Dose-dependent relationship between nocturnal gastroesophageal reflux and chronic rhinosinusitis in a middle-aged population: results from the SCAPIS pilot.

BACKGROUND: Gastroesophageal reflux (GER) has been associated with several upper- and lower-airway diseases. It would be plausible if nightly occurring reflux via laryngopharyngeal reflux (LPR) might affect the upper airways. Still, the role of nocturnal gastroesophageal reflux (nGER) in chronic rhinosinusitis (CRS) is not fully established. The aim of this population-based study was to investigate the association between nGER and CRS. METHODOLOGY: This cross-sectional population-based study comprises 1,111 randomly selected subjects from Gothenburg, Sweden, aged 50-64 years. The study is based on self-reported validated questionnaires. CRS was defined according to EPOS criteria. nGER was reported in relation to frequency. RESULTS: CRS was more common among subjects with nGER than in those without (13 vs. 4.8%). There was a dose-response association between the frequency of nGER episodes and the risk of having CRS. In the logistic regression adjusted for (age, sex, BMI, educational level, smoking, and asthma). CRS was associated with nGER, OR 1.43 and the odds ratio increased if episodes were reported 'almost every night' OR 4.6. CONCLUSIONS: The study shows an association between nocturnal GER and CRS in a middle-aged population. The revealed dose dependency supports, though does not prove causality.

Subclinical motor impairment assessed with an engineered glove correlates with magnetic resonance imaging tissue damage in radiologically isolated syndrome.

BACKGROUND: An engineered glove measuring finger motor performance previously showed ability to discriminate early-stage multiple sclerosis (MS) patients from healthy controls (HCs). Radiologically isolated syndrome (RIS) classifies asymptomatic subjects with brain magnetic resonance imaging (MRI) abnormalities suggestive of multiple sclerosis. METHODS: Seventeen asymptomatic subjects with RIS and 17 HCs were assessed. They performed finger-to-thumb opposition sequences at their maximal velocity, metronome-paced bimanual movements and conventional and diffusion tensor MRI. RESULTS: Subjects with RIS showed lower (P = 0.005) maximal velocity and higher (P = 0.006) bimanual coordination impairment than HCs. In RIS, bimanual coordination correlated with T2-lesion volume, fractional anisotropy and radial diffusivity in the white matter. CONCLUSIONS: These findings point out the relevance of fine hand measures as a robust marker of subclinical disability.

Relationship between extralaryngeal endoscopic findings, proton pump inhibitor (PPI) response, and pH measures in suspected laryngopharyngeal reflux.

Laryngopharyngeal reflux (LPR) is a clinical entity diagnosed by history laryngoscopic findings that has a variable response to empiric proton-pump inhibitor (PPI) therapy. While the reflux finding score (RFS), an endoscopic scoring scheme, has been advanced as a measure of LPR, it has not been externally validated against symptom severity in practice. Extralaryngeal pharyngeal endoscopic findings may have diagnostic utility but remain underexplored. This study assesses the correlation between extralaryngeal findings and (1) 24-hour oropharyngeal pH & (2) PPI response in patients with suspected LPR. Subjects presented to a tertiary care center with laryngeal symptoms ≥1 month and reflux symptom index (RSI) ≥13. Following baseline questionnaires, laryngoscopy, and a 24-hour oropharyngeal pH probe study, subjects were prescribed 8-12 week omeprazole trials. Baseline endoscopic findings were scored in a blinded fashion using the RFS and extralaryngeal score criteria, summatively the 'ELS.' PPI response was defined as ≥50% improvement in RSI. Thirty-three subjects with flexible endoscopic recordings completed baseline and follow-up questionnaires. The cohort's baseline mean RSI was 23.0 ± 7.2 with a ΔRSI = 9.8 after PPI therapy. The baseline RFS score averaged 5.3 ± 2.7. 45% of our subjects was found to be PPI responsive. The Cohen's kappa for the ELS but not the RFS was significant. There were no significant differences between the RFS (P = 0.10) or ELS (P = 0.07) for PPI responders & nonresponders. Oropharyngeal pH measures did not correlate with the RFS or ELS. In conclusion, endoscopic scores of laryngeal and extralaryngeal findings did not predict PPI response or oropharyngeal acid exposure in suspected LPR.

N-3 PUFA diet enrichment prevents amyloid beta-induced depressive-like phenotype.

