Effectiveness and safety of erenumab in chronic migraine: A Croatian real-world experience.

OBJECTIVE: To determine the real-world effectiveness and safety of erenumab after 6 months of treatment in chronic migraine patients with therapeutic resistance to multiple classes of prophylactic medication. METHODS: The patients were recruited from the Headache Outpatient Clinic of the University Hospital Centre Zagreb, Croatia between March 2019 and November 2019. All participants received erenumab 70 mg for 6 months. Interviews with participants were conducted at baseline and after the treatment period. The following parameters were analysed: reduction percentage of monthly migraine days, monthly migraine days (MMDs), monthly non-migraine headache days (MNDs), monthly headache days (MHDs), pain intensity measured by the visual-analogue scale (VAS), monthly acute migraine medication intake and reported side-effects. Additionally, we analysed the data for migraine with and without aura separately. RESULTS: There was a significant decrease in the mean value of headache frequency and pain intensity parameters after 6 months of treatment with erenumab. Out of the 54 participants included in the analysis, 70.37% had a ≥ 50% reduction in MMDs, while 40.74% had a ≥ 75% reduction. The mean values of MMDs and MHDs were reduced from 10.37 ± 0.38 to 4.59 ± 0.43 days (P < 0.001) and from 22.24 ± 0.70 to 9.74 ± 0.91 days (P < 0.001), respectively. Furthermore, the mean migraine VAS score decreased from 10.00 ± 0 to 6.69 ± 0.24 (P < 0.001). There was no significant difference in effectiveness between participants with migraine with and without aura. Nine participants reported side-effects. CONCLUSION: Our study indicates that erenumab is a safe and effective therapeutic option for chronic migraine patients.

Heterophile antibodies, false-positive troponin, and acute coronary syndrome: a case report indicating a pitfall in clinical practice.

BACKGROUND: Heterophile antibodies are one of the most common causes of false-positive troponin. CASE SUMMARY: We report a case of a 53-year-old woman with false-positive troponin elevation and a clinical presentation understood and treated as non-ST-elevation acute coronary syndrome. Because of chronic basal elevation of troponin (at a 'plateau' level) and chest pain, the patient underwent several invasive coronary angiograms until false-positive increase of troponin due to heterophile antibodies was suspected. Borderline stenosis of a left circumflex coronary artery found on first coronary angiogram was a coincidental finding and heterophile antibodies in the patient's serum were confirmed. DISCUSSION: This interesting case report aims to remind the clinicians about the possibility of false-positive troponin level due to laboratory analytical interference caused by heterophile antibodies. In this case, it is important to suspect false-positive troponin elevation, even when coronary artery disease is found. This rare and less mentioned and/or recognized cause of troponin elevation may lead to unnecessary invasive diagnostics and aggressive treatment of patients.

Idiopathic Trigeminal Neuralgia (ITN): Facts and Fiction.

In this paper the authors present neuroanatomical and neurophysiological arguments against the microvascular compression in the root entry zone of trigeminal nerve nerve as an ethiopathogenetic factor of ITN. Clinical experience has proven that compression of mixed sensorymotor nerve (peripheral or central one), cannot provoke paroxysmal neuralgic pain. The authors conclude that the well known fact that dental pulp has only pain sensory modality brings up the question what might be consequence of tooth extraction where neural fibers are broken in the innervation areas of maxillar and mandibular nerve. The answer could be only one. If exclusive algophoric deafferentation hypersensitivity after tooth extraction exceeds a certain threshold, patients will experience paroxysmal neuralgic pain. Broken neural fibers develop pathological ephaptic communication with other trigeminal sensory modalities through supraspinal central structures responsible for the transmision of dental pulp pain. This can explain trigger phenomena and latency between the touching of circumoral areas and onset of neuralgic paroxysm, which is a central epileptic phenomenon. In conclusion, the so-called idiopathic trigeminal neuralgia (ITN) is the expression of algophoric deafferentation hypersensitivity after tooth extraction.

Acupuncture as a Complementary Method of Traditional Psoriasis Treatment: Myth or Reality?

