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Background/Objectives: Acute retinal ischemia, including central retinal artery occlusion (CRAO), is recognized as a stroke equivalent by the American Heart Association/American Stroke Association (AHA/ASA), necessitating immediate multidisciplinary evaluation and management. However, referral patterns among ophthalmologists remain inconsistent, and evidence-based therapeutic interventions to improve visual outcomes are currently lacking. CRAO is associated with a significantly elevated risk of subsequent acute ischemic stroke (AIS), particularly within the first week following diagnosis, yet the role of intravenous thrombolysis (IVT) in this setting remains controversial. This case report presents a unique case of CRAO with concurrent internal carotid artery (ICA) occlusion, followed by an AIS affecting the middle cerebral artery (MCA). Case presentation: An 83-year-old woman presented with acute, painless monocular vision loss to the emergency department. IVT was administered within 4.5 h of admission for suspected CRAO associated with ICA occlusion (ICAO) identified on CT-angiography (CTA). One hour post-thrombolysis, CT-perfusion (CTP) confirmed MCA occlusion (MCAO), necessitating mechanical thrombectomy (MT). Successful recanalization was achieved without complications, and the patient demonstrated no functional impairments at discharge. Conclusions: This case underscores the importance of maintaining a vigilant approach to stroke management in CRAO patients. It highlights the diagnostic challenges encountered in clinical practice and advocates for further research into the role of IVT in CRAO cases with ICAO, emphasizing the need for consensus in treatment.
Background/Objectives: Internal tremor (IT) is often reported by patients with post-acute sequelae of SARS-CoV-2, also known as Long COVID, as a distressing and disabling symptom. Similarly, physicians are typically perplexed by the nature and etiology of IT and find it extremely challenging to manage. Methods: We describe a patient with Long COVID who experienced IT as part of post-COVID postural orthostatic tachycardia syndrome (POTS) and small fiber neuropathy (SFN) and review the limited literature available on this topic. Results: Our patient's IT improved significantly after intravenous saline infusions, but there was no effect on IT with oral hydration, increased oral sodium chloride intake, neuropathic pain medications, muscle relaxants, or medications used for the treatment of POTS. Conclusions: Based on this case, our clinical experience, and the limited literature available to date, we believe IT is a manifestation of POTS and SFN, which may be driven by hypovolemia, cerebral hypoperfusion, sympathetic overactivity, neuropathic pain, and mast cell hyperactivation. Subjective description, objective findings, and diagnostic and therapeutic considerations in patients with IT and Long COVID are discussed.
Background/objectives: Drug development involves multiple stages, spanning from initial discovery to clinical trials. This intricate process entails understanding disease mechanisms, identifying potential drug targets, and evaluating the efficacy and safety of candidate drugs. Clinical trials are designed to assess the effects of drugs on humans, focusing on determining safety profiles, appropriate modes of administration, and comparative efficacy against placebos. Notably, neuroscience drug development encounters distinct challenges, including the complex nature of diseases, limitations imposed by the blood-brain barrier, the absence of reliable predictive preclinical models, and regulatory hurdles. Ethical and safety considerations are pivotal due to the potential cognitive and motor effects of CNS-active drugs.
Methods: Our manuscript outlines the procedures for CNS clinical trials and highlights the key elements of study design, methodological considerations, and ethical frameworks. To achieve our objectives, we considered the official websites of regulatory authorities, the EQUATOR network, and recent publications in the field. The paper includes key elements such as criteria for subject selection, methods of evaluation, variable analysis, and statistical methodology approaches.
Results: We want to furnish a concise and comprehensive guide tailored to individuals new to CNS clinical trials, providing foundational elements necessary for the design and execution of such trials. The manuscript seeks to outline sources of relevant materials and elucidate adaptability, particularly in instances where sponsors may be absent.
Conclusions: By meeting the needs of less-experienced researchers or those with limited resources, the intention is to facilitate an understanding of the intricate nature of the process and offer guidance on appropriately navigating its complexities. It is essential to note that this manuscript does not aim to be exhaustive but endeavors to serve as a structured checklist. Through its approach, the manuscript aspires to offer guidance and support to individuals navigating the challenges inherent in this intricate domain.
