[Blepharospasm, dry eye and extractable nuclear antigen antibodies (French translation of the article)]. / Blépharospasme, sécheresse oculaire et anticorps anti-nucléaires solubles.

PURPOSE: The goal of this study is to determine a link between benign essential blepharospasm and Sjogren's syndrome by analyzing the presence of extractable nuclear antigens in this population. METHODS: Seventy-two patients with benign essential blepharospasm (BEB) were included in this study. We eliminated patients with hemifacial spasm or blepharospasm secondary to corneal pathology. We collected the values of the Schirmer I test and the results of the anti-SSA and anti-SSB antibodies. RESULTS: Our study included 72 patients (144 eyes) whose 62 women (86.1%). Mean age was 74.3 years±10.73. Average Schirmer I test was 3.14mm±4.00mm. Five women (8% of this female population) had positive anti-SSA and SSB antibodies. Their mean age was 65.66 years±13.24 whereas the negative antibody patients had an average age of 75.42±9.27. There was no significant difference between their Schimer I test and the Schirmer I of negative antibody population. CONCLUSION: This study illustrates the possible association between the presence of Sjögren's syndrome and the occurrence of a BEB justifying the search for anti-SSA and anti SSB in blepharospasm patients.

Blepharospasm, dry eye and extractable nuclear antigen antibodies.

PURPOSE: To study whether there is an association between benign essential blepharospasm and Sjögren's syndrome by analyzing the presence of antibodies to extractable nuclear antigens in this population. METHODS: Seventy-two patients with benign essential blepharospasm (BEB) were included in this study. We excluded patients with hemifacial spasm or blepharospasm secondary to known corneal pathology. We recorded results of Schirmer I testing as well as levels of anti-SSA/Ro and anti-SSB/La antibodies. RESULTS: Our study included 72 patients (144 eyes), of which 62 (86.1%) were women. The mean age was 74.3±10.73 years. The mean Schirmer I test result was 3.14±4.00mm. Five women (8% of this female population) were found to have positive anti-SSA/Ro and anti-SSB/La antibodies. Their mean age was 65.66±13.24 years, while the mean age of the antibody-negative patients was 75.42±9.27 years. There was no statistically significant difference between the Schirmer I tests of the antibody positive and negative patients. CONCLUSION: This study demonstrates a possible association between Sjögren's syndrome and benign essential blepharospasm, justifying anti-SSA/Ro and anti-SSB/La testing in these patients.

Serum calcium, magnesium, phosphorus, and vitamin D in benign essential blepharospasm.

PURPOSE: This study aims to compare serum calcium, magnesium, phosphorus, and 25-hydroxy (OH)-vitamin D levels in patients with benign essential blepharospasm (BEB) and healthy subjects and to determine their association with disease severity and frequency. METHODS: This is a prospective study conducted in a tertiary care hospital. Fifty patients (female, 39; male, 11) with BEB and 22 healthy subjects (female, 15; male, 7) included in the study. Serum calcium, magnesium, phosphorus, and vitamin D levels of BEB and healthy groups were measured. Blepharospasm severity and frequency were assessed using scales ranging from 0 to 4 by following the Jankovic Rating Scale (JRS). RESULTS: Though there was no significant difference regarding magnesium, phosphorus, and 25(OH)-vitamin D levels between the two groups, serum calcium levels of the BEB group were significantly lower than the control group (9.5 ± 0.4 and 9.9 ± 0.4 mg/dl, respectively; P = 0.002), although in the normal range (9-10.5 mg/dl). In the BEB group, the mean Jankovic severity and frequency scores were 3.29 ± 0.54 and 3.59 ± 0.61, respectively. There was a moderate negative correlation between serum 25(OH)-vitamin D levels and Jankovic severity score (r = - 0.332; P = 0.022). CONCLUSION: Serum calcium levels of the BEB group were significantly lower than the healthy group. Serum vitamin D levels showed a moderate negative correlation with disease severity. The role of calcium and vitamin D in the evolution of the BEB need further investigation at the cellular and anatomical levels.

High prevalence of neutralizing antibodies after long-term botulinum neurotoxin therapy.

OBJECTIVE: To investigate the prevalence of neutralizing antibodies (NAbs) against botulinum neurotoxin type A (BoNT/A) during long-term BoNT/A treatment in different neurologic indications. METHODS: In this monocentric, observational cross-sectional study, 596 outpatients treated with BoNT/A for different indications were tested for BoNT/A binding antibodies by ELISA. Positive samples were investigated for NAbs with the mouse hemidiaphragm test. The prevalence of NAbs was analyzed for different indications: facial hemispasm, blepharospasm, cervical dystonia, other dystonia, and spasticity. Besides the rate of NAb-positive patients overall and per patient subgroup, a Kaplan-Meier analysis of the probability of remaining NAb negative with duration of treatment is provided, and a stepwise binary logistic regression analysis is performed to identify factors significantly contributing to the induction of NAbs. RESULTS: Overall, 83 of 596 patients (13.9%) had measurable NAbs. The probability of developing NAbs increased with the single and cumulative dose of treatment and was influenced by the BoNT/A formulation, while all other factors analyzed, including disease entity and treatment duration, had no additional influence. CONCLUSIONS: We present the largest study to date of the prevalence of BoNT/A NAbs in a large unbiased cohort of patients including the relevant neurologic indications. Repeated injections of BoNT/A inevitably bear the risk of developing NAbs. However, in addition to avoiding booster injections and providing short intervals between injections, reducing the individual injected doses may diminish the risk of NAb induction independently of the indication for which BoNT/A is used.

