Long-Term Neuroradiological and Clinical Evaluation of NBIA Patients Treated with a Deferiprone Based Iron-Chelation Therapy.

Neurodegeneration with brain iron accumulation (NBIA) comprises various rare clinical entities with brain iron overload as a common feature. Magnetic resonance imaging (MRI) allows diagnosis of this condition, and genetic molecular testing can confirm the diagnosis to better understand the intracellular damage mechanism involved. NBIA groups disorders include: pantothenate kinase-associated neurodegeneration (PKAN), mutations in the gene encoding pantothenate kinase 2 (PANK2); neuroferritinopathy, mutations in the calcium-independent phospholipase A2 gene (PLA2G6); aceruloplasminemia; and other subtypes with no specific clinical or MRI specific patterns identified. There is no causal therapy, and only symptom treatments are available for this condition. Promising strategies include the use of deferiprone (DFP), an orally administered bidentate iron chelator with the ability to pass through the blood-brain barrier. This is a prospective study analysis with a mean follow-up time of 5.5 ± 2.3 years (min-max: 2.4-9.6 years) to define DFP (15 mg/kg bid)'s efficacy and safety in the continuous treatment of 10 NBIA patients through clinical and neuroradiological evaluation. Our results show the progressive decrease in the cerebral accumulation of iron evaluated by MRI and a substantial stability of the overall clinical neurological picture without a significant correlation between clinical and radiological findings. Complete ferrochelation throughout the day appears to be of fundamental importance considering that oxidative damage is generated, above, all by non-transferrin-bound iron (NTBI); thus, we hypothesize that a (TID) administration regimen of DFP might better apply its chelating properties over 24 h with the aim to also obtain clinical improvement beyond the neuroradiological improvement.

A multinational consensus on dysphagia in Parkinson's disease: screening, diagnosis and prognostic value.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder characterized by a combination of motor and non-motor dysfunction. Dysphagia is a common symptom in PD, though it is still too frequently underdiagnosed. Consensus is lacking on screening, diagnosis, and prognosis of dysphagia in PD. OBJECTIVE: To systematically review the literature and to define consensus statements on the screening and the diagnosis of dysphagia in PD, as well as on the impact of dysphagia on the prognosis and quality of life (QoL) of PD patients. METHODS: A multinational group of experts in the field of neurogenic dysphagia and/or PD conducted a systematic revision of the literature published since January 1990 to February 2021 and reported the results according to PRISMA guidelines. The output of the research was then analyzed and discussed in a consensus conference convened in Pavia, Italy, where the consensus statements were drafted. The final version of statements was subsequently achieved by e-mail consensus. RESULTS: Eighty-five papers were used to inform the Panel's statements even though most of them were of Class IV quality. The statements tackled four main areas: (1) screening of dysphagia: timing and tools; (2) diagnosis of dysphagia: clinical and instrumental detection, severity assessment; (3) dysphagia and QoL: impact and assessment; (4) prognostic value of dysphagia; impact on the outcome and role of associated conditions. CONCLUSIONS: The statements elaborated by the Consensus Panel provide a framework to guide the neurologist in the timely detection and accurate diagnosis of dysphagia in PD.

Consensus on the treatment of dysphagia in Parkinson's disease.

BACKGROUND: Dysphagia is common in Parkinson's disease (PD). The effects of antiparkinsonian drugs on dysphagia are controversial. Several treatments for dysphagia are available but there is no consensus on their efficacy in PD. OBJECTIVE: To conduct a systematic review of the literature and to define consensus statements on the treatment of dysphagia in PD and related nutritional management. METHODS: A multinational group of experts in the field of neurogenic dysphagia and/or Parkinson's disease conducted a systematic evaluation of the literature and reported the results according to PRISMA guidelines. The evidence from the retrieved studies was analyzed and discussed in a consensus conference organized in Pavia, Italy, and the consensus statements were drafted. The final version of statements was subsequently achieved by e-mail consensus. RESULTS: The literature review retrieved 64 papers on treatment and nutrition of patients with PD and dysphagia, mainly of Class IV quality. Based on the literature and expert opinion in cases where the evidence was limited or lacking, 26 statements were developed. CONCLUSIONS: The statements developed by the Consensus panel provide a guidance for a multi-disciplinary treatment of dysphagia in patients with PD, involving neurologists, otorhinolaryngologists, gastroenterologists, phoniatricians, speech-language pathologists, dieticians, and clinical nutritionists.

