An Exploratory, Randomized, Double-Blind Clinical Trial of Dipraglurant for Blepharospasm.

BACKGROUND: Blepharospasm is treated with botulinum toxin, but obtaining satisfactory results is sometimes challenging. OBJECTIVE: The aim is to conduct an exploratory trial of oral dipraglurant for blepharospasm. METHODS: This study was an exploratory, phase 2a, randomized, double-blind, placebo-controlled trial of 15 participants who were assigned to receive a placebo or dipraglurant (50 or 100 mg) and assessed over 2 days, 1 and 2 hours following dosing. Outcome measures included multiple scales rated by clinicians or participants, digital video, and a wearable sensor. RESULTS: Dipraglurant was well tolerated, with no obvious impact on any of the measurement outcomes. Power analyses suggested fewer subjects would be required for studies using a within-subject versus independent group design, especially for certain measures. Some outcome measures appeared more suitable than others. CONCLUSION: Although dipraglurant appeared well tolerated, it did not produce a trend for clinical benefit. The results provide valuable information for planning further trials in blepharospasm. © 2024 International Parkinson and Movement Disorder Society.

Supplementary motor area driving changes of structural brain network in blepharospasm.

Blepharospasm is traditionally thought to be a movement disorder that results from basal ganglia dysfunction. Recently, accumulating morphometric studies have revealed structural alterations outside the basal ganglia, such as in the brainstem, cerebellum and sensorimotor cortex, suggesting that blepharospasm may result from network disorders. However, the temporal and causal relationships between structural alterations and whether there are disease duration-related hierarchical structural changes in these patients remain largely unknown. Structural MRI was performed in 62 patients with blepharospasm, 62 patients with hemifacial spasm and 62 healthy controls to assess the structural alterations using voxel-based morphology and structural covariance networks. The use of the causal structural covariance network, modularity analysis and functional decoding were subsequently performed to map the causal effect of grey matter change pattern, hierarchical topography and functional characterizations of the structural network throughout the disease duration of blepharospasm. Greater grey matter volume in the left and right supplementary motor areas was identified in patients with blepharospasm compared to that in patients with hemifacial spasm and healthy controls, whereas no significant difference was identified between patients with hemifacial spasm and healthy controls. In addition, increased grey matter volume covariance between the right supplementary motor area and right brainstem, left superior frontal gyrus, left supplementary motor area and left paracentral gyrus was found in patients with blepharospasm compared to healthy controls. Further causal structural covariance network, modularity analysis and functional decoding showed that the right supplementary motor area served as a driving core in patients with blepharospasm, extending greater grey matter volume to areas in the cortico-basal ganglia-brainstem motor pathway and cortical regions in the vision-motor integration pathway. Taken together, our results suggest that the right supplementary motor area is an early and important pathologically impaired region in patients with blepharospasm. With a longer duration of blepharospasm, increased grey matter volume extends from the right supplementary motor area to the cortico-basal ganglia motor and visual-motor integration pathways, showing a hierarchy of structural abnormalities in the disease progression of blepharospasm, which provides novel evidence to support the notion that blepharospasm may arise from network disorders and is associated with a wide range of grey matter abnormalities.

Long-term Efficacy of Bilateral Globus Pallidus Stimulation in the Treatment of Meige Syndrome.

