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Disease Resources

Ataxias

Guidelines & consensus papers:
  • EFNS/ENS Consensus on the diagnosis and management of chronic ataxias in adulthood. van de Warrenburg BP, van Gaalen J, Boesch S, Burgunder JM, Dürr A, Giunti P, Klockgether T, Mariotti C, Pandolfo M, Riess O. Eur J Neurol. 2014 Apr;21(4):552-62. doi: 10.1111/ene.12341. Epub 2014 Jan 13.
  • Consensus clinical management guidelines for Friedreich ataxia. Louise A Corben, David Lynch, Massimo Pandolfo, Jörg B Schulz, Martin B Delatycki Orphanet Journal of Rare Diseases 2014, 9:184  doi:10.1186/s13023-014-0184-7
  • Consensus paper: management of degenerative cerebellar disorders, W. Ilg, A. J. Bastian, S. Boesch, et al., Cerebellum, vol. 13, no. 2, pp. 248–268, 2014
  • Neuroimaging
  • Clinical Guidelines Ataxia UK
  • Needs:
    • Clinical guidelines for diagnosis and management of childhood and adulthood ataxias
    • Evidence-based guidelines for physiotherapy and other neurorehabilitative treatments
    • Clinical guidelines for management of speech, communication and swallowing
Evidence:
  • Physiotherapy: W. Ilg, M. Synofzik, D. Brötz, S. Burkard, M. A. Giese, and L. Schöls, “Intensive coordinative training improves motor performance in degenerative cerebellar disease,” Neurology, vol. 73, no. 22, pp. 1823–1830, 2009; W. Ilg, D. Brötz, S. Burkard, M. A. Giese, L. Schöls, and M. Synofzik, “Long-term effects of coordinative training in degenerative cerebellar disease,” Movement Disorders, vol. 25, no. 13, pp. 2239–2246, 2010. Synofzik M, Ilg W (2014) Motor Training in Degenerative Spinocerebellar Disease: Ataxia-Specific Improvements by Intensive Physiotherapy and Exergames. BioMed Research International 2014:Article ID 583507
  • Rehabilitation: Gait ataxia-specific cerebellar influences and their rehabilitation. W. Ilg and D. Timmann, Movement Disorders, vol. 28, no. 11, pp. 1566–1575, 2013.     Miyai I, Ito M, Hattori N et al. (2012) Cerebellar ataxia rehabilitation trial in degenerative cerebellar diseases. Neurorehabil Neural Repair 26:515-522
  • Speech and communication: Treatment for speech disorder in Friedreich ataxia and other hereditary ataxia syndromes. Vogel AP, Folker J, Poole ML  Cochrane Database Syst Rev. 2014 Oct 28;10:CD008953. doi: 10.1002/14651858.CD008953.pub2.
Registries:
Scales:
  • Scale for the Assessment and Rating of Ataxia (SARA): SARA is a clinical scale that is based on a semiquantitative assessment of cerebellar ataxia on an impairment level. SARA has 8 items that are related to gait, stance, sitting, speech, finger-chase test, nose-finger test, fast alternating movements and heel-shin test. Although the cerebellum is directly involved in the coordination of eye movements, oculomotor functions are not considered, as the validation trials indicated that they are determined by other factors than appendicular and midline ataxia. SARA underwent a rigorous validation procedure involving three large multi-center trials in SCA and non-SCA ataxia patients, as well as controls.
    • Schmitz-Hübsch T, Tezenas du Montcel S, Baliko L, Berciano J, Boesch S et al. Scale for the assessment and rating of ataxia: development of a new clinical scale. Neurology 2006;66:1717-1720.
    • Schmitz-Hübsch T, Fimmers R, Rakowicz M, Rola R, Zdzienicka E, Fancellu R et al. Responsiveness of different rating instruments in spinocerebellar ataxia patients. Neurology 2010;74:678-84
    • Weyer A, Abele M, Schmitz-Hübsch T, Schoch B, Frings M et al. Reliability and validity of the Scale for the Assessment and Rating of Ataxia: A Study in 64 ataxia patients. Mov Disord 2007;22:1633-1637.
  • Download: SARA.pdf
  • Composite Cerebellar Functional Severity Score (CCFS):
    CCFS consists of two tests: Nine-hole pegboard and click test
    Nine-hole pegboard test
    The patient is seated and holds nine dowels (5mm in diameter and 38mm long) in one hand and places them randomly, one by one, with the other hand in a board with nine holes. Timing begins when the first peg is placed in a hole and ends when the last peg is placed. The examiner holds the board steady on the table during the test. The trial is performed with the dominant hand. If the patient drops a peg the examiner stops the timer and the patient starts the test again once from the beginning.
    Click test