Among neuropsychiatric diseases, depression is one of the most prevalent. Many pathologies have been indicated as comorbid with depression and in particular, neurodegenerative disorders such as Alzheimer's diseases (AD). In this regard, several evidences endorse a strong relationship between depression and AD, so much that this mental illness has been proposed either as a risk factor for AD or as a prodromic AD phase. Furthermore, amyloid beta (Aß) peptide, the main constituent of amyloid plaques commonly considered the principal hallmark of AD brains, has been shown to be increased, in its soluble form, in depressed patients. Accordingly, we have previously found that Aß, intracerebroventricularly (i.c.v.) injected, is able to evoke a depressive-like profile in rats accompanied by low cortical serotonin and reduced neurotrophin content. Taking into account the great increase in AD and depression prevalence, many environmental factors have been under study, particularly dietary factors, and the role of polyunsaturated fatty acids (PUFA) is becoming central in this field of research. Thus, aim of the present study was to evaluate the neurobehavioral effects of lifelong exposure to either n-3 PUFA rich or n-3 PUFA poor diet after Aß central administration. Results showed that n-3 PUFA enriched diet prevented the Aß- induced depressive-like behaviors, as reveled by the reduction in the immobility time in the FST test. Furthermore, n-3 PUFA rich diet exposure reverted also serotonin and neurotrophin level reduction in prefrontal cortex of Aß treated rats. Taken together, our data support the concept that supplementation of diet with n-3 PUFA represents a valid approach to reduce the risk of developing depressive symptoms, as well as reducing the risk of Aß-related pathologies, such as AD.

Eosinophils from eosinophilic oesophagitis patients have T cell suppressive capacity and express FOXP3.

Eosinophilic esophagitis (EoE) is an antigen-driven T cell-mediated chronic inflammatory disease where food and environmental antigens are thought to have a role. Human eosinophils express the immunoregulatory protein galectin-10 and have T cell suppressive capacity similar to regulatory T cells (Tregs ). We hypothesized that one function of eosinophils in EoE might be to regulate the T cell-driven inflammation in the oesophagus. This was tested by evaluating the suppressive capacity of eosinophils isolated from the blood of adult EoE patients in a mixed lymphocyte reaction. In addition, eosinophilic expression of forkhead box protein 3 (FOXP3), the canonical transcription factor of Tregs , was determined by conventional and imaging flow cytometry, quantitative polymerase chain reaction (qPCR), confocal microscopy and immunoblotting. It was found that blood eosinophils from EoE patients had T cell suppressive capacity, and that a fraction of the eosinophils expressed FOXP3. A comparison of EoE eosinophils with healthy control eosinophils indicated that the patients' eosinophils had inferior suppressive capacity. Furthermore, a higher percentage of the EoE eosinophils expressed FOXP3 protein compared with the healthy eosinophils, and they also had higher FOXP3 protein and mRNA levels. FOXP3 was found in the cytosol and nucleus of the eosinophils from both the patients and healthy individuals, contrasting with the strict nuclear localization of FOXP3 in Tregs . To conclude, these findings suggest that the immunoregulatory function of eosinophils may be impaired in EoE.

Differences in eosinophil molecular profiles between children and adults with eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) afflicts both children and adults. It has been debated whether pediatric EoE and adult EoE represent different disease entities. The objectives of this study were to determine whether the blood eosinophil molecular pattern of children with EoE is (i) distinct from that of healthy children; and (ii) different from that of adults with EoE. METHODS: Blood eosinophils from children and adults with EoE, and healthy controls, were analyzed with flow cytometry regarding levels of CD23, CD44, CD54, CRTH2, FOXP3, and galectin-10. Eosinophil FOXP3 and galectin-10 mRNA levels were determined by qPCR. The data were analyzed using a multivariate method of pattern recognition. RESULTS: An eosinophil molecular pattern capable of distinguishing children with EoE from control children was identified. A smaller fraction of eosinophils from children with EoE expressed CD44 and a larger fraction expressed CRTH2 than the controls. Eosinophils from children with EoE also had higher levels of galectin-10 mRNA and lower levels of FOXP3 mRNA. The eosinophils from children with EoE had lower levels of surface CD54 and of FOXP3 mRNA compared with the eosinophils from the adult patients. A key finding was the detection in healthy individuals of age-related differences in the levels of several eosinophil markers. CONCLUSIONS: Children with EoE can be distinguished from healthy children based on the molecular patterns of their blood eosinophils. Age-related physiologic differences in eosinophil molecular patterns may partly explain the different blood eosinophil phenotypes in children vs adults with EoE.

