Real-world, long-term evaluation of the tolerability and therapy retention of Epidiolex® (cannabidiol) in patients with refractory epilepsy.

OBJECTIVE: Epidiolex® (CBD) is FDA-approved for seizures associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and tuberous sclerosis complex (TSC). Phase III studies suggest that certain adverse effects (AEs), possibly linked to pharmacokinetic/pharmacodynamic (PK/PD) interactions may be therapy-limiting. We sought to identify these factors that contribute to treatment success and retention of therapy. METHODS: A single-center, retrospective review of patients with refractory epilepsy taking Epidiolex® was performed. Kaplan-Meier analysis was performed to describe Epidiolex® retention, as a measure of overall effectiveness. RESULTS: One hundred and twelve patients were screened; 4 were excluded due to loss to follow-up or never starting Epidiolex®. Of 108 patients, mean age was 20.3 years (13.1, range 2 to 63), and 52.8% were female. Mean initial and maintenance doses were 5.3 mg/kg/day (1.3) and 15.3 mg/kg/day (5.8), respectively. At the final evaluation, 75% of patients remained on Epidiolex®. The 25th percentile for discontinuation was 19 months. 46.3% of patients experienced at least one treatment-emergent adverse effect (TEAE) with 14.5% d/c Epidiolex® due to treatment emerging adverse effects (TEAE). The most common reasons for discontinuation were lack of efficacy (37%), increased seizure activity (22%), worsened behavior (22%), and sedation (22%). One out of 27 discontinuations was due to liver function test (LFT) elevations (3.7%). At initiation, 47.2% were concurrently taking clobazam, and 39.2% of those patients had an initial clobazam dose decrease. 53% of patients were able to either discontinue or lower the dose of at least one other antiseizure medication. SIGNIFICANCE: Epidiolex® is generally well-tolerated and the majority continued long-term treatment. Patterns of adverse effects were similar to clinical trials, however gastrointestinal complaints, and significant LFT elevations were less common. Our data suggest most patients discontinue within the first several months of treatment and suggest that further studies designed to evaluate early identification and potential mitigation of adverse effects and including drug interactions are warranted.

Cost avoidance from health system specialty pharmacist interventions in patients with multiple sclerosis.

BACKGROUND: Specialty pharmacists monitor patients taking multiple sclerosis (MS) disease-modifying therapies (DMTs) to evaluate response to therapy and intervene on adverse effects. These interventions have the potential to avoid health care costs by discontinuing inappropriate therapies and avoiding downstream health care utilization. OBJECTIVE: To calculate the costs avoided by specialty pharmacist interventions in MS. METHODS: A retrospective observational cohort study including patients at the Vanderbilt MS Clinic who received a specialty pharmacist intervention between February 1, 2022, and July 31, 2022, was performed. A panel of 3 investigators categorized each intervention based on the potential for cost avoidance: (1) no cost avoidance, (2) direct cost avoidance, and (3) indirect cost avoidance. A single intervention may have one or both cost avoidance types. Direct costs avoided included the cost of the potential service or medication avoided due to the intervention. Medication costs were calculated using the range of the average wholesale price and average wholesale price - 20%. For indirect costs avoided, the range of costs of a consequence (self-care, ambulatory visit, emergency department visit, hospitalization, or death) occurring had the intervention not been performed were multiplied by the range of probabilities for the consequence occurring (from zero [0] to very likely [0.5]). Self-care indirect cost savings equated to $0. Descriptive statistics summarized types of pharmacist interventions, the patients impacted, and costs avoided. In patients with an intervention that resulted in cost avoidance, chart review was performed to collect patient demographics, disease history, and MS-related health care usage during the 12 months prior to the pharmacist intervention. RESULTS: 485 pharmacist interventions in 354 individual patients were included. Fifty interventions in 38 individual patients (76% female, median age 51 years, 68% White) resulted in cost avoidance. The total estimated costs avoided in 6 months ranged from $123,733 to $156,265. In total, $138,410 were direct costs and $1,890 were indirect costs. Reasons for direct costs avoided (n = 13) were often safety monitoring (69%) or common side effects management (23%). Indirect costs avoidance (n = 37) resulted primarily from interventions on common side effects management (57%) and safety monitoring (22%). Self-care was the most common type of indirect cost avoided (n = 27). Interventions resulting in costs avoided were commonly seen in patients with relapsing-remitting MS (82%). The median time from MS diagnosis was 15 years and 42% of patients had previously trialed 1 other MS DMT. CONCLUSIONS: There is a potential for significant health care savings after specialty pharmacist interventions in MS, primarily from preventing the dispensing of inappropriate therapies.

