Search Results (53)

Background and Clinical Significance: Adults suffering from cerebellar metastases are often at high risk for rapid deterioration of their neurological status because the posterior fossa has limited compliance and the location of these metastases are close to the brain stem and important cerebrospinal fluid (CSF) pathways. In this paper, we present a longitudinal, patient-centered report on the history of an elderly individual who suffered from cognitive comorbidities and experienced a sudden loss of function in her cerebellum. Our goal in reporting this case is to provide a comparison between the patient’s pre-operative and post-operative neurological examinations; the imaging studies she had before and after surgery; the surgical techniques utilized during her operation; and the outcome of her post-operative course in a way that will be helpful to other patients who have experienced a similar situation. Case Presentation: We report the case of an 80-year-old woman who initially presented with progressive ipsilateral limb-trunk ataxia, impaired smooth pursuit eye movement, and rebound nystagmus, but preserved pyramidal and sensory functions. Her quantitative bedside assessments included some of the components of the Scale for the Assessment and Rating of Ataxia (SARA), and a National Institute of Health Stroke Scale (NIHSS) score of 3. These findings indicated dysfunction of the left neocerebellar hemisphere and possible dentate nucleus involvement. The patient’s magnetic resonance imaging (MRI) results demonstrated an expansive mass with surrounding vasogenic edema and marked compression and narrowing of the exits of the fourth ventricle which placed the patient’s CSF pathways at significant risk of occlusion, while the aqueduct and inlets were patent. She then underwent a left lateral suboccipital craniectomy with controlled arachnoidal CSF release, preservation of venous drainage routes, subpial corticotomy oriented along the lines of the folia, stepwise internal debulking, and careful protection of the cerebellar peduncles and dentate nucleus. Dural reconstruction utilized a watertight pericranial graft to restore the cisternal compartments. Her post-operative intensive care unit (ICU) management emphasized optimal venous outflow, normoventilation, and early mobilization. Histopathology confirmed the presence of metastatic carcinoma, and staging suggested that the most likely source of the primary tumor was the lungs. Immediately post-operation, computed tomography (CT) imaging revealed a smooth resection cavity with open foramina of Magendie and Luschka, intact contours of the brain stem, and no evidence of bleeding or hydrocephalus. The patient’s neurological deficits, including dysmetria, scanning dysarthria, and ataxic gait, improved gradually during the first 48 h post-operatively. Upon discharge, the patient demonstrated an improvement in her limb-kinetic subscore on the International Cooperative Ataxia Rating Scale (ICARS) and demonstrated independent ambulation. At two weeks post-operation, CT imaging revealed decreasing edema and stable cavity size, and the patient’s modified Rankin scale had improved from 3 upon admission to 1. There were no episodes of CSF leakage, wound complications, or new cranial nerve deficits. A transient post-operative psychotic episode that was likely secondary to her underlying Alzheimer’s disease was managed successfully with short-course pharmacotherapy. Conclusions: The current case study demonstrates the value of anatomy-based microsurgical planning, preservation of venous and CSF pathways, and targeted peri-operative management to facilitate rapid recovery of function in older adults who suffer from cerebellar metastasis and cognitive comorbidities. The case also demonstrates the importance of early multidisciplinary collaboration to allow for timely initiation of both adjuvant stereotactic radiosurgery and molecularly informed systemic therapy. Full article

Objectives: This study examined the effects of a four-week low-dose mindfulness intervention on ratings of perceived exertion, heart rate, attentional allocation, and performance outcomes, including power output, distance rowed, and strokes per minute, during a rowing task. Methods: Thirty-two participants between 18 and 37 years of age (21.09 ± 3.67) who met the World Health Organization (WHO) physical activity guidelines and had no previous experience with mindfulness or meditation completed a four-week intervention. Participants were either in the mindfulness intervention (n = 17) or the placebo group (n = 15). Participants completed ten visits over four weeks, each consisting of watching an episode of either Headspace Guide to Meditation or Wild Babies on Netflix, followed by a 25 min rowing task. Results: Results indicated no significant group-by-session interaction for any variables. However, a significant main effect for session showed that perceived exertion was significantly lower at the post-assessment compared to the pre-assessment for all participants (p = 0.013, η_p² = 0.19). Additionally, a significant main effect for time revealed a linear increase in perceived exertion across the rowing task (p < 0.001, η_p² = 0.81). Both groups also showed a significant shift from dissociative to associative attention (p < 0.001, η_p² = 0.25). For performance, a significant main effect for session was observed, with greater power output (p = 0.008, η_p² = 0.22) and distance rowed (p = 0.013, η_p² = 0.19) at the post-assessment for both groups. Conclusions: The lack of significant group differences suggests that a low-dose, pre-exercise mindfulness video intervention is likely ineffective for altering psychophysiological responses, indicating that future research should prioritize higher-dosage or real-time guided interventions. Full article

