Quantitative EEG in Parkinson's disease: when REM sleep behavior disorder onset really matters.

Parkinson's Disease (PD) body-first subtype is characterized by prodromal autonomic symptoms and REM sleep behavior disorder (RBD), symmetric dopaminergic degeneration, and increased risk of dementia. On the other hand, the PD brain-first subtype has fewer non-motor symptoms and a milder motor phenotype. The temporal relationship between RBD onset and motor symptoms onset may differentiate these two subtypes. We aimed to investigate electrocortical differences between brain-first and body-first PD patients. PD patients with an available routinely collected EEG were retrospectively selected. RBD was diagnosed using the RBD screening questionnaire (≥ 6). According to the onset of RBD patients were classified into PD-RBDpre (RBD onset before motor symptoms) and PD-RBDpost (RBD onset after motor symptoms). Patients without RBD were classified as PD-RBD-. Presence of Mild Cognitive Impairment (MCI) was diagnosed according to the MDS criteria. EEG Spectral analysis was performed in resting state by computing the Power Spectral Density (PSD) of site-specific signal epochs for the common frequency bands (delta, theta, alpha, beta). Thirty-eight PD-RBD-, 14 PD-RBDpre and 31 PD-RBDpost patients were recruited. Comparing both global and site-specific absolute values, we found a significant trend toward beta band reduction going from PD-RBD-, PD-RBDpost and PD-RBDpre. No significant differences were found between PD-RBDpost and PD-RBD- patients. PD-RBDpre patients may represent a different subset of patients as compared to patients without RBD, while patients with later onset have intermediate EEG spectral features. Quantitative EEG may provide new hints in PD subtyping.

Retinal Thickness in Essential Tremor and Early Parkinson Disease: Exploring Diagnostic Insights.

BACKGROUND: Essential tremor (ET) represents a heterogeneous condition which may overlap with Parkinson disease (PD) even at early stages, by sharing some subtle clinical aspects. Longstanding ET demonstrated also higher risk of developing PD, especially with a Tremor-dominant (TD-PD) phenotype. Therefore, differential diagnosis between ET and early PD could be quite challenging. Optical coherence tomography (OCT) has been recognized as a reliable tool to assess the retina as a proxy of neurodegeneration. We aimed to explore the possible role of retinal assessment in differential diagnosis between ET and early PD. METHODS: Macular layers and peripapillary retinal nerve fiber layer (RNFL) thickness among ET, early PD, and healthy controls (HCs) were assessed using OCT. RESULTS: Forty-two eyes from 23 ET, 41 eyes from 21 early PD, and 33 eyes from 17 HCs were analyzed. Macular RNFL, ganglion cell layer, inner plexiform layer, and inner nuclear layer were thinner in PD as compared with ET and even more in HCs. Differences between ET and PD were more evident when considering the TD-PD subgroup, especially for RNFL. Among ET patients, thickness of the inner macular layers showed negative linear relationship with both age at onset and disease duration. Peripapillary temporal quadrant thinning was found in ET compared with HCs. CONCLUSIONS: Macular inner retina was thinner in patients with ET and early PD compared with HCs. These findings suggest that the retinal assessment may have a utility in the differential diagnosis between ET and PD.

Brain linear measurements for differentiating normal pressure hydrocephalus from Alzheimer's disease: an exploratory study.

BACKGROUND AND PURPOSE: Easy and reliable tools for the differential diagnosis between idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer's disease (AD) are needed. MATERIALS AND METHODS: In this cross-sectional study iNPH and AD patients referred to the Neurology Unit of the University of Catania from 1 January 2020 to 1 December 2022 were enrolled. The following brain linear measurements (BLMs) were calculated: Evan's index (EI), the parieto-occipital ratio (POR) and the temporal ratio (TR). For each index, sensitivity, specificity and the area under the curve (AUC) were calculated. Moreover, a cumulative index, the BLM index, was also considered. RESULTS: Fifty patients (25 iNPH and 25 AD) were enrolled. In differentiating iNPH from AD, EI had the highest AUC (0.956), POR had the highest specificity (100%) whilst TR had the highest sensitivity (92%). The BLM index differentiated iNPH and AD with a sensitivity of 96%, a specificity of 92% and an AUC of 0.963 with an optimal cut-off value of 0.303. CONCLUSION: Evan's index, POR and TR may be useful in the differential diagnosis between iNPH and AD. At an individual level, the BLM index represents a valid and reliable tool to achieve an accurate differentiation between these two conditions.

The role of laboratory investigations in the classification of tremors.

INTRODUCTION: Tremor is the most common movement disorder. Although clinical examination plays a significant role in evaluating patients with tremor, laboratory tests are useful to classify tremors according to the recent two-axis approach proposed by the International Parkinson and Movement Disorders Society. METHODS: In the present review, we will discuss the usefulness and applicability of the various diagnostic methods in classifying and diagnosing tremors. We will evaluate a number of techniques, including laboratory and genetic tests, neurophysiology, and neuroimaging. The role of newly introduced innovative tremor assessment methods will also be discussed. RESULTS: Neurophysiology plays a crucial role in tremor definition and classification, and it can be useful for the identification of specific tremor syndromes. Laboratory and genetic tests and neuroimaging may be of paramount importance in identifying specific etiologies. Highly promising innovative technologies are being developed for both clinical and research purposes. CONCLUSIONS: Overall, laboratory investigations may support clinicians in the diagnostic process of tremor. Also, combining data from different techniques can help improve understanding of the pathophysiological bases underlying tremors and guide therapeutic management.

Turning and Sitting in Early Parkinsonism: Differences Between Idiopathic Normal Pressure Hydrocephalus Associated with Parkinsonism and Parkinson's Disease.

