Vismodegib in Gorlin-Goltz syndrome: A systematic review.

Treatment with Hedgehog Inhibitors in Gorlin-Goltz syndrome (GGS) yields favourable objective clinical responses, yet secondary resistance and class-related toxicity restrict treatment duration. This study aims to review current data on GGS patients undergoing vismodegib therapy, focusing on treatment duration, clinical outcomes and schedule modifications. A systematic search of the PubMed database was conducted for English articles from 1993 to 2023, identifying 31 papers suitable for inclusion. A total of 351 patients, with a mean age of 52 years, were analysed. The average treatment duration was 9.3 months for patients who discontinued treatment, and 25.1 months for those who continued vismodegib at the time this study was published. Vismodegib achieved a complete response rate of 44%. Treatment interruption predominantly occurred due to side effects (69.1%) and secondary resistance (9.1%). The use of alternative regimens, although not compromising efficacy, may enhance treatment compliance. Further investigations are warranted to ascertain the optimal treatment regimen and timeline for GGS patients. Schedule modifications offer promise in ameliorating side effects and facilitating long-term treatment.

Ictal Cotard delusion as a manifestation of nonconvulsive status epilepticus: A case report and commentary.

Psychosis of epileptic origin can present a wide range of cognitive and affective symptoms and is often underrecognized. Usually occurring in the inter- and postictal phase, epileptic psychosis is mostly related to temporal lobe epilepsy. Here, we describe the clinical presentation and diagnostic workup including routine EEG recording and brain MRI of a 63-year-old woman expressing isolated nihilistic delusions comprising belief of being dead and denial of self-existence. EEG showed an ictal pattern fulfilling the Salzburg criteria of nonconvulsive status epilepticus and brain MRI revealed extensive peri-ictal hyperperfusion. Delusional symptoms and EEG abnormalities subsided after acute antiseizure treatment. Our case illustrates how nihilistic delusions can occur as a direct clinical correlate of seizure activity, thereby expanding the spectrum of ictal neuropsychiatric phenomena in temporal lobe epilepsy and highlighting the need to consider an epileptic origin in patients presenting with psychotic symptoms.

Use of Picosecond Laser for Melasma Treatment: A Narrative Review.

Background: Melasma results from the imbalance of the mechanisms that regulate skin pigmentation, causing the appearance of hyperpigmented patches. Treatment includes topical and oral agents, chemical peelings, microneedling, and laser therapy. The picosecond laser was developed to minimize pain and skin discoloration, which can sometimes be associated with laser treatments. It emits short pulses of energy that last from 300 to 500 picoseconds, leading to a more significant fragmentation of melanin, with miniminal risk of scarring and thermal lesions in the surrounding skin. Objective: The authors aimed to review the use of picosecond laser in the treatment of melasma and further provide an overview of the other current available options. Conclusions: While the use of picosecond laser for the treatment of melasma has yielded good results, further studies with longer follow-up periods and a higher number of patients are needed.

Optimizing Care for High-Risk Multiple Pregnancy with POCUS - A Case of Quadruplet Pregnancy Early Diagnosis.

Managing multiple pregnancies is challenging and requires careful evaluation. Point of care ultrasound (POCUS) has emerged as a potentially crucial tool in assessing suspected first-trimester pregnancies. However, its role in evaluating multiple pregnancies remains uncertain. We present the case of a 36-year-old Ghanaian female who presented with acute vaginal bleeding after undergoing in vitro fertilization. A bedside transabdominal POCUS identified four intrauterine gestations with fetal poles and cardiac activity, suggesting a quadruplet viable pregnancy. A subsequent transvaginal ultrasound confirmed the findings. The patient was discharged with a follow-up appointment with an Obstetrician-Gynecologist. This case highlights the significance of POCUS in early pregnancy diagnosis, facilitating accurate identification and appropriate referral for further management. It also demonstrates the utility of POCUS in determining gestational age and viability. To our knowledge, no published case reports specifically address the diagnosis of a quadruplet pregnancy, emphasizing the role of POCUS in optimizing care for high-risk multiple pregnancies.

