ABSTRACT
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.
Subject(s)
Charcot-Marie-Tooth Disease , GTP-Binding Protein gamma Subunits/metabolism , Hereditary Sensory and Motor Neuropathy , Adult , Aged , Charcot-Marie-Tooth Disease/diagnostic imaging , Charcot-Marie-Tooth Disease/genetics , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Mutation , PhenotypeABSTRACT
Three patients (two females and one male) with radiculospinal neurologic involvement secondary to different forms of neurofibromatosis are reported. The first two met the diagnostic criteria for NF-1, although case 2 had a posterior fossa meningioma, which is an uncommon finding in this group. The male patient had an apparently sporadic NF-2, with bilateral acoustic nerve neurinoma, multiple meningioma, multiple radicular neurinoma and an intraspinal tumor apparent in magnetic resonance imaging. In the three cases the whole central nervous system was evaluated with gadolinium-enhanced magnetic resonance imaging. A great number of radicular tumors, many of which were asymptomatic, were detected. In spite of the severity of the clinical features, the three patients showed a dramatic improvement after the surgical removal of the symptomatic tumors. The use of magnetic resonance is encouraged, owing to its high resolution and safety, for the assessment of incidence, character and localization of tumors in neurofibromatosis and to establish a good clinico-lesional correlation before surgery. This technique may help to a better understanding of the spectrum of abnormalities in each type of neurofibromatosis, thus facilitating the evaluation of this complex condition.