Background: Differential diagnosis between idiopathic normal pressure hydrocephalus (iNPH) associated with parkinsonism (iNPH-P) and Parkinson's disease (PD) may prove difficult when evaluating patients with early parkinsonism. The objective of this study was to evaluate differences in mobility during standardized tasks between iNPH-P and PD. Methods: We selected 21 iNPH-P and 21 pharmacologically untreated PD patients. They all performed the instrumented Timed Up and Go test at the time of diagnosis. Results: Turning tasks showed longer duration and lower speed in iNPH-P than in PD. Vertical variation in acceleration during the sit-to-stand phase was lower in iNPH-P patients, whereas the duration of the stand-to-sit phase was longer. On walking, iNPH-P showed smaller stride length and a longer gait cycle duration. In multivariate analysis adjusting for age and cognitive status as potential confounders, average angular speed on turning before sitting was the discriminating parameter between the two groups. Conclusions: Patients with iNPH-P showed specific abnormal mobility performances with respect to untreated PD, specifically during the turning-to-sitting transition.

iNPH with parkinsonism: response to lumbar CSF drainage and ventriculoperitoneal shunting.

OBJECTIVES: To evaluate clinical response after external lumbar drainage (ELD) and ventriculoperitoneal shunting (VPS) in a cohort of patients with idiopathic normal pressure hydrocephalus associated with parkinsonism (iNPH-P), considering parkinsonism as clinical primary outcome. METHODS: Patients underwent long-term 72-h intracranial pressure-controlled CSF ELD. Clinical motor response before and after ELD was evaluated using changes in UPDRS-ME as outcome measure. A standardized cognitive assessment was also performed. iNPH-P patients who underwent VPS were clinically followed-up after surgery. RESULTS: Fourteen iNPH-P patients (age: 69.3 ± 11.6 years) were studied. The time of evaluation after ELD removal was 3.5 ± 1.8 days. We observed a significant motor improvement after the drainage in eight (57.1%) patients. Percent clinical motor response was 18.4 ± 6.7%. Twelve (85.7%) patients underwent VPS. Nine patients were examined after surgery at 31.6 ± 7 months. Four (44.4%) patients presented a clinically detectable improvement in motor response after VPS. No significant changes in cognitive performances were detected. CONCLUSIONS: A clinically detectable motor response on parkinsonian signs was observed in a consistent part of iNPH-P patients few days after ELD as well as over two and half years after VPS. Parkinsonism should be considered as outcome measure for the clinical management of patients with iNPH-P.

Clinical-Instrumental patterns of neurodegeneration in Essential Tremor: A data-driven approach.

INTRODUCTION: Essential Tremor (ET) is increasingly recognized as a complex disorder with additional clinical signs other than tremor. It is still unknown whether a unique pathophysiologic or neurodegenerative process underlies progression and prognosis of the disease. The aim of the study was to identify ET phenotypes through a clinical-instrumental data-driven approach and to characterize possible patterns of neurodegeneration. METHODS: ET patients were categorized using spatio-temporal and kinematic variables related to mobility and dynamic stability processed by motion transducers. Differences between the identified groups in clinical-demographic variables, neuropsychological performances and retinal parameters by Optical Coherence Tomography (OCT) segmentation analysis were tested. RESULTS: Twenty-five ET patients were studied. Based on clustering of kinematic and spatio-temporal gait parameters, two independent groups were identified: cluster "A" (N = 15) and cluster "B" (N = 10). Compared to group A, group B had overall worse performance in mobility, especially on turning tasks. Identified clusters did not differ in terms of age, age at onset and disease duration. Patients in group B had more head tremor and more severe action tremor in the upper limbs as compared to group A, demonstrating also worse performances on cognitive assessments. Based on OCT analysis, group B presented a reduced thickness of the retinal inner layer as compared to group A, suggesting underlying neurodegenerative processes. CONCLUSIONS: The presence of gait and mobility impairment, associated with midline tremor, cognitive decline and retinal degeneration suggests a subtype of ET associated with neurodegeneration.

Electrocortical networks in Parkinson's disease patients with Mild Cognitive Impairment. The PaCoS study.

INTRODUCTION: Parkinson's Disease (PD) is frequently associated with cognitive dysfunction ranging from Mild Cognitive Impairment (PD-MCI) to dementia. Few electrophysiological studies are available evaluating potential pathogenetic mechanisms linked to cognitive impairment in PD since its initial phases. The objective of the study is to analyze electrocortical networks related with cognitive decline in PD-MCI for identifying possible early electrophysiological markers of cognitive impairment in PD. METHODS: From the PaCoS (Parkinson's disease Cognitive impairment Study) cohort, a sample of 102 subjects including 46 PD-MCI and 56 PD with normal cognition (PD-NC) was selected based on the presence of a neuropsychological assessment and at least one EEG recording. EEG signal epochs were analysed using Independent Component Analysis LORETA and spectral analysis by computing the Power Spectral Density (PSD) of site-specific signal epochs. RESULTS: LORETA analysis revealed significant differences in PD-MCI patients compared to PD-NC, with a decreased network involving alpha activity over the occipital lobe, an increased network involving beta activity over the frontal lobe associated with a reduction over the parietal lobe, an increased network involving theta and delta activity over the frontal lobe and a reduction of networks involving theta and delta activity in the parietal lobe. Quantitative EEG analysis showed a significant decrease of alpha PSD over the occipital regions and an increase of delta PSD over the left temporal region in PD-MCI as compared to PD-NC. CONCLUSION: Electrocortical abnormalities detected in PD-MCI patients may represent the instrumental counterpart of early cognitive decline in PD.