HLA-DRB1*15 association with multiple sclerosis is confirmed in a multigenerational Italian family.

Environmental and genetic factors seem to play a pathogenetic role in multiple sclerosis (MS). The genetic component is partly suggested by familial aggregation of cases; however, MS families with affected subjects over different generations have rarely been described. The aim of this study was to report clinical and genetic features of a multigenerational MS family and to perform a review of the literature on this topic. We describe a multigenerational Italian family with six individuals affected by MS, showing different clinical and neuroradiological findings. HLA-DRB1* typing revealed the presence of the DRB1*15:01 allele in all the MS cases and in 4/5 non-affected subjects. Reports on six multigenerational MS families have previously been published, giving similar results. The HLA-DRB1*15:01 allele was confirmed to be linked to MS disease in this family; moreover, its presence in non-affected subjects suggests the involvement of other susceptibility factors in the development and expression of the disease, in accordance with the complex disease model now attributed to MS.

[1]  C. Molina,et al.  Ischemic stroke outcome: A review of the influence of post-stroke complications within the different scenarios of stroke care. , 2016, European journal of internal medicine.

[2]  Katharina Stibrant Sunnerhagen,et al.  Early prediction of long-term upper limb spasticity after stroke , 2015, Neurology.

[3]  Sheng Li,et al.  New insights into the pathophysiology of post-stroke spasticity , 2015, Front. Hum. Neurosci..

[4]  N. Smania,et al.  Improving the quality of life of stroke survivors: what to do next? The Italian action for the implementation of a Poststroke Checklist. , 2015, European journal of physical and rehabilitation medicine.

[5]  High doses of onabotulinumtoxinA in post-stroke spasticity: a retrospective analysis , 2015, Journal of Neural Transmission.

[6]  J. Wissel,et al.  Post‐stroke Spasticity: Predictors of Early Development and Considerations for Therapeutic Intervention , 2015, PM & R : the journal of injury, function, and rehabilitation.

[7]  N. Smania,et al.  Accuracy of botulinum toxin type A injection into the forearm muscles of chronic stroke patients with spastic flexed wrist and clenched fist: manual needle placement evaluated using ultrasonography. , 2014, Journal of rehabilitation medicine.

[8]  Stefano Tamburin,et al.  Topical distribution of initial paresis of the limbs to predict clinically relevant spasticity after ischemic stroke: a retrospective cohort study. , 2014, European journal of physical and rehabilitation medicine.

[9]  G. Ebersbach,et al.  Early botulinum toxin treatment for spastic pes equinovarus – a randomized double‐blind placebo‐controlled study , 2014, European journal of neurology.

[10]  F. Molteni,et al.  Management of stroke patients submitted to botulinum toxin type A therapy: a Delphi survey of an Italian expert panel of specialist injectors. , 2014, European journal of physical and rehabilitation medicine.

[11]  Stefano Tamburin,et al.  Association between Severe Upper Limb Spasticity and Brain Lesion Location in Stroke Patients , 2014, BioMed research international.

[12]  N. Smania,et al.  Botulinum toxin injection into the forearm muscles for wrist and fingers spastic overactivity in adults with chronic stroke: a randomized controlled trial comparing three injection techniques , 2014, Clinical rehabilitation.

[13]  A. Bentivoglio,et al.  Use of botulinum toxin type A in the management of patients with neurological disorders: a national survey. , 2013, Functional neurology.

[14]  M. Walker,et al.  Development of a poststroke checklist to standardize follow-up care for stroke survivors. , 2013, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.

[15]  V. Shaygannejad,et al.  A Literature Review on the Efficacy and Safety of Botulinum Toxin: An Injection in Post-Stroke Spasticity , 2013, International journal of preventive medicine.

[16]  Michael Brainin,et al.  Toward an epidemiology of poststroke spasticity , 2013, Neurology.

[17]  Nicola Smania,et al.  Botulinum Toxin Type A Injection Into the Gastrocnemius Muscle for Spastic Equinus in Adults With Stroke: A Randomized Controlled Trial Comparing Manual Needle Placement, Electrical Stimulation and Ultrasonography-Guided Injection Techniques , 2012, American journal of physical medicine & rehabilitation.

[18]  Nicola Smania,et al.  Accuracy of botulinum toxin type A injection into the gastrocnemius muscle of adults with spastic equinus: manual needle placement and electrical stimulation guidance compared using ultrasonography. , 2012, Journal of rehabilitation medicine.

[19]  S. Hesse,et al.  An early botulinum toxin A treatment in subacute stroke patients may prevent a disabling finger flexor stiffness six months later: a randomized controlled trial , 2012, Clinical rehabilitation.

[20]  V. Mok,et al.  Botulinum Toxin Injection for Hypertonicity of the Upper Extremity Within 12 Weeks After Stroke , 2012, Neurorehabilitation and neural repair.

[21]  A. Ward,et al.  A literature review of the pathophysiology and onset of post‐stroke spasticity , 2012, European journal of neurology.

[22]  S. Carda,et al.  Casting, taping or stretching after botulinum toxin type A for spastic equinus foot: a single-blind randomized trial on adult stroke patients , 2011, Clinical rehabilitation.

[23]  C. Stinear,et al.  Prediction of recovery of motor function after stroke , 2010, The Lancet Neurology.

[24]  N. Smania,et al.  Rehabilitation procedures in the management of spasticity. , 2010, European journal of physical and rehabilitation medicine.

[25]  Thomas Bauermann,et al.  Occurence and Clinical Predictors of Spasticity After Ischemic Stroke , 2010, Stroke.

[26]  J. Gracies,et al.  Assessment: Botulinum neurotoxin for the treatment of spasticity (an evidence-based review): Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of NeurologySYMBOL , 2008, Neurology.

[27]  G. Molenaers,et al.  Safety and efficacy of botulinum toxin type A following long‐term use , 2006, European journal of neurology.

[28]  J. Jankovic,et al.  Safety of botulinum toxin type A: a systematic review and meta-analysis , 2004, Current medical research and opinion.

[29]  James W. Lance,et al.  The control of muscle tone, reflexes, and movement , 1980, Neurology.