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Importance: Parkinsonism is associated with traumatic brain injury and chronic traumatic encephalopathy (CTE), a neurodegenerative disease associated with repetitive head impact (RHI) exposure, but the neuropathologic substrates that underlie parkinsonism in individuals with CTE are yet to be defined., Objective: To evaluate the frequency of parkinsonism in individuals with CTE and the association of RHI and neuropathologic substrates with parkinsonism in these individuals., Design, Setting, and Participants: This cross-sectional study included brain donors with neuropathologically diagnosed CTE without other significant neurodegenerative disease and with information on parkinsonism from the Understanding Neurologic Injury and Traumatic Encephalopathy brain bank between July 2015 and May 2022., Exposure: Years of contact sports participation as a proxy for RHI., Main Outcomes and Measures: The main outcomes were frequency of parkinsonism in individuals with CTE and associations between (1) RHI with substantia nigra (SN) Lewy bodies (LBs) and neurofibrillary tangles (NFTs); (2) LBs, NFTs, and arteriolosclerosis with SN neuronal loss; and (3) SN neuronal loss, LBs, NFTs, and arteriolosclerosis with parkinsonism, tested by age-adjusted logistic regressions., Results: Of 481 male brain donors with neuropathologically diagnosed CTE, parkinsonism occurred frequently in individuals with CTE (119 [24.7%]; 362 [75.3%] did not have parkinsonism). Participants with parkinsonism had a higher mean (SD) age at death (71.5 [13.0] years) than participants without parkinsonism (54.1 [19.3] years) (P < .001) and higher rates of dementia (104 [87.4%] vs 105 [29.0%]), visual hallucinations (45 [37.8%] vs 51 [14.1%]), and probable rapid eye movement sleep behavior disorder (52 [43.7%] vs 58 [16.0%]) (P < .001 for all). Participants with parkinsonism had a more severe CTE stage (eg, stage IV: 35 [29.4%] vs 39 [10.8%]) and nigral pathology than those without parkinsonism (NFTs: 50 of 117 [42.7%] vs 103 of 344 [29.9%]; P = .01; neuronal loss: 61 of 117 [52.1%] vs 59 of 344 [17.1%]; P < .001; and LBs: 28 of 116 [24.1%] vs 20 of 342 [5.8%]; P < .001). Years of contact sports participation were associated with SN NFTs (adjusted odds ratio [AOR], 1.04; 95% CI, 1.00-1.07; P = .03) and neuronal loss (AOR, 1.05; 95% CI, 1.01-1.08; P = .02). Nigral neuronal loss (AOR, 2.61; 95% CI, 1.52-4.47; P < .001) and LBs (AOR, 2.29; 95% CI, 1.15-4.57; P = .02) were associated with parkinsonism. However, SN neuronal loss was associated with SN LBs (AOR, 4.48; 95% CI, 2.25-8.92; P < .001), SN NFTs (AOR, 2.51; 95% CI, 1.52-4.15; P < .001), and arteriolosclerosis (AOR, 2.27; 95% CI, 1.33-3.85; P = .002). In American football players, regression analysis demonstrated that SN NFTs and neuronal loss mediated the association between years of play and parkinsonism in the context of CTE (β, 0.012; 95% CI, 0.001-0.038)., Conclusions and Relevance: In this cross-sectional study of contact sports athletes with CTE, years of contact sports participation were associated with SN tau pathology and neuronal loss, and these pathologies were associated with parkinsonism. Repetitive head impacts may incite neuropathologic processes that lead to symptoms of parkinsonism in individuals with CTE.

Parkinsonism-hyperpyrexia syndrome (PHS) is a rare, fatal complication of Parkinson's disease (PD) that manifests in patients who abruptly discontinue or reduce their antiParkinsonian medication. To the best of our knowledge, this is the first report of a PHS case occurring in a patient undergoing general anesthesia. In the perioperative period of PD patients, it is important for anesthesiologists to prevent PHS as well as monitor patients to enable early detection and prompt response when it occurs., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 International Anesthesia Research Society.)

Competing Interests: The authors have no conflict of interest to declare.

Snakebites are a major cause of morbidity and mortality worldwide. Snake envenomation can cause acute local and systemic effects leading to severe complications, even death. Neurological complications such as intracranial hemorrhage, subarachnoid bleed, ischemic strokes, acute disseminated encephalomyelitis, and leukoencephalopathy have been reported. Anti-snake venom which forms the mainstay of therapy also has its own set of early and delayed complications. This report describes a rare case of snakebite resulting in leukoencephalopathy and parkinsonian features., (Copyright © 2024 Copyright: © 2024 Annals of African Medicine.)