Dear Editor, the practitioners of traditional Chinese medicine described psoriasis some 2000 years ago (1). Psoriasis vulgaris is a common, chronic inflammatory skin disease whose worldwide prevalence ranges from 0.1-3% (2,3). Understanding the role of the immune system in psoriasis and the interplay between the innate and adaptive immune system has helped to manage this complex disease, which affects patients far beyond the skin changes themselves (2). In addition to the usual and widely accepted methods of treatment of psoriasis, including topical therapies, phototherapy, and conventional and biological systemic therapies, data can be found in the literature that suggest a favorable effect of acupuncture on the course of psoriasis (4,5). Despite that, this complementary method of traditional treatment of various diseases is not yet widely accepted worldwide. According to the World Health Organization (WHO), acupuncture has been an officially recognized method of treatment for more than 50 diseases from 1979 (5). At the Department of Neurology at the University Hospital Center Zagreb, acupuncture has been used since 2011 for the treatment of various types of headaches, trigeminal neuralgia, and spinal pain syndromes. We report the case of a patient with a known history of psoriasis who was treated for chronic migraines with acupuncture. The 49-year-old female patient was examined for headache of a pulsating character that she had had for 16 years. The headache was mainly located on the left side of head and accompanied by nausea, vomiting, and both photophobia and phonophobia, and there was a worsening of symptoms upon exertion. The headaches were occurring once a week with an average duration of 2-3 continuous days. The patient also had frequent mild headaches. Additionally, the patient was diagnosed with psoriasis at the age of 29 and was occasionally treated with phototherapy. Systemic therapy for psoriasis had not been given to the patient thus far. After the clinical evaluation and considering the medical history and clinical findings, the diagnosis of chronic migraine was established and prophylactic therapy with dual antidepressant was introduced. On follow-up examinations, a reduction in the frequency and intensity of migraine headaches was observed. After one year there was a progression of symptoms, and treatments with acupuncture were started. Stainless steel filiform needles of 25 mm in length were inserted perpendicularly into points on the head, arm, and legs and retained for 30 minutes. The treatment was administered once a day for 10 days with an interval of 2-3 days between treatments. The patient showed significant improvement for a period of 6 months after the acupuncture treatment, which is why the treatment with acupuncture was repeated. The patient stated that very soon after the beginning of each acupuncture treatment, she had noticed a significant improvement regarding psoriatic lesions as a "side effect". On the first day of acupuncture, extensive erythematosquamous plaques were noticed on the skin of the dorsum of the feet (Figure 1), palms, and elbows. It is important to emphasize that the patient did not use any specific topical antipsoriatic therapies during the acupuncture treatment, but only bland emollients. During the third week of treatment, a significant improvement was observed, or according to the patient, "she has not had such a good skin for a long time" (Figure 2). The improvement of the clinical status can be explained by overlapping acupuncture points used in the treatment of pain syndromes and psoriasis or to the holistic effect of acupuncture. In recent years, several high-quality evidence-based Western medicine guidelines have been developed for the treatment of psoriasis (6,7). In addition to that modern approach, several studies confirmed the effectiveness of acupuncture in the treatment of psoriasis. The recent review by Coyle et al. (4) indicates promising evidence of the efficacy of acupuncture for psoriasis treatment with an increasing number of people achieving clinical and statistical improvements. Furthermore, Wang et al. (8) have recently published the protocol for a systematic review which aims to assess the effectiveness and safety of acupuncture for patients with psoriasis. In acupuncture, hair-thin needles are inserted into the skin, releasing natural pain killers such as adenosine, endorphins, and serotonin into the body. It is known that patients with psoriatic arthritis can benefit from the treatment. Some patients may be concerned that acupuncture needles could worsen a skin flare-up but an acupuncturist uses sterile needles to prevent any risk to flaring skin. The advantage of acupuncture is that it is a very safe alternative medicine treatment and is not likely to interfere with any existing psoriasis treatment. It is important to note that acupuncture is a 5000-year-old alternative medicine treatment and that it has been officially recognized by the WHO for more than three decades (5). After achieving clinical improvement and regression of psoriatic plaques during the acupuncture for headache, the authors reviewed the literature and found reports about possible benefits of treating psoriasis with acupuncture. Therefore, the purpose of this letter and case study is to raise awareness and inform dermatologists about the different and until now under-explored possibilities of acupuncture in treating psoriasis.

Epidemiology of Primary Headaches Among 1,876 Adolescents: A Cross-Sectional Survey.