    The patient is seated facing the examiner across a table on which is placed a device composed of two mechanical counters fixed on a wooden board 39 cm apart. The patient uses his index finger to press the buttons on the counters alternately 10 times. Timing begins when the first button is pressed and stops when the second counter reaches 10. The trial is performed once with the dominant hand.
    Literature
    • Tezenas du Montcel S, Charles P, Ribai P, Goizet C, Le Bayon A et al. Composite cerebellar functional severity score: validation of a quantitative score of cerebellar impairment. Brain 2008;131:1352-1361.
  • Download as PDF-Document: CCFS
  • Inventory of Non-Ataxia Signs (INAS)
    INAS provides structured information on non-ataxia signs in ataxia patients. INAS consists of 30 items, each of which is related to one of the following 16 signs or syndromes: areflexia, hyperreflexia, extensor plantar response, spasticity, paresis, amyotrophy, fasciculations, myoclonus, rigidity, chorea, dystonia, resting tremor, sensory symptoms, brainstem oculomotor signs (horizontal and vertical ophthalmoparesis, slowing of saccades), urinary dysfunction and cognitive impairment.
    For a semiquantitative assessement of non-ataxia signs, the number of non-ataxia signs is counted yielding the INAS count, a dimensionless value with a range from 0 to 16. To determine the INAS count, only the presence or absence of one of the 16 signs is considered. A sign is recorded as present if at least one item related to this sign is positive. Reliability of INAS ratings was tested in two large multi-center trials that served to validate SARA. For most INAS items, it was found to be acceptable.
    • Schmitz-Hübsch T, Coudert M, Bauer P, Giunti P, Globas C et al. Spinocerebellar ataxia type 1, 2, 3 and 6: Disease severity and non-ataxia symptoms. Neurology 2008;71:982-989.
    • Schmitz-Hübsch T, Fimmers R, Rakowicz M, Rola R, Zdzienicka E, Fancellu
      R et al. Responsiveness of different rating instruments in
      spinocerebellar ataxia patients. Neurology 2010;74:678-84
    • Jacobi H, Rakowicz M, Rola R, Fancellu R, Mariotti C, Charles P, Dürr A, Küper M, Timmann D, Linnemann C, Schöls L, Kaut O, Schaub C, Filla A, Baliko L, Melegh B, Kang JS, Giunti P, van de Warrenburg BP, Fimmers R, Klockgether T. Inventory of Non-Ataxia Signs (INAS): Validation of a New Clinical Assessment Instrument. Cerebellum. 2013 Jun;12(3):418-28
  • Download as PDF-Document: Inventory-of-Non-Ataxia-Signs
  • Spinocerebellar ataxia Functional Index (SCAFI):
    Quantitative performance measures or timed tests are used to supplement the results of clinical rating scales. Presumed advantages include high interrater and retest reliabilities. The SCAFI is composed of a timed 8m walk at maximum speed (8MW), the 9-hole peg test (9HPT), and the PATA rate, a measure of speech performance. SCAFI was validated in a large multi-center cohort of SCA patients.
    • Schmitz-Hübsch T, Giunti P, Globas C, Baliko L, Saccà F et al. SCA Functional Index - usefulness of a compound performance measure in spinocerebellar ataxia patients. Neurology 2008;71:486-492.
    • Schmitz-Hübsch T, Fimmers R, Rakowicz M, Rola R, Zdzienicka E, Fancellu
      R et al. Responsiveness of different rating instruments in
      spinocerebellar ataxia patients. Neurology 2010;74:678-84
  • Download as PDF-Document: SCAFI
  • Spinocerebellar ataxia Functional Index (FARS):
    FARS includes neurological signs that specifically reflect neural substrates affected in FRDA. Based on a neurological examination bulbar, upper limb, lower limb, peripheral nerve, and upright stability/gait functions are assessed. Further, a functional staging and activities of daily living (ADL) assessment are incorporated. The scales are supplemented by quantitative performance measures including 8m walk at maximum speed (8MW), the 9-hole peg test (9HPT), PATA rate and low-contrast letter acuity.
    • Subramony SH, May W, Lynch D, Gomez C, Fischbeck K et al. Measuring Friedreich ataxia: Interrater reliability of a neurologic rating scale. Neurology 2005;64:1261-1262.
    • Lynch DR, Farmer JM, Tsou AY, Perlman S, Subramony SH et al. Measuring Friedreich ataxia: complementary features of examination and performance measures. Neurology 2006; 66:1711-1716.
  • Download as PDF-Document: FARS
Networks and study groups:
Advocacy and support groups