OBJECTIVE: This study aimed to investigate the long-term efficacy and prognosis of bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) in patients with benign essential blepharospasm (BEB) and complete Meige syndrome, and to search for the best therapeutic subregion within the GPi. MATERIALS AND METHODS: Data were collected for 36 patients with Meige syndrome who underwent bilateral GPi-DBS surgery at our hospital between March 2014 and February 2022. Using the Burk-Fahn-Marsden Dystonia Rating Scale (BFMDRS)-Movement (BFMDRS-M) and BFMDRS-Disability (BFMDRS-D), the severity of the symptoms of patients with complete Meige syndrome was evaluated before surgery and at specific time points after surgery. Patients with BEB were clinically evaluated for the severity of blepharospasm using BFMDRS-M, the Blepharospasm Disability Index (BDI), and Jankovic Rating Scale (JRS). Three-dimensional reconstruction of the GPi-electrode was performed in some patients using the lead-DBS software, and the correlation between GPi subregion volume of tissue activated (VTA) and symptom improvement was analyzed in patients six months after surgery. The follow-up duration ranged from six to 99 months. RESULTS: Compared with preoperative scores, the results of all patients at six months after surgery and final follow-up showed a significant decrease (p < 0.05) in the mean BFMDRS-M score. Among them, the average BFMDRS-M improvement rates in patients with BEB at six months after surgery and final follow-up were 60.3% and 69.7%, respectively, whereas those in patients with complete Meige syndrome were 54.5% and 58.3%, respectively. The average JRS and BDI scores of patients with BEB also decreased significantly (p < 0.05) at six months after surgery and at the final follow-up (JRS improvement: 38.6% and 49.1%, respectively; BDI improvement: 42.6% and 57.4%, respectively). We were unable to identify significantly correlated prognostic factors. There was a significant correlation between GPi occipital VTA and symptom improvement in patients at six months after surgery (r = 0.34, p = 0.025). CONCLUSIONS: Our study suggests that bilateral GPi-DBS is an effective treatment for Meige syndrome, with no serious postoperative complications. The VTA in the GPi subregion may be related to the movement score improvement. In addition, further research is needed to predict patients with poor surgical outcomes.

Genetic Update and Treatment for Dystonia.

A neurological condition called dystonia results in abnormal, uncontrollable postures or movements because of sporadic or continuous muscular spasms. Several varieties of dystonia can impact people of all ages, leading to severe impairment and a decreased standard of living. The discovery of genes causing variations of single or mixed dystonia has improved our understanding of the disease's etiology. Genetic dystonias are linked to several genes, including pathogenic variations of VPS16, TOR1A, THAP1, GNAL, and ANO3. Diagnosis of dystonia is primarily based on clinical symptoms, which can be challenging due to overlapping symptoms with other neurological conditions, such as Parkinson's disease. This review aims to summarize recent advances in the genetic origins and management of focal dystonia.

Does blepharospasm effect biometric parameters and intraocular lens power calculations?

PURPOSE: To investigate the effect of botulinum toxin-A (BTX-A) treatment on corneal topography, ocular biometry and keratometry in patients with benign essential blepharospasm (BEB) and hemifacial spasm (HFS). METHODS: This study comprised 66 eyes of 33 patients with BEB and 5 eyes of 5 patients with HFS who underwent BTX-A injections consecutively. Refractive error values, tear break-up time (TBUT), corneal topography [corneal power of flat axis (K1) and steep axis (K2), mean corneal power (Km), corneal astigmatism (K2-K1)] and ocular optical biometry [axial length (AL), anterior chamber depth (ACD)] were recorded before BTX-A treatment and 1 month after BTX-A treatment. The researchers calculated the expected emmetropic intraocular lens power (emm-IOL) using the SRK-T, Holladay, Hoffer-Q and Haigis formulas at each examination. RESULTS: K1 (43.48 ± 2.02 vs. 43.57 ± 2.08, p = 0.036), Km (43.91 ± 1.99 vs. 43.99 ± 2.06, p = 0.024) and ACD (3.22 (2.77-3.76) vs. 3.41 (2.99-4.02), p < 0.001) values were found to be significantly higher. The expected emm-IOL according to the SRK-T (21.04 ± 1.6 vs. 20.93 ± 1.6, p = 0.048), Holladay (21.05 ± 1.6 vs. 20.91 ± 1.62, p = 0.037) and Hoffer-Q (21.08 ± 1.65 vs. 20.94 ± 1.68, p = 0.038) decreased significantly. The expected emm-IOL according to the Haigis formula slightly decreased, but it was not significant (p = 0.386). Additionally, TBUT was found to be significantly lower (p < 0.001) after BTX-A injection. Other parameters were not statistically significant (p > 0.05). CONCLUSIONS: Our study is the first in the literature to compare optic biometry data and intraocular lens power calculation formulas before and after BTX-A injection in eyes with BEB and HFS. BTX-A injection could play an important role in changing the keratometric and ACD values. It should be considered that IOL power calculations that might be unpredictable due to blepharospasm, so repeated measurements and especially measurements after releasing the spasm with BTX-A injections, are necessary in BEB and HFS.