Dual task gait deteriorates gait performance in cervical dystonia patients: a pilot study.

Day-to-day walking-related activities frequently involve the simultaneous performance of two or more tasks (i.e., dual task). Dual task ability is influenced by higher order cognitive and cortical control mechanisms. Recently, it has been shown that the concomitant execution of an attention-demanding task affected postural control in subject with cervical dystonia (CD). However, no study has investigated whether dual tasking might deteriorate gait performance in CD patients. To investigate whether adding a concomitant motor and cognitive tasks could affect walking performance in CD subjects.17 CD patients and 19 healthy subjects (HS) participated in this pilot case-control study. Gait performance was evaluated during four walking tasks: usual, fast, cognitive dual task and obstacle negotiation. Spatiotemporal parameters, dual-task cost and coefficients of variability (CV%) were measured by GaitRite® and were used to detect differences between groups. Balance performance was also assessed with Mini-BEST and Four Step Square tests. In CD participants, correlation analysis was computed between gait parameters and clinical data. Significant differences in complex gait and balance performance were found between groups. CD patients showed lower speed, longer stance time and higher CV% and dual-task cost compared to HS. In CD, altered gait parameters correlated with balance performance and were not associated with clinical features of CD. Our findings suggest that complex walking performance is impaired in patients with CD and that balance and gait deficits might be related.

The Current Evidence for the Use of Safinamide for the Treatment of Parkinson's Disease.

INTRODUCTION: Parkinson's therapeutic interventions are only symptomatic. An optimal treatment should therefore address the largest number of motor and non-motor symptoms, to manage patients at best. Safinamide is one of the most recent approved drugs for fluctuating patients, in add-on to levodopa, that remains the gold standard treatment. It has a unique mechanism of action, both dopaminergic (as MAO-B inhibitor) and glutamatergic (through Na+ channel blockade). Results from Phase III trials, post-hoc analyses and real-life experiences suggest a beneficial effect on motor (such as tremor, bradykinesia, rigidity and gait) and non-motor (pain, mood, sleep) symptoms. AREAS COVERED: Here, the authors discuss clinical efficacy and safety of safinamide, identifying the patients' profiles that could benefit most. A search in PubMed was performed in September 2020, with no time limits. Publications' abstracts were reviewed. CONCLUSION: Safinamide is peculiar due to its double mechanism of action. Its benefits in improving motor functions and fluctuations, and some non-motor symptoms, could have a valuable impact on patients' quality of life (QoL), together with its safety profile.

Dysphagia in multiple system atrophy consensus statement on diagnosis, prognosis and treatment.

Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by a combination of autonomic failure plus cerebellar syndrome and/or parkinsonism. Dysphagia is a frequent and disabling symptom in MSA and its occurrence within 5 years of motor onset is an additional diagnostic feature. Dysphagia can lead to aspiration pneumonia, a recognized cause of death in MSA. Guidelines for diagnosis and management of dysphagia in MSA are lacking. An International Consensus Conference among experts with methodological support was convened in Bologna to reach consensus statements for the diagnosis, prognosis, and treatment of dysphagia in MSA. Abnormalities of the oral and pharyngeal phases of swallowing, esophageal dysfunction and aspiration occur in MSA and worsen as the disease progresses. According to the consensus, dysphagia should be investigated through available screening questionnaires and clinical and instrumental assessment (videofluoroscopic study or fiberoptic endoscopic evaluation of swallowing and manometry) at the time of MSA diagnosis and periodically thereafter. There is evidence that dysphagia is associated with poor survival in MSA, however effective treatments for dysphagia are lacking. Compensatory strategies like diet modification, swallowing maneuvers and head postures should be applied and botulinum toxin injection may be effective in specific conditions. Percutaneous endoscopic gastrostomy may be performed when there is a severe risk of malnutrition and pulmonary complications, but its impact on survival is undetermined. Several research gaps and unmet needs for research involving diagnosis, prognosis, and treatment were identified.

A European Observational Study to Evaluate the Safety and the Effectiveness of Safinamide in Routine Clinical Practice: The SYNAPSES Trial.

