Leitlinien „Chorea/Morbus Huntington“ für die deutschsprachigen Länder neu überarbeitet^[*]

Zusammenfassung

Die neu überarbeiteten Leitlinien Chorea/Morbus Huntington geben auf S2k Niveau einen Überblick über den Stand der Forschung zum Erkrankungsverlauf sowie zu neuen Ansätzen der symptomatischen und verlaufsmodifizierenden Therapie bei der Huntington-Krankheit. Im Gegensatz zu vielen anderen Leitlinien bevorzugen die Autoren aus den deutschsprachigen Ländern als Erstlinienbehandlung der Chorea Tiaprid. Aufgrund von Nebenwirkungen, welche unter Tetrabenazin auftreten können – wie etwa Depression oder Akathisie, ist es gängige Praxis, Tetrabenazin erst in zweiter Linie einzusetzen. Die Leitlinien nehmen Stellung zu rechtlichen Fragen der Präimplantationsdiagnostik (PID) und der pränatalen Diagnostik (PD) in Deutschland, Österreich und der Schweiz sowie zu den Unterschieden zwischen dem prädiktiven und dem differenzialdiagnostischen Einsatz der molekulargenetischen Diagnostik. In den Leitlinien wird darüber hinaus sehr ausführlich zu den möglichen Differenzialdiagnosen bei einer Chorea ungeklärter Ätiologie Stellung genommen.

Abstract

The updated and revised guidelines (S2k level) on ‘Chorea and Huntington’s Disease (HD)’ review the present understanding of the natural history of HD including rate of progression and describe new approaches to symptomatic and disease course-modifying therapies in HD. In contrast to other guidelines, the expert opinion in the German speaking countries favors tiapride as a first line treatment of chorea. Because of the side effect profile of tetrabenazine, including depression or akathisia, the authors prefer to use tetrabenazine as second line treatment. The current guidelines address medico-legal aspects of preimplantation genetic diagnosis (PGD) and prenatal testing in Germany, Austria and Switzerland as well as differences between a predictive and a diagnostic setting of molecular genetic diagnosis. In addition, the guidelines comment in detail on the differential diagnoses of a chorea of unknown origin.

Schlüsselwörter

Huntington - chorea - prädiktiv - antidopaminerg

Keywords

Huntingtonʼs disease - chorea - predictive - antidopaminergic

^* Den Leitlinientext zusammen mit der Interessenkonflikterklärung finden Sie auch auf www.dgn.org sowie www.awmf.de.

• Literatur

• 1 Frank S, Testa CM. et al. Huntington Study G. Effect of deutetrabenazine on chorea among patients with Huntington disease: a randomized clinical trial. JAMA 2016; 316: 40-50
• 2 Huntington Study Group HI. A randomized, double-blind, placebo-controlled trial of pridopidine in Huntingtonʼs disease. Mov Disord 2013; 28: 1407-1415
• 3 de Yebenes JG, Landwehrmeyer B, Squitieri F. et al. Pridopidine for the treatment of motor function in patients with Huntingtonʼs disease (MermaiHD): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Neurol 2011; 10: 1049-1057
• 4 Gelderblom H, Wustenberg T, McLean T. et al. Bupropion for the treatment of apathy in Huntingtonʼs disease: a multicenter, randomised, double-blind, placebo-controlled, prospective crossover trial. PLoS One 2017; 12: e0173872
• 5 McGarry A, McDermott M, Kieburtz K. et al. A randomized, double-blind, placebo-controlled trial of coenzyme Q10 in Huntington disease. Neurology 2017; 88: 152-159
