Highlights
- •The prevalence of large fiber neuropathy in idiopathic PD is estimated to be 16%.
- •The role of levodopa on the development of PN is still unclear.
- •Large studies with neurophysiologically confirmed neuropathy in PD are needed.
Abstract
Background
Parkinson's disease (PD) has been associated with peripheral neuropathy (PN). PN has
been demonstrated in some rare genetic forms of PD (e.g. PARK2 mutations) but has
also been linked to levodopa exposure.
Objective
The aim of this systematic review is to clarify any evidence of peripheral nervous
system involvement in idiopathic PD.
Methods
A systematic computer-based literature search was conducted on PubMed database.
Findings
The pooled estimate of the prevalence of large fiber PN in PD was 16.3% (based on
1376 patients). The pooled estimate of the prevalence of biopsy-proven small fiber
neuropathy was 56.9% (based on 72 patients).
Large fiber PN in PD is in the majority of cases distal, symmetrical, axonal and predominantly
sensory. There are, however, few reports of chronic idiopathic demyelinating polyneuropathy
and very occasional cases of acute neuropathies. Although nerve conduction studies
have been performed in the majority of the studies, they included only a limited number
of nerves, mainly in the lower limbs.
There is little evidence to support a direct link between levodopa treatment and the
development of PN in idiopathic PD. In the majority of the cases PN has been linked
to abnormalities in vitamin B12, methylmalonic acid or fasting homocysteine levels.
Additional aetiological risk factors for PN may be responsible for any apparent link
between PD and PN.
Conclusions
Large-scale prospective studies with long-term follow-up with detailed baseline assessments
are needed in order to understand the natural history of PN in PD, both on clinical
and neurophysiological parameters.
Keywords
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References
- Chronic idiopathic axonal polyneuropathy: a systematic review.J. Neurol. 2016 Oct; 263: 1903-1910
- Epidemiology of peripheral neuropathy.J. Neurol. Neurosurg. Psychiatry. 1997; 62: 310-318
- Prevalence of peripheral neuropathy in the Parsi community of Bombay.Neurology. 1991; 41: 1315-1317
- Chronic symmetric symptomatic polyneuropathy in the elderly: a field screening investigation in two Italian regions. I. Prevalence and general characteristics of the sample.Neurology. 1995; 45: 1832-1836
- Prevalence of polyneuropathy in the general middle-aged and elderly population.Neurology. 2016 Nov 1; 87: 1892-1898
- Depression and chronic pain in the elderly: links and management challenges.Clin. Interv. Aging. 2017; 21: 709-720
- Reduced amplitude of the sural nerve sensory action potential in PARK2 patients.Neurology. 2005 Aug 9; 65: 459-462
- Neuropathy and levodopa in Parkinson's disease: evidence from a multicenter study.Mov. Disord. 2013 Sep; 28: 1391-1397
- Controlled release levodopa/carbidopa (Sinemet CR4) in Parkinson's disease—an open evaluation of efficacy and safety.Aust. NZ J. Med. 1991 Aug; 21: 397-400
- Is chronic levodopa therapy associated with distal symmetric polyneuropathy in Parkinson's disease?.Parkinsonism Relat. Disord. 2013 Mar; 19: 391-393
- Levodopa, methylmalonic acid, and neuropathy in idiopathic Parkinson disease.Ann. Neurol. 2010 Jul; 68: 28-36
- Small (autonomic) and large fiber neuropathy in Parkinson disease and parkinsonism.BMC Neurol. 2016 Aug 17; 16: 139
- The clinical approach to small fibre neuropathy and painful channelopathy.Pract. Neurol. 2014 Dec; 14: 368-379
- Skin biopsy for diagnosis of small fiber neuropathy: a critically appraised topic.Neurologist. 2010 Jan; 16: 61-63
- Small fiber neuropathy in Parkinson's disease: a clinical, pathological and corneal confocal microscopy study.Parkinsonism Relat. Disord. 2015 Dec; 21: 1454-1460
- Evidence for small fiber neuropathy in early Parkinson's disease.Parkinsonism Relat. Disord. 2016 Jul; 28: 94-99
- Dermal sheet preparations in the evaluation of dermal innervation in Parkinson's disease and multiple system atrophy.J. Cutan. Pathol. 2009 Mar; 36: 296-301
- Sensory deficit in Parkinson's disease: evidence of a cutaneous denervation.Brain. 2008 Jul; 131: 1903-1911
- Neuropathy in idiopathic Parkinson disease: an iatrogenic problem?.Ann. Neurol. 2011 Feb; 69: 427-428
- Cutaneous neuropathy in Parkinson's disease: a window into brain pathology.Acta Neuropathol. 2014 Jul; 128: 99-109
- Skin biopsy and I-123 MIBG scintigraphy findings in idiopathic Parkinson's disease and parkinsonism: a comparative study.Mov. Disord. 2015 Jun; 30: 986-989
- α-Synuclein in cutaneous autonomic nerves.Neurology. 2013 Oct 29; 81: 1604-1610
- Neuropathy as a potential complication of levodopa use in Parkinson's disease.Mov. Disord. 2008 Oct 15; 23: 1850-1859
- A case series of peripheral neuropathy in patients with Parkinson's disease.Ann. Neurol. 2010 Dec; 68: 973-975