Prosopagnosia Due to Metastatic Brain Tumor: A Case-Based Review.

Prosopagnosia, also referred to as "face blindness," is a type of visual agnosia characterized by a decreased capacity to recognize familiar faces with a preserved ability to identify individuals based on non-facial visual traits or voice. Prosopagnosia can be categorized as developmental (DP) or acquired (AP) owing to a variety of underlying conditions, including trauma, neurodegenerative diseases, stroke, neuroinfections, and, less frequently, malignancies. Facial recognition is a complex process in which different neuronal networks are involved. The infrequent but notable higher visual-processing abnormalities can be caused by lesions of the inferior longitudinal fasciculus (ILF) in the non-dominant temporal lobe. We report a rare case of AP in a 69-year-old patient who is right-hand dominant with rectal carcinoma cerebral metastases. The patient complained of dizziness, vertigo, falls, and trouble recognizing her family members' faces. The CT scan of the head with contrast revealed two metastatic brain lesions with vasogenic edema, as one of them was in the right cerebellar hemisphere, causing dislocation and compression of the ILF. Corticosteroids and osmotherapy were utilized as a conservative treatment approach, which resulted in the prosopagnosia being completely withdrawn. In conclusion, patients with primary brain tumors or metastatic disease rarely present with an isolated cognitive deficit such as prosopagnosia. Based on the anatomical features and the personalized approach, a conservative or surgical approach may be useful to improve higher cortical functioning.

High prevalence of cestodes in Artemia spp. throughout the annual cycle: relationship with abundance of avian final hosts.

Brine shrimp, Artemia spp., act as intermediate hosts for a range of cestode species that use waterbirds as their final hosts. These parasites can have marked influences on shrimp behavior and fecundity, generating the potential for cascading effects in hypersaline food webs. We present the first comprehensive study of the temporal dynamics of cestode parasites in natural populations of brine shrimp throughout the annual cycle. Over a 12-month period, clonal Artemia parthenogenetica were sampled in the Odiel marshes in Huelva, and the sexual Artemia salina was sampled in the Salinas de Cerrillos in Almería. Throughout the year, 4-45 % of A. parthenogenetica were infected with cestodes (mean species richness = 0.26), compared to 27-72 % of A. salina (mean species richness = 0.64). Ten cestode species were recorded. Male and female A. salina showed similar levels of parasitism. The most prevalent and abundant cestodes were those infecting the most abundant final hosts, especially the Greater Flamingo Phoenicopterus ruber. In particular, the flamingo parasite Flamingolepis liguloides had a prevalence of up to 43 % in A. parthenogenetica and 63.5 % in A. salina in a given month. Although there was strong seasonal variation in prevalence, abundance, and intensity of cestode infections, seasonal changes in bird counts were weak predictors of the dynamics of cestode infections. However, infection levels of Confluaria podicipina in A. parthenogenetica were positively correlated with the number of their black-necked grebe Podiceps nigricollis hosts. Similarly, infection levels of Anomotaenia tringae and Anomotaenia microphallos in A. salina were correlated with the number of shorebird hosts present the month before. Correlated seasonal transmission structured the cestode community, leading to more multiple infections than expected by chance.

Congenital myasthenic syndrome due to a genetic mutation.