Grade of eosinophilia versus symptoms in patients with dysphagia and esophageal eosinophilia.

The aim of this study was to assess whether the symptom severity and health-related quality of life (HRQL) of patients with dysphagia and esophageal eosinophilia correlate with disease activity as expressed by the number of eosinophils in the esophageal mucosa. This study included newly diagnosed (n = 58) or relapsed patients (n = 7), where 40% were diagnosed in connection with esophageal bolus impaction. The mean age was 45 years (19-88), and 74% were men. Symptoms and HRQL were recorded using the Watson Dysphagia Scale (WDS), the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Oesophageal Module 18 and the Short Form-36 Questionnaire. Histological samples gathered from the proximal and distal esophageal mucosa were stained using both hematoxylin and eosin (HE) and an immunohistochemical (IHC) technique against 'Eosinophil Major Basic Protein,' and the peak number of eosinophils per high-power field was assessed. More eosinophils were detected after IHC staining than HE staining (P < 0.001). No correlation was found between symptoms or the HRQL and the number of eosinophils. However, higher numbers of eosinophils at the proximal esophagus were found in patients with concomitant bolus impaction (IHC P < 0.05 and HE P < 0.05) and could serve as a risk marker.

Kodamaea ohmeri isolate from two immunocompromised patients: first report in Italy.

Kodamaea ohmeri is an unusual yeast-form fungus that has recently been identified as an important aetiological agent of fungaemia, endocarditis, cellulitis, funguria and peritonitis in immunocompromised patients. We present two new isolated of K. ohmeri. The microorganisms were identified by CHROMagar Candida medium, VitekII system and API ID32C. Biochemical identification of the two yeast isolates was confirmed by sequence analysis of the 26S ribosomal DNA. Antifungal susceptibility testing done by Sensititre YeastOne showed that the isolates were susceptible to amphotericin B, voriconazole and itraconazole. This work is the first report of isolation of K. ohmeri in immunocompromised patients in Italy.

Bacterial flora of the human oral cavity, and the upper and lower esophagus.

This reference study aims to survey the bacterial flora of the healthy lower human esophagus and to compare it with that of the upper esophagus and oral mucosa. The use of biopsies, in addition to brush samples, allows inclusion of not only transient bacteria present on the surface but also bacteria residing in the epithelia, and the yield of the two methods can be compared. Forty patients scheduled for surgery for reasons with no known influence on esophageal flora and with no symptoms or endoscopic signs of esophageal disease were included. Samples were collected from the oral, upper esophageal, and lower esophageal mucosa using sealed brushes and biopsy forceps. Colonies cultivated on agar plates were classified and semiquantified. Twenty-three different bacterial species were identified, with similar strains present at the three sites. The most common group of bacteria was viridans streptococci, with an occurrence rate in brush samples and biopsies of 98% and 95%, respectively. The median number of species occurring in the oral cavity, upper esophagus, and lower esophagus was between 3 and 4 (range 0-7). The total number of species in the oral cavity was significantly higher when compared with either level in the esophagus, while the yields obtained by brush and biopsy sampling were highly correlated. Hence, the normal human esophagus is colonized with a resident bacterial flora of its own, which has similarities to that of the oral mucosa. There are diverse species that make up this flora, although in relatively low amounts. The most frequent inhabitants of the esophagus are streptococci, with an occurrence rate in brush samples and biopsies of 95-98%. Comparative studies of patients with eosinophilic esophagitis and gastroesophageal reflux disease are warranted.

[Acute liver failure due to human herpesvirus 6 in an infant]. / Insufficienza epatica acuta da Human Herpesvirus 6 in un lattante.

