Autonome Diagnostik bei der Amyotrophen Lateralsklerose

Zusammenfassung

Bei der Amyotrophen Lateralsklerose (ALS) handelt sich um eine neurodegenerative Multisystemerkrankung. Diese äußert sich neben den motorischen Defiziten mit nicht-motorischen Symptomen. Hierzu zählen auch autonome Störungen, die von veränderter Schweißsekretion über Tachykardie bis zu gastrointestinalen Symptomen reichen. Autonome Störungen können mit verschiedenen Methoden, wie Selbsterhebungsfragebögen, Messung der Herzfrequenzvariabilität, QTc-Intervallmessung, Erhebung der sudomotorischen Funktion und Sonographie des Nervus vagus erfasst werden, die in diesem Artikel dargestellt werden. Die bislang bei der ALS eingesetzten Methoden der autonomen Diagnostik ergeben zum Teil deutlich divergierende Ergebnisse über die Aktivität des Sympathikus im Krankheitsverlauf. Relevante autonome Störungen scheinen zumeist erst im fortgeschrittenen Krankheitsstadium aufzutreten, wobei multizentrische Studien mit longitudinalem Ansatz ausstehen.

Abstract

Amyotrophic lateral sclerosis represents a neurodegenerative multi-systemic disease. Patients present non-motoric symptoms beside the well-known motoric deficits. Autonomic disturbances are part of the non-motoric symptoms, e. g. changes in perspiration, tachycardia and gastrointestinal symptoms. Autonomic disorders are measurable by different methods such as self-assessment questionnaire, heart frequency variability, QTc measurement, sudomotoric function evaluation and vagus nerve sonography, which are presented in this article. The methods of autonomic diagnostics in ALS display divergent results regarding the sympathetic function during course of disease. Relevant autonomic disorders seem to appear in advanced disease. However, longitudinal multicentre studies for autonomic disorders in ALS are pending.

Schlüsselwörter

Amyotrophe Lateralsklerose - Autonome Störung - Nicht-motorische Symptome - Autonomer Sturm

Key words

amyotrophic lateral sclerosis - autonomic disorder - non-motor symptoms - autonomic storm

