Single-Pulse Transcranial Magnetic Stimulation for the preventive treatment of difficult-to-treat migraine: a 12-month prospective analysis.

BACKGROUND: Initial evidence have shown the short-term efficacy of sTMS in the acute and preventive treatment of migraine. It is unknown whether this treatment approach in the long-term is effective and well tolerated in difficult-to-treat migraine. METHODS: This is a prospective, single centre, open-label, real-world analysis conducted in difficult-to-treat patients with high-frequency episodic migraine (HFEM) and chronic migraine (CM) with and without medication overuse headache (MOH), who were exposed to sTMS therapy. Patients responding to a three-month sTMS treatment, continued the treatment and were assessed again at month 12. The cut-off outcome for treatment continuation was reduction in the monthly moderate to severe headache days (MHD) of at least 30% (headache frequency responders) and/or a ≥ 4-point reduction in headache disability using the Headache Impact test-6 (HIT-6) (headache disability responders). RESULTS: One hundred fifty-three patients were included in the analysis (F:M = 126:27, median age 43, IQR 32.3-56.8). At month 3, 93 out of 153 patients (60%) were responders to treatment. Compared to baseline, the median reduction in monthly headache days (MHD) for all patients at month 3 was 5.0 days, from 18.0 (IQR: 12.0-26.0) to 13.0 days (IQR: 5.75-24.0) (P = 0.002, r = - 0.29) and the median reduction in monthly migraine days (MMD) was 4.0 days, from 13.0 (IQR: 8.75-22.0) to 9.0 (IQR: 4.0-15.25) (P = 0.002, r = - 0.29). Sixty-nine out of 153 patients (45%) reported a sustained response to sTMS treatment at month 12. The percentage of patients with MOH was reduced from 52% (N = 79/153) at baseline to 19% (N = 29/153) at month 3, to 8% (N = 7/87) at month 12. There was an overall median 4-point reduction in HIT-6 score, from 66 (IQR: 64-69) at baseline to 62 at month 3 (IQR: 56-65) (P < 0.001, r = - 0.51). A total of 35 mild/moderate adverse events were reported by 23 patients (15%). One patient stopped sTMS treatment due to scalp sensitivity. CONCLUSIONS: This open label analysis suggests that sTMS may be an effective, well-tolerated treatment option for the long-term prevention of difficult-to-treat CM and HFEM.

Radiological assessment of response and adverse events associated with novel systemic oncological therapies.

The last decade has seen a paradigm shift in medical oncology treatment with the rise of novel systemic agents, principally molecular targeted therapy and immunotherapy. These new groups of anti-cancer treatment have revolutionised the prognostic landscape for certain patient cohorts with advanced disease, and it is hoped that through ongoing extensive clinical research, significant survival benefits may be demonstrated in the majority of tumour types. However, radiological response assessment of these new agents has become more nuanced for radiologists, as the behaviour of both responding and progressing tumour burden can be more diverse than with conventional chemotherapy. Additionally, radiologists need to be aware of adverse events associated with these treatments as some side effects carry a high morbidity/mortality and may manifest radiologically before they become clinically apparent. This review discusses radiological response assessment and adverse events associated with these novel agents, which have become fundamental aspects of systemic oncological therapy.

The fifth cranial nerve in headaches.

The fifth cranial nerve is the common denominator for many headaches and facial pain pathologies currently known. Projecting from the trigeminal ganglion, in a bipolar manner, it connects to the brainstem and supplies various parts of the head and face with sensory innervation. In this review, we describe the neuroanatomical structures and pathways implicated in the sensation of the trigeminal system. Furthermore, we present the current understanding of several primary headaches, painful neuropathies and their pharmacological treatments. We hope that this overview can elucidate the complex field of headache pathologies, and their link to the trigeminal nerve, to a broader field of young scientists.

A multicentre assessment of prostate MRI quality and compliance with UK and international standards.