• 6 Wojtecki L, Groiss SJ, Ferrea S. et al. A Prospective pilot trial for pallidal deep brain stimulation in Huntingtonʼs disease. Front Neurol 2015; 6: 177
• 7 Paulsen JS, Long JD, Johnson HJ. et al. Clinical and biomarker changes in premanifest Huntington disease show trial feasibility: a decade of the PREDICT-HD Study. Front Aging Neurosci 2014; 6: 78
• 8 Paulsen JS, Long JD, Ross CA. et al. Prediction of manifest Huntingtonʼs disease with clinical and imaging measures: a prospective observational study. Lancet Neurol 2014; 13: 1193-1201
• 9 Stout JC, Paulsen JS, Queller S. et al. Neurocognitive signs in prodromal Huntington disease. Neuropsychology 2011; 25: 1-14
• 10 Tabrizi SJ, Langbehn DR, Leavitt BR. et al. Biological and clinical manifestations of Huntingtonʼs disease in the longitudinal TRACK-HD study: cross-sectional analysis of baseline data. Lancet Neurol 2009; 8: 791-801
• 11 Tabrizi SJ, Reilmann R, Roos RA. et al. Potential endpoints for clinical trials in premanifest and early Huntingtonʼs disease in the TRACK-HD study: analysis of 24 month observational data. Lancet Neurol 2012; 11: 42-53
• 12 Tabrizi SJ, Scahill RI, Durr A. et al. Biological and clinical changes in premanifest and early stage Huntingtonʼs disease in the TRACK-HD study: the 12-month longitudinal analysis. Lancet Neurol 2011; 10: 31-42
• 13 Tabrizi SJ, Scahill RI, Owen G. et al. Predictors of phenotypic progression and disease onset in premanifest and early-stage Huntingtonʼs disease in the TRACK-HD study: analysis of 36-month observational data. Lancet Neurol 2013; 12: 637-649
• 14 [Anonym] Identification of Genetic Factors that Modify Clinical Onset of Huntingtonʼs Disease. Cell 2015; 162: 516-526
• 15 Harbo HF, Finsterer J, Baets J. et al. EFNS guidelines on the molecular diagnosis of neurogenetic disorders: general issues, Huntingtonʼs disease, Parkinsonʼs disease and dystonias. Eur J Neurol 2009; 16: 777-785
• 16 [Anonym] Guidelines for the molecular genetics predictive test in Huntingtonʼs disease. International Huntington Association (IHA) and the World Federation of Neurology (WFN) Research Group on Huntingtonʼs Chorea. Neurology 1994; 44: 1533-1536
• 17 Hensman Moss DJ, Poulter M, Beck J. et al. C9orf72 expansions are the most common genetic cause of Huntington disease phenocopies. Neurology 2014; 82: 292-299
• 18 Schneider SA, Bhatia KP. Huntingtonʼs disease look-alikes. Handb Clin Neurol 2011; 100: 101-112
• 19 Pedroso JL, de Freitas ME, Albuquerque MV. et al. Should spinocerebellar ataxias be included in the differential diagnosis for Huntingtonʼs diseases-like syndromes?. J Neurol Sci 2014; 347: 356-358
• 20 Danek A. [Progress in molecular chorea diagnosis. McLeod syndrome and chorea acanthocytosis]. Nervenarzt 2002; 73: 564-569
• 21 Cardoso F, Seppi K, Mair KJ. et al. Seminar on choreas. Lancet Neurol 2006; 5: 589-602
• 22 Santens P, Van Damme T, Steyaert W. et al. RNF216 mutations as a novel cause of autosomal recessive Huntington-like disorder. Neurology 2015; 84: 1760-1766
• 23 Synofzik M, Schule R, Schulte C. et al. Complex hyperkinetic movement disorders associated with POLG mutations. Mov Disord 2010; 25: 2472-2475
• 24 Macaya A, Munell F, Burke RE. et al. Disorders of movement in Leigh syndrome. Neuropediatrics 1993; 24: 60-67