Chorea

RESOURCES

Guidelines, consensus papers

Leitlinie „Chorea“ der Dt. Ges. f. Neurologie (DGN) in Zusammenarbeit mit der Dt. Ges. f. Psychiatrie, Psychotherapie und Nervenheilkunde
(DGPPN) und der Ges. f. Humangenetik (GfH)
http://www.awmf.org/uploads/tx_szleitlinien/030-028l_S1_Chorea_2011-05.pdf

Protocole National de Diagnostic et de Soins (PNDS) Maladie de Huntington
Centre de Référence National sur la maladie de Huntington Août 2015
http://www.has-sante.fr/portail/upload/docs/application/pdf/2015-08/pnds_-_maladie_de_huntington.pdf

Physiotherapy: Physiotherapy clinical guidelines for Huntington’s disease. Lori Quinn & Monica Busse*; On behalf of the European Huntington’s Disease Network Physiotherapy Working Group Neurodegenerative Disease Management Vol. 2, No. 1, Pages 21-31 , DOI 10.2217/nmt.11.86 http://www.futuremedicine.com/doi/full/10.2217/nmt.11.86

http://www.euro-hd.net
http://www.nhs.uk/conditions/huntingtons-disease/Pages/Introduction.aspx

Guidelines on diagnosis and management are in preparation by the Movement Disorders Society in collaboration with EAN and by the EHDN.

Needs:

According to patients organization (the European Huntington Association and newly constituted local organizations), there is a clear need of improvement in management, specifically of Huntington’s disease in Eastern European Countries.

Evidence

Burgunder, J.-M. (2013). Recent advances in the management of choreas.Therapeutic Advances in Neurological Disorders, 6(2), 117–127. doi:10.1177/1756285612471700

Treatment approach for HD http://bestpractice.bmj.com/best-practice/monograph/513/treatment/step-by-step.html

Registrie
  • REGISTRY –
    REGISTRY is a multi-centre, multi-national, European (with some associate partners wordlkwide) observational study of Huntington’s disease sponsored by CHDI, a non-profit organisation that supports a variety of research projects seeking to find treatments for HD.
    The major aims of Registry include
    • Obtain natural history data on a wide spectrum of individuals affected by HD
    • Relate clinical characteristics with genetic factors (‘genetic modifiers’), data derived from the study of body fluids (blood and urine, also called ‘wet biomarkers’) and imaging data (‘dry biomarkers’)
    • Expedite identification and recruitment of participants for clinical trials
    • Plan for future research studies (observational and interventional trials aimed at better symptom control, and postponing the onset or slowing the progression of HD)
    • Develop novel measures to track and/or predict disease onset and progression, as well as improve the existing tools.
  • ENROLL-HD –
    Enroll-HD is now replacing Registry in a gobal setting, including centres in North and South America Oceania and with planned extension in China.
    The aims are
  1. to better understand Huntington’s disease as it happens in people , to give us insights into developing new drugs
  2. to improve the design of clinical trials to give us clear answers more quickly. We want better, smarter, faster clinical trials so that we can move as quickly as possible to find the treatments that work
  3. to improve clinical care for HD patients by identifying the best clinical practices across all Enroll-HD sites around the world and then working to ensure that all families get that standard of care
Scales

A comprehensive set of scales has been established for Huntington’s disease, they are often used for choreas of other origins. They include the dimensions of motor, cognitive and behavioural signs and symptoms. Training and Online Certification is available https://www.euro-hd.net/html/certification, they are now further developed in the context of the Enroll-HD platform.

Networks and study groups

European Huntington’s Disease Network (EHDN)

Twitter @EHDN_GRANTM

Advocacy and support groups

European Huntington’s Association
Huntington’s disease associations are found in a number of European countries.

Dystonia

Guidelines, consensus papers
  • Albanese A, Bhatia K, Bressman SB, Delong MR, Fahn S, Fung VS, Hallett M, Jankovic J, Jinnah HA, Klein C, Lang AE, Mink JW, Teller JK. Phenomenology and classification of dystonia: a consensus update. Mov Disord. 2013 Jun 15;28(7):863-73.
  • Fung VS, Jinnah HA, Bhatia K, Vidailhet M. Assessment of patients with isolated or combined dystonia: an update on dystonia syndromes. Mov Disord. 2013 Jun 15;28(7):889-98.
  • Albanese A, Asmus F, Bhatia KP, Elia AE, Elibol B, Filippini G, Gasser T, Krauss JK, Nardocci N, Newton A, Valls-Solé J. EFNS guidelines on diagnosis and treatment of primary dystonias. Eur J Neurol. 2011 Jan;18(1):5-18.
  • Bronte-Stewart H, Taira T, Valldeoriola F, Merello M, Marks WJ Jr, Albanese A, Bressman S, Moro E. Inclusion and exclusion criteria for DBS in dystonia. Mov Disord. 2011 Jun;26 Suppl 1:S5-16.
  • van Egmond ME, Kuiper A, Eggink H, Sinke RJ, Brouwer OF, Verschuuren-Bemelmans CC, Sival DA, Tijssen MA, de Koning TJ. Dystonia in children and adolescents: asystematic review and a new diagnostic algorithm. J Neurol Neurosurg Psychiatry. 2015 Jul;86(7):774-81.
Needs:
  • Clinical guidelines for management of childhood and adulthood dystonias
  • Multidisciplinary approach to dystonia syndromes
  • Evidence-based guidelines for physiotherapy and other neurorehabilitative treatments
  • Practical approach for botulinum toxin treatment
Registries