We report a case of a 4-months infant with fever in the absence of other specific symptoms that has rapidly and unexpectedly developed acute liver failure (ALF) with coagulopathy and complicated with bone marrow failure without encephalopathy. The main viral infection agents (hepatitis virus A, B, C, Citomegalovirus, Ebstain Barr virus, Parvovirus B19, Adenovirus), drug-induced hepatotoxicity and metabolic disorders associated to ALF were excluded. Quantitative determination of Human Herpesvirus 6 (HHV6) genome was positive with a significant number of copies for mL. A favorable evolution of the clinical symptoms and a progressive hematochemical resolution were obtained. Plasma and Vitamin K were administrated as a support therapy for treating coagulopathy. The present case report and the cases' review from the literature, evidence the importance of always including screening for HHV6 infection in the diagnostic approach to acute onset of liver failure. HHV6 is a common virus in the pediatric population with a greater number of cases of fulminant viral non-A, non-B, non-C hepatitis in immunocompetent patients due to this virus: these forms have often a high mortality rate and maybe necessitate liver transplantation; for this reason correct etiological agent identification is mandatory for the prognosis and it has to be based on the quantitative search of the virus's genome. Pathogenesis of liver-induced damage associated to HHV6 remains unclear; however in vitro studies demonstrate the potential hepatotoxicity effects of this virus.

Use of near infrared spectroscopy for hemodynamic monitoring in pediatrics. / Utilidad del monitoreo hemodinámico con espectroscopia cercana infrarroja en pediatría.

Near infrared spectroscopy (NIRS) is a non-invasive optical technique for the evaluation of regional tissue oxygenation using transcutaneous detectors. In recent years, publications about this topic have increased exponentially; this reflects the growing interest among investigators and clinicians about this new technology and its potential benefits for pediatric patients. The objective of this review is to know the functioning and potential uses of regional saturation measured by NIRS and establish future challenges.

La espectroscopia cercana infrarroja (NIRS, por su sigla en inglés), es una técnica óptica no invasiva y no ionizante utilizada para medir la oxigenación tisular regional a través de sensores transcutáneos. En los últimos años, han aumentado de manera exponencial las publicaciones sobre este tema; esto refleja el creciente interés de investigadores y clínicos por la utilización de esta nueva tecnología y los beneficios que podría ofrecerles a los pacientes pediátricos. El objetivo de esta revisión es dar a conocer el funcionamiento y las posibles aplicaciones de la saturación regional medida por NIRS, así como los desafíos en el futuro.

Impairment in explicit visuomotor sequence learning is related to loss of microstructural integrity of the corpus callosum in multiple sclerosis patients with minimal disability.

Sequence learning can be investigated by serial reaction-time (SRT) paradigms. Explicit learning occurs when subjects have to recognize a test sequence and has been shown to activate the frontoparietal network in both contralateral and ipsilateral hemispheres. Thus, the left and right superior longitudinal fasciculi (SLF), connecting the intra-hemispheric frontoparietal circuits, could have a role in explicit unimanual visuomotor learning. Also, as both hemispheres are involved, we could hypothesize that the corpus callosum (CC) has a role in this process. Pathological damage in both SLF and CC has been detected in patients with Multiple Sclerosis (PwMS), and microstructural alterations can be quantified by Diffusion Tensor Imaging (DTI). In light of these findings, we inquired whether PwMS with minimal disability showed impairments in explicit visuomotor sequence learning and whether this could be due to loss of white matter integrity in these intra- and inter-hemispheric white matter pathways. Thus, we combined DTI analysis with a modified version of SRT task based on finger opposition movements in a group of PwMS with minimal disability. We found that the performance in explicit sequence learning was significantly reduced in these patients with respect to healthy subjects; the amount of sequence-specific learning was found to be more strongly correlated with fractional anisotropy (FA) in the CC (r=0.93) than in the left (r=0.28) and right SLF (r=0.27) (p for interaction=0.005 and 0.04 respectively). This finding suggests that an inter-hemispheric information exchange between the homologous areas is required to successfully accomplish the task and indirectly supports the role of the right (ipsilateral) hemisphere in explicit visuomotor learning. On the other hand, we found no significant correlation of the FA in the CC and in the SLFs with nonspecific learning (assessed when stimuli are randomly presented), supporting the hypothesis that inter-hemispheric integrity is specifically relevant for explicit sequence learning.

Esophageal symptoms questionnaire for the assessment of dysphagia, globus, and reflux symptoms: initial development and validation.