BACKGROUND: Safinamide modulates both dopaminergic and glutamatergic systems with positive effects on motor and non-motor symptoms of Parkinson's disease (PD). The drug utilization study SYNAPSES was designed to investigate the use of safinamide in routine clinical practice, as recommended by the European Medicines Agency. OBJECTIVE: To describe the occurrence of adverse events in PD patients treated with safinamide in real-life conditions. METHODS: The SYNAPSES trial is an observational, European, multicenter, retrospective-prospective cohort study. Patients were followed up to 12 months with analyses performed in the overall population and in patients aged >75 years, with relevant comorbidities and with psychiatric conditions. RESULTS: Of the 1610 patients included, 82.4% were evaluable after 12 months with 25.1% of patients >75 years, 70.8% with relevant comorbidities and 42.4% with psychiatric conditions. During observation 45.8% patients experienced adverse events, 27.7% patients had adverse drug reactions and 9.2% patients had serious adverse events. The adverse events were those already described in the patients' information leaflet. The majority were mild or moderate and completely resolved and no differences were detected between the subgroup of patients. Clinically significant improvements were seen in the UPDRS motor score and in the UPDRS total score in ≥40% of patients, according to the criteria developed by Shulman et al.Conclusion:The SYNAPSES study confirms the good safety profile of safinamide even in special groups of patients. Motor complications and motor scores improved with clinically significant results in the UPDRS scale maintained in the long-term.

Motor and Sensory Features of Cervical Dystonia Subtypes: Data From the Italian Dystonia Registry.

Introduction: Cervical dystonia (CD) is one of the most common forms of adult-onset isolated dystonia. Recently, CD has been classified according to the site of onset and spread, in different clinical subgroups, that may represent different clinical entities or pathophysiologic subtypes. In order to support this hypothesis, in this study we have evaluated whether different subgroups of CD, that clinically differ for site of onset and spread, also imply different sensorimotor features. Methods: Clinical and demographic data from 842 patients with CD from the Italian Dystonia Registry were examined. Motor features (head tremor and tremor elsewhere) and sensory features (sensory trick and neck pain) were investigated. We analyzed possible associations between motor and sensory features in CD subgroups [focal neck onset, no spread (FNO-NS); focal neck onset, segmental spread (FNO-SS); focal onset elsewhere with segmental spread to neck (FOE-SS); segmental neck involvement without spread (SNI)]. Results: In FNO-NS, FOE-SS, and SNI subgroups, head tremor was associated with the presence of tremor elsewhere. Sensory trick was associated with pain in patients with FNO-NS and with head tremor in patients with FNO-SS. Conclusion: The frequent association between head tremor and tremor elsewhere may suggest a common pathophysiological mechanism. Two mechanisms may be hypothesized for sensory trick: a gating mechanism attempting to reduce pain and a sensorimotor mechanism attempting to control tremor.

Recommendations for the Organization of Multidisciplinary Clinical Care Teams in Parkinson's Disease.

BACKGROUND: Optimal management in expert centers for Parkinson's disease (PD) usually involves pharmacological and non-pharmacological interventions, delivered by a multidisciplinary approach. However, there is no guideline specifying how this model should be organized. Consequently, the nature of multidisciplinary care varies widely. OBJECTIVE: To optimize care delivery, we aimed to provide recommendations for the organization of multidisciplinary care in PD. METHODS: Twenty expert centers in the field of multidisciplinary PD care participated. Their leading neurologists completed a survey covering eight themes: elements for optimal multidisciplinary care; team members; role of patients and care partners; team coordination; team meetings; inpatient versus outpatient care; telehealth; and challenges towards multidisciplinary care. During a consensus meeting, outcomes were incorporated into concept recommendations that were reviewed by each center's multidisciplinary team. Three patient organizations rated the recommendations according to patient priorities. Based on this feedback, a final set of recommendations (essential elements for delivery of multidisciplinary care) and considerations (desirable elements) was developed. RESULTS: We developed 30 recommendations and 10 considerations. The patient organizations rated the following recommendations as most important: care is organized in a patient-centered way; every newly diagnosed patient has access to a core multidisciplinary team; and each team has a coordinator. A checklist was created to further facilitate its implementation. CONCLUSION: We provide a practical tool to improve multidisciplinary care for persons with PD at the organizational level. Future studies should focus on implementing these recommendations in clinical practice, evaluating their potential applicability and effectiveness, and comparing alternative models of PD care.

The TANDEM investigation: efficacy and tolerability of levodopa-carbidopa intestinal gel in (LCIG) advanced Parkinson's disease patients.

