Peripheral neuropathy has also been associated with RLS. A recent case-control study (Hattan E et al 2009) in a Quebec population examined 245 patients with a diagnosis of peripheral neuropathy and 245 age and gender matched controls. The authors considered a positive response to three of the four essential criteria to be 'screen-positive'. All 'screen-positive' patients were subsequently evaluated by a blinded movement disorders specialist. Of the 245 peripheral neuropathy patients, 26.5% were 'screen-positive', compared to 10.2% of controls. Confirmation by neurologist, however, revealed only 46% of the 'screen-positive' peripheral neuropathy patients were felt to truly have a diagnosis of RLS compared to 80% of the 'screen-positive' control patients. After this diagnostic confirmation, the overall prevalence of RLS did not differ between the peripheral neuropathy patients and the control group. The prevalence of RLS was evaluated in a cohort of 99 Italian patients with acquired diabetic peripheral neuropathy (Gemignani et al, 2007). Using IRRLSG diagnostic criteria, RLS was found to be present in a third of the patients in this study population (33/99). The authors reported that of the various forms of diabetic neuropathy represented within this population, small fiber sensory neuropathy was more common than other forms. A prominent symptom associated with RLS was 'burning feet'. The authors suggest that RLS may be triggered peripherally by abnormal sensory inputs from small fibers. A case series of 12 patients with essential mixed cryoglobulinemia and associated peripheral neuropathy reported a frequency of RLS, using pre-2003 diagnostic measures, of one third (4/12) (Gemignani et al, 1997).
A recent report (Bachmann CG et al 2010) suggest response to specific stimuli may be able to distinguish between primary RLS and RLS secondary to small fiber neuropathy. In this study of 21 primary RLS patients and 13 patients with secondary RLS related to small fiber neuropathy, the authors describe thermal hypoesthesia to cold and warm in those with secondary RLS compared to both the primary RLS study patients and controls. They also suggest support for the RLS pathogenesis concept of central disinhibition of nociceptive pathways which might be induced by conditioning afferent input from damaged small fiber neurons in secondary RLS.
Restless legs syndrome has been reported as increased in prevalence in German hereditary spastic paresis patients (Sperfeld AD, et al, 2007) and in Argentinian patients with Fabry's disease (Dominguez RO, et al, 2007). RLS has also been reported to be present in 18.1% of
227 Charcot-Marie Tooth disease patients compared to 234 controls with a 5.6% prevalence. RLS severity was correlated with worse sleep quality and reduced health-related quality of life measures. Variation in prevalence was not observed between subtypes of Charcot-Marie Tooth disease, but women were more severely affected by RLS than male patients (Boentert M, et al 2010). A series of 28 patients with Friedreich's Ataxia were surveyed for prevalence of RLS with 32% meeting diagnostic criteria (Synofzik M et al, 2011). In a population of 28 chronic inflammatory demyelinating polyneuropathy (CIDP), a prevalence of 39.3% for RLS was found, compared to 7.1% prevalence in age and gender matched control patients. Isolated case reports of RLS symptomatology following development of hyperparathyroidism (Agarwal P et al, 2008), administration of interferon therapy (LaRochelle JS, et al, 2004), development of multifocal motor neuropathy (Lo Coco D, et al, 2009), and Guillain-Barre syndrome have been reported (Marin LF, et al, 2010). Additionally, a case report has been published reporting a patient who experienced remission of severe RLS following excision of multiple foot neuromata (Lettau LA, et al 2010). The question has also been raised as to whether RLS in seen in a higher prevalence in patients with Parkinson's Disease. This has been addressed in an Italian population of 118 Parkinson's Disease outpatients using a case-control study design. The authors report a failure to demonstrate increased prevalence of RLS in the Parkinson's patients in comparison to age and gender matched control patients. They further acknowledge the RLS prevalence assessment may be impeded by the concurrent treatment of Parkinson's Disease with dopaminomimetic drugs, which may also be expected to impact on RLS symptomatology (Calzetti et al, 2009). Another study from the Netherlands in 269 non-demented Parkinson's Disease patients, found RLS to be present in 11% of patients. RLS severity was noted to correlate positively with Parkinson's Disease severity. RLS was also significantly more common in male patients than female. The authors note the similar prevalence of RLS in their study population to the general population and submit that this could potentially relate to concurrent dopaminergic therapy. They also suggest that in view of the relationship of severity of RLS to severity of Parkinson's Disease related primarily non-dopaminergic symptoms, that non-dopaminergic systems may play a role in any potential relationship between RLS and Parkinson's Disease (Verbaan D, et al, 2010). In a reverse style of assessment, 23,119 participants in the Health Professional Follow-up study who were free of diabetes and arthritis were surveyed. The IRRLSG diagnostic criteria were applied and concurrent diagnoses of Parkinson's Disease were investigated. The adjusted odds ratios for Parkinson's Disease in men with RLS symptoms with frequency from 5-14 times per month was 1.1, and in those with a frequency of RLS of 15 or more times per month the odds ratio was higher at 3.09. The authors concluded that men with RLS symptomatology were more likely to have concurrent Parkinson's Disease (Gao X, et al, 2010).
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