Levodopa-Induced Dyskinesias and Dyskinesias-Reduced-Self-Awareness in Parkinson’s Disease: A Neurocognitive Approach

Levodopa-induced dyskinesias are one of the most common disabling motor complications in advanced Parkinson’s disease. The subjective perception of motor impairment is a clinical phenomenon that needs to be adequately analyzed. Indeed, the determination of patient dyskinesias-reduced-self-awareness (DRSA) and of its relationship to daily dysfunction is an important aspect of the debate on the gold standard for treatment. As the association with executive dysfunction is a matter of debate and we hypothesize it plays an important role in DRSA, we analyzed metacognitive abilities related to action monitoring and other factors, such as response-inhibition and “Theory of Mind,” which represent a novel explanation of the phenomenon. Moreover, we investigated whether and how a dysfunction in action monitoring related to the cingulo-frontal-ventral striatal circuit would be associated with DRSA using an event-related Go-NoGo fMRI experiment. Our findings suggest the presence of executive dysfunctions in DRSA pathogenesis, with a key leading role played by the cingulo-frontal network as part of a functionally impaired response-inhibition network

Pure autonomic failure versus prodromal dysautonomia in Parkinson’s disease: Insights from the bedside

Autonomic failure may include orthostatic hypotension, supine hypertension, bowel and bladder disturbances, impaired thermal regulation, and sexual dysfunction, all of which can be features of Parkinson's disease (PD) and other a‐synucleinopathies. All patients with pure autonomic failure, most patients with multiple system atrophy, and 18% of patients with PD will develop symptomatic orthostatic hypotension. However, the extent of central and peripheral norepinephrine deficiency, parasympathetic nuclei degeneration, and arterial baroreflex failure may be differentially impaired in these disorders. Consequently, clinical features and prognostic implications of autonomic dysfunction in a‐synucleinopathies may be more complex than previously envisioned. The case described in this report highlights the clinical similarities between PD and pure autonomic failure, raising the question of whether pure autonomic failure represents a restricted Lewy body synucleinopathy or an early manifestation of PD

SARS-CoV-2 vaccination, Parkinson's disease, and other movement disorders: case series and short literature review

BACKGROUND: Several neurological complications have been reported following SARS-Cov-2 vaccination, without a clear causal relationship ever being verified, including some cases of worsening of Parkinson’s disease (PD) symptoms and new onset of movement disorders in non-parkinsonian patients. METHODS: We describe two new cases of PD patients treated with device-aided therapy who developed worsening of parkinsonian symptoms after receiving the third vaccine dose (booster). We also conducted a short review of the cases reported in literature of PD symptoms worsening and new onset of movement disorders in non-parkinsonian patients after SARS-Cov-2 vaccination. RESULTS: The first patient, a 46-year-old man implanted with bilateral Subthalamic Deep Brain Stimulation, experienced temporary motor and non-motor symptoms worsening after mRNA-1273 booster, improved after stimulation settings modification. The second patient, a 55-year-old man implanted with percutaneous endoscopic transgastric jejunostomy (PEG-J) for levodopa-carbidopa intestinal gel (LCIG) infusion experienced severe temporary worsening of dyskinesia and managed through temporary LCIG dose reduction. Other seven cases of vaccine-related movement disorder are currently reported in literature, four describing PD symptoms worsening and three the onset of new movement disorders in otherwise healthy people. CONCLUSION: Both our patients and the cases described so far completely recovered after few days with parkinsonian therapy modification, symptomatic treatment, or even spontaneously, underlining the transient and benign nature of side effects from vaccine. Patients should be reassured about these complications, manageable through a prompt evaluation by the reference neurologist. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10072-022-06182-w

Home monitoring of motor fluctuations in Parkinson's disease patients

In Parkinson's disease, motor fluctuations (worsening of tremor, bradykinesia, freezing of gait, postural instability) affect up to 70% of patients within 9 years of \textsc {l}-dopa therapy. Nevertheless, the assessment of motor fluctuations is difficult in a medical office, and is commonly based on poorly reliable self-reports. Hence, the use of wearable sensors is desirable. In this preliminary trial, we have investigated bradykinesia and freezing of gait—FOG—symptoms by means of inertial measurement units. To this purpose, we have employed a single smartphone on the patient's waist for FOG experiment (38 patients), and on patient thigh for LA (93 subjects). Given the sound performance achieved in this trial (AUC = 0.97 for FOG and AUC = 0.92 for LA), motor fluctuations may be estimated in domestic environments. To this end, we plan to perform measures and data processing on SensorTile, a tiny IoT module including several sensors, a microcontroller, a BlueTooth low-energy interface and microSD card, implementing an electronic diary of motor fluctuations, posture and dyskinesia during activity of daily living

Pisa Syndrome in Parkinson's Disease Is Associated With Specific Cognitive Alterations

Background: Pisa syndrome (PS) is a lateral flexion of the trunk frequently associated with Parkinson's disease (PD). The pathophysiology of PS remains unclear, but the role of cognitive deficits has been postulated.Methods: We included 12 consecutive PD patients with PS (PS+) and 12 PD patients without PS (PS–) matched for gender, age, level of education, PD duration, and PD stage. As primary aim, we compared the neuropsychological scores of 16 tests evaluating 6 cognitive domains between PS+ and PS–. Additionally, we evaluated the presence of misperception of the trunk position in PS+, defined as a mismatch between the objective vs. subjective evaluation of the trunk bending angle >5°, and analyzed whether a correlation exists between the misperception of the trunk position and alterations in the visual-spatial abilities.Results: PS+ group showed significantly worse performances in the visual-spatial abilities (p: 0.008), attentional domain (p: 0.001), and language domain (p: 0.023). No differences were found in the other cognitive domains nor in the general cognitive assessment. All PS+ patients showed a misperception of the trunk position, with an average underestimation of the trunk bending angle of 11.7° ± 4.3. The degree of misperception of the trunk position showed a trend toward a correlation with the visual-spatial scores (p: 0.089).Conclusions: The study reveals an association between PS and specific cognitive alterations, suggesting a possible link between the abnormal posture of PD patients with PS and their cognitive functions

Smartphone-based estimation of item 3.8 of the MDS-UPDRS-III for assessing leg agility in people with Parkinson’s disease”

In this paper we investigated the use of smartphone sensors and Artificial Intelligence techniques for the automatic quantification of the MDS-UPDRS-Part III Leg Agility (LA) task, representative of lower limb bradykinesia. Methods: We collected inertial data from 93 PD subjects. Four expert neurologists provided clinical evaluations. We employed a novel Artificial Neural Network approach in order to get a continuous output, going beyond the MDS-UPDRS score discretization. Results: We found a Pearson correlation of 0.92 between algorithm output and average clinical score, compared to an inter-rater agreement index of 0.88. Furthermore, the classification error was less than 0.5 scale point in about 80% cases.Conclusions:Weproposedanobjectiveandreliabletoolfor theautomaticquantificationoftheMDS-UPDRSLegAgilitytask. In perspective, this tool is part of a larger monitoring program to be carried out during activities of daily living, and managed by the patients themselves

What Happens When I Watch a Ballet and I Am Dyskinetic? A fMRI Case Report in Parkinson Disease.

The identical sets of neurons – the mirror neuron system (MNS) – can be activated by simply observing specific, specific movements, decoded behaviors and even facial expressions performed by other people. The same neurons activated during observation are those recruited during the same movements and actions. Hence the mirror system plays a central role in observing and executing movements. Little is known about MNS in a neurodegenerative motor disorder, such as Parkinson’s Disease (PD) is