Background: The clinical features and outcomes of post-COVID parkinsonism have not been organized systematically, and the possible correlations between COVID-19 and parkinsonism have not been elucidated. This scoping review addresses these two unmet needs., Methods: We searched two databases (Pubmed, Embase) for all published cases of post-COVID parkinsonism. Data were extracted from eligible studies using standardized forms and predefined inclusion and exclusion criteria. The patients' clinical features, their diagnosis and outcomes were assessed objectively., Results: Twenty-six cases of post-COVID parkinsonism were reported in 17 publications. Their presenting features were grouped into three clinical syndromes: typical parkinsonian motor syndrome (12 patients), parkinsonism with postural instability and gait disorder (three), or encephalopathy with parkinsonism (10). Patients had the following diagnoses: clinically established Parkinson's disease (PD, three cases), clinically probable PD (eight), clinically probable multiple system atrophy (one), acquired parkinsonism (six), unclassified parkinsonism (eight). Isolated parkinsonian motor syndromes typically followed uncomplicated COVID-19 illness or pneumonia; instead, encephalopathy with parkinsonism was observed following a wide spectrum of COVID-19-related presentations, including severe forms. PD cases mainly occurred following uncomplicated COVID-19, whereas acquired or unclassified parkinsonism were reported following different COVID-19 presentations., Conclusions: Patients with uncomplicated COVID-19 are more likely to present PD and no signs of encephalopathy. There is no demonstration of a causative role of COVID-19, which can be coincidental in several cases. Patients with encephalopathy and parkinsonism constitute a distinct subset, suggesting a potentially different pathogenic role of SARS-CoV-2 infection. These findings provide a basis for further studies in the post-pandemic phase., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Alberto Albanese reports financial support was provided by Cariplo Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Intracranial dural arteriovenous fistulas (IDAVFs) are abnormal vascular connections between dural arteries and various venous structures within the brain. IDAVFs, rarely present with parkinsonism and dementia concurrently, making this a unique and underexplored clinical scenario. To the best of our knowledge, this is the first systematic review to comprehensively analyze cases of IDAVFs manifesting as both parkinsonism and dementia., Methods: We assessed databases from inception to September 18, 2023. We identified studies describing patients with IDAVFs initially presenting with dementia or parkinsonism. Inclusion criteria encompassed case reports and case series, while excluding review articles, guidelines, technical notes, comments, conference abstracts, and editorials., Results: The systematic search resulted in the initial screening of 383 studies, with 33 articles meeting the inclusion criteria. Among these, 29 were case reports, often describing 3 or fewer patients. From the remaining 4 case series, data pertinent to patients presenting both parkinsonism and dementia were selectively extracted, yielding a total study population of 43 patients. The anatomical distribution of IDAVFs within this cohort was diverse, with the transverse and sigmoid sinuses being the most common locations. Although most of these patients received endovascular therapy, a few underwent microsurgical occlusion or combined surgical and endovascular treatment., Conclusions: IDAVFs presenting with both parkinsonism and dementia represent a rare clinical entity. This systematic review provides valuable insights into the clinical characteristics, treatment options, and outcomes for such cases. However, additional research involving larger cohorts is essential to better comprehend the underlying mechanisms and establish standardized therapeutic guidelines., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Vascular Parkinsonism (VP) is clinical term represents a progressive ischemic changes and subcortical lacunar infarct leading to Parkinsonism mainly in the lower limbs so called lower body Parkinsonism. The VP neuropathology is differed from that of PD neuropathology which rarely associated with basal ganglion lesions. Dopamine transporters are normal in VP but are highly reduced in PD, and dopaminergic agonists had no effective role on VP. The neuropathological mechanisms of VP are related to vascular injury which induces the interruption of the neural connection between basal ganglion and cerebral cortex. Hyperlipidemia and other cardiometabolic risk factors augment VP risk and the related neuropathology. Targeting of these cardiometabolic disorders by lipid-lowering statins may be effective in the management of VP. Therefore, this mini-review aims to clarify the possible role of statins in the management of VP. Statins have neuroprotective effects against different neurodegenerative diseases by anti-inflammatory, antioxidant and antithrombotic effects with enhancement of endothelial function. In conclusion, statins can prevent and treat VP by inhibiting inflammatory and oxidative stress disorders, mitigating of white matter hyperintensities and improving of neuronal signaling pathways. Additional preclinical, clinical trials and prospective studies are warranted in this regard., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Fahr's disease is a rare condition characterised by the presence of idiopathic familial bilateral basal ganglia calcifications, transmitted in an autosomal-dominant fashion. Diagnosis is based on clinical features of neuropsychiatric and somatic symptoms in conjunction with radiological findings. Our patient, a man in his early 50s, presented with pneumonia. History was significant for five admissions in the last 2 years for pneumonia and falls, with gradual cognitive and motor decline since his late 30s. Hypophonia, bradykinesia and dementia were noted on examination. CT of the brain revealed bilateral thalamic calcinosis, consistent with Fahr's syndrome. Further investigations and retrospective history taking, and similar radiological findings within first-degree and second-degree relatives with early deaths, transitioned the diagnosis from Fahr's syndrome to Fahr's disease. We present this case of Fahr's disease to emphasise the value of collaboration among multidisciplinary professionals to improve quality of care for such patients., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The Amyotrophic Lateral Sclerosis-Parkinsonism-Dementia Complex (ALS-PDC) was first described in the islands of Guam. This pathology presented its peak incidence in the 1950s. Due to the rarity of the association, we report a clinical case with this complex. The objective was to describe the nosological and pathogenic implications of these neurodegenerative disorder, since they are not frequent to find in our population., Clinical Case: We present a case of Latinoamerican origin who initially manifested systemic symptoms of more than 6 years of evolution, with subsequent cognitive alterations. Later, patient began with gait disturbances and motor symptoms suggestive of parkinsonism with atypical data and data of motor neurone disease (MND). More studies were carried out and confirmed findings compatible with upper and lower motor neuron involvement. A mutation in the POLG gene was observed, related to mitochondrial depletion syndrome., Conclusion: Despite the knowledge of this association, it is an entity whose clinical diagnosis could be very difficult to achieve. In addition, molecular mechanisms have not been fully identified, the most common genes related to Parkinsonism and ALS have been excluded, and even attempts to locate the locus were made, without achieving accurate results. Unfortunately, being a neurodegenerative disease, the prognosis is fatal, with no disease-modifying treatment., (Licencia CC 4.0 (BY-NC-ND) © 2023 Revista Médica del Instituto Mexicano del Seguro Social.)