• Literatur

• 1 Günther R, Richter N, Sauerbier A. et al. Non-Motor Symptoms in Patients Suffering from Motor Neuron Diseases. Front Neurol 2016; 7: 117
• 2 Baltadzhieva R, Gurevich T, Korczyn AD.. Autonomic impairment in amyotrophic lateral sclerosis. Curr Opin Neurol 2005; 18: 487-493
• 3 Shimizu T.. Sympathetic Hyperactivity and Sympathovagal Imbalance in Amyotrophic Lateral Sclerosis. European Neurological Review 2012; 8: 46
• 4 Shimizu T, Hayashi H, Kato S. et al. Circulatory collapse and sudden death in respirator-dependent amyotrophic lateral sclerosis. Journal of the Neurological Sciences 1994; 124: 45-55
• 5 Beswick E, Forbes D, Hassan Z. et al. A systematic review of non-motor symptom evaluation in clinical trials for amyotrophic lateral sclerosis. J Neurol 2022; 269: 411-426
• 6 Low PA.. Composite Autonomic Scoring Scale for Laboratory Quantification of Generalized Autonomic Failure. Mayo Clinic Proceedings 1993; 68: 748-752
• 7 Piccione EA, Sletten DM, Staff NP. et al. Autonomic system and amyotrophic lateral sclerosis. Muscle Nerve 2015; 51: 676-679
• 8 Suarez GA, Opfer-Gehrking TL, Offord KP. et al. The Autonomic Symptom Profile: a new instrument to assess autonomic symptoms. Neurology 1999; 52: 523-528
• 9 Sletten DM, Suarez GA, Low PA. et al. COMPASS 31: a refined and abbreviated Composite Autonomic Symptom Score. Mayo Clinic Proceedings 2012; 87: 1196-1201
• 10 Ozturk R, Karlsson P, Hu X. et al. Stereological and electrophysiological evaluation of autonomic involvement in amyotrophic lateral sclerosis. Neurophysiol Clin 2022;
• 11 Papadopoulou M, Bakola E, Papapostolou A. et al. Autonomic dysfunction in amyotrophic lateral sclerosis: A neurophysiological and neurosonology study. J Neuroimaging 2022; 32: 710-719
• 12 Weise D, Menze I, Metelmann MCF. et al. Multimodal assessment of autonomic dysfunction in amyotrophic lateral sclerosis. Eur J Neurol 2022; 29: 715-723
• 13 İşcan D, Karaaslan MB, Deveci OS. et al. The importance of heart rate variability in predicting cardiac autonomic dysfunction in patients with amyotrophic lateral sclerosis. Int J Clin Pract 2021; 75: e14536
• 14 Hayashi K, Mochizuki Y, Koide R. et al. A Japanese familial ALS patient with autonomic failure and a p.Cys146Arg mutation in the gene for SOD1 (SOD1 ). Neuropathology 2016; 36: 551-555
• 15 Yamada T, Itoh K, Matsuo K. et al. Concomitant alpha-synuclein pathology in an autopsy case of amyotrophic lateral sclerosis presenting with orthostatic hypotension and cardiac arrests. Neuropathology 2014; 34: 164-169
• 16 Pimentel RMM, Macedo H, Valenti VE. et al. Decreased Heart Rate Variability in Individuals With Amyotrophic Lateral Sclerosis. Respir Care 2019; 64: 1088-1095
• 17 Electrophysiology TFotESoCtNA. Heart Rate Variability. Circulation 1996; 93: 1043-1065
• 18 Pavlovic S, Stevic Z, Milovanovic B. et al. Impairment of cardiac autonomic control in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler 2010; 11: 272-276
• 19 Merico A, Cavinato M.. Autonomic dysfunction in the early stage of ALS with bulbar involvement. Amyotroph Lateral Scler 2011; 12: 363-367
• 20 Pinto S, Pinto A, Carvalho de M. Decreased heart rate variability predicts death in amyotrophic lateral sclerosis. Muscle Nerve 2012; 46: 341-345
• 21 Moore E.. Mechanisms and models to predict a QTc effect. The American Journal of Cardiology 1993; 72: B4-B9
• 22 Perticone F, Ceravolo R, Maio R. et al. Heart rate variability and sudden infant death syndrome. Pacing Clin Electrophysiol 1990; 13: 2096-2099
• 23 Asai H, Hirano M, Udaka F. et al. Sympathetic disturbances increase risk of sudden cardiac arrest in sporadic ALS. Journal of the Neurological Sciences 2007; 254: 78-83