• 25 Saracchi E, Castelli M, Bassi MT. et al. A novel heterozygous SETX mutation in a patient presenting with chorea and motor neuron disease. Amyotroph Lateral Scler Frontotemporal Degener 2014; 15: 138-140
• 26 Malik GM, Mubarik M, Khan MD. et al. Laurence-Moon-Biedl-Bardet syndrome with chorea. J Assoc Physicians India 1995; 43: 295-296
• 27 Hanna MG, Davis MB, Sweeney MG. et al. Generalized chorea in two patients harboring the Friedreich's ataxia gene trinucleotide repeat expansion. Mov Disord 1998; 13: 339-340
• 28 Prohaska R, Sibon OC, Rudnicki DD. et al. Brain, blood, and iron: perspectives on the roles of erythrocytes and iron in neurodegeneration. Neurobiol Dis 2012; 46: 607-624
• 29 Tonekaboni SH, Mollamohammadi M. Neurodegeneration with brain iron accumulation: an overview. Iran J Child Neurol 2014; 8: 1-8
• 30 Arber CE, Li A, Houlden H. et al. Review: Insights into molecular mechanisms of disease in neurodegeneration with brain iron accumulation: unifying theories. Neuropathol Appl Neurobiol 2016; 42: 220-241
• 31 Le Ber I, Moreira MC, Rivaud-Pechoux S. et al. Cerebellar ataxia with oculomotor apraxia type 1: clinical and genetic studies. Brain 2003; 126: 2761-2772
• 32 Anheim M, Monga B, Fleury M. et al. Ataxia with oculomotor apraxia type 2: clinical, biological and genotype/phenotype correlation study of a cohort of 90 patients. Brain 2009; 132: 2688-2698
• 33 Kovacs GG, Murrell JR, Horvath S. et al. TARDBP variation associated with frontotemporal dementia, supranuclear gaze palsy, and chorea. Mov Disord 2009; 24: 1843-1847
• 34 Adler CH, Wrabetz L. Lesch-Nyhan variant: dystonia, ataxia, near-normal intelligence, and no self-mutilation. Mov Disord 1996; 11: 583-584
• 35 Josephs KA, Van Gerpen MW, Van Gerpen JA. Adult onset Niemann-Pick disease type C presenting with psychosis. J Neurol Neurosurg Psychiatry 2003; 74: 528-529
• 36 Nass R, Petito C, Stoner E. et al. Neuronal ceroid lipofuscinosis with hypergonadotropic hypogonadism. J Child Neurol 1986; 1: 142-144
• 37 Mizuguchi M, Kamoshita S. [Movement disorders in miscellaneous disorders--inherited metabolic diseases]. Nihon Rinsho 1993; 51: 2919-2923
• 38 Shah PA, Kuchhai FA. Galactosemia with chorea – an unusual presentation. Indian J Pediatr 2009; 76: 97-98
• 39 Klein C. Genetics in dystonia. Parkinsonism Relat Disord 2014; 20 (Suppl. 01) S137-142
• 40 Carapito R, Paul N, Untrau M. et al. A de novo ADCY5 mutation causes early-onset autosomal dominant chorea and dystonia. Mov Disord 2015; 30: 423-427
• 41 Wright RA, Pollock M, Donaldson IM. Chorea and tuberous sclerosis. Mov Disord 1992; 7: 87-89
• 42 Papandreou A, Schneider RB, Augustine EF. et al. Delineation of the movement disorders associated with FOXG1 mutations. Neurology 2016; 86: 1794-1800
• 43 Dale RC, Merheb V, Pillai S. et al. Antibodies to surface dopamine-2 receptor in autoimmune movement and psychiatric disorders. Brain 2012; 135: 3453-3468
• 44 Robottom BJ, Weiner WJ. Chorea gravidarum. Handb Clin Neurol 2011; 100: 231-235
• 45 Hacohen Y, Wright S, Waters P. et al. Paediatric autoimmune encephalopathies: clinical features, laboratory investigations and outcomes in patients with or without antibodies to known central nervous system autoantigens. J Neurol Neurosurg Psychiatry 2013; 84: 748-755
