Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Neurological Sciences
Published in: Neurological Sciences 7/2021

01-07-2021 | Multiple Sclerosis | Review Article

Peripheral nervous system in multiple sclerosis—understanding the involvement via autonomic nervous system

Authors: Ivan Adamec, Magdalena Krbot Skorić, Mario Habek

Published in: Neurological Sciences | Issue 7/2021

Login to get access

Abstract

Aim

The aim of this review is to summarize the clinical and paraclinical findings that demonstrate that multiple sclerosis (MS) affects the peripheral nervous system (PNS) as well as the central nervous system (CNS). Methods: Narrative review.

Results

MS is traditionally defined as a chronic demyelinating immune-mediated disease of the CNS. However, there is emerging evidence that MS is a disease that does not solely affect the CNS but can manifest with PNS involvement as well. Several pathology studies have reported on signs of demyelination in the PNS, as well as on structural and functional involvement of the PNS in persons with MS (pwMS). From the functional aspect, several studies have shown autonomic nervous system (ANS) involvement in the form of sudomotor dysfunction measured with quantitative sudomotor axon reflex test (QSART) in different stages of MS, adding to the growing body of evidence that indicate PNS involvement in MS. In this review the clinical, pathological, neurophysiological, and imaging findings that demonstrate that MS affects the PNS as well as the CNS are summarized, with the emphasis on the ANS abnormalities.