The TANDEM investigation was carried out in 17 Italian Movement Disorder centers on behalf of a joint initiative of neurologist members of the Italian Academy for Parkinson's disease and Movement Disorders (LIMPE-DISMOV Academy) and gastroenterologist members of the Italian Society of Digestive Endoscopy (SIED) to evaluate the efficacy and tolerability of levodopa-carbidopa intestinal gel (LCIG) in patients with advanced Parkinson's disease (PD) in routine medical care. Motor scores in "ON" and OFF" state (UPDRS-III), complications of therapy (UPDRS-IV), activities of daily living, sleep disorders and quality of life were evaluated at baseline and at two follow-up assessments (FUV1 and FUV2) within the initial 12-month LCIG treatment. In 159 patients (55% males) with a mean age of 69.1 ± 6.6 years and a diagnosis of PD since 13.6 ± 5.5 years, the UPDRS-III total score (in "OFF") decreased from baseline (45.8 ± 13.2) to FUV1 (41.0 ± 17.4; p < 0.001) and FUV2 (40.5 ± 15.5; p < 0.001), the UPDRS-IV total score decreased from baseline (8.8 ± 2.9) to FUV1 (5.1 ± 3.4; p < 0.001) and FUV2 (5.5 ± 3.2; p < 0.001). The percentage of patients exhibiting freezing, dystonia, gait/walking disturbances, falls, pain and sleep disorders was significantly reduced. Twenty-eight device complications were reported and 11 (6.9%) patients prematurely terminated the study. LCIG after 12-month treatment led to sustained improvement of time spent in "OFF", complications of therapy, PD-associated symptoms and sleep disorders. LCIG tolerability was consistent with the established safety profile of LCIG.

Defective Human Motion Perception in Cervical Dystonia Correlates With Coexisting Tremor.

BACKGROUND: The ability to predict temporal outcome of body movement is abnormal in idiopathic dystonia and can be altered by cerebellar neuromodulation. Tremor in cervical dystonia might be associated with performance on motion perception tasks. METHODS: A total of 15 cervical dystonia patients with and 14 without tremor and 15 age-matched healthy participants estimated the termination of videos showing different movements (handwriting a sentence, ball reaching a target) after these were darkened at different time intervals. RESULTS: Cervical dystonia patients with tremor exhibited greater absolute timing error across all intervals of the hand motion task (group × task interaction effect, F2,41 = 4.57; P = 0.016). The percentage of responses in anticipation for both motion tasks did not differ across groups, suggesting lack of timing error directionality. CONCLUSIONS: Temporal processing of perceived motion in cervical dystonia is associated with the presence of tremor. Cortico-cerebellar network abnormalities in cervical dystonia might account for motion processing changes in these patients. © 2020 International Parkinson and Movement Disorder Society.

Tactile and proprioceptive dysfunction differentiates cervical dystonia with and without tremor.

OBJECTIVE: To determine whether different phenotypes of cervical dystonia (CD) express different types and levels of somatosensory impairment. METHODS: We assessed somatosensory function in patients with CD with and without tremor (n = 12 each) and in healthy age-matched controls (n = 22) by measuring tactile temporal discrimination thresholds of the nondystonic forearm and proprioceptive acuity in both the dystonic (head/neck) and nondystonic body segments (forearm/hand) using a joint position-matching task. The head or the wrist was passively displaced along different axes to distinct joint positions by the experimenter or through a robotic exoskeleton. Participants actively reproduced the experienced joint position, and the absolute joint position-matching error between the target and the reproduced positions served as a marker of proprioceptive acuity. RESULTS: Tactile temporal discrimination thresholds were significantly elevated in both CD subgroups compared to controls. Proprioceptive acuity of both the dystonic and nondystonic body segments was elevated in patients with CD and tremor with respect to both healthy controls and patients with CD without tremor. That is, tactile abnormalities were a shared dysfunction of both CD phenotypes, while proprioceptive dysfunction was observed in patients with CD with tremor. CONCLUSIONS: Our findings suggest that the pathophysiology in CD can be characterized by 2 abnormal neural processes: a dysfunctional somatosensory gating mechanism involving the basal ganglia that triggers involuntary muscle spasms and abnormal processing of proprioceptive information within a defective corticocerebellar loop, likely affecting the feedback and feedforward control of head positioning. This dysfunction is expressed mainly in CD with tremor.

A Multimodal Training Modulates Short Afferent Inhibition and Improves Complex Walking in a Cohort of Faller Older Adults With an Increased Prevalence of Parkinson's Disease.