Recent studies have demonstrated that atypical parkinsonism can be presented in autoimmune encephalitis and paraneoplastic neurological syndromes. However, it is unclear which anti-neural antibodies are involved and when these diseases should be suspected. To address these clinical questions, we conducted a scoping review and analyzed 38 articles. The literature shows that many anti-neural antibodies, including unknown ones, have been reported in progressive supranuclear palsy, corticobasal syndrome, and multiple system atrophy. Moreover, the following symptoms and signs suggest the possibility of autoimmune encephalitis and paraneoplastic neurological syndromes: early onset, acute or subacute progression, the presence of a neoplasm, significant weight loss, abnormal cerebrospinal fluid findings, the absence of typical brain magnetic resonance imaging findings, and the existence of atypical physical examination signs.

BACKGROUND A first psychotic episode requires the exclusion of toxic-metabolic, inflammatory, infective, and neoplastic causes. Wilson disease is a rare, autosomal recessive disorder of copper metabolism and can present with neuropsychiatric symptoms secondary to copper accumulation in the brain. CASE REPORT We describe the case of a 48-year-old man with parkinsonism on a background of longstanding schizophrenia and psychotic depression in the setting of previously undiagnosed Wilson disease. The common history of neuropsychiatric disturbance and neuroleptic use complicated the assessment of parkinsonism. However, close attention to the temporal appearance of symptoms and signs differentiated his case from drug-induced parkinsonism, which commonly develops hours to weeks after commencement or uptitration of antipsychotic medication. The early features of sialorrhea and dysarthria were also atypical for idiopathic Parkinson disease. The diagnosis was confirmed by serum copper testing and supported by Kayser-Fleischer rings on bedside ophthalmological examination. Magnetic resonance imaging (MRI) of the brain demonstrated copper accumulation in the basal ganglia and pons, contributing to the characteristic neurological manifestations of an akinetic-rigid syndrome with dysarthria. CONCLUSIONS Serum copper testing is easily obtained and should be considered as part of the first-line investigations for new neuropsychiatric disturbances. Although rare, Wilson disease, if diagnosed early, is a potentially treatable and reversible cause of psychosis. With advanced disease, extrapyramidal findings on examination correlate with MRI brain changes, aiding the clinical assessment in differentiating the disease from drug-induced parkinsonism.

Introduction: Neuropsychiatric manifestations in systemic lupus erythematosus (SLE) occur in about half of the patients; however, movement disorders like Parkinsonism are rare. We describe a case of SLE who presented solely with features of Parkinsonism., Case Report: 50-year-old female presented with global slowing of movements and slowing of speech since 2 months. On examination, she had mask-like facies with a faint malar rash sparing the nasolabial folds, hard palate ulcer, cog-wheel rigidity, and proximal muscle weakness. Lab evaluation revealed lymphopenia, high ESR, elevated lactate dehydrogenase, creatinine phosphokinase, AST, and ALT levels. She had high anti-dsDNA levels with low complements. Urinalysis showed proteinuria and hematuria. ANA was positive at a titer of 1:320, and she had positive anti-ribosomal-P antibody. She had severe flare with a SLEDAI of 33. She was treated with pulse IV methylprednisolone followed by cyclophosphamide (NIH protocol). At 4 weeks follow-up, she had dramatic improvement in her Parkinsonian symptoms and her proximal muscle weakness., Discussion: The prevalence of movement disorders in cases of neuropsychiatric SLE is very low at 0.7%, with chorea being most frequent and Parkinsonism rare. The pathogenesis is multifactorial including anti-dopaminergic antibodies or associated anti-phospholipids causing microvascular thrombosis or vasculitis of the thalamostriatal arteries or disease activity itself. As in our case, immunosuppression and optimal treatment of active lupus reverts symptoms in most cases., Conclusion: A high index of suspicion needs to be exercised in cases of SLE presenting with Parkinsonism as adequate immunosuppression translates to near-complete recovery.