AIM: To assess prostate magnetic resonance imaging (MRI) image quality and compliance with technical standards between centres in the South West region of the UK. MATERIALS AND METHODS: Fifteen imaging sites in the region submitted seven consecutive anonymised MRI studies. These were assessed by two experienced radiologists in consensus. Overall, subjective image quality for T2-weighted imaging (T2W), diffusion weighted imaging (DWI), and dynamic contrast enhancement (DCE) was scored on a five-point Likert scale. Five additional quality parameters were also assessed visually, including image noise, motion, artefact, and distortion. The degree of compliance by each site with 21 published technical standards was also assessed. RESULTS: Ninety-four MRI examinations were reviewed from across all sites (mean 6.3 scans per site, range 5-7). Mean compliance with technical standards was 63% (range 38-86%). Forty-seven percent of sites did not perform DCE. One site used a 3 T scanner. The percentage of patients with overall quality scores of ≥3 (diagnostically acceptable) were 68% for T2W, 81% for DWI, and 60% for both T2W and DWI. Ninety-three percent of the 45 patients who underwent DCE had diagnostically acceptable studies. By scanner age, the percentage of patients with diagnostically acceptable T2W scores was 53% for scanners ≥7 years and 80% when <7 years (p=0.006). Comparing individual sites, the mean overall quality scores were 2.9 (range 2.2-4.2) for T2W, 3.2 (1.8-4.7) for DWI, and 3.4 (2.5-4.7) for DCE. CONCLUSION: There is wide variation in compliance with recognised technical standards and image quality across sites. If MRI is to replace biopsy in selected low-risk patients, improvements in image quality may be required.

Prospective real-world analysis of OnabotulinumtoxinA in chronic migraine post-National Institute for Health and Care Excellence UK technology appraisal.

BACKGROUND AND PURPOSE: The National Institute for Health and Care Excellence (NICE) in the UK recommends the use of OnabotulinumtoxinA (BoNTA, Botox® ) in the management of chronic migraine (CM) following specific guidelines within the National Health Service. In view of the lack of data on the efficacy of this therapy following implementation of these guidelines in clinical practice and on the evaluation of guidance compliance, we aimed to evaluate the effectiveness and safety of BoNTA in patients with CM following the NICE guidelines. METHODS: This was a prospective real-life audit study. RESULTS: After two treatments, 127 of 200 patients (63.5%) obtained at least a 30% reduction in headache days. Those who continued the treatment up to 3 years reported a stable beneficial effect compared with baseline. Amongst responders, 68 patients (53.5%) were reclassified as episodic migraineurs. A total of 57 of these patients (83.8%) converted to an episodic migraine pattern at 6-month follow-up. The majority of those whose migraine became episodic after BoNTA extended the treatment intervals beyond 3 months (range 4-8 months) before noticing any worsening of headache. We observed no significant differences in the efficacy measures in patients treated with 155 U BoNTA compared with those treated with >155 U BoNTA. CONCLUSIONS: When administered according to the NICE guidance, BoNTA produced a clinically meaningful effect in the long-term management of CM with and without medication overuse headache. Treatment discontinuation when CM becomes episodic may be useful in clinical practice to identify those who may benefit from extended treatment intervals. Our clinical experience indicates a lack of additional benefit from using the 'follow-the-pain' paradigm.

Pharmacology of reflex blinks in the rat: a novel model for headache research.

BACKGROUND: Migraineurs are highly sensitive to the nitric oxide donor glyceryl trinitrate which triggers attacks in many sufferers. In animal studies, glyceryl trinitrate increases neuronal activity in the trigeminovascular pathway and elevates neurotransmitter levels in the brainstem. Many migraineurs also display alterations in blink reflexes, known to involve brainstem circuits. We investigated the effect of GTN on evoked blinks in the anaesthetised rat to determine whether such reflexes may prove useful as the basis for a novel animal model to evaluate potential anti-migraine therapeutic agents. METHOD: In anaesthetised rats the electromyogram associated with the reflex blink evoked by corneal airpuff was recorded. Rats were infused with glyceryl trinitrate, sumatriptan plus glyceryl trinitrate or vehicle control. Changes in the magnitude of the reflex blink-associated electromyogram following these treatments were measured. RESULTS: Glyceryl trinitrate potentiated the evoked reflex blink-associated EMG response from 2 h after infusion. That effect was abolished by simultaneous infusion of sumatriptan with glyceryl trinitrate. CONCLUSIONS: These results show that simple skin surface measurements of evoked electromyographic activity in the rat can reliably detect the evoked blink reflex that can be potentiated by nitric oxide donors. This novel model may be an effective tool for evaluating putative anti-migraine therapeutic agents.

