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).

Evaluation of leg joint trajectories while carrying out passive manipulation by NEUROBike.

During the last decades, many robotic platforms aimed at post-stroke neurorehabilitation of locomotion have been developed. These devices have been designed to enhance the possibilities of conventional rehabilitation providing safe, highly accurate, intensive and prolonged treatments. Nevertheless, up to now, robotic aided therapy has not yet promoted improvements of the motor performance significantly greater than those achieved by the conventional therapy. According to previous studies, we believe that this result may be partially ascribed to two main issues: the rehabilitation mediated by robots is usually provided too late from the trauma and it mainly consists of passive and cyclic manipulation of the legs. Our proposal to overcome some of the supposed limits is NEUROBike, an operative mechatronic platform able to lead leg manipulation as soon as possible after the trauma, that is when patients still lie on their own beds. Moreover, NEUROBike has been designed to provide both passive and cyclic manipulation of leg joints with trajectories similar to those related to natural walking, and motor task involving random efforts. This work presents the comparison between desired and measured leg joint trajectories while NEUROBike provides cyclic and passive leg manipulation. The results show that angular excursions at proximal joints were reasonably comparable with those obtained by the velocity based model even though they were affected by a positive offset involving emphasized flexion of hip and knee during the gait cycle.

Prognostic value of standard EEG in traumatic and non-traumatic disorders of consciousness following coma.

OBJECTIVE: To investigate the prognostic value of standard electroencephalogram (EEG) in predicting the improvement of the level of consciousness in patients suffering from severe disturbances of consciousness following coma caused by acute brain injuries. METHODS: A standard EEG was recorded at admission in our rehabilitation department in a total of 46 patients with impaired consciousness states following coma (22 patients with traumatic brain injuries, 24 patients with non-traumatic brain injuries). We quantified the EEG abnormalities using the scale of Synek (1988) and correlated them with the basal level of cognitive functioning (LCF) scale score and with its variation after three months. RESULTS: EEG scores correlated with LCF scores at admission (p<0.01) and with LCF scores' variation after three months (p<0.01) in patients with traumatic brain injury; EEG scores correlated only with LCF scores variation after three months (p<0.01) in patients with non-traumatic brain injury. CONCLUSIONS: Standard EEG, analysed using the Synek scale, has a good prognostic value in both groups of patients with disorders of consciousness. SIGNIFICANCE: This work may have implications for clinical care, rehabilitative programs and medical-legal decisions in patients with impaired consciousness states following coma due to acute brain injuries.

A protocol for the assessment of 3D movements of the head in persons with cervical dystonia.

OBJECTIVE: To design and test a protocol for the assessment of neck movements in patients affected by cervical dystonia by using an electromagnetic system. This approach could overcome the limits of the current assessment scales in this specific field. BACKGROUND: Initial assessment and function recovery during treatments are diagnosed by the clinician using outcome scales which present many drawbacks in terms of easiness of use, sensitivity, and reliability. DESIGN: A three-dimensional motion analysis system was used to record six different head movements. METHODS: Six able-bodied subjects and 10 subjects affected by cervical dystonia participated in this study. For the different head movements three kinematic parameters (a symmetry index and two indexes related to the reduction of the range of motion) have been extracted in order to compare the performance of able-bodied and disabled persons. RESULTS: The features selected allowed highlighting of the differences between able-bodied and disabled subjects for the degrees of freedom of the neck. CONCLUSIONS: Using a motion analysis system, three kinematic features were extracted from head movements. They seem to allow a more objective assessment of the disability and a more appropriated strategy for the management of patients affected by cervical dystonia.

Role of the dopamine D5 receptor (DRD5) as a susceptibility gene for cervical dystonia.

Cervical dystonia (CD) is one of the most common forms of primary dystonia. The pathogenesis of the disease is still unknown, although evidence suggests a role for genetic factors. Recently, a polymorphism in the dopamine D5 receptor (DRD5) gene has been associated with the disease in a British population, suggesting that DRD5 is a susceptibility gene for CD. To confirm these data, we performed a case-control study of the microsatellite (CT/GT/GA)(n) at the DRD5 locus in 104 Italian CD patients and 104 healthy controls. The frequency of allele 4 was higher in the CD patients compared to the controls. This resulted in a twofold increased risk of developing the disease. These results provide further evidence of an association between DRD5 and cervical dystonia, supporting the involvement of the dopamine pathway in the pathogenesis of CD.

