DMD causes progressive lethal respiratory muscle weakness and the long-term effects of cortico-steroids on respiratory function is still under debate. We aim to investigate the effect of steroid therapy on a longitudinal study in our cohort of DMD patients. Since 2006, we have been monitoring the respiratory function in 95 DMD patients (age range: 6-24 years) who were evaluated once per year until the age of 10-11 years or until wheelchair bounding and then twice per year after wheelchair bounding or first signs of respiratory or cardiac impairment, making a total of 429 evaluations. During every visit, forced vital capacity, nocturnal arterial oxygen saturation and the supine abdominal percentage contribution to resting tidal volume (an index of the action of the diaphragm 1 ) were respectively measured with spirometry, pulse oximetry and opto-electronic plethysmography. 46 patients underwent continuous therapy with steroid for at least 2 years while 49 never assumed steroid or they did it for l 2 years and used as controls. No differences (p=0.12) were found in forced vital capacity, nocturnal saturation and action of the diaphragm between the 231 evaluations of the steroid group and the 198 evaluations of the controls (figure). The steroid therapy seems not to have ameliorative effects on the respiratory function decline in DMD patients. 1 Lo Mauro et al, Eur Respir J. 2010 May;35(5):1118-25

Non progressive cognitive impairment and increased rates psychosocial disorders, ADHD and Autism are reported in DMD patients. Through structured and validated questionnaire (Wechsler scales or Griffiths developmental scale, CBCL, Youth Self Report, Strengths and Difficulties Questionnaire, ADOS and DAWBA) we explored the possible role of cognitive impairment on the neuropsychiatric comorbidity in 32 boys with DMD (4–18 years). Our preliminary analysis shows a mean Full Intelligence Quotient of the whole group of 83.90 ± 16.68, lower in the patients with deletions in the distal portion of the gene (78.28 ± 16.72) than in the ones with proximal deletions (88.52 ± 15.62), with a very high frequency of Autism (about 20%) particularly in children with lower IQ level, and a high frequency of internalizing problems at CBCL, in boys with FIQ within the normal range, suggesting a role of cognitive capabilities in DMD children psychopathology. Non progressive cognitive impairment and increased rates psychosocial disorders, ADHD and Autism are reported in DMD patients. Through structured and validated questionnaire (Wechsler scales or Griffiths developmental scale, CBCL, Youth Self Report, Strengths and Difficulties Questionnaire, ADOS and DAWBA) we explored the possible role of cognitive impairment on the neuropsychiatric comorbidity in 32 boys with DMD (4–18 years). Our preliminary analysis shows a mean Full Intelligence Quotient of the whole group of 83.90 ± 16.68, lower in the patients with deletions in the distal portion of the gene (78.28 ± 16.72) than in the ones with proximal deletions (88.52 ± 15.62), with a very high frequency of Autism (about 20%) particularly in children with lower IQ level, and a high frequency of internalizing problems at CBCL, in boys with FIQ within the normal range, suggesting a role of cognitive capabilities in DMD children psychopathology.

We have been monitoring the respiratory function in 95 DMD patients (aged between 6 and 24 years) who were evaluated once or twice a year in relation to age and clinical conditions, making a total of 429 evaluations. During every evaluation, forced vital capacity, nocturnal oxygen saturation and the abdominal percentage contribution to tidal volume (an index of the action of the diaphragm) were respectively measured with spirometry, pulse oximetry and opto-electronic plethysmography. 46 patients underwent therapy with steroid while the remaining 49 never assumed steroid. No differences (p = 0.122) were found in forced vital capacity, nocturnal saturation and the action of the diaphragm between the 231 evaluations of the steroid group and the 198 evaluations of the sham group. Steroid therapy seems not to have any effects on the respiratory function decline in DMD patients. We have been monitoring the respiratory function in 95 DMD patients (aged between 6 and 24 years) who were evaluated once or twice a year in relation to age and clinical conditions, making a total of 429 evaluations. During every evaluation, forced vital capacity, nocturnal oxygen saturation and the abdominal percentage contribution to tidal volume (an index of the action of the diaphragm) were respectively measured with spirometry, pulse oximetry and opto-electronic plethysmography. 46 patients underwent therapy with steroid while the remaining 49 never assumed steroid. No differences (p = 0.122) were found in forced vital capacity, nocturnal saturation and the action of the diaphragm between the 231 evaluations of the steroid group and the 198 evaluations of the sham group. Steroid therapy seems not to have any effects on the respiratory function decline in DMD patients.

In the respiratory management of DMD patients it is still under debate what parameter should indicate the correct timing for institution of nocturnal non-invasive ventilation (NIV), in addition to forced vital capacity, which is generally considered as a prognostic marker of disease progression. The aim of this study was to determine if volume variations of rib cage and abdominal compartments measured by Opto-Electronic Plethysmography can be helpful to distinguish between those patients who are in the early stages of nocturnal oxygen desaturation development and those who do not yet. Pulmonary function, abdominal contribution to tidal volume and to inspiratory capacity (%Abd IC) and a set of breathing pattern indexes were assessed in 40 DMD patients older than 14 years and not yet under nocturnal NIV. ROC analysis revealed that among all the considered parameters, %Abd IC in supine position was the best discriminator between DeSat (at least 10% of the night time with SpO(2) < 95%) and NonDeSat patients, providing an area under the curve with 95%CI equal to 0.752. In conclusion, in adolescents and adults DMD patients who present either no sign or only mild nocturnal oxygen desaturation, a reduced abdominal contribution to inspiratory capacity is a marker of the onset of diaphragm weakness and should be considered to identify the correct timing for the institution of nocturnal NIV.

