Disease progression in blepharospasm: a 5-year longitudinal study.

BACKGROUND AND PURPOSE: The clinical manifestation of dystonic spasms in blepharospasm (BSP) patients may be heterogeneous. Whether the varying phenomenology of eyelid spasms becomes manifest sequentially during the course of the disease or aggregates in separate clusters according to different disease courses is still unclear. For this purpose, the clinical features in BSP patients were evaluated longitudinally over a 5-year period and also the blink reflex recovery cycle was tested in a subgroup of BSP patients. METHODS: Sixty BSP patients were videotaped at time 0 and after approximately 5 years of follow-up. Two experts in movement disorders, who were blinded to the video order, reviewed the videotapes and scored the severity of BSP using the Blepharospasm Severity Rating Scale. Changes in the R2 recovery index were also evaluated in 18 patients twice, i.e. upon enrolment and at the follow-up. RESULTS: The severity of BSP worsened significantly over the 5-year follow-up period owing to the appearance or the increased duration and frequency of prolonged spasms. It was also found that the blink reflex recovery cycle worsened at follow-up in comparison with the baseline. CONCLUSIONS: This study shows that the disease progression of BSP is characterized by the appearance or worsening of prolonged spasms. Prolonged spasms are accompanied by changes in the excitability of brainstem interneurons. Aging-related effects may exacerbate the pathophysiological mechanisms underlying spasms.

Corticobasal syndrome: neuroimaging and neurophysiological advances.

Corticobasal degeneration (CBD) is a neurodegenerative condition characterized by 4R tau protein deposition in several brain regions that clinically manifests itself as a heterogeneous atypical parkinsonism typically expressed in adulthood. The prototypical clinical phenotype of CBD is corticobasal syndrome (CBS). Important insights into the pathophysiological mechanisms underlying motor and higher cortical symptoms in CBS have been gained by using advanced neuroimaging and neurophysiological techniques. Structural and functional neuroimaging studies often show asymmetric cortical and subcortical abnormalities, mainly involving perirolandic and parietal regions and basal ganglia structures. Neurophysiological investigations including electroencephalography and somatosensory evoked potentials provide useful information on the origin of myoclonus and on cortical sensory loss. Transcranial magnetic stimulation demonstrates heterogeneous and asymmetric changes in the excitability and plasticity of primary motor cortex and abnormal hemispheric connectivity. Neuroimaging and neurophysiological abnormalities in multiple brain areas reflect asymmetric neurodegeneration, leading to asymmetric motor and higher cortical symptoms in CBS.

Re-emergent tremor in Parkinson's disease: the effect of dopaminergic treatment.

BACKGROUND AND PURPOSE: Patients with Parkinson's disease (PD) with resting tremor may be affected by a tremor that appears after a varying latency while a posture is maintained, a phenomenon referred to as re-emergent tremor (RET). The aim of the study was to evaluate the occurrence and clinical features of RET in patients with PD tested off and on treatment, and to compare the effect of dopaminergic treatment on RET with the effect on resting and action tremor. METHODS: We consecutively enrolled 100 patients with PD. Patients were clinically evaluated 24 h after withdrawal of therapy (off-treatment phase) and 60 min after therapy administration (on-treatment phase). We collected the demographic and clinical data of patients with PD. The severity of the disease was assessed by means of the Hoehn and Yahr scale and Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale part III. We evaluated the latency, severity and body side affected both off and on treatment in patients with RET. RESULTS: Re-emergent tremor was present in 24% of the patients with PD off treatment and in 19% of the patients on treatment. Dopaminergic treatment reduced the clinical severity of RET. Dopaminergic treatment increased the number of patients with unilateral RET and reduced the number of those who had bilateral RET. RET and resting tremor responded similarly to dopaminergic treatment, whereas action tremor was less responsive. Patients with RET had milder motor symptoms than patients without RET both off and on treatment. CONCLUSIONS: Dopaminergic treatment modified RET occurrence, severity and body distribution. Dopaminergic depletion plays a role in the pathophysiology of RET.

Spread of dystonia in patients with idiopathic adult-onset laryngeal dystonia.

