Rayaz Malik

Diabetic neuropathies: Update on definitions, diagnostic criteria, estimation of severity, and treatments

Preceding the joint meeting of the 19th annual Diabetic Neuropathy Study Group of the European Association for the Study of Diabetes (NEURODIAB) and the 8th International Symposium on Diabetic Neuropathy in Toronto, Canada, 13–18 October 2009, expert panels were convened to provide updates on classification, definitions, diagnostic criteria, and treatments of diabetic peripheral neuropathies (DPNs), autonomic neuropathy, painful DPNs, and structural alterations in DPNs.

W1.3 Corneal confocal microscopy: a novel non-invasive means to diagnose neuropathy in patients with Fabry disease

Methods: We restrospectively revised patients with MMN diagnosed in our EMG laboratory during last 15 years with a follow-up higher than 5 years and analyze clinical and electrophysiological findings in 3 stages of the disease evolution. We quantified the number and sites of definite conduction blocks (CB), probable CB, anomalous temporal dispersion (ATD), and axonal degeneration (AD). We established the diagnosis of definite MMN, probable MMN and MADSAM according to AANEM criteria at the moment of diagnosis, after 2 years and 5 or more years of monitoring. Results: We found 11 patients (7 male:4 female, mean age of 43 years) with MMN followed between 5 and 11 years. A significant decrease of definite and probable CB and increase of nerves with AD has been found. Sensory involvement appeared in 3 patients, one of them with worst clinical and electrophysiological evolution. Five patients changed the diagnosis during the follow-up. Conclusions: In the follow-up of patients with MMN during more than 5 years there are changes in the pathophysiology of nerve injury (definite and probable CB, ATD and AD), in sensory involvement and diagnosis according to criteria of AANEM. This fact complicates the diagnosis and monitoring of this disease.

EP 41. Corneal confocal microscopy in chronic inflammatory demyelinating polyneuropathies

Objective There is an unmet need for better diagnostic tools to further delineate clinical subsets of heterogeneous chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) to facilitate treatment decisions. Corneal confocal microscopy (CCM) is a non-invasive and reproducible nerve imaging technique. This study evaluates the potential of CCM as a diagnostic surrogate in CIDP and MMN. Methods In a cross-sectional prospective approach 182 patients and healthy controls were studied using CCM to quantify corneal nerve damage and immune cell infiltration. Results Patients with CIDP and MMN had a reduction in corneal nerve fiber (CNF) measures and an increase in corneal immune cell infiltrates. In CIDP, CNF parameters decreased with increasing duration of disease. The number of dendritic cells in proximity to corneal nerve fibers was increased in patients with early disease and correlated with the degree of motor affection. A further reduction in CNF parameters and an increase in non-dendritic cells was observed in patients with painful neuropathy. In CIDP patients with anti-neuronal antibodies the number of non-dendritic cells was increased. Interpretation Our findings suggest that corneal nerve fiber loss may reflect severity of neuropathy and quantification of distinct cells around the CNF plexus may help in stratifying CIDP subtypes, clinical course and disease activity. However, further longitudinal studies are required before CCM can be considered as a valid surrogate end point for patients with CIDP and MMN.

FC41.1Corneal confocal microscopy: A non-invasive surrogate marker of small nerve fibre damage in patients with small fiber neuropathy

Background: Repetitive transcranial magnetic stimulation (rTMS) represents an important therapeutic tool and it has been suggested that some of these therapeutic effects are mediated through enhanced cortical inhibition (CI). Therefore, this study endeavored to explore the effects of several different rTMS stimulus conditions on inhibition and excitability in the human motor cortex. Methods: Twelve healthy control subjects participated in this study. Subjects were randomly assigned to receive either 1, 10 or 20 Hz rTMS for a total of 900 stimulations or priming rTMS (10 subjects) (i.e., 600 6 Hz stimuli followed by 600 1 Hz stimuli) all separated by 1 week. CI was indexed using single pulse and paired TMS paradigms including short interval cortical inhibition (SICI) and cortical silent period (CSP), respectively. Cortical excitability was indexed using the rest EMG during the rTMS stimulus train and motor threshold and motor evoked potential (MEP) size after the stimulus train. Results: Across all stimulus conditions there was a significant increase in the CSP. There was also a significant increase in SICI, particularly in those subjects with reduced baseline SICI. There was no significant difference in the extent of inhibition (i.e., CSP, SICI) induced by different stimulus conditions. There was also a strong correlation between rest EMG activity and stimulation frequency during the stimulus train but no significant change in measures of excitability (e.g., MT and MEP size) after the stimulus train. Conclusions: These findings suggest that rTMS increases inhibition following an rTMS course and that higher rTMS frequency stimulation results in greater cortical excitability during the stimulus train but not afterward. Future studies designed to replicate these initial findings as well as assessing the effects of repeated administration of rTMS courses on CI are warranted to elucidate potential novel therapeutic mechanisms involved in this exciting new treatment.

Vascular Changes and Diabetic Neuropathy

Human diabetic neuropathy is characterized by dysfunction of the somatic and autonomic nervous systems. A simple definition was recently agreed on at an international consensus meeting: “The presence of symptoms and/or signs of peripheral nerve dysfunction in people with diabetes after the exclusion of other causes” (1). The clinical manifestations, underlying pathology, and etiology of the diabetic neuropathies are varied. Classification has previously been based on pathologic and etiologic considerations, but a clinical classification of the neuropathies is favored (Table 1) (2). For research, epidemiologic, and clinical trial purposes, a more detailed definition that includes subclinical neuropathy is required (3,4). The Rochester Diabetic Neuropathy Study has established a paradigm for clinical trial design (3) that includes the following factors: (1) neuropathic symptoms (neuropathy symptom score [NSS]); (2) neuropathic deficits (neuropathy impairment score [NIS]); (3) motor/sensory nerve conduction velocity (MS NCV); (4) quantitative sensory testing (QST); and (5) autonomic function testing (AFT). The minimum criteria for a diagnosis of neuropathy required two or more abnormalities among the criteria listed, with at least one criterion including three or five. Staging was as follows: NO, no neuropathy (minimum criteria unfulfilled); Nl, asymptomatic neuropathy (NSS = 0); N2, symptomatic neuropathy; and N3, disabling neuropathy.