BACKGROUND: The main goal of our research was to perform an epidemiological study of migraine and tension-type headache (TTH) among high school students in the Republic of Croatia. METHODS: The authors surveyed 1,876 students attending high schools in the Republic of Croatia using a self-administered 36-item questionnaire. RESULTS: Among 1,876 students who completed the questionnaire, prevalence of migraine was 12.8% (17% in women and 8.1% in men) and prevalence of TTH was 38.3% (40.6% in women and 35.7% in men). Prevalence of migraine with TTH was 2.9% (3.1% in women and 2.7% in men). The authors found a significantly greater prevalence of migraine in female than in male students (OR = 2.3), as in TTH (OR = 1.23). Compared with students with TTH, migraine sufferers were more inclined to take medications (OR = 3.29) and use health care (OR = 8.12) and were more likely to smoke (OR = 2.34). CONCLUSION: The prevalence of primary headaches in Croatia is similar to that in other countries of the world. TTH is the most common primary headache, occurring later in relation to migraine, and both types are more common in females. Teenagers who suffer from migraines are more likely to smoke in comparison to TTH. Although migraine patients visit the doctor and take medications more frequently than those with TTH, both headaches are being underdiagnosed and undertreated.

Changes in Heart Rate Variability after Coronary Artery Bypass Grafting and Clinical Importance of These Findings.

Heart rate variability is a physiological feature indicating the influence of the autonomic nervous system on the heart rate. Association of the reduced heart rate variability due to myocardial infarction and the increased postinfarction mortality was first described more than thirty years ago. Many studies have unequivocally demonstrated that coronary artery bypass grafting surgery generally leads to significant reduction in heart rate variability, which is even more pronounced than after myocardial infarction. Pathophysiologically, however, the mechanisms of heart rate variability reduction associated with acute myocardial infarction and coronary artery bypass grafting are different. Generally, heart rate variability gradually recovers to the preoperative values within six months of the procedure. Unlike the reduced heart rate variability in patients having sustained myocardial infarction, a finding of reduced heart rate variability after coronary artery bypass surgery is not considered relevant in predicting mortality. Current knowledge about changes in heart rate variability in coronary patients and clinical relevance of such a finding in patients undergoing coronary artery bypass grafting are presented.

Left ventricular diastolic function in diabetes mellitus type 2 patients: correlation with heart rate and its variability.

AIMS: To assess the prevalence of left ventricular diastolic dysfunction in a population of patients with type 2 diabetes mellitus; to determine correlation of diastolic dysfunction with heart rate and its variability. METHODS: The study included 202 patients with type 2 diabetes mellitus. Echocardiography was performed with special reference to diastolic function, and heart rate variability was analysed using standard deviation of normal RR intervals, root mean square of successive differences and percentage of successive R-R intervals greater than 50 ms (pNN 50 %) in a 24-h electrocardiogram recording. RESULTS: Diastolic dysfunction is present in 79 % of type 2 diabetes mellitus patients: grade 1 in 52 %, grade 2 in 26 % and grade 3 in 1 % of patients. The subjects with grade 1 diastolic dysfunction had a statistically significantly higher heart rate variability compared with those with grade 2 diastolic dysfunction (LSD, post hoc test, p = 0.001). In the group with diastolic dysfunction, grade 2 reduced heart rate variability was recorded in 83 % of patients (37 and 7 % for grade 1 and normal diastolic function). An increase in the severity of diastolic dysfunction was associated with decreased heart rate variability and increased heart rate. CONCLUSION: Progression of diastolic dysfunction is associated with a significantly greater prevalence of reduced heart rate variability, which is accompanied by increased heart rate.

Outcome of patients with normal and decreased heart rate variability after coronary artery bypass grafting surgery.

BACKGROUND: Previous studies have shown that after coronary artery bypass grafting (CABG), heart rate variability (HRV) becomes decreased, even more significantly than in patients after myocardial infarction (MI). According to some reports, unlike in patients after MI, decreased postoperative HRV does not increase mortality in CABG patients. The aim of this study was to compare differences in mortality rate in CABG patients with normal vs. decreased postoperative HRV. METHODS: This study included 206 consecutive patients who underwent CABG. During stationary rehabilitation, 24-hours Holter ECG was performed on all the patients, and HRV was analyzed from its recordings. After leaving cardiac rehabilitation, all patients were contacted in writing to provide data on their health in the follow-up period. In the analysis of survival rate depending on HRV findings log-rank analysis and Kaplan-Meier method were used. RESULTS: Seventy four CABG patients (36%) had SDNN <93ms while 132 patients (64%) had normal overall HRV (SDNN≥93ms). The average time of follow-up period was 3.0±1.8years. In the follow up period 16 (7.8%) adverse coronary events were recorded. Out of the 16 CABG patients, 13 patients had decreased HRV and 3 had normal HRV (p=0.001). CONCLUSIONS: Contrary to previous reports, results of this study show that the CABG patients with postoperative decreased HRV have a higher mortality rate than patients with normal HRV.