Smartphone and custom-made software to assess the effect of botulinum toxin in essential blepharospasm: Initial results.

BACKGROUND AND PURPOSE: It is challenging to assess essential blepharospasm (EB) patients objectively because they exhibit chaotic patterns of abnormal eyelid movements. Previously employed objective approaches used systems with low levels of accuracy systems or were too complex to be applied in routine clinical practice. We aimed to develop a practical tool using a smartphone camera and custom-made software to objectively assess the therapeutic effects of botulinum toxin in blepharospasm patients. METHODS: Thirty-four patients with EB were evaluated before and 15 days after receiving onabotulinumtoxinA injections. The control group was composed of 19 age-matched healthy individuals. A smartphone (iPhone 6 S; Apple) was used to record spontaneous eyelid movements for 3 min, after which eyelid movement frequency was analysed using custom-made software. RESULTS: Before treatment, eyelid movement frequency was significantly higher in the EB group (21.55 ± 13.30 movements/min) compared to the control group (8.26 ± 8.89 eyelid movements/min; p < 0.001). The frequency of spontaneous eyelid movements was significantly reduced after treatment in the EB patients (8.46 ± 6.32 eyelid movements/min; p < 0.001). After treatment, no statistically significant difference in eyelid movement rate was observed between the EB patients and the control group (p = 0.32). CONCLUSIONS: Assessment of the spontaneous eyelid movements obtained with the smartphone camera and analysed with the custom-made software enabled us to objectively measure the therapeutic effects of botulinum toxin in patients with blepharospasm. Further refinement of this system could enable customized and fine adjustments to botulinum toxin doses based on each patient's needs.

Evaluation of non-motor symptoms in cervical dystonia, hemifacial spasm, and blepharospasm patients and their correlation with motor symptoms.

BACKGROUND: Awareness of non-motor symptoms has been increasing in recent years, but there are still few studies on this topic. OBJECTIVE: Our aim was to evaluate various non-motor symptoms, especially psychiatric disorders, cognitive status, and sleep, in cervical dystonia (CD), hemifacial spasm (HFS), and blepharospasm (BPS) patients and to investigate whether these symptoms are related to the severity of motor symptoms. METHODS: This was a single-center cross-sectional, observational, case-control study. Motor severity scales were used to determine disease severity. We evaluated non-motor symptoms with commonly used scales. A total of 73 patients and 73 control groups participated. RESULTS: In CD patients, the MoCA total score, 'language', 'abstraction', and 'orientation' scores were statistically significantly lower; PSQI, ESS, and NMSQ scores were statistically significantly higher than controls. In the BPS group, the MoCA total score and the 'language' score were significantly lower, and the NMSQ score was statistically significantly higher than the controls. In the HFS group, MoCA total score, 'executive functions', 'language', and 'abstraction' scores were statistically significantly lower; PSQI scores are statistically significantly higher than controls. There was a positive correlation between the severity score and the PSQI score in the CD group and between the severity score and the NMSQ score in the BPS group. All three groups had significant cognitive impairments. CONCLUSIONS: In CD, BPS, and HFS, non-motor symptoms are apparent with undeniable frequency in addition to common motor symptoms. Importantly, these NMS may cause significant deterioration in the quality of life of the patients.

Relations between nonmotor manifestations and motor disorders in patients with benign essential blepharospasm.