COST dystonia registry
Dystonia Coalition (USA based)

Scales

Albanese A(1), Sorbo FD, Comella C, Jinnah HA, Mink JW, Post B, Vidailhet M, Volkmann J, Warner TT, Leentjens AF, Martinez-Martin P, Stebbins GT, Goetz CG, Schrag A. Dystonia rating scales: critique and recommendations. Mov Disord. 2013 Jun 15;28(7):874-83.

  • Blepharospasm Disability Index for blefarospasm
  • Cervical Dystonia Impact Scale & Toronto Western Spasmodic Torticollis Rating Scale for cervical dystonia
  • Craniocervical Dystonia Questionnaire for blepharospasm and cervical dystonia
  • Voice Handicap Index (VHI) and the Vocal Performance Questionnaire (VPQ) for laryngeal dystonia
  • Fahn-Marsden Dystonia Rating Scale for rating generalized dystonia.
Networks and study groups

European network for the study of dystonia syndromes

Dystonia Europe

Dystonia Coalition (USA based)

Advocacy and support groups

Dystonia Europe

FTD – Frontotemporal Dementia

Guidelines, consensus papers
  • Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Rascovsky K, Hodges JR, Knopman D, Mendez MF, Kramer JH, Neuhaus J, van Swieten JC, Seelaar H, Dopper EG, Onyike CU, Hillis AE, Josephs KA, Boeve BF, Kertesz A, Seeley WW, Rankin KP, Johnson JK, Gorno-Tempini ML, Rosen H, Prioleau-Latham CE, Lee A, Kipps CM, Lillo P, Piguet O, Rohrer JD, Rossor MN, Warren JD, Fox NC, Galasko D, Salmon DP, Black SE, Mesulam M, Weintraub S, Dickerson BC, Diehl-Schmid J, Pasquier F, Deramecourt V, Lebert F, Pijnenburg Y, Chow TW, Manes F, Grafman J, Cappa SF, Freedman M, Grossman M, Miller BL. Brain. 2011 Sep;134(Pt 9):2456-77.
  • Classification of primary progressive aphasia and its variants. Gorno-Tempini ML, Hillis AE, Weintraub S, Kertesz A, Mendez M, Cappa SF, Ogar JM, Rohrer JD, Black S, Boeve BF, Manes F, Dronkers NF, Vandenberghe R, Rascovsky K, Patterson K, Miller BL, Knopman DS, Hodges JR, Mesulam MM, Grossman M. Neurology. 2011 Mar 15;76(11):1006-14.
Needs:
  • Evidence-based guidelines for diagnosis
  • Clinical guidelines for management of behavioural symptoms
Evidence
  • None
Registries
  • Currently none – North American registry being set up at present
Scales
Networks and study groups
Advocacy and support groups

