296
Views
0
CrossRef citations to date
0
Altmetric
Review

The pharmacological management of the behavioral aspects of Parkinson’s disease: an update

, , , , , & ORCID Icon show all
Pages 1693-1701 | Received 28 May 2023, Accepted 20 Jul 2023, Published online: 26 Jul 2023

References

  • Barone P, Antonini A, Colosimo C, et al. The PRIAMO study: A multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson’s disease. Mov Disord. 2009;24(11):1641–1649.
  • Chaudhuri KR, Odin P, Antonini A, et al. Parkinson’s disease: the non-motor issues. Parkinsonism Relat Disord. 2011;17(10):717–723. doi: 10.1016/j.parkreldis.2011.02.018
  • Chaudhuri KR, Sauerbier A, Rojo JM, et al. The burden of non-motor symptoms in Parkinson’s disease using a self-completed non-motor questionnaire: a simple grading system. Parkinsonism Relat Disord. 2015;21(3):287–291. doi: 10.1016/j.parkreldis.2014.12.031
  • la Riva P D, Smith K, Xie SX, et al. Course of psychiatric symptoms and global cognition in early Parkinson disease. Neurology. 2014;83(12):1096–1103. doi: 10.1212/WNL.0000000000000801
  • Antonini A, Barone P, Marconi R, et al. The progression of non-motor symptoms in Parkinson’s disease and their contribution to motor disability and quality of life. J Neurol. 2012;259(12):2621–2631. doi: 10.1007/s00415-012-6557-8.
  • Aarsland D, Kurz MW. The epidemiology of dementia associated with Parkinson’s disease. Brain Pathol. 2010;20(3):633–639. doi: 10.1111/j.1750-3639.2009.00369.x
  • Biundo R, Weis L, Antonini A. Cognitive decline in Parkinson’s disease: the complex picture. NPJ Parkinsons Dis. 2016;2(1):16018. doi: 10.1038/npjparkd.2016.18
  • Weintraub D, Aarsland D, Biundo R, et al. Management of psychiatric and cognitive complications in Parkinson’s disease. BMJ. 2022;379:e068718.
  • NMSS Validation Group, Martinez-Martin P, Rodriguez-Blazquez C, Kurtis MM, et al. The impact of non-motor symptoms on health-related quality of life of patients with Parkinson’s disease. Mov Disord. 2011;26(3):399–406.
  • Brandão PRP, Munhoz RP, Grippe TC, et al. Cognitive impairment in Parkinson’s disease: A clinical and pathophysiological overview. J Neurol Sci. 2020;419:117177. doi: 10.1016/j.jns.2020.117177
  • Dunlop BW, Nemeroff CB. The role of dopamine in the pathophysiology of depression. Arch Gen Psychiatry. 2007;64(3):327–337. doi: 10.1001/archpsyc.64.3.327
  • Kapur S, Mann JJ. Role of the dopaminergic system in depression. Biol Psychiatry. 1992;32(1):1–17. doi: 10.1016/0006-3223(92)90137-O
  • Heinzel S, Berg D, Gasser T, et al. Update of the MDS research criteria for prodromal Parkinson’s disease. Mov Disord. 2019;34(10):1464–1470. doi: 10.1002/mds.27802
  • Marsh L. Depression and Parkinson’s disease: current knowledge. Curr Neurol Neurosci Rep. 2013;13(12):409. doi: 10.1007/s11910-013-0409-5
  • Macías-García P, Rashid-López R, Cruz-Gómez ÁJ, et al. Neuropsychiatric symptoms in clinically defined parkinson’s disease: an updated review of literature. Behav Neurol. 2022;2022:1–16. doi: 10.1155/2022/1213393
  • Weintraub D, Moberg PJ, Duda JE, et al. Recognition and treatment of depression in Parkinson’s disease. J Geriatr Psychiatry Neurol. 2003;16(3):178–183. doi: 10.1177/0891988703256053
  • Leentjens AF. Depression in Parkinson’s disease: conceptual issues and clinical challenges. J Geriatr Psychiatry Neurol. 2004;17(3):120–126. doi: 10.1177/0891988704267456
  • Leentjens AF, Moonen AJ, Dujardin K, et al. Modeling depression in Parkinson disease: disease-specific and nonspecific risk factors. Neurology. 2013;81(12):1036–1043. doi: 10.1212/WNL.0b013e3182a4a503
  • Kritzinger C, Vollstedt EJ, Hückelheim K, et al. Qualitative characteristics of depression in parkinson’s patients and controls. Behav Neurol. 2015;2015:1–5. doi: 10.1155/2015/961372
  • Hemmerle AM, Herman JP, Seroogy KB. Stress, depression and Parkinson’s disease. Exp Neurol. 2012;233:79–86. doi: 10.1016/j.expneurol.2011.09.035