Background: Cryoglobulinemia is a rare immune-mediated condition, in which abnormal proteins (cryoglobulins) precipitate at cold temperatures, leading to blood vessel inflammation. It affects approximately 1 in 100,000 individuals globally and often goes undiagnosed due to its overlapping symptoms with common conditions such as stroke. When the central nervous system (CNS) is involved—primarily in Type 2 cryoglobulinemia—it can cause serious neurological events, including seizures, confusion, and stroke-like episodes. Despite this, there is limited awareness and minimal research on this condition in South Africa. Objective: The aims of this study were to describe neurological manifestations of cryoglobulinemia using global case reports, evaluate outcomes associated with delayed diagnosis, and highlight the importance of early detection in patients with unexplained neurological symptoms. Methods: A qualitative systematic review of published case reports (2015–2024) was conducted. The study focused on adults (≥18 years) who were diagnosed with cryoglobulinemia involving CNS manifestations. Reports from hospital-based studies in Europe, North America, and Asia were retrieved from medical databases. Data on symptoms, diagnosis, treatment, and outcomes were summarized numerically and by identifying common patterns. Results: Seventeen relevant cases were identified. The most common neurological symptoms were ischemic stroke (35%), reversible posterior encephalopathy syndrome (24%), seizures (18%), and intracranial hemorrhage (12%). Most cases were associated with Type 2 cryoglobulinemia. Neuroimaging frequently revealed vasculitis, infarcts, or cerebral edema. All patients received immunosuppressive therapy, mainly corticosteroids. Outcomes showed that 76% improved, 12% partially recovered, and 12% died—mostly due to delayed diagnosis. Conclusions: Neurological involvement in cryoglobulinemia is uncommon but potentially fatal. Stroke-like presentations dominate due to vasculitis injury and vascular occlusion. Early diagnosis significantly improves outcomes, while delays can be deadly. Increased clinical awareness is essential in South Africa, where this condition is rarely reported. Clinicians should consider cryoglobulinemia as a possible cause in patients presenting with unexplained neurological symptoms. Full article

Background/Objectives: Atrial fibrillation (AF) often occurs in episodes that are sudden and go unnoticed, reducing the chances of anticoagulation. We evaluated a two-stage AI ECG screening protocol that uses a single ECG model at initial screening and, if necessary, a serial ECG model after short interval follow-up to enhance accuracy while saving monitoring resources. Methods: We analyzed 248,612 12-lead ECGs from 164,793 adults (AF, n = 10,735) for model development and assessed the protocol in 11,349 eligible patients with longitudinal ECGs. The proposed algorithm first applied a single-ECG AI model at the initial visit, followed by a serial-ECG AI model three months later if AF was not initially detected. The model’s performance was evaluated using several metrics, including the area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, accuracy, and F1 score. Results: The protocol achieved an AUROC of 0.908 with a sensitivity of 88.1%, specificity of 78.7%, positive predictive value (PPV) of 30.2%, negative predictive value (NPV) of 98.4%, accuracy of 79.6%, and an F1 score of 0.450. Among patients with a history of stroke (n = 551), 84.9% were correctly identified as AF-positive under the protocol. Conclusions: A sequential AI ECG strategy maintains high NPV at entry and improves PPV with longitudinal confirmation. This approach can prioritize ambulatory monitoring for those most likely to benefit and merits prospective, multi-center validation and cost-effectiveness assessment. Full article

