An update on stem cell and stem cell-derived extracellular vesicle-based therapy in the management of Alzheimer's disease.

Globally, neurological diseases pose a major burden to healthcare professionals in terms of the management and prevention of the disorder. Among neurological diseases, Alzheimer's disease (AD) accounts for 50%-70% of dementia and is the fifth leading cause of mortality worldwide. AD is a progressive, degenerative neurological disease, with the loss of neurons and synapses in the cerebral cortex and subcortical regions. The management of AD remains a debate among physicians as no standard and specific "disease-modifying" modality is available. The concept of 'Regenerative Medicine' is aimed at regenerating the degenerated neural tissues to reverse the pathology in AD. Genetically modified engineered stem cells modify the course of AD after transplantation into the brain. Extracellular vesicles (EVs) are an emerging new approach in cell communication that involves the transfer of cellular materials from parental cells to recipient cells, resulting in changes at the molecular and signaling levels in the recipient cells. EVs are a type of vesicle that can be transported between cells. Many have proposed that EVs produced from mesenchymal stem cells (MSCs) may have therapeutic promise in the treatment of AD. The biology of AD, as well as the potential applications of stem cells and their derived EVs-based therapy, were explored in this paper.

Concussion-Induced Oromandibular Dyskinesia.

We present a rare case of concussion-induced chronic oromandibular dyskinesia. The patient is a 51-year-old Caucasian male with complex medical history (including a history of multiple concussions) who presented to the emergency department for suicidal and paranoid ideation. At the time of the visit, the patient was noted to be exhibiting an oromandibular dyskinesia in the form of "teeth-chattering." The first documented episode of his oromandibular dyskinesia dates back to a medical visit in December 2017. During this visit, the patient presented with teeth-chattering and tremors in his legs, hands, and head after a concussive event. Similar symptoms were noted by two different providers during two unrelated appointments one month later in January 2018. These symptoms were not mentioned in his records for four years and three months following the initial onset. They were noted again during an outpatient encounter for insomnia. During these four years, he was treated for a variety of conditions in both inpatient and outpatient settings, including gout, human immunodeficiency virus (HIV), stage four lymphoma, insomnia, and hepatitis C. Curiously, the dyskinesia symptoms reappeared several months after the completion of six cycles of etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin hydrochloride (R-EPOCH) chemotherapy in May 2021. Since reappearing, the symptoms have been worsening and significantly impacting the patient's quality of life. Although concussion-induced dyskinesia has been previously described in the literature, this is to our knowledge the first described case of concussion-induced oromandibular dyskinesia.

Efficacy of Electroconvulsive Therapy for the Treatment of Movement Disorders: A Literature Review.

Electroconvulsive therapy (ECT) is a safe and effective treatment modality for various psychiatric disorders. However, evidence suggests a putative role of ECT in treating movement disorders that are refractory to less invasive modalities. ECT is primarily used in treatment-resistant psychiatric disorders. However, growing evidence exists for its use in movement disorders with and without psychiatric comorbidity. The primary objective of this systematic review was to examine the efficacy of ECT as a primary treatment modality for movement disorders. Relevant, peer-reviewed publications were retrieved from PubMed, SCOPUS, CINAHL, and PsycINFO. Keywords related to ECT and movement disorders were used as search phrases to identify relevant articles. A total of 90 articles that met the inclusion criteria were included in this review. Core findings were subsequently appraised on the role of ECT in treating movement disorders. Inclusion and exclusion criteria were developed to guide the search and selection process. Sources that met the inclusion criteria were those published between 2001 and January 2023. Additionally, peer-reviewed journals published in the English language covering the role of ECT in movement disorders were deemed appropriate for inclusion. Sources published before 2001, written in a non-English language, and not from peer-reviewed journals were excluded from this systematic review. The exclusion criteria also entailed eliminating duplicates from the review list. Most reviewed sources revealed that ECT improved outcomes in symptoms associated with various movement symptoms. However, ECT does not have a long-lasting impact on neuroacanthocytosis symptoms. Additionally, ECT is negatively associated with aggression and agitation, two of the most critical movement symptoms of Alzheimer's disease. Evidence affirms the efficacy of ECT in providing symptomatic relief for movement disorders aside from psychiatric comorbidities. This positive association highlights the need for randomized controlled studies to identify movement disorder sub-populations that may respond to ECT.

Pregabalin Toxicity-Induced Posterior Reversible Encephalopathy Syndrome.