Parkinsonism can have many causes, among them cerebrovascular disease. Vascular parkinsonism can be caused by infarction or haemorrhage in the nigrostriatal pathway, resulting in hemiparkinsonism, or by widespread small vessel disease in the white matter, leading to the gradual development of bilateral symptoms in the lower extremities. Compared to patients with Parkinson's disease, individuals with vascular parkinsonism have earlier onset of gait disturbance, are more likely to have urinary incontinence and cognitive impairment, and have poorer treatment response and prognosis; however, they are less likely to have tremor. With its unclear pathophysiology, varying clinical picture and overlap with other diseases, vascular parkinsonism remains a little known and somewhat controversial diagnosis.

Background: Parkinsonism after ventriculoperitoneal shunt in patients with hydrocephalus is a rare and profound complication that is often misdiagnosed, causing treatment to be delayed. To date, the characteristics of this disease have not been well described and summarized. Here, we report a rare case of parkinsonism after ventriculoperitoneal shunt; symptoms were aggravated by antipsychotic drugs but showed a good response to Madopar. Such cases have rarely been reported previously., Case Presentation: A 44-year-old man presented with parkinsonism, bilateral pyramidal tract signs, and oculomotor impairment four years after a successful ventriculoperitoneal shunt for idiopathic aqueduct stenosis resulting in obstructive hydrocephalus. Brain magnetic resonance imaging and computed tomography showed fluctuations in the lateral ventricle and the third ventricle without any intervention. The patient's condition was aggravated by antipsychotic drugs but showed a good response to Madopar., Conclusion: This observation suggests that parkinsonism in this patient was caused by reversible dysfunction of the presynaptic nigrostriatal dopaminergic pathway due to fluctuations in the lateral ventricle, representing the first hit to the dopaminergic signalling pathway, and antipsychotic drugs had an antagonistic effect on dopamine D2 receptors, representing the second hit. In addition, we summarize the pathophysiological mechanisms, clinical manifestations, treatments, and prognoses of this complication in 38 patients who met the inclusion criteria in 24 previous studies to increase neurologists' understanding of the disease., (© 2023. The Author(s).)

Dementia with Lewy bodies (DLB) is clinically defined by the presence of visual hallucinations, fluctuations, rapid eye movement (REM) sleep behavioral disorder, and parkinsonism. Neuropathologically, it is characterized by the presence of Lewy pathology. However, neuropathological studies have demonstrated the high prevalence of coexistent Alzheimer's disease, TAR DNA-binding protein 43 (TDP-43), and cerebrovascular pathologic cases. Due to their high prevalence and clinical impact on DLB individuals, clinical trials should account for these co-pathologies in their design and selection and the interpretation of biomarkers values and outcomes. Here we discuss the frequency of the different co-pathologies in DLB and their cross-sectional and longitudinal clinical impact. We then evaluate the utility and possible applications of disease-specific and disease-nonspecific biomarkers and how co-pathologies can impact these biomarkers. We propose a framework for integrating multi-modal biomarker fingerprints and step-wise selection and assessment of DLB individuals for clinical trials, monitoring target engagement, and interpreting outcomes in the setting of co-pathologies., (© 2022 the Alzheimer's Association.)

Background: Coronavirus disease 2019 (COVID-19) is an infectious disease mainly affecting the respiratory system; however, a significant prevalence of neurological symptoms has been noted., Objectives: To investigate the incidence and characteristics of post-COVID-19 parkinsonism and to study dyskinesia related to COVID-19 vaccines., Material and Methods: The MEDLINE, PubMed, Scopus, and Web of Science databases were searched for all manuscripts relevant to post-COVID-19 parkinsonism and dyskinesia related to COVID-19 vaccines. Subsequently, we extracted and analysed data from the manuscripts in a structured manner., Results: We found 24 patients with post-COVID-19 parkinsonism, with a mean onset age of 58 years after a mean of 30 days from the COVID-19 onset. Akinetic-rigid (n = 11) and mixed (n = 6) subtypes were the most common. Asymmetry was present in 13/15 patients. Brain MRI was unremarkable in 11/19, whereas dopaminergic system imaging was abnormal in 8/8 patients. Responsiveness to dopaminergic treatment was observed in 12/15 patients. Four patients improved after immunomodulatory therapy. Comorbidities were present in 9/24, encephalopathy symptoms in 11/24, and loss of smell in 9/13 patients. Most patients (n = 14) suffered serious COVID-19- related complications and three were treated with haloperidol. Parkinsonism improved (n = 5) or resolved (n = 4) during the follow-up. Five patients, with a mean age of 52, developed dyskinesia at a mean of 25 hours after receiving the COVID-19 mRNA vaccines. One patient had a history of neuropsychiatric symptoms and developed functional dyskinesia of the tongue. Four patients had a previous history of Parkinson's Disease (PD) with a mean duration of 10 years and developed dyskinesia and dystonia, which resolved (n = 2) or improved (n = 2) during the follow-up., Conclusions: Post-COVID-19 parkinsonism is a very rare complication, and it is likely that this is an umbrella syndrome that includes many different etiologies. Dyskinesia due to COVID-19 vaccines is exceedingly rare and probably has the same pathophysiological basis as in other conditions with exacerbation of PD symptoms.

