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We are grateful for the five constructive contributions to the discussion. Prof. Brandl points out that a neurological microcirculation disorder, which among other things occurs as chronic ischemia in about 20% of the patients with peripheral arterial disease (PAD), should not be overlooked. Ischemia of the peripheral nerve often leads to neuropathic pain. In addition to anamnesis and examination, quantitative sensory testing (QST) and, if necessary, determination of intraepidermal nerve fiber density are helpful. In addition to drug therapy with non-opioid and opioid analgesics, or antidepressants and anticonvulsants, maintaining mobility of the foot and toes may be used to some degree as a prophylaxis, if necessary. However, controlled studies are lacking. Alternatively, there may be an indication for the use of spinal cord stimulation (SCS) with good evidence (1).

Dr. Pillhatsch suggests that pre-stages of diabetes may be associated with polyneuropathy, and that there is no direct correlation between optimization of management of type 2 diabetes and diabetic neuropathy. Indeed, this unexpected difference to type 1 diabetes–associated neuropathy underscores that these diseases must have distinct pathomechanisms, despite similar clinical syndromes (2). The differences in pathomechanisms concern the polyol pathway, the hexosamine pathway, protein kinase C isoforms, accumulation of “advanced glycation end products” (AGEs), and the proportion of glucose and fatty acids in diabetic nerves. Nonetheless, intensified diabetes therapy is important for vascular-associated and retinal events.

Dr. Maurer supplements the spectrum of polyneuropathy with post-actinic, severe plexus polyneuropathies and, in particular, with the important topic of delayed damage from radiation therapy (3). Performing a nerve biopsy is of course a surgical and diagnostic procedure, but in the hands of an experienced surgeon does not present a high risk. No matter the positive therapeutic effects shown for a drug therapy in studies, the individual risk profile and possible side effects must of course be taken into account when giving information to a patient.

Dr. Gürkov comments on the importance of amiodarone-induced vestibulopathy in the differential diagnosis of a gait disorder. Therefore, in our opinion, the vestibulo-ocular reflex should be checked routinely during the initial clinical examination.

Dr. von Au recalls an important but rare cause of neuropathy, namely leprosy. This is mostly a multilocular distribution of hypoesthetic areas, which provides an important differential diagnosis to a classic distal symmetric polyneuropathy syndrome.

DOI: 10.3238/arztebl.2018.0297

Prof. Dr. med. Benedikt Schoser
Friedrich-Baur Institute, Department of Neurology
Ludwig-Maximilians-Universität München
benedikt.schoser@med.uni-muenchen.de

Prof. Dr. med. Claudia Sommer
Department of Neurology, University Hospital Würzburg

PD Dr. med. Christian Geber, DRK Pain Center Mainz

Prof. Dr. med. Raimund Forst, University Orthopedic Clinic Erlangen

Prof. Dr. med. Peter Young, Department of Sleep Medicine and Neuromuscular Disorders, Münster University

Prof. Dr. med. Frank Birklein, Klinik für Neurologie,
Universitätsklinikum Mainz

Conflict of interest statement

Prof. Schoser has received conference fee and travel cost reimbursement as well as speaking honoraria from CSL Behring.

Prof. Sommer has received consultant honoraria from AirLiquide, Astellas, Baxter/Baxalta, CSL Behring, and Genzyme, LFB; speaking honoraria from Baxalta, Genzyme, Kedrion, Novartis, and Pfizer; and study support (third-party funds) from Kedrion and CSL Behring.

Dr. Geber has received consultant honoraria from Pfizer.

Prof. Young has received consultant honoraria, reimbursement for conference fees and travel costs, and study support (third-party funds) from Pharnext.

Prof. Birklein has received speaking honoraria from Pfizer and study support (third-party funds) from Pfizer and Lilly.

Prof. Forst declares that no conflict of interest exists.

1.
Lang PM.: Ischämische schmerzhafte Neuropathie. Der Nervenarzt 2015; 86: 151–5 CrossRef MEDLINE
2.
Callaghan BC, Hur J, Feldman EL: Diabetic neuropathy: one disease or two? Curr Opin Neurol 2012; 25: 536–41 CrossRef MEDLINE PubMed Central
3.
Pradat PF, Delanian S: Late radiation injury to peripheral nerves. Handb Clin Neurol 2013; 115: 743–58 CrossRef MEDLINE
4.
Sommer C, Geber C, Young P, Forst R, Birklein F, Schoser B: Polyneuropathies—etiology, diagnosis, and treatment options. Dtsch Arztebl Int 2018; 115: 83–90 VOLLTEXT
1.Lang PM.: Ischämische schmerzhafte Neuropathie. Der Nervenarzt 2015; 86: 151–5 CrossRef MEDLINE
2.Callaghan BC, Hur J, Feldman EL: Diabetic neuropathy: one disease or two? Curr Opin Neurol 2012; 25: 536–41 CrossRef MEDLINE PubMed Central
3.Pradat PF, Delanian S: Late radiation injury to peripheral nerves. Handb Clin Neurol 2013; 115: 743–58 CrossRef MEDLINE
4.Sommer C, Geber C, Young P, Forst R, Birklein F, Schoser B: Polyneuropathies—etiology, diagnosis, and treatment options. Dtsch Arztebl Int 2018; 115: 83–90 VOLLTEXT

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