[The Impact of Tumor Cell Proliferation on Occult Micrometastases, Tumor Recurrence and Patient Outcome Following Resection for Liver Malignancies]. / Stellenwert des Proliferationsreizes auf die okkulte Mikrometastasierung sowie Rezidivhäufigkeit und Prognose nach Resektion von Lebermalignomen.

Liver resection is currently considered to be essential part of the curative treatment of primary and secondary liver malignancies. However, long-term survival in these patients is limited by the high incidence of tumor recurrence. Recent clinical and experimental studies have indicated that cellular and molecular mechanisms associated with liver regeneration after partial hepatectomy may have a proliferative effect on occult micrometastases and circulating tumor cells and are thus responsible for recurrent disease. Growth factors and cytokines involved in liver regeneration have also been shown to influence tumour growth and metastasis. However, the underlying mechanisms explaining the interactions between regenerating liver tissue and tumour cell proliferation remain unclear. The development of modern agents specifically targeting these processes may improve disease-free and overall survival rates after oncological hepatectomy.

The prognostic significance of MRI-detected extramural venous invasion in rectal carcinoma.

AIM: To assess whether there is a significant difference in the incidence of patients with metastases of rectal carcinoma at 1 year follow-up between magnetic resonance imaging (MRI)-detected extramural venous invasion (EMVI) and those without. MATERIALS AND METHODS: A search of our institution's cancer registry revealed 788 patients with rectal carcinoma between January 2007 and April 2012. Those who were initially staged using MRI and computed tomography (CT) chest/abdomen/pelvis, and followed-up with a CT chest/abdomen/pelvis examination at 1 year were included in this retrospective study. Patients with synchronous metastases were excluded, leaving a cohort of 202 cases. Two consultant radiologists reviewed all MRI images and gave a consensus opinion regarding EMVI grade and vessel size involved. All CT images were reviewed for metastases. Results were analysed using chi-squared and Fisher's exact tests. RESULTS: There were 53 cases (26.2%) of EMVI-positive rectal carcinoma. Of the patients with EMVI, 24.5% developed metastases at 1 year follow-up, compared to 6.7% of those without. There is a significant difference in prognosis between those patients with and those without MRI-detected EMVI (χ(2) = 12.29, p < 0·001). Those with EMVI have a 3.7 times increased relative risk of developing metachronous metastases within 1 year of diagnosis. CONCLUSION: MRI-detected EMVI-positive rectal carcinomas are associated with an increased risk of metachronous metastases within 1 year of diagnosis. Currently, EMVI status does not directly influence the initial management of rectal carcinoma. This available and potentially prognostic feature could be used to guide treatment pathways to increase disease-free survival.

Twenty-year longitudinal follow-up after orthotopic liver transplantation: a single-center experience of 313 consecutive cases.

With excellent short-term survival in liver transplantation (LT), we now focus on long-term outcome and report the first European single-center 20-year survival data. Three hundred thirty-seven LT were performed in 313 patients (09/88-12/92). Impact on long-term outcome was studied and a comparison to life expectancy of matched normal population was performed. A detailed analysis of 20-years follow-up concerning overweight (HBMI), hypertension (HTN), diabetes (HGL), hyperlipidemia (HLIP) and moderately or severely impaired renal function (MIRF, SIRF) is presented. Patient and graft survival at 1, 10, 20 years were 88.4%, 72.7%, 52.5% and 83.7%, 64.7% and 46.6%, respectively. Excluding 1-year mortality, survival in the elderly LT recipients was similar to normal population. Primary indication (p < 0.001), age (p < 0.001), gender (p = 0.017), impaired renal function at 6 months (p < 0.001) and retransplantation (p = 0.034) had significant impact on patient survival. Recurrent disease (21.3%), infection (20.6%) and de novo malignancy (19.9%) were the most common causes of death. Prevalence of HTN (57.3-85.2%, p < 0.001), MIRF (41.8-55.2%, p = 0.01) and HBMI (33.2-45%, p = 0.014) increased throughout follow-up, while prevalence of HLIP (78.0-47.6%, p < 0.001) declined. LT has conquered many barriers to achieve these outstanding long-term results. However, much work is needed to combat recurrent disease and side effects of immunosuppression (IS).

Measurement reproducibility of perfusion fraction and pseudodiffusion coefficient derived by intravoxel incoherent motion diffusion-weighted MR imaging in normal liver and metastases.