We experienced a young patient who presented with progressive parkinsonism and cerebellar ataxia. Brain magnetic resonance imaging revealed progressive brain calcification, expanding from the bilateral basal ganglia to the central pons, caused by a delayed reaction to the radiation therapy that she had received to treat craniopharyngioma 14 years earlier. Heterogeneous clinical symptoms due to radiation-induced brain calcification have been described, but parkinsonism has never been reported. While dopamine transporter-single photon emission computed tomography revealed only slight damage to the dopaminergic striatal pathway, the extension of calcification to the periventricular white matter was likely responsible for her parkinsonism.

Competing Interests: Declaration of interests We declare no competing interests.

The findings regarding whether the greater iron level or intake is a risk factor to Parkinson's disease (PD) or parkinsonism was not clear. The purpose of this study is to establish a consistent association between iron supplementation and parkinsonism risk, we conducted a large-scale prospective cohort study using comprehensive longitudinal data from the UK Biobank. The longitudinal cohort data of 385,898 participants (including 911 cases) who were middle to old aged British adults and joined the UK Biobank study from 2006 to 2010 and were followed up until 2018 was analyzed. The associations between iron supplement intake, hemoglobin levels and all cause subsequent parkinsonism risk after corrections of potential confounders (sex, age, household income, education length, employment status, deprivation level, body mass index, physical activity level, household numbers, smoking and drinking levels, health status, blood pressure) were investigated. Analyses revealed that (a) iron supplementation was significantly associated with higher parkinsonism risk, (b) greater hemoglobin was weakly and insignificantly associated with lower parkinsonism risk, and (c) multivitamin or vitamin C supplement intake was not significantly associated with parkinsonism risk. Regardless of whether the subjects were classified as anemic, normal, or polycythemic or in the hemoglobin level quintile, there was no nonlinear association between hemoglobin and parkinsonism risk. Parkinsonism risk did not differ between participants reporting supplementary iron intake with or without vitamin C or multivitamin supplement intake. Furthermore, polygenic risk score of PD negatively correlated with hemoglobin level, while it did not associate with intake of iron supplement or multivitamin or vitamin C supplement intake. The results suggest excessive iron intake may increase parkinsonism risk. Interventional studies are warranted to examine whether iron intake restriction is beneficial for individuals without clinical iron deficiency.

Cat scratch disease (CSD) is a zoonotic infection caused by Bartonella henselae typically resulting in self-limited regional lymphadenopathy. Encephalitis is a complication with a supposedly benign prognosis, but we encountered an exceptional case. A 19-year-old Japanese woman presented with status epilepticus. She was diagnosed with CSD-associated encephalitis based on her history of contact with a kitten and a high titre of serum IgG to B. henselae. Multimodal treatment ameliorated her encephalitis, but neurological sequelae including spastic paraparesis, persisted. After several months, she developed age-disproportionate parkinsonism inconsistent with a neurodegenerative disease. In conclusion, CSD-associated encephalitis can result in severe neurological sequelae and post-encephalitic parkinsonism.

Parkinsonism secondary to viral infections is not an uncommon occurrence and has been brought under the spotlight with the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A variety of viruses have been described with a potential of inducing or contributing to the occurrence of parkinsonism and Parkinson's disease (PD), although the relationship between the two remains a matter of debate originating with the description of encephalitis lethargica in the aftermath of the Spanish flu in 1918. While some viral infections have been linked to an increased risk for the development of PD, others seem to have a causal link with the occurrence of parkinsonism. Here, we review the currently available evidence on viral-induced parkinsonism with a focus on potential pathophysiological mechanisms and clinical features. We also review the evidence on viral infections as a risk factor for developing PD and the link between SARS-CoV-2 and parkinsonism, which might have important implications for future research and treatments., (© 2022. The Author(s).)

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease after Alzheimer's disease, globally. Dopaminergic neuron degeneration in substantia nigra pars compacta and aggregation of misfolded alpha-synuclein are the PD hallmarks, accompanied by motor and non-motor symptoms. Several viruses have been linked to the appearance of a post-infection parkinsonian phenotype. Coronavirus disease 2019 (COVID-19), caused by emerging severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, has evolved from a novel pneumonia to a multifaceted syndrome with multiple clinical manifestations, among which neurological sequalae appear insidious and potentially long-lasting. Exosomes are extracellular nanovesicles bearing a complex cargo of active biomolecules and playing crucial roles in intercellular communication under pathophysiological conditions. Exosomes constitute a reliable route for misfolded protein transmission, contributing to PD pathogenesis and diagnosis. Herein, we summarize recent evidence suggesting that SARS-CoV-2 infection shares numerous clinical manifestations and inflammatory and molecular pathways with PD. We carry on hypothesizing that these similarities may be reflected in exosomal cargo modulated by the virus in correlation with disease severity. Travelling from the periphery to the brain, SARS-CoV-2-related exosomal cargo contains SARS-CoV-2 RNA, viral proteins, inflammatory mediators, and modified host proteins that could operate as promoters of neurodegenerative and neuroinflammatory cascades, potentially leading to a future parkinsonism and PD development.

