Search

Background: Progressive supranuclear palsy (PSP) is a progressive neurodegenerative disorder involving motor and cognitive dysfunction. Currently, there is no effective treatment either for symptomatic relief or disease modification. This relates, in part, to a lack of knowledge of the underlying neurochemical abnormalities, including cholinergic receptor status in the basal ganglia. Aim: To measure muscarinic M2 and M4 receptors in the basal ganglia in PSP. Methods: The muscarinic M2 (presynaptic) and M4 (postsynaptic) receptors in the striatum, pallidum and adjacent insular cortex were autoradiographically measured in pathologically confirmed cases of PSP (n = 18), and compared with cases of Lewy body dementias (LBDs; n = 45), Alzheimer’s disease (AD; n = 39) and controls (n = 50). Results: In cases of PSP, there was a reduction in M2 and M4 receptors in the posterior caudate and putamen compared to controls, but no significant changes in the pallidum. Cases with AD showed lower M2 receptors in the posterior striatum. Groups with LBD and AD showed higher M2 binding in the insular cortex compared with controls. Conclusions: The results suggest loss of posterior striatal cholinergic interneurones in PSP, and reduction in medium spiny projection neurones bearing M4 receptors. These results should be taken in the context of more widespread pathology in PSP, but may have implications for future trials of cholinergic treatments.

Background: Multifocal motor neuropathy (MMN) is characterised by asymmetrical weakness and muscle atrophy, in the arms more than the legs, without sensory loss. Despite a beneficial response to treatment with intravenous immunoglobulins (IVIg), weakness is slowly progressive. Histopathological studies in MMN revealed features of demyelination and axon loss. It is unknown to what extent demyelination and axon loss contribute to weakness. Unlike demyelination, axon loss has not been studied systematically in MMN. Aims/Methods: To assess the independent determinants of weakness in MMN, 20 patients with MMN on IVIg treatment were investigated. Using a standardised examination in each patient, muscle strength was determined in 10 muscles. In the innervating nerve of each muscle, axon loss was assessed by concentric needle electromyography, and conduction block or demyelinative slowing by motor nerve conduction studies. Multivariate analysis was used to assess independent determinants of weakness. Results: Needle electromyography abnormalities compatible with axon loss were found in 61% of all muscles. Axon loss, and not conduction block or demyelinative slowing, was the most significant independent determinant of weakness in corresponding muscles. Furthermore, axon loss and conduction block were independently associated with each other. Conclusion: Axon loss occurs frequently in MMN and pathogenic mechanisms leading to axonal degeneration may play an important role in the outcome of the neurological deficit in patients with MMN. Therapeutic strategies aimed at prevention and reduction of axon loss, such as early initiation of treatment or additional (neuroprotective) agents, should be considered in the treatment of patients with MMN.

Significance: A noninvasive method based on surface-enhanced Raman spectroscopy (SERS) of tears was proposed as a support for diagnosing neurodegenerative pathologies, including different forms of dementia and Alzheimer’s disease (AD). In this field, timely and reliable discrimination and diagnosis are critical aspects for choosing a valid medical therapy, and new methods are highly required. Aim: The aim is to evince spectral differences in SERS response of human tears from AD affected, mild cognitive impaired (MCI), and healthy control (Ctr) subjects. Approach: Human tears were characterized by SERS coupled with multivariate data analysis. Thirty-one informed subjects (Ctr, MCI, and AD) were considered. Results: Average SERS spectra from Ctr, MCI, and AD subjects evidenced differences related to lactoferrin and lysozyme protein components. Quantitative changes were also observed by determining the intensity ratio between selected bands. We also constructed a classification model that discriminated among AD, MCI, and Ctr subjects. The model was built using the scores obtained by performing principal component analysis on specific spectral regions (i-PCA). Conclusions: The results are very encouraging with interesting perspectives for medical applications as support of clinical diagnosis and discrimination of AD from other forms of dementia.