OBJECTIVE: To determine the measurement reproducibility of perfusion fraction f, pseudodiffusion coefficient D and diffusion coefficient D in colorectal liver metastases and normal liver. METHODS: Fourteen patients with known colorectal liver metastases were examined twice using respiratory-triggered echo-planar DW-MRI with eight b values (0 to 900 s/mm(2)) 1 h apart. Regions of interests were drawn around target metastasis and normal liver in each patient to derive ADC (all b values), ADC(high) (b values ≥ 100 s/mm(2)) and intravoxel incoherent motion (IVIM) parameters f, D and D by least squares data fitting. Short-term measurement reproducibility of median ADC, ADC(high), f, D and D values were derived from Bland-Altman analysis. RESULTS: The measurement reproducibility for ADC, ADC(high) and D was worst in colorectal liver metastases (-21 % to +25 %) compared with liver parenchyma (-6 % to +8 %). Poor measurement reproducibility was observed for the perfusion-sensitive parameters of f (-75 % to +241 %) and D (-89 % to +2,120 %) in metastases, and to a lesser extent the f (-24 % to +25 %) and D (-31 % to +59 %) of liver. CONCLUSIONS: Estimates of f and D derived from the widely used least squares IVIM fitting showed poor measurement reproducibility. Efforts should be made to improve the measurement reproducibility of perfusion-sensitive IVIM parameters.

A single infusion of intravenous lidocaine for primary headaches and trigeminal neuralgia: a retrospective analysis.

Introduction: Intravenous (IV) lidocaine has been used as a transitional treatment in headache and facial pain conditions, typically as an inpatient infusion over several days, which is costly and may increase the risk of adverse effects. Here we report on our experience using a single one-hour IV lidocaine infusion in an outpatient day-case setting for the management of refractory primary headache disorders with facial pain and trigeminal neuralgia. Methods: This is a retrospective, single-center analysis on patients with medically refractory headache with facial pain and trigeminal neuralgia who were treated with IV lidocaine between March 2018 and July 2022. Lidocaine 5 mg.kg-1 in 60 mL saline was administered over 1 h, followed by an observation period of 30 min. Patients were considered responders if they reported reduction in pain intensity and/or headache frequency of 50% or greater. Duration of response was defined as short-term (< 2 weeks), medium-term (2-4 weeks) and long-term (> 4 weeks). Results: Forty infusions were administered to 15 patients with trigeminal autonomic cephalalgias (n = 9), chronic migraine (n = 3) and trigeminal neuralgia (n = 3). Twelve patients were considered responders (80%), eight of whom were complete responders (100% pain freedom). The average duration of the treatment effect for each participant was 9.5 weeks (range 1-22 weeks). Six out of 15 patients reported mild and self-limiting side effects (40%). Conclusion: A single infusion of IV lidocaine might be an effective and safe transitional treatment in refractory headache conditions with facial pain and trigeminal neuralgia. The sustained effect of repeated treatment cycles in some patients may suggest a role as long-term preventive therapy in some patients.

OnabotulinumtoxinA in elderly patients with chronic migraine: insights from a real-life European multicenter study.

INTRODUCTION: Although migraine prevalence decreases with aging, some older patients still suffer from chronic migraine (CM). This study aimed to investigate the outcome of OnabotulinumtoxinA (OBT-A) as preventative therapy in elderly CM patients. METHODS: This is a post hoc analysis of real-life prospectively collected data at 16 European headache centers on CM patients treated with OBT-A over the first three treatment cycles (i.e., Cy1-3). We defined: OLD patients aged ≥ 65 years and nonOLD those < 65-year-old. The primary endpoint was the changes in monthly headache days (MHDs) from baseline to Cy 1-3 in OLD compared with nonOLD participants. The secondary endpoints were the responder rate (RR) ≥ 50%, conversion to episodic migraine (EM) and the changes in days with acute medication use (DAMs). RESULTS: In a cohort of 2831 CM patients, 235 were OLD (8.3%, 73.2% females, 69.6 years SD 4.7). MHDs decreased from baseline (24.8 SD 6.2) to Cy-1 (17.5 SD 9.1, p < 0.000001), from Cy-1 to Cy-2 (14.8 SD 9.2, p < 0.0001), and from Cy-2 to Cy-3 (11.9 SD 7.9, p = 0.001). DAMs progressively reduced from baseline (19.2 SD 9.8) to Cy-1 (11.9 SD 8.8, p < 0.00001), to Cy-2 (10.9 SD 8.6, p = 0.012), to Cy-3 (9.6 SD 7.4, p = 0.049). The 50%RR increased from 30.7% (Cy-1) to 34.5% (Cy-2), to 38.7% (Cy-3). The above outcome measures did not differ in OLD compared with nonOLD patients. CONCLUSION: In a population of elderly CM patients with a long history of migraine OBT-A provided a significant benefit, over the first three treatment cycles, as good as in non-old patients.

