Thrombolysis after dabigatran reversal: A nation-wide Italian multicentre study, systematic review and meta-analysis.

Introduction: Recent anticoagulant intake represents a contraindication for thrombolysis in acute ischemic stroke. Idarucizumab reverses the anticoagulant effect of dabigatran, potentially allowing for thrombolysis. This nation-wide observational cohort study, systematic review, and meta-analysis evaluated the efficacy and safety of thrombolysis preceded by dabigatran-reversal in people with acute ischemic stroke. Patients and methods: We recruited people undergoing thrombolysis following dabigatran-reversal at 17 stroke centers in Italy (reversal-group), people on dabigatran treated with thrombolysis without reversal (no-reversal group), and age, sex, hypertension, stroke severity, and reperfusion treatment-matched controls in 1:7 ratio (control-group). We compared groups for symptomatic intracranial hemorrhage (sICH, main outcome), any brain hemorrhage, good functional outcome (mRS 0-2 at 3 months), and death. The systematic review followed a predefined protocol (CRD42017060274), and odds ratio (OR) meta-analysis was implemented to compare groups. Results: Thirty-nine patients in dabigatran-reversal group and 300 matched controls were included. Reversal was associated with a non-significant increase in sICH (10.3% vs 6%, aOR = 1.32, 95% CI = 0.39-4.52), death (17.9% vs 10%, aOR = 0.77, 95% CI = 0.12-4.93) and good functional outcome (64.1% vs 52.8%, aOR = 1.41, 95% CI = 0.63-3.19). No hemorrhagic events or deaths were registered in no-reversal group (n = 12). Pooling data from 3 studies after systematic review (n = 1879), reversal carried a non-significant trend for sICH (OR = 1.53, 95% CI = 0.67-3.50), death (OR = 1.53, 95% CI = 0.73-3.24) and good functional outcome (OR = 2.46, 95% CI = 0.85-7.16). Discussion and conclusion: People treated with reperfusion strategies after dabigatran reversal with idarucizumab seem to have a marginal increase in the risk of sICH but comparable functional recovery to matched patients with stroke. Further studies are needed to define treatment cost-effectiveness and potential thresholds in plasma dabigatran concentration for reversal.

The ultimate guide to the anti-CGRP monoclonal antibodies galaxy.

BACKGROUND: Anti-CGRP monoclonal antibodies have represented a real revolution in the field of headaches, being the result of an extraordinary process of translation of new pathophysiological discoveries into successful therapies. Nonetheless, clinical practice is far more complex than pivotal trials setting, and real-world studies are blooming to deepen knowledge of these revolutionary medications. OBJECTIVE: To provide an updated guide for evidence-based clinical practice. METHODS: Pivotal phase 3 randomised clinical trials for each anti-CGRP(-R) monoclonal antibody were considered. We evaluated prospective real-world studies and summarised evidence on anti-CGRP mAbs use beyond episodic and chronic migraine. RESULTS: All phase 3 RCTs showed an unprecedented profile of efficacy and safety in migraine prevention for the four anti-CGRP mAbs. However, plenty of questions remained open after the approval process. Real-world studies filled the gap and effectiveness results equalled or unexpectedly outperformed RCTs figures in most cases; safety results showed a lower incidence of adverse events, but a higher frequency of reported constipation compared to RCTs. Almost all studies displayed a rapid and progressive headache worsening following treatment suspension. Several positive response predictors were suggested, such as unilateral pain, allodynia in episodic migraineurs, response to triptans, and a lower number of failed prophylaxes. Comparable effectiveness was observed in resistant/refractory patients. In medication overuse headache patients, a clear clinical benefit was observed irrespective of any possible detoxification program. CONCLUSIONS: Our narrative review restates the remarkable efficacy, effectiveness, and safety profile in both RCTs and real-world settings and provides scientific evidence for clinical practice.

FDG-PET findings and alcohol-responsive myoclonus in a patient with Unverricht-Lundborg disease.

