Dementia with Lewy Bodies
Marc E. Agronin in Alzheimer's Disease and Other Dementias, 2014
Other dementias that have a clinical resemblance to DLB due to their prominent extra-pyramidal features include progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and multiple system atrophy (MSA). Because PSP and CBD both involve significant frontal lobe dysfunction, they are described in Chapter 7. MSA is a degenerative neurological disorder that is characterized by parkinsonism, upper motor neuron impairment, cerebellar dysfunction, and dysautonomia (e.g., urinary incontinence, sexual dysfunction, orthostatic hypotension). The average age at onset is in the mid-50s, with a mean survival of 6–7 years (Wenning, Geser, Stampfer-Kountchev, & Tison, 2003). Neuronal loss and gliosis are seen throughout the basal ganglia and brainstem nuclei, with variable involvement of thalamic nuclei, olivopontocerebellar tracts, intermediolateral columns, and pyramidal tracts. The histopathologic findings include glial and, to a lesser extent, neuronal cytoplasmic inclusions that, like LBs, stain positive for the proteins ubiquitin and alpha-synuclein. Mild to moderate dementia with frontal lobe impairment is seen in some individuals with MSA; this typically is less severe than in DLB or AD (Stefanova, Bücke, Duerr, & Wenning, 2009). Although several agents including riluzole, recombinant human growth hormone, and minocycline have been studied, none have shown efficacy in the treatment of MSA (Stefanova et al., 2009).
Medicare Set-Asides
Julie Dickinson, Anne Meyer, Karen J. Huff, Deborah A. Wipf, Elizabeth K. Zorn, Kathy G. Ferrell, Lisa Mancuso, Marjorie Berg Pugatch, Joanne Walker, Karen Wilkinson in Legal Nurse Consulting Principles and Practices, 2019
As stated above, there is no legal obligation to fund an MSA. No one will find such a requirement in any state or federal law or regulation. Nevertheless, technically, an MSA has been created any time consideration is provided in an insurance settlement in exchange for a release from the legal liability for future related medical expenses. Medicare is excluded to the extent another payer is primarily responsible, so the fact that the insurer provided payment for related medical treatment in advance of its occurrence does not change Medicare’s secondary payer status until that money has been spent on related medical expenses. An MSA report is nice in that it identifies the specific amount allocated and the calculation methodology used, but Medicare’s statutory exclusion will occur without an MSA report just the same.
Adrenergic Antagonists
Sahab Uddin, Rashid Mamunur in Advances in Neuropharmacology, 2020
It is an antagonist of the adrenergic β receptor and is cardioselective. It does not show MSA. It produces weak bronchodilating and vasodilating action due to β2 agonism and produces a relaxation action on smooth muscle (Milne et al., 1991; Florey, 2008). It also blocks peripheral α2 receptors, promotes NO production, and inhibits oxidative stress. At β2 receptor it produces intrinsic sympathomimetic action. It lowers the BP and the rate of the heart. The adverse events include headache, fatigue, dizziness, and swollen ankles. The drug absorption is fast from gastrointestinal tract after an oral dose and there is no first pass metabolism. It is employed in treating angina and hypertension (Brunton et al., 2011; Florey, 2008). The drug has a bioavailability of 30–70% and reaches a maximum plasma concentration at 2–4 h. About 25% of given dose of the drug is protein bound. The drug is not affected by first-pass effect and excretion is majorly via feces with about 11% through the urine. For parenteral administered drug 50% excretion happens via urine and 31% through feces.
Animal models of synucleinopathies and how they could impact future drug discovery and delivery efforts
Published in Expert Opinion on Drug Discovery, 2019
MSA, a rare fatal adult-onset synucleinopathy of presumed sporadic origin, is morphologically characterized by distinctive glial cytoplasmic inclusions (Papp-Lantos bodies) containing misfolded αSyn within oligodendroglial and other cells, with neuronal multisystem degeneration [30]. It is clinically featured by autonomic failure and motor impairment with variable combinations of poorly L-dopa-responsive parkinsonism, cerebellar ataxia, tremor, and corticospinal tract dysfunction [31,32]. Diagnostic criteria recommend classification into two subtypes: MSA-P (predominant parkinsonism, 70–80% in the Western world) and MSA-C (predominant cerebellar features associated with olivopontocerebellar atrophy [OPCA], 20–67%), more frequent in Asian populations (67–84%), with rather frequent-mixed phenotypes [33]. Red flag categories – characteristic symptoms including inspiratory stridor, pyramidal signs, postural instability – had a specificity of 98.3% and sensitivity of 84.2% [34]. Revised criteria differentiate possible, probable, and definite MSA, the latter confirmed by postmortem examination [35].
Alpha-synuclein levels in patients with multiple system atrophy: a meta-analysis
Published in International Journal of Neuroscience, 2018
Fei Yang, Wan-Jun Li, Xu-Sheng Huang
Multiple system atrophy (MSA) is a sporadic, adult-onset neurodegenerative disease characterized by the accumulation of alpha (α)-synuclein in the oligodendroglial cytoplasmic inclusions [1]. It is a progressive disease with parkinsonism, ataxia and autonomic dysfunction [2,3]. Due to autonomic dysfunction, orthostatic hypotension, bowel and bladder disturbances and sexual dysfunction may occur in MSA patients [3,4]. Macroscopic atrophy of brain regions such as the putamen and pontis with microscopic neuronal loss and astrocytosis are important histopathological features of MSA [5]. In MSA patients, if Parkinson's disease symptoms are predominant, the disease is termed as MSA-P and if cerebellar dysfunction symptoms predominate, it is classified as MSA-C [6]. The annual incidence of MSA is approximately 3 per 100,000 individuals over the age of 50 years [7,8]. The survival of MSA patients is reported to be up to 10 years and the onset age ranges from 53 to 63 years [9–11]. Late onset age, and early or initial autonomic symptoms [12,13] are associated with worse survival outcomes whereas late autonomic dysfunction has been reported as a favourable prognostic factor [14,15].
Severe rhabdomyolysis due to idiopathic inflammatory myopathies, a wary manifestation of a heterogenous pathology
Published in Acta Clinica Belgica, 2023
Niels Schepens, Pauline H. Herroelen, An-Sofie Decavele, An Vanacker
This case showed a single high positive result for anti-NXP2 on LIA. This result could not be verified by another Belgian laboratory as they all use LIA or DB and no immunoprecipitation (IP) was available. As false-positive results are frequently detected, one should consider the intensity of the reaction, which was high (100) on LIA Euroimmun, indicating a higher probability of a true positive result. When interpreting MSA results, correlation with the result obtained by Hep-2 IIFA (ANA) is necessary. For example, a speckled cytoplasmic pattern is highly associated with anti-SRP and anti-ARS antibodies. However, for most MSA, no strong association exists. In case of anti-NXP2, multiple nuclear dots (AC-6) are described, but with low sensitivity, hence a negative ANA does not exclude anti-NXP2. Therefore, when clinical suspicion for IIM is high, a negative ANA result does not exclude IIM and the first test of choice remains a multi-specific immunoassay for the whole spectrum of MSA [13].
Related Knowledge Centers
- Ataxia
- Balance Disorder
- Hypokinesia
- Parkinsonism
- Tremor
- Dysautonomia
- Basal Ganglia
- Brain
- Neurodegenerative Disease
- Neuron