Pregabalin, a prescription medication typically used for neuropathic pain, has increasingly been overused and abused. We present a unique case of a 51-year-old woman with a history of polysubstance use disorder and on methadone therapy who presented to the emergency department with altered mental status after consuming an unknown supratherapeutic amount of pregabalin. She was stabilized and discharged. Within 24 hours, she ingested another 1000mg of pregabalin, presenting again with altered mental status, along with tachycardia and hypertension. Computed tomography (CT) without contrast and fluid-attenuated inversion recovery magnetic resonance imaging (FLAIR MRI) revealed subcortical white matter edema in the bilateral frontal and occipital lobes as well as the left parietal lobe, suggestive of posterior reversible encephalopathy syndrome (PRES). The patient recovered after four days of supportive treatment with an antihypertensive and an antiepileptic. PRES is a neurological phenomenon in which vasogenic edema, most commonly accumulating in the posterior parieto-occipital white matter, causes headaches, altered mental status, and seizures. To our knowledge, there has not been an established link between pregabalin toxicity and PRES, and the awareness of this potential complication can help in the early diagnosis and management of the disease to prevent further progression.

Platelet lysate for COVID-19 pneumonia-a newer adjunctive therapeutic avenue.

The linchpin for COVID-19 pathogenesis is the severe inflammatory process in the respiratory tract wherein the accumulation of excessive cytokines paves the way for a series of systemic hemodynamic alterations and mortality. The mortality rate is higher in individuals with co-morbidities and advancing age. The absence of a specific therapy is responsible for this uncontrolled spread and the significant mortality. This renders potential insight for considering biologics as a plausible option to repair and regenerate the affected lung tissue and pulverize the causative organism. The plausible role of megakaryocytes against invading microbes was not clearly understood. Platelet lysate is an acellular product consisting of regenerative molecules released from a cluster of platelets. It attenuates the changes caused by immune reactions in allogenic utility with the introduction of growth factors, cytokines, and proteins at supraphysiologic levels and thereby serves as a regenerative immunomodulatory agent to combat COVID-19. This platelet lysate can be used in nebulized form for such acute respiratory distress conditions in COVID-19 elderly patients. Platelet lysate may emerge as a pivotal player provided investigations pace up in this context. Here, we discuss how the platelet lysate can plausibly perquisite to relegate COVID-19. Undertaking prospective randomized controlled trials to prove its efficacy is the need of the hour in this pandemic scenario.

Excited Catatonia - A Delayed Neuropsychiatric Complication of COVID-19 Infection.

An increasing number of patients have been presenting with neuropsychiatric signs and symptoms associated with coronavirus disease (COVID-19). We present a case of a 69-year-old female with no prior psychiatric history who was brought to the emergency department due to bizarre behavior and paranoid thoughts for four to six weeks, worsening over the last two weeks. Psychiatric evaluation found that the patient had extreme restlessness and agitation, poor eye contact, paranoid delusions, visual hallucinations, and a flat affect with stereotypic repetition of speech and loose associations. The patient's family noted that two months prior she had symptoms of common cold associated with a severe cough and 20 pounds of weight loss. Suspicion for prior COVID-19 infection prompted an IgG antibody test, which was positive. Our patient displayed at least three of the signs needed to diagnose catatonia - agitation, rigidity, and echolalia - and had a therapeutic response to lorazepam, confirming suspicions of excited catatonia. Her seropositivity for IgG against COVID-19 suggested a COVID-induced brief psychotic disorder with catatonia, which makes this the first known case, to our knowledge, of a patient with delayed onset catatonia after COVID-19 infection. This suggests that clinicians should, after ruling out more plausible stressors, suspect possible coronavirus involvement in sudden onset psychotic disorders, especially in patients who do not fit the demographic of new-onset schizophrenia-spectrum diagnoses. Further research is needed on the pathophysiology behind COVID-19 altering neuronal function and neurotransmitter pathways.

Effect of High-Dose Vitamin C Infusion in a Glucose-6-Phosphate Dehydrogenase-Deficient Patient.

Vitamin C supplementation is generally regarded as benign. There has been a resurgence of interest in the general medical community regarding the use of vitamin C most notably in the care of sepsis. Nonetheless, caution must be taken if supraphysiologic vitamin C supplementation is being administered as it should be considered a medication just like any other. We present a case of hemolysis in a glucose-6-phosphate dehydrogenase- (G6PD-) deficient patient receiving high-dose vitamin C infusions for his rheumatoid arthritis.