Esophageal symptoms often co-occur. A validated self-report measure encompassing multiple esophageal symptoms is necessary to determine their frequency and severity both independently and in association with each other. Such a questionnaire could streamline the diagnostic process and guide patient management. We aimed to develop an integrative measure that provides a clinical 'snapshot' of common esophageal symptoms. Internal reliability and content validity of a 38-item self-report Esophageal Symptoms Questionnaire (ESQ), measuring the frequency and severity of typical esophageal symptoms using Likert-rating scales were assessed in 211 patients presenting to gastroenterology and ENT outpatient tertiary care clinics. Reproducibility, concurrent and predictive validity were evaluated using the reduced-item ESQ. The 38-item ESQ had high internal reliability. Principal component analyses and item reduction methods identified three components, to which 30 of 38 items contributed significantly, providing 59% of total variance. The test-retest correlations were moderate-to-strong for 24 of 30 new items (r(s) ≥ 0.44, P < 0.05). The resultant subscales measuring dysphagia (ESQ-D), globus (ESQ-G), and reflux (ESQ-R) compared well against concurrent physician's 'working' diagnosis (odds ratio 1.04-1.09). The receiver operating characteristics were adequate-to-good for ESQ-D (area under the curve [AUC]= 0.87) and ESQ-G (AUC = 0.74), but poor for ESQ-R (AUC = 0.61) although it matched the content of the validated Reflux Disease Questionnaire. The brief 30-item ESQ shows good internal reliability and content validity as a summary of the extent of dysphagia, globus and reflux symptoms. As a tool measuring more than one esophageal symptom, ESQ could guide patient management by indicating which of the coexisting symptoms needs to be addressed first.

[Earthquake in Abruzzo, public health interventions. Preliminary report]. / Interventi sanitari in occasione del sisma in Abruzzo. Rapporto preliminare.

On 6th April 2009, at 3.32 AM, there was in L'Aquila and in some neighbouring villages, after an earthquake swarm last some months, an earthquake of M(L) = 5.8 (Richter magnitude scale) on depth of 8.8 km. The event was sensed in a very broad area, till in Rome and Ancon. The operative committee of the Civil Protection Department immediately gathered and a first operating group was despatched in the epicentre; the voluntary association of civil protection were in a pre-alarm situation and then were activated. This work want describe all the activities from 6th April 2009 till 31th August 2009, giving too a synthesis of the normative lines in case of catastrophic events typology C, otherwise all that events impossible to manage without national intervention.

Familiarity with a Tool Influences Peripersonal Space and Primary Motor Cortex Excitability of Muscles Involved in Haptic Contact.

Long-term experience with a tool stably enlarges peripersonal space (PPS). Also, gained experience with a tool modulates internal models of action. The aim of this work was to understand whether the familiarity with a tool influences both PPS and motor representation. Toward this goal, we tested in 13 expert fencers through a multisensory integration paradigm the embodiment in their PPS of a personal (pE) or a common (cE) épée. Then, we evaluated the primary motor cortex excitability of proximal (ECR) and distal (APB) muscles during a motor imagery (MI) task of an athletic gesture when athletes handled these tools. Results showed that pE enlarges subjects' PPS, while cE does not. Moreover, during MI, handling tools increased cortical excitability of ECR muscle. Notably, APB's cortical excitability during MI only increased with pE as a function of its embodiment in PPS. These findings indicate that the familiarity with a tool specifically enlarges PPS and modulates the cortical motor representation of those muscles involved in the haptic contact with it.

The patients' perspective on the perceived difficulties of dual-tasking: development and validation of the Dual-task Impact on Daily-living Activities Questionnaire (DIDA-Q).

BACKGROUND: Everyday-life activities often require performing dual tasks (DT), with consequent possible occurrence of motor-cognitive or motor-motor interference. This could reduce quality of life, in particular in people with neurological diseases. However, there is lack of validated tools to assess the patients' perspective on DT difficulties in this population. Therefore, we developed the Dual-task Impact on Daily-living Activities-Questionnaire (DIDA-Q) and tested its psychometric properties in people with multiple sclerosis (PwMS). METHODS: Items were generated based on existing scales, DT paradigms used in previous studies and the opinion of a multi-stakeholder group, including both experts and PwMS. Twenty DT constituted the preliminary version of the DIDA-Q which was administered to 230 PwMS. The psychometric properties of the scale were evaluated including internal consistency, validity and reliability. RESULTS: Nineteen items survived after exploratory factor analysis, showing a three-factor solution which identifies the components mostly contributing to DT perceived difficulty (i.e., balance and mobility, cognition and upper-limb ability). The DIDA-Q appropriately fits the graded response model, with first evaluations supporting internal consistency (Cronbach's alpha=0.95), validity (70% of the hypotheses for convergent and discriminant constructs confirmed) and reliability (intraclass correlation coefficients=0.95) of this tool. CONCLUSION: The DIDA-Q could be used in research and clinical settings to discriminate individuals with low vs. high cognitive-motor or motor-motor interference, and to develop and evaluate the efficacy of personalized DT rehabilitative treatments in PwMS.