HSP – Hereditary Spastic Paraplegia

Guidelines, consensus papers
  • Gasser T, Finsterer J, Baets J, Van Broeckhoven C, Di Donato S, Fontaine B, DeJonghe P, Lossos A, Lynch T, Mariotti C, Schöls L, Spinazzola A, Szolnoki Z, Tabrizi SJ, Tallaksen CM, Zeviani M, Burgunder JM, Harbo HF; EFNS. EFNSguidelines on the molecular diagnosis of ataxias and spastic paraplegias. Eur J Neurol. 2010 Feb;17(2):179-88.
  • Dressler D, Berweck S, Chatzikalfas A, Ebke M, Frank B, Hesse S, Huber M,Krauss JK, Mücke KH, Nolte A, Oelmann HD, Schönle PW, Schmutzler M, PickenbrockH, Van der Ven C, Veelken N, Vogel M, Vogt T, Saberi FA. Intrathecal Baclofen therapy in Germany: Proceedings of the IAB-Interdisciplinary Working Group for Movement Disorders Consensus Meeting. J Neural Transm (Vienna). 2015 Nov;122(11):1573-9. doi: 10.1007/s00702-015-1425-1. Epub 2015 Jul 16.
Needs:
  • Clinical guidelines for diagnosis and management of hereditary spastic paraparesis
  • Evidence-based guidelines for physiotherapy and other neurorehabilitative treatments
  • Clinical guidelines for management of urinary symptoms and pain
Evidence
    • Bertolucci F, Di Martino S, Orsucci D, Ienco EC, Siciliano G, Rossi B, Mancuso M, Chisari C. Robotic gait training improves motor skills and quality of life in hereditary spastic paraplegia. NeuroRehabilitation. 2015;36(1):93-9.
    • Seo HG, Oh BM, Kim K. Robot-assisted gait training in a patient with hereditary spastic paraplegia. PM R. 2015 Feb;7(2):210-3.
    • Geva-Dayan K, Domenievitz D, Zahalka R, Fattal-Valevski A. Botulinum toxin injections for pediatric patients with hereditary spastic paraparesis. J ChildNeurol. 2010 Aug;25(8):969-75.
    • Klimpe S, Schüle R, Kassubek J, Otto S, Kohl Z, Klebe S, Klopstock T, Ratzka S, Karle K, Schöls L. Disease severity affects quality of life of hereditary spastic paraplegia patients. Eur J Neurol. 2012 Jan;19(1):168-71.
Registries
Scales
  • Spastic Paraplegia Rating Scale (SPRS): SPRS is suitable for all subtypes of SP including familial and sporadic forms as well as pure and complicated phenotypes. As SPRS uses standard neurologic examination procedures in most of its items, instructions for test performance and scoring could be kept short for most items without endangering interrater reliability. Completion of SPRS require less than 15 minutes and does not depend on any special equipment. The variety of signs and symptoms that accounts for clinical variability in complicated forms of SP is listed in an inventory. This inventory thus provides a standardized tool to document multisystem involvement of the disease. The inventory is adapted to a routine neurologic examination and avoids additional time-consuming tests.
    • Schüle R, Holland-Letz T, Klimpe S, Kassubek J, Klopstock T, Mall V, Otto S,Winner B, Schöls L. The Spastic Paraplegia Rating Scale (SPRS): a reliable and valid measure of disease severity. Neurology. 2006 Aug 8;67(3):430-4.
  • Spinocerebellar Degeneration Functional Score (SDFS), which rates the disability stages from 0 (asymptomatic) to 7 (bedridden)
    • Le Ber I, Moreira MC, Rivaud-Péchoux S, Chamayou C, Ochsner F, Kuntzer T, Tardieu M, Saïd G, Habert MO, Demarquay G, Tannier C, Beis JM, Brice A, Koenig M, Dürr A. Cerebellar ataxia with oculomotor apraxia type 1: clinical and genetic studies. Brain. 2003 Dec;126(Pt 12):2761-72. Epub 2003 Sep 23.
Networks and study groups
  • SPATAX
  • GeNeMove/DZNE
  • NeurOmics
  • BRAIN-TEAM network: National French Network for Rare Neurological diseases including 9 certified centres of reference, 25 specialized centers, 25 competent centres, >260 CNS diseases, 37 patient associations, and ~100,000 patients (website under development).
Advocacy and support groups

