Espasmo hemifacial: da morfologia à clínica
Data
2025-01-10
Autores
Gameiro, Gustavo Rosa 
Orientadores
Schor, Paulo
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Esta tese busca expandir o entendimento dos mecanismos envolvidos no espasmo hemifacial e suas implicações clínicas, integrando análises musculares e funcionais também para avaliar a resposta ao tratamento. Objetivos: 1) Avaliar amostras de biópsia do músculo orbicular oculi (MOO) de ambos os lados (clinicamente afetado e não afetado) de pacientes portadores de espasmo hemifacial (EH). 2) Analisar objetivamente a cinemática dos movimentos palpebrais em pacientes com espasmo hemifacial pré e pós-tratamento com toxina botulínica A (BoNT-A) e compará-la com a de indivíduos controles. 3) Demonstrar objetivamente o efeito do tratamento nos pacientes com EH utilizando smartphone e software customizado que usa o conceito de eye aspect ratio (EAR). Métodos: 1) Foram processadas e quantificadas amostras da porção pré-septal do MOO de pacientes com EH virgens de tratamento (lados afetado e não afetado) e de indivíduos normais para avaliação morfológica, histoquímica e imuno-histoquímica. 2) Ademais, avaliaram-se pacientes com espasmo hemifacial e controles. A análise da dinâmica palpebral foi possível através da gravação de um vídeo de 3 minutos por câmera de alta velocidade com auxílio de LEDs fixados nas pálpebras superiores. 3) Vídeos padronizados, gravados por um smartphone, pré e pós aplicação de BoNT-A em pacientes portadores de EH foram analisados calculando-se o EAR médio de cada vídeo para cada lado através de um software customizado. Resultados: 1) O MOO do lado clinicamente afetado de pacientes com EH mostrou fibras musculares com maior área, menor densidade de fibras, maior taxa de tecido conectivo, maior taxa de desorganização e metabolismo oxidativo aumentado das fibras musculares, além de maior porcentagem de fibras lentas quando comparados a amostras do grupo controle. O lado clinicamente não afetado também apresentou alterações em menor magnitude, porém alinhadas com o lado clinicamente afetado. 2) As injeções de BoNT-A em pacientes com EH reduziram significativamente vários parâmetros palpebrais. Após 30 dias, a amplitude do piscar diminuiu 20%, a frequência do piscar 39% e a velocidade máxima de fechamento palpebral, 26%. Além disso, antes mesmo do tratamento, a velocidade de fechamento palpebral no lado afetado já era significativamente menor em comparação com o grupo controle. 3) As injeções de BoNT-A causaram um aumento de 10,4% no valor de EAR médio (p=0,017) no lado afetado de pacientes com EH. Antes das aplicações, o EAR era significativamente menor (16,2%) no lado afetado dos pacientes com EH (0,25 ± 0,05) do que nos controles (0,30 ± 0,05, p=0,004). Conclusões: 1) Este estudo sugere que contrações crônicas repetidas em pacientes com EH podem causar hipertrofia das fibras do músculo orbicular oculi, aumento do metabolismo mitocondrial e possível conversão de fibras musculares rápidas em lentas. Essas alterações ocorrem tanto nos lados afetados quanto nos não afetados (em menor magnitude), reforçando a ideia de que o lado não afetado também apresenta anormalidades nessa condição específica. 2) Após o tratamento com BoNT-A, pacientes com EH mostraram uma frequência de piscar mais próxima do normal, mas a amplitude e a velocidade do piscar mostraram-se significativamente menores em comparação com indivíduos saudáveis. Além disso, observou-se que a velocidade de fechamento das pálpebras nesses pacientes era significativamente menor que o grupo controle, mesmo antes do tratamento. 3) A aplicação do conceito de EAR demonstrou objetivamente alívio dos espasmos palpebrais em pacientes com EH. Aperfeiçoamentos desse sistema poderiam permitir avaliações mais precisas das respostas ao tratamento para cada paciente, viabilizando seu uso rotineiro na prática clínica.