BACKGROUND AND PURPOSE: Adult-onset laryngeal dystonia (LD) can be isolated or can be associated with dystonia in other body parts. Combined forms can be segmental at the onset or can result from dystonia spread to or from the larynx. The aim of this study was to identify the main clinical and demographic features of adult-onset idiopathic LD in an Italian population with special focus on dystonia spread. METHODS: Data were obtained from the Italian Dystonia Registry (IDR) produced by 37 Italian institutions. Clinical and demographic data of 71 patients with idiopathic adult-onset LD were extracted from a pool of 1131 subjects included in the IDR. RESULTS: Fifty of 71 patients presented a laryngeal focal onset; the remaining subjects had onset in other body regions and later laryngeal spread. The two groups did not show significant differences of demographic features. 32% of patients with laryngeal onset reported spread to contiguous body regions afterwards and in most cases (12 of 16 subjects) dystonia started to spread within 1 year from the onset. LD patients who remained focal and those who had dystonia spread did not show other differences. CONCLUSIONS: Data from IDR show that dystonic patients with focal laryngeal onset will present spread in almost one-third of cases. Spread from the larynx occurs early and is directed to contiguous body regions showing similarities with clinical progression of blepharospasm. This study gives a new accurate description of LD phenomenology that may contribute to improving the comprehension of dystonia pathophysiology.

Correction to: The Italian Dystonia Registry: rationale, design and preliminary findings.

In the original article, Gina Ferrazzano was affiliated to Department of Neurology and Psychiatry, Neuromed Institute IRCCS, Sapienza University of Rome, Pozzilli, Italy.The corrected affiliation should be: Neuromed Institute IRCCS, Pozzilli, IS, Italy.

Relationship between pain and motor and non-motor symptoms in Parkinson's disease.

BACKGROUND AND PURPOSE: Although female gender, depressive symptoms and medical conditions predisposing to pain are more common in patients with Parkinson's disease (PD) with pain, no study has yet explored the relationship between pain and other non-motor symptoms (NMS). METHODS: A total of 321 consecutive patients with PD [190 men/131 women aged 68.3 (SD 9.2) years] attending four Italian movement disorder clinics were studied. Demographic/clinical data were obtained by a standardized interview and the NMS scale. The association of pain with motor and NMS was assessed by multivariable logistic regression models. RESULTS: At the time of the study, 180 patients with PD (56%) reported chronic pain that, in most cases, was described as being muscular or arthralgic pain. Pain preceded the onset of motor signs in 36/180 patients. In the main-effect model, factors independently associated with pain were female sex [odds ratio (OR), 2.1; P = 0.01], medical conditions predisposing to pain (OR, 2.9; P < 0.001), Hoehn-Yahr staging (OR, 1.9; P = 0.04), motor complications (OR, 4.7; P = 0.04) and NMS belonging to the sleep/fatigue (OR, 1.6; P = 0.04) and mood/cognition (OR, 1.6; P = 0.03) domains. Most explanatory variables in the multivariable analysis were similarly distributed in patients in whom pain may have been related to PD or to a cause other than PD. CONCLUSIONS: We confirm that pain in PD is more frequent in women and in subjects with medical conditions predisposing to painful symptoms. Moreover, this strengthens the association between pain and motor severity measures and NMS domains, particularly sleep and mood disturbances.

BDNF and LTP-/LTD-like plasticity of the primary motor cortex in Gilles de la Tourette syndrome.

Gilles de la Tourette syndrome (GTS) is characterized by motor and vocal tics and often associated with obsessive-compulsive disorder (OCD). Responses to intermittent/continuous theta-burst stimulation (iTBS/cTBS), which probe long-term potentiation (LTP)-/depression (LTD)-like plasticity in the primary motor cortex (M1), are reduced in GTS. ITBS-/cTBS-induced M1 plasticity can be affected by brain-derived neurotrophic factor (BDNF) polymorphism. We investigated whether the BDNF polymorphism influences iTBS-/cTBS-induced LTP-/LTD-like M1 plasticity in 50 GTS patients and in 50 age- and sex-matched healthy subjects. In GTS patients, motor and psychiatric (OCD) symptom severity was rated using the Yale Global Tic Severity Scale (YGTSS) and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). We compared M1 iTBS-/cTBS-induced plasticity in healthy subjects and in patients with GTS. We also compared responses to TBS according to BDNF polymorphism (Val/Val vs Met carriers) in patients and controls. Fourteen healthy subjects and 13 GTS patients were Met carriers. When considering the whole group of controls, as expected, iTBS increased whereas cTBS decreased MEPs. Differently, iTBS/cTBS failed to induce LTP-/LTD-like plasticity in patients with GTS. When comparing responses to TBS according to BDNF polymorphism, in healthy subjects, Met carriers showed reduced MEP changes compared with Val/Val individuals. Conversely, in patients with GTS, responses to iTBS/cTBS were comparable in Val/Val individuals and Met carriers. YGTSS and Y-BOCS scores were comparable in Met carriers and in Val/Val subjects. We conclude that iTBS and cTBS failed to induce LTP-/LTD-like plasticity in patients with GTS, and this was not affected by BDNF genotype.