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a rare disease with variable clinical manifestations. MELAS is most often caused by the human mitochondrial DNA (mtDNA) m.3243A>G variant. We describe cardiac magnetic resonance (CMR) imaging findings and clinical features of 22 subjects with the m.3243A>G mutation and endeavored to discover the role of CMR in MELAS cardiomyopathy diagnostics. The clinical symptoms, ECG findings, and laboratory tests were retrospectively collected from the electronic medical record. Ten subjects (46%) had cardiac symptoms, and eighteen subjects (82%) had some clinical symptoms or signs of MELAS. Seventeen subjects (77%) showed cardiac findings compatible with MELAS. An ECG showed a short PR interval in six subjects (27%). Two patients had a first-degree atrioventricular block. Repolarization changes in the ECG were observed in thirteen subjects (59%), whereas left ventricular hypertrophy voltage criteria were only observed in one subject. Patients with ECG abnormalities had a strong link between proBNP value and cardiac tissue composition (T1 relaxation, p < 0.02) and showed decreased CMR-based strain (p < 0.025). The CMR findings are heterogeneous in subjects with m.3243A>G. Cardiac MELAS may include left ventricular hypertrophy, which mimics sarcomericcardiomyopathy but maypredispose individuals to severe heart failure episodes triggered by acute critical situations. CMR may be used to clarify ECG findings. This study indicates that the genetic testing of MELAS should be considered in new cases of HCM or sudden heart failure phenotypes of unknown etiology. Full article

The m.13513G>A (p.Asp393Asn) substitution in the MT-ND5 (Mitochondrially Encoded NADH/Ubiquinone Oxidoreductase Core Subunit 5) gene is a common pathogenic variant associated with primary mitochondrial disorders. It frequently causes Leigh syndrome and mitochondrial encephalomyopathy with lactate acidosis and stroke-like episodes (MELAS). In this study, we present clinical data, heteroplasmy levels in various tissues (blood, urine, and skin fibroblasts), and bioenergetic characteristics from a cohort of 20 unrelated patients carrying the m.13513G>A mutation, classified according to the following phenotypes: Leigh syndrome (n = 12), MELAS (n = 2), and Leber’s hereditary optic neuropathy (LHON, n = 6). We observed a significant correlation between high respiratory ratios and heteroplasmy levels in fibroblast cell lines of the patients. Furthermore, fibroblast cell lines with heteroplasmy levels exceeding 55% exhibited markedly reduced mitochondrial membrane potential. These findings contribute to a better understanding of the clinical and bioenergetic profiles of patients with m.13513G>A-variant-related phenotypes across different heteroplasmy levels, based on data from a single genetic center. Our data suggest that even a slight shift in heteroplasmy can improve cellular function and, consequently, the patients’ phenotype, providing a solid foundation for the development of future gene therapies for mtDNA diseases. Full article

Background. Sturge–Weber syndrome (SWS) is a rare non-hereditary neurovascular disorder characterized by capillary–venous malformations on the face, ocular vascular anomalies, and leptomeningeal capillary–venous malformations. Patients with SWS often experience cerebral perfusion impairment, increasing their risk for stroke-like episodes, seizures, and motor and cognitive impairments. Methods. We report the case of a 2-year-old boy diagnosed with SWS who developed a stroke-like episode following dye laser therapy under deep sedation. Results. Despite initial diagnostic challenges and persistent seizures, appropriate management led to full neurological recovery. Conclusions. This case highlights the importance of considering stroke-like episodes in children with SWS after stressful events such as medical procedures. Full article

Sturge–Weber Syndrome (SWS) is a rare neurocutaneous disorder caused by a somatic nonsynonymous mosaic mutation most commonly in the GNAQ gene (G protein guanine Nucleotide-binding protein Alpha subunit q). SWS is characterized by capillary-venous malformations in the brain and eyes and a characteristic facial port wine (PW) birthmark (previously called port wine stain/PWS) in the head/neck region. Clinical manifestations vary and include epilepsy, stroke-like episodes, migraine headaches, cognitive delays, glaucoma, ocular vascular anomalies, heterochromia of the iris, visual field defects, and endocrine disorders like growth hormone deficiency or central hypothyroidism. The pathognomonic findings seen in neuroimaging with magnetic resonance imaging (MRI) include the presence of unilateral intracranial leptomeningeal angiomatosis, typically ipsilateral to the facial birthmark. SWS does not currently have a definitive cure, and management strategies focus on symptomatic management such as anti-seizure medications, limited surgical resection of the epileptogenic tissue or hemispherectomy for cases of drug-resistant epilepsy (DRE), selective photo-thermolysis of the PWS using a pulsed dye laser, and the medical and/or surgical management of glaucoma. In addition to these symptomatic treatments, the use of preventive, modifying, or stabilizing treatments like low-dose aspirin in reducing the frequency and severity of seizures and stroke-like events and the use of newer therapies like cannabidiols and mTOR inhibitors are being reviewed and have shown promising early results. This comprehensive narrative review summarizes the current literature on clinical management strategies, ongoing research studies, and future directions in the diagnosis and management of SWS. Full article