  • Chaudhuri KR, Schapira AH. Non-motor symptoms of Parkinson’s disease: dopaminergic pathophysiology and treatment. Lancet Neurol. 2009;8(5):464–474. doi: 10.1016/S1474-4422(09)70068-7
  • Antonini A, Tesei S, Zecchinelli A, et al. Randomized study of sertraline and low-dose amitriptyline in patients with Parkinson’s disease and depression: effect on quality of life. Mov Disord. 2006;21(8):1119–1122. doi: 10.1002/mds.20895
  • Barone P, Scarzella L, Marconi R, et al. Pramipexole versus sertraline in the treatment of depression in Parkinson’s disease: a national multicenter parallel-group randomized study. J Neurol. 2006;253(5):601–607. doi: 10.1007/s00415-006-0067-5
  • Mills KA, Greene MC, Dezube R, et al. Efficacy and tolerability of antidepressants in Parkinson’s disease: A systematic review and network meta-analysis. Int J Geriatr Psychiatry. 2018;33(4):642–651. doi: 10.1002/gps.4834
  • Seppi K, Ray Chaudhuri K, Coelho M, et al. Update on treatments for nonmotor symptoms of Parkinson’s disease—an evidence-based medicine review. Mov Disord. 2019;34(2):180–198. doi: 10.1002/mds.27602
  • Prange S, Klinger H, Laurencin C, et al. Depression in patients with parkinson’s disease: current understanding of its neurobiology and implications for treatment. Drugs Aging. 2022;39(6):417–439. doi: 10.1007/s40266-022-00942-1
  • Djamshidian A, Friedman JH. Anxiety and depression in Parkinson’s disease. Curr Treat Options Neurol. 2014;16(4):285. doi: 10.1007/s11940-014-0285-6
  • Chaudhuri KR, Martinez-Martin P, Antonini A, et al. Rotigotine and specific non-motor symptoms of Parkinson’s disease: post hoc analysis of RECOVER. Parkinsonism Relat Disord. 2013;19(7):660–665. doi: 10.1016/j.parkreldis.2013.02.018
  • Barone P, Poewe W, Albrecht S, et al. Pramipexole for the treatment of depressive symptoms in patients with Parkinson’s disease: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2010;9(6):573–580. doi: 10.1016/S1474-4422(10)70106-X
  • Ziaei E, Emami Ardestani P, Chitsaz A. Comparison of pramipexole and citalopram in the treatment of depression in Parkinson’s disease: A randomized parallel-group trial. J Res Med Sci. 2022;27(1):55. doi: 10.4103/jrms.jrms_790_21
  • Santos García D, Alonso Losada MG, Cimas Hernando I, et al. Vortioxetine improves depressive symptoms and cognition in parkinson’s disease patients with major depression: an open-label prospective study. Brain Sci. 2022;12(11):1466. doi: 10.3390/brainsci12111466
  • Maillet A, Météreau E, Tremblay L, et al. Serotonergic and dopaminergic lesions underlying parkinsonian neuropsychiatric signs. Mov Disord. 2021;36(12):2888–2900. doi: 10.1002/mds.28722
  • Pagonabarraga J, Kulisevsky J, Strafella AP, et al. Apathy in Parkinson’s disease: clinical features, neural substrates, diagnosis, and treatment. Lancet Neurol. 2015;14(5):518–531. doi: 10.1016/S1474-4422(15)00019-8
  • Richard IH, Maughn A, Kurlan R. Do serotonin reuptake inhibitor antidepressants worsen Parkinson’s disease? A retrospective case series. Mov Disord. 1999;14(1):155–157. doi: 10.1002/1531-8257(199901)14:1<155:AID-MDS1026>3.0.CO;2-Z
  • Cummings JL, Masterman DL. Depression in patients with Parkinson’s disease. Int J Geriatr Psychiatry. 1999;14(9):711–718. doi: 10.1002/(SICI)1099-1166(199909)14:9<711:AID-GPS4>3.0.CO;2-1
  • Antonini A. Unraveling depression in Parkinson’s disease. Eur J Neurol. 2008 Sep;15(9):885–886. doi: 10.1111/j.1468-1331.2008.02216.x
  • Belvisi D, Berardelli I, Ferrazzano G, et al. The clinical correlates of suicidal ideation in Parkinson’s disease. Parkinsonism Relat Disord. 2019;63:54–59. doi: 10.1016/j.parkreldis.2019.02.047
  • Chen YY, Yu S, Hu YH, et al. Risk of suicide among patients with parkinson disease. JAMA Psychiatry. 2021;78(3):293–301. doi: 10.1001/jamapsychiatry.2020.4001
  • Lee T, Lee HB, Ahn MH, et al. Increased suicide risk and clinical correlates of suicide among patients with Parkinson’s disease. Parkinsonism Relat Disord. 2016;32:102–107.