Complex coronary artery anatomy in a patient with prolapsing left atrial myxoma.

The case of an asymptomatic patient with prolapsing left atrial myxoma, in whom preoperative coronary angiography revealed a rare coronary artery anatomy in the absence of atherosclerotic obstructive disease, is presented. There was a type IV dual left anterior descending (LAD) artery with intraseptal course of the right aortic sinus-connected (long) LAD artery and an ectopic left circumflex artery originating from the right aortic sinus and having a retroaortic course. The patient underwent successful surgical excision of the mass which was confirmed by histology to be cardiac myxoma. This particular coronary artery anatomy has only been described once, and this is the first reported case of its combination with cardiac myxoma. This report highlights the importance of differentiating between the possible courses of such ectopic coronary arteries. The angiographic signs which enabled differentiation of the intraseptal course of the long LAD artery from the malignant interarterial course with which it is frequently confused are presented.

Isolated single coronary artery with dual right coronary artery distribution. A rare anatomical variation.

We present the case of a 76-year-old patient in whom coronary angiography, performed due to non-ST-segment elevation myocardial infarction, revealed an isolated single coronary (SCA) artery with dual right coronary artery (RCA) distribution. One RCA arose from the mid segment of the left anterior descending (LAD) artery and followed a prepulmonic course to the right, while the other RCA arose as the terminal extension of the left circumflex artery beyond the crux cordis. This is the second reported case of the combination of these two variants of SCA and the first such case in which the LAD-derived RCA originated as a single branch. Furthermore, this is the first report presenting a sinus node artery with origin from an ectopic LAD-connected RCA. The clinical implications of this rare coronary artery pattern are discussed.

Isolated right ventricular infarction during percutaneous coronary intervention.

Isolated right ventricular infarction (RVI) is an increasingly recognized cause of precordial ST-segment elevation (STE). A patient is described who developed STE in leads V1-V5 secondary to occlusion of the right ventricular branch during stent angioplasty to the right coronary artery. The pattern of precordial STE was thought to be suggestive of anteroseptal myocardial infarction because of progressive STE toward lead V3. Repeat angiography disclosed a patent left anterior descending artery. Subsequent scrutiny of the electrocardiogram (ECG) revealed that leads V2 and V3 were switched and ECG interpretation considering this technical error revealed STE in V2>V3, which favored RVI. Furthermore, the mean spatial ST vector was approximately +120° in the frontal plane producing ST-segment depression in lead I which argued against anteroseptal myocardial infarction and indicated right ventricular epicardial injury. This report highlights that analysis of the ECG using vector concepts is a useful adjunct to pattern recognition for the diagnosis of RVI.

Association of the PTPN22 R620W polymorphism with increased risk for SLE in the genetically homogeneous population of Crete.

Autoimmune diseases affect approximately 5% of the population, but much work remains to define the genetic risk factors and pathogenic mechanisms underlying these conditions. There is accumulating evidence that common genetic factors might predispose to multiple autoimmune disorders. Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are complex autoimmune disorders with multiple susceptibility genes. The functional R620W (C1858T) polymorphism of the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene, a member of the PTPs that negatively regulate T-cell activation, has been recently associated with susceptibility to various autoimmune diseases. The aim of this study was to assess whether the C1858T polymorphism of PTPN22 also confers increased risk for SLE and RA in the genetically homogeneous population of Crete. It was found that the minor T allele of the PTPN22 C1858T SNP was more common in SLE patients than in control individuals (odds ratio [OR] = 1.91, 95% confidence interval [CI] = 1.11 to 3.9, p = 0.017). No significant difference was observed in the frequency of this allele when RA patients were compared with controls (OR = 1.14, 95% CI = 0.65 to 1.9, p = 0.64). Although the PTPN22 1858 T allele is found at decreased frequency in Southern Europe, including Crete, an association was found between this allele and SLE in the population studied.