Sporadic failure of botulinum toxin treatment in usually responsive patients with adductor spasmodic dysphonia.

Botulinum toxin (BT) injections into vocalis (thyroarytenoid) muscle is currently considered the first-choice treatment for adductor spasmodic dysphonia, producing improvement for an average period of 3 months. In our experience, sporadic failure of BT efficacy can occur even in patients usually responsive to this therapy. The reasons for these episodes have not been clarified. In a retrospective, open trial, we investigated the effect toxin preparation (Botox or Dysport) and injection monitoring (electromyography or laryngoscopy) on the success rate of BT treatment. We studied 15 patients with adductor dysphonia usually responsive to BT therapy. BT was administered into the vocalis muscle in 112 and 36 injections under electromyographic or laryngoscopic guidance, respectively. Botox and Dysport were used in 106 and 42 sessions, respectively. In 29% of all injections, no subjective or objective changes, nor side effects were observed. Failure rate did not differ using electromyographic (28.6%) or laryngoscopic (30.5%) guidance. Failure rates with Botox and Dysport were 30.2% and 26.2%, respectively, but this difference was not statistically significant. These data suggest that treatment failure may occur regardless of the method of injection and of the drug preparation used, possibly due to mislocalisation of vocal folds.

Transcranial magnetic stimulation and silent period in spasmodic torticollis.

OBJECTIVE: Our objective was to study the corticobulbar projections to neck muscles in cervical dystonia. DESIGN: We compared both the motor evoked potentials and the electromyographic silent period after transcranial magnetic stimulation from sternocleidomastoid and trapezius muscles in a group of 13 patients with spasmodic torticollis with those of 20 healthy volunteers. RESULTS: With the target muscle at rest, no changes of motor threshold, motor evoked potentials latency, and amplitude were observed in dystonic patients. With facilitation, the mean amplitude of the motor evoked potentials was increased in patients compared with controls, the significant difference being for the trapezius muscle, whereas the latency did not differ between groups. The cortical silent period was significantly shorter in dystonic patients than in healthy subjects in both muscles. The duration of the cortical silent period recorded from the sternocleidomastoid muscle showed a positive correlation with the degree of neurologic disability assessed by Tsui's scale. No abnormalities of both nerve conduction velocity and peripheral silent period by stimulation of accessory nerve were found. CONCLUSIONS: These results indicate an impairment of the mechanisms of inhibitory motor control in patients with spasmodic torticollis, which could be the result of a decrease of the basal ganglia inhibitory output over the motor cortex.

Risk factors for spread of primary adult onset blepharospasm: a multicentre investigation of the Italian movement disorders study group.

OBJECTIVES: Little is known about factors influencing the spread of blepharospasm to other body parts. An investigation was carried out to deterrmine whether demographic features (sex, age at blepharospasm onset), putative risk, or protective factors for blepharospasm (family history of dystonia or tremor, previous head or face trauma with loss of consciousness, ocular diseases, and cigarette smoking), age related diseases (diabetes, hypertension), edentulousness, and neck or trunk trauma preceding the onset of blepharospasm could distinguish patients with blepharospasm who had spread of dystonia from those who did not. METHODS: 159 outpatients presenting initially with blepharospasm were selected in 16 Italian Institutions. There were 104 patients with focal blepharospasm (mean duration of disease 5.3 (SD 1.9) years) and 55 patients in whom segmental or multifocal dystonia developed (mainly in the cranial cervical area) 1.5 (1.2) years after the onset of blepharospasm. Information was obtained from a standardised questionnaire administered by medical interviewers. A Cox regression model was used to examine the relation between the investigated variables and spread. RESULTS: Previous head or face trauma with loss of consciousness, age at the onset of blepharospasm, and female sex were independently associated with an increased risk of spread. A significant association was not found between spread of dystonia and previous ocular diseases, hypertension, diabetes, neck or trunk trauma, edentulousness, cigarette smoking, and family history of dystonia or tremor. An unsatisfactory study power negatively influenced the validity and accuracy of the negative findings relative to diabetes, neck or trunk trauma, and cigarette smoking. CONCLUSIONS: The results of this exploratory study confirm that patients presenting initially with blepharospasm are most likely to experience some spread of dystonia within a few years of the onset of blepharospasm and suggest that head or face trauma with loss of consciousness preceding the onset, age at onset, and female sex may be relevant to spread. The suggested association between edentulousness and cranial cervical dystonia may be apparent because of the confounding effect of both age at onset and head or face trauma with loss of consciousness. The lack of influence of family history of dystonia on spread is consistent with previous findings indicating that the inheritance pattern is the same for focal and segmental blepharospasm.

