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Background Longitudinal cohort studies provide important information about the clinical effectiveness of an intervention in the routine clinical setting, and are an opportunity to understand how a population presents for treatment and is managed. Methods INTEREST IN CD2 (NCT01753349) is a prospective, international, 3-year, longitudinal, observational study following the course of adult idiopathic cervical dystonia (CD) treated with botulinum neurotoxin type A (BoNT-A). The primary objective is to document long-term patient satisfaction with BoNT-A treatment. Here we report baseline data. Results This analysis includes 1036 subjects (67.4% of subjects were female; mean age was 54.7 years old; mean TWSTRS Total score was 31.7). BoNT-A injections were usually given in line with BoNT-A prescribing information. The most commonly injected muscles were splenius capitis (87.3%), sternocleidomastoid (82.6%), trapezius (64.3%), levator scapulae (40.9%) and semispinalis capitis (26.9%); 35.5% of subjects were injected using a guidance technique. Most subjects (87.8%) had been previously treated with BoNT-A (median interval between last pre-study injection and study baseline was 4 months); of these 84.8% reported satisfaction with BoNT-A treatment at peak effect during their previous treatment cycle and 51.5% remained satisfied at the end of the treatment. Analyses by geographical region revealed heterogeneity in the clinical characteristics and BoNT-A injection practice of CD subjects presenting for routine treatment. Conclusions These baseline analyses provide sizeable data regarding the epidemiology and clinical presentation of CD, and demonstrate an international heterogeneity of clinical practice. Future longitudinal analyses of the full 3-year study will explore how these factors impact treatment satisfaction. Electronic supplementary material The online version of this article (10.1007/s00415-017-8698-2) contains supplementary material, which is available to authorized users.

Objective: To describe the utility of a structured approach to assessing effectiveness following injection with botulinum toxin-A alongside physical therapies, within the first cycle of the Upper Limb International Spasticity-III (ULIS-III) study. Methods: ULIS-III (registered at clinicaltrials.gov as NCT02454803) is a large international, observation-al, longitudinal study of adults treated for upper-limb spasticity. It introduces novel methods for the structured evaluation of person-centred goal attainment alongside targeted standardized outcome measures: the Upper limb Spasticity Index, and the Upper Limb Spasticity Therapy Recording Schedule. Results: A total of 953/1,004 enrolled patients (95%) completed cycle 1. Mean overall goal attainment scaling (GAS) T scores were 49.8 (95% confidence interval 49.2–50.3; 67.1% of patients met their primary goal, with highest achievement rates for goals related to involuntary movement, (75.6%) and range of movement (74.4%). Standardized measures of spasticity, pain, involuntary movements, active and passive function, all improved significantly over the treatment cycle. Overall, 59.7% of patients saw a therapist following botulinum toxin-A injection. Interventions varied, as expected, with the set treatment goals. After controlling for concomitant therapies using the upper limb spasticity therapy recording schedule, significant differences in injection intervals (p

BACKGROUND: Pain is often experienced by patients with functional dystonia and idiopathic cervical dystonia and is likely to be determined by different neural mechanisms. OBJECTIVE: In this exploratory study, we tested the sensory-discriminative and cognitive-emotional component of pain in patients with functional and idiopathic dystonia. METHODS: Ten patients with idiopathic cervical dystonia, 12 patients with functional dystonia, and 16 age- and sex-matched healthy controls underwent psychophysical testing of tactile and pain thresholds and pain tolerance. We delivered electrical pulses of increasing intensity to the index finger of each hand and the halluces of each foot. Pain threshold and pain tolerance were respectively defined as the (1) intensity at which sensation changed from unpainful to faintly painful and (2) intensity at which painful sensation was intolerable. RESULTS: No differences were found between the three groups for tactile and pain thresholds assessed in hands and feet. Pain tolerance was significantly increased in all body regions only in functional dystonia. Patients with continuous functional dystonia had higher pain tolerance compared to subjects with paroxysmal functional dystonia and idiopathic cervical dystonia. There was no correlation between pain tolerance and pain scores, depression, anxiety, disease duration, and motor disability in both groups. CONCLUSIONS: Patients with functional dystonia have a dissociation between the sensory-discriminative and cognitive-emotional components of pain, as revealed by normal pain thresholds and increased pain tolerance. Abnormal connectivity between the motor and limbic systems might account for abnormal pain processing in functional dystonia. © 2018 International Parkinson and Movement Disorder Society.

Background\ud Movement disorders associated with complex regional pain syndrome type I have been a subject of controversy over the last 10 years regarding their nature and pathophysiology, with an intense debate about the functional (psychogenic) nature of this disorder. The aim of this study was to test sensorimotor plasticity and cortical excitability in patients with complex regional pain syndrome type I who developed a fixed posture of the hand.\ud \ud Methods\ud Ten patients with complex regional pain syndrome type I in the right upper limb and a fixed posture of the hand (disease duration less than 24 months) and 10 age‐matched healthy subjects were enrolled. The following parameters of corticospinal excitability were recorded from the abductor pollicis brevis muscle of both hands by transcranial magnetic stimulation: resting and active motor thresholds, short‐interval intracortical inhibition and facilitation, cortical silent period, and short‐ and long‐latency afferent inhibition. Sensorimotor plasticity was tested using the paired associative stimulation protocol.\ud \ud Results\ud Short‐interval intracortical inhibition and long‐latency afferent inhibition were reduced only in the affected right hand of patients compared with control subjects. Sensorimotor plasticity was comparable to normal subjects, with a preserved topographic specificity.\ud \ud Conclusions\ud Our data support the view that motor disorder in complex regional pain syndrome type I is not associated with abnormal sensorimotor plasticity, and it shares pathophysiological abnormalities with functional (psychogenic) dystonia rather than with idiopathic 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.