  • Kummer A, Cardoso F, Teixeira AL. Suicidal ideation in Parkinson’s disease. CNS Spectr. 2009;14(8):431–436. doi: 10.1017/S109285290002040X
  • Du J, Liu X, Zhou X, et al. Parkinson’s disease-related risk of suicide and effect of deep brain stimulation: meta-analysis. Parkinsons Dis. 2020;2020:8091963. doi: 10.1155/2020/8091963
  • Giannini G, Francois M, Lhommée E, et al. Suicide and suicide attempts after subthalamic nucleus stimulation in Parkinson disease. Neurology. 2019;93(1):e97–e105. doi: 10.1212/WNL.0000000000007665
  • Lieberman A. Depression in Parkinson’s disease – a review. Acta Neurol Scand. 2006;113(1):1–8. doi: 10.1111/j.1600-0404.2006.00536.x
  • Duica L, Dragulescu V, Pirlog M. Neurobiological elements of hopelessness and impulsivity in suicidal behavior. Int J Med Rev Case Rep. 2020;4(Reports in Clinical Medicine and):1–4. doi: 10.5455/IJMRCR.suicidal-behaviour-neuro
  • Lim S, Fox SH, Lang AE. Overview of the extranigral aspects of parkinson disease. Arch Neurol. 2009;66(2):167–172. doi: 10.1001/archneurol.2008.561
  • Ray Chaudhuri K, Leta V, Bannister K, et al. The noradrenergic subtype of Parkinson disease: from animal models to clinical practice. Nat Rev Neurol. 2023;19(6):333–345. doi: 10.1038/s41582-023-00802-5
  • Dissanayaka NN, Sellbach A, Matheson S, et al. Anxiety disorders in Parkinson’s disease: prevalence and risk factors. Mov Disord. 2010;25(7):838–845. doi: 10.1002/mds.22833
  • Fiorenzato E, Antonini A, Bisiacchi P, et al. Asymmetric dopamine transporter loss affects cognitive and motor progression in Parkinson’s disease. Mov Disord. 2021;36(10):2303–2313. doi: 10.1002/mds.28682
  • Biundo R, Weis L, Facchini S, et al. Cognitive profiling of Parkinson disease patients with mild cognitive impairment and dementia. Parkinsonism Relat Disord. 2014;20(4):394–399. doi: 10.1016/j.parkreldis.2014.01.009
  • Aarsland D, Batzu L, Halliday GM, et al. Parkinson disease-associated cognitive impairment. Nat Rev Dis Primers. 2021;7(1):47. doi: 10.1038/s41572-021-00280-3
  • McKinlay A, Grace RC, Dalrymple-Alford JC, et al. Characteristics of executive function impairment in Parkinson’s disease patients without dementia. J Int Neuropsychol Soc. 2010;16(2):268–277. doi: 10.1017/S1355617709991299
  • González-Usigli HA, Ortiz GG, Charles-Niño C, et al. Neurocognitive psychiatric and neuropsychological alterations in parkinson’s disease: a basic and clinical approach. Brain Sci. 2023;13(3):508. doi: 10.3390/brainsci13030508
  • Hoogland J, van Wanrooij LL, Boel JA, et al. Validation of mild cognitive impairment in parkinson disease. detecting mild cognitive deficits in Parkinson’s disease: comparison of neuropsychological tests. Mov Disord. 2018;33(11):1750–1759. doi: 10.1002/mds.110
  • Rolinski M, Fox C, Maidment I, et al. Cholinesterase inhibitors for dementia with Lewy bodies, Parkinson’s disease dementia and cognitive impairment in Parkinson’s disease. Cochrane Database Of Systematic Reviews. 2012;2012(7):CD006504. doi: 10.1002/14651858.CD006504.pub2
  • Wang HF, Yu JT, Tang SW, et al. Efficacy and safety of cholinesterase inhibitors and memantine in cognitive impairment in Parkinson’s disease, Parkinson’s disease dementia, and dementia with Lewy bodies: systematic review with meta-analysis and trial sequential analysis. J Neurol Neurosurg Psychiatry. 2015;86(2):135–143. doi: 10.1136/jnnp-2014-307659
  • de la Riva P, Smith K, Xie SX, et al. Course of psychiatric symptoms and global cognition in early parkinson disease. Neurology. 2014;83(12):1096–1103. doi: 10.1212/WNL.0000000000000801