Parkinson's disease--challenges in new drug development.

Idiopathic Parkinson's disease (IPD) is the second most common neurodegenerative disorder after Alzheimer's disease. Treatment aims in IPD include the provision of symptomatic relief reduction of functional disability, halting or slowing of the neurodegenerative process, and the prevention of long-term complications by proper initiation of therapy. At present, pharmacotherapeutic strategies allow the amelioration of motor symptoms of IPD only, whereas non-motor manifestations are not helped by dopamine replacement strategies. In addition, levodopa-induced fluctuation and dyskinesia are still challenging, particularly in long-term treatment. Despite advances in pharmacotherapy that have improved quality of life for these patients, the mortality rate remains largely unchanged. Sustained interest in IPD will hopefully allow increased funding of research to develop new and better treatments.

Heart rate variability differences in post-myocardial infarction patients based on initial treatment during acute phase of disease.

The aim of study was to asses the heart rate variability (HRV) differences in 128 post-myocardial infarction (MI) patients based on initial treatment during acute phase of disease. The patients were divided into groups: group 1 patients who underwent primary PCI, group 2 patients who received fibrinolysis and group 3 patients who were treated conservatively. In comparison with groups 2 and 3, group 1 patients had all HRV analyzed parameters higher except for LF/HF ratio. The results of study suggest that patients who were treated by primary PCI had better preserved autonomic cardiac function compared with patients who received fibrinolysis or those who were treated conservatively in the acute phase of MI.

Characteristics of heart rate variability in war veterans with post-traumatic stress disorder after myocardial infarction.

OBJECTIVE: The goal of the study was to evaluate differences in heart rate variability (HRV) among post-myocardial infarction (MI) patients, depending on their participation in the Croatian war and on established diagnoses of post-traumatic stress disorder (PTSD). METHODS: The study included 34 male war veterans with diagnosed PTSD who had suffered a first MI and 34 age-matched post-MI patients without PTSD. Cardiac autonomic balance was evaluated through HRV analysis. RESULTS: There were no differences in the mean R-R interval or overall HRV between the analyzed groups. Post-MI patients with PTSD had lower values for the square root of the mean of squared successive differences in R-R intervals (p = 0.02), the percentage of R-R intervals that were > or =50 milliseconds different from the previous interval (p = 0.03), and the high-frequency component (p = 0.03) but had higher values for the low-frequency component (p = 0.01) and the low-frequency/high-frequency ratio (p = 0.02), compared with post-MI patients without PTSD. CONCLUSION: Post-MI patients with PTSD have higher sympathetic and lower parasympathetic heart rate modulation activity, compared with patients with MI and no PTSD.

Progressive impairment of autonomic control of heart rate in patients with multiple sclerosis.

BACKGROUND: Data regarding the autonomic control of heart rate in multiple sclerosis (MS) patients depending on the disease duration are lacking in the literature. The goal of this study was to evaluate differences in heart rate variability (HRV) in patients with MS according to the duration of the disease. METHODS: The study included 39 patients (23 female and 16 male; median age 42 years, range 34-53 years) with relapsing-remitting MS (RRMS) in stable phase and 39 age- and sex-matched healthy controls. RRMS patients were divided into two groups: group 1 with 21 patients within 5 years and group 2 with 18 patients with >5 years from the diagnosis of MS. HRV analysis was done with 24-h Holter ECG. RESULTS: Patients with RRMS had a significantly lower overall HRV than controls: SDNN 91+/-18 msec vs. 135+/-24 msec, p<0.001. RRMS patients with lower duration of disease (Group 1) had all higher HRV parameters except LF/HF ratio compared with RRMS patients with >5 years from the diagnosis of MS (Group 2): SDNN 94+/-24 vs. 88+/-21 msec, p=0.008; TP 2028+/-1326 vs. 1683+/-1017 ms2, p=0.006. CONCLUSIONS: Results of the study suggested that the autonomic control of heart rate depends on the disease duration in RRMS patients. Longer disease duration led to progressive impairment of cardiac autonomic balance in MS patients.