Leukodystrophies

Guidelines, consensus papers
  • Consensus statement on preventive and symptomatic care of leukodystrophy patients Van Haren K, Bonkowsky JL, Bernard G, Murphy JL, Pizzino A,Helman G, Suhr D, Waggoner J, Hobson D, Vanderver A, Patterson MC on behalf of the GLIA Consortium. Molecular Genetics and Metabolism 2015 114(4):516-26
  • Disease specific therapies in leukodystrophies and leukoencephalopathies. Helman G, Van Haren K, Bonkowsky JL, Bernard G, Pizzino A, Braverman N, Suhr D, Patterson MC, Fatemi SA, Leonardk J, van der Knaap MS, Back SA, Damiani S, Goldman SA, Takanohashi A, Petryniak M, Rowitch D, Messing A, Wrabetz L, Schiffmann R, Eichler F, Escolar ML, Vanderver A on behalf of the GLIA Consortium Molecular Genetics and Metabolism 114 (2015) 527–536
  • Case definition and classification of leukodystrophies and leukoencephalopathies Vanderver A, Prust M, Tonduti D, Mochel F, Hussey HM, Helman G, Garbern J, Eichler F, Labauge P, Aubourg P, Rodriguez D, Patterson MC, Van Hove JL, Schmidt J, Wolf NI, Boespflug-Tanguy O, Schiffmann R, van der Knaap MS; GLIA Consortium Molecular Genetics and Metabolism 114 (2015) 494–500
  • A clinical approach to the diagnosis of patients with leukodystrophies and genetic leukoencephelopathies. Parikh S, Bernard G, Leventer RJ, van der Knaap MS, van Hove J, Pizzino A, McNeill NH, Helman G, Simons C, Schmidt JL, Rizzo WB, Patterson MC, Taft RJ, Vanderver A; GLIA Consortium. Mol Genet Metab. 2015 Apr;114(4):501-15. Review
  • Leukodystrophien im Erwachsenenalter, Leitlinien in der Neurologie 80 Schöls L, Krägeloh-Mann I, Köhler W, Rolfs A
Needs:
  • Implementation of clinical guidelines for diagnosis and management of childhood and adulthood leukodystrophies
  • Evidence-based guidelines for physiotherapy and other neurorehabilitative treatments
  • Clinical guidelines for management of speech, communication and swallowing
Evidence
  • Stem cell transplantation: Krivit W. Allogeneic stem cell transplantation for the treatment of lysosomal and peroxisomal metabolic diseases. Springer Semin Immunopathol 2004; 26: 119–32.
  • Miller WP, Rothman SM, Nascene D, Kivisto T, DeFor TE, Ziegler RS, Eisengart J, Leiser K, Raymond G, Lund TC, Tolar J, Orchard PJ. Outcomes after allogeneic hematopoietic cell transplantation for childhood cerebral adrenoleukodystrophy: the largest single-institution cohort report. Blood. 2011;118:1971-8.
  • Krägeloh-Mann I, Groeschel S, Kehrer C, et al Juvenile metachromatic leukodystrophy 10 years post-transplant compared to a non-transplanted cohort. Bone Marrow Transplantation 48:369-75 (2013)
  • van Egmond ME, Pouwels PJW, Boelens J-J, et al. Improvement of white matter changes on neuroimaging modalities after stem cell transplant in metachromatic leukodystrophy. JAMA Neurol 2013; 70: 779–82.
  • Boucher AA, Miller W, Shanley R, et al. Long-term outcomes after allogeneic hematopoietic stem cell transplantation for metachromatic leukodystrophy: the largest single-institution cohort report. Orphanet J Rare Dis 2015; 10: 94
  • Gene therapy: Biffi A, Montini E, Lorioli L, et al. Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy. Science 2013; 341: 1233158.
  • Natural course: Groeschel S, í Dali Ch, Clas P, et al Cerebral gray and white matter changes and clinical course in metachromatic leukodystrophy. Neurology, 2012 Oct 16;79(16):1662-70
  • Tillema JM, Derks MGM, Pouwels PJW, et al Volumetric MRI data correlate to disease severity in metachromatic leukodystrophy Annals of Clinical and Translational Neurology 2015; 2(9): 932–940
  • Kehrer C, Blumenstock G, Gieselmann V, Krageloh-Mann I. The natural course of gross motor deterioration in Metachromatic Leukodystrophy. DevMedChild Neurol 2011; 53: 850–5.
  • Kehrer C, Groeschel S, Kustermann-Kuhn B, et al. Language and cognition in children with metachromatic leukodystrophy: onset and natural course in a nationwide cohort. Orphanet J Rare Dis 2014; 9: 18.
  • Rehabilitation: no specific evidence
  • Speech and communication:. no specific evidence
Registries
  • Metachromatic leukodystrophy
    • Leukonet
  • Leukodystophies
    • Leukotreat
Scales
  • Scale for the Assessment and Rating of gross motor deficits Kehrer C, Blumenstock G, Raabe C, Krägeloh-Mann I Development and reliability of a classification system for gross motor function in children with metachromatic leucodystrophy Dev Med Child Neurol Feb; 53(2):156-60 (2011)
  • In addition ataxia rating scales (see ataxias), no specific rating scales for spasticity in leukodystrophies
  • Scale for the Assessment and Rating leukodystrophy changes: Eichler F, Grodd W Grant E, Sessa M, Bizzi A, Bley A, Kohlschuetter A, Loes D, Krägeloh-Mann I Metachromatic Leukodystrophy: A Scoring System for Brain MR Observations AJNR 30:1893-97 (2009)
  • Loes DJ, Peters Ch, Krivit W Globoid Cell Leukodystrophy: Distinguishing Early-Onset from Late-Onset Disease Using a Brain MR Imaging Scoring Method AJNR 20:316–323
  • Loes DJ, Hite S, Moser H, Stillman AE, Shapiro E, Lockman L, Latchaw RE, Krivit W. Adrenoleukodystrophy: a scoring method for brain MR observations. AJNR Am J Neuroradiol. 1994 Oct;15(9):1761-6.
Networks and study groups
Advocacy and support groups

