Multiple system atrophy (MSA) is a rare neurodegenerative disorder that affects multiple systems in the body, including the nervous, autonomic, and motor systems. It is characterized by progressive loss of nerve cells (neurons) in specific areas of the brain, leading to a wide range of symptoms.
AKA Shy-Drager syndrome. Parkinsonism (indistinguishable from IPA), PLUS idiopathic orthostatic hypotension, PLUS other signs of autonomic nervous system (ANS) dysfunction (ANS findings may precede parkinsonism and may include urinary sphincter disturbance and hypersensitivity to noradrenaline or tyramine infusions). Degeneration of preganglionic lateral horn neurons of the thoracic spinal cord. Unlike IPA, most do not respond to dopa therapy. NB: classic IPA may eventually produce orthostatic hypotension from inactivity or as a result of progressive autonomic failure.
It is a rare neurodegenerative disorder characterized by autonomic dysfunction, tremors, slow movement, muscle rigidity, and postural instability (collectively known as parkinsonism) due to dysfunction of the basal ganglia, and ataxia.
There are two types of MSA: MSA with predominant Parkinsonism (MSA-P) and MSA with predominant cerebellar ataxia (MSA-C). MSA-P is characterized by Parkinsonism, which includes symptoms such as rigidity, tremors, and slowed movements. MSA-C is characterized by cerebellar ataxia, which includes symptoms such as gait and balance problems, slurred speech, and difficulty with fine motor movements.
In addition to Parkinsonism or cerebellar ataxia, MSA can also cause autonomic dysfunction, which affects the body's automatic functions such as blood pressure regulation, digestion, and bladder control. Autonomic dysfunction can cause symptoms such as orthostatic hypotension (a drop in blood pressure upon standing), urinary incontinence, and constipation.
The exact cause of MSA is not known, but it is thought to be related to the accumulation of a protein called alpha-synuclein in the brain. Alpha-synuclein forms clumps called Lewy bodies, which are also found in other neurodegenerative disorders such as Parkinson's disease.
There is no cure for MSA, and treatment is mainly focused on managing symptoms. Medications can be used to manage Parkinsonism or cerebellar ataxia symptoms, while lifestyle modifications can help manage autonomic dysfunction. In some cases, physical therapy and rehabilitation can also be helpful in managing the movement and balance problems associated with MSA.
Laryngeal stridor is an additional feature for MSA diagnosis, showing a high diagnostic positive predictive value, and its early occurrence might contribute to shorten survival. A consensus definition of stridor in MSA is lacking, and disagreement persists about its diagnosis, prognosis, and treatment. An International Consensus Conference among experts with methodological support was convened in Bologna in 2017 to define stridor in MSA and to reach consensus statements for the diagnosis, prognosis, and treatment. Stridor was defined as a strained, high-pitched, harsh respiratory sound, mainly inspiratory, occurring only during sleep or during both sleep and wakefulness, and caused by laryngeal dysfunction leading to narrowing of the rima glottidis. According to the consensus, stridor may be recognized clinically by the physician if present at the time of examination, with the help of a witness, or by listening to an audio recording. Laryngoscopy is suggested to exclude mechanical lesions or functional vocal cord abnormalities related to different neurologic conditions. If the suspicion of stridor needs confirmation, drug-induced sleep endoscopy or video polysomnography may be useful. The impact of stridor on survival and quality of life remains uncertain. Continuous positive airway pressure and tracheostomy are both suggested as symptomatic treatment of stridor, but whether they improve survival is uncertain. Several research gaps emerged involving diagnosis, prognosis, and treatment. Unmet needs for research were identified 1).
The pattern and role of microglial activation in multiple system atrophy is largely unclear. The objective of this study was to use [11 C](R)-PK11195 PET to determine the extent and correlation of activated microglia with clinical parameters in MSA patients.
METHODS: Fourteen patients with the parkinsonian phenotype of MSA (MSA-P) with a mean disease duration of 2.9 years (range 2-5 years) were examined with [11 C](R)-PK11195 PET and compared with 10 healthy controls.
RESULTS: Patients with the parkinsonian phenotype of MSA showed a significant (P ≤ 0.01) mean increase in binding potentials compared with healthy controls in the caudate nucleus, putamen, pallidum, precentral gyrus, orbitofrontal cortex, presubgenual anterior cingulate cortex, and the superior parietal gyrus. No correlations between binding potentials and clinical parameters were found.
CONCLUSIONS: In early clinical stages of the parkinsonian phenotype of MSA, there is widespread microglial activation as a marker of neuroinflammatory changes without correlation to clinical parameters in our patient population 2).
retrospectively included patients with MSA and PD as well as healthy controls. A DNP was trained on manual segmentations of the putamen as ground truth. For this, the cohort was randomly split into a training (N = 131) and test set (N = 120). The DNP's performance was compared with putaminal segmentations as derived by Automatic Anatomic Labelling, Freesurfer and Fastsurfer. For validation, we assessed the diagnostic accuracy of the resulting segmentations in the delineation of MSA vs. PD and healthy controls.
Results: A total of 251 subjects (61 patients with MSA, 158 patients with PD, and 32 healthy controls; mean age of 61.5 ± 8.8 years) were included. Compared to the dice-coefficient of the DNP (0.96), we noted significantly weaker performance for AAL3 (0.72; p < .001), Freesurfer (0.82; p < .001), and Fastsurfer (0.84, p < .001). This was corroborated by the superior diagnostic performance of MSA vs. PD and HC of the DNP (AUC 0.93) versus the AUC of 0.88 for AAL3 (p = 0.02), 0.86 for Freesurfer (p = 0.048), and 0.85 for Fastsurfer (p = 0.04).
Conclusion: By utilization of a DNP, accurate segmentations of the putamen can be obtained even if substantial atrophy is present. This allows for more precise extraction of imaging parameters or shape features from the putamen in relevant patient cohorts 3)