  • Montagnese M, Vignando M, Ffytche D, et al. Cognitive and visual processing performance in Parkinson’s disease patients with vs without visual hallucinations: A meta-analysis. Cortex. 2022;146:161–172. doi: 10.1016/j.cortex.2021.11.001
  • Forsaa EB, Larsen JP, Wentzel-Larsen T, et al. A 12-year population-based study of psychosis in Parkinson disease. Arch Neurol. 2010;67(8):996–1001. doi: 10.1001/archneurol.2010.166
  • Rabey JM. Hallucinations and psychosis in Parkinson’s disease. Park Relat Disord. 2009;15:105–S110. doi: 10.1016/S1353-8020(09)70846-6
  • Kyle K, Bronstein JM. Treatment of psychosis in Parkinson’s disease and dementia with Lewy Bodies: A review. Parkinsonism Relat Disord. 2020;75:55–62. doi: 10.1016/j.parkreldis.2020.05.026
  • Schrag A, Hovris A, Morley D, et al. Caregiver-burden in parkinson’s disease is closely associated with psychiatric symptoms, falls, and disability. Parkinsonism Relat Disord. 2006;12(1):35–41. doi: 10.1016/j.parkreldis.2005.06.011
  • Emre M, Aarsland D, Albanese A, et al. Rivastigmine for dementia associated with Parkinson’s disease. N Engl J Med. 2004;351(24):2509–2518. doi: 10.1056/NEJMoa041470
  • Parkinson Study Group. Low-dose clozapine for the treatment of drug-induced psychosis in Parkinson’s disease. N Engl J Med. 1999;340(10):757–763. doi: 10.1056/NEJM199903113401003
  • Pollak P, Tison F, Rascol O, et al. Clozapine in drug induced psychosis in Parkinson’s disease: a randomised, placebo-controlled study with open follow up. J Neurol Neurosurg Psychiatry. 2004;75(5):689–695. doi: 10.1136/jnnp.2003.029868
  • Ondo WG, Tintner R, Dat Voung K, et al. Double-blind, placebo-controlled, unforced titration parallel trial of quetiapine for dopaminergic-induced hallucinations in Parkinson’s disease, Mov. Mov Disord. 2005;20(8):958–963. doi: 10.1002/mds.20474
  • Rabey JM, Prokhorov T, Miniovitz A, et al. Effect of quetiapine in psychotic Parkinson’s disease patients: a double-blind labeled study of 3 months’ duration, Mov. Mov Disord. 2007;22(3):313–318. doi: 10.1002/mds.21116
  • Shotbolt P. A randomized controlled trial of quetiapine for psychosis in Parkinson’s disease. Neuropsychiatr Dis Treat. 2009;5:327. doi: 10.2147/NDT.S5335
  • Fernandez HH, Friedman JH, Jacques C, et al. Quetiapine for the treatment of drug-induced psychosis in Parkinson’s disease. Mov Disord. 1999;14(3):484–487. doi: 10.1002/1531-8257(199905)14:3<484:AID-MDS1016>3.0.CO;2-B
  • Reddy S, Factor SA, Molho ES, et al. The effect of quetiapine on psychosis and motor function in parkinsonian patients with and without dementia. Mov Disord. 2002;17(4):676–681. doi: 10.1002/mds.10176
  • Juncos JL, Roberts VJ, Evatt ML, et al. Quetiapine improves psychotic symptoms and cognition in Parkinson’s disease. Mov Disord. 2004;19(1):29–35. doi: 10.1002/mds.10620
  • Fernandez HH, Trieschmann ME, Burke MA, et al. Long-term outcome of quetiapine use for psychosis among Parkinsonian patients. Mov Disord. 2003;18(5):510–514. doi: 10.1002/mds.10374
  • Friedman JH. Pharmacological interventions for psychosis in Parkinson’s disease patients, expet opin. Pharmacother. 2018;19(5):499–505. doi: 10.1080/14656566.2018.1445721
  • Yasue I, Matsunaga S, Kishi T, et al. Serotonin 2A receptor inverse agonist as a treatment for Parkinson’s disease psychosis: a systematic review and meta-analysis of serotonin 2A receptor negative modulators. J Alzheim Dis. 2016;50(3):733–740. doi: 10.3233/JAD-150818