PURPOSE: To evaluate the relations between nonmotor manifestations (dry eye, mood disorders, and sleep disturbance) and motor disorders in patients with benign essential blepharospasm (BEB), and to determine whether relieving motor disorders by botulinum neurotoxin can improve the nonmotor manifestations. METHODS: In this prospective case series study, 123 BEB patients were enrolled for evaluations. Among them, 28 patients underwent botulinum neurotoxin therapy and attended another two postoperative visits at 1 month and 3 months. Motor severity was measured with Jankovic Rating Scale (JRS) and Blepharospasm Disability Index (BSDI). We assessed dry eye using OSDI questionnaire, Schirmer test, tear break-up time (TBUT), tear meniscus height, lipid layer thickness (LLT) and corneal fluorescence staining. Zung's Self-rating Anxiety and Depression Scale (SAS, SDS) and Pittsburgh Sleep Quality Index (PSQI) were for mood status and sleep quality evaluations. RESULTS: Patients with dry eye or mood disorders had higher JRS scores (5.78 ± 1.13, 5.97 ± 1.30) than those without (5.12 ± 1.40, 5.50 ± 1.16; P = 0.039, 0.019, respectively). BSDI values of patients with sleep disturbance (14.61 ± 4.71) was higher than those without (11.89 ± 5.44, P = 0.006). Correlations were found between JRS, BSDI and SAS, SDS, PSQI, OSDI, TBUT. Botulinum neurotoxin effectively relieved JRS, BSDI and improved PSQI, OSDI, TBUT, LLT (8.11 ± 5.81, 21.77 ± 15.76, 5.04 ± 2.15 s, 79.61 ± 24.11 nm) at the 1-month visit compared to baseline (9.75 ± 5.60, 33.58 ± 13.27, 4.14 ± 2.21 s, 62.33 ± 22.01 nm; P = 0.006, < 0.001, = 0.027, < 0.001, respectively). CONCLUSIONS: The BEB patients with dry eye, mood disorders, or sleep disturbance had more severe motor disorders. Motor severity was associated with the severity of the nonmotor manifestations. Relieving motor disorders by botulinum neurotoxin was effective in improving dry eye and sleep disturbance.

Genetic Screening of a Hungarian Cohort with Focal Dystonia Identified Several Novel Putative Pathogenic Gene Variants.

Dystonia is a rare movement disorder which is characterized by sustained or intermittent muscle contractions causing abnormal and often repetitive movements, postures, or both. The two most common forms of adult-onset focal dystonia are cervical dystonia (CD) and benign essential blepharospasm (BSP). A total of 121 patients (CD, 74; BSP, 47) were included in the study. The average age of the patients was 64 years. For the next-generation sequencing (NGS) approach, 30 genes were selected on the basis of a thorough search of the scientific literature. Assessment of 30 CD- and BSP-associated genes from 121 patients revealed a total of 209 different heterozygous variants in 24 genes. Established clinical and genetic validity was determined for nine heterozygous variations (three likely pathogenic and six variants of uncertain significance). Detailed genetic examination is an important part of the work-up for focal dystonia forms. To our knowledge, our investigation is the first such study to be carried out in the Middle-European region.

Visual evoked potential changes following Botox administration in patients with blepharospasm.

PURPOSE: To examine visual evoked potential (VEP) changes following botulinum toxin type A (BTA) administration in patients with blepharospasm. METHODS: Patients diagnosed with blepharospasm receiving BTA administration were included in the study. Three groups, a control group and two study groups (patients examined 14 days after BTA administration-Study Group 1, and patients examined 28 days after BTA administration-Study Group 2) were evaluated. Dilated fundus examinations were performed following detailed ophthalmological examinations and VEP tests. Keypoint (Dantec, Denmark) and ISCEV criteria were adopted for pattern VEP (PVEP) recording. BTA was applied in the form of local injections at a total 15-30 units, at 2.5-5 units per injection. RESULTS: A mean 19.4 ± 3.2 units of BTA was used for each eye. N70 (ms), P100 (ms), and P100 (uV) values were statistically significantly lower in both study groups following drug administrations compared to the control group (p < 0.001 for all). Significant positive correlation was observed between increased P100 amplitudes and age in the control group (p = 0.008, r = 0.200). Significant negative correlation was observed between the BTA units used and decreased P100 amplitudes in both study groups 1 and 2 following drug administrations (p = 0.017, r = - 0.180 and p = 0.043, r = - 0.153, respectively). CONCLUSION: VEP may be an important method in the diagnosis and follow-up of blepharospasm and in determining the success of drug administration and additional therapeutic requirements.

