Non-motor symptoms in patients with hereditary spastic paraplegia caused by SPG4 mutations K. R. Servelhere a , I. Faber a , J. A. M. Saute b , M. Moscovich c , A. D’Abreu a , L. B. Jardim b , H. A. G. Teive c , I. Lopes-Cendes d and M. C. Franca Jr a a Department of Neurology, University of Campinas – UNICAMP, Campinas, SP; b Medical Genetics Service, Federal University of Rio Grande do Sul – UFRGS, Porto Alegre, RS; c Neurology Service, Federal University of Paran a – UFPR, Curitiba, PR; and d Department of Medical Genetics, University of Campinas – UNICAMP, Campinas, SP, Brazil Keywords: depression, fatigue, non- motor symptoms, pain, spastic paraplegia, SPG4 Received 13 April 2015 Accepted 3 August 2015 European Journal of Neurology 2016, 23: 408–411 doi:10.1111/ene.12839 Background and purpose: Non-motor manifestations are frequently overlooked in degenerative disorders and little is known about their fre- quency and clinical relevance in SPG4 hereditary spastic paraplegia (SPG4- HSP). Methods: Thirty patients with SPG4-HSP and 30 healthy controls answered the Modified Fatigue Impact Scale, Epworth Sleepiness Scale, Brief Pain Inventory and Beck Depression Inventory. Student’s t test was used to compare groups and linear regression was used to assess correlations. Results: Patients had higher fatigue scores than controls (31.0  16.5 vs. 14.5  16.0, P = 0.002) as well as pain (3.4  2.7 vs. 1.0  1.6, P = 0.001) and depression (12.7  8.9 vs. 4.4  3.8, P < 0.001, respectively). Fatigue was associated with depression and possibly with disease severity (P = 0.008 and 0.07, respectively). Conclusions: Fatigue, pain and depression are frequent and often severe man- ifestations in patients with SPG4-HSP. Introduction Progressive spasticity and weakness of the lower limbs are the core clinical features of hereditary spastic paraplegia (HSP) [1,2]. Mutations in the SPG4 gene are the most frequent cause of autosomal dominant HSP (SPG4-HSP), accounting for 40%–50% of all cases [3,4]. Non-motor manifestations have been increasingly recognized in neurodegenerative disorders and may even overshadow motor handicap, but little is known about their impact in HSP [5–7]. Therefore, a study was designed to investigate the frequency and severity of pain, fatigue, depression and daytime sleepiness in a representative cohort of patients with SPG4-HSP [8]. Methods Subject selection Thirty adult patients with molecular confirmation of SPG4-HSP from three Brazilian centers [University of Campinas (UNICAMP), Federal University of Rio Grande do Sul (UFRGS) and Federal University of Paran a (UFPR)] and 30 age- and sex-matched healthy controls were evaluated between June 2013 and June 2014. Patients with concomitant neurological disor- ders and those younger than 15 years were excluded. This research protocol was approved by each insti- tution’s research ethics committee and a written informed consent was obtained from all patients. Clinical assessment Disease severity was quantified through the Spastic Paraplegia Rating Scale (SPRS). Patients and controls answered Brazilian Portuguese validated versions of Correspondence: M. C. Franca Jr, Department of Neurology, University of Campinas – Rua Tess alia Vieira de Camargo, 126 Campinas, SP-13083-887, Brazil (tel.: +551935219217; fax: +551935217933; e-mail: mcfrancajr@uol.com.br). © 2016 EAN 408 SHORTCOMMUNICATION EUROPEANJOURNALOFNEUROLOGY