Corneal Confocal Microscopy Detects Small Fibre Neuropathy in Patients with Upper Gastrointestinal Cancer and Nerve Regeneration in Chemotherapy Induced Peripheral Neuropathy.

Maryam Ferdousi,Ioannis Nikolaos Petropoulos,Mitra Tavakoli,Imaan Malik,Rayaz Ahmed Malik,Hassan Fadavi,Wasat Mansoor,Shazli Azmi,Andrew Marshall,Georgios Ponirakis

doi:10.1371/journal.pone.0139394

Abstract

There are multiple neurological complications of cancer and its treatment. This study assessed the utility of the novel non-invasive ophthalmic technique of corneal confocal microscopy in identifying neuropathy in patients with upper gastrointestinal cancer before and after platinum based chemotherapy. In this study, 21 subjects with upper gastrointestinal (oesophageal or gastric) cancer and 21 healthy control subjects underwent assessment of neuropathy using the neuropathy disability score, quantitative sensory testing for vibration perception threshold, warm and cold sensation thresholds, cold and heat induced pain thresholds, nerve conduction studies and corneal confocal microscopy. Patients with gastro-oesophageal cancer had higher heat induced pain (P = 0.04) and warm sensation (P = 0.03) thresholds with a significantly reduced sural sensory (P<0.01) and peroneal motor (P<0.01) nerve conduction velocity, corneal nerve fibre density (CNFD), nerve branch density (CNBD) and nerve fibre length (CNFL) (P<0.0001). Furthermore, CNFD correlated significantly with the time from presentation with symptoms to commencing chemotherapy (r = -0.54, P = 0.02), and CNFL (r = -0.8, P<0.0001) and CNBD (r = 0.63, P = 0.003) were related to the severity of lymph node involvement. After the 3rd cycle of chemotherapy, there was no change in any measure of neuropathy, except for a significant increase in CNFL (P = 0.003). Corneal confocal microscopy detects a small fibre neuropathy in this cohort of patients with upper gastrointestinal cancer, which was related to disease severity. Furthermore, the increase in CNFL after the chemotherapy may indicate nerve regeneration.

Highlights

Neurological complications of cancer include direct tumour compression or infiltration, paraneoplastic neurological syndromes (PNS), metabolic and nutritional deficiencies and chemotherapy induced peripheral neuropathy (CIPN) [1]
Nerve morphology can be rapidly assessed using in vivo corneal confocal microscopy (IVCCM), and over the past decade we have pioneered the use of this technique to assess peripheral neuropathy in a range of neuropathies including diabetic neuropathy [12,13,14], Idiopathic small fibre neuropathy (ISFN) [15], Fabry’s disease [16] and Charcot-Marie-Tooth Neuropathy Type 1 (CMT1A) [17]
We provide the first report of a detailed study relating CCM to clinical and neurological evaluation in patients with upper GI cancer before and after platinum based chemotherapy

Summary

Introduction

Neurological complications of cancer include direct tumour compression or infiltration, paraneoplastic neurological syndromes (PNS), metabolic and nutritional deficiencies and chemotherapy induced peripheral neuropathy (CIPN) [1]. Nerve morphology can be rapidly assessed using in vivo corneal confocal microscopy (IVCCM), and over the past decade we have pioneered the use of this technique to assess peripheral neuropathy in a range of neuropathies including diabetic neuropathy [12,13,14], Idiopathic small fibre neuropathy (ISFN) [15], Fabry’s disease [16] and Charcot-Marie-Tooth Neuropathy Type 1 (CMT1A) [17]. Others have deployed it in non-length dependent and autoimmune neuropathies [18, 19]. We have undertaken a detailed study using CCM in patients with upper GI cancer before and after receiving chemotherapy

Methods

Results

Conclusion