Persistent headache attributed to past cervicocephalic artery dissection: clinical characteristics and contributors to headache persistence.

BACKGROUND: Persistent headache/facial/neck pain attributed to past cervicocephalic arterial dissection is under-documented in literature. Our main goal was to evaluate clinical characteristics and contributors to this persistence. METHODS: A retrospective cohort study which included patients with a radiologically confirmed cervicocephalic arterial dissection (2015-2020) in a Portuguese tertiary hospital. Headache persistence was identified through clinical records. A questionnaire aimed to characterize headache in three moments: previous, persistent, and headache at the time of the interview (on average 2.5 years post-event). RESULTS: Ninety-two patients were identified; 24 (26.1%) had headache persistence ≥3 months, and 20 (22.2%) on average after 2.5 years post-event. There were no differences regarding demographics and vascular risk factors among patients with (n = 22) and without (n = 68) headache persistence. The first group had higher previous headache history (68.2% vs 4.4%, p < 0.001), delay in diagnosis (3.6 vs 1.9 days, p < 0.001), and headache/cervicalgia as the first symptom (81.8% vs 41.2%, p < 0.001). At the time of the interview, 20% still reported daily headache. A logistic regression model depicted headache history (OR = 59.8, p < 0.001), acute headache/cervicalgia (odds ratio, OR = 25.4, p = 0.005), posterior circulation dissection (OR = 7.6, p < 0.001), and less than 4 points by National Institutes of Health Stroke Scale score (OR = 5.0, p = 0.025) as contributors to headache persistence. CONCLUSION: Headache persistence post-cervicocephalic arterial dissection is common, and frequently affects patients daily. As it potentially affects functional outcomes and quality of life, the contributors identified in this study may help clinicians manage patients after the acute event.

MR Imaging Findings in Anti-Leucine-Rich Glioma Inactivated Protein 1 Encephalitis: A Systematic Review and Meta-analysis.

BACKGROUND: Antibodies against leucine-rich glioma inactivated protein 1 (LGI1) constitute a common form of autoimmune encephalitis. On MR imaging, it may show T2 FLAIR hyperintensities of the medial temporal lobe (T2 FLAIR-MTL), involve the basal ganglia, or be unremarkable. PURPOSE: We performed a systematic review and meta-analysis to obtain prevalence estimates of abnormal findings on MR imaging in anti-LGI1 encephalitis. A human brain map of the LGI1 microarray gene expression was derived from the Allen Human Brain Atlas. DATA SOURCES: PubMed and Web of Science were searched with the terms "LGI1" and "encephalitis" from inception to April 7, 2022. STUDY SELECTION: Thirty-one research publications, encompassing case series and retrospective cohort and case-control studies, with >10 patients with anti-LGI1 encephalitis and MR imaging data were included. DATA ANALYSIS: Pooled prevalence estimates were calculated using Freeman-Tukey double-arcsine transformation. Meta-analysis used DerSimonian and Laird random effects models. DATA SYNTHESIS: Of 1318 patients in 30 studies, T2 FLAIR-MTL hyperintensities were present in 54% (95% CI, 0.48-0.60; I2 = 76%). Of 394 patients in 13 studies, 27% showed bilateral (95% CI, 0.19-0.36; I2 = 71%) and 24% unilateral T2 FLAIR-MTL abnormalities (95% CI, 0.17-0.32; I2 = 61%). Of 612 patients in 15 studies, basal ganglia abnormalities were present in 10% (95% CI, 0.06-0.15; I2 = 67%). LGI1 expression was highest in the amygdala, hippocampus, and caudate nucleus. LIMITATIONS: Only part of the spectrum of MR imaging abnormalities in anti-LGI1 encephalitis could be included in a meta-analysis. MR imaging findings were not the main outcomes in most studies, limiting available information. I2 values ranged from 62% to 76%, representing moderate-to-large heterogeneity. CONCLUSIONS: T2 FLAIR-MTL hyperintensities were present in around one-half of patients with anti-LGI1. The prevalence of unilateral and bilateral presentations was similar, suggesting unilaterality should raise the suspicion of this disease in the appropriate clinical context. Around 10% of patients showed basal ganglia abnormalities, indicating that special attention should be given to this region. LGI1 regional expression coincided with the most frequently reported abnormal findings on MR imaging. Regional specificity might be partially determined by expression levels of the target protein.

Exploring the use of ChatGPT in predicting anterior circulation stroke functional outcomes after mechanical thrombectomy: a pilot study.

