Painless diabetic motor neuropathy: a variant of diabetic lumbosacral radiculoplexus Neuropathy?

OBJECTIVE: Occasionally, diabetic patients develop painless, lower-limb, motor predominant neuropathy. Whether this is a variant of diabetic lumbosacral radiculoplexus neuropathy (DLRPN) (a painful disorder from ischemic injury and microvasculitis), a variant of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) or another disorder is unsettled. Here, we characterize the clinical and pathological features of painless diabetic motor predominant neuropathy. METHODS: We identified patients with this syndrome who underwent nerve biopsy. We compared pathological features to 33 DLRPN and 25 CIDP biopsies. RESULTS: 23 patients were identified (22 had type 2 diabetes mellitus); 12 men; median age 62.2 years (range 36-78); median weight loss 30 pounds (range 0-100). Overall, the clinical features were similar to DLRPN except painless patients had more symmetrical and upper limb involvement, with slower progression and more severe impairment. Physiological testing demonstrated pan-modality sensory loss, autonomic abnormalities and axonal polyradiculoneuropathies. Nerve biopsies were similar to DLPRN showing ischemic injury (multifocal fiber loss [11/23], perineural thickening [18/23], injury neuroma [11/23], neovascularization [17/23]) and evidence of altered immunity and microvasculitis (epineurial perivascular inflammation [23/23], prior bleeding [11/23], vessel wall inflammation [15/23], and microvasculitis [3/23]). In contrast, CIDP biopsies did not show ischemic injury or microvasculitis but revealed demyelination and onion-bulbs. INTERPRETATION: 1) Painless diabetic motor neuropathy is painless DLRPN and not CIDP and is caused by ischemic injury and microvasculitis. 2) The clinical features of painless DLRPN are different from typical DLPRN being more insidious and symmetrical with slower evolution. 3) The slower evolution may explain the lack of pain.

Good nutritional control may prevent polyneuropathy after bariatric surgery.

Previously we showed that peripheral neuropathy occurs after bariatric surgery and was associated with malnutrition (mainly sensory polyneuropathy). This study asks whether a multidisciplinary approach to bariatric surgery lowers risk for developing peripheral neuropathy. We performed a retrospective cohort study of all patients with bariatric surgery at the Mayo Clinic between 1985 and 2002. Patients underwent intensive nutritional management before and after surgery. Potential risk factors were analyzed using life-table methods (Cox regression). Univariate analysis showed the following risk factors: increased serum glycosylated hemoglobin and triglycerides, prolonged hospitalization, postoperative gastrointestinal symptoms, and nausea and vomiting. Peripheral neuropathy occurred less frequently (7% vs. 13%, P < 0.01) and specifically the sensory polyneuropathy subtype (1% vs. 7%, P < 0.0001) than in our prior cohort. A systematic, multidisciplinary approach of intensive nutritional management before and after surgery with frequent follow-up greatly decreased development of peripheral neuropathy (especially sensory polyneuropathy) in patients receiving bariatric surgery.

Challenges in design of multicenter trials: end points assessed longitudinally for change and monotonicity.

OBJECTIVE: Assessing clinimetric performance of diabetic sensorimotor polyneuropathy (DSPN) end points in single and multicenter trials. RESEARCH DESIGN AND METHODS: Assessed were placebo-treated patients with DSPN in the Viatris and Eli Lilly trials and an epidemiologic cohort. RESULTS: Test reproducibility in clinical trial cohorts (r(I) approximately 0.7-0.85) approached that in the epidemiologic cohort (r(I) approximately 0.85-0.95). Associations between pairs of end points explained <10% of the variability of data (sometimes 15-35%), being higher in the epidemiologic cohort and the Viatris trial than in the Lilly trial. Most end points did not show monotonic worsening over 4 years. However, sural nerve amplitude and peroneal motor conduction velocity did. A nerve conduction score (Sigma 5 NC nds [5 attributes of nerve conduction expressed as normal deviates]) did not show monotonic worsening in established DSPN. In the epidemiologic cohort followed for 9.5 years, monotonic worsening of small magnitude occurred for sural amplitude, vibration detection threshold, and especially for composite quantitative sensation. CONCLUSIONS: The main reason why it is difficult to demonstrate monotonic worsening of neuropathic end points appears to be a very slow worsening of DSPN, a placebo effect for symptoms and signs, and measurement noise. Demonstrating disease progression in controlled trials of DSPN is more likely when 1) patients with developing rather than established DSPN are selected, 2) type 1 diabetic patients are preferentially recruited, 3) patients are selected who cannot or will not achieve ideal glycemic control, 4) end points chosen are known to show monotonic worsening, and 5) a restricted number of centers and expert examiners (trained, certified, using standard approaches, and reference values and interactive surveillance of tests) are used.