• 24 Rosenbohm A, Schmid B, Buckert D. et al. Cardiac Findings in Amyotrophic Lateral Sclerosis: A Magnetic Resonance Imaging Study. Front Neurol 2017; 8: 479
• 25 Pontico M, Brunotti G, Conte M. et al. The prognostic value of 123I-mIBG SPECT cardiac imaging in heart failure patients: a systematic review. J Nucl Cardiol 2022; 29: 1799-1809
• 26 Dimitriu-Leen AC, Scholte AJHA, Jacobson AF.. 123I-MIBG SPECT for Evaluation of Patients with Heart Failure. J Nucl Med 2015; 56 Suppl 4 25S-30S
• 27 Druschky A, Spitzer A, Platsch G. et al. Cardiac sympathetic denervation in early stages of amyotrophic lateral sclerosis demonstrated by 123I-MIBG-SPECT. Acta Neurol Scand 1999; 99: 308-314
• 28 Nomoto N, Orimo S, Uchihara T. et al. Lewy pathology in an autopsy case of FTLD-MND with reduced cardiac MIBG uptake and depletion of cardiac sympathetic fibers. Parkinsonism Relat Disord 2013; 19: 472-473
• 29 Yamamoto T, Tamura N, Nomura K. et al. A case of familial amyotrophic lateral sclerosis with markedly decreased accumulation on 123I-MIBG myocardiac scintigraphy and atonic bladder. Rinsho Shinkeigaku 1996; 36: 341-344
• 30 Tanaka Y, Yamada M, Koumura A. et al. Cardiac sympathetic function in the patients with amyotrophic lateral sclerosis: analysis using cardiac 123I MIBG scintigraphy. J Neurol 2013; 260: 2380-2386
• 31 Beck M, Giess R, Magnus T. et al. Progressive sudomotor dysfunction in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 2002; 73: 68-70
• 32 Cariga P, Catley M, Mathias CJ. et al. Organisation of the sympathetic skin response in spinal cord injury. J Neurol Neurosurg Psychiatry 2002; 72: 356-360
• 33 Shahani BT, Halperin JJ, Boulu P. et al. Sympathetic skin response – a method of assessing unmyelinated axon dysfunction in peripheral neuropathies. J Neurol Neurosurg Psychiatry 1984; 47: 536-542
• 34 Baum P.. Neurophysiologische Diagnostik des autonomen Nervensystems. Das Neurophysiologie-Labor 2018; 40: 95-110
• 35 Ke J-Q, Shao S-M, Zheng Y-Y. et al. Sympathetic skin response and heart rate variability in predicting autonomic disorders in patients with Parkinson disease. Medicine (Baltimore) 2017; 96: e6523
• 36 Oliveira Santos M, Castro I, Castro J. et al. Assessment of sympathetic sudomotor function in amyotrophic lateral sclerosis with electrochemical skin conductance. Clin Neurophysiol 2021; 132: 2032-2036
• 37 Sletten DM, Weigand SD, Low PA.. Relationship of Q-sweat to quantitative sudomotor axon reflex test (QSART) volumes. Muscle Nerve 2010; 41: 240-246
• 38 Everett TH, Doytchinova A, Cha Y-M. et al. Recording sympathetic nerve activity from the skin. Trends Cardiovasc Med 2017; 27: 463-472
• 39 Chen J-J, Lin C, Hsiao W-P. et al. Complex dynamics of skin sympathetic nerve activities as a prognostic predictor for critically ill patients. J Formos Med Assoc 2021; 120: 660-667
• 40 Hagbarth KE, Hallin RG, Hongell A. et al. General characteristics of sympathetic activity in human skin nerves. Acta Physiol Scand 1972; 84: 164-176
• 41 Shindo K, Watanabe H, Ohta E. et al. Sympathetic sudomotor neural function in amyotrophic lateral sclerosis. Amyotroph Lateral Scler 2011; 12: 39-44
• 42 Samara VC, Jerant P, Gibson S. et al. Bowel, bladder, and sudomotor symptoms in ALS patients. Journal of the Neurological Sciences 2021; 427: 117543
• 43 Kim SY, Moon MH, Park HE. et al. Correlation between sudomotor dysfunction and functional status in patients with amyotrophic lateral sclerosis. Annals of Physical and Rehabilitation Medicine 2018; 61: e249-e250
• 44 Kihara M, Takahashi A, Sugenoya J. et al. Sudomotor dysfunction in amyotrophic lateral sclerosis. Funct Neurol 1994; 9: 193-197
• 45 Santos-Bento M, Carvalho de M, Evangelista T. et al. Sympathetic sudomotor function and amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 2001; 2: 105-108