ABSTRACT: Congenital myasthenic syndrome (CMS) is a group of rare genetic disorders that mimics the symptoms of myasthenia gravis, but it is due to a genetic defect. We present a case of a male CMS patient, and the course of the disease through the years. The patient initially presented with generalized muscle weakness and difficulty swallowing. During the follow-up, he developed difficulty in chewing, bilateral external ophthalmoparesis with an almost full block of eye movements and bulbar syndrome. The case illustrates both the clinical heterogeneity and the progressive worsening of the symptoms of the disease over the years. The optimal treatment for CMS is based on the molecular defect and its localization in the neuromuscular junction. In our case, treatment with pyridostigmine resulted in good long-term control of symptoms. As a result of the patient's good compliance with treatment, he was not admitted to hospital because of respiratory distress. The lack of a unified protocol for the treatment of CMS highlights the need for a more personalized approach when dealing with patients with rare diseases.

Central Pontine Myelinolysis as a Late Complication After Hyponatremia and COVID-19 Infection.

Osmotic demyelination syndrome (ODS) is a rare but serious condition that is hypothesized to be a result of rapid correction of hyponatremia, with a catastrophic prognosis. The foci of demyelination may occur in either the pontine area or within the white matter of the cerebral hemispheres, which denotes a specific clinical presentation. We present the case of a post-COVID-19 patient who was diagnosed with ODS with typical clinical and radiological characteristics of both forms: central pontine myelinolysis and extrapontine myelinolysis. The clinical assessment of ODS encompasses a variety of differential diagnoses, including stroke, neuroinfection, neoplasia, and other demyelinating diseases. A specific characteristic of ODS is the delayed clinical manifestation after the hyponatremic state. Furthermore, it is noteworthy that there might be discrepancies between the clinical manifestations and the neuroimaging findings. The association between COVID-19 and ODS is unclear at the moment, although it can possibly be explained by the viral infection through multiple mechanisms such as renal dysfunction, diarrhea, or vomiting. ODS should be considered in cases of hyponatremia and neurological deterioration during the course of COVID-19 infection. Despite the fact that early detection and treatment of this syndrome can reduce the risk of short-term mortality and long-term disability, they do not guarantee complete recovery.

Hyperglycemic hemichorea due to diabetic striatopathy: case-based review.

Diabetic Striatopathy (DS) is a rare complication of diabetes mellitus (DM) with poor glycemic control and typical neuroimaging findings. DS predominantly leads to a unilateral reversible injury of the basal ganglia resulting in various movement disorders such as hemichorea and hemibalismus. We present a rare case of DS with left-sided hemichorea as a first presentation for a newly diagnosed Diabetes Mellitus (DM) type II and to make a thorough review of this disorder and to provide a practical approach to its management. A 63-year-old female was admitted to the neurology ward with symptoms of involuntary hyperkinetic movements for the left limbs and the left half of the face. The blood samples revealed random serum glucose of 30.8 mmol/l and an HbA1c of 15.13%. The computed tomography of the brain showed asymmetric, unilateral hyperdensity in the right basal ganglia (BG) - the putamen and nucleus caudatus. The patient was managed with Insulin and Haloperidol as the symptoms entirely resolved on the tenth day. In conclusion (DS) is a condition with a good prognosis and reversible clinical and neuroimaging findings after a prompt diagnosis and management. DS should be considered a possible differential diagnosis in patients with abrupt onset of hyperkinetic movement disorders.

Streptococcus Agalactiae Meningitis Presented with Cerebral Infarction in Adult Patient - Clinical Case and Review.