[Functional capacity in patients after myocardial infarction dependent on treatment strategy in acute phase of disease]. / Funkcionalni kapacitet bolesnika s preboljelim infarktom miokarda ovisno o nacinu lijecenja u akutnoj fazi bolesti.

BACKGROUND AND AIM: Recently published studies suggest that percutaneous coronary inetrvention (PCI) is superior to fibrinolysis in terms of early and late mortality in patients with acute myocardial infarction (MI) with ST-elevation. The aim of this study was to evaluate the influence of treatment strategy in the acute phase of MI on postinfarction functional capacity. PATIENTS AND METHODS: This prospective study included 128 consecutive patients with MI, with ST-elevation over 12 weeks from the disease onset. There were 92 (72%) male and 36 (28%) female patients, mean age 59 +/- 10 years. Inclusion criteria were age under 70, first MI with ST-elevation, and sinus rhythm. Exclusion criteria were previous MI, non ST-elevation MI, acute heart failure, atrial fibrillation, unstable angina pectoris, re-IM or necessity for coronarography and PCI during rehabilitation, and other acute disease. Patients were divided into three groups according to treatment modality: group 1, 38 (30%) patients treated with primary PCI; group 2, 46 (36%) patients treated with fibrinolysis; and group 3, 44 (34%) conservatively treated patients. There were no significant between-group differences according to age, sex, risk factors for coronary artery disease, infarct site, and frequency of complications in the acute phase of MI. The functional capacity of patients was evaluated by symptom-limited exercise test. Echocardiographic examinations were also done in each patient. Statistical analysis was performed by using the commercial software package, Microsoft SPSS for Windows, Version 8.0. Results were expressed as a mean standard deviation. Differences between the groups were tested by analysis of variance (ANOVA) and post hoc Tuckey test. The value of p < 0.05 was considered statistically significant. RESULTS: At the end of rehabilitation, the mean values of exercise capacity in groups 1, 2 and 3 were 6.1 +/- 1.3, 5.5 +/- 1.2, and 4.8 +/- 1.3 METs, respectively (group 1 vs. 2, p = 0.03; group 1 vs. 3, p < 0.001; group 2 vs. 3, p = 0.01). The mean values of ejection fraction in groups 1, 2 and 3 were 56 +/- 10, 53 +/- 9 and 47 +/- 11, respectively (group 1 vs. 2, p = 0.03; group 1 vs. 3, p < 0.001: group 2 vs. 3, p = 0.009). Four (3%) patients were excluded from the study because of complications during rehabilitation treatment. CONCLUSION: Postinfarction functional capacity in patients with MI depends on treatment strategy in the acute phase of disease. Patients who underwent PCI in the acute phase of MI had a higher functional capacity and better preserved systolic function of the left ventricle in comparison with patients who received fibrinolysis or those who were treated conservatively.

Association of refractory complex partial seizures with a polymorphism of ApoE genotype.

Apolipoprotein E (ApoE) is a constituent of many types of lipoproteins that play a role in metabolism of cholesterol and lipids in the body as well as in the brain. ApoE is synthesised in astrocytes and microglia and enter to neurons through LDL, LRP and VLDL receptors. Recently it was shown that ApoE is also produced in neurons. ApoE has a role in modulating learning and memory, structural plasticity, mobilization of cholesterol in repair, growth and maintenance of myelin and neuronal membranes during development and aging, and cell death after ischemic, convulsive, or other type of brain injury. The aim of this research was to investigate the possible association of ApoE gene polymorphism with the development of resistance to pharmacological therapy in patients with partial complex seizures with or without secondary generalization. In this prospective matched-pair controlled study, 60 patients with cryptogenic epilepsy with complex partial seizures, with or without secondary generalization, who have been suffering for five or more years, were studied. The first group comprised 30 patients refractory to the current therapy, while the second group consisted of patients with well-controlled seizures. The refractory and non-refractory groups of patients differed significantly in their phenotypes. Phenotype E3/4 was six times more frequent in refractory group than among non-refractory group. The lack of response was shown to be significantly associated with the presence of epsilon4 allele. This study provided evidence that the presence of epsilon4 allele is more often associated with a lack of response to current antiepileptic drugs as compared to epsilon2 and epsilon3 alleles.