BACKGROUND: Falls are frequent in Parkinson's disease and aging. Impairments in the cholinergic-mediated attentional supervision of gait may contribute to increased fall risk, especially when obstacles challenge gait. Interventions combining motor-cognitive approaches have been shown to improve motor performance, cognitive skills, and falls number. Here, we hypothesized that an intervention simulating an attention-demanding walking condition could affect not only complex gait performance and fall risk but also short-latency afferent inhibition (SAI), as a marker of cholinergic activity. METHODS: Thirty-nine participants at falls risk (24 Parkinson's disease participants and 15 older adults) were recruited in a randomized controlled trial. Participants were assigned to treadmill training or treadmill training with non-immersive virtual reality intervention and trained three times a week for 6 weeks. SAI, a transcranial magnetic stimulation paradigm, was used to assess cholinergic activity. Gait kinematics was measured during usual walking and while negotiating physical obstacles. Transcranial magnetic stimulation and gait assessments were performed pre, post, and 6 months post-intervention. RESULTS: Treadmill training combined with non-immersive virtual reality induced an increase in inhibition of the SAI protocol on cortical excitability, improved obstacle negotiation performance, and induced a reduction of the number of falls compared with treadmill training. Furthermore, the more SAI increased after training, the more the obstacle negotiation performance improved and fall rate decreased. CONCLUSIONS: We provide evidence that an innovative rehabilitation approach targeting cognitive components of complex motor actions can induce changes in cortical cholinergic activity, as indexed by SAI, thereby enabling functional gait improvements.

Stridor in multiple system atrophy: Consensus statement on diagnosis, prognosis, and treatment.

Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by a combination of autonomic failure, cerebellar ataxia, and parkinsonism. Laryngeal stridor is an additional feature for MSA diagnosis, showing a high diagnostic positive predictive value, and its early occurrence might contribute to shorten survival. A consensus definition of stridor in MSA is lacking, and disagreement persists about its diagnosis, prognosis, and treatment. An International Consensus Conference among experts with methodological support was convened in Bologna in 2017 to define stridor in MSA and to reach consensus statements for the diagnosis, prognosis, and treatment. Stridor was defined as a strained, high-pitched, harsh respiratory sound, mainly inspiratory, occurring only during sleep or during both sleep and wakefulness, and caused by laryngeal dysfunction leading to narrowing of the rima glottidis. According to the consensus, stridor may be recognized clinically by the physician if present at the time of examination, with the help of a witness, or by listening to an audio recording. Laryngoscopy is suggested to exclude mechanical lesions or functional vocal cord abnormalities related to different neurologic conditions. If the suspicion of stridor needs confirmation, drug-induced sleep endoscopy or video polysomnography may be useful. The impact of stridor on survival and quality of life remains uncertain. Continuous positive airway pressure and tracheostomy are both suggested as symptomatic treatment of stridor, but whether they improve survival is uncertain. Several research gaps emerged involving diagnosis, prognosis, and treatment. Unmet needs for research were identified.

Haptic perception of verticality correlates with postural and balance deficits in patients with Parkinson's disease.

INTRODUCTION: Perception of verticality is fundamental for postural stability that is often impaired in patients with Parkinson's disease (PD). Haptic perception of verticality has not been fully investigated in PD. The aim of the study was to assess subjective haptic vertical (SHV) in PD patients in relation to postural and balance impairments. METHODS: 39 PD patients (mean age 72.87 ±â€¯5.78) and 28 gender and age-matched healthy elderly (ELD, mean age 69.16 ±â€¯13.89) were enrolled. The Pull test and the Activities-specific Balance Confidence (ABC) were used for evaluating balance performance, whereas measurement of posture was performed using the Physical Analyzer System®. For evaluating SHV, participants were instructed to provide their subjective vertical by manipulating with two hands a road while standing with their eyes closed. RESULTS: SHV data showed that PD subjects had a greater deviation from the objective vertical than controls (p < 0.001). Significant differences in balance performance (ABC and Pull test) and postural alignment were found between PD and ELD. Only in PD participants, SHV deviations significantly correlated with the lateral inclination of the trunk (r = 0.618, p < 0.001), pull test (r = 0.519; p = 0.001) and ABC (r = 0.471, p = 0.002) scores. CONCLUSIONS: The perception of verticality, driven by multimodal sensory integration, is defective in PD subjects. Deficits in SHV correlated with postural alignment and balance performances, independently from age, disease severity or cognitive decline. Our findings support that PD pathology is associated with a decline in haptic perception suggesting that perception per se might have a causal role in postural and balance deficits.