Background: Bacterial meningitis (BM) is an inflammation of the meninges, associated with the invasion of bacteria. The etiologic agents vary by age group. BM because of Group B streptococcus (GBS) is common for the neonatal period but considered as rare in adult patients. Acute BM can have various presentations and adverse effects, such as ischemic stroke in 10% to 29% of the cases. Objective: This study aimed to present a rare case of GBS meningitis presented with cerebral infarction (CI) in an adult patient and to make a brief review of the etiology and incidence of GBS infections in adults. Case Report: We present a case of a 62-year-old female who presented with acute onset of central lesion of the right facial nerve, mild hemiparesis on the right, and partial sensorimotor aphasia. There were no signs of meningoradicular irritation. The pupils were equal, with slow reaction to light, and unaffected eye movements. There was a central lesion of the right facial nerve and mild hemiparesis on the right. Tendon reflexes were unremarkable and Babinski's sign was negative bilaterally. Discussion: This review shows an increasing incidence of cases in elderly patients. A higher risk of GBS is found in adults with more medical comorbidities. CI, as a rare adverse effect in BM, is both a sign for severity and a predictor of a poor clinical outcome with a high lethal rate. GBS infections are a growing problem in older adults and those with chronic medical conditions. The involvement of the central nervous system as meningitis is a less common manifestation with a high lethal rate. Conclusions: CI is a rare adverse effect of neuro infections leading to an even worse clinical outcome. Early recognition of the infection and appropriate antimicrobial therapy are the crucial moments of successful management of GBS disease.

Learning to Discover Explainable Clinical Features With Minimum Supervision.

Purpose: To compare supervised transfer learning to semisupervised learning for their ability to learn in-depth knowledge with limited data in the optical coherence tomography (OCT) domain. Methods: Transfer learning with EfficientNet-B4 and semisupervised learning with SimCLR are used in this work. The largest public OCT dataset, consisting of 108,312 images and four categories (choroidal neovascularization, diabetic macular edema, drusen, and normal) is used. In addition, two smaller datasets are constructed, containing 31,200 images for the limited version and 4000 for the mini version of the dataset. To illustrate the effectiveness of the developed models, local interpretable model-agnostic explanations and class activation maps are used as explainability techniques. Results: The proposed transfer learning approach using the EfficientNet-B4 model trained on the limited dataset achieves an accuracy of 0.976 (95% confidence interval [CI], 0.963, 0.983), sensitivity of 0.973 and specificity of 0.991. The semisupervised based solution with SimCLR using 10% labeled data and the limited dataset performs with an accuracy of 0.946 (95% CI, 0.932, 0.960), sensitivity of 0.941, and specificity of 0.983. Conclusions: Semisupervised learning has a huge potential for datasets that contain both labeled and unlabeled inputs, generally, with a significantly smaller number of labeled samples. The semisupervised based solution provided with merely 10% labeled data achieves very similar performance to the supervised transfer learning that uses 100% labeled samples. Translational Relevance: Semisupervised learning enables building performant models while requiring less expertise effort and time by using to good advantage the abundant amount of available unlabeled data along with the labeled samples.

Neuro-Behcet´s disease - case report and review.

INTRODUCTION: Behcet's disease (BD) is a multisystem autoimmune relapsing vasculitis with almost unknown etiology, which involves both large and small vessels. The involvement of the central nervous system (CNS) is rare, divided into two main sub-types- parenchymal nad and non-parenchymal. The peripheral nervous system is generally preserved or involved in very rare cases. CASE REPORT: We present a rare case of neuro-Behcet's Disease (NBD) in a young 25-year-old female. The patient presented to our clinic with sudden onset complaints of general weakness, quadriparesis more prevalent for the right limbs, slurred speech, and swallowing disorders. Initially, a clinical diagnosis of cerebral infarction was made, but later the condition was defined as parenchymal Neuro-Behcet disease and the patient underwent corticosteroid and immunosuppressive treatment. DISCUSSION: NBD remains a difficult diagnosis to establish as other diseases and conditions may have a similar clinical presentation. The diagnosis is based on the clinical presentation and the typical lesions in brain magnetic resonance imaging (MRI). The development and disappearance of lesions at MRI in relation with disease-specific treatment may correlate with the course of clinical neurologic deficits. CONCLUSIONS: Differential diagnosis of NBD should be considered in cerebrovascular disease, brain tumors, and demyelinating processes.