Blepharospasm with elevated anti-acetylcholine receptor antibody titer.

OBJECTIVES: To determine whether serum levels of anti-acetylcholine receptor antibody (anti-AChR-Abs) are related to clinical parameters of blepharospasm (BSP). METHODS: Eighty-three adults with BSP, 60 outpatients with hemifacial spasm (HFS) and 58 controls were recruited. Personal history, demographic factors, response to botulinum toxin type A (BoNT-A) and other neurological conditions were recorded. Anti-AChR-Abs levels were quantified using an enzyme-linked immunosorbent assay. RESULTS: The anti-AChR Abs levels were 0.237 ± 0.022 optical density units in the BSP group, which was significantly different from the HFS group (0.160 ± 0.064) and control group (0.126 ± 0.038). The anti-AChR Abs level was correlated with age and the duration of response to the BoNT-A injection. CONCLUSION: Patients with BSP had an elevated anti-AChR Abs titer, which suggests that dysimmunity plays a role in the onset of BSP. An increased anti-AChR Abs titer may be a predictor for poor response to BoNT-A in BSP.

Blepharospasm with elevated anti-acetylcholine receptor antibody titer / Blefaroespasmo com título elevado de anticorpos antirreceptores de acetilcolina

ABSTRACT Objective: To determine whether serum levels of anti-acetylcholine receptor antibody (anti-AChR-Abs) are related to clinical parameters of blepharospasm (BSP). Methods: Eighty-three adults with BSP, 60 outpatients with hemifacial spasm (HFS) and 58 controls were recruited. Personal history, demographic factors, response to botulinum toxin type A (BoNT-A) and other neurological conditions were recorded. Anti-AChR-Abs levels were quantified using an enzyme-linked immunosorbent assay. Results: The anti-AChR Abs levels were 0.237 ± 0.022 optical density units in the BSP group, which was significantly different from the HFS group (0.160 ± 0.064) and control group (0.126 ± 0.038). The anti-AChR Abs level was correlated with age and the duration of response to the BoNT-A injection. Conclusion: Patients with BSP had an elevated anti-AChR Abs titer, which suggests that dysimmunity plays a role in the onset of BSP. An increased anti-AChR Abs titer may be a predictor for poor response to BoNT-A in BSP.

RESUMO Objetivo: Determinar se os níveis séricos do anticorpo antirreceptor de acetilcolina (anti-AChR-Abs) estão relacionados aos parâmetros clínicos do blefaroespasmo (BSP). Métodos: Fora recrutados 83 adultos com BSP, 60 pacientes ambulatoriais com espasmo hemifacial (HFS) e 58 controles. Foi aplicado um questionário para registrar história pessoal, fatores demográficos, resposta à toxina botulínica tipo A (BoNT-A) e outras condições neurológicas. Os níveis de anti-AChR-Abs foram quantificados usando um ensaio imunoenzimático. Resultados: O nível de anti-AChR-Abs foi de 0,237 ± 0,022 unidades de densidade óptica (OD) no grupo BSP, significativamente diferente em comparação com o grupo HFS (0,160 ± 0,064) e o grupo controle (0,126 ± 0,038). O nível de anti-AChR-Abs se correlacionou com a idade e a duração da resposta à injeção de BoNT-A. Conclusão: Pacientes com BSP apresentaram títulos elevados de anti-AChR-Abs, o que sugere que a desimunidade desempenha um papel no surgimento de BSP. O aumento do título de anti-AChR-Abs pode ser um preditor de resposta insuficiente à BoNT-A em BSP.

Aceruloplasminemia: molecular characterization of this disorder of iron metabolism.

Ceruloplasmin is an abundant alpha 2-serum glycoprotein that contains 95% of the copper found in the plasma of vertebrate species. We report here on the identification of a genetic defect in the ceruloplasmin gene in a patient previously noted to have a total absence of circulating serum ceruloplasmin in association with late-onset retinal and basal ganglia degeneration. In this patient T2 (transverse relaxation time)-weighted magnetic resonance imaging of the brain revealed basal ganglia densities consistent with iron deposition, and liver biopsy confirmed the presence of excess iron. Although Southern blot analysis of the patient's DNA was normal, PCR amplification of 18 of the 19 exons composing the human ceruloplasmin gene revealed a distinct size difference in exon 7. DNA sequence analysis of this exon revealed a 5-bp insertion at amino acid 410, resulting in a frame-shift mutation and a truncated open reading frame. The validity of this mutation was confirmed by analysis of DNA from the patient's daughter, which revealed heterozygosity for this same 5-bp insertion. The presence of this mutation in conjunction with the clinical and pathologic findings demonstrates an essential role for ceruloplasmin in human biology and identifies aceruloplasminemia as an autosomal recessive disorder of iron metabolism. These findings support previous studies that identified ceruloplasmin as a ferroxidase and are remarkably consistent with recent studies on the essential role of a homologous copper oxidase in iron metabolism in yeast. The clinical and laboratory findings suggest that additional patients with movement disorders and nonclassical Wilson disease should be examined for ceruloplasmin gene mutations.