• 46 Leypoldt F, Armangue T, Dalmau J. Autoimmune encephalopathies. Ann N Y Acad Sci 2015; 1338: 94-114
• 47 Sabater L, Gaig C, Gelpi E. et al. A novel non-rapid-eye movement and rapid-eye-movement parasomnia with sleep breathing disorder associated with antibodies to IgLON5: a case series, characterisation of the antigen, and post-mortem study. Lancet Neurol 2014; 13: 575-586
• 48 OʼToole O, Lennon VA, Ahlskog JE. et al. Autoimmune chorea in adults. Neurology 2013; 80: 1133-1144
• 49 Vynogradova I, Savitski V, Heckmann JG. Hemichorea associated with CASPR2 antibody. Tremor Other Hyperkinet Mov (N Y) 2014; 4: 239
• 50 Crespo-Burillo JA, Hernando-Quintana N, Ruiz-Palomino P. et al. Chorea secondary to striatal encephalitis due to anti-CV2/CRMP5 antibodies. Case description and review of the literature. Neurologia (Barcelona, Spain) 2015; 30: 451-453
• 51 Lopes AS, Clemente G, Len CA. et al. [Chorea: a rare manifestation of Takayasuʼs arteritis]. Revista brasileira de reumatologia 2015; 55: 384-386
• 52 Gambardella A, Andermann F, Shorvon S. et al. Limited chronic focal encephalitis: another variant of Rasmussen syndrome?. Neurology 2008; 70: 374-377
• 53 Walker RH. Further evidence for celiac disease-associated chorea. Tremor Other Hyperkinet Mov (N Y) 2011; 1: tre-01-32-96-03
• 54 Taurin G, Golfier V, Pinel JF. et al. Choreic syndrome due to Hashimotoʼs encephalopathy. Mov Disord 2002; 17: 1091-1092
• 55 Peregrin J, Malikova H. Primary Whipple disease of the brain: case report with long-term clinical and MRI follow-up. Neuropsychiatr Dis Treat 2015; 11: 2461-2469
• 56 Ataya A, Harman E. Images in clinical medicine. Hemichoreoathetosis in neurosarcoidosis. N Engl J Med 2015; 372: e27
• 57 Chang KH, Tsou JC, Chen ST. et al. Temporal features of magnetic resonance imaging and spectroscopy in non-ketotic hyperglycemic chorea-ballism patients. Eur J Neurol 2010; 17: 589-593
• 58 Edvardsson B, Persson S. Chorea associated with vitamin B12 deficiency. Eur J Neurol 2011; 18: e138-139
• 59 Venkatesan EP, Ramadoss K, Balakrishnan R. et al. Essential thrombocythemia: rare cause of chorea. Ann Indian Acad Neurol 2014; 17: 106-107
• 60 Saft C, Reber D, Streuer M. et al. Post pump chorea in a 77-year-old male. Neurol Sci 2011; 32: 699-701
• 61 Krakauer M, Law I. FDG PET brain imaging in neuropsychiatric systemic lupus erythematosis with choreic symptoms. Clin Nucl Med 2009; 34: 122-123
• 62 Weiner SM, Otte A, Schumacher M. et al. Alterations of cerebral glucose metabolism indicate progress to severe morphological brain lesions in neuropsychiatric systemic lupus erythematosus. Lupus 2000; 9: 386-389
• 63 Mackay M, Tang CC, Volpe BT. et al. Brain metabolism and autoantibody titres predict functional impairment in systemic lupus erythematosus. Lupus Sci Med 2015; 2: e000074
• 64 Curiel R, Akin EA, Beaulieu G. et al. PET/CT imaging in systemic lupus erythematosus. Ann N Y Acad Sci 2011; 1228: 71-80
• 65 Arning L, Witt CN, Epplen JT. et al. Genetic Counselling for predictive testing in Huntingtonʼs disease in one centre since 1993. Gender-specific aspects of decision-making. J Huntingtons Dis 2015; 4: 87-98
• 66 Pechlivanis I, Andrich J, Scholz M. et al. Chronic subdural haematoma in patients with Huntingtonʼs disease. Br J Neurosurg 2006; 20: 327-329
• 67 Cardoso F. Sydenham's chorea. Handb Clin Neurol 2011; 100: 221-229