Conclusion

Further large-scale research is needed in order to fully understand the frequency and importance of PNS affection in MS.
Literature
1.
2.
Salvetti M, Giovannoni G, Aloisi F (2009) Epstein-Barr virus and multiple sclerosis. Curr Opin Neurol 22:201–206PubMedCrossRef
3.
Stys PK, Zamponi GW, van Minnen J, Geurts JJ (2012) Will the real multiple sclerosis please stand up? Nat Rev Neurosci 13:507–514 Erratum in: Nat Rev Neurosci. 2012;13:597PubMedCrossRef
4.
Oudejans E, Luchicchi A, Strijbis EMM, Geurts JJG, van Dam AM (2021) Is MS affecting the CNS only?: Lessons from clinic to myelin pathophysiology. Neurol Neuroimmunol Neuroinflamm 8(1):e914PubMedCrossRef
5.
6.
7.
Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin FD, Montalban X, O'Connor P, Sandberg-Wollheim M, Thompson AJ, Waubant E, Weinshenker B, Wolinsky JS (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69:292–302PubMedPubMedCentralCrossRef
8.
Jende JME, Hauck GH, Diem R, Weiler M, Heiland S, Wildemann B, Korporal-Kuhnke M, Wick W, Hayes JM, Pfaff J, Pham M, Bendszus M, Kollmer J (2017) Peripheral nerve involvement in multiple sclerosis: demonstration by magnetic resonance neurography. Ann Neurol 82:676–685PubMedCrossRef
9.
Adamec I, Crnošija L, Junaković A, Krbot Skorić M, Habek M (2018) Progressive multiple sclerosis patients have a higher burden of autonomic dysfunction compared to relapsing remitting phenotype. Clin Neurophysiol 129:1588–1594PubMedCrossRef
10.
Habek M, Crnošija L, Lovrić M, Junaković A, Krbot Skorić M, Adamec I (2016) Sympathetic cardiovascular and sudomotor functions are frequently affected in early multiple sclerosis. Clin Auton Res 26:385–393PubMedCrossRef
11.
Mendell JR, Kolkin S, Kissel JT, Weiss KL, Chakeres DW, Rammohan KW (1987) Evidence for central nervous system demyelination in chronic inflammatory demyelinating polyradiculoneuropathy. Neurology 37:1291–1294PubMedCrossRef
12.
Strahuber A (1903) Ueber degenerations-und proliferationsvorgange bei multipler sklerose des nervensystems. Beitr Z Path Anat U Z Allg Pathol 33:409
13.
Hasson J, Terry RD, Zimmerman HM (1958) Peripheral neuropathy in multiple sclerosis. Neurology 8:503–510PubMedCrossRef
14.
Schoene WC, Carpenter S, Behan PO, Geschwind N (1977) ‘Onion bulb’ formations in the central and peripheral nervous system in association with multiple sclerosis and hypertrophic polyneuropathy. Brain 100:755–773PubMedCrossRef
15.
16.
Poser CM (1987) The peripheral nervous system in multiple sclerosis. A review and pathogenetic hypothesis. Neurol Sci 79:83–90CrossRef
17.
Pollock M, Calder C, Allpress S (1977) Peripheral nerve abnormality in multiple sclerosis. Ann Neurol 2:41–48PubMedCrossRef
18.
Caputo D, Ghezzi A, Zaffaroni M, Zibetti A (1982) Polyneuritic onset in multiple sclerosis. Ital J Neurol Sci 3:355–357PubMedCrossRef
19.
Ramirez-Lassepas M, Tulloch JW, Quinones MR, Snyder BD (1992) Acute radicular pain as a presenting symptom in multiple sclerosis. Arch Neurol 49:255–258PubMedCrossRef
20.
Lassmann H, Budka H, Schnaberth G (1981) Inflammatory demyelinating polyradiculitis in a patient with multiple sclerosis. Arch Neurol 38:99–102PubMedCrossRef
21.
Etemadifar M, Roomizadeh P, Abtahi SH et al (2012) Linkage of multiple sclerosis and Guillain-Barre syndrome: a population-based survey in Isfahan, Iran. Autoimmune Dis 2012:232139PubMedPubMedCentral
22.
Kawamura N, Yamasaki R, Yonekawa T (2013) Anti-neurofascin antibody in patients with combined central and peripheral demyelination. Neurology 81:714–722PubMedCrossRef
23.
Cortese A, Franciotta D, Alfonsi E, Visigalli N, Zardini E, Diamanti L, Prunetti P, Osera C, Gastaldi M, Berzero G, Pichiecchio A, Piccolo G, Lozza A, Piscosquito G, Salsano E, Ceroni M, Moglia A, Bono G, Pareyson D, Marchioni E (2016) Combined central and peripheral demyelination: clinical features, diagnostic findings, and treatment. J Neurol Sci 363:182–187PubMedCrossRef
24.
Frohman TC, Davis SL, Beh S, Greenberg BM, Remington G, Frohman EM (2013) Uhthoff’s phenomena in MS-clinical features and pathophysiology. Nat Rev Neurol 9:535–540PubMedCrossRef
25.
Cheshire WP Jr (2016) Thermoregulatory disorders and illness related to heat and cold stress. Auton Neurosci 196:91–104PubMedCrossRef
26.
Huang M, Morris NB, Jay O, Davis SL (2014) Thermoregulatory dysfunction in multiple sclerosis patients during moderate exercise in a thermoneutral environment. FASEB J 28(Supplement 1):1104.17
27.
Anlar O, Tombul T, Kisli M (2003) Peripheral sensory and motor abnormalities in patients with multiple sclerosis. Electromyogr Clin Neurophysiol 43:349–351PubMed
28.
Khan A, Kamran S, Ponirakis G, Akhtar N, Khan R, George P, Babu BM, Ibrahim FM, Petropoulos IN, Canibano BG, Wilins SS, Deleu D, Shuaib A, Malik RA (2018) Peripheral neuropathy in patients with multiple sclerosis. PLoS One 13(3):e0193270PubMedPubMedCentralCrossRef
29.
Merchut MP, Gruener G (1993) Quantitative sensory threshold testing in patients with multiple sclerosis. Electromyogr Clin Neurophysiol 33:119–124PubMed
30.
Hopf HC (1965) Leitgeschwindigkeit motorischer Nerven bei der Multiplen Sklerose und unter dem Einfluss hoher Cortison Medikation. Deutsche Zeitschrift fur Nervenheilkunde 187:522–526PubMedCrossRef