The Italian Dystonia Registry: rationale, design and preliminary findings.

The Italian Dystonia Registry is a multicenter data collection system that will prospectively assess the phenomenology and natural history of adult-onset dystonia and will serve as a basis for future etiological, pathophysiological and therapeutic studies. In the first 6 months of activity, 20 movement disorders Italian centres have adhered to the registry and 664 patients have been recruited. Baseline historical information from this cohort provides the first general overview of adult-onset dystonia in Italy. The cohort was characterized by a lower education level than the Italian population, and most patients were employed as artisans, builders, farmers, or unskilled workers. The clinical features of our sample confirmed the peculiar characteristics of adult-onset dystonia, i.e. gender preference, peak age at onset in the sixth decade, predominance of cervical dystonia and blepharospasm over the other focal dystonias, and a tendency to spread to adjacent body parts, The sample also confirmed the association between eye symptoms and blepharospasm, whereas no clear association emerged between extracranial injury and dystonia in a body site. Adult-onset dystonia patients and the Italian population shared similar burden of arterial hypertension, type 2 diabetes, coronary heart disease, dyslipidemia, and hypothyroidism, while hyperthyroidism was more frequent in the dystonia population. Geographic stratification of the study population yielded no major difference in the most clinical and phenomenological features of dystonia. Analysis of baseline information from recruited patients indicates that the Italian Dystonia Registry may be a useful tool to capture the real world clinical practice of physicians that visit dystonia patients.

Validity and reliability of the Italian version of the short Parkinson's evaluation scale (SPES/SCOPA).

Background: In the medical and rehabilitative field, it is essential to employ tools such as evaluation scales and performance tests to assess the impact of Parkinson's disease on QoL of affected individuals. The Short Parkinson's Evaluation Scale (SPES) is a reliable and valid tool, applicable both in research and clinical practices, useful in assessing motor damage, activities of daily living, and motor complications in patients with Parkinson's disease. The aim of the study is to investigate validity and reliability of the Italian version of the SPES-SCOPA scale. Methods: Translation and cultural adaptation were performed. Included patients had diagnosis of Parkinson's disease, no concurrent pathologies, MiniMental test score above 2 and signed informed consent; they were recruited at the Department of Human Neurosciences in Sapienza University of Rome, from February 2023 to November 2023. Test-retest reliability was evaluated through Intraclass Correlation Coefficient (ICC), internal consistency was assessed using Cronbach's Alpha and construct validity using Pearson's correlation between SPES-SCOPA and the gold standard PDQ-39. Results: 101 patients were recruited. Inter-rater evaluation was conducted on 62 patients, while 39 underwent an intra-rater assessment. The analysis showed statistically significant data with a Cronbach's Alpha value of 0.89 for the entire scale; test-retest reliability results are statistically significant for all subscales. Correlation between PDQ-39 domains and SPES/SCOPA subscales were statistically significant for most measurements. Conclusion: This research shows that the Italian version of SPES-SCOPA scale has excellent psychometric properties.

Somatosensory temporal discrimination threshold may help to differentiate patients with multiple system atrophy from patients with Parkinson's disease.

BACKGROUND AND PURPOSE: Somatosensory temporal discrimination threshold (STDT) is defined as the threshold at which two tactile stimuli applied to the skin are perceived as clearly distinct. The aim of the study was to investigate whether the extent of STDT alterations differs between patients with parkinsonian type multiple system atrophy (MSA-P) and patients with Parkinson's disease (PD). Possible differences between the two groups may help to differentiate MSA-P from PD. METHODS: STDT was investigated in 20 patients with MSA-P, 21 patients with PD and 18 age-matched healthy subjects. The clinical evaluation included the Mini-Mental State Examination, Hoehn and Yahr Scale, Frontal Assessment Battery, Unified Multiple System Atrophy Rating Scale for patients with MSA-P, and Unified Parkinson's Disease Rating Scale for patients with PD. STDT was investigated by delivering paired electrical stimuli starting with an inter-stimulus interval (ISI) of 0 ms (simultaneous pair), and progressively increasing the ISIs in 10-ms steps. RESULTS: Between-group anova showed that STDT statistically differed in MSA-P versus patients with PD and healthy subjects. Post hoc showed that STDT values in patients with MSA-P were significantly higher than those in patients with PD and healthy subjects. Receiver operating characteristic curve analysis showed that STDT testing yielded high diagnostic specificity and sensitivity. CONCLUSIONS: STDT is abnormal in patients with MSA-P and PD. The degree of STDT abnormalities is higher in patients with MSA-P than in patients with PD.