The aim of this report is to describe clinical, EEG, and neuroimaging findings in a patient with Unverricht-Lundborg disease (ULD), the most common form of progressive myoclonus epilepsy (PME). A 23-year-old male with genetically confirmed ULD had a phenotype consisting of myoclonus, generalized seizures, intellectual disability, ataxia, and dysarthria. Myoclonus and gait disturbance were strongly ameliorated by alcohol consumption. EEG revealed a posterior dominant rhythm with alpha variant, mild bilateral slowing, and anterior-predominant epileptiform abnormalities. Brain MRI showed mild cerebellar atrophy. FDG-PET revealed hypometabolism more prominent in the posterior brainstem, thalami, frontal and parietal lobes. This report confirms that alcohol may ameliorate myoclonus in a subset of patients with PME, including genetically confirmed ULD. In addition, the presence of FDG-PET hypometabolism predominant in the frontoparietal region and thalami has not been previously described in ULD, yet is consistent with previous brain morphometry studies showing motor cortex and thalamic atrophy in ULD, and brings into question the possibility of a shared metabolic pattern with other PMEs, notably Lafora disease.

Multiple sclerosis in patients with hereditary spastic paraplegia: a case report and systematic review.

INTRODUCTION: An increasing number of cases of comorbid hereditary spastic paraplegia (HSP) and multiple sclerosis (MS) have been described. We report a patient with the SPG3A form of HSP and features of relapsing-remitting MS (RRMS). We took this opportunity to review the current literature of co-occurring MS and HSP. METHOD: The patient underwent clinical, laboratory and neuroimaging evaluations. We performed a literature search for cases of HSP and MS. The 2017 McDonalds Criteria for MS were retrospectively applied to the selected cases. RESULTS: A 34-year-old woman, presenting a molecular diagnosis of SPG3A, complained subacute sensory-motor symptoms. Spinal MRI disclosed T2-hyperintense lesions at C2, T6 and T4 level, the latter presenting contrast-enhancement. CSF analysis showed oligoclonal bands. She was treated with intravenous high-dose steroids, with symptom resolution. The literature review yielded 13 papers reporting 20 possible cases of MS and HSP. Nine patients (5 M, median age 34) met the 2017 McDonald criteria. Five (25%) received a diagnosis of RRMS and four (20%) of primary progressive MS. Brain MRI showed multiple WM lesions, mostly periventricular. Six of seven cases (85.7%) had spinal cord involvement. Oligoclonal bands were found in 6/8 (75%) patients. Seven patients (77.7%) improved/stabilized on immunotherapy. CONCLUSION: This is the first description on the association between SPG3A type of HSP and MS. This report adds to the other reported cases of co-occurring HSPs and MS. Although it remains unclear if this association is casual or causal, clinicians should be aware that an HSP diagnosis does not always exclude a concomitant MS.

Detoxification vs non-detoxification before starting an anti-CGRP monoclonal antibody in medication overuse headache.

BACKGROUND: Medication overuse headache significantly contributes to the chronification process and treatment refractoriness of migraine. Currently, abrupt discontinuation of the overused medication still represents the best management strategy for these patients, challenging public health system resources. METHODS: In this prospective study, chronic migraine and medication overuse headache sufferers with at least 28 days of analgesic consumption per month were included. Assessment of efficacy outcomes at three months were compared among patients who underwent in-hospital abrupt discontinuation of overused acute medication (YES-DETOX group) and patients who did not (NO-DETOX group) before starting an anti-CGRP monoclonal antibody. RESULTS: Of 401 patients who received either erenumab or galcanezumab, 28% (n = 111) satisfied inclusion criteria (YES-DETOX n = 28; NO-DETOX n = 83). After three months of treatment, 59% (n = 65; 47/83 YES-DETOX; 18/28 NO-DETOX) patients reverted from medication overuse headache and 51% (n = 57; 42/83 YES-DETOX; 15/28 NO-DEOTX) achieved ≥50% reduction in monthly headache days; yet no statistical differences were observed between the two groups (p = 0.4788 and p = 0.8393, respectively). Monthly consumption of pain medication was the only baseline prognostic factor in multivariate analysis in the overall cohort (p = 0.016). CONCLUSION: Our results support the emerging evidence that anti-CGRP monoclonal antibodies may be effective in medication overuse headache patients irrespective of detoxification, yet further studies are needed to draw definitive conclusions.

Unusual dermoscopic patterns of basal cell carcinoma mimicking melanoma.