MEK inhibitor-induced paronychia in a paediatric population: A tertiary centre experience.

The cutaneous toxicity of MEK inhibitors may limit treatment adherence. The authors present a retrospective study of 41 paediatric patients with NF-1 undergoing therapy with selumetinib and propose a treatment algorithm.

Association of stroke lesion shape with newly detected atrial fibrillation - Results from the MonDAFIS study.

Paroxysmal Atrial fibrillation (AF) is often clinically silent and may be missed by the usual diagnostic workup after ischemic stroke. We aimed to determine whether shape characteristics of ischemic stroke lesions can be used to predict AF in stroke patients without known AF at baseline. Lesion shape quantification on brain MRI was performed in selected patients from the intervention arm of the Impact of standardized MONitoring for Detection of Atrial Fibrillation in Ischemic Stroke (MonDAFIS) study, which included patients with ischemic stroke or TIA without prior AF. Multiple morphologic parameters were calculated based on lesion segmentation in acute brain MRI data. Multivariate logistic models were used to test the association of lesion morphology, clinical parameters, and AF. A stepwise elimination regression was conducted to identify the most important variables. A total of 755 patients were included. Patients with AF detected within 2 years after stroke (n = 86) had a larger overall oriented bounding box (OBB) volume (p = 0.003) and a higher number of brain lesion components (p = 0.008) than patients without AF. In the multivariate model, OBB volume (OR 1.72, 95%CI 1.29-2.35, p < 0.001), age (OR 2.13, 95%CI 1.52-3.06, p < 0.001), and female sex (OR 2.45, 95%CI 1.41-4.31, p = 0.002) were independently associated with detected AF. Ischemic lesions in patients with detected AF after stroke presented with a more dispersed infarct pattern and a higher number of lesion components. Together with clinical characteristics, these lesion shape characteristics may help in guiding prolonged cardiac monitoring after stroke.

Comprehensive Evaluation of Cerebral Hemodynamics and Oxygen Metabolism in Revascularization of Asymptomatic High-Grade Carotid Stenosis.

INTRODUCTION: Revascularization procedures in carotid artery stenosis have shown a positive effect in the restoration of cerebral oxygen metabolism as assessed by T2' (T2 prime) imaging as well as capillary homeostasis by measurement of capillary transit time heterogeneity (CTH); however, data in patients with asymptomatic carotid stenosis without manifest brain lesions are scarce. PATIENTS AND METHODS: The effect of revascularization on the hemodynamic profile and capillary homeostasis was evaluated in 13 patients with asymptomatic high-grade carotid stenosis without ischemic brain lesions using dynamic susceptibility contrast perfusion imaging and oxygenation-sensitive T2' mapping before and 6-8 weeks after revascularization by endarterectomy or stenting. The cognitive performance at both timepoints was further assessed. RESULTS: Perfusion impairment at baseline was accompanied by an increased CTH (p = 0.008) in areas with a time to peak delay ≥ 2 s in the affected hemisphere compared to contralateral regions. Carotid intervention improved the overall moderate hemodynamic impairment at baseline by leading to an increase in normalized cerebral blood flow (p = 0.017) and a decrease in mean transit time (p = 0.027), oxygen extraction capacity (OEC) (p = 0.033) and CTH (p = 0.048). The T2' values remained unchanged. CONCLUSION: This study presents novel evidence of a state of altered microvascular function in patients with high-grade carotid artery stenosis in the absence of ischemic brain lesions, which shows sustained normalization after revascularization procedures.

Familial Cases of PENS: A Review of the Literature.

Papular epidermal nevus with "skyline" basal cell layer (PENS) is a keratinocytic nevus that can occur sporadically or has a familial transmission. There are 5 families reported with PENS, in which there are 2 family members affected with each case. We present the sixth familial case, with the peculiarity of being the first time in which there are 3 family members with PENS, while reviewing the other cases described until now. In addition, we present a new histopathological finding, an inflammatory lichenoid infiltrate on the upper dermis in PENS lesions. This finding could be the result of trauma to the biopsied lesion, or it may represent a new inflammatory histological variant.