BACKGROUND: Accurate prediction of functional outcomes is crucial in stroke management, but this remains challenging. OBJECTIVE: To evaluate the performance of the generative language model ChatGPT in predicting the functional outcome of patients with acute ischemic stroke (AIS) 3 months after mechanical thrombectomy (MT) in order to assess whether ChatGPT can used to be accurately predict the modified Rankin Scale (mRS) score at 3 months post-thrombectomy. METHODS: We conducted a retrospective analysis of clinical, neuroimaging, and procedure-related data from 163 patients with AIS undergoing MT. The agreement between ChatGPT's exact and dichotomized predictions and actual mRS scores was assessed using Cohen's κ. The added value of ChatGPT was measured by evaluating the agreement of predicted dichotomized outcomes using an existing validated score, the MT-DRAGON. RESULTS: ChatGPT demonstrated fair (κ=0.354, 95% CI 0.260 to 0.448) and good (κ=0.727, 95% CI 0.620 to 0.833) agreement with the true exact and dichotomized mRS scores at 3 months, respectively, outperforming MT-DRAGON in overall and subgroup predictions. ChatGPT agreement was higher for patients with shorter last-time-seen-well-to-door delay, distal occlusions, and better modified Thrombolysis in Cerebral Infarction scores. CONCLUSIONS: ChatGPT adequately predicted short-term functional outcomes in post-thrombectomy patients with AIS and was better than the existing risk score. Integrating AI models into clinical practice holds promise for patient care, yet refining these models is crucial for enhanced accuracy in stroke management.

Pituitary Adenoma "Pneumo-Apoplexy".

Tension pneumosella has been recognized as a very rare complication of pituitary transsphenoidal surgery. To the best of our knowledge, we report the second case of a pituitary adenoma "pneumo-apoplexy", which is characterized by findings consistent with tension pneumosella in the context of apoplexy of a pituitary adenoma; although it is an extremely rare diagnosis, it should be considered in patients with compatible clinical and radiological findings, particularly with a previous history of transsphenoidal pituitary surgery.

Successful Treatment of a Child With Epileptic Encephalopathy With Spike-Wave Activation in Sleep and GRIN2A Variant Using Sulthiame.

Epileptic encephalopathy with spike-wave activation in sleep (EE-SWAS) and developmental EE-SWAS (DEE-SWAS) are characterized by variable combinations of cognitive, language, behavioral, and/or motor regression associated with continuous or near-continuous diffuse spike-and-wave complexes during sleep. Glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A) variants have been associated with EE-SWAS. It encodes the most relevant GluN2 subunit of the N-methyl-D-aspartate receptor (NMDAR). Sulthiame reduces NMDAR-mediated neuronal excitability and has been progressively used as monotherapy in self-limited epilepsy with centrotemporal spikes (SeLECTS) or as add-ontherapy in EE-SWAS/DEE-SWAS. A five-year-old female, with family history of epilepsy, was initially diagnosed with SeLECTS and medicated with valproic acid (VPA). One year later, she presented a focal to bilateral tonic-clonic seizure during sleep and learning difficulty. The electroencephalogram revealed continuous spike-and-wave during sleep leading to the diagnosis of EE-SWAS. Prednisolone was effective, but there was repeated recurrence after its discontinuation and associated adverse effects. As an alternative, sulthiame was added to VPA. Four years later, she remains clinically stable. Genetic testing revealed a GRIN2A missense variant, C.3228C>A (p.Asn1076Lys). Sulthiame appeared effective in this recurrent EE-SWAS child, who presented a GRIN2A missense variant with possible NMDAR gain-of-function and adverse effects of corticosteroids. Functional studies​​​​​​​ of GRIN2A variants might become a future tool for individualized therapies.

Contralateral Axillary Lymph Node Metastasis in a Patient with Relapsed Breast Cancer: Locoregional Event or Distant Metastasis Disease?

INTRODUCTION: Contralateral axillary lymph node metastasis (CAM) is a rare clinical condition in patients with breast cancer. It can be explained from hematogenous spread from the original primary tumor (stage IV) to aberrant regional lymphatic drainage to the contralateral axilla. However, according to the current clinical guidelines, regardless of its origin, CAM is considered as metastatic disease. CASE PRESENTATION: A 68-year-old woman presented with relapsed right breast cancer; lymphoscintigraphy showed only one sentinel lymph node (SLN) in the contralateral axilla (left region). Twenty-four hours later, the patient underwent upper internal quadrantectomy and bilateral selective lymph node biopsy. The final pathological analysis revealed one contralateral macrometastasis (>4 mm) in one left SLN. Subsequently, second-level left lymphadenectomy was performed. Currently the patient is being treated with chemotherapy, with appropriate clinical response. DISCUSSION: Our patient was considered to be node-positive rather than having metastatic disease since the preoperative lymphoscintigraphy demonstrated contralateral lymphatic drainage. Through preoperative scan in patients with relapsed breast cancer with clinically negative lymph nodes and CAM, it is possible to identify those cases that would benefit from therapy with curative intention.

Multiple Sclerosis in rheumatic patients treated with tumor necrosis factor alpha inhibitors: a single-center retrospective case series and literature review.