  • Leta V, van Wamelen DJ, Aureli F, et al. The real-life effect of catechol-O-methyltransferase inhibition on non-motor symptoms in levodopa-treated Parkinson’s disease: opicapone versus entacapone. J Neural Transm (Vienna). 2023;130(7):925–930. Epub ahead of print. PMID: 37036498. doi: 10.1007/s00702-023-02603-y
  • Antonini A, Cilia R. Behavioural adverse effects of dopaminergic treatments in Parkinsonʼs disease. Drug Saf. 2009;32(6):475–488. doi: 10.2165/00002018-200932060-00004
  • Antonini A, Barone P, Bonuccelli U, et al. ICARUS study: prevalence and clinical features of impulse control disorders in Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2017;88(4):317–324. doi: 10.1136/jnnp-2016-315277
  • Weintraub D, David AS, Evans AH, et al. Clinical spectrum of impulse control disorders in Parkinson’s disease. Mov Disord. 2015;30(2):121–127. doi: 10.1002/mds.26016
  • Biundo R, Weis L, Abbruzzese G, et al. Impulse control disorders in advanced Parkinson’s disease with dyskinesia: The ALTHEA study. Mov Disord. 2017;32(11):1557–1565. doi: 10.1002/mds.27181
  • EUROPAR and the IPMDS Non-Motor-PD-Study Group, Rizos A, Sauerbier A, Antonini A, et al. A European multicentre survey of impulse control behaviours in Parkinson’s disease patients treated with short- and long-acting dopamine agonists. Eur J Neurol. 2016;23(8):1255–1261.
  • Garcia-Ruiz PJ, Martinez Castrillo JC, Alonso-Canovas A, et al. Impulse control disorder in patients with Parkinson’s disease under dopamine agonist therapy: a multicentre study. J Neurol Neurosurg Psychiatry. 2014;85(8):840–844. doi: 10.1136/jnnp-2013-306787
  • Costello H, Berry AJ, Reeves S, et al. Disrupted reward processing in Parkinson’s disease and its relationship with dopamine state and neuropsychiatric syndromes: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2022;93(5):555–562. doi: 10.1136/jnnp-2021-327762
  • Faouzi J, Corvol JC, Mariani LL. Impulse control disorders and related behaviors in Parkinson’s disease: risk factors, clinical and genetic aspects, and management. Curr Opin Neurol. 2021;34(4):547–555. doi: 10.1097/WCO.0000000000000955
  • Healy S, Shepherd H, Mooney N, et al. The effect of deep brain stimulation on impulse control related disorders in Parkinson’s disease - a 10-year retrospective study of 137 patients. J Neurol Sci. 2022;440:120339. doi: 10.1016/j.jns.2022.120339
  • Chaudhuri KR, Todorova A, Nirenberg MJ, et al. A pilot prospective, multicenter observational study of dopamine agonist withdrawal syndrome in Parkinson’s disease. Mov Disord Clin Pract. 2015;2(2):170–174. doi: 10.1002/mdc3.12141
  • Decourt M, Jiménez-Urbieta H, Benoit-Marand M, et al. Neuropsychiatric and cognitive deficits in Parkinson’s disease and their modeling in rodents. Biomedicines. 2021;9(6):684. doi: 10.3390/biomedicines9060684
  • Ossig C, Antonini A, Buhmann C, et al. Wearable sensor-based objective assessment of motor symptoms in Parkinson’s disease. J Neural Transm. 2016;123(1):57–64. doi: 10.1007/s00702-015-1439-8
  • Guerra A, D’Onofrio V, Ferreri F, et al. Objective measurement versus clinician-based assessment for Parkinson’s disease. Expert Rev Neurother. 2023 1-14;1–14. doi: 10.1080/14737175.2023.2229954
  • Antonini A, Emmi A, Campagnolo M. Beyond the Dopaminergic system: lessons learned from L-Dopa resistant symptoms in Parkinson’s disease. Mov Disord Clin Practice. 2023; (in press). doi: 10.1002/mdc3.13786.
