Inflammation and oxidative stress are recognized as important contributors to Parkinson's disease pathogenesis. As such, genetic variability in these pathways could have a role in susceptibility for ...the disease as well as in the treatment outcome. Dopaminergic treatment is effective in management of motor symptoms, but poses a risk for motor and non-motor adverse events. Our aim was to evaluate the impact of selected single-nucleotide polymorphisms in genes involved in inflammation and oxidative stress on Parkinson's disease susceptibility and the occurrence of adverse events of dopaminergic treatment.
In total, 224 patients were enrolled, and their demographic and clinical data on the disease course were collected. Furthermore, a control group of 146 healthy Slovenian blood donors were included for Parkinson's disease' risk evaluation. Peripheral blood was obtained for DNA isolation. Genotyping was performed for NLRP3 rs35829419, CARD8 rs2043211, IL1β rs16944, IL1β rs1143623, IL6 rs1800795, CAT rs1001179, CAT rs10836235, SOD2 rs4880, NOS1 rs2293054, NOS1 rs2682826, TNF-α rs1800629, and GPX1 rs1050450. Logistic regression was used for analysis of possible associations.
We observed a nominally significant association of the IL1β rs1143623 C allele with the risk for Parkinson's disease (OR = 0.59; 95%CI = 0.38-0.92, p = 0.021). CAT rs1001179 A allele was significantly associated with peripheral edema (OR = 0.32; 95%CI = 0.15-0.68; p = 0.003). Other associations observed were only nominally significant after adjustments: NOS1 rs2682826 A allele and excessive daytime sleepiness and sleep attacks (OR = 1.75; 95%CI = 1.00-3.06, p = 0.048), SOD2 rs4880 T allele and nausea/vomiting (OR = 0.49, 95%CI = 0.25-0.94; p = 0.031), IL1β rs1143623 C allele and orthostatic hypotension (OR = 0.57, 95%CI = 0.32-1.00, p = 0.050), and NOS1 rs2682826 A allele and impulse control disorders (OR = 2.59; 95%CI = 1.09-6.19; p = 0.032). We did not find any associations between selected polymorphisms and motor adverse events.
Apart from some nominally significant associations, one significant association between CAT genetic variability and peripheral edema was observed as well. Therefore, the results of our study suggest some links between genetic variability in inflammation- and oxidative stress-related pathways and non-motor adverse events of dopaminergic treatment. However, the investigated polymorphisms do not play a major role in the occurrence of the disease and the adverse events of dopaminergic treatment.
Myoclonus is a sudden, brief, involuntary muscle jerk. It is caused by abrupt muscle contraction, in the case of positive myoclonus, or by sudden cessation of ongoing muscular activity, in the case ...of negative myoclonus (NM). Myoclonus may be classified in a number of ways, although classification based on the underlying physiology is the most useful from the therapeutic viewpoint. Given the large number of possible causes of myoclonus, it is essential to take a good history, to clinically characterize myoclonus and to look for additional findings on examination in order to limit the list of possible investigations. With regards to the history, the age of onset, the character of myoclonus, precipitating or alleviating factors, family history and associated symptoms and signs are important. On examination, it is important to see whether the myoclonus appears at rest, on keeping posture or during action, to note the distribution of jerks and to look for the stimulus sensitivity. Electrophysiological tests are very helpful in determining whether myoclonus is cortical, subcortical or spinal. A single pharmacological agent rarely control myoclonus and therefore polytherapy with a combination of drugs, often in large dosages, is usually needed. Generally, antiepileptic drugs such as valproate, levetiracetam and piracetam are effective in cortical myoclonus, but less effective in other forms of myoclonus. Clonazepam may be helpful with all types of myoclonus. Focal and segmental myoclonus, irrespective of its origin, may be treated with botulinum toxin injections, with variable success.
Dystonia in atypical parkinsonian disorders Marsili, Luca; Bologna, Matteo; Kojovic, Maja ...