Etiologic Evaluation of Ischemic Stroke in Young Adults: A Comparative Study between Two European Centers.

INTRODUCTION: Identifying the cause of ischemic stroke in young adults is often difficult. Our objective was to compare the etiologic diagnostic strategy for ischemic stroke in young adults between 2 European centers and investigate the influence of workup variations in the diagnosed etiologies. PATIENTS AND METHODS: We included patients aged 18-55 years admitted for ischemic stroke or transient ischemic attack to the stroke units of Santa Maria Hospital in Lisbon, Portugal, and Innsbruck University Hospital in Innsbruck, Austria, between 2014 and 2016. Etiology and diagnostic procedures were compared between centers. RESULTS: We included 156 patients from Innsbruck University Hospital and 110 patients from Santa Maria Hospital. Search for intracranial large-vessel disease was performed mainly by computed tomography/magnetic resonance angiography in Innsbruck (83.9% versus 52.7%; P < .01) and by transcranial Doppler in Lisbon (91.8% versus 43.2%; P < .01). Transoesophageal echocardiography was preferred in Innsbruck for detecting paradoxical embolism (80.0% versus 68.2%; P < .05), whereas in Lisbon contrast transcranial Doppler was preferred (80.9% versus 3.9%; P < .01). For investigation of other causes, Lisbon patients were more commonly screened for thrombophilia (100.0% versus 92.3%; P < .05) and autoimmune disorders (91.7% versus 44.5%; P < .01) while in Innsbruck consultation by other specialists was more frequent (51.6% versus 10.0%; P < .01). No significant differences were found in etiologies between centers. CONCLUSION: The differences in diagnostic workup did not influence etiologic diagnosis. Extensive laboratory testing does not seem to influence diagnosis of stroke of other determined cause, emphasizing the importance of a clinically-oriented approach for the etiologic diagnosis of stroke in young adults.

Ultrasound for assessment of diaphragm in ALS.

OBJECTIVE: To evaluate the correlation between diaphragm thickness assessed by ultrasound (US) with respiratory function tests and the diaphragm motor responses, in patients with amyotrophic lateral sclerosis (ALS). METHODS: 42 consecutive ALS patients were studied (11 with bulbar-onset), excluding patients with marked orofacial paresis. Investigation included: revised ALS functional rating scale (ALSFRS-R), forced vital capacity (FVC), maximal voluntary ventilation (MVV), maximal inspiratory (MIP) and expiratory (MEP) pressures, nasal inspiratory pressure during sniff (SNIP); peak-to-peak amplitude of the diaphragmatic motor response to phrenic nerve stimulation (Diaphragm-CMAP), diaphragmatic thickness measured by ultrasound during maximal inspiration and during maximal expiration. Patients were analysed in bulbar or spinal subgroups. Correlations and multiple linear regression models were studied. RESULTS: The mean age at disease onset was 58.4 ± 11.1 years and with a mean disease duration of 17.8 ± 13.6 months. Ultrasound studies of diaphragm thickness in full inspiration correlated with diaphragm CMAP in the whole population and in spinal-onset patients; and were similar in the two groups. Multiple linear modelling showed that FVC, SNIP and MVV were dependent on the change of thickness (p=0.001, 0.001 and 0.020, respectively) and that MIP and MEP were related to diaphragm CMAP p=0.003 and p=0.025, respectively). CONCLUSION: Diaphragm thickness correlates with Diaphragm-CMAP, except in bulbar-onset patients. Respiratory tests are dependent on both diaphragm thickness and Diaphragm-CMAP. SIGNIFICANCE: US thickness of the diaphragm correlates with the number of functional motor units as assessed by the phrenic nerve motor amplitude.