External shock waves therapy in dystonia: preliminary results.

BACKGROUND AND PURPOSE: Extracorporeal shock wave therapy (ESWT) has been shown to reduce hypertonia in patients with upper motor neuron syndrome without any side effect. The aim of the present study is to investigate whether ESWT could be useful also in patients with dystonia. METHODS: We evaluated three patients with secondary dystonia and three patients with idiopathic writer's cramp. Placebo treatment was performed in each patient. ESWT was administered during four sessions (once weekly) to the target muscles of hand and forearm using an electromagnetic lithotripter (Modulith SLK--Storz Medical). Clinical evaluation was performed using the Unified Dystonia Rating Scale in patients with secondary dystonia and the Arm Dystonia Disability Scale in patients with writer's cramp. RESULTS: After treatment, the three patients with secondary dystonia showed a marked improvement which lasted at least until 1 month after the last session. In the patients with writer's cramp, the improvement after ESWT was less consistent being effective only in two subjects. There were no associated adverse effects. CONCLUSIONS: Extracorporeal shock wave therapy is probably an effective and safe treatment for upper limb dystonia, particularly for the secondary forms. Larger randomized studies are needed to confirm these preliminary results.

Influence of inherited and acquired thrombophilic defects on the clinical manifestations of mixed cryoglobulinaemia.

OBJECTIVE: To investigate the contribution of inherited and acquired thrombophilic defects to the clinical manifestations of mixed cryoglobulinaemia vasculitis. METHODS: The following thrombophilic defects were investigated in 64 consecutive patients with HCV-associated mixed cryoglobulinaemia: aPLs, lupus anti-coagulant, homocysteinaemia, protein C and protein S concentrations, activated protein C resistance, plasminogen activator inhibitor-1 4G4G and 5G5G genotypes, and the presence of mutations of factor V (Leiden and H1299R), of prothrombin (G20210A) and of methyl tetrahydrofolate reductase (C677T and A1298C). Additional variables were demographic data, duration of the disease, cryocrit level and vascular risk factors (diabetes, hypertension, hypercholesterolaemia and smoking habit). The following clinical manifestations of mixed cryoglobulinaemia were analysed as dependent covariates: severity of purpura, presence of necrotic skin ulcers, presence of peripheral neuropathy and presence of kidney disease. RESULTS: Logistic regression analysis identified hyperhomocysteinaemia as a risk factor for severe purpura (P < 0.0001) and for the presence of skin ulcers (P < 0.0001), whereas none of the other thrombophilic defects influenced the clinical presentation of mixed cryoglobulinaemia. Purpura improved in two patients after lowering homocysteine with vitamin supplementation. CONCLUSIONS: Hyperhomocysteinaemia may be a risk factor for severe cutaneous manifestations in mixed cryoglobulinaemia.

Intrafusal effects of botulinum toxin in post-stroke upper limb spasticity.

A previous study in subjects with focal dystonia suggested that the greater and longer-lasting effect induced by botulinum toxin type A (BoNT-A) on the tonic vibration reflex (TVR) than on the maximal M-wave (M-max) might be the physiological marker of the toxin's action at the level of intrafusal muscle fibres. With this approach, we investigated the possible effect of BoNT-A on fusimotor synapses in eight patients with post-stroke spasticity (four with no residual motor capacity before treatment and four with partially spared muscle strength and residual motor capacity). TVR and M-max were recorded from the wrist and finger flexor muscles before treatment and at 1, 4 and 7 months afterwards. The TVR reduction was greater than the M-max reduction and remained fairly constant over time only in the subjects with a residual motor capacity before the treatment. This pilot study suggests that some degree of strength and active movement is necessary for the action of BoNT-A on intrafusal fibres.