Phenotypic correlations in a large single-center cohort of patients with BSCL2 nerve disorders: a clinical, neurophysiological and muscle magnetic resonance imaging study
Por:
Fernandez-Eulate, G, Fernandez-Torron, R, Guisasola, A, Gaspar, MTI, Diaz-Manera, J, Maneiro, M, Zulaica, M, Olasagasti, V, Formica, AF, Espinal, JB, Ruiz, M, Schluter, A, Pujol, A, Poza, JJ, de Munain, AL
Publicada:
1 ago 2020
Ahead of Print:
1 may 2020
Resumen:
Background and purpose BSCL2 heterozygote mutations are a common cause of distal hereditary motor neuropathies (dHMNs). A series of BSCL2 patients is presented and clinical, neurophysiological and muscle magnetic resonance imaging (MRI) findings are correlated.
Methods Twenty-six patients from five families carrying the p.N88S mutation were identified. Age of onset, clinical phenotype (dHMN, Charcot-Marie-Tooth, spastic paraplegia), physical examination, disability measured as a modified Rankin Scale score and neurophysiological findings were collected. A whole body muscle MRI had been performed in 18 patients. The pattern of muscle involvement on T1-weighted and short time inversion recovery sequences was analysed. Hierarchical analysis using heatmaps and an MRI Composite Score were generated. Statistical analysis was carried out with STATA SE v.15 (TX, USA).
Results The mean age was 51.54 +/- 19.94 years and 14 patients were men. dHMN was the most common phenotype (50%) and five patients (19.23%) showed no findings on examination. Disease onset was commonly in childhood and disability was low (modified Rankin Scale score 1.34 +/- 1.13) although median time since onset of disease was 32 years (range 10-47). Charcot-Marie-Tooth-like patients were more disabled and disability correlated with age. On muscle MRI, thenar eminence, soleus and tibialis anterior were most frequently involved, irrespective of clinical phenotype. MRI Composite Score was strongly correlated with disability.
Conclusion Patients with the p.N88S BSCL2 gene mutation are phenotypically variable, although dHMN is most frequent and generally slowly progressive. Muscle MRI pattern is consistent regardless of phenotype and correlates with disease severity, probably serving as a reliable outcome measure for future clinical trials.
Filiaciones:
Fernandez-Eulate, G:
Donostia Univ Hosp, Dept Neurol, Paseo Doctor Begiristain S-N, San Sebastian 20014, Spain
Hop La Pitie Salpetriere, Reference Ctr Neuromuscular Disorders, Inst Myol, Paris, France
Fernandez-Torron, R:
Donostia Univ Hosp, Dept Neurol, Paseo Doctor Begiristain S-N, San Sebastian 20014, Spain
Biodonostia Hlth Res Inst, Grp Neurodegenerat Dis, Neuromuscular Area, San Sebastian, Spain
Guisasola, A:
Osatek, Dept Radiol, San Sebastian, Spain
Gaspar, MTI:
Donostia Univ Hosp, Clin Epidemiol Unit, San Sebastian, Spain
Diaz-Manera, J:
Hosp Santa Creu & Sant Pau, Serv Neurol, Unitat Malaties Neuromuscularis, Barcelona, Spain
Univ Newcastle, John Walton Muscular Dystrophy Res Ctr, Newcastle, England
Maneiro, M:
Donostia Univ Hosp, Dept Neurol, Paseo Doctor Begiristain S-N, San Sebastian 20014, Spain
Zulaica, M:
Biodonostia Hlth Res Inst, Grp Neurodegenerat Dis, Neuromuscular Area, San Sebastian, Spain
Olasagasti, V:
Donostia Univ Hosp, Dept Neurol, Paseo Doctor Begiristain S-N, San Sebastian 20014, Spain
Formica, AF:
Donostia Univ Hosp, Dept Neurol, Paseo Doctor Begiristain S-N, San Sebastian 20014, Spain
Espinal, JB:
Donostia Univ Hosp, Dept Neurol, Paseo Doctor Begiristain S-N, San Sebastian 20014, Spain
Ruiz, M:
Bellvitge Biomed Res Inst IDIBELL, Neurometab Dis Lab, Lhospitalet De Llobregat, Spain
Inst Hlth Carlos III, Ctr Biomed Res Rare Dis CIBERER, Madrid, Spain
Schluter, A:
Bellvitge Biomed Res Inst IDIBELL, Neurometab Dis Lab, Lhospitalet De Llobregat, Spain
Pujol, A:
Bellvitge Biomed Res Inst IDIBELL, Neurometab Dis Lab, Lhospitalet De Llobregat, Spain
Inst Hlth Carlos III, Ctr Biomed Res Rare Dis CIBERER, Madrid, Spain
Catalan Inst Res & Adv Studies ICREA, Barcelona, Spain
Poza, JJ:
Donostia Univ Hosp, Dept Neurol, Paseo Doctor Begiristain S-N, San Sebastian 20014, Spain
de Munain, AL:
Donostia Univ Hosp, Dept Neurol, Paseo Doctor Begiristain S-N, San Sebastian 20014, Spain
Biodonostia Hlth Res Inst, Grp Neurodegenerat Dis, Neuromuscular Area, San Sebastian, Spain
Univ Basque Country, Neurosci Dept, Sch Med, San Sebastian, Spain
Inst Carlos III, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Green Accepted
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