Summary of the recommendations of the EFNS/MDS-ES review on therapeutic management of Parkinson's disease.

OBJECTIVE: To summarize the 2010 EFNS/MDS-ES evidence-based treatment recommendations for the management of Parkinson's disease (PD). This summary includes the treatment recommendations for early and late PD. METHODS: For the 2010 publication, a literature search was undertaken for articles published up to September 2009. For this summary, an additional literature search was undertaken up to December 2010. Classification of scientific evidence and the rating of recommendations were made according to the EFNS guidance. In cases where there was insufficient scientific evidence, a consensus statement ('good practice point') is made. RESULTS AND CONCLUSIONS: For each clinical indication, a list of therapeutic interventions is provided, including classification of evidence.

Adherence to anti-Parkinson drug therapy in the "REASON" sample of Italian patients with Parkinson's disease: the linguistic validation of the Italian version of the "Morisky Medical Adherence Scale-8 items".

Information about patients' adherence to therapy represents a primary issue in Parkinson's disease (PD) management. To perform the linguistic validation of the Italian version of the self-rated 8-Item Morisky Medical Adherence Scale (MMAS-8) and to describe in a sample of Italian patients affected by PD the adherence to anti-Parkinson drug therapy and the association between adherence and some socio-demographic and clinical features. MMAS-8 was translated into Italian language by two independent Italian mother-tongue translators. The consensus version was then back-translated by an English mother-tongue translator. This translation process was followed by a consensus meeting between the authors of translation and investigators and then by two comprehension tests. The translated version of the MMAS-8 scale was then administered at the baseline visit of the "REASON" study (Italian Study on the Therapy Management in Parkinson's disease: Motor, Non-Motor, Adherence and Quality Of Life Factors) in a large sample of PD patients. The final version of the MMAS-8 was easily understood. Mean ± SD MMAS-8 score was 6.1 ± 1.2. There were no differences in adherence to therapy in relationship to disease severity, gender, educational level or decision to change therapy. The Italian version of MMAS-8, the key tool of the REASON study to assess the adherence to therapy, has shown to be understandable to patients with PD. Patients enrolled in the REASON study showed medium therapy adherence.

Botulinum toxin A modulates afferent fibers in neurogenic detrusor overactivity.

BACKGROUND: Although botulinum toxin (BoNT/A) injected into the detrusor muscle improves overactive bladder symptoms in patients with neurogenic detrusor overactivity, how it does so remains unclear. In this study, we investigated whether BoNT/A improves detrusor overactivity by modulating bladder afferent activity. METHODS: To do so, during urodynamic assessment, we tested the soleus muscle Hoffmann (H) reflex during bladder filling before and after intradetrusor BoNT/A in patients with Parkinson's disease (PD) and in patients with complete chronic spinal cord lesion (SCI) and detrusor overactivity refractory to conventional therapy. Healthy subjects underwent H reflex studies during urodynamic assessment and acted as controls. RESULTS: Our findings show that BoNT/A injected into the detrusor muscle effectively reduces clinical overactive bladder symptoms in patients with PD and SCI. In healthy subjects and patients with PD, bladder filling [at maximum cystometric capacity, (MCC)] significantly decreased the H reflex size, whereas in patients with SCI, it slightly facilitated the H reflex size. At MCC, in patients with PD, BoNT/A significantly reduced the expected H reflex inhibition, whereas in those with SCI, BoNT/A turned the H reflex facilitation at maximum bladder filling into a slight inhibition. CONCLUSIONS: These findings show that BoNT/A injected into the detrusor muscle in patients with PD and SCI modulates bladder afferent activity. Modulation of bladder afferents possibly explains why BoNT/A improves detrusor overactivity.

Observational study of sleep-related disorders in Italian patients with Parkinson's disease: usefulness of the Italian version of Parkinson's disease sleep scale.