Abnormal dynamic brain activity and functional connectivity of primary motor cortex in blepharospasm.

BACKGROUND AND PURPOSE: Accumulating evidence indicates that dynamic amplitude of low-frequency fluctuations (dALFF) or dynamic functional connectivity (dFC) can provide complementary information, distinct from static amplitude of low-frequency fluctuations (sALFF) or static functional connectivity (sFC), in detecting brain functional abnormalities in brain diseases. We aimed to examine whether dALFF and dFC can offer valuable information for the detection of functional brain abnormalities in patients with blepharospasm. METHODS: We collected resting-state functional magnetic resonance imaging data from 46 patients each of blepharospasm, hemifacial spasm (HFS), and healthy controls (HCs). We examined intergroup differences in sALFF and dALFF to investigate abnormal regional brain activity in patients with blepharospasm. Based on the dALFF results, we conducted seed-based sFC and dFC analyses to identify static and dynamic connectivity changes in brain networks centered on areas showing abnormal temporal variability of local brain activity in patients with blepharospasm. RESULTS: Compared with HCs, patients with blepharospasm displayed different brain functional change patterns characterized by increased sALFF in the left primary motor cortex (PMC) but increased dALFF variance in the right PMC. However, differences were not found between patients with HFS and HCs. Additionally, patients with blepharospasm exhibited decreased dFC strength, but no change in sFC, between right PMC and ipsilateral cerebellum compared with HCs; these findings were replicated when patients with blepharospasm were compared to those with HFS. CONCLUSIONS: Our findings highlight that dALFF and dFC are complementary to sALFF and sFC and can provide valuable information for detecting brain functional abnormalities in blepharospasm. Blepharospasm may be a network disorder involving the cortico-ponto-cerebello-thalamo-cortical circuit.

A patient-initiated treatment model for blepharospasm and hemifacial spasm: a randomized controlled trial.

BACKGROUND: To test, in a two-arm, single center, superiority, randomized controlled trial, the effectiveness of and costs associated with a patient-initiated treatment model for people with hemifacial spasm (HFS) and blepharospasm (BEB) in comparison to usual care. METHODS: One hundred and thirty patients with HFS or BEB, aged 18 years or over, were recruited from a nurse-led botulinum toxin type A clinic at an eye hospital in the United Kingdom (UK), completed baseline measures and were randomized (1:1). The intervention group determined their own botulinum toxin type A (BoNT/A) treatment schedule during the trial period (9 months) and received an information leaflet with a "hotline" number to book an appointment. Usual care appointments were scheduled by treating clinicians. Data analysts were blind to study group. The primary outcomes were disease severity and functional disability, as measured by the Jankovic Rating Scale and Blepharospasm Disability Index, respectively. Secondary outcomes included quality of life, anxiety and depression, satisfaction with care, confidence in the service, economic costs and employment days lost. RESULTS: Sixty-five patients were randomized to each group. The intervention demonstrated no statistically significant difference to usual care for any of primary outcomes. On secondary outcomes the levels of anxiety differed significantly (F2, 142.39 = 1.65, p = 0.02), with the intervention arm exhibiting a decrease and the control arm an increase (Hedges' g = - 0.26 [99% CI -0.83, 0.32]). No other statistically significant differences were found for secondary outcomes. Overall healthcare costs and costs to the patient were on average £198.95 less (95% CI -£256.76, £654.67; p = 0.10) per participant for those in the intervention compared to usual care, although this finding was not significant. CONCLUSIONS: We did not observe differences between the patient-initiated treatment model and usual care for people with BEB or HFS, on any primary outcome measure, quality of life, or depression. The patient-initiated treatment model may, however, have the potential to save healthcare costs and reduce anxiety. Patients using this new model were also equally as satisfied in the service and confident in their care as those receiving treatment as usual. TRIAL REGISTRATION: Clinicaltrials.gov ID NCT02577224 , 16th October 2015.