Ankle inversion injury is common in military populations but associated biomechanical risk factors are largely unknown. This prospective study examined the association between pressure and kinematic variables, and ankle inversion injury risk in Royal Marine (RM) recruits. It was hypothesised that a more medially concentrated pressure at the heel-off phase of stance, greater impulse and peak pressure at the first metatarsal head, greater peak rearfoot eversion angle and greater eversion excursion would be associated with ankle inversion injury.Data from 145 male, injury-free RM recruits were recorded in week-2 of a 32-week military training programme. Each recruit completed five running trials at 3.6 m s−1, along a 2 m pressure plate. Kinematic data were simultaneously recorded. Injuries sustained during the training programme were prospectively recorded.Data from eleven recruits who had suffered an ankle inversion injury during RM training were compared with 20 uninjured controls. The injury group displayed a higher (P < 0.05) peak first metatarsal pressure, peak metatarsal impulse and more medially concentrated pressure at heel-off than control recruits. There were no differences in kinematic variables between groups. The injury group had a lower body mass than controls (P < 0.05).The findings from this study support existing literature, providing evidence that high medial concentration of vertical forces when running are associated with increased ankle inversion injury risk. This may be due to the lateral ankle ligaments being less accustomed to loading, resulting in relatively weak lateral ligaments, or ligaments less able to deal with fatigue than those of the control group.

European Journal of NeurologyVolume 19, Issue 11 p. e127-e129 Letter to the Editor Atypical adult onset complicated spastic paraparesis with thin corpus callosum in two patients carrying a novel FA2H mutation A. Tonelli, A. Tonelli Laboratory of Molecular Biology, E. Medea Scientific Institute, Bosisio Parini, Lecco, ItalySearch for more papers by this authorM. G. D'Angelo, M. G. D'Angelo Neuromuscular Unit, Department of Neurorehabilitation, E. Medea Scientific Institute, Bosisio Parini, Lecco, ItalySearch for more papers by this authorF. Arrigoni, F. Arrigoni Neuroimaging Unit, E. Medea Scientific Institute, Bosisio Parini, Lecco, ItalySearch for more papers by this authorE. Brighina, E. Brighina Neuromuscular Unit, Department of Neurorehabilitation, E. Medea Scientific Institute, Bosisio Parini, Lecco, ItalySearch for more papers by this authorA. Arnoldi, A. Arnoldi Laboratory of Molecular Biology, E. Medea Scientific Institute, Bosisio Parini, Lecco, ItalySearch for more papers by this authorA. Citterio, A. Citterio Laboratory of Molecular Biology, E. Medea Scientific Institute, Bosisio Parini, Lecco, ItalySearch for more papers by this authorN. Bresolin, N. Bresolin Laboratory of Molecular Biology, E. Medea Scientific Institute, Bosisio Parini, Lecco, Italy Dino Ferrari Center, IRCCS Ca' Granda Foundation Ospedale Maggiore Policlinico, Department of Neurological Sciences, University of Milan, Milan, ItalySearch for more papers by this authorM. T. Bassi, Corresponding Author M. T. Bassi Laboratory of Molecular Biology, E. Medea Scientific Institute, Bosisio Parini, Lecco, ItalyCorrespondence: M. T. Bassi, Laboratory of Molecular Biology, E. Medea Scientific Institute, Via d. L. Monza 20, 23842 Bosisio Parini, Lecco, Italy (tel.: 0039 031877111; fax: 0039 031877499; e-mail: [email protected]).Search for more papers by this author A. Tonelli, A. Tonelli Laboratory of Molecular Biology, E. Medea Scientific Institute, Bosisio Parini, Lecco, ItalySearch for more papers by this authorM. G. D'Angelo, M. G. D'Angelo Neuromuscular Unit, Department of Neurorehabilitation, E. Medea Scientific Institute, Bosisio Parini, Lecco, ItalySearch for more papers by this authorF. Arrigoni, F. Arrigoni Neuroimaging Unit, E. Medea Scientific Institute, Bosisio Parini, Lecco, ItalySearch for more papers by this authorE. Brighina, E. Brighina Neuromuscular Unit, Department of Neurorehabilitation, E. Medea Scientific Institute, Bosisio Parini, Lecco, ItalySearch for more papers by this authorA. Arnoldi, A. Arnoldi Laboratory of Molecular Biology, E. Medea Scientific Institute, Bosisio Parini, Lecco, ItalySearch for more papers by this authorA. Citterio, A. Citterio Laboratory of Molecular Biology, E. Medea Scientific Institute, Bosisio Parini, Lecco, ItalySearch for more papers by this authorN. Bresolin, N. Bresolin Laboratory of Molecular Biology, E. Medea Scientific Institute, Bosisio Parini, Lecco, Italy Dino Ferrari Center, IRCCS Ca' Granda Foundation Ospedale Maggiore Policlinico, Department of Neurological Sciences, University of Milan, Milan, ItalySearch for more papers by this authorM. T. Bassi, Corresponding Author M. T. Bassi Laboratory of Molecular Biology, E. Medea Scientific Institute, Bosisio Parini, Lecco, ItalyCorrespondence: M. T. Bassi, Laboratory of Molecular Biology, E. Medea Scientific Institute, Via d. L. Monza 20, 23842 Bosisio Parini, Lecco, Italy (tel.: 0039 031877111; fax: 0039 031877499; e-mail: [email protected]).Search for more papers by this author First published: 04 December 2012 https://doi.org/10.1111/j.1468-1331.2012.03838.xCitations: 19Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Supporting Information Filename Description ene3838-sup-0001-DataS1.docWord document, 94 KB Data S1. Methods. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. References 1Norton WT, Cammer W. Isolation and characterization of myelin. In: P Morell, ed. Myelin. New York: Plenum Press, 1984: 147–195. 2Edvardson S, Hama H, Shaag A, et al. Mutations in the fatty acid 2-hydroxylase gene are associated with leukodystrophy with spastic paraparesis and dystonia. Am J Hum Genet 2008; 83: 643–648. 3Dick KJ, Eckhardt M, Paisán-Ruiz C, et al. Mutation of FA2H underlies a complicated form of hereditary spastic paraplegia (SPG35). Hum Mutat 2010; 31: E1251–E1260. 4Kruer MC, Paisán-Ruiz C, Boddaert N, et al. Defective FA2H leads to a novel form of neurodegeneration with brain iron accumulation (NBIA). Ann Neurol 2010; 68: 611–618. 5Garone C, Pippucci T, Cordelli DM, et al. FA2H-related disorders: a novel c.270+3A>T splice-site mutation leads to a complex neurodegenerative phenotype. Dev Med Child Neurol 2011; 53: 958–961. 6Pierson TM, Simeonov DR, Sincan M, et al. Exome sequencing and SNP analysis detect novel compound heterozygosity in fatty acid hydroxylase-associated neurodegeneration. Eur J Hum Genet 2012; 20: 476–479. 7Alderson NL, Rembiesa BM, Walla MD, et al. The human FA2H gene encodes a fatty acid 2-hydroxylase. J Biol Chem 2004; 279: 48562–48568. Citing Literature Volume19, Issue11November 2012Pages e127-e129 ReferencesRelatedInformation

