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Diagnosis and management of patients with polyneuropathy

Author/s: 
Mirian, A., Aljohani, Z., Grushka, D., Florendo-Cumbermack, A.

Polyneuropathy is a common neurologic condition with an overall prevalence in the general population of about 1%–3%, increasing to roughly 7% among people older than 65 years. Polyneuropathy has many causes, and can present in many different ways; thus, it requires a logical clinical approach for evaluation, diagnosis and management. We review the approach to evaluating a patient with polyneuropathy by highlighting important aspects of the history and neurologic examination. We focus on the role of diagnostic investigations for distal symmetric polyneuropathy (DSP), the most common subtype, and an approach to the symptomatic treatment of painful diabetic polyneuropathy (PDN). We draw on practice based guidelines, meta-analyses and systematic reviews, where
possible, as they represent the highest levels of evidence (Box 1).

Keywords 
polyneuropathy diagnosis Pain treatment therapy

The relationship between exacerbated diabetic peripheral neuropathy and metformin treatment in type 2 diabetes mellitus

Author/s: 
Hashem, Manal Mohammed, Esmael, Ahmed, Nassar, Abdelfattah Kasem, El-Sherif, Mohammed

Metformin-treated diabetics (MTD) showed a decrease in cobalamin, a rise in homocysteine, and methylmalonic acid, leading to accentuated diabetic peripheral neuropathy (DPN). This study aimed to determine whether or not metformin is a risk factor for DPN. We compared MTD to non-metformin-treated diabetics (NMTD) clinically using the Toronto Clinical Scoring System (TCSS), laboratory (methylmalonic acid, cobalamin, and homocysteine), and electrophysiological studies. Median homocysteine and methylmalonic acid levels in MTD vs. NMTD were 15.3 vs. 9.6 µmol/l; P < 0.001 and 0.25 vs. 0.13 µmol/l; P = 0.02, respectively with high statistical significance in MTD. There was a significantly lower plasma level of cobalamin in MTD than NMTD. Spearman's correlation showed a significant negative correlation between cobalamin and increased dose of metformin and a significant positive correlation between TCSS and increased dose of metformin. Logistic regression analysis showed that MTD had significantly longer metformin use duration, higher metformin dose > 2 g, higher TCSS, lower plasma cobalamin, and significant higher homocysteine. Diabetics treated with metformin for prolonged duration and higher doses were associated with lower cobalamin and more severe DPN.

Keywords 
diabetes, type 2 metformin insulin Metformin Treatment

Ameliorative Effects Of N-Acetylcysteine As Adjunct Therapy On Symptoms Of Painful Diabetic Neuropathy

Author/s: 
Heidari, N., Sajedi, F., Mohammadi, Y., Mirjalili, M., Mehrpooya, M.

PURPOSE:

Painful diabetic neuropathy (PDN) is a variant of diabetic peripheral neuropathy which is highly prevalent and distressing in diabetic patients. Despite its high burden, the optimal treatment of PDN has remained a clinical challenge. To explain the emergence and maintenance of PDN, increasing attention has been focused on dimensions of inflammation and oxidative toxic stress (OTS). Accordingly, the aim of this study was to investigate the effects of oral N-acetylcysteine (NAC), an agent with known anti-oxidant and anti-inflammatory effects, as an adjunct therapy in patients suffering from PDN.

PATIENTS AND METHODS:

113 eligible patients with type 2 diabetes suffering from PDN were randomly assigned to either the pregabalin + placebo or pregabalin + NAC group for 8 weeks (pregabalin at a dose of 150 mg per day, NAC and matched placebo at doses of 600 mg twice a day). Mean pain score was evaluated at baseline, week 1, 2, 4, 6, and 8 of the study based on the mean 24 hr average pain score, using an 11-point numeric rating scale (NRS). As secondary efficacy measures, mean sleep interference score (SIS) resulting from PDN, responder rates, Patient Global Impression of Change (PGIC), Clinical Global Impression of Change (CGIC), and safety were also assessed. Additionally, serum levels of total antioxidant capacity (TAC), total thiol groups (TTG), catalase activity (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), nitric oxide (NO), and malondialdehyde (MDA) were assessed at baseline and at the end of the study.

RESULTS:

Ninety patients completed the eight-week course of the study. The decrease in mean pain scores and mean sleep interference score in pregabalin + NAC group was greater in comparison with pregabalin + placebo group (p value<0.001 in both conditions). Moreover, more responders (defined as ≥50% reduction in mean pain score from baseline to end-point) were observed in the pregabalin + NAC group, in comparison with pregabalin + placebo group (72.1% vs 46.8%). More improvement in PGIC and CGIC from baseline to the end of the study was reported in pregabalin + NAC group. Oral NAC had minimal adverse effects and was well tolerated in almost all patients. Furthermore, in respect to OTS biomarkers, adjuvant NAC significantly decreased serum level of MDA and significantly increased serum levels of SOD, GPx, TAC, and TTG.

CONCLUSION:

The pattern of results suggests that compared to placebo and over a time period of 8 weeks, adjuvant NAC is more efficacious in improving neuropathic pain associated with diabetic neuropathy than placebo. Ameliorative effects of NAC on OTS biomarkers demonstrated that NAC may alleviate painful symptoms of diabetic neuropathy, at least in part by its antioxidant effects.

Keywords 
N-acetylcysteine oxidative stress painful diabetic neuropathy pregabalin

Duloxetine: Painful Diabetic Neuropathy and Fibromyalgia

Author/s: 
Sultan, Asquad, Gaskell, Helen, Derry, Sheena, Moore, R. Andrew

Clinical bottom line

There is good evidence that duloxetine at doses of 60 or 120 mg daily helps some people with painful diabetic neuropathy or fibromyalgia. The NNT for one person to have at least 50% pain relief is about 6. Nausea, somnolence constipation and reduced appetite are common adverse events.

Keywords 
duloxetine hydrochloride Fibromyalgia diabetic neuropathies
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