Repeatability of surface EMG variables during voluntary isometric contractions of the biceps brachii muscle.

The repeatability of initial value and rate of change of mean spectral frequency (MNF), average rectified values (ARV) and muscle fiber conduction velocity (CV) was investigated in the dominant biceps brachii of ten normal subjects during sustained isometric voluntary contractions. Four levels of contraction were studied: 10%, 30%, 50% and 70% of the maximal voluntary contraction level (MVC). Each contraction was repeated three times in each of three different days for a total of nine contractions/level/subject and 90 contractions per level across the ten subjects. Repeatability was investigated using the Intraclass Correlation Coefficient (ICC) and the standard error of the mean (SEM) of the estimates for each subject. Contrary to observations in other muscles, CV estimates appeared to be very repeatable both within and between subjects. CV showed a small but significant increase when contraction force increased from 10% to 50% MVC but no change for further increase of force. As force increased, MNF showed a slight decrease possibly related to a wider spreading of the CV values. The rate of time decrement of MNF and CV increased with the level of contraction. The normalized decrement (% of initial value per second) was in general higher for MNF than for CV and was more repeatable between subjects at 10% MVC than at 70% MVC. A final observation is that a resting time of 5 minutes may not be sufficient after a contraction at 50% or 70% MVC.

Possible risk factors for primary adult onset dystonia: a case-control investigation by the Italian Movement Disorders Study Group.

OBJECTIVES: Little is known about the aetiology of idiopathic adult onset dystonia. The Italian Movement Disorders Study Group promoted a case-control study on some hypothetical risk factors including past medical events, life events, life habits, occupational hazards, and family history of dystonia, parkinsonism, and tremor. METHODS: Cases affected by idiopathic adult onset dystonia (age at symptom onset >20 years, duration of disease >one year and

Guidelines for the therapeutic use of botulinum toxin in movement disorders. Italian Study Group for Movement Disorders, Italian Society of Neurology.

Since its introduction in the early '80s the use of botulinum toxin has improved the quality of life of the patients affected by movement disorders. Toxin's neuromuscular blocking action allows a symptomatic treatment of those clinical conditions characterised by excessive muscular activity. Although the dosages used are safe and the side-effects are reversible, a correct use of botulinum toxin depends on the knowledge of its clinical pharmacology and of the anatomy of the body segments to be injected. In addition, the treatment of more complex conditions, i.e. laringeal dystonia, imposes an inter-disciplinary approach and specialised injection techniques. In this review, the Italian Study Group on Movement Disorders presents the consensus guidelines for the therapeutic use of botulinum toxin in movement disorders. The main toxin types, their use and administration modalities, and the training guidelines will be presented.

Amelioration of nerve conduction velocity following simultaneous kidney/pancreas transplantation is due to the glycaemic control provided by the pancreas.

Diabetic polyneuropathy is a common, disabling chronic complication of diabetes mellitus. Previous studies have suggested that combined pancreas-kidney transplantation can ameliorate nerve conduction. The relative contribution of the correction of hyperglycaemia and uraemia on nerve function is still a matter of debate. Nerve conduction velocity (NCV) was assessed before and after simultaneous pancreas and kidney transplantation, and before and after pancreas graft failure in five insulin-dependent diabetic (IDDM) patients affected by severe diabetic polyneuropathy. Sensory and motor NCV were recorded in five nerves and expressed as a cumulative index for each patient. Metabolic control was evaluated by fasting blood glucose and glycosylated haemoglobin levels. NCV index was below normal values before transplant: -3.8 +/- 0.7 (normal value: 0.89), improved 1 and 2 years after transplant: -3.1 +/- 1.3 and -2.6 +/- 0.9 (p = 0.0019), stabilised until pancreas failure and deteriorated to pre-transplant values 2 years after pancreas graft failure: -3.6 +/- 1.0 (p = 0.034). Fasting blood glucose levels worsened after pancreas graft failure. HbA1c levels, in the normal range during functioning pancreas graft (6.6 +/- 0.6%), deteriorated after its failure (8.0 +/- 0.6%, p = 0.04). Kidney function was preserved. These data support a positive effect of pancreas transplantation per se on NCV in IDDM subjects with diabetic polyneuropathy, thus demonstrating that metabolic control provided by a self-regulated source of insulin not only halts but also ameliorates nerve function, even if polyneuropathy is advanced.