BACKGROUND: Basal cell carcinoma can simulate melanoma and specific dermoscopic criteria have not yet been defined in a large cohort. OBJECTIVE: To identify dermoscopic "trump" characteristics for differential diagnosis, identify cluster groups and assess the clinical impact of this study's findings. METHODS: Retrospective, multicentric comparative study of atypical, non-facial basal cell carcinoma (≥1 seven-point checklist criteria) and melanoma (with at least one BCC criteria) at dermoscopy. Observed dermoscopic features were used to develop a proposed score. Lesion clusters were defined with hierarchical analysis. Clinical impact was assessed with a blinded reader study following this study's results. RESULTS: A total of 146 basal cell carcinoma and 76 melanoma were included. Atypical vascular pattern was common to most lesions (74.5%). Twelve trump features were included in the proposed score (sensitivity 94.1% and specificity 79.5%). Cluster analysis identified 3 basal cell carcinoma and 3 melanoma clusters. Findings improved overall diagnostic accuracy and confidence (26.8% and 13.8%, respectively; p < 0.001). CONCLUSIONS: These findings support the notion that atypical vascular pattern should be considered a shared feature of both melanoma and atypical basal cell carcinoma. Our proposed score improves diagnostic accuracy and confidence. Absence of pigmented features was associated with lower diagnostic accuracy and confidence.

Real-life assessment of erenumab in refractory chronic migraine with medication overuse headache.

OBJECTIVE: To determine whether erenumab is effective and safe in refractory chronic migraine with medication overuse headache. METHODS: In this prospective, multicentric, real-life study, chronic migraine with medication overuse headache patients who received erenumab were recruited. Study inclusion was limited to patients who previously failed onabotulinumtoxinA in addition to at least three other pharmacological commonly used migraine preventive medication classes. RESULTS: Of 396 patients who received erenumab, 38% (n = 149) met inclusion criteria. After 3 months, 51% (n = 76) and 20% (n = 30) patients achieved ≥ 50% and ≥ 75% reduction in monthly headache days, respectively. Monthly pain medications intake decreased from 46.1 ± 35.3 to 16.8 ± 13.9 (p < 0.001), while monthly headache days decreased from 25.4 ± 5.4 to 14.1 ± 8.6 (p < 0.001). Increasing efficacy of erenumab over the study period was observed. Allodynia was a negative predictive factor of erenumab response (odds ratio = 0.47; p = 0.03). Clinical conversion to episodic migraine with no medication overuse was observed in 64% (n = 96) patients. No serious adverse events were observed. CONCLUSIONS: Erenumab reduced significantly migraine frequency and pain medication intake in refractory chronic migraine with MOH patients.

Recurrent Aphthous Stomatitis: Treatment and Management.

BACKGROUND: Recurrent aphthous stomatitis consists of the presence of abrasions or ulcerations located on mucosae (oral or genital). OBJECTIVES: The aim of this article is to review the current literature providing the main causes related to recurrent aphthous stomatitis and insights into treatment and management of this clinical condition. METHODS: Articles matching terms that correlated with "recurrent aphthous stomatitis" were searched on PubMed, EMBASE, and Cochrane Library and selected according to their pertinence. RESULTS: Several forms of aphthous stomatitis have been described, based on the extent (minor, major), morphology (herpetiform) and associations to other signs (Behçet syndrome or more complex inflammatory syndromes). Topical as well as systemic treatments have been described to obtain a faster remission of the aphthosis or to reduce associated symptoms such as pain. CONCLUSIONS: Recurrent aphthous stomatitis can have a mild-to-severe clinical appearance, being mainly localized on the oral mucosa or at the level of the genital area. Different strategies have been described so far for its management and treatment.

Clinical efficacy and safety of certolizumab pegol in cutaneous symptoms on psoriasis in patients with psoriatic arthritis: A retrospective analysis in real life.

