Treatment for IgG and IgA paraproteinaemic neuropathy

Paraproteinaemic neuropathy refers to those neuropathies associatedwith amonoclonal gammopathy or paraprotein. Themost common of these present with a chronic, predominantly sensory, symmetrical neuropathy, similar to chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) but with relatively more sensory involvement, both clinically and neurophysiologically. The optimal treatment for neuropathies associated with IgG and IgA monoclonal gammopathy of uncertain significance is not known. This is an update of a review first published in 2007. Objectives To assess the effects of any treatment for IgG or IgA paraproteinaemic peripheral neuropathy. Search methods On 18 January 2014 we searched the Cochrane NeuromuscularDisease Group Trials Specialized Register, CENTRAL, MEDLINE and EMBASE. We also checked bibliographies for controlled trials of treatments for IgG or IgA paraproteinaemic peripheral neuropathy. We checked clinical trials registries for ongoing studies in November 2014. Selection criteria We considered for inclusion randomised controlled trials (RCTs) and quasi-RCTs using any treatment for IgG or IgA paraproteinaemic peripheral neuropathy. We excluded people with IgM paraproteins. We excluded people where the monoclonal gammopathy was considered secondary to an underlying disorder. We included participants of any age with a diagnosis of monoclonal gammopathy of uncertain significance with a paraprotein of the IgG or IgA class and a neuropathy. Included participants were not required to fulfil specific electrophysiological diagnostic criteria. Data collection and analysis We used standard Cochrane methodology to select studies, extract data and analyse results. One trial author provided additional data and clarification. Main results We identified one RCT, with 18 participants, that fulfilled the predetermined inclusion criteria. The trial compared plasma exchange to sham plasma exchange in participants with IgG or IgA paraproteinaemic neuropathy over a three-week follow-up period. We identified four other studies but these were not RCTs or quasi-RCTs. The included RCT did not report our predefined primary outcome measure, change in disability six months after randomisation. The trial revealed a modest benefit of plasma exchange in the weakness component of the Neuropathy Disability Score (NDS, now the Neuropathy Impairment Score); the mean improvement with plasma exchange was 17 points (95% confidence interval (CI) 5.2 to 28.8 points) versus 1 point (95% CI -7.7 to 9.7 points) in the sham exchange group at three weeks' follow-up (mean difference (MD) 16.00; 95% CI 1.37 to 30.63, low quality evidence). There was no statistically significant difference in the overall NDS (MD 18.00; 95% CI -2.03 to 38.03, low quality evidence), vibration thresholds or neurophysiological indices. Adverse events were not reported. The trial was at low risk of bias overall, although limitations of trial size and duration reduce the quality of the evidence in support of its conclusions. Authors' conclusions The evidence fromRCTs for the treatment of IgGor IgA paraproteinaemic neuropathy is currently inadequate. More RCTs of treatments are required. These should have adequate follow-up periods and contain larger numbers of participants, perhaps through multicentre collaboration, considering the relative infrequency of this condition. Observational or open trial data provide limited support for the use of treatments such as plasma exchange, cyclophosphamide combined with prednisolone, intravenous immunoglobulin, and corticosteroids. These interventions show potential therapeutic promise but the potential benefits must be weighed against adverse effects. Their optimal use and the long-term benefits need to be considered and validated with well-designed RCTs

Effect of enzyme therapy and prognostic factors in 69 adults with Pompe disease: An open-label single-center study

Abstract. Background: Enzyme replacement therapy (ERT) in adults with Pompe disease, a progressive neuromuscular disorder, is of promising but variable efficacy. We investigated whether it alters the course of disease, and also identified potential prognostic factors. Methods. Patients in this open-label single-center study were treated biweekly with 20 mg/kg alglucosidase alfa. Muscle strength, muscle function, and pulmonary function were assessed every 3-6 months and analyzed using repeated-measures ANOVA. Results: Sixty-nine patients (median age 52.1 years) were followed for a median of 23 months. Muscle strength increased after start of ERT (manual muscle testing 1.4 percentage points per year (pp/y); hand-held dynamometry 4.0 pp/y; both p < 0.001). Forced vital capacity (FVC) remained stable when measured in upright, but declined in supine position (-1.1 pp/y; p = 0.03). Muscle function did not improve in all patients (quick motor function test 0.7 pp/y; p = 0.14), but increased significantly in wheelchair-independent patients and those with mild and moderate muscle weakness.Relative to the pre-treatment period (49 patients with 14 months pre-ERT and 22 months ERT median follow-up), ERT affected muscle strength positively (man

Clinical features and predictors for disease natural progression in adults with Pompe disease: A nationwide prospective observational study

Background: Due partly to physicians' unawareness, many adults with Pompe disease are diagnosed with great delay. Besides, it is not well known which factors influence the rate of disease progression, and thus disease outcome. We delineated the specific clinical features of Pompe disease in adults, and mapped out the distribution and severity of muscle weakness, and the sequence of involvement of the individual muscle groups. Furthermore, we defined the natural disease course and identified prognostic factors for disease progression. Methods. We conducted a single-center, prospective, observational study. Muscle strength (manual muscle testing, and hand-held dynamometry), muscle function (quick motor function test), and pulmonary function (forced vital capacity in sitting and supine positions) were assessed every 3-6 months and analyzed using repeated-measures ANOVA. Results: Between October 2004 and August 2009, 94 patients aged between 25 and 75 years were includ

