Initial experience with novel CGRP-receptor inhibitor therapy in Migraine in the United Arab Emirates: a retrospective observational study.

BACKGROUND: Erenumab is a calcitonin gene-related peptide (CGRP)-receptor antibody inhibiting CGRP function. CGRP is prominently involved in the pathophysiology of migraine through nociceptive modulation in the trigeminovascular system. This study aims to explore the treatment effect of erenumab in a real-life setting. METHODS: In this retrospective observational study, we analyzed the data of 91 patients with migraine receiving at least three consecutive monthly injections of erenumab and followed up for 3-12 months. The primary objective was to describe the reduction in monthly migraine days throughout the follow-up period. To identify patients who responded to treatment, we analyzed the association between different patient characteristics and their treatment outcomes. RESULTS: Seventy-three patients (80.2%) responded to erenumab treatment, defined as ≥50% reduction of migraine days per month, across all migraine types. It was noted that ethnicity (p-value = 0.015) and older age (p-value = 0.035) were associated with clinically relevant improvement of symptoms. Middle Eastern ethnicity was related to less improvement of symptoms while Europeans were more likely to benefit from erenumab therapy (odds ratio: 12.788, p = 0.037). Patients aged from 31 to 40 and 41-65 years benefited most from erenumab treatment with a response rate of 77.8 and 89.9%, respectively, also confirmed by logistic regression (p = 0.047). Neither gender nor dose increase of erenumab showed association with the reported clinically relevant improvement of the symptoms. An association between clinically relevant improvement of headaches and the type of migraine was also noted. Around 87.9% of patients with episodic migraine responded to treatment, followed by 84.1% of chronic migraine patients and 50% of medication overuse headache patients. Medication overuse headache showed a lower probability of therapy success with erenumab (odds ratio: 0.126, p = 0.039). An improvement of headaches was eminent in patients who received 140 mg erenumab monthly (2 × 70 mg injections) and patients who had one injection every two weeks. CONCLUSIONS: Erenumab is a novel preventive treatment for all migraine types. Clinically relevant improvement of headaches and reduction of monthly migraine days were demonstrated in patients that continued the treatment course. In real-life, a substantial number of patients suspended therapy early, reasons for which need further investigation.

Consensus-Based Recommendations on the Use of CGRP-Based Therapies for Migraine Prevention in the UAE.

INTRODUCTION: Migraine is a common debilitating neurological disorder affecting a large proportion of the general population. Calcitonin gene-related peptide (CGRP), a 37-amino acid neuropeptide, plays a key role in the pathophysiology of migraine, and the development of therapies targeting the anti-CGRP pathway has revolutionized the field of migraine treatment. METHODS: An expert task force of neurologists in the United Arab Emirates (UAE) developed and critically assessed recommendations on the use of CGRP-based therapies in migraine treatment and management in the UAE, based on available published literature. A consensus was reached for each statement by means of an open-voting process, based on a predefined agreement level of at least 60%. RESULTS: The consensus recommendations advocate the need for guidelines for the appropriate use of CGRP-based therapies by defining patient cohorts and appropriate monitoring of therapeutic response as well as standardizing the initiation, assessment, and cessation of treatment. The consensus recommendations were primarily formulated on the basis of international studies, because of the limited availability of regional and local data. As such, they may also act as guidelines for global healthcare providers. CONCLUSIONS: These are the first consensus recommendations for the UAE that address the use of CGRP-based therapies in the treatment and management of migraine, integrating both clinical evidence and medical expertise to enhance clinical judgment and decision-making.

Nonfibrillar Abeta 1-42 inhibits glutamate uptake and phosphorylates p38 in human fibroblasts.

Alzheimer disease (AD) is the most prevalent neurodegenerative disease, characterized by an increased deposition of ß-amyloid (Abeta) within the central nervous system, leading to neuronal death. The availability of effective models, in which confirming novel pathogenic hypotheses and developing therapeutic targets, represents a very important goal for the field of AD. Fibroblasts from these patients may be relevant models in which addressing these issues, as they display biochemical alterations mirroring SNC ones. In this work, fibroblasts obtained from controls were studied after exposure to nonfibrillar Abeta 1-42, showing decreased glutamate uptake, similar to that observed in AD cells, in absence of transporters modifications. Nonfibrillar Abeta 1-42 was able to induce in control cells mitochondrial alterations and p38-phosphorylation, mirroring similar alterations found in AD fibroblasts. Under our experimental conditions, this treatment induced neither apoptosis nor necrosis. To investigate a putative role of p38-modulation in mediating nonfibrillar Abeta 1-42 toxicity, fibroblasts from controls were pretreated with retinoic-acid, and SB203580, a p38-inhibitor. These pretreatments prevented both p38-phosphorylation and glutamate uptake inhibition. Our results suggest that nonfibrillar Abeta 1-42 downregulates glutamate transporters activity interfering with p38-activation and mitochondrial stress. Thus, modulating complex kinase signaling pathway might represent a future therapeutic target in AD.

MM2-thalamic Creutzfeldt-Jakob disease: neuropathological, biochemical and transmission studies identify a distinctive prion strain.

In Creutzfeldt-Jakob disease (CJD), molecular typing based on the size of the protease resistant core of the disease-associated prion protein (PrP(Sc) ) and the M/V polymorphism at codon 129 of the PRNP gene correlates with the clinico-pathologic subtypes. Approximately 95% of the sporadic 129MM CJD patients are characterized by cerebral deposition of type 1 PrP(Sc) and correspond to the classic clinical CJD phenotype. The rare 129MM CJD patients with type 2 PrP(Sc) are further subdivided in a cortical and a thalamic form also indicated as sporadic fatal insomnia. We observed two young patients with MM2-thalamic CJD. Main neuropathological features were diffuse, synaptic PrP immunoreactivity in the cerebral cortex and severe neuronal loss and gliosis in the thalamus and olivary nucleus. Western blot analysis showed the presence of type 2A PrP(Sc) . Challenge of transgenic mice expressing 129MM human PrP showed that MM2-thalamic sporadic CJD (sCJD) was able to transmit the disease, at variance with MM2-cortical sCJD. The affected mice showed deposition of type 2A PrP(Sc) , a scenario that is unprecedented in this mouse line. These data indicate that MM2-thalamic sCJD is caused by a prion strain distinct from the other sCJD subtypes including the MM2-cortical form.

C-reactive protein and aetiological subtypes of cerebral infarction.

OBJECTIVE: We have sought to relate C-reactive protein (CRP), a peripheral marker of inflammation frequently elevated in stroke patients, with aetiology and prognosis of acute cerebral infarction. PATIENTS AND METHODS: Patients were included after a first-ever CT/MR documented cerebral infarction. CRP was measured from blood samples taken within the 6th hour of the onset. Titres of C-reactive protein were stratified in quartiles. Aetiology of stroke was from TOAST criteria. Prognosis was mortality within 14 days of stroke. RESULTS: The study included 648 stroke patients. They were 335 women and 313 men, with a mean age of 70.3 years (median 72). CRP quartiles were mostly increased in cardioembolic strokes, After logistic regression analysis CRP remained an independent factor of 14-day mortality. CONCLUSIONS: Our study suggests that in the acute phase of the cerebral infarction CRP might be either a marker of cardioembolism or a predictive factor for short-term mortality.