Competing Interests: The authors have no conflict of interests to declare.

The relationship between cerebrovascular disease and parkinsonism is commonly seen in everyday clinical practice but remains ill-defined and under-recognised with little guidance for the practising neurologist. We attempt to define this association and to illustrate key clinical, radiological and pathological features of the syndrome of Vascular Parkinsonism (VaP). VaP is a major cause of morbidity in the elderly associated with falls, hip fractures and cognitive impairment. Although acute parkinsonism is reported in the context of an acute cerebrovascular event, the vast majority of VaP presents as an insidious syndrome usually in the context of vascular risk factors and radiological evidence of small vessel disease. There may be an anatomic impact on basal ganglia neuronal networks, however the effect of small vessel disease (SVD) on these pathways is not clear. There are now established reporting standards for radiological features of SVD on MRI. White matter hyperintensities and lacunes have been thought to be the representative radiological features of SVD but other features such as the perivascular space are gaining more importance, especially in context of the glymphatic system. It is important to consider VaP in the differential diagnosis of Parkinson disease (PD) and in these situations, neuroimaging may offer diagnostic benefit especially in those patients with atypical presentations or refractoriness to levodopa. Proactive management of vascular risk factors, monitoring of bone density and an exercise program may offer easily attainable therapeutic targets in PD and VaP. Levodopa therapy should be considered in patients with VaP, however the dose and effect may be different from use in PD. This article is part of the Special Issue "Parkinsonism across the spectrum of movement disorders and beyond" edited by Joseph Jankovic, Daniel D. Truong and Matteo Bologna., (Copyright © 2021. Published by Elsevier B.V.)

Secondary parkinsonism, namely parkinsonism due to causes other than idiopathic neurodegeneration, may have multiple etiologies. Common secondary etiologies of parkinsonism such as drug-induced or vascular etiologies are well documented. Other secondary causes of parkinsonism such as infectious (mainly viral and prion-like diseases), autoimmune (systemic/drug-induced) and paraneoplastic etiologies are rare but are a topic of increasing interest. Older examples from the existing literature demonstrate the intricacies of viral infection from the last pandemic of the 20th century on the development of hypokinetic symptoms experienced in post-encephalitic patients. Viral and prion-like infections are only part of a complex interplay between the body's immune response and aberrant cell cycle perturbations leading to malignancy. In addition to the classic systemic autoimmune diseases (mainly systemic lupus erythematosus - SLE, and Sjögren syndrome), there have been new developments in the context of the current COVID-19 pandemic as well as more prominent use of immunotherapies such as immune checkpoint inhibitors in the treatment of solid tumors. Both of these developments have deepened our understanding of the underlying pathophysiologic process. Increased awareness and understanding of these rarer etiologies of parkinsonism is crucial to the modern diagnostic evaluation of a patient with parkinsonian symptoms as the potential treatment options may differ from the conventional levodopa-based therapeutic regimen of idiopathic Parkinson's disease. This review article aims to give an up-to-date review of the current literature on parkinsonian symptoms, their pathogenesis, diagnostic methods, and available treatment options. Many potential future directions in the field of parkinsonian conditions remain to be explored. This article is part of the Special Issue "Parkinsonism across the spectrum of movement disorders and beyond" edited by Joseph Jankovic, Daniel D. Truong and Matteo Bologna., (Copyright © 2021 Elsevier B.V. All rights reserved.)

We report a case of a 67-year-old male recipient of a second renal allograft, presenting with a 9-month history of progressive cognitive and physical decline with features of Parkinsonism. He was HIV-negative. Serum and cerebrospinal fluid (CSF) cryptococcal antigen was positive though CSF culture was sterile. He had progressive deterioration despite induction and consolidation antifungal treatment. Postmortem brain examination confirmed a large burden of yeast forms in the substantia nigra with widespread chronic meningitis. The significant delay in presentation and diagnosis owing to the atypical, subacute neurocognitive features serves as a timely reminder of the variety of neurological presentations that may be associated with cryptococcal infection in solid organ transplant recipients., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Ankylosing spondylitis (AS) is an immune-mediated, chronic inflammatory rheumatic disorder. The etiology of Parkinson's disease (PD) is multifactorial; however, inflammation is receiving an increasing amount of attention as an underlying cause of the neurodegenerative process of PD., Objective: We performed a nationwide longitudinal, population-based matched cohort study to assess the association with the later development of parkinsonism in Korea., Methods: This study was conducted using records from the Health Insurance Review and Assessment Service database. The cumulative incidence rate of PD was estimated. Fine-Gray subdistribution hazard models were used to identify hazards associated with PD development based on the presence of AS. Exposure to anti-inflammatory drugs was measured and analyzed to determine the protective effect of these medications. Additionally, the hazard ratio (HR) for atypical parkinsonism was estimated., Results: The results of the Fine-Gray subdistribution hazard model revealed that the HR for PD development in the AS group was 1.82 (95%confidence interval [CI], 1.38-2.39, p < 0.001). A significant decrease in PD development was observed in patients with AS taking non-steroidal anti-inflammatory drugs (NSAIDs). The HR for atypical parkinsonism in the AS group was 3.86 (95%CI, 1.08-13.78, p < 0.05)., Conclusion: We found that AS was associated with an increased risk of PD and atypical parkinsonism. NSAIDs used for AS control have some protective effects against PD. Further studies assessing whether biological treatment mitigates PD risk in patients with high activity are warranted.

