Neuropathological examination suggests impaired brain iron acquisition in restless legs syndrome

@article{Connor2003NeuropathologicalES,
  title={Neuropathological examination suggests impaired brain iron acquisition in restless legs syndrome},
  author={James R. Connor and Philip J. Boyer and Sharon L. Menzies and Bart Dellinger and Richard P. Allen and William G Ondo and Christopher J. Earley},
  journal={Neurology},
  year={2003},
  volume={61},
  pages={304 - 309}
}
Objective: To assess neuropathology in individuals with restless legs syndrome (RLS). Methods: A standard neuropathologic evaluation was performed on seven brains from individuals who had been diagnosed with RLS. The substantia nigra was examined in greater detail for iron staining and with immunohistochemistry for tyrosine hydroxylase and proteins involved in iron management. Five age-matched individuals with no neurologic history served as controls. Results: There were no histopathologic… 

Figures and Tables from this paper

Mitochondrial Ferritin in the Substantia Nigra in Restless Legs Syndrome
TLDR
The results suggest that increased numbers of mitochondria in neurons in RLS and increased FtMt might contribute to insufficient cytosolic iron levels in R LS SN neurons; they are consistent with the hypothesis that energy insufficiency in these neurons may be involved in the pathogenesis of RLS.
Profile of altered brain iron acquisition in restless legs syndrome.
TLDR
There are alterations in the iron management protein profile in restless legs syndrome compared with controls at the site of blood-brain interface suggesting fundamental differences in brain iron acquisition in individuals with restless legs Syndrome.
Altered iron metabolism in lymphocytes from subjects with restless legs syndrome.
TLDR
The findings indicate a balance between input and output with no net iron change but probable overall increase in iron turnover, and that iron management proteins from lymphocytes are at a minimum an alternative and independent marker of cellular iron metabolism.
BRAIN IRON DEFICIENCY IN HUMANS AND ANIMAL MODELS
TLDR
The results establish a protein standard in RLS, provide a comparative analysis of protein-controlled vs. volumetric immunoblot techniques, and argue for a profound loss of iron storage capacity in the brain in R LS, specifically in the early-onset RLS phenotype.
Ferritin subunits in CSF are decreased in restless legs syndrome.
Extracellular Vesicles Reveal Abnormalities In Neuronal Iron Metabolism In Restless Legs Syndrome.
TLDR
Given the neuronal origin and diversity of EV cargo, nEVs provide an important platform for exploring the underlying pathophysiology and possible biomarkers of RLS.
Altered brain iron homeostasis and dopaminergic function in Restless Legs Syndrome (Willis-Ekbom Disease).
MRI-determined regional brain iron concentrations in early- and late-onset restless legs syndrome.
Altered dopaminergic profile in the putamen and substantia nigra in restless leg syndrome.
TLDR
A clear indication of dopamine pathology in RLS is revealed for the first time and cellular regulation of dopamine production that closely matches the data from cellular and animal iron insufficiency models is suggested.
...
...

References

SHOWING 1-10 OF 37 REFERENCES
Striatal dopaminergic function in restless legs syndrome
TLDR
PET findings support the hypothesis of central dopaminergic dysfunction in RLS, and six of the 13 RLS patients had caudate and putamen D2 binding reduced below the control range.
Iron status and restless legs syndrome in the elderly.
TLDR
Iron deficiency, with or without anaemia, is an important contributor to the development of RLS in elderly patients, and iron supplements can produce a significant reduction in symptoms.
Iron and the restless legs syndrome.
TLDR
These data are consistent with those from a prior unblinded study and suggest that RLS patients will have fewer symptoms if they have ferritin levels greater than 50 mcg/l.
Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB)
TLDR
This work identified progressive disabling mental impairment progressing to dementia as the central feature of DLB, and identified optimal staining methods for each of these and devised a protocol for the evaluation of cortical LB frequency based on a brain sampling procedure consistent with CERAD.
SPECT imaging of striatal pre- and postsynaptic dopaminergic status in restless legs syndrome with periodic leg movements in sleep
TLDR
The hypothesis that a central DA dysfunction is involved in the physiopathology of RLS-PLMS is supported by the results of the SPECT studies, which revealed a significantly lower binding in patients of both RLS and PLMS.
Cerebral amyloid angiopathy without and with cerebral hemorrhages: A comparative histological study
TLDR
The features of brains from patients with CAA that are most consistently related to cerebral hemorrhage are a severe degree of CAA and the presence of fibrinoid necrosis, with or without microaneurysms.
Abnormalities in CSF concentrations of ferritin and transferrin in restless legs syndrome
TLDR
The presence of reduced ferritin and elevated transferrin levels in CSF is indicative of low brain iron in patients with idiopathic RLS.
Microscopic R2* mapping of reduced brain iron in the Belgrade rat
TLDR
Surprisingly, it is found that the same brain regions are affected (ie, the globus pallidus, substantia nigra, and cerebellar dentate nucleus), which suggests a much more extensive role for these structures in regulating overall brain iron homeostasis.
Iron status and neural functioning.
TLDR
Future studies with more specific measures of neurodevelopment in iron-deficient human infants, and animal models, will allow investigators to more clearly define causal roles of brain iron in neural development and functioning.
...
...