- DADS neuropathy associated with anti-TNF-α therapy.BMJ Case Rep. 2015; (2015 Nov 25)https://doi.org/10.1136/bcr-2015-211781
- Parkinson's disease associated with myasthenia gravis and rheumatoid arthritis.Neurol. Sci. 2014 May; 35: 797-799
- Neuroleptic malignant syndrome and acute motor axonal neuropathy after Campylobacter jejuni infection.Neurophysiol. Clin. 2009 Aug; 39: 135-138
- Guillain-Barre/CIDP-like neuropathy in two parkinsonian patients following intestinal levodopa/carbidopa treatment.Parkinsonism Relat. Disord. 2014 Jan; 20: 125-127
- Subacute axonal neuropathy in Parkinson's disease with cobalamin and vitamin B6 deficiency under duodopa therapy.Mov. Disord. 2010 Aug 15; 25: 1748-1752
- Severe ataxic polyneuropathy associated with chronic levodopa use in Parkinson's disease.Parkinsonism Relat. Disord. 2013 Sep; 19: 847-849
- Long-term levodopa/carbidopa intestinal gel in advanced Parkinson's disease.J. Neurol. 2014 Mar; 261: 561-569
- Intra-axonal protein aggregation in the peripheral nervous system.J. Peripher. Nerv. Syst. 2014 Mar; 19: 44-49
- Skin nerve α-synuclein deposits: a biomarker for idiopathic Parkinson disease.Neurology. 2014 Apr 15; 82: 1362-1369
- Peripheral nerve involvement and severity of motor disorder in Parkinson's disease: a correlational study.Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech Repub. 2009 Mar; 153: 59-62
- Neuropathy in Parkinson's disease patients with intestinal levodopa infusion versus oral drugs.PLoS One. 2013 Jun 20; 8: e66639
- Neuropathy in Parkinson disease: prevalence and determinants.Neurology. 2011 Nov 29; 77: 1947-1950
- Prevalence and features of peripheral neuropathy in Parkinson's disease patients under different therapeutic regimens.Parkinsonism Relat. Disord. 2014 Jan; 20: 27-31
- Reversible encephalopathy and axonal neuropathy in Parkinson's disease during duodopa therapy.Mov. Disord. 2009 Nov 15; 24: 2293-2294
- Polyneuropathy while on duodenal levodopa infusion in Parkinson's disease patients: we must be alert.J. Neurol. 2012 Aug; 259: 1668-1672
- Intraduodenal levodopa-carbidopa intestinal gel infusion improves both motor performance and quality of life in advanced Parkinson's disease.J. Clin. Neurosci. 2016 Mar; 25: 41-45
- Prospective assessment of peripheral neuropathy in Duodopa-treated parkinsonian patients.Acta Neurol. Scand. 2014 Jan; 129: e1-e5
- Levodopa, vitamins, ageing and the neuropathy of Parkinson's disease.J. Neurol. 2013 Nov; 260: 2844-2848
- Transcutaneous port for continuous duodenal levodopa/carbidopa administration in Parkinson's disease.Mov. Disord. 2011 Feb 1; 26: 331-334
- Levodopa and neuropathy risk in patients with Parkinson disease: effect of COMT inhibition.Parkinsonism Relat. Disord. 2016 Jun; 27: 81-84
- Malnutritional neuropathy under intestinal levodopa infusion.J. Neural. Transm. (Vienna). 2012 Mar; 119: 369-372
- Subacute peripheral neuropathy under duodopa therapy without cobalamin deficiency and despite supplementation.J. Neural. Transm. (Vienna). 2014 Oct; 121: 1269-1272
- Peripheral neuropathy associated with levodopa-carbidopa intestinal infusion: a long-term prospective assessment.Eur. J. Neurol. 2016 Mar; 23: 501-509
- Levodopa/carbidopa intestinal gel therapy for advanced Parkinson disease: AN early toxic effect for small nerve fibers?.Muscle Nerve. 2016 Nov; 54: 970-972
- Non-motor symptoms profile and burden in drug naïve versus long-term Parkinson's disease patients.J. Parkinsons Dis. 2014; 4: 541-547
- Non-motor symptoms burden in treated and untreated early Parkinson's disease patients: argument for non-motor subtypes.Eur. J. Neurol. 2015 Aug; 22: 1145-1150
- The range and nature of non-motor symptoms in drug-naive Parkinson's disease patients: a state-of-the-art systematic review.NPJ Parkinson's Dis. 2015 Jul 9; 1: 15013
- Treatment with levodopa can affect latent vitamin B 12 and folic acid deficiency. Patients with Parkinson disease runt the risk of elevated homocysteine levels.Lakartidningen. 2003 Aug; 100: 2674-2677
- An overview of pain in Parkinson's.in: An Introduction to Pain and Its Relation to Nervous System Disorders. 2. Wiley Publishers, 2016 May: 387
- Sural/radial amplitude ratio in the diagnosis of mild axonal polyneuropathy.Muscle Nerve. 1997 Oct; 20: 1236-1241
- Tibial nerve motor conduction to the abductor hallucis.Am. J. Phys. Med. Rehabil. 1999 Nov–Dec; 78: S15-S20
- Painful sensory neuropathy: prospective evaluation using skin biopsy.Neurology. 1999 Nov 10; 53: 1641-1647
- Small fiber neuropathy: a common and important clinical disorder.J. Neurol. Sci. 2004 Dec 15; 227: 119-130
Article info
Publication history
Published online: May 11, 2017
Accepted:
May 10,
2017
Received in revised form:
May 9,
2017
Received:
January 23,
2017
Identification
Copyright
© 2017 Elsevier B.V. All rights reserved.