Manganese (Mn) is an essential trace element required for various biological processes. However, excess Mn causes serious side effects in humans, including parkinsonism. Thus, elucidation of Mn homeostasis at the systemic, cellular, and molecular levels is important. Many metal transporters and channels can be involved in the transport and homeostasis of Mn, and an increasing body of evidence shows that several zinc (Zn) transporters belonging to the ZIP and ZNT families, specifically, ZNT10, ZIP8, and ZIP14, play pivotal roles in Mn metabolism. Mutations in the genes encoding these transporter proteins are associated with congenital disorders related to dysregulated Mn homeostasis in humans. Moreover, single nucleotide polymorphisms of ZIP8 are associated with multiple clinical phenotypes. In this review, we discuss the recent literature on the structural and biochemical features of ZNT10, ZIP8, and ZIP14, including transport mechanisms, regulation of expression, and pathophysiological functions. Because a disturbance in Mn homeostasis is closely associated with a variety of phenotypes and risk of human diseases, these transporters constitute a significant target for drug development. An understanding of the roles of these key transporters in Mn metabolism should provide new insights into pharmacological applications of their inhibitors and enhancers in human diseases., Competing Interests: Declaration of competing interest Both authors declare no competing financial and non-financial interests., (Copyright © 2021 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

We herein report a case of sudden-onset parkinsonism, with no other symptoms, caused by intracranial dural arteriovenous fistulas (DAVFs). Diffusion-weighted magnetic resonance imaging (MRI) revealed an increased signal intensity in the bilateral lenticular nucleus. Endovascular embolization improved the patient's parkinsonism and MRI findings. DAVF should be suspected in cases of sudden-onset parkinsonism.

Considering the similarities with other pandemics due to respiratory virus infections and subsequent development of neurological disorders (e.g. encephalitis lethargica after the 1918 influenza), there is growing concern about a possible new wave of neurological complications following the worldwide spread of SARS-CoV-2. However, data on COVID-19-related encephalitis and movement disorders are still limited. Herein, we describe the clinical and neuroimaging (FDG-PET/CT, MRI and DaT-SPECT) findings of two patients with COVID-19-related encephalopathy who developed prominent parkinsonism. None of the patients had previous history of parkinsonian signs/symptoms, and none had prodromal features of Parkinson's disease (hyposmia or RBD). Both developed a rapidly progressive form of atypical parkinsonism along with distinctive features suggestive of encephalitis. A possible immune-mediated etiology was suggested in Patient 2 by the presence of CSF-restricted oligoclonal bands, but none of the patients responded favorably to immunotherapy. Interestingly, FDG-PET/CT findings were similar in both cases and reminiscent of those observed in post-encephalitic parkinsonism, with cortical hypo-metabolism associated with hyper-metabolism in the brainstem, mesial temporal lobes, and basal ganglia. Patient's FDG-PET/CT findings were validated by performing a Statistical Parametric Mapping analysis and comparing the results with a cohort of healthy controls (n = 48). Cerebrum cortical thickness map was obtained in Patient 1 from MRI examinations to evaluate the structural correlates of the metabolic alterations detected with FDG-PET/CT. Hypermetabolic areas correlated with brain regions showing increased cortical thickness, suggesting their involvement during the inflammatory process. Overall, these observations suggest that SARS-CoV-2 infection may trigger an encephalitis with prominent parkinsonism and distinctive brain metabolic alterations., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: The National Institute on Aging Alzheimer's Disease Research Center program added the Lewy body dementia module (LBD-MOD) to the Uniform Data Set to facilitate LBD characterization and distinguish dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). We tested the performance of the LBD-MOD., Methods: The LBD-MOD was completed in a single-site study in 342 participants: 53 controls, 78 AD, and 110 DLB; 79 mild cognitive impairment due to AD (MCI-AD); and 22 MCI-DLB., Results: DLB differed from AD in extrapyramidal symptoms, hallucinations, apathy, autonomic features, REM sleep behaviors, daytime sleepiness, cognitive fluctuations, timed attention tasks, and visual perception. MCI-DLB differed from MCI-AD in extrapyramidal features, mood, autonomic features, fluctuations, timed attention tasks, and visual perception. Descriptive data on LBD-MOD measures are provided for reference., Discussion: The LBD-MOD provided excellent characterization of core and supportive features to differentiate DLB from AD and healthy controls while also characterizing features of MCI-DLB., (© 2021 the Alzheimer's Association.)