MDS evidence-based review of treatments for essential tremor.

BACKGROUND: Essential tremor is one of the most prevalent movement disorders. Many treatments for essential tremor have been reported in clinical practice, but it is uncertain which options have the most robust evidence. The International Parkinson and Movement Disorder Society commissioned a task force on tremor to review clinical studies of treatments for essential tremor. OBJECTIVES: To conduct an evidence-based review of current pharmacological and surgical treatments for essential tremor, using standardized criteria defined a priori by the International Parkinson and Movement Disorder Society. METHODS: We followed the recommendations of the International Parkinson and Movement Disorder Society Evidence Based Medicine Committee. RESULTS: Sixty-four studies of pharmacological and surgical interventions were included in the review. Propranolol and primidone were classified as clinically useful, similar to Topiramate, but only for doses higher than 200 mg/day. Alprazolam and botulinum toxin type A were classified as possibly useful. Unilateral Ventralis intermedius thalamic DBS, radiofrequency thalamotomy, and MRI-guided focused ultrasound thalamotomy were considered possibly useful. All the above recommendations were made for limb tremor in essential tremor. There was insufficient evidence for voice and head tremor as well as for the remaining interventions. CONCLUSION: Propranolol, primidone, and topiramate (>200 mg/day) are the pharmacological interventions in which the data reviewed robustly supported efficacy. Their safety profile and patient preference may guide the prioritization of these interventions in clinical practice. MRI-guided focused ultrasound thalamotomy was, for the first time, assessed and was considered to be possibly useful. There is a need to improve study design in essential tremor and overcome the limitation of small sample sizes, cross-over studies, short-term follow-up studies, and use of nonvalidated clinical scales. © 2019 International Parkinson and Movement Disorder Society.

Efficacy and safety of deferiprone for the treatment of superficial siderosis: results from a long-term observational study.

BACKGROUND: Superficial siderosis (SS) of the central nervous system is a rare and heterogeneous condition due to deposition of hemosiderin on the surface of the brain and spinal cord. The usually progressive clinical course is characterized by a combination of hearing loss, cerebellar ataxia, and myelopathy. There is no known treatment for SS, but the iron chelator deferiprone (DFP) has been proposed as a potentially useful treatment. METHODS: We present a long-term (average 3.7 years) evaluation of four cases of SS treated with DFP (15 mg/kg po bid). RESULTS: Treatment with DFP proved safe and well tolerated. Two out of the four subjects were unchanged while the other two presented a clinical improvement with reduction of postural instability and cerebellar signs. Blinded evaluation of magnetic resonance imaging (performed every 6 months during follow-up) showed a reduction of the abnormal iron deposition for all patients. CONCLUSIONS: This long-term observational study suggests that DFP may be effective in the management of the neurological manifestations associated with iron accumulation in SS. CLINICALTRIALS. GOV IDENTIFIER: NTC00907283.

Spastic dystonia in stroke subjects: prevalence and features of the neglected phenomenon of the upper motor neuron syndrome.

OBJECTIVE: Spastic dystonia is one of the positive phenomena of the upper motor neuron syndrome (UMNS). It is characterised by the inability to relax a muscle leading to a spontaneous, although stretch-sensitive, tonic contraction. Although spastic dystonia is a recognized cause of muscle hypertonia, its prevalence among hypertonic muscles of stroke subjects has never been investigated. Differently from spasticity, which is an exaggerated stretch reflex, spastic dystonia is viewed as an efferent phenomenon, due to an abnormal central drive to motoneurons. METHODS: In 23 hemiparetic stroke subjects showing increased muscle tone of wrist flexors, surface EMG was used to investigate the presence of spontaneous, stretch-sensitive EMG activity in flexor carpi radialis. RESULTS: Spontaneous, stretch-sensitive EMG activity was found in 17 subjects. In the remaining 6 subjects, no spontaneous EMG activity was found. CONCLUSIONS: The majority of stroke subjects is affected by spastic dystonia in their hypertonic wrist flexor muscles. Only a minority of subjects is affected by spasticity. SIGNIFICANCE: To stop spastic dystonia from being the neglected aspect of UMNS, it is essential to link its definition to increased muscle tone, as occurred for spasticity. Recognizing the real phenomena underling muscle hypertonia could improve its management.