Sleep disturbances are common in patients with Parkinson's disease (PD). We aimed to evaluate prevalence and severity of nighttime sleep disturbances in Italian PD patients and to validate the Italian version of the Parkinson's disease sleep scale. A total of 221 PD patients and 57 healthy controls participated in a cross-sectional study with retest. PDSS, Epworth Sleepiness Scale (ESS), Hamilton Depression Rating Scale, Unified Parkinson's Disease Rating Scale (UPDRS), and Hoehn and Yahr staging were applied. PDSS total and individual items scores from patients were significantly lower than those in controls. Internal consistency of PDSS scale was satisfactory and intraclass correlation coefficient for test-retest reliability was 0.96 for total PDSS score. A significant negative correlation was found between total PDSS and ESS scores, and between total PDSS and HDRS scores. PDSS scores were also related to UPDRS sections II, III and IV, and H&Y stage. PDSS and ESS scores were not related to levodopa equivalent dose. Daytime sleepiness, depressive symptoms and disease severity correlate with sleep disturbances in Italian PD patients. The PDSS is a valid and reliable tool to evaluate sleep disturbances in Italian patients.

Cutaneous innervation and trigeminal pathway function in a patient with facial pain associated with Parry-Romberg syndrome.

Parry-Romberg syndrome (PRS) is a rare condition manifesting with progressive hemifacial atrophy. Although reported PRS clinical disturbances include facial pain and recent studies raised the possibility that PRS-related pain is a neuropathic pain condition due to the trigeminal nerve damage, no studies have directly investigated cutaneous innervation and trigeminal pathway function in patients with this rare condition. In a 50-year-old woman presenting with a 10-year history of slowly progressive hemifacial atrophy and facial pain, we investigated large myelinated fibres with masticatory muscle electromyography and trigeminal reflexes, and tested small myelinated and unmyelinated fibres with laser-evoked potentials. We also investigated cutaneous innervation by measuring the intraepidermal nerve fibre (IENF) density after skin biopsy of the supraorbital regions. We found that neurophysiological data and IENF density came within normal ranges, with no differences between normal and affected side. Our study showing that the standard reference techniques for assessing cutaneous innervation and trigeminal pathway function disclosed no abnormalities in this patient with PRS suggest that this rare and disabling condition is not associated with trigeminal system damage. These findings indicate that in this patient PRS-related pain is not a neuropathic pain condition, rather it probably arises from the musculoskeletal abnormalities.

Correlation between Quality of Life and severity of Parkinson's Disease by assessing an optimal cut-off point on the Parkinson's Disease questionnaire (PDQ-39) as related to the Hoehn & Yahr (H&Y) scale.

Purpose: Strong evidence shows that symptoms in individuals with Parkinson's Disease (PD) restrict both their independence and social participation, leading to a low Quality of Life (QoL). Conversely, a reduced QoL has a negative impact on symptoms. The aim is to evaluate the correlation between QoL and severity of PD by assessing the presence of an optimal cut-off point on the Parkinson's disease questionnaire (PDQ-39) as related to the Hoehn &Yahr (H&Y) scale in a cohort of Italian adults with PD. Methods: A multicenter, cross-sectional study was performed. This study was conducted on a cohort of consecutive individuals. All participants were evaluated with the PDQ-39, and the severity of PD was recorded according to the H&Y scale by a neurologist. Receiver op-erating characteristic (ROC) curves and coordinates, visually inspected, were used to find cut-off points with optimal sensitivity and specificity. These were in turn used to determine the optimal PDQ-39 cut-off score for identifying disease severity according to H&Y stages. Results: 513 individuals were included in the study. The ROC curve analysis showed that QoL worsened with an increase in disease severity and age. Moreover, QoL was worse in females. Conclusions: The results of this study allowed for the correlation of QoL and disease severity in a cohort of individuals with PD. With this cut-off point, it is now possible to make a determination of QoL of an individual with PD at a certain stage of the disease, in a specific age range, and of a particular gender.

Dopamine influences primary motor cortex plasticity and dorsal premotor-to-motor connectivity in Parkinson's disease.