Background/objectives: Orthostatic hypotension (OH) is highly prevalent in hospitalized patients and can lead to major consequences. The prevalence of OH among patients with stroke has also been reported to be high in in-patient cohorts. However, no previous analysis has focused exclusively on patients with hemorrhagic stroke, a group that may have a different disease profile, including a greater need for blood pressure control and surgical intervention. This study aims to examine the prevalence of OH, its risk factors, and potential impact in patients who were hospitalized due to hemorrhagic stroke.
Methods: A retrospective analysis of in-patient records between 1 January 2021 and 30 April 2023 was conducted for patients with stroke due to intracerebral hemorrhage (ICH) or subarachnoid hemorrhage (SAH) who were referred to rehabilitation at a tertiary hospital in Singapore. OH was defined as a drop in systolic blood pressure of ≥20 mmHg or diastolic blood pressure of ≥10 mmHg during the sit-up test as part of the rehabilitation assessment. Additional data collected included demographic information, length of stay, antihypertensive medications used at the time of assessment, comorbidities, and discharge functional outcomes as measured by a modified Rankin Scale.
Results: A total of 77 patients (65 [84.4%] with ICH and 12 [15.6%] with SAH) were included in the analysis. The prevalence of OH was 37.7%. A history of surgical intervention was identified as the major risk factor for the development of OH (odds ratio 4.28, 95% confidence interval 1.37 to 13.35, p = 0.009). There was no difference in hospital length of stay or discharge modified Rankin Scale scores between the two groups.
Conclusions: OH was frequently observed among patients with hemorrhagic stroke during the acute/subacute stage and should be monitored, especially in patients who require surgical intervention.
Intracranial hemorrhage associated with primary or metastatic brain tumors is a critical condition that requires urgent intervention, often through open surgery. Nevertheless, surgical interventions may not always be feasible due to two main reasons: (1) extensive hemorrhage can obscure the underlying tumor mass, limiting radiological assessment; and (2) intracranial hemorrhage may occasionally present as the first symptom of a brain tumor without prior knowledge of its existence. The current review of case studies suggests that advanced radiological imaging techniques can improve diagnostic power for tumoral hemorrhage. Adding proton magnetic resonance spectroscopy (1H-MRS), which profiles biochemical composition of mass lesions could be valuable: it provides unique information about tumor states distinct from hemorrhagic lesions bypassing the structural obliteration caused by the hemorrhage. Recent advances in 1H-MRS techniques may enhance the modality's reliability in clinical practice. This perspective proposes that 1H-MRS can be utilized in clinical settings to enhance diagnostic power in identifying tumors underlying intracranial hemorrhage.
Background: Paraneoplastic neurological syndromes (PNSs) are rare conditions characterized by immune-mediated pathogenesis, frequently associated with the presence of a neoplasm. Although a single antineuronal antibody mediates a specific syndrome, atypical manifestations mediated by the same antibody have been described. Methods: The aim of this study was to report on an atypical case of PNS with dual positivity for anti-GAD65 and anti-CRMP5/CV2 antibodies, simultaneously characterized by cognitive decline associated with progressive ataxia and parkinsonism. We also reviewed the current literature for published cases of PNSs with parkinsonism associated with anti-GAD65 and anti- CRMP5/CV2 antibodies. Results: A 68-year-old man with an insidious onset of bradykinesia, cognitive decline, and gait instability that began the year before our evaluation had been diagnosed with parkinsonian syndrome. Analysis of the cerebrospinal fluid showed lymphocytic pleocytosis, and a panel for PNS tested positive for anti-GAD65 and anti- CRMP5/CV2 antibodies. After investigation, a microcitoma was found in the lung. Conclusions: In light of our findings, we suggest considering PNS as an alternative diagnosis to parkinsonism-plus syndromes, in particular if bradykinetic syndrome is accompanied by other clinical manifestations including cognitive decline or ataxia in rapidly deteriorating patients. Earlier detection of PNS would lead to timelier identification of any occult tumors, therein promising improvement in the patient's prognosis.