MSA – Multiple System Atrophy

Guidelines, consensus papers
  • Second consensus statement on the diagnosis of multiple system atrophy. Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ, Trojanowski JQ, Wood NW, Colosimo C, Dürr A, Fowler CJ, Kaufmann H, Klockgether T, Lees A, Poewe W, Quinn N, Revesz T, Robertson D, Sandroni P, Seppi K, Vidailhet M. Neurology. 2008 Aug 26;71(9):670-6. doi: 10.1212/01.wnl.0000324625.00404.15.
  • EFNS/MDS-ES/ENS [corrected] recommendations for the diagnosis of Parkinson's disease. Berardelli A, Wenning GK, Antonini A, Berg D, Bloem BR, Bonifati V, Brooks D, Burn DJ, Colosimo C, Fanciulli A, Ferreira J, Gasser T, Grandas F, Kanovsky P, Kostic V, Kulisevsky J, Oertel W, Poewe W, Reese JP, Relja M, Ruzicka E, Schrag A, Seppi K, Taba P, Vidailhet M. Eur J Neurol. 2013 Jan;20(1):16-34. doi: 10.1111/ene.12022.
  • Proposed neuroimaging criteria for the diagnosis of multiple system atrophy. Brooks DJ, Seppi K. Neuroimaging Working Group on MSA. Mov Disord. 2009 May 15;24(7):949-64. doi: 10.1002/mds.22413.
  • Proposed neuropathological criteria for the post mortem diagnosis of multiple system atrophy. Trojanowski JQ, Revesz T. Neuropathology Working Group on MSA. Neuropathol Appl Neurobiol. 2007 Dec;33(6):615-20.
Needs:
  • Clinical guidelines for diagnosis and management of multiple system atrophy
  • Clinical guidelines to diagnose early stage and pre-symptomatic patients .
  • To overcome key gaps in the knowledge of the natural history of MSA.
  • Development of consensus guidelines for the standard of care in MSA.
  • Further research on symptomatic and disease-modifying therapies.
  • Recommendations for physiotherapy and other neurorehabilitative treatments.
  • Clinical guidelines for management of speech, communication and swallowing
Registries
Scales
  • Unified MSA Rating Scale (UMSARS): UMSARS is a rating scale for MSA comprising the following components: Part I, historical, 12 items; Part II, motor examination, 14 items; Part III, autonomic examination; and Part IV, global disability scale. It has been validated for MSA patients and appears to be a reliable scale for semiquantitative clinical assessments. Wenning GK, Tison F, Seppi K, et al. Development and validation of the Unified Multiple System Atrophy Rating Scale (UMSARS). Mov Disord. 2004 Dec;19(12):1391-402.
  • MSA Health-Related Quality of Life scale (MSA-QoL): The MSA-Qol is a disease-specific scale capturing diverse aspects affecting the quality of life of MSA patients. Measuring health-related quality of life in MSA: the MSA-QoL. Schrag A, Selai C, Mathias C, et al. Mov Disord. 2007 Dec;22(16):2332-8.
  • Unified Parkinson's Disease Rating Scale (UPDRS)
  • Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS)
  • Medical Outcome Study Short Form (SF-36)
  • European Quality of Life Five Dimensions EQ-5D
  • Composite Autonomic Symptom Scale (COMPASS and COMPASS-31)
  • Orthostatic Hypotension Questionnaire (OHQ)
  • Scales for Outcomes in Parkinson's Disease-Autonomic questionnaire (SCOPA-AUT)
  • Scale for the Assessment and Rating of Ataxia (SARA)
  • Berg Balance Scale (BBS)
  • Beck Depression Inventory (BDI)
  • Mini-Mental state examination (MMSE)
Networks and study groups
Advocacy and support groups

