The dichotomy between the hypo- versus hyperkinetic nature of Parkinson's disease (PD) and dystonia, respectively, is thought to be reflected in the underlying basal ganglia pathophysiology. In this ...study, we investigated differences in globus pallidus internus (GPi) neuronal activity, and short- and long-term plasticity of direct pathway projections. Using microelectrode recording data collected from the GPi during deep brain stimulation surgery, we compared neuronal spiketrain features between people with PD and those with dystonia, as well as correlated neuronal features with respective clinical scores. Additionally, we characterized and compared readouts of short- and long-term synaptic plasticity using measures of inhibitory evoked field potentials. GPi neurons were slower, bustier, and less regular in dystonia. In PD, symptom severity positively correlated with the power of low-beta frequency spiketrain oscillations. In dystonia, symptom severity negatively correlated with firing rate and positively correlated with neuronal variability and the power of theta frequency spiketrain oscillations. Dystonia was moreover associated with less long-term plasticity and slower synaptic depression. We substantiated claims of hyper- versus hypofunctional GPi output in PD versus dystonia, and provided cellular-level validation of the pathological nature of theta and low-beta oscillations in respective disorders. Such circuit changes may be underlain by disease-related differences in plasticity of striato-pallidal synapses.
Freezing of gait in people with Parkinson’s disease (PwP) is associated with executive dysfunction and motor preparation deficits. We have recently shown that electrophysiological markers of motor ...preparation, rather than decision-making, differentiate PwP with freezing of gait (FOG +) and without (FOG −) while sitting. To examine the effect of locomotion on these results, we measured behavioural and electrophysiological responses in PwP with and without FOG during a target response time task while sitting (single-task) and stepping-in-place (dual-task). Behavioural and electroencephalographic data were acquired from 18 PwP (eight FOG +) and seven young controls performing the task while sitting and stepping-in-place. FOG + had slower response times while stepping compared with sitting. However, response times were significantly faster while stepping compared with sitting for controls. Electrophysiological responses showed no difference in decision-making potentials (centroparietal positivity) between groups or conditions but there were differences in neurophysiological markers of response inhibition (N2) and motor preparation (lateralized readiness potential, LRP) in FOG + while performing a dual-task. This suggests that the addition of a second complex motor task (stepping-in-place) impacts automatic allocation of resources in FOG +, resulting in delayed response times. The impact of locomotion on the generation of the N2 and LRP potentials, particularly in freezers, indirectly implies that these functions compete with locomotion for resources. In the setting of multiple complex tasks or cognitive impairment, severe motor dysfunction may result, leading to freezing of gait.
Myoclonus-dystonia is an early onset genetic disorder characterised by subcortical myoclonus and less prominent dystonia. Its primary causative gene is the epsilon-sarcoglycan gene but the syndrome ...of “myoclonic dystonia” has been shown to be a heterogeneous group of genetic disorders. The underlying pathophysiology of myoclonus-dystonia is incompletely understood, although it may relate to dysfunction of striatal monoamine neurotransmission or disruption of cerebellothalamic networks (possibly via a GABAergic deficit of Purkinje cells). A broad range of oral medical therapies have been used in the treatment of myoclonus-dystonia with a varying response, and limited data relating to efficacy and tolerability, yet this condition responds dramatically to alcohol. Few well conducted randomized controlled trials have been undertaken leading to an empirical ad hoc approach for many patients. We review the current evidence for pharmacological therapies in myoclonus-dystonia, discuss implications for underlying pathogenesis of the condition and propose a treatment algorithm for these patients.
•Myoclonus-dystonia is a complex disorder with many different facets, for which there remains a paucity of data on specific medical therapies.•Oral medications typically have a variable response in M-D, with poor tolerability limiting their use in many patients.•We review the current evidence for pharmacological therapies in M-D and discuss implications for underlying pathogenesis of the condition.•Large controlled studies are required in genetically well-defined cohorts to further validate the therapeutic options in this condition.
