A peripheral pathway to restless legs syndrome? Clues from familial amyloid polyneuropathy.
BACKGROUND
The relationship between restless legs syndrome (RLS) and peripheral neuropathy remains unclear. In order to clarify this relationship, we investigated if RLS is increased in familial amyloid polyneuropathy related to transthyretin (TTR-FAP) and investigated factors associated with RLS in this population.


METHODS
RLS frequency was compared between TTR-FAP patients and controls. Secondly, TTR-FAP patients with and without RLS were compared regarding demographic and clinical characteristics.


RESULTS
RLS frequency was significantly increased in TTR-FAP, with 18/98 (18.4%) cases contrasting with 5/104 (4.8%) controls (p-value 0.002). This difference remained significant after adjusting for confounders. In TTR-FAP patients, female sex (p-value 0.037), obesity (p-value 0.036) and weight excess (p-value 0.048) were associated with RLS, contrary to other classical RLS risk factors.


CONCLUSIONS
RLS frequency is increased in TTR-FAP, thus supporting an association between RLS and neuropathy. This may represent a peripheral pathway in RLS pathogenesis. Furthermore, our results suggest that female sex and obesity/weight excess may be risk factors for RLS development among TTR-FAP patients.
Department of Neurology, Hospital de Santa Maria, Lisboa, Portugal; Clinical Pharmacology Unit, Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisboa, Portugal; St Georges University London, London, United Kingdom. Electronic address: tiagoteodoro@gmail.com.
Tiago
T
Teodoro
Department of Neurology, Hospital de Santa Maria, Lisboa, Portugal.
Pedro
P
Viana
Clinical Pharmacology Unit, Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisboa, Portugal.
Daisy
D
Abreu
Department of Neurology, Hospital de Santa Maria, Lisboa, Portugal; Translational and Clinical Physiology Unit, Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisboa, Portugal.
Isabel
I
Conceição
Department of Neurology, Hospital de Santa Maria, Lisboa, Portugal; EEG/Sleep Laboratory, Hospital de Santa Maria, Lisboa, Portugal.
Rita
R
Peralta
Department of Neurology, Hospital de Santa Maria, Lisboa, Portugal; Clinical Pharmacology Unit, Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisboa, Portugal.
Joaquim J
JJ
Ferreira
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D028227:Amyloid Neuropathies, Familial / Q000150:complications / Q000453:epidemiology* / Q000503:physiopathology; D015992:Body Mass Index; D015897:Comorbidity; D015986:Confounding Factors, Epidemiologic; D005260:Female; D006801:Humans; D000090463:Iron Deficiencies; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers / Q000473:pathology; D050177:Overweight / Q000453:epidemiology*; D010525:Peripheral Nerves / Q000503:physiopathology*; D011228:Prealbumin / Q000378:metabolism; D015995:Prevalence; D012148:Restless Legs Syndrome / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology*; D012307:Risk Factors; D055815:Young Adult
D011228:Prealbumin
Familial amyloid polyneuropathy; Neuropathy; Pathogenesis; Restless legs syndrome