Simultaneous Parkinsonism and Dementia as Initial Presentation of Intracranial Dural Arteriovenous Fistulas: A Systematic Review.

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.

Fahr's disease in a patient with recurrent pneumonias, parkinsonism and dementia.

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.

New insight on the possible role of statins in Vascular Parkinsonism: A need for presumptive therapy.

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.

[Parkinson-dementia and amyotrophic lateral sclerosis association (complex of Guam). Diagnostic challenge, Mexican patient]. / Asociación Parkinson-demencia y esclerosis lateral amiotrófica (complejo Guam). Reto diagnóstico, paciente mexicano.

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.

Introducción: el complejo parkinsonismo-demencia-esclerosis lateral amiotrófica fue descrito por primera vez en las islas de Guam. Esta patología presentó su pico de incidencia en los años 50. Debido a la rareza de la asociación, informamos sobre un caso clínico que la presenta. El objetivo fue describir las implicaciones nosológicas y patogénicas de este trastorno neurodegenerativo, ya que no es frecuente encontrar esta asociación en nuestra población. Caso clínico: presentamos un caso de origen latinoamericano que inicialmente se manifestó con síntomas sistémicos de más de 6 años de evolución, con posteriores alteraciones cognitivas. Después presentó alteraciones de la marcha y síntomas motores sugestivos de parkinsonismo con datos atípicos y datos de enfermedad de motoneurona. Se hicieron estudios de extensión que confirmaron hallazgos compatibles con afectación en motoneurona superior e inferior. Observamos mutación en gen POLG, relacionada con síndrome de depleción mitocondrial. Conclusión: a pesar del conocimiento de esta asociación, es una entidad cuyo diagnóstico clínico puede ser muy difícil de obtener. Además, no se han identificado del todo los mecanismos moleculares, se han excluido los genes más comunes relacionados con parkinsonismos y esclerosis lateral amiotrófica e incluso se intentó localizar el locus, sin lograr resultados certeros. Desafortunadamente al ser una enfermedad neurodegenerativa el pronóstico es fatal, sin que haya tratamiento modificador de la enfermedad.

Wilson Disease: A Case Report of Psychosis Preceding Parkinsonism.

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.

[Autoimmune encephalitis and paraneoplastic neurological syndromes presenting atypical parkinsonism: a scoping review].

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.

Parkinsonism as the presenting manifestation of lupus: A case-based review.

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.

Vascular parkinsonism. / Vaskulær parkinsonisme.

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.

Parkinsonism may aggravate dysphagia in myotonic dystrophy type 1: two case reports.

Introduction: Weakness of trunk muscles, fatigue and reduced mobility are features of myotonic dystrophy type 1 (DM1) and may also characterize patients with extrapyramidal disorders.Dysphagia is common in DM1 and parkinsonism and can be predominant compared to other symptom, often requiring surgical tratment. Methods: We describe two cases of patients with DM1 and parkinsonism who arrived at our Center for worsening dysphagia and who showed very similar and peculiar clinical features. Case reports: The first patient presented initially at the outpatient clinic reporting a 7 year history of progressive difficulties in swallowing and movement slowness. Neurologic examination showed a general bradykinesia, plastic rigidity of upper limbs, diffuse hypotrophy and deep tendon reflexes weakness. MRI scan of brain and spine was unremarkable, but neurophysiological evaluation revealed diffuse myotonic discharges on distal limb muscles. Genetic testing confirmed DM1 diagnosis (CTG range E1).The second patient, presented with an initial diagnosis of parkinsonism due to a 10 years history of gait impairment, generalized weakness and dysphagia. Due to low back pain a neurophysiological study was performed after 5 years from diagnosis of parkinsonism detecting diffuse myotonic discharges and genetic testing confirmed diagnosis of DM1 (CTG range E2).Percutaneous endoscopic gastrostomy (PEG) was severe and burdensome for both patients.To date, only one case of molecularly confirmed DM1 along with parkinsonism has been described. We have described two cases of DM1 and parkinsonism in which swallowing function has been affected by a synergic effect triggered by both muscle condition and extrapyramidal disease.

Incidence and characteristics of post-COVID-19 parkinsonism and dyskinesia related to COVID-19 vaccines.

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.

Parkinsonism after ventriculoperitoneal shunt for hydrocephalus.

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.

Dementia with Lewy bodies: Impact of co-pathologies and implications for clinical trial design.

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.

A Prospective Study on the Relationship between Iron Supplement Intake, Hemoglobin Concentration, and Risk of Parkinsonism.

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.