Apathy is a prevalent and highly debilitating non-motor symptom of Parkinson's disease (PD) that is often overlooked in clinical practice due to its subtle nature. This review aims to provide a ...comprehensive overview of the current evidence for the treatment of apathy in PD, highlighting recent advancements and emerging therapeutic avenues. In this review, we analyse a diverse array of treatment strategies for apathy in PD, including pharmacological interventions, non-pharmacological approaches, and emerging neuromodulation techniques. We evaluate the efficacy, safety, and limitations of established pharmacotherapies, such as dopaminergic agents, antidepressants, and cognitive enhancers. Additionally, we examine the promising role of non-pharmacological interventions, encompassing psychotherapies and behavioural interventions, in ameliorating apathetic symptoms. Furthermore, this review explores the effects of neuromodulation techniques on apathy, including the modulation of apathy via deep brain stimulation and emerging data on the potential influence of transcranial magnetic stimulation (TMS) on apathy in PD. Ultimately, a deeper understanding of effective treatment strategies for apathy has the potential to significantly improve the quality of life and overall well-being of individuals living with PD.
Studies focusing on the relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coronavirus disease 2019 (COVID-19), and Parkinson's disease (PD) have provided conflicting ...results. We review the literature to investigate: 1) Are PD patients at higher risk for contracting COVID-19 and are there specific contributing factors to that risk? 2) How does COVID-19 affect PD symptoms? 3) How does COVID-19 present in PD patients? 4) What are the outcomes in PD patients who contract COVID-19? 5) What is the impact of COVID-19 on PD care? 6) Does COVID-19 increase the risk of developing PD? A literature search was performed from 1979 to 2020 using the terms: 'Parkinson's disease' and 'parkinsonism' combined with: 'COVID-19'; 'SARS-CoV-2' and 'coronavirus'. It does not appear that PD is a specific risk factor for COVID-19. There is evidence for direct/indirect effects of SARS-CoV-2 on motor/non-motor symptoms of PD. Although many PD patients present with typical COVID-19 symptoms, some present atypically with isolated worsening of parkinsonian symptoms, requiring increased anti-PD therapy and having worse outcomes. Mortality data on PD patients with COVID-19 is inconclusive (ranging from 5.2%to 100%). Patients with advanced PD appear to be particularly vulnerable. Single cases of acute hypokinetic-rigid syndrome have been described but no other convincing data has been reported. The rapidity with which COVID-19 has swept across the globe has favored the proliferation of studies which lack scientific rigor and the PD literature has not been immune. A coordinated effort is required to assimilate data and answer these questions in larger PD cohorts.
Cervical dystonia (CD) presents as a motor disorder but has a number of non-motor features. Studies have demonstrated diverse changes in cognition in patients with CD. The rarity of this disorder, ...phenotypic heterogeneity, and, in particular, a lack of consistency in cognitive testing measures limits clear definition of cognitive changes in this disorder. The relationship between cognition, motor symptoms and quality of life has not been well defined. We undertook a comprehensive analysis of cognition in CD.
Patients with adult onset idiopathic isolated CD (AOICD) who had completed a battery of cognitive assessments- general intellectual functioning, verbal and visual memory, executive functions and social cognition measures, were included. Participants were assessed for mood symptoms, motor severity and quality of life.
13 patients (8 women) with AOICD were included covering 40 cognitive subtests. Mean age was 59.9 years and mean TWSTRS-2 severity was 11. Mean estimated premorbid function was in the normal range. Overall performance on most measures were within normal limits. The lowest mean z-score was observed in Florida Affect Battery (social cognition) subtests, z = −1.75 and −0.81. and in verbal recall, z = −0.82. The majority of patients (75%) scored below population mean on spatial working memory and (62%) performed below population mean on word retrieval and working memory.
We provide detailed cognitive results across a wide range of measures. Although patients tended towards average outcomes on the majority of tests, poorer performance than expected averages were noted in measures of social cognition, word retrieval, spatial working memory and, processing speed.
Background:
Headaches represent a significant proportion of referrals to any neurology consult service, of which many are migrainous. Regular use of opioids can lead to medication overuse headache in ...these patients and in some cases, dependence. The epidemic of opioid abuse represents a serious public health concern, with long term use of opioids associated with risk of misuse, abuse, addiction and even overdose.
Methods:
We audited headache referrals to the neurology consult service in an acute tertiary hospital over three 6-month periods between 2012 and 2019. Appropriateness of referrals with respect to NICE guidelines and initial treatments strategies were assessed.
Results:
The majority of headache disorders seen were migrainous and we found an alarming and repeated trend of early opioid prescribing in the initial acute setting (up to 56%).
Conclusions:
Further education of healthcare professionals and patients is urgently required to prevent this group becoming victims of the growing global opioid epidemic.
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