NBIA – Neurodegeneration with Brain Iron Accumulation

RESOURCES
Guidelines, consensus papers
  • no targeted guidelines or consensus papers so far, but one guideline on “Best Practices in PKAN” is currently developed by Susan Hayflick and international collaborators
  • Review papers:
    • Hogarth P. Neurodegeneration with brain iron accumulation: diagnosis and management. J Mov Disord. 2015;8(1):1-13.
    • Hartig M, Prokisch H, Meitinger T, Klopstock T. Mitochondrial membrane protein-associated neurodegeneration (MPAN). Int Rev Neurobiol. 2013;110:73-84.
    • Kurian MA, Hayflick SJ. Pantothenate kinase-associated neurodegeneration (PKAN) and PLA2G6-associated neurodegeneration (PLAN): review of two major neurodegeneration with brain iron accumulation (NBIA) phenotypes. Int Rev Neurobiol. 2013;110:49-71.
    • Hartig MB, Prokisch H, Meitinger T, Klopstock T. Pantothenate kinase-associated neurodegeneration. Curr Drug Targets. 2012;13(9):1182-9.
    • Kruer MC, Boddaert N. Neurodegeneration with brain iron accumulation: a diagnostic algorithm. Semin Pediatr Neurol. 2012;19(2):67-74.
    • Schneider SA, Bhatia KP. Syndromes of neurodegeneration with brain iron accumulation. Semin Pediatr Neurol. 2012 Jun;19(2):57-66.
    • Kruer MC, Boddaert N, Schneider SA, Houlden H, Bhatia KP, Gregory A, Anderson JC, Rooney WD, Hogarth P, Hayflick SJ. Neuroimaging features of neurodegeneration with brain iron accumulation. AJNR Am J Neuroradiol. 2012;33(3):407-14.
Needs:
  • Clinical guidelines for the diagnostic pathway in NBIA
  • Evidence-based guidelines for the symptomatic management of NBIA, including the use of antidystonic pharmacotherapy, botulinum toxin and deep brain stimulation
  • Evidence-based guidelines for physiotherapy and other neurorehabilitative treatments
  • Clinical guidelines for management of speech, communication and swallowing
  • Evidence-based guidelines for the use of iron chelation therapy
Evidence
  • Symptomatic management: Delnooz CC, van de Warrenburg BP. Current and future medical treatment in primary dystonia. Ther Adv Neurol Disord. 2012;5(4):221-40.
  • Deep brain stimulation: Timmermann L, Pauls KA, Wieland K, Jech R, Kurlemann G, Sharma N, Gill SS, Haenggeli CA, Hayflick SJ, Hogarth P, Leenders KL, Limousin P, Malanga CJ, Moro E, Ostrem JL, Revilla FJ, Santens P, Schnitzler A, Tisch S, Valldeoriola F, Vesper J, Volkmann J, Woitalla D, Peker S. Dystonia in neurodegeneration with brain iron accumulation: outcome of bilateral pallidal stimulation. Brain. 2010;133(Pt 3):701-12.
  • Iron chelation: Cossu G, Abbruzzese G, Matta G, Murgia D, Melis M, Ricchi V, Galanello R, Barella S, Origa R, Balocco M, Pelosin E, Marchese R, Ruffinengo U, Forni GL. Efficacy and safety of deferiprone for the treatment of Pantothenate kinase-associated neurodegeneration (PKAN) and neurodegeneration with brain iron accumulation (NBIA): results from a four years follow-up. Parkinsonism Relat Disord. 2014;20(6):651-4.
Registries
  • the international TIRCON NBIA registry
Scales
  • Albanese A, Sorbo FD, Comella C, Jinnah HA, Mink JW, Post B, Vidailhet M, Volkmann J, Warner TT, Leentjens AF, Martinez-Martin P, Stebbins GT, Goetz CG, Schrag A. Dystonia rating scales: critique and recommendations. Mov Disord. 2013;28(7):874-83.
  • Fahn-Marsden Dystonia Rating Scale for rating generalized dystonia
  • Barry-Albright Dystonia (BAD) Scale
Networks and study groups
  • the TIRCON group (Treat Iron-Related Childhood-Onset Neurodegeneration)
Advocacy and support groups

PSP – Progressive Supranuclear Palsy

Guidelines, consensus papers
  • Revised diagnostic criteria for PSP, Movement Disorders Society-endorsed PSP Study group, International Consensus Meeting in Munich, March 2016.
Needs:
  • Clinical guidelines for diagnosis and management of prodromal PSP
  • Evidence-based guidelines for physiotherapy and other neurorehabilitative treatments
  • Clinical guidelines for management of speech, communication and swallowing
Registries
  • Germany
    • DescribePSP: a prospective cohort study of DZNE clinical centers
    • ProPSP: a prospective cohort study of German and Luxemburg academic hospitals
  • UK
Scales
  • PSP Rating Scale (PSP-RS): the PSP-RS is a disease-specific scale capturing the diverse clinical dimensions of PSP. It has been validated in several prospective mono- and multicentric studies. It is sensitive to measure change over time with a reproducible and stable progression rate. Golbe LI, Ohman-Strickland PA. A clinical rating scale for progressive supranuclear palsy. Brain 2007;130:1552–65
  • PSP Quality of Live (PSP-QoL): the PSP-QoL is a disease-specific scale capturing diverse aspects affecting the quality of life of PSP patients. It has not been used so far in a multi-centric setting. Schrag A, Selai C, Quinn N, et al. Measuring quality of life in PSP: the PSP-QoL. Neurology 2006;67:39–44
Networks and study groups
Advocacy and support groups