In patients with spastic hemiparesis, centre of foot pressure (CoP) is shifted toward the unaffected limb during quiet stance. We hypothesised that abnormal gait features would correlate with the degree of asymmetry during stance. In 15 patients and 17 normals we recorded CoP and body sway by a force platform and measured spatial–temporal variables of gait with pedobarography. In patients CoP was shifted toward the unaffected limb and sway was larger than in normals. CoP position was associated with the decrease in strength of the affected lower-limb muscles. Spatio-temporal variables of gait were also affected by the disease. Cadence and velocity were decreased, duration of single support on the unaffected limb and of double support were increased with respect to normals. The degree of impairment of gait variables correlated with CoP. We found a negative relationship between velocity or cadence and CoP, and a positive relationship between duration of single support and CoP in the unaffected but not in the affected limb. Duration of double support correlated positively with CoP. CoP asymmetry during both standing and walking suggests that postural and gait problems share some common neural origin in hemiparetic patients. This asymmetry affects gait performance by increasing the time and effort needed to shift body weight toward the affected limb. The degree of postural asymmetry measured by stabilometry is associated with the level of impairment of gait variables.

CXCL10 (interferon-gamma-inducible protein-10) levels are increased in cerebrospinal fluid of multiple sclerosis (MS) patients with symptomatic attacks of inflammatory demyelination, supporting a role for this molecule in MS pathogenesis. Two hundred and twenty-six patients with MS and 235 controls were genotyped for G --> C and T --> C single nucleotide polymorphisms (SNPs) in exon 4 of CXCL10 gene. Haplotypes were tested for association and correlated with clinical variables. The two SNPs studied were in complete linkage disequilibrium. None of the determined haplotypes was associated with MS. However, carriers of the GGTT haplotype (defined as wild type, according to the sequence in National Centre for Biotechnology Information (NCBI) database) had a significantly lower progression index than non-carriers (P = 0.016). Furthermore, amongst patients who had an initial relapsing remitting (RR) course of the disease, the time between onset and second episode was significantly longer in GGTT carriers (P = 0.021). Considering secondary progressive (SP)-MS patients, the time between the initial RR form and the subsequent worsening to SP was longer in this group (P = 0.08). Therefore, the GGTT haplotype of the CXCL10 gene is not a susceptibility factor for the development of MS, but is probably to influence the course of MS, possibly contributing to slow down the progression of the disease.