The purpose of this review is to compile and discuss available evidence in humans on the efficacy of YHM supplementation on performance in different exercise modalities. Yohimbine (YHM) is a naturally occurring alkaloid that induces increases in sympathetic nervous system (SNS) activation effectively initiating "fight or flight" responses. In supplement form, YHM is commonly sold as an isolated product or combined into multi-ingredient exercise supplements and is widely consumed in fitness settings despite the lack of empirical support until recently. YHM primarily acts as an α2-adrenergic receptor antagonist effectively increasing norepinephrine release from sympathetic neurons. YHM has been implicated in improving or altering cardiovascular function, blood flow, lactate metabolism, and muscle function. Emerging evidence has suggested that YHM may have the potential to improve performance in a wide range of exercise modes including endurance, sprint, and resistance exercise. Performance enhancement with YHM is mediated by mechanistic underpinnings of physiological and psychological alterations to exercise responses including increased sympathetic activation, adaptive hemodynamic changes, increased alertness, and decreased fatigue. However, YHM use is not without risk as it has high interindividual variability in bioavailability, can be deceptively potent, lacks widely accepted dosing recommendations, and, when taken in large doses, has been empirically documented to result in serious side effects. Despite this, the evidence presented in this review suggests low doses of YHM are tolerable and may serve as an ideal exercise training aid due to acute enhancement of physical performance. However, safety concerns remain outstanding and temperance should be used when using YHM and similar sympathomimetics.
Background: Several significant associations between certain Human Leukocyte Antigen (HLA) alleles and myasthenia gravis (MG) subtypes were established in populations from Western Europe and North America and, to a lesser extent, from China and Japan. However, such data are scarcely available for Eastern Europe. This study aimed to analyze the associations of HLA Class I and II alleles with MG and its serological subtypes (with anti-acetylcholine receptor autoantibodies, RAch+MG, and double-seronegative, dSNMG) in myasthenic patients of Romanian descent. Methods: We consecutively enrolled adult Romanian unrelated myasthenic patients, which were genotyped by next-generation sequencing for HLA-A, -B, -C, -DRB1 and -DQB1. The descent-matched controls were represented by two separate groups of random normal subjects genotyped for the main five HLA loci at the two-digit and four-digit levels, respectively, collected from the Allele Frequency Net Database. Results: A total of 40 patients (females: 80.00%; median age at onset: 42.5 years, range: 1-78; RAch+MG: 75.00%; dSNMG: 22.50%) were included. We were able to confirm previously acknowledged allelic associations: positive for HLA-B*08, DRB1*14:54 and DRB1*16:01 and negative for DRB1*13. However, we found some potential novel significant positive associations between MG and the HLA-A*02:36, B*47, B*73, B*44:27 and B*57:02 alleles. All alleles positively associated with MG remained significantly associated with RAch+MG, regardless of the patients' clinical and thymic heterogeneity. We found significant positive associations between dSNMG and the HLA-B*47, B*44:27 and DRB1*14:54 alleles that are shared with RAch+MG. Conclusions: These results suggest both distinct and common etiopathogenic mechanisms between dSNMG and RAch+MG. Our study pioneers allele associations in Romanian MG patients.
Background: Ophthalmoplegic migraine (OM) is an uncommon variant of migraine characterised by headache and cranial nerve palsy, posing significant diagnostic and therapeutic challenges.
Objective: This study aimed to describe an extremely rare OM variant with a partial therapeutic response.
Clinical case: A 34-year-old pregnant woman in gestational week 19.1 (G6P2A3) with a history of three consecutive spontaneous abortions presented at the emergency services with insidious onset and mild-to-moderate-intensity pulsatile bifrontal headache for 15 days, and the positional changes exacerbated this. At peak intensity, she experienced nausea, vomiting, tinnitus, and photophobia without phonophobia or osmophobia, prompting multiple visits to the emergency department. Despite a broad range of treatments, including intravenous fluids, analgesia, pericranial blocks, and preventive management, there was a non-significative improvement in the symptomatology described above. However, spontaneous resolution of this clinical picture was observed during the postpartum period.
Results: This case highlights the complexity of ophthalmoplegic migraine, especially in the context of pregnancy, and raises questions about the underlying pathophysiological mechanisms. The absence of structural lesions on neuroimaging and postpartum resolution suggests a potential association with the hormonal and physiological changes associated with pregnancy.
Conclusions: Despite limited scientific evidence, this report contributes to expanding the knowledge of this rare entity and emphasises the importance of a multidisciplinary approach to its management.