This study aimed to examine the effects of different intensities of endurance training combined with standard neurorehabilitation on selected blood biomarkers and physical outcomes of post-stroke individuals. We randomised patients with first-episode ischaemic stroke to an experimental group that received 4 × 45 min sessions of moderate-intensity continuous training (MICT) each week and 2 × 45 min of standard rehabilitation each day or to a control group that received 4 × 45 min sessions of low-intensity continuous training (LICT) each week and 2 × 45 min of standard rehabilitation each day. We measured the following outcomes at baseline and 3 weeks after the intervention: aerobic capacity; cognitive and motor function; and blood levels of brain-derived neurotrophic factor (BDNF), glial cell line–derived neurotrophic factor (GDNF), vascular endothelial growth factor A (VEGF-A), insulin-like growth factor-1 (IGF-1), and irisin. We included 52 patients with a mean age of 66.1 ± 8.0 years. After 3 weeks of rehabilitation, there was a clinically significant improvement in the Rivermead Motor Assessment—arm score in the MICT group. The study showed that after 3 weeks, an intervention combining MICT with standard neurorehabilitation was significantly more beneficial in improving aerobic capacity and arm motor function than an intervention combining LICT and standard neurorehabilitation. Full article

Background: There is no cure for mitochondrial diseases which manifest in numerous ways including fatigue, muscle weakness, and exercise intolerance. Medical treatment varies and focuses on managing symptoms. Photobiomodulation (PBM) can decrease mitochondrial damage thereby increasing energy production and decreasing cell death. This pilot study will apply PBM to people with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) to examine the safety of application, and if changes occur in symptoms and signs after cross-over application/withdrawal of a sham or active PBM treatment including a two-week period of washout. Methods: This study is an exploratory, prospective series N-of-1 (single patient) studies. The protocol is guided by the CONSORT extension for reporting N-of-1 trials (CENT 2015), chosen due to the rarity of mitochondrial diseases, the fluctuating symptomology, and heterogeneity of the clinical presentation. The primary outcome is patient-reported fatigue assessed using the Checklist of Individual Strength and with concomitant evaluation of safety. Secondary measures are of depression, anxiety and stress, sleepiness, physical activity, blood lactate and creatine kinase, physical measures of sit-to-stand, and heel raise capability. Mitochondrial function will be evaluated using hydrogen magnetic resonance spectroscopy for lactate. PBM will be a participant-administered, home-based therapy using a multiple diode flexible array (BeniLight iLED-Pro Multi-Wave Multi-Pulse belt; 465 nm, 660 nm, 850 nm; average irradiance 5.23 mW/cm²; total joules: 770.1 J/treatment, all sites; 5 KHz; 20% duty ratio) over the anterior thigh muscles, posterior calf muscles and abdomen for 10 min to each site, three times/week. The safety of the intervention will be assessed. Descriptive statistics, causal analyses of time series data and dynamic modelling will be applied as relevant to the variables collected. Hydrogen magnetic resonance spectra will be acquired and averaged to obtain the content of the targeted hydrogen levels. Discussion: The study will provide guidance on whether and how to progress to a larger, randomised cohort study with sham control. Full article

Mitochondria are vital organelles responsible for ATP production and metabolic regulation, essential for energy-intensive cells such as retinal ganglion cells. Dysfunction in mitochondrial oxidative phosphorylation or mitochondrial DNA (mtDNA) pathogenic variants can disrupt ATP synthesis, cause oxidative stress, and lead to cell death. This has profound implications for tissues such as the retina, optic nerve, and retinal pigment epithelium, which are dependent on robust mitochondrial function. In this review, we provide a comprehensive compilation of pathogenic variants in the mtDNA associated with various ophthalmic diseases, including Leber’s hereditary optic neuropathy, chronic progressive external ophthalmoplegia, Leigh syndrome, mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes, among others. We highlight the genetic variants implicated in these conditions, their pathogenic roles, and the phenotypic consequences of mitochondrial dysfunction in ocular tissues. In addition to well-established mutations, we also discuss the emerging evidence of the role of mtDNA’s variants in complex multifactorial diseases, such as non-arteritic anterior ischemic optic neuropathy, primary open-angle glaucoma, and age-related macular degeneration. The review aims to serve as a valuable resource for clinicians and researchers, providing a detailed overview of mtDNA pathogenic variants and their clinical significance in the context of mitochondrial-related eye diseases. Full article

