Annotated Bibliography – Parkinsons Disease and Movement Disorders

Bloem, B. R., Okun, M. S., & Klein, C. (2021). Parkinson's disease. The Lancet, 397(10291), 2284-2303. https://repository.ubn.ru.nl/bitstream/handle/2066/235670/235670.pdf

This key study by recognized movement disorder experts presents the most complete and up-to-date description of Parkinson’s disease (PD), a serious neurodegenerative movement disorder that is becoming an increasingly common global health concern. The authors carefully examine all key features of Parkinson’s disease, beginning with its epidemiology and emphasizing that its expanding global frequency equals that of a pandemic, although without an infectious source. They dive into the complicated genetic underpinnings, noting that while the majority of cases are non-monogenic, known PD genes account for 3-5% of monogenic PD cases, and 90 genetic risk variants jointly explain 16-36% of heritability. The clinical presentation of Parkinson’s disease is discussed in detail, including not only the fundamental motor elements essential for diagnosis (bradykinesia with stiffness or rest tremor) but also the wide range of non-motor symptoms that add to the disease’s complexity. Importantly, the authors emphasize that clinically evident Parkinson’s disease is frequently preceded by a potentially lengthy prodromal period with early symptoms such as constipation, despite the fact that recognizing this prodromal stage has no therapeutic relevance beyond symptom management.

The main focus areas include the diagnosis and treatment of PD. The authors also stress that ancillary testing should be given more attention in unrevealing cases since the diagnosis is still clinical, given the current criteria. They give a good overview of the purpose of treatment and the necessity of understanding and acknowledging that everyone is different and has different goals. Unfortunately, there are currently no therapeutic approaches that can influence disease progression, but the authors illustrate the continually growing list of symptomatic therapies. Levodopa is most frequently employed as the first-line medication; however, the best treatment for PD requires an interprofessional team that encompasses pharmacological and non-pharmacological management programs individualized to fit the patient’s needs and goals.

The authors discuss several interesting disease-modifying treatment approaches currently being tested based on advances in the genetic makeup of PD and pathological processes, including neuronal death. In general, this uniformly peer-reviewed reference offers a bird’s-eye view of PD while also offering a systematic integration of recent research across all major areas. Given its broad scope and focus on humanized, individualized treatment, this reference is ideal and essential for the study of this essential movement disorder.

Lange, L. M., Gonzalez‐Latapi, P., Rajalingam, R., Tijssen, M. A., Ebrahimi‐Fakhari, D., Gabbert, C., ... & Task Force on Genetic Nomenclature in Movement Disorders. (2022). Nomenclature of genetic movement disorders: recommendations of the International Parkinson and Movement Disorder Society task force–an update. Movement Disorders, 37(5), 905-935. https://movementdisorders.onlinelibrary.wiley.com/doi/pdf/10.1002/mds.28982

This seminal publication contains the most recent recommendations from the distinguished International Parkinson and Movement Disease Society (MDS) task force on hereditary movement disease nomenclature. Standardized nomenclature is essential for enabling clear communication and joint research efforts in this constantly growing sector. The authors recognize that since their groundbreaking 2016 guidelines suggested a systematic naming system, a significant number of unique disease-causing genes have been uncovered, and changes need to be made to account for these new discoveries. A significant upgrade is the planned separation of the imaging-based categories of “Primary Familial Brain Calcification” and “Neurodegeneration with Brain Iron Accumulation,” with both genetic disorders being reclassified based on their dominant clinical movement disorder manifestation. The authors introduce the new category of “Mixed Movement Disorders” to describe disorders characterized by numerous equally significant movement disorder symptoms, reflecting the complicated genetic heterogeneity that is frequently observed. Perhaps the most valuable contribution is the provision of meticulously updated lists covering 89 newly confirmed monogenic causes across the full spectrum of movement disorder phenotypes. These span parkinsonism (6 genes), dystonia (21 genes), dominant and recessive ataxia (38 genes), chorea (5 genes), myoclonus (7 genes), spastic paraplegia (13 genes), paroxysmal movement disorders (3 genes), and the new mixed movement disorder category (6 genes). Additionally, ten genes linked to combined phenotypes have been assigned two new prefixes per the naming system.

