Four-Repeat Tauopathies: Current Management and Future Treatments.
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ABSTRACT:
SUBMITTER: VandeVrede L
PROVIDER: S-EPMC7851277 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionProgressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), are the most common four-repeat tauopathies (4RT), and both frequently occur with varying degree of Alzheimer's disease (AD) copathology. Intriguingly, patients with 4RT and patients with AD are at opposite ends of the wakefulness spectrum-AD showing reduced wakefulness and excessive sleepiness whereas 4RT showing decreased homeostatic sleep. The neural mechanisms underlying these distinct phenotypes in the comorbid condition of 4RT and AD are unknown. The objective of the current study was to define the alpha oscillatory spectrum, which is prominent in the awake resting-state in the human brain, in patients with primary 4RT, and how it is modified in comorbid AD-pathology.MethodIn an autopsy-confirmed case series of 4R-tauopathy patients (n = 10), whose primary neuropathological diagnosis was either PSP (n = 7) or CBD (n = 3), using high spatiotemporal resolution magnetoencephalography (MEG), we quantified the spectral power density within alpha-band (8-12 Hz) and examined how this pattern was modified in increasing AD-copathology. For each patient, their regional alpha power was compared to an age-matched normative control cohort (n = 35).ResultPatients with 4RT showed increased alpha power but in the presence of AD-copathology alpha power was reduced.ConclusionsAlpha power increase in PSP-tauopathy and reduction in the presence of AD-tauopathy is consistent with the observation that neurons activating wakefulness-promoting systems are preserved in PSP but degenerated in AD. These results highlight the selectively vulnerable impacts in 4RT versus AD-tauopathy that may have translational significance on disease-modifying therapies for specific proteinopathies.
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Project description:BackgroundPermanent postsurgical hypoparathyroidism (POSH) is a major complication of anterior neck surgery in general and of thyroid surgery in particular. Depending on diagnostic criteria, up to 10% of patients undergoing bilateral thyroid surgery develop POSH. This leads to a multitude of symptoms that decrease the quality of life and burden the healthcare provision through complex needs for medication and treatment of specific complications, such as seizures and laryngospasm.MethodsNarrative review of current medical treatments for POSH and of the experience accumulated with parathyroid allotransplantation.ResultsIn most patients, POSH is controlled with regular use of calcium supplements and active vitamin D analogues but a significant proportion of patients continue to experience severe symptoms requiring repeated emergency admissions. Replacement therapy with synthetic PTH compounds (PTH1-34, Natpara® and PTH1-84, teriparatide, Forsteo®) has been assessed in multicentre trials, but the use of this medication is restricted by costs and concerns related to the risk of development of osteosarcoma. Based on recent case reports of successful allotransplantation of parathyroid tissue between siblings, there is renewed interest in this technique. Data on selection of donors, parathyroid cell preparation before allotransplantation, site and timing of transplantation, need for immunosuppression and long-term outcomes are reviewed.ConclusionA prospective trial to assess the efficacy of parathyroid allotransplantation in patients with severely symptomatic protracted post-surgical hypoparathyroidism is warranted.
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