31.
32.
Misawa S, Kuwabara S, Mori M, Hayakawa S, Sawai S, Hattori T (2008) Peripheral nerve demyelination in multiple sclerosis. Clin Neurophysiol 119:1829–1833PubMedCrossRef
33.
Ayromlou H, Mohammad-Khanli H, Yazdchi-Marandi M et al (2013) Electrodiagnostic evaluation of peripheral nervous system changes in patients with multiple sclerosis. Malays J Med Sci 20:32–38PubMedPubMedCentral
34.
Görgülü Ü, Ergün U, Ertuğrul L (2020) Peripheral nerve conductions in relapsing remitting multiple sclerosis (RRMS) patients. J Clin Neurosci 74:93–97PubMedCrossRef
35.
Grana EA, Kraft GH (1994) Electrodiagnostic abnormalities in patients with multiple sclerosis. Arch Phys Med Rehabil 75:778–782PubMedCrossRef
36.
Habek M, Adamec I, Barun B, Crnošija L, Gabelić T, Krbot Skorić M (2017) Clinical neurophysiology of multiple sclerosis. Adv Exp Med Biol 958:129–139PubMedCrossRef
37.
Skorić MK, Adamec I, Mađarić VN, Habek M (2014) Evaluation of brainstem involvement in multiple sclerosis. Can J Neurol Sci 41:346–349PubMedCrossRef
38.
Snooks SJ, Swash M (1985) Motor conduction velocity in the human spinal cord: slowed conduction in multiple sclerosis and radiation myelopathy. J Neurol Neurosurg Psychiatry 48:1135–1139PubMedPubMedCentralCrossRef
39.
Mills KR, Murray NM (1986) Neurophysiological evaluation of associated demyelinating peripheral neuropathy and multiple sclerosis: a case report. J Neurol Neurosurg Psychiatry 49:320–323PubMedPubMedCentralCrossRef
40.
Adamec I, Habek M (2013) Autonomic dysfunction in multiple sclerosis. Clin Neurol Neurosurg 115(Suppl 1):S73–S78PubMedCrossRef
41.
Habek M, Crnošija L, Gabelić T, Barun B, Adamec I, Junaković A, Ruška B, Pavičić T, Krbot Skorić M (2019) Longitudinal assessment of autonomic nervous system in patients with first demyelinating event suggestive of multiple sclerosis. Eur J Neurol 26:1377–1383PubMedCrossRef
42.
Saari A, Tolonen U, Pääkkö E et al (2019) Sweating impairment in patients with multiple sclerosis. Acta Neurol Scand 120:358–363CrossRef
43.
Davis SL, Wilson TE, Vener JM, Crandall CG, Petajan JH, White AT (2005) Pilocarpine-induced sweat gland function in individuals with multiple sclerosis. J Appl Physiol 1985:1740–1744CrossRef
44.
Novak P (2011) Quantitative autonomic testing. J Vis Exp 19:2502
45.
Krbot Skorić M, Crnošija L, Gabelić T, Barun B, Adamec I, Junaković A, Pavičić T, Ruška B, Habek M (2019) Autonomic symptom burden can predict disease activity in early multiple sclerosis. Mult Scler Relat Disord 28:250–255PubMedCrossRef
46.
Drulović J, Gavrilović A, Crnošija L et al (2017) Validation and cross-cultural adaptation of the COMPASS-31 in Croatian and Serbian patients with multiple sclerosis. Croat Med J 58:342–348PubMedCrossRef
47.
Fisniku LK, Brex PA, Altmann DR, Miszkiel KA, Benton CE, Lanyon R, Thompson AJ, Miller DH (2008) Disability and T2 MRI lesions: a 20-year follow-up of patients with relapse onset of multiple sclerosis. Brain 131(Pt 3):808–817PubMedCrossRef
48.
Blackmore D, Siddiqi ZA (2017) Diagnostic criteria for small fiber neuropathy. J Clin Neuromuscul Dis 18:125–131PubMedCrossRef
49.
Ohl K, Tenbrock K, Kipp M (2016) Oxidative stress in multiple sclerosis: central and peripheral mode of action. Exp Neurol 277:58–67PubMedCrossRef
50.
Latini A, Pereira PJS, Couture R, Campos MM, Talbot S (2019) Oxidative stress: neuropathy, excitability, and neurodegeneration. Oxidative Med Cell Longev 2019:2715326CrossRef
51.
Saidu NEB, Kavian N, Leroy K et al (2019) Dimethyl fumarate, a two-edged drug: current status and future directions. Med Res Rev 39:1923–1952PubMedCrossRef
52.
Kawashiri T, Miyagi A, Shimizu S, Shigematsu N, Kobayashi D, Shimazoe T (2018) Dimethyl fumarate ameliorates chemotherapy agent-induced neurotoxicity in vitro. J Pharmacol Sci 137:202–211PubMedCrossRef
Metadata
Title
Peripheral nervous system in multiple sclerosis—understanding the involvement via autonomic nervous system
Authors
Ivan Adamec
Magdalena Krbot Skorić
Mario Habek
Publication date
01-07-2021
Publisher
Springer International Publishing
Published in
Neurological Sciences / Issue 7/2021
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI
https://doi.org/10.1007/s10072-021-05309-9

Other articles of this Issue 7/2021

Neurological Sciences 7/2021 Go to the issue

COVID-19

Neuro-telehealth for fragile patients in a tertiary referral neurological institute during the COVID-19 pandemic in Milan, Lombardy

Review Article

Primary headache research output and association with socioeconomic factors in Southeast Asia: a bibliometric analysis

Original Article

Does anodal trans-cranial direct current stimulation of the damaged primary motor cortex affects wrist flexor muscle spasticity and also activity of the wrist flexor and extensor muscles in patients with stroke?: a Randomized Clinical Trial

Original Article

GLP-1R activation alters performance in cognitive tasks in a sex-dependent manner

Original Article

Effect of whole-body vibration on freezing and flexibility in Parkinson’s disease—a pilot study

Brief Communication

Device-aided therapies for advanced Parkinson disease: insights from an international survey