We report on a new maternally-inherited syndrome characterized by a combination of sensorineural hearing loss, ataxia and myoclonus in a large kindred from Sicily, Hearing loss was the most widespread and sometimes the only symptom found in family members. Sequence analysis of the mitochondrial DNA regions encompassing the tRNA genes revealed the presence of a heteroplasmic insertion at nucleotide position 7472. The insertion adds a seventh cytosine to a six-cytosine run that is part of the mitochondrial tRNA(Ser(UCN)) gene, Conformational analysis showed that this mutation is likely to alter the structure of the T Psi C loop in the tRNA(Ser(UCN)) clover leaf secondary structure, Moreover, the degree of heteroplasmy in blood and muscle was correlated with the clinical phenotype, and homoplasmic mutant cybrids showed decreased complex I activity, low oxygen consumption and high lactic acid output, indicating faulty oxidative phosphorylation, Finally, mutation was absent in 381 unrelated maternal lineages, suggesting specific segregation with the disease. We propose that the C7472 insertion-mutation is pathogenic, and etiologically related to hearing loss and other symptoms that define a novel maternally-inherited clinical entity.

A man who was using 9-alpha-fluoroprednisolone-containing nasal spray preparation for allergic rhinitis developed a pseudohyperaldosteronism and an acute hypokalemic myopathy. Muscle biopsy changes included variation in fiber size with preserved type 2a fibers, necrosis, phagocytosis and regeneration. This factitious mineralocorticoid excess syndrome, induced by uncontrolled use of intranasally administered steroid, should be considered among the various causes of hypokalemic myopathy.

We used a CAPSIT-based questionnaire to estimate the percentage of parkinsonian patients suitable for subthalamic nucleus (STN) deep brain stimulation (DBS) in a movement disorders clinic. We found that out of 641 consecutive PD patients only 1.6% fulfilled strict STN-DBS criteria. When we applied more flexible criteria, the percentage of eligibility increased to 4.5%. Most patients (60%) were ineligible because they did not satisfy multiple questionnaire items. Items related to disease severity were responsible for the largest number of exclusions. This knowledge will help make decisions on resource allocation in centres wishing to start DBS surgery.

Cognitive dysfunction is considered one of the clinical markers of multiple sclerosis (MS). However, in the literature there are inconsistent reports on the prevalence of cognitive dysfunction, and separate data for the relapsing-remitting (RR) type of the disease are not always presented. In this study, we submitted 461 RRMS patients to a battery of neuropsychological tests to investigate their impairment in various cognitive domains. As a consequence of the exclusion criteria, the sample is not fully representative of the entire population of RRMS patients. In this selected sample, when only the eight scores of a core battery (Mental Deterioration Battery) were considered (with respective cutoffs), it emerged that 31% of the patients were affected by some degree of cognitive deficit. In particular, 15% had mild, 11.2% moderate and 4.8% had severe impairment. Information processing speed was the most frequently impaired area, followed by memory. When two other tests (SDMT and MCST) were added and cognitive domains were considered, it emerged that 39.3% of the patients were impaired in two or more domains. When four subgroups were obtained by means of cluster analysis and then compared, it emerged that information processing speed and memory deficits differentiated the still cognitively unimpaired from the mildly impaired MS patients. Significant associations were found between cognitive and clinical characteristics. However, due to the large sample size, clinically irrelevant relationships may also have emerged. Even with the limitations imposed by the sample selection and the possible underestimation of the prevalence and severity of cognitive dysfunction, these results seem to provide further evidence that information processing speed deficit may be an early and important marker of cognitive impairment in MS patients.

Background: Diagnosis of focal dystonia is based on clinical grounds and is therefore open to bias. To date, diagnostic guidelines have been only proposed for blepharospasm and laryngeal dystonia. To provide practical guidance for clinicians with less expertise in dystonia, a group of Italian Movement Disorder experts formulated clinical diagnostic recommendations for cervical, oromandibular, and limb dystonia. Methods: A panel of four neurologists generated a list of clinical items related to the motor phenomenology of the examined focal dystonias and a list of clinical features characterizing neurological/non-neurological conditions mimicking dystonia. Thereafter, ten additional expert neurologists assessed the diagnostic relevance of the selected features and the content validity ratio was calculated. The clinical features reaching a content validity ratio > 0.5 contributed to the final recommendations. Results: The recommendations retained patterned and repetitive movements/postures as the core feature of dystonia in different body parts. If present, a sensory trick confirmed diagnosis of dystonia. In the patients who did not manifest sensory trick, active exclusion of clinical features related to conditions mimicking dystonia (features that would be expected to be absent in dystonia) would be necessary for dystonia to be diagnosed. Discussion: Although reliability, sensitivity, and specificity of the recommendations are yet to be demonstrated, information from the present study would hopefully facilitate diagnostic approach to focal dystonias in the clinical practice and would be the basis for future validated diagnostic guidelines.

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.