• 68 Oosterveer DM, Overweg-Plandsoen WC, Roos RA. Sydenhamʼs chorea: a practical overview of the current literature. Pediatr Neurol 2010; 43: 1-6
• 69 Mohammad SS, Nosadini M, Grattan-Smith P. et al. Intravenous immunoglobulin in acute Sydenhamʼs chorea: A systematic review. J Paediatr Child Health 2015; 51: 1235-1238
• 70 Rullan E, Sigal LH. Rheumatic fever. Curr Rheumatol Rep 2001; 3: 445-452
• 71 Kim JA, Jung S, Kim MJ. et al. A case of vascular hemichorea responding to topiramate. J Mov Disord 2009; 2: 80-81
• 72 D'Amelio M, Callari G, Gammino M. et al. Levetiracetam in the treatment of vascular chorea: a case report. Eur J Clin Pharmacol 2005; 60: 835-836
• 73 Friederich RL. Benign hereditary chorea improved on stimulant therapy. Pediatr Neurol 1996; 14: 326-327
• 74 Mestre T, Ferreira J, Coelho MM. et al. Therapeutic interventions for disease progression in Huntingtonʼs disease. Cochrane Database Syst Rev 2009; CD006455.pub2: CD006455
• 75 Shannon KM, Fraint A. Therapeutic advances in Huntingtonʼs disease. Mov Disord 2015; 30: 1539-1546
• 76 Huntington Study G. A randomized, placebo-controlled trial of coenzyme Q10 and remacemide in Huntingtonʼs disease. Neurology 2001; 57: 397-404
• 77 Verbessem P, Lemiere J, Eijnde BO. et al. Creatine supplementation in Huntingtonʼs disease: a placebo-controlled pilot trial. Neurology 2003; 61: 925-930
• 78 Bonelli RM, Wenning GK. Pharmacological management of Huntingtonʼs disease: an evidence-based review. Curr Pharm Des 2006; 12: 2701-2720
• 79 Bonelli RM, Hofmann P. A systematic review of the treatment studies in Huntingtonʼs disease since 1990. Expert Opin Pharmacother 2007; 8: 141-153
• 80 Mestre T, Ferreira J, Coelho MM. et al. Therapeutic interventions for symptomatic treatment in Huntingtonʼs disease. Cochrane Database Syst Rev 2009; CD006456.pub2: CD006456
• 81 Rutkowski M, Grzegorczyk K. Adverse effects of antioxidative vitamins. Int J Occup Med Environ Health 2012; 25: 105-121
• 82 Huntington Study Group DI. A futility study of minocycline in Huntingtonʼs disease. Mov Disord 2010; 25: 2219-2224
• 83 Bachoud-Levi AC. Neural grafts in Huntingtonʼs disease: viability after 10 years. Lancet Neurol 2009; 8: 979-981
• 84 Barker RA, Mason SL, Harrower TP. et al. The long-term safety and efficacy of bilateral transplantation of human fetal striatal tissue in patients with mild to moderate Huntingtonʼs disease. J Neurol Neurosurg Psychiatry 2013; 84: 657-665
• 85 Isomura T, Suzuki S, Origasa H. et al. Liver-related safety assessment of green tea extracts in humans: a systematic review of randomized controlled trials. Eur J Clin Nutr 2016; 70: 1340
• 86 Reilmann R, Squitieri F, Priller J. et al. N02 safety and tolerability of selisistat for the treatment of Huntington’s disease: results from a randomised, double-blind, placebo-controlled phase Ii trial. J Neurol Neurosurg Psychiatry 2014; 85: A102-A102
• 87 Sussmuth SD, Haider S, Landwehrmeyer GB. et al. An exploratory double-blind, randomized clinical trial with selisistat, a SirT1 inhibitor, in patients with Huntingtonʼs disease. Br J Clin Pharmacol 2015; 79: 465-476
• 88 Adanyeguh IM, Rinaldi D, Henry PG. et al. Triheptanoin improves brain energy metabolism in patients with Huntington disease. Neurology 2015; 84: 490-495