• 46 Pelz J, Weise D.. Sonographie des N. vagus – Methodik und Indikation. Das Neurophysiologie-Labor 2019; 41: 91-98
• 47 Pelz JO, Belau E, Henn P. et al. Sonographic evaluation of the vagus nerves: Protocol, reference values, and side-to-side differences. Muscle Nerve 2018; 57: 766-771
• 48 Grimm A, Décard BF, Schramm A. et al. Ultrasound and electrophysiologic findings in patients with Guillain-Barré syndrome at disease onset and over a period of six months. Clin Neurophysiol 2016; 127: 1657-1663
• 49 Pelz JO, Belau E, Menze I. et al. Correlation between sonographic morphology and function of the cervical vagus nerves. Auton Neurosci 2019; 220: 102552
• 50 Pelz JO, Belau E, Fricke C. et al. Axonal Degeneration of the Vagus Nerve in Parkinson's Disease-A High-Resolution Ultrasound Study. Front Neurol 2018; 9: 951
• 51 Tsukita K, Taguchi T, Sakamaki-Tsukita H. et al. The vagus nerve becomes smaller in patients with Parkinson's disease: A preliminary cross-sectional study using ultrasonography. Parkinsonism Relat Disord 2018; 55: 148-149
• 52 Holzapfel K, Naumann M.. Ultrasound Detection of Vagus Nerve Atrophy in Bulbar Amyotrophic Lateral Sclerosis. J Neuroimaging 2020; 30: 762-765
• 53 Tawfik EA.. Vagus nerve ultrasound in a patient with amyotrophic lateral sclerosis. Muscle Nerve 2016; 54: 978-979
• 54 Toepfer M, Folwaczny C, Klauser A. et al. Gastrointestinal dysfunction in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 1999; 1: 15-19
• 55 Parra-Cantu C, Zaldivar-Ruenes A, Martinez-Vazquez M. et al. Prevalence of Gastrointestinal Symptoms, Severity of Dysphagia, and Their Correlation with Severity of Amyotrophic Lateral Sclerosis in a Mexican Cohort. Neurodegener Dis 2021; 21: 42-47
• 56 Nübling GS, Mie E, Bauer RM. et al. Increased prevalence of bladder and intestinal dysfunction in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener 2014; 15: 174-179
• 57 Arlandis S, Vázquez-Costa JF, Martínez-Cuenca E. et al. Urodynamic findings in amyotrophic lateral sclerosis patients with lower urinary tract symptoms: Results from a pilot study. Neurourol Urodyn 2017; 36: 626-631
• 58 Vázquez-Costa JF, Arlandis S, Hervas D. et al. Clinical profile of motor neuron disease patients with lower urinary tract symptoms and neurogenic bladder. Journal of the Neurological Sciences 2017; 378: 130-136
• 59 Ohno T, Shimizu T, Kato S. et al. Effect of tamsulosin hydrochloride on sympathetic hyperactivity in amyotrophic lateral sclerosis. Autonomic Neuroscience 2001; 88: 94-98
• 60 Shimizu T, Kato S, Hayashi M. et al. Amyotrophic lateral sclerosis with hypertensive attacks: blood pressure changes in response to drug administration. Clin Auton Res 1996; 6: 241-244
• 61 Shimizu T, Hayashi H, Hayashi M. et al. Hyposensitivity of peripheral α-adrenoceptors in respiratordependent amyotrophic lateral sclerosis assessed by intravenous norepinephrine infusion. Clin Auton Res 1995; 5: 165-169
• 62 Brown TE, Beightol LA, Koh J. et al. Important influence of respiration on human R-R interval power spectra is largely ignored. J Appl Physiol (1985) 1993; 75: 2310-2317
• 63 Hecht MJ, Brown CM, Mittelhamm F. et al. Increased hypoxic blood pressure response in patients with amyotrophic lateral sclerosis. Journal of the Neurological Sciences 2003; 213: 47-53
• 64 Kimura F.. Tracheostomy and invasive mechanical ventilation in amyotrophic lateral sclerosis: decision-making factors and survival analysis. Rinsho Shinkeigaku 2016; 56: 241-247
• 65 Spittel S, Maier A, Kettemann D. et al. Non-invasive and tracheostomy invasive ventilation in amyotrophic lateral sclerosis: Utilization and survival rates in a cohort study over 12 years in Germany. Eur J Neurol 2021; 28: 1160-1171