This comprehensive genetic update from the preeminent international society represents an essential resource not just for clinicians and researchers in the movement disorders field but also for all professionals engaged in neurogenetics. Its standardized nomenclature facilitates seamless integration of new genomic findings while providing a shared lexicon for interdisciplinary collaboration. By systematically classifying both established and newly identified genetic causes across all major movement disorder phenotypes, including PD and parkinsonism, this source is directly relevant and valuable for advancing research and clinical care in this domain.

Mei, Y. L., Yang, J., Wu, Z. R., Yang, Y., & Xu, Y. M. (2021). Transcranial Sonography of the Substantia Nigra for the Differential Diagnosis of Parkinson’s Disease and Other Movement Disorders: A Meta‐Analysis. Parkinson’s Disease, 2021(1), 8891874. https://onlinelibrary.wiley.com/doi/pdf/10.1155/2021/8891874

The differentiation between Parkinson’s disease and other movement disorders, particularly in early or atypical presentations, remains a challenge with significant prognostic potential. This meta-analysis aims to synthesize the available evidence for the utility of TCS of the SN, an affordable and noninvasive neuroimaging technique, in this differential diagnostic process. The authors provided a systematic review of the studies that compared SN echogenicity on TCS between IPD and non-IPD patients published between 2015 and 2020. They only included nine studies that met the eligibility criteria and involved 1046 participants, of whom 669 had PD, to evaluate the pooled diagnostic performance measures of SN hyperechogenicity for discriminating PD. Their results demonstrated that SN hyperechogenicity on TCS has a promising diagnostic profile, with a pooled sensitivity of 0.85 and specificity of 0.71 for differentiating idiopathic PD from other movement disorder etiologies. The area under the summary receiver operating characteristic curve was a respectable 0.94, indicating high overall diagnostic accuracy.

These findings highlight the validity and clinical relevance of TCS as an additional tool for differentiating Parkinson’s disease from other movement disorders. While not intended to replace comprehensive clinical evaluation, TCS can provide an important piece of objective neuroimaging evidence to increase diagnostic confidence, particularly in ambiguous cases. As a safe, inexpensive, and widely available technique, TCS of the SN represents a practical option for enhancing diagnostic rigor when PD is suspected, but other possibilities remain. This meta-analysis makes a valuable contribution by systematically quantifying the diagnostic performance of TCS for discriminating PD in the context of other movement disorders. Its positive findings are directly relevant and can help guide clinicians in judiciously incorporating this neuroimaging modality into their diagnostic workup where appropriate. In the challenging realm of movement disorder diagnosis, every additional valid tool that improves accuracy has meaningful implications for ensuring optimal patient management and treatment selection.

Papa, S. M., Brundin, P., Fung, V. S., Kang, U. J., Burn, D. J., Colosimo, C., ... & MDS‐Scientific Issues Committee. (2020). Impact of the COVID‐19 pandemic on Parkinson's disease and movement disorders. Movement disorders clinical practice, 7(4), 357. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7197322/pdf/MDC3-7-357.pdf

This timely paper provides critical insights into the profound impact of the COVID-19 global pandemic on the vulnerable population of patients with Parkinson’s disease and other movement disorders. The authors commence by reviewing the latest understanding of COVID-19 epidemiology, symptomatology, pathophysiology, and clinical management perspectives as of early 2020 when the pandemic was rapidly intensifying worldwide. A key emphasis is on the heightened risks and challenges faced specifically by movement disorder patients during this crisis. Older age and common comorbidities like hypertension, cardiovascular disease, and diabetes are highlighted as major risk factors for developing severe COVID-19 requiring hospitalization. These risk factors are highly prevalent in the PD and movement disorder population, rendering them particularly susceptible.