This thesis aims to expand the understanding of the mechanisms involved in hemifacial spasm and its clinical implications, integrating muscle and functional analyses to also evaluate the response to treatment. Objectives: 1) To evaluate biopsy samples of orbicularis oculi muscle (OOM) from both sides (clinically affected and unaffected) of patients with hemifacial spasm (HFS). 2) To objectively analyze the kinematics of eyelid movements in patients with hemifacial spasm before and after treatment with botulinum toxin A (BoNT-A) and compare them with those of control subjects. 3) To objectively demonstrate the effect of treatment in patients with HFS using a smartphone and custom software that utilizes the concept of eye aspect ratio (EAR). Methods: 1) Samples from the preseptal portion of the OOM of treatment-naive patients with HFS (affected and unaffected sides) and control subjects were processed and quantified for morphological, metabolic, and immunohistochemical evaluation. 2) Additionally, patients with hemifacial spasm and controls were evaluated. The analysis of eyelid dynamics was made possible through the recording of a 3-minute video by a high-speed camera with the aid of LEDs attached to the upper eyelids. 3) Standardized videos, recorded by a smartphone before and after the application of BoNT-A in patients with HFS, were analyzed by calculating the average EAR of each video for each side using custom software. Results: 1) The OOM on the clinically affected side of patients with HFS showed greater fiber area, lower density of fibers, higher rate of connective tissue, greater rate of disorganization and oxidative metabolism of muscle fibers, and a higher percentage of slow fibers when compared to controls. The clinically unaffected side also showed changes, albeit of a lesser magnitude, yet aligned with the clinically affected side. 2) BoNT-A injections in patients with HFS significantly reduced various eyelid parameters. After 30 days, the amplitude of blinking decreased by 20%, the frequency of blinking by 39%, and the maximum speed of eyelid closure by 26%, compared to baseline. Furthermore, even before treatment, the eyelid closing velocity was significantly lower compared to the control group. 3) BoNT-A injections increased the average EAR value in 10.4% (p=0.017) on the affected side of patients with HFS. Before the applications, the EAR was significantly lower (16.2%) on the affected side of patients with HFS (0.25 ± 0.05) compared to the controls (0.30 ± 0.05, p=0.004). Conclusions: 1) This study suggests that chronic repeated contractions in patients with HFS can cause hypertrophy of the fibers of the orbicularis oculi muscle, increased mitochondrial metabolism, and possible conversion of fast muscle fibers into slow ones. These changes occur on both the affected and unaffected sides (to a lesser extent), reinforcing the idea that the unaffected side also presents abnormalities in this specific condition. 2) After treatment with BoNT-A, patients with HFS showed a blinking frequency closer to normal, but the amplitude and eyelid closing velocity were significantly lower compared to healthy individuals. Moreover, it was observed that the eyelid closing velocity in these patients was already significantly lower than the control group, even before treatment. 3) The application of the EAR concept objectively demonstrated relief of eyelid spasm in patients with HFS. Improvements to this system could allow for more precise evaluations of treatment responses for each patient, making its routine use in clinical practice feasible.
This thesis aims to expand the understanding of the mechanisms involved in hemifacial spasm and its clinical implications, integrating muscle and functional analyses to also evaluate the response to treatment. Objectives: 1) To evaluate biopsy samples of orbicularis oculi muscle (OOM) from both sides (clinically affected and unaffected) of patients with hemifacial spasm (HFS). 2) To objectively analyze the kinematics of eyelid movements in patients with hemifacial spasm before and after treatment with botulinum toxin A (BoNT-A) and compare them with those of control subjects. 3) To objectively demonstrate the effect of treatment in patients with HFS using a smartphone and custom software that utilizes the concept of eye aspect ratio (EAR). Methods: 1) Samples from the preseptal portion of the OOM of treatment-naive patients with HFS (affected and unaffected sides) and control subjects were processed and quantified for morphological, metabolic, and immunohistochemical evaluation. 2) Additionally, patients with hemifacial spasm and controls were evaluated. The analysis of eyelid dynamics was made possible through the recording of a 3-minute video by a high-speed camera with the aid of LEDs attached to the upper eyelids. 3) Standardized videos, recorded by a smartphone before and after the application of BoNT-A in patients with HFS, were analyzed by calculating the average EAR of each video for each side using custom software. Results: 1) The OOM on the clinically affected side of patients with HFS showed greater fiber area, lower density of fibers, higher rate of connective tissue, greater rate of disorganization and oxidative metabolism of muscle fibers, and a higher percentage of slow fibers when compared to controls. The clinically unaffected side also showed changes, albeit of a lesser magnitude, yet aligned with the clinically affected side. 2) BoNT-A injections in patients with HFS significantly reduced various eyelid parameters. After 30 days, the amplitude of blinking decreased by 20%, the frequency of blinking by 39%, and the maximum speed of eyelid closure by 26%, compared to baseline. Furthermore, even before treatment, the eyelid closing velocity was significantly lower compared to the control group. 3) BoNT-A injections increased the average EAR value in 10.4% (p=0.017) on the affected side of patients with HFS. Before the applications, the EAR was significantly lower (16.2%) on the affected side of patients with HFS (0.25 ± 0.05) compared to the controls (0.30 ± 0.05, p=0.004). Conclusions: 1) This study suggests that chronic repeated contractions in patients with HFS can cause hypertrophy of the fibers of the orbicularis oculi muscle, increased mitochondrial metabolism, and possible conversion of fast muscle fibers into slow ones. These changes occur on both the affected and unaffected sides (to a lesser extent), reinforcing the idea that the unaffected side also presents abnormalities in this specific condition. 2) After treatment with BoNT-A, patients with HFS showed a blinking frequency closer to normal, but the amplitude and eyelid closing velocity were significantly lower compared to healthy individuals. Moreover, it was observed that the eyelid closing velocity in these patients was already significantly lower than the control group, even before treatment. 3) The application of the EAR concept objectively demonstrated relief of eyelid spasm in patients with HFS. Improvements to this system could allow for more precise evaluations of treatment responses for each patient, making its routine use in clinical practice feasible.
Descrição
Citação
GAMEIRO, G. R. Espasmo hemifacial: da morfologia à clínica. 2025. 92 f. Tese (Doutorado em Oftalmologia e Ciências Visuais) – Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, 2025.
ODS
3. Saúde e bem-estar