DYT1 mutation carriers. We propose that differential pathophysiological and compensatory mechanisms lead to brain structure changes in non-DYT1 primary adult-onset dystonias and DYT1 gene carriers. Given the range of age of onset, there may be differential genetic modulation of brain development that in turn determines clinical expression. Alternatively, a DYT1 gene dependent primary defect of motor circuit development may lead to stress-induced remodelling of the basal ganglia and hence dystonia.

Are indexes of arm recovery related to daily life autonomy in patients with stroke?

AIM: The level of daily life autonomy in patients with stroke may be related to recovery of affected arm function. The aim of the study was to assess whether four simple bedside indexes of arm recovery can predict levels of autonomy in daily life activities. METHODS: A consecutive sample of 48 patients presenting with upper limb paresis/plegia in the acute stage after stroke was selected. Patients underwent five evaluation sessions at 7, 14, 30, 90 and 180 days after stroke. Forward stepwise multiple regression analysis was used to clarify the role of four potential predictors of upper limb recovery (active finger extension, shoulder abduction, shoulder shrug and hand movement scales). Dependent variables in these models were the Barthel Index score and sub-items of the Burke-Fahn-Marsden Scale. RESULTS: The active finger extension scale showed a highly significant statistical correlation with patient performance in nearly all outcome measures. The shoulder shrug correlated with the BI score, and with the dressing and hygiene Burke-Fahn-Marsden Scale sub-items. Shoulder abduction and hand movement scale played only a minor role. CONCLUSIONS: The active finger extension scale proved to be a strong early predictor of recovery of daily life autonomy in patients with stroke. This finding could be important in order to planning a specific rehabilitation treatment after the onset.

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.

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 with 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 between two stimuli that were either simultaneous or sequential (temporal discrimination threshold, TDT). Pairs of tactile stimuli were delivered with increasing or decreasing inter-stimulus intervals from 0 to 400 ms (in 10-ms steps) to the hands or on the skin over the orbicularis oculi muscle. RESULTS: Tactile stimuli elicited similar TDTs in control subjects and patients with hemifacial spasm, but significantly higher TDTs in patients with blepharospasm, regardless of whether stimuli were applied to the orbicularis muscle or the hand. CONCLUSIONS: As 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.