Genetic screening in patients of Meige syndrome and blepharospasm.

OBJECTIVE: Meige syndrome (MS) is cranial dystonia, including bilateral eyelid spasms (blepharospasm; BSP) and involuntary movements of the jaw muscles (oromandibular dystonia; OMD). Up to now, the pathogenic genes of MS and BSP are still unclear. METHODS: We performed Sanger sequencing of GNAL, TOR1A, TOR2A, THAP1, and REEP4 exons on 78 patients, including 53 BSP and 25 MS and 96 healthy controls. RESULTS: c.845G > C[R282P] of TOR1A, c.629delC[p.Gly210AlafsTer60] of TOR2A, c.1322A > G[N441S] of GNAL, c.446G > A[R149Q], and c.649C > T[R217C] of REEP4 were identified and predicated as deleterious probably damaging variants. Three potential alterations of splicing variants of TOR1A and TOR2A were identified in patients. The frequencies of TOR1A rs1435566780 and THAP1 rs545930392 were higher in patients than in controls. CONCLUSIONS: TOR1A rs1435566780 (c.*16G > C(G > A)) and THAP1 rs545930392 (c.192G > A[K64K]) may contribute to the etiology of MS and BSP. Other identified rare mutations predicted as deleterious probably damaging need further confirmation. Larger MS and BSP cohorts and functional studies will need to be performed further to elucidate the association between these genes and the diseases.

Diagnostic and therapeutic recommendations in adult dystonia: a joint document by the Italian Society of Neurology, the Italian Academy for the Study of Parkinson's Disease and Movement Disorders, and the Italian Network on Botulinum Toxin.

The diagnostic framework and the therapeutic management of patients with adult dystonia can represent a challenge for clinical neurologists. The objective of the present paper is to delineate diagnostic and therapeutic recommendations for dystonia provided by a panel of Italian experts afferent to the Italian Society of Neurology, the Italian Academy for the Study of Parkinson's Disease and Movement Disorders, and the Italian Network on Botulinum Toxin. We first discuss the clinical approach and the instrumental assessment useful for diagnostic purpose. Then, we analyze the pharmacological, surgical, and rehabilitative therapeutic options for adult dystonia. Finally, we propose a hospital-territory network model for adult dystonia management.

Medical cannabis oil for benign essential blepharospasm: a prospective, randomized controlled pilot study.

OBJECTIVE: To examine the efficacy and safety of medical cannabis in benign essential blepharospasm (BEB). METHODS: This is a prospective, double-blind, placebo-controlled study. All consecutive adult BEB patients who had been treated with BTX-A injections without success between 3/2019 and 2/2020 were recruited. The study patients were randomly allocated into a treatment and a control (placebo) group in a 1:1 ratio. The treatment group used cannabis drops and the control group used cannabis oil drops during the first 6 weeks of the study, and both groups were treated with the medical cannabis drops during the second 6 weeks. The cannabis dose was gradually increased for each patient depending upon effect and tolerability. RESULTS: Three patients were included in each group (treatment and control groups). The mean duration of spasm attack during the first 6 weeks was 4.29 min in the treatment group and 73.9 min in the placebo group (P < 0.01). During the last 6 weeks, the treatment group used an average of 6.27 drops and the placebo group used an average of 5.36 drops (P = 0.478). There were 61 spasm events in the treatment group and 94 spasm events in the placebo group (P = 0.05). The mean duration of spasm attack was 1.77 and 8.96 min, respectively (P < 0.01). The side effects were mild, and they included general fatigue, dry mouth, and insomnia. CONCLUSIONS: Medical cannabis can be an effective and safe treatment for BEB as a second line after BTX-A injections when used for 3 months. No significant ocular or systemic side effects was associated with the treatment.

