d'Orsi Giuseppe, Di Claudio Maria Teresa, Liantonio Antonella, Imbrici Paola, Altomare Cosimo Damiano, Palumbo Orazio, Palumbo Pietro, Benvenuto Mario, Gambacorta Nicola, Lolli Graziano, Carella Massimo
Neurology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini, 1, 71013, San Giovanni Rotondo, FG, Italy.
Department of Pharmacy - Drug Sciences, University of Bari "Aldo Moro", Bari, Italy.
Orphanet J Rare Dis. 2025 Aug 21;20(1):447. doi: 10.1186/s13023-025-03976-x.
Lafora disease (LD) is an ultra-rare, autosomal recessive neurodegenerative disorder characterized by the accumulation of Lafora bodies in the brain, leading to drug-resistant epilepsy, myoclonus, progressive dementia, and cerebellar dysfunction. This retrospective study describes the clinical course and management challenges of LD in a cohort of patients from the Apulia region of Southern Italy, where the disease prevalence appears to be higher than in other populations.
We retrospectively analyzed clinical, electroencephalographic, and management data from six unrelated families with a confirmed diagnosis of LD, followed at the Neurology Unit of the Scientific Institute Casa Sollievo della Sofferenza Hospital between 2010 and 2024. Demographic information, clinical presentation, treatment history, disease progression, and outcomes were collected.
Our analysis identified three distinct electroclinical stages: an initial Presenting Symptoms Stage with the onset of seizures and subsequent development of myoclonus; a Progressive Neurodegeneration Stage characterized by drug-resistant epilepsy, dementia, and ataxia; and a Terminal Stage marked by severe disability, frequent seizure emergencies, and medical complications. Management in the late stages proved particularly challenging, requiring a multidisciplinary approach to address refractory seizures, status epilepticus, and medical complications such as aspiration pneumonia and respiratory failure. Home-based care, with specialized team support, played a crucial role in minimizing hospitalizations.
Our findings underscore the importance of early diagnosis and a multidisciplinary approach in the management of LD. The late stages of the disease are characterized by significant clinical challenges necessitating close collaboration among neurologists, epileptologists, and other healthcare professionals, supported by effective home-based care. The apparent higher prevalence in Apulia warrants further investigation into potential genetic or environmental factors.
This study highlights the significant clinical burden of LD and emphasizes the importance of multidisciplinary management, particularly in the advanced stages. Home-based care supported by specialized teams and caregivers is essential for optimizing patient well-being. Further research is needed to identify early biomarkers and develop targeted therapies for this devastating condition.
拉福拉病（LD）是一种极为罕见的常染色体隐性神经退行性疾病，其特征是大脑中出现拉福拉小体，导致耐药性癫痫、肌阵挛、进行性痴呆和小脑功能障碍。这项回顾性研究描述了意大利南部普利亚地区一组LD患者的临床病程及管理挑战，该地区的疾病患病率似乎高于其他人群。
我们回顾性分析了2010年至2024年期间在科学研究所卡萨索利耶沃德拉索费伦扎医院神经科接受随访的6个确诊为LD的非相关家庭的临床、脑电图及管理数据。收集了人口统计学信息、临床表现、治疗史、疾病进展及结果。
我们的分析确定了三个不同的电临床阶段：初始的症状出现阶段，伴有癫痫发作及随后肌阵挛的发展；进行性神经退行性阶段，其特征为耐药性癫痫、痴呆和共济失调；以及终末期，其特点是严重残疾、频繁的癫痫急症和医疗并发症。后期管理被证明特别具有挑战性，需要多学科方法来应对难治性癫痫、癫痫持续状态以及诸如吸入性肺炎和呼吸衰竭等医疗并发症。在专业团队支持下的居家护理在尽量减少住院方面发挥了关键作用。
我们的研究结果强调了早期诊断和多学科方法在LD管理中的重要性。疾病后期存在重大临床挑战，需要神经科医生、癫痫专家和其他医疗保健专业人员密切合作，并辅以有效的居家护理。普利亚地区明显较高的患病率值得进一步调查潜在的遗传或环境因素。
本研究突出了LD的重大临床负担，并强调了多学科管理的重要性，特别是在疾病晚期。由专业团队和护理人员支持的居家护理对于优化患者福祉至关重要。需要进一步研究以确定早期生物标志物并开发针对这种毁灭性疾病的靶向治疗方法。