Intravenous immunoglobulin treatment in multifocal motor neuropathy and other chronic immune-mediated neuropathies.

This review deals with the use of intravenous IVIg immunoglobulins in the treatment of chronic immune-mediated neuropathies: multifocal motor neuropathy, chronic inflammatory demyelinating polyneuropathy, neuropathies associated with monoclonal gammopathies. A particular attention is given to case series and trials which compare IVIg to other therapies, such as steroid treatment immunosuppressors and plasma exchange. At present clinical and instrumental data seem to indicate the short term efficacy of IVIg in multifocal motor neuropathies, especially as early treatment; further studies are need in order to prove its long term efficacy in this disease. Concerning chronic inflammatory demyelinating polyneuropathies, short term IVIg efficacy is comparable to that of plasma exchange and in the long term most patients need repeated treatments. Most patients respond to the initial therapy and the initial nonresponders usually improve with a second treatment modality.

Basal ganglia and thalamo-cortical hypermetabolism in patients with spasmodic torticollis.

UNLABELLED: The basal ganglia are thought to be involved in the primary dystonias, largely because of the repeated demonstration of neuropathological changes in these nuclei in the secondary dystonias. A hyperactivity of a network involving basal ganglia has been suggested in experimental animal dystonia. To test this hypothesis in humans, we studied the functional correlates of primary cervical dystonia using [18F]FDG and PET. MATERIAL AND METHODS: Regional cerebral glucose metabolism (rCMRglc) was measured in 10 patients with idiopathic torticollis (6 drug-free and 4 drug-naive) and in 15 normal controls, using 2-[18F]-fluoro-2-deoxy-D-glucose ([18F]FDG) and positron emission tomography (PET). RESULTS: A significant hypermetabolism in the basal ganglia, thalamus, premotor-motor cortex and cerebellum in the patients compared with normal controls was found. The patients were correctly assigned to their clinical category by a discriminant function analysis with a total accuracy of 96%. CONCLUSION: The results support the hypothesis that a dysfunction of a subcortical-cortical motor network may play a role in the pathogenesis of focal dystonia, in agreement with the experimental dystonia models.

Clinical and neurophysiological assessment of immunoglobulin therapy in five patients with multifocal motor neuropathy.

High dose intravenous immunoglobulin (IVIg) is an effective treatment for demyelinating neuropathies. IVIg was given to five patients with multifocal motor neuropathy, a motor neuropathy showing a clinical syndrome of asymmetrical weakness and amyotrophy, electrophysiological evidence of motor conduction block and, in many cases, high titres of serum anti-GM1 antibodies. Muscle strength was evaluated by a conventional score before and after each IVIg course. In all patients there was relevant improvement on muscle strength after each immunoglobulin course, but in most cases the clinical benefits partially declined after three to eight weeks. At the eight month follow up, however, the pretreatment examination showed a significant improvement compared with the initial evaluation. The effects of each IVIg course were still present after a number of courses. Electrophysiological study revealed a decrease in conduction block in one or more nerves in all patients. However, conduction block was unchanged or increased in other sites. IVIg treatment did not affect anti-GM1 antibody titres.

Intravenous immunoglobulin treatment in patients with chronic inflammatory demyelinating neuropathy not responsive to other treatments.

Nine patients with chronic inflammatory demyelinating poliradiculoneuropathy (CIDP) were treated with intravenous immunoglobulin. All patients had been previously treated with prednisone and/or plasma exchange without effect. Objective improvement in clinical condition occurred in six patients. One patient became refractory after two treatment courses, two patients had no response. The results indicate that intravenous immunoglobulin has beneficial effects in a high percentage of patients with CIDP who are unresponsive to other treatments.