Beyond vulnerability to the viral infection itself, the authors astutely examine the widespread disruptions and barriers to ongoing care and disease management precipitated by the pandemic. Issues like difficulties accessing movement disorder specialists, procedure and surgery cancellations or delays, and interruptions to medication supply chains are all highlighted. The mental health toll of isolation and increased caregiver burden is also discussed. Importantly, the authors speculate about the potential neurological consequences of COVID-19 itself, theorizing that it could precipitate or exacerbate parkinsonism and other movement disorders based on emerging anecdotal evidence. While still an area requiring further research, this possibility adds another layer of concern.

Though focused specifically on the COVID-19 context, this paper is highly relevant as it encapsulates the multitude of direct and indirect ways in which a global health emergency can profoundly impact a neurological patient population with specialized care needs. Its forward-looking perspective identifies key areas requiring advocacy, resources, and study to safeguard the well-being of movement disorder patients during public health emergencies and beyond. By comprehensively examining the multifaceted challenges of COVID-19 for the PD and related movement disorder population, this paper calls crucial attention to an issue of paramount importance. Its insights can inform efforts by clinicians, healthcare systems, professional societies, and policymakers to develop strategies and contingencies that ensure continuous, high-quality care for these vulnerable patient groups, even amidst crises of this scale.

Rascol, O., Fabbri, M., & Poewe, W. (2021). Amantadine in the treatment of Parkinson's disease and other movement disorders. The Lancet Neurology, 20(12), 1048-1056. https://www.sciencedirect.com/science/article/am/pii/S1474442221002490

This authoritative review provides a timely reappraisal of amantadine, one of the oldest medications for Parkinson’s disease (PD), examining its unique pharmacological profile and therapeutic potential across the spectrum of movement disorders. The authors trace amantadine’s serendipitous origins, initially developed as an anti-influenza drug before its antiparkinsonian effects were discovered by observant clinicians in the 1960s. They underscore how amantadine has endured decades of use, unlike many repurposed drugs that are ultimately abandoned.

A key focus is on amantadine’s dual dopaminergic and glutamatergic mechanisms of action, a highly unusual combination accounting for its efficacy in treating not only Parkinsonian motor symptoms but also levodopa-induced dyskinesias (LID). Notably, amantadine remains the only medication with proven efficacy for LID, a debilitating complication of long-term levodopa therapy. The authors provide an in-depth discussion of the evidence supporting amantadine’s use across various stages and aspects of PD management, from early untreated PD to motor fluctuations, LID, and non-motor symptoms. Extending beyond its established PD indications, the authors comprehensively review amantadine’s off-label use in other movement disorders based on empirical experience. Applications in conditions like atypical Parkinsonian disorders, Huntington’s disease, dystonia, and tics are critically evaluated. Despite being an old drug, the authors argue that amantadine’s full therapeutic potential likely remains underexplored due to an incomplete understanding of its pleiotropic pharmacology and mechanisms.

A key take-home argument is the need to revive rigorous scientific inquiry into this unique but relatively neglected drug. New studies could not only enhance the use of amantadine in treating PD but also enhance its potential for repurposing in other MDs and neurological conditions associated with dopaminergic or glutamatergic dysfunction. Recent scientific discoveries linking the genetic and molecular mechanisms of most movement disorders offer a compelling reason to reconsider the role of amantadine under the prism of contemporary knowledge. In identifying amantadine as a multifaceted therapeutic agent needing a revival of studies, this broad review provides an invaluable contribution to the treatment of PD and other movement disorders. Its call to better leverage this distinctive pharmacological agent could open new avenues for therapeutic innovation and repurposing in an era of rapidly evolving mechanistic insights across neurological disease. Amantadine is an outstanding candidate for new studies because it has a strong evidence base from different decades and a rather broad therapeutic window.

In summary, these 5 sources offer a comprehensive view of Parkinson’s disease and other movement disorders. These include epidemiology, genetics, clinical manifestations, investigation, management, and recent developments. These are relevant sources as they focus on the main research question from different perspectives and present updated knowledge and findings on this relevant category of neurological disorders.