Beneficial effect of an ACTH4 9 analogue on experimentally induced diabetic autonomic neuropathy in the eye of the rat under general anaesthesia

While peripheral polyneuropathy is a well-known complication in diabetes mellitus, and the subject of a great deal of study, the clinical importance of autonomic diabetic neuropathy is increasingly recognised. Using an animal model, where the pupil diameter of the eye serves as a parameter of autonomic function, we produced an age and weight curve of pupil diameter and studied the development of autonomic neuropathy in rats with streptozotocin-induced diabetes. We show that diabetic rats develop significantly (P <0.009) smaller pupils compared with controls, most probably due to a defective sympathetic input, caused by sympathetic neuropathy. Treatment with the neurotrophic peptide Org 2766, a synthetic ACTH4-9 analogue, prevents the occurrence of this sympathetic neuropathy, as the pupil diameters in the ACTH4-9 analogue-treated group are significantly (P <0.05) larger than the pupils of placebo-treated rats, and are comparable to the pupil diameters of the rats in the control grou

Experimentally induced autonomic neuropathy: beneficial effect of a systemic ACTH4-9 analogue on oculomotor nerve regeneration

While the regenerating capacity of peripheral nerves has been the subject of intensive study, little is known about the regenerative capacity of the autonomic nervous system. Using an animal model, where the pupil diameter of the eye in the rat serves as a parameter of autonomic function, we studied whether systemic treatment with the neuropeptide Org 2766, a synthetic ACTH4-9, analogue, facilitates the functional recovery of parasympathetic nerve fibres after transection, and after a crush lesion of the oculomotor nerve. By simply photographing the rat's pupil under standardised conditions, we show that sectioning the oculomotor nerve leads to an immediate mydriasis, followed by spontaneous regeneration in 30 days. Systemic treatment with an ACTH4-9 analogue had no effect on the rate or quality of recovery. However, systemic treatment with an ACTH4-9 analogue after a crush lesion of the oculomotor nerve (spontaneous regeneration time 16 days) did enhance the speed of recovery of the parasympathetic nerve fibres in the oculomotor nerve, especially in the initial stages of regeneration. We conclude that the animal model used in this study is valuable for studying the regenerative capacity of the autonomic nervous system and the influence of neurotrophic peptides on autonomic neuropathies. Evidence is presented that synthetic ACTH4-9 analogue exerts beneficial neurotrophic effects, not only in peripheral sensorimotor neuropathies but also in autonomic neuropathie

Neural influences on the iris of diabetic rats and effect of oculomotor nerve crush

Using an animal model where the pupil diameter of the eye in anaesthetized and dark-adapted rats serves as a parameter of autonomic function, we studied the functional recovery of the parasympathetic nerve fibres in the oculomotor nerve after a crush lesion in rats with streptozotocin-induced diabetes compared with normal controls. Prior to the crush lesion, diabetic rats develop significantly (P <0.001) smaller pupils compared with controls, and this occurs early in the course of the diabetes mellitus. As the difference in pupil diameter between control and diabetic rats persists immediately after the crush lesion, when the nervous control of the pupil is entirely due to sympathetic nerves, we suggest that the reduction in pupil diameter is due to a sympathetic neuropathy. Furthermore, we show that the functional recovery of the parasympathetic input to the iris after a crush lesion of the oculomotor nerve is not as good in diabetic rats as it is in normal control rat

Experimentally-induced autonomic neuropathy : beneficial effect of a topical ACTH4-9 analogue on oculomotor nerve regeneration

Melanocortins, peptides related to corticotropin (ACTH) and melanocyte-stimulating hormone, are known to exert beneficial neurotrophic effects in peripheral sensorimotor neuropathies. This has been demonstrated after both systemic and local administration of the peptides. By photographing the rat's pupil under standardized conditions, the authors have previously shown that systemic administration of a synthetic ACTH4-9 analogue can also be beneficial in autonomic neuropathies. The present study demonstrates that topical application of a synthetic ACTH4-9 analogue incorporated in a two-component fibrin glue enhances the speed of recovery of the parasympathetic nerve fibers in the oculomotor nerve after a crush lesion. This may have implications for future use in neurosurgery

Surgery for Symptomatic Neuroma: Anatomic Distribution and Predictors of Secondary Surgery

BACKGROUND: Neuromas are caused by irregular and disorganized regeneration following nerve injury. Many surgical techniques have been described to address neuroma with varying success. The aim of this study was to evaluate predictive factors for secondary surgery after initial surgical intervention for symptomatic neuroma along with a description of the anatomical distribution of surgically treated symptomatic neuromas. METHODS: Five hundred ninety-eight patients with 641 neuromas that underwent primary surgery for neuroma were identified retrospectively. The diagnosis of neuroma was based on physical examination and patient history in the medical charts. Neuromas were treated by excision, implantation in muscle or bone, excision with direct neurorrhaphy with or without nerve grafting, or other treatments. RESULTS: The rate of secondary surgery for neuroma was 7.8 percent, and secondary operations were performed at a median of 16.1 months. Excision alone or excision with implantation into bone or muscle had higher rates of secondary surgery compared with excision and direct neurorrhaphy with or without nerve graft. Neuromas were located in the upper extremity (49.61 percent), lower extremity (46.65 percent), and the groin/trunk (3.74 percent). CONCLUSIONS: Symptomatic neuromas are located predominantly in the extremities, and surgery can improve pain, with low secondary surgery rates. Excision with direct neurorrhaphy with or without nerve grafting was associated with lower reoperation rates. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III