  • Outeiro T, Alcalay RN, Antonini A, et al. Defining the riddle in order to solve it: there is more than one “Parkinson’s disease”. Mov Disord. 2023; doi: 10.1002/mds.29419
  • Emmi A, Sandre M, Russo FP, et al. Duodenal alpha‐Synuclein Pathology and Enteric Gliosis in Advanced Parkinson's Disease. Mov Disord. 2023;38(5):885–894. doi: 10.1002/mds.29358
  • Emmi A, Rizzo S, Barzon L, et al. Detection of SARS-CoV-2 viral proteins and genomic sequences in human brainstem nuclei. npj Parkinsons Dis. 2023;9(1): doi: 10.1038/s41531-023-00467-3
  • Robinson JL, Lee EB, Xie SX, et al. Neurodegenerative disease concomitant proteinopathies are prevalent, age-related and APOE4-associated. Brain. 2018;141(7):2181–2193. doi: 10.1093/brain/awy146
  • Bayram E, Shan G, Cummings JL. Associations between comorbid TDP-43, lewy body pathology, and neuropsychiatric symptoms in Alzheimer’s disease. J Alzheimers Dis. 2019;69(4):953–961. doi: 10.3233/JAD-181285
  • Nelson RS, Abner EL, Jicha GA, et al. Neurodegenerative pathologies associated with behavioral and psychological symptoms of dementia in a community-based autopsy cohort. Acta Neuropathol Commun. 2023;11(1):89. doi: 10.1186/s40478-023-01576-z
  • Parker KL, Lamichhane D, Caetano MS, et al. Executive dysfunction in Parkinson’s disease and timing deficits. Front Integr Neurosci. 2013;7:75. doi: 10.3389/fnint.2013.00075
  • Rowe JB, Hughes L, Ghosh BC, et al. Parkinson’s disease and dopaminergic therapy—differential effects on movement, reward and cognition. Brain. 2008;131(8):2094–2105. doi: 10.1093/brain/awn112
  • Isaacson SH, Goldstein M, Pahwa R, et al. Ulotaront, a trace amine-associated receptor 1/serotonin 5-HT 1A agonist, in patients with parkinson disease psychosis. Neurol Clin Pract. 2023;13(4):e200175.
  • Ferreira JJ, Poewe W, Rascol O, et al. Effect of opicapone on levodopa pharmacokinetics in patients with fluctuating Parkinson’s disease. Mov Disord. 2022;37(11):2272–2283. doi: 10.1002/mds.29193
  • Antonini A, Moro E, Godeiro C, et al. Medical and surgical management of advanced Parkinson’s disease. Mov Disord. 2018;33(6):900–908. doi: 10.1002/mds.27340
  • van Laar T, Chaudhuri KR, Antonini A, et al. Infusion therapies in the treatment of Parkinson’s disease [published online ahead of print, 2023 Jun 12]. J Parkinsons Dis. 2023;10.3233/JPD-225112. doi: 10.3233/JPD-225112
  • Martinez-Martin P, Falup Pecurariu C, Odin P, et al. Gender-related differences in the burden of non-motor symptoms in Parkinson’s disease. J Neurol. 2012;259(8):1639–1647. doi: 10.1007/s00415-011-6392-3

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.