Tumor necrosis factor alpha inhibitors (TNFi) are basilar treatments in a number of inflammatory rheumatic conditions and autoimmune phenomena such as de novo neuroinflammatory events were already described in these populations under TNFi. We conducted a single-center retrospective study in a cohort of rheumatic patients treated with TNFi to characterize neurological demyelinating/inflammatory disease in these patients. We report 3 cases (n= 744): all of them had spondyloarthritis, the onset of neurological manifestations occurred between 37 and 58 years old and all of them initially presented with an optic neuritis. The neurological symptoms emerged between 13 and 26 months after starting TNFi. All patients discontinued treatment with TNFi, but one resumed therapy with symptomatic worsening, having to interrupt treatment again. All patients, latter on, fulfilled multiple sclerosis (MS) McDonald criteria 1 and were diagnosed with relapsing-remitting MS. Our study support the prior view of a risk, disease-dependent or agent-dependent, although a causal relationship is yet to be enlightened.

The Future of Telemedicine in the Management of Heart Failure Patients.

Telemedicine (TM) is potentially a way of escalating heart failure (HF) multidisciplinary integrated care. Despite the initial efforts to implement TM in HF management, we are still at an early stage of its implementation. The coronavirus disease 2019 pandemic led to an increased utilisation of TM. This tendency will probably remain after the resolution of this threat. Face-to-face medical interventions are gradually transitioning to the virtual setting by using TM. TM can improve healthcare accessibility and overcome geographic inequalities. It promotes healthcare system efficiency gains, and improves patient self-management and empowerment. In cooperation with human intervention, artificial intelligence can enhance TM by helping to deal with the complexities of multicomorbidity management in HF, and will play a relevant role towards a personalised HF patient approach. Artificial intelligence-powered/telemedical/heart team/multidisciplinary integrated care may be the next step of HF management. In this review, the authors analyse TM trends in the management of HF patients and foresee its future challenges within the scope of HF multidisciplinary integrated care.

Aplidin induces the mitochondrial apoptotic pathway via oxidative stress-mediated JNK and p38 activation and protein kinase C delta.

Aplidin, a new antitumoural drug presently in phase II clinical trials, has shown both in vitro and in vivo activity against human cancer cells. Aplidin effectively inhibits cell viability by triggering a canonical apoptotic program resulting in alterations in cell morphology, caspase activation, and chromatin fragmentation. Pro-apoptotic concentrations of Aplidin induce early oxidative stress, which results in a rapid and persistent activation of both JNK and p38 MAPK and a biphasic activation of ERK. Inhibition of JNK and p38 MAPK blocks the apoptotic program induced by Aplidin demonstrating its central role in the integration of the cellular stress induced by the drug. JNK and p38 MAPK activation results in downstream cytochrome c release and activation of caspases -9 and -3 and PARP cleavage, demonstrating the mediation of the mitochondrial apoptotic pathway in this process. We also demonstrate that protein kinase C delta (PKC-delta) mediates the cytotoxic effect of Aplidin and that it is concomitantly processed and activated late in the apoptotic process by a caspase mediated mechanism. Remarkably, cells deficient in PKC-delta show enhanced survival upon drug treatment as compared to its wild type counterpart. PKC-delta thus appears as an important component necessary for full caspase cascade activation and execution of apoptosis, which most probably initiates a positive feedback loop further amplifying the apoptotic process.

Aplidin induces apoptosis in human cancer cells via glutathione depletion and sustained activation of the epidermal growth factor receptor, Src, JNK, and p38 MAPK.

We report that Aplidin, a novel antitumor agent of marine origin presently undergoing Phase II clinical trials, induced growth arrest and apoptosis in human MDA-MB-231 breast cancer cells at nanomolar concentrations. Aplidin induced a specific cellular stress response program, including sustained activation of the epidermal growth factor receptor (EGFR), the non-receptor protein-tyrosine kinase Src, and the serine/threonine kinases JNK and p38 MAPK. Aplidin-induced apoptosis was only partially blocked by the general caspase inhibitor benzyloxycarbonyl-VAD-fluoromethyl ketone and was also sensitive to AG1478 (an EGFR inhibitor), PP2 (an Src inhibitor), and SB203580 (an inhibitor of JNK and p38 MAPK) in MDA-MB-231 cells. Supporting a role for EGFR in Aplidin action, EGFR-deficient mouse embryo fibroblasts underwent apoptosis upon treatment more slowly than wild-type EGFR fibroblasts and also showed delayed JNK and reduced p38 MAPK activation. N-Acetylcysteine and ebselen (but not other antioxidants such as diphenyleneiodonium, Tiron, catalase, ascorbic acid, and vitamin E) reduced EGFR activation by Aplidin. N-Acetylcysteine and PP2 also partially inhibited JNK and p38 MAPK activation. The intracellular level of GSH affected Aplidin action; pretreatment of cells with GSH or N-acetylcysteine inhibited, whereas GSH depletion caused, hyperinduction of EGFR, Src, JNK, and p38 MAPK. Remarkably, Aplidin also induced apoptosis and activated EGFR, JNK, and p38 MAPK in two cell lines (A-498 and ACHN) derived from human renal cancer, a neoplasia that is highly refractory to chemotherapy. These data provide a molecular basis for the anticancer activity of Aplidin.