The role of the injection botulinum toxin A in cases of blepharospasm syndrome, hemifacial spasm and Meige's syndrome. Bastola P,Chaudhary M,Agrawal J P,Shah D N Kathmandu University medical journal (KUMJ) BACKGROUND:Benign Essential Blepharospasm Symdrome is a neuropathologic disorder. The cause of blepharospasm is multifactorial. It is unlikely that a single defect in this elusive control centre is the primary cause of this disease. OBJECTIVES:To evaluate the role of botulinum toxin A in treating cases of Essential Blepharospasm Symdrome, Hemifacial Spasm and Meige's Syndrome, and to assess orbicularis oculi muscle post treatment, in the patients who attended neuro-ophthalmology clinic and the general outpatient department of BP Koirala Lions Centre for Ophthalmic studies. METHODS:A prospective, interventional study was carried out on all the patients of Essential Blepharospasm Symdrome, Hemifacial Spasm and Meige's syndrome who underwent treatment with botulinum toxin A in BP Koirala Lions Centre for Ophthalmic studies during a study period of one and half years. Pre- treatment grading of the spasm was done with Jankovic spasm grading and post treatment response was seen with assessment of orbicularis oculi muscle and improvement in functional impairment scale. Relevant findings were noted. RESULTS:A total of 40 cases were enrolled in the study. The mean Jankovic spasm grading in cases of essential blepharospasm, hemifacial spasm and Meige's syndrome was 3.61 (+/- Standard deviation 0.50, range 3-4), 3.21 (+/- Standard deviation 0.63, range 2-4) and 3.67 (+/- Standard deviation 0.57, range 3-4) respectively. The mean value for reappearance of significant spasms (in months) in cases of essential blepharospasm, hemifacial spasm and Meige's syndrome was 4.3 (+/- Standard deviation 1.6, range 2.0-6.5), 5.8 (+/- Standard deviation 1.4, range 3-8) and 4.5 (+/- Std.deviation 2.8, range 2.5-6.5) respectively. Blepharoptosis was the commonest complication accounting for 66.6% of the complications. CONCLUSIONS:The movement disorders like Essential Blepharospasm, Hemifacial Hpasm and Meige's syndrome are treated by different modalities. An acceptable and effective treatment modality has been a long felt need in these cases. Our study has shown that injection of botulinum toxin A has been a safe and effective method of treating these cases in Nepal. 10.3126/kumj.v8i3.6217

Whole-exome sequencing for variant discovery in blepharospasm. Molecular genetics & genomic medicine BACKGROUND:Blepharospasm (BSP) is a type of focal dystonia characterized by involuntary orbicularis oculi spasms that are usually bilateral, synchronous, and symmetrical. Despite strong evidence for genetic contributions to BSP, progress in the field has been constrained by small cohorts, incomplete penetrance, and late age of onset. Although several genetic etiologies for dystonia have been identified through whole-exome sequencing (WES), none of these are characteristically associated with BSP as a singular or predominant manifestation. METHODS:We performed WES on 31 subjects from 21 independent pedigrees with BSP. The strongest candidate sequence variants derived from in silico analyses were confirmed with bidirectional Sanger sequencing and subjected to cosegregation analysis. RESULTS:Cosegregating deleterious variants (GRCH37/hg19) in CACNA1A (NM_001127222.1: c.7261_7262delinsGT, p.Pro2421Val), REEP4 (NM_025232.3: c.109C>T, p.Arg37Trp), TOR2A (NM_130459.3: c.568C>T, p.Arg190Cys), and ATP2A3 (NM_005173.3: c.1966C>T, p.Arg656Cys) were identified in four independent multigenerational pedigrees. Deleterious variants in HS1BP3 (NM_022460.3: c.94C>A, p.Gly32Cys) and GNA14 (NM_004297.3: c.989_990del, p.Thr330ArgfsTer67) were identified in a father and son with segmental cranio-cervical dystonia first manifest as BSP. Deleterious variants in DNAH17, TRPV4, CAPN11, VPS13C, UNC13B, SPTBN4, MYOD1, and MRPL15 were found in two or more independent pedigrees. To our knowledge, none of these genes have previously been associated with isolated BSP, although other CACNA1A mutations have been associated with both positive and negative motor disorders including ataxia, episodic ataxia, hemiplegic migraine, and dystonia. CONCLUSIONS:Our WES datasets provide a platform for future studies of BSP genetics which will demand careful consideration of incomplete penetrance, pleiotropy, population stratification, and oligogenic inheritance patterns. 10.1002/mgg3.411

Blepharospasm: A genetic screening study in 132 patients. Hammer Monia,Abravanel Alexandra,Peckham Elizabeth,Mahloogi Ava,Majounie Elisa,Hallett Mark,Singleton Andrew Parkinsonism & related disorders INTRODUCTION:Blepharospasm is a common type of focal dystonia that involves involuntary eyelid spasms and eye closure. In familial cases, an autosomal dominant pattern of inheritance is noted with reduced penetrance. Few genes have been associated with the disease including GNAL and CIZ1. A whole exome sequencing study published lately suggested TOR2A and REEP4 as potential candidate genes. METHODS:Sanger sequencing of GNAL, CIZ1, TOR2A and REEP4 exons including exon-intron boundaries in 132 patients diagnosed primarily with blepharospasm and/or Meige's syndrome. RESULTS:All variants detected in GNAL, CIZ1 and TOR2A seem to be benign. Sequencing of REEP4 revealed the presence of two nonsynonymous SNVs, one potential splice site variant and one indel all predicted to be damaging by in silico algorithms. CONCLUSION:Sequencing REEP4 in larger blepharospasm cohorts and functional studies will need to be performed to further elucidate the association between REEP4 and the disease. 10.1016/j.parkreldis.2019.04.003