Outcome of pallidal deep brain stimulation for treating isolated orofacial dystonia.

BACKGROUND: Isolated orofacial dystonia is a rare segmental neurological disorder that affects the eye, mouth, face, and jaws. Current literature on pallidal surgery for orofacial dystonia is limited to case reports and small-scale studies. This study was to investigate clinical outcomes of deep brain stimulation (DBS) of the globus pallidus internus (GPi) in patients with isolated orofacial dystonia. METHODS: Thirty-six patients who underwent GPi DBS at Incheon St. Mary's Hospital, The Catholic University of Korea, between 2014 and 2019 were included in this study. Burke-Fahn-Marsden Dystonia Rating Scale, Unified Dystonia Rating Scale, and Global Dystonia Severity Rating Scale were retrospectively retrieved for analysis before surgery, at 6-month follow-up as short-term outcome, and at follow-up over 1 year (12 months to 69 months) as long-term results. RESULTS: Mean total BFMDRS-M scores at the three time points (baseline, 6 months, and over 1 year follow-up) were 11.6 ± 4.9, 6.1 ± 5.2 (50.3 ± 29.9% improvement, p < 0.05), and 4.3 ± 4.2 (65.0 ± 24.2% improvement, p < 0.05), respectively. In terms of UDRS and GDS, improvement rates were 45.1% (p < 0.001) and 47.7% (p < 0.001) at 6 months, and 63.8% (p < 0.001) and 65.7% (p < 0.001) at over 1 year after surgery, respectively. CONCLUSIONS: Bilateral GPi DBS in isolated orofacial dystonia can be effective if conservative treatment option fails. Its benefit is not only observed in a short term, but also maintained in a long-term follow-up.

Tear meniscus, corneal topographic and aberrometric changes after botulinum toxin-a injection in patients with blepharospasm and hemifacial spasm.

PURPOSE: To investigate the effect of botulinum neurotoxin-A (BTX-A) treatment on dry eye symptoms, tear meniscus, corneal topography and corneal aberrometry in patients with benign essential blepharospasm (BEB) and hemifacial spasm (HFS). MATERIALS AND METHODS: This prospective study comprised of 6 patients with BEB and 20 patients with HFS. Tear meniscus height (TMH) and depth (TMD), tear break-up time (TBUT), corneal fluorescein staining score (CFSS), Schirmer I test, ocular surface disease index (OSDI) score, corneal topography [corneal power of flat axis (K1), corneal power of steep axis (K2), mean corneal power (Km), astigmatism and thinnest pachymetry] and anterior corneal aberrometry [spherical aberration (SA), vertical coma (vcoma), horizontal coma (hcoma), higher order root mean square (hRMS) and total RMS] were evaluated before BTX-A treatment, 3 weeks after BTX-A treatment and 2 months after BTX-A treatment. RESULTS: Six patients with BEB and 20 patients with HFS treated with BTX-A were evaluated in this study. Twenty contralateral spasm free eyes of 20 HFS patients were taken as control group. TMH and TMD were found to be significantly higher in eyes with spasm at both 3 weeks and 2 months after injection (TMH: 279.0 ± 123.2 at pretreatment, 380.5 ± 174.7 at third week and 317.0 ± 125.5 at second month p < 0.001 and p = 0.02, respectively), (TMD: 183.7 ± 59.7 at pretreatment, 235.7 ± 91.1 at third week and 209.8 ± 77.1 at second month p < 0.01 and p = 0.015, respectively). TBUT, CFSS, Schirmer I test values were similar (p > 0.05). OSDI scores decreased significantly from 29.6 ± 25.3 to 19.8 ± 20. p = 0.03 at third week and increased again by second month. K2 (43.9 ± 1.7 vs. 43.7 ± 1.6, p = 0.03) and astigmatism (0.8 ± 0.5 vs. 0.6 ± 0.4, p = 0.04) values were significantly lower at third week and increased again by second month. Pachymetry and aberrometric values did not change significantly. In the control group only Schirmer I test value decreased significantly at second month (10.5 ± 6.5 vs. 7.2 ± 5.6, p = 0.008), other parameters did not change. CONCLUSION: BTX-A injection increases tear meniscus and decrease symptoms related to dry eye disease in BEB and HFS patients. It decrease astigmatism and keratometry values, it does not cause a significant change in corneal aberrations. However the positive effects of BTX-A injection on ocular surface is temporary.