We present the results on retrospective analysis about the efficacy of Certolizumab pegol (CZP), an antitumor necrosis factor-alpha agent, as monotherapy on skin psoriasis (PsO) in patients affect both by psoriatic arthritis (PsA) and mild-severe PsO. To date, the CZP is authorized for the treatment of PsA, PsO beyond that rheumatoid arthritis, axial spondyloarthritis/ankylosing spondylitis, and Crohn's. Assessments included an evaluation of the Psoriasis Area and Severity Index (PASI). Twelve patients (9M and 3F mean age 57.8 ± 8 years) were enrolled in our study. Nine patients had been previously treated with others biologic agents, three patients were naïve. Clinical and laboratory evaluations including PASI, erythrosedimentation rate, and C-reactive protein were performed at baseline (BL), at Week 12 (W12), Week 24 (W24), and Week 52 (W52) of treatment. Although the combination between methotrexate and CZP is allowed, we included, in our study, patients treated only with CZP. In such a way as to be as specific as possible, topical corticosteroids, vitamin D derivatives, retinoid creams, anthralin derivatives as well as p-UVA or UV-B have been forbidden to enrolled patients. With the same purpose, all the patients used the identical moisturizing cream two times a day. Mean PASI score decreased from 18 (BL) to 0 (W52) as follows: 18 at BL, 4 at W12, 0 at W24, and 0 at W52. Severe adverse events were not reported. Safety evaluations were performed every 3 months: liver and renal functions were monitored in all patients during the treatment, and no patient presented abnormal values. To the best of our knowledge, this is the first report that highlights the efficacy of CZP as monotherapy in psoriasis with mild to severe cutaneous involvement. Although to date the drug is authorized only for PsA, our results demonstrate that CZP is safe and effective on both cutaneous and joint components representing, therefore, an effective option in the treatment of cutaneous symptoms of PsO. Limitations of our study are presented by the relatively short observation time (W52) and by numeric small study group. Long-term data with a larger number of enrolled patients are necessary in order to confirm our preliminary observations.

Characterization of comorbid conditions burdening hidradenitis suppurativa: a multicentric observational study.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, disabling, inflammatory skin disorder that primarily affects the hair follicle localized at the apocrine-gland-bearing areas of the body, including axillary, inguinal, buttocks, and anogenital areas, and it may be associated with a wide array of comorbid conditions. This study aimed to described comorbid conditions affecting HS patients and to detect any correlation with disease severity. METHODS: Analyzing clinic database, we included all charts of patients visited at the HS outpatient clinic of three University Dermatologic Departments in order to describe demographic data, anthropometric measures, disease features, personal habits, clinical history, and presence of comorbidities. RESULTS: Two hundred thirty-four patients, mostly females (62%), were enrolled in this study. Based on Hurley staging classification 41% of patients were classified as Hurley Stage I, 43.0% as Hurley II, and 16% Hurley III, with a mean mSartorius Score value of 24.7 (SD: ±19.39) and a mean AISI score value of 12.5 (SD: ±11.93). The most frequently observed comorbidities were: obesity (26.1%), polycystic ovary syndrome (PCOS) (13.8% of the overall study population and 22.3% of females), hypertension (11.9%), dyslipidemia (9.9%), type II diabetes (9.5%), thyroid disorders (9.1%), nervous system disorders (7.1%), acne (6.7%), metabolic syndrome (4.4%), and Crohn's disease (3.6%). Obesity represented a key-comorbid condition increasing the likelihood of having more severe HS and PCOS (odds ratio 3.35 and 3.74, respectively). CONCLUSIONS: HS is associated with a variety of comorbid conditions that should be considered to perform targeted routine screening and to improve HS management.

Clindamycin versus clindamycin plus rifampicin in hidradenitis suppurativa treatment: Clinical and ultrasound observations.

BACKGROUND: Antibiotics are recognized as first-line treatments for hidradenitis suppurativa (HS), but the data on their efficacy are limited. OBJECTIVE: Evaluate the efficacy of oral clindamycin versus that of clindamycin plus rifampicin in patients with HS. METHODS: A total of 60 patients with mild-to-moderate-severe HS who were classified according to their International Hidradenitis Suppurativa Severity Score System (IHS4) and Hurley scores, were subdivided into 2 groups of 30 patients each (group A, the members of which received clindamycin plus rifampicin, and group B, the members of which were treated with clindamycin alone) and retrospectively studied. The main objective was to evaluate and compare the clinical and ultrasound responses between the groups after 8 weeks of treatment according to the Hidradenitis Suppurativa Clinical Response measure. RESULTS: After the treatment, 17 of 30 patients in group A and 19 of 30 in group B met the primary outcome. Both groups showed a similar improvement of IHS4 score, whereas the Dermatology Life Quality Index and pain Visual Analogue Scale scores improved more in group B. In particular, the reductions in nodule and abscess counts were similar between the 2 groups, whereas the number of draining tunnels decreased more in group B. The factors significantly associated with Hidradenitis Suppurativa Clinical Response score were age, body mass index, IHS4 score, and absence of axillary involvement. Disease-free survival was similar between the 2 groups. LIMITATIONS: The study was not randomized or placebo-controlled. CONCLUSION: Clindamycin may be a useful treatment alternative to antibiotic combination regardless of HS clinical stage.