Background: Dementia is a chronic loss of neurocognitive function that is progressive and irreversible. Dural arteriovenous fistulas (DAVFs) are acquired lesions that account for 10-15% of intracranial vascular malformations that could present with a rapid decline in neurocognitive function with or without Parkinson-like symptoms and evolve in a rapidly progressive dementia (RPD). Often the DAVFs are not even included in the differential hypotheses of this type of dementia and are not present in any type of diagnostic algorithm for evaluating RPD., Methods: We performed a systematic review of the international literature and adding the cases coming from our institutional experience and we have collected all the reported cases of DAVFs that debut with ROD identifying the most frequent forms in terms of location and type, reporting the neurological characteristics and the outcome of each patient., Results: The exact pathogenesis for developing dementia in patients with DAVFs remains largely unknown. The imaging changes and pathologic findings support the hypothesis that the clinical course results from the delivery of excessive volumes of blood flow into a venous system with outflow obstruction and venous congestion. The large variety of clinical manifestations of DAVFs depends on its location but this is not exactly valid for the onset of dementia. It supposed that the highly variable clinical manifestation of DAVFs has been convincingly related to the pattern of venous drainage more than location., Conclusions: Neurologists and clinicians generally are familiar with the differential diagnoses of slowly progressive neurodegenerative dementias, but the diagnosis of RPD entails a different diagnostic approach. Due to their curable nature, the diagnosis of DAVFs must be suspected when facing a RPD picture, even more so if it is associated with characteristic abnormalities of the hemispheric white matter., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Chronic subdural hematoma (CSDH) is one of the most common neurosurgical cases, especially in elderly individuals. Secondary parkinsonism due to CSDH is a rare entity. The mechanism of parkinsonism symptoms in chronic subdural hematoma has been suggested to include direct mechanical compression of the basal ganglia due to hematoma or indirectly through brain structure changes due to space lesions and vascular disorders. Surgery on the subdural hematoma provides a favorable outcome for parkinsonism symptoms., Objectives: To systematically review the literature on CSDH-induced parkinsonism., Search Methods: This is a systematic review on case reports. Literature search was performed using the predefined keywords on PubMed, ProQuest, and Google Scholar. We also provided our own case report and compared it with published studies., Result: Sixteen cases from 13 case reports/series were identified, predominantly consisting of male patients with the mean age of 66.5 ± 9.73 years. The most common symptoms were rigidity, gait disturbance, and bradykinesia, observed in 12 (75%) cases each. The second and third most common symptoms were tremor (11; 68.75%) and facial masking (8; 50%), respectively. Other reported symptoms were dysphasia (3; 18.75%), dysarthria (3; 18.75%), and urinary incontinence (2; 12. 5%). Time gap between the symptom onset and CSDH diagnosis and unilateral location seemed to influence the outcome., Conclusion: Only 16 CSDH-induced parkinsonism were identified since the 1960s. This condition is thought to occur due to basal ganglia compression. Surgery on the subdural hematoma provides a favorable outcome for parkinsonism symptoms. Timely CSDH diagnosis might yield better outcome. However, further research on CSDH-induced parkinsonism is needed, especially in the mechanisms and treatment outcomes., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Multiple system atrophy (MSA) presents with various combinations of autonomic dysfunction, parkinsonism, and cerebellar ataxia. Although clinical diagnostic criteria have been widely used, the sensitivity and specificity are suboptimal. This study aims to provide evidence supporting the revision of the current diagnostic criteria for MSA., Methods: Medical records of 171 patients with autopsy-confirmed MSA in the Mayo Clinic brain bank were reviewed with regard to their clinical features and diagnoses. Pathologic features, including concomitant pathologies (i.e., Alzheimer-related and Lewy-related pathologies), were also assessed., Results: The cohort included 133 MSA-parkinsonian type, 36 MSA-cerebellar type, and 2 unclassified MSA patients who did not show significant motor symptoms. Twenty-three patients (13%) were not clinically diagnosed with MSA, but instead with progressive supranuclear palsy, Parkinson's disease (PD), PD with dementia (PDD), or dementia with Lewy bodies (DLB). Three patients with PDD and DLB also had concomitant Lewy body pathology. Six patients had late-onset MSA, with an age of onset greater than 75 years. Erectile dysfunction was frequent in male patients (60/63; 95%) in all age ranges. REM sleep behavior disorder (RBD) was present in 82 patients (48%) and was the initial symptom in 13 patients. Cognitive impairment was present in 60 patients (35%), but was an initial symptom in only two patients., Conclusions: Our findings support the conclusion that late-onset presentation should not exclude MSA. The findings of this large autopsy-based cohort provides valuable insights for improving clinical criteria for MSA., (Copyright © 2021. Published by Elsevier Ltd.)