Atypical Blepharospasm with Oromandibular Dystonia Associated with Cerebral Amyloid Angiopathy.

A case of atypical blepharospasm with oromandibular dystonia is presented in a patient found to have cerebral amyloid angiopathy on magnetic resonance imaging and a shared mechanism is discussed.

THE EFFECT OF BOTULINUM TOXIN TYPE A IN PATIENTS WITH ESSENTIAL BLEPHAROSPASM.

The aim of this study was to determine the effect of botulinum toxin type A and satisfaction in patients with essential blepharospasm. The study included 12 subjects suffering from essential blepharospasm who received therapy with botulinum toxin type A injections. Respondents were given a Blepharospasm Disability Index (BSDI) survey before and three weeks after the procedure with questions related to quality of life. They were also given a Jankovic Rating Scale with questions related to the severity and frequency of symptoms. The overall level of difficulties was reduced, meaning the quality of life increased after the application of botulinum toxin, and the study found that the increase was statistically significant (p = 0.003). The severity of symptoms after the application of botulinum toxin was reduced, which meant that there was a decrease in the severity of the difficulties, and the study found a statistically significant difference (p=0.003). The frequency of symptoms was reduced after botulinum toxin administration, and the study revealed a statistically significant difference (p = 0.012). From the results of this study, we can determine that the use of botulinum toxin type A increases the quality of life and that the severity and frequency of symptoms are statistically significantly reduced.

Cortical neurophysiology of primary isolated dystonia and non-dystonic adults: A meta-analysis.

Transcranial magnetic stimulation (TMS) is a non-invasive method to assess neurophysiology of the primary motor cortex in humans. Dystonia is a poorly understood neurological movement disorder, often presenting in an idiopathic, isolated form across different parts of the body. The neurophysiological profile of isolated dystonia compared to healthy adults remains unclear. We conducted a systematic review with meta-analysis of neurophysiologic TMS measures in people with isolated dystonia to provide a synthesized understanding of cortical neurophysiology associated with isolated dystonia. We performed a systematic database search and data were extracted independently by the two authors. Separate meta-analyses were performed for TMS measures of: motor threshold, corticomotor excitability, short interval intracortical inhibition, cortical silent period, intracortical facilitation and afferent-induced inhibition. Standardized mean differences were calculated using a random effects model to determine overall effect sizes and confidence intervals. Heterogeneity was explored using dystonia type subgroup analysis. The search resulted in 78 studies meeting inclusion criteria, of these 57 studies reported data in participants with focal hand dystonia, cervical dystonia, blepharospasm or spasmodic dysphonia, and were included in at least one meta-analysis. The cortical silent period, short-interval intracortical inhibition and afferent-induced inhibition was found to be reduced in isolated dystonia compared to controls. Reduced GABAergic-mediated inhibition in the primary motor cortex in idiopathic isolated dystonia's suggest interventions targeted to aberrant cortical disinhibition could provide a novel treatment. Future meta-analyses require neurophysiology studies to use homogeneous cohorts of isolated dystonia participants, publish raw data values, and record electromyographic responses from dystonic musculature where possible.