• 89 Marder K, Gu Y, Eberly S. et al. Relationship of Mediterranean diet and caloric intake to phenoconversion in Huntington disease. JAMA Neurol 2013; 70: 1382-1388
• 90 Trembath MK, Horton ZA, Tippett L. et al. A retrospective study of the impact of lifestyle on age at onset of Huntington disease. Mov Disord 2010; 25: 1444-1450
• 91 Schultz JL, Kamholz JA, Moser DJ. et al. Substance abuse may hasten motor onset of Huntington disease: Evaluating the Enroll-HD database. Neurology 2017; 88: 909-915
• 92 Zuccato C, Valenza M, Cattaneo E. Molecular mechanisms and potential therapeutical targets in Huntingtonʼs disease. Physiol Rev 2010; 90: 905-981
• 93 Johnson CD, Davidson BL. Huntingtonʼs disease: progress toward effective disease-modifying treatments and a cure. Hum Mol Genet 2010; 19: R98-R102
• 94 Wild EJ, Tabrizi SJ. Targets for future clinical trials in Huntingtonʼs disease: whatʼs in the pipeline?. Mov Disord 2014; 29: 1434-1445
• 95 Desamericq G, Youssov K, Charles P. et al. Guidelines for clinical pharmacological practices in Huntingtonʼs disease. Rev Neurol (Paris) 2016; 172: 423-432
• 96 Killoran A, Biglan KM. Therapeutics in Huntingtonʼs disease. Current Treatment Options in Neurology 2012; 14: 137-149
• 97 [Anonym] Tetrabenazine as antichorea therapy in Huntington disease: a randomized controlled trial. Neurology 2006; 66: 366-372
• 98 Killoran A, Biglan KM. Current therapeutic options for Huntingtonʼs disease: good clinical practice versus evidence-based approaches?. Mov Disord 2014; 29: 1404-1413
• 99 Brusa L, Orlacchio A, Moschella V. et al. Treatment of the symptoms of Huntingtonʼs disease: preliminary results comparing aripiprazole and tetrabenazine. Mov Disord 2009; 24: 126-129
• 100 Ciammola A, Sassone J, Colciago C. et al. Aripiprazole in the treatment of Huntingtonʼs disease: a case series. Neuropsychiatr Dis Treat 2009; 5: 1-4
• 101 Johnston TG. Risperidone long-acting injection and Huntingtonʼs disease: case series with significant psychiatric and behavioural symptoms. Int Clin Psychopharmacol 2011; 26: 114-119
• 102 Ferreira JJ, Rosser A, Craufurd D. et al. Ethyl-eicosapentaenoic acid treatment in Huntingtonʼs disease: A placebo-controlled clinical trial. Mov Disord 2015; 30: 1426-1429
• 103 Ondo WG, Mejia NI, Hunter CB. A pilot study of the clinical efficacy and safety of memantine for Huntingtonʼs disease. Parkinsonism Relat Disord 2007; 13: 453-454
• 104 Sagredo O, Pazos MR, Valdeolivas S. et al. Cannabinoids: novel medicines for the treatment of Huntingtonʼs disease. Recent Pat CNS Drug Discov 2012; 7: 41-48
• 105 Armstrong MJ, Miyasaki JM. American Academy of N. Evidence-based guideline: pharmacologic treatment of chorea in Huntington disease: report of the guideline development subcommittee of the American Academy of Neurology. Neurology 2012; 79: 597-603
• 106 Curtis A, Mitchell I, Patel S. et al. A pilot study using nabilone for symptomatic treatment in Huntingtonʼs disease. Mov Disord 2009; 24: 2254-2259
• 107 Lopez-Sendon Moreno JL, Garcia Caldentey J, Trigo Cubillo P. et al. A double-blind, randomized, cross-over, placebo-controlled, pilot trial with Sativex in Huntingtonʼs disease. J Neurol 2016; 263: 1390-1400
• 108 Kenney C, Hunter C, Jankovic J. Long-term tolerability of tetrabenazine in the treatment of hyperkinetic movement disorders. Mov Disord 2007; 22: 193-197