We investigated abnormal premotor to motor (PMd-to-M1) connectivity in Parkinson's disease (PD) with repetitive transcranial magnetic stimulation (rTMS). We studied 28 patients off and on dopaminergic therapy and 28 healthy subjects. We delivered 5 Hz rTMS over M1 before and after conditioning PMd with 5 Hz rTMS. In healthy subjects, motor-evoked potentials (MEPs) elicited by M1-rTMS were facilitated and PMd-rTMS left MEPs unchanged. In patients, before PMd-rTMS, M1-rTMS induced no MEP facilitation, whereas after PMd-rTMS, it significantly facilitated MEPs only when patients were on therapy. In the second experiment, we delivered M1-rTMS under 3 different attention-demanding tasks: eyes closed, attention directed to the stimulated hand, and attention directed to the nonstimulated hand. In healthy subjects, a more pronounced MEP facilitation was present when subjects directed attention to the stimulated hand. In patients, the MEP facilitation was present when attention was directed to the stimulated hand only when patients were on therapy. Finally, we delivered M1-rTMS in patients on therapy while they were looking at the stimulated hand, before and after 1 Hz PMd-rTMS. PMd-rTMS reduced the attention-induced MEP facilitation. We conclude that in addition to abnormal M1 plasticity, the reduced MEP facilitation in PD also reflects altered PMd-to-M1 connectivity.

Instrumental Timed Up and Go test discloses abnormalities in patients with Cervical Dystonia.

Background Cervical dystonia is a movement disorder characterized by involuntary and sustained contraction of the neck muscles that determines abnormal posture. The aim of this study was to investigate whether dystonic posture in patients with cervical dystonia affects walking and causes postural changes. Methods Patients with cervical dystonia and a group of age-matched healthy controls underwent an instrumental evaluation of the Timed Up and Go Test. Findings All the spatio-temporal parameters of the sub-phases of the Timed up and go test had a significantly higher duration in cervical dystonia patients compared to the control group while no differences in flection and extension angular amplitudes were observed. Indeed, we found that Cervical Dystonia patients had abnormalities in turning, as well as in standing-up and sitting-down from a chair during the Timed up and go test than healthy controls. Interpretation Impairment in postural control in cervical dystonia patients during walking and postural changes prompts to develop rehabilitation strategies to improve postural stability and reduce the risk of fall in these patients.

Craniocervical dystonia: clinical and pathophysiological features.

Blepharospasm, oromandibular, lingual, laryngeal and cervical dystonia are common forms of adult-onset dystonia. Each condition may appear in isolation or manifest along with other forms of craniocervical dystonia. Although the various craniocervical dystonias typically present with involuntary muscle spasms causing abnormal postures, they differ for some clinical features. Neurophysiologic and neuroimaging studies have shown a number of motor and sensory abnormalities at cortical and subcortical levels, probably reflecting a dysfunction in the basal ganglia-thalamo-cortical circuits. The best treatment for craniocervical dystonia is botulinum toxin injected into the overactive muscles.

Electrical activation of the orbicularis oculi muscle does not increase the effectiveness of botulinum toxin type A in patients with blepharospasm.

BACKGROUND: Our primary aim in this study was to determine whether electrically induced activation of the injected muscle increases effectiveness of botulinum type A toxin (BonT-A) in patients with blepharospasm (BPS). The second aim was to assess the safety of BonT-A by investigating whether BonT-A injection alters the excitability of blink reflex circuits in the brainstem. METHODS: Twenty-three patients with BPS received BonT-A (Botox) injected bilaterally into the orbicularis oculi muscle at a standard dose. In 18 patients, electrically induced muscle activation of the orbicularis oculi muscle on one side was performed for 60 min (4 Hz frequency) in a single session, immediately after BonT-A injection and in five patients for 60 min once a day for five consecutive days. The severity of BPS was assessed clinically with the BPS score. Compound muscle action potential (cMAPs) from the orbicularis oculi muscles were measured bilaterally. The blink reflex recovery cycle was studied at interstimulus intervals of 250 and 500 ms. Participants underwent clinical and neurophysiological assessment before BonT-A injection (T0) and 2 weeks thereafter (T1). RESULTS: Compound muscle action potential amplitude significantly decreased at T1 but did not differ between stimulated and non-stimulated orbicularis oculi in the two groups. BonT-A injection left the blink reflex recovery cycle tested on the stimulated and non-stimulated sides unchanged. CONCLUSIONS: In patients with BPS, the electrically induced muscle activation neither increases the effectiveness of BonT-A nor produces larger electrophysiological peripheral effects. The lack of BonT-A-induced changes in the blink reflex recovery cycle provides evidence that BonT-A therapy is safe in patients with BPS.