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a rare mitochondrial disorder primarily presenting in pediatric patients, with onset after 40 years being exceptionally rare (1–6%). Here, we report a complex diagnostic journey of a 47-year-old male presenting with new-onset seizures, hemiparesis, and neurocognitive deficits. Initial work-up, including MRI, CSF analysis, and extensive antibody screening, yielded inconclusive results, prompting differential considerations such as autoimmune encephalitis and neoplastic conditions. Finally muscle biopsy findings, coupled with genetic confirmation of the m.3243A>G mutation in the MT-TL1 gene, ultimately established the diagnosis of MELAS. This case depicts the atypical presentation of adult-onset MELAS without initial lactic acidemia, diabetes, or hearing impairment. The prolonged diagnostic process underscores the challenges of identifying rare diseases under today’s financial and administrative constraints. Still ee emphasize the importance of comprehensive diagnostics in rare cases to advance generall understanding and improve future patient outcomes, also amidst resource limitations. Full article

Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a complex mitochondrial disorder characterized by a wide range of systemic manifestations. Key clinical features include recurrent stroke-like episodes, seizures, lactic acidosis, muscle weakness, exercise intolerance, sensorineural hearing loss, diabetes, and progressive neurological decline. MELAS is most commonly associated with mutations in mitochondrial DNA, particularly the m.3243A>G mutation in the MT-TL1 gene, which encodes tRNALeu (CUR). These mutations impair mitochondrial protein synthesis, leading to defective oxidative phosphorylation and energy failure at the cellular level. The clinical presentation and severity vary widely among patients, but the syndrome often results in significant morbidity and reduced life expectancy because of progressive neurological deterioration. Current management is largely focused on conservative care, including anti-seizure medications, arginine or citrulline supplementation, high-dose taurine, and dietary therapies. However, these therapies do not address the underlying genetic mutations, leaving many patients with substantial disease burden. Emerging experimental treatments, such as gene therapy and mitochondrial replacement techniques, aim to correct the underlying genetic defects and offer potential curative strategies. Further research is essential to understand the pathophysiology of MELAS, optimize current therapies, and develop novel treatments that may significantly improve patient outcomes and extend survival. Full article

Primary mitochondrial disease (MD) is a group of rare genetic diseases reported to have a prevalence of 1:5000 and is currently without a cure. This group of diseases includes mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), maternally inherited diabetes and deafness (MIDD), Leber’s hereditary optic neuropathy (LHON), Leigh syndrome (LS), Kearns–Sayre syndrome (KSS), and myoclonic epilepsy and ragged-red fiber disease (MERRF). Additionally, secondary mitochondrial dysfunction has been implicated in the most common current causes of mortality and morbidity, including cardiovascular disease (CVD) and cancer. Identifying key genetic contributors to both MD and secondary mitochondrial dysfunction may guide clinicians to assess the most effective treatment course and prognosis, as well as informing family members of any hereditary risk of disease transmission. Identifying underlying genetic causes of primary and secondary MD involves either genome sequencing (GS) or small targeted panel analysis of known disease-causing nuclear- or mitochondrial genes coding for mitochondria-related proteins. Due to advances in GS, the importance of long non-coding RNA (lncRNA) as functional contributors to the pathophysiology of MD is being unveiled. A limited number of studies have thus far reported the importance of lncRNAs in relation to MD causation and progression, and we are entering a new area of attention for clinical geneticists in specific rare malignancies. This commentary provides an overview of what is known about the role of lncRNAs as genetic and molecular contributors to disease pathophysiology and highlights an unmet need for a deeper understanding of mitochondrial dysfunction in serious human disease burdens. Full article

The human brain is highly dependent on oxygen, utilizing approximately 20% of the body’s oxygen at rest. Oxygen deprivation to the brain can lead to loss of consciousness within seconds and death within minutes. Recent studies have identified regions of the brain with spontaneous episodic hypoxia, referred to as “hypoxic pockets”. Hypoxia can also result from impaired blood flow due to conditions such as heart disease, blood clots, stroke, or hemorrhage, as well as from reduced oxygen intake or excessive oxygen consumption caused by factors like low ambient oxygen, pulmonary diseases, infections, inflammation, and cancer. Severe hypoxia in the brain can manifest symptoms similar to Parkinson’s disease (PD), including cerebral edema, mood disturbances, and cognitive impairments. Additionally, the development of PD appears to be closely associated with hypoxia and hypoxic pathways. This review seeks to investigate the molecular interactions between hypoxia and PD, emphasizing the pathological role of hypoxic pathways in PD and exploring their potential as therapeutic targets. Full article