• 109 Holl AK, Wilkinson L, Painold A. et al. Combating depression in Huntingtonʼs disease: effective antidepressive treatment with venlafaxine XR. Int Clin Psychopharmacol 2010; 25: 46-50
• 110 Abbott SM, Videnovic A. Chronic sleep disturbance and neural injury: links to neurodegenerative disease. Nat Sci Sleep 2016; 8: 55-61
• 111 van Wamelen DJ, Roos RA, Aziz NA. Therapeutic strategies for circadian rhythm and sleep disturbances in Huntington disease. Neurodegener Dis Manag 2015; 5: 549-559
• 112 Como PG, Rubin AJ, O'Brien CF. et al. A controlled trial of fluoxetine in nondepressed patients with Huntingtonʼs disease. Mov Disord 1997; 12: 397-401
• 113 van Duijn E, Craufurd D, Hubers AA. et al. Neuropsychiatric symptoms in a European Huntingtonʼs disease cohort (REGISTRY). J Neurol Neurosurg Psychiatry 2014; 85: 1411-1418
• 114 Volz HP, Moller HJ. [Opipramol in anxiety and somatoform disorders. Results of a controlled study]. Fortschr Neurol Psychiatr 1998; 66 (Suppl. 01) S21-24
• 115 Rosenblatt A. Neuropsychiatry of Huntingtonʼs disease. Dialogues Clin Neurosci 2007; 9: 191-197
• 116 van Duijn E. Treatment of irritability in Huntington’s disease. Curr Treat Options Neurol 2010; 12: 424-433
• 117 Fisher CA, Sewell K, Brown A. et al. Aggression in Huntingtonʼs disease: a systematic review of rates of aggression and treatment methods. J Huntingtons Dis 2014; 3: 319-332
• 118 Leonard DP, Kidson MA, Brown JG. et al. A double blind trial of lithium carbonate and haloperidol in Huntingtonʼs chorea. Aust N Z J Psychiatry 1975; 9: 115-118
• 119 Hassler F, Reis O. Pharmacotherapy of disruptive behavior in mentally retarded subjects: A review of the current literature. Dev Disabil Res Rev 2010; 16: 265-272
• 120 Torres AR, Cerqueira AT. Exhibitionism treated with clomipramine. Am J Psychiatry 1993; 150: 1274
• 121 Khan O, Ferriter M, Huband N. et al. Pharmacological interventions for those who have sexually offended or are at risk of offending. Cochrane Database Syst Rev 2015; CD007989.pub2: Cd007989
• 122 Li Y, Hai S, Zhou Y. et al. Cholinesterase inhibitors for rarer dementias associated with neurological conditions. Cochrane Database Syst Rev 2015; CD009444.pub3: CD009444
• 123 Group HIotHS. European Huntingtonʼs Disease N. A randomized, double-blind, placebo-controlled study of latrepirdine in patients with mild to moderate Huntington disease. JAMA Neurol 2013; 70: 25-33
• 124 Bohlen S, Ekwall C, Hellstrom K. et al. Physical therapy in Huntingtonʼs disease – toward objective assessments?. Eur J Neurol 2013; 20: 389-393
• 125 Quinn L, Debono K, Dawes H. et al. Task-specific training in Huntington disease: a randomized controlled feasibility trial. Phys Ther 2014; 94: 1555-1568
• 126 Rollnik JD. [Huntingtonʼs disease]. Nervenarzt 2015; 86: 725-735
• 127 Frese S, Petersen JA, Ligon-Auer M. et al. Exercise effects in Huntington disease. J Neurol 2017; 264: 32-39
• 128 Saft C, Andrich JE, Müller T. et al. Oral and dental health in Huntingtonʼs disease – an observational study. BMC Neurol 2013; 13: 114
• 129 Saft C, Lauter T, Kraus PH. et al. Dose-dependent improvement of myoclonic hyperkinesia due to Valproic acid in eight Huntington’s Disease patients: a case series. BMC Neurol 2006; 28: 11