Parkinsonism & related disorders,
September 2019, 2019-09-00, 20190901, Volume:
66
Journal Article
Peer reviewed
Open access
Dystonia is common in the classic atypical parkinsonian disorders such as multiple system atrophy, progressive supranuclear palsy and corticobasal degeneration, and to a lesser extent in dementia ...with Lewy bodies. Its clinical phenomenology, including body distribution, timing of appearance, severity, and relationship to dopaminergic and other medications may vary considerably within and between atypical parkinsonian disorders. From a pathophysiological standpoint, the coexistence of dystonia with parkinsonism challenges the functional model of the basal ganglia. Clinical recognition of specific dystonic features may assist in the differential diagnosis of atypical parkinsonian disorders and in distinguishing them from Parkinson's disease. The presence of dystonia in atypical parkinsonian disorders informs management decisions. Reduction or withdrawal of levodopa should be considered if there is a close relationship between the onset of dystonia with periods of high dopaminergic tone. Botulinum neurotoxin may be considered in focal presentations. We here provide an updated overview of dystonia arising in the setting of atypical parkinsonian disorders, summarizing relevant clinical and clinicopathological studies, underlying pathophysiological mechanisms, diagnostic clues and potential pitfalls in the diagnosis. Finally, we suggest a tailored therapeutic approach for the management of these patients.
•Dystonia is a common feature of atypical parkinsonian disorders.•Dystonia patterns assist in the differential diagnosis of parkinsonisms.•Body distribution and relationship with dopaminergic medication can be distinctive.•Therapies include reduction of dopaminergic medications and botulinum neurotoxin.
Background. Motivational improvement of movement speed in Parkinson’s disease (PD) is observed in life-threatening situations and has been empirically demonstrated in experimental studies using ...reaction time paradigms. Objectives. To address two clinically relevant questions: first, if in PD, motivational modulation through provision of monetary incentive on a sorting task that approximates performance on everyday life tasks affects movement speed. Second, how this effect is compared between PD patients treated with medication or subthalamic deep brain stimulation. Methods. We used the Card Arranging Reward Responsivity Objective Test that shares component processes with everyday life tasks to compare reward responsivity of movement speed in 10 PD patients with STN-DBS, 10 nonoperated medicated PD patients, both OFF and ON their usual medications/stimulation, and 11 age-matched healthy controls. Results. Despite longer disease duration and more severe motor symptoms, STN-DBS PD patients with the stimulator turned ON showed greater improvement of movement speed with the prospect of monetary incentive compared to both medicated PD patients and healthy participants. Discussion. The effect of monetary incentive on movement speed in PD patients is more pronounced with STN-DBS than dopaminergic medications, suggesting that motivational modulation of movement speed may be enhanced as a direct consequence of STN stimulation.
Majority of movements in everyday situations are complex and involve volition, planning of the movement and selection of the motor programme, all occurring before movement execution. Higher order ...motor disorders may be defined as abnormal motor behaviours resulting from disruption of any of the cortical processes that precede execution of the motor act. They are common in patients with neurodegenerative disorders, psychiatric diseases and structural brain lesions. These abnormal behaviours may be overlooked in the clinic, unless specifically evoked by the examiner. We discuss clinical and pathophysiological aspects of higher order motor disorders including: (1) disorders of disinhibition, such as grasp reflex and grasping behaviour, utilisation and imitation behaviour, motor preservations and paratonia; (2) disorders of motor intention such as motor neglect and motor impersistence; (3) alien limb syndrome; and (4) motor overflow phenomena, such as mirror movements and synkinesias. A video illustration of each phenomenon is provided. We place the findings from recent neurophysiological studies within the framework of theories of motor control to provide better insight into pathophysiology of different disorders.
fMRI studies show activation of cerebellum during transcutaneous auricular vagal nerve stimulation (taVNS); however, there is no evidence whether taVNS induced activation of the cerebellum translates ...to the cerebellar closed loops involved in motor functions. We assessed the propensity of taVNS at 25 Hz (taVNS25) and 100 Hz (taVNS100) to modulate cerebello-thalamo-cortical pathways using transcranial magnetic stimulation. In our double blind within-subjects study thirty-two participants completed one visit during which cerebellar brain inhibition (CBI) was assessed at baseline (no stimulation) and in a randomized order during taVNS100, taVNS25, and sham taVNS (xVNS). Generalized linear mixed models with gamma distribution were built to assess the effect of taVNS on CBI. The estimated marginal means of linear trends during each taVNS condition were computed and compared in a pairwise fashion with Benjamini-Hochberg correction for multiple comparisons. CBI significantly increased during taVNS100 compared to taVNS25 and xVNS (
p
= 0.0003 and
p
= 0.0465, respectively). The taVNS current intensity and CBI conditioning stimulus intensity had no significant effect on CBI. taVNS has a frequency dependent propensity to modulate the cerebello-thalamo-cortical pathway. The cerebellum participates in closed-loop circuits involved in motor, cognitive, and affective operations and may serve as an entry for modulating effects of taVNS.
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