Sodium valproate in migraine without aura and medication overuse headache: A randomized controlled trial

Objective: To assess the efficacy, safety and tolerability of sodium valproate (800. mg/die) compared with placebo in medication-overuse headache patients with a history of migraine without aura. Methods: This is a multicenter, randomized, double-blind, placebo-controlled study enrolled medication-overuse headache patients for a 3-month treatment period with sodium valproate (800. mg/day) or placebo after a 6 day outpatient detoxification regimen, followed by a 3-month follow-up. Primary outcome was defined by the proportion of patients achieving ≥50% reduction in the number of days with headache per month (responders) from the baseline to the last 4 weeks of the 3-month treatment. Multivariate logistic regression models were used on the primary endpoint, adjusting for age, sex, disease duration, comorbidity and surgery. The last-observation-carried-forward method was used to adjust for missing values. Results: Nine sites enrolled 130 patients and, after a 6-day detoxification phase, randomized 88 eligible patients. The 3-month responder rate was higher in the sodium valproate (45.0%) than in the placebo arm (23.8%) with an absolute difference of about 20% (p=0.0431). Sodium valproate had safety and tolerability profiles comparable to placebo. Conclusions: The present study supports the efficacy and safety of sodium valproate in the treatment of medication overuse headache with history of migraine after detoxification

A multicenter phase II study of the combination of oxaliplatin, irinotecan and capecitabine in the first-line treatment of metastatic colorectal cancer

The triple drug combination consisting of irinotecan, oxaliplatin and 5-fluorouracil (FOLFOXIRI) has demonstrated higher activity and efficacy compared to the doublet FOLFIRI. 5-Fluorouracil could be substituted in FOLFOXIRI regimen by capecitabine, an oral fluoropyrimidine with similar efficacy. Recently, a dose-finding trial has demonstrated the feasibility of the combination of irinotecan, oxaliplatin and capecitabine (XELOXIRI) and established their recommended doses. The aim of this study was to evaluate the activity of XELOXIRI. A total of 36 patients with unresectable metastatic colorectal cancer received irinotecan 165 mg m−2 and oxaliplatin 85 mg m−2 on day 1 plus capecitabine 2000 mg m−2 per day orally in two doses from day 1 to day 7, every 2 weeks. Grade 3–4 toxicities were infrequent, expect for neutropenia and diarrhoea, which were each observed in 30% of patients. Two complete and twenty-two partial responses were obtained, corresponding to an overall response rate of 67% (95% CI 51.4–82%). After a median follow-up of 17.7 months, the median progression-free and overall survival were 10.1 and 17.9 months, respectively

A migraine variant with abdominal colic and Alice in wonderland syndrome: a case report and review

<p>Abstract</p> <p>Background</p> <p>Abdominal migraine is a commonly described migraine variant in children and young adults, but associations with Alice in Wonderland syndrome and lilliputian hallucinations are exceptional.</p> <p>Case presentation</p> <p>A 20 years-old male experienced frequent and prolonged attacks of abdominal colic associated with autonomic manifestations started at the age of ten. At the age of 17, he additionally described prolonged attacks (≥ 7 days) of distortions of shape, size or position of objects or subjects. He said "Quite suddenly, objects appear small and distant (teliopsia) or large and close (peliopsia). I feel as I am getting shorter and smaller "shrinking" and also the size of persons are not longer than my index finger (a lilliputian proportion). Sometimes I see the blind in the window or the television getting up and down, or my leg or arm is swinging. I may hear the voices of people quite loud and close or faint and far. Occasionally, I experience attacks of migrainous headache associated with eye redness, flashes of lights and a feeling of giddiness. I am always conscious to the intangible changes in myself and my environment". There is a strong family history of common migraine. Clinical examination, brain-MRI and EEG were normal. Transcranial magnetic stimulation and evoked potentials revealed enhanced cortical excitability in multiple brain regions. Treatment with valproate resulted in marked improvement of all clinical and neurophysiological abnormalities.</p> <p>Conclusions</p> <p>The association between the two migraine variants (abdominal migraine and Alice in Wonderland Syndrome) might have clinical, pathophysiological and management implications. I think this is the first description in the literature.</p

Proteomic analysis of urine in medication-overuse headache patients: possible relation with renal damages

Medication-overuse headache (MOH) is a chronic disorder associated with overuse of analgesic drugs, triptans, non-steroidal anti-inflammatory drugs (NSAIDs) or other acute headache compounds. Various epidemiologic investigations proved that different drug types could cause nephrotoxicity, particularly in chronic patients. The aim of the present work was to analyze, by a proteomic approach, the urinary protein profiles of MOH patients focusing on daily use of NSAIDs, mixtures and triptans that could reasonably be related to potential renal damage. We selected 43 MOH patients overusing triptans (n = 18), NSAIDs (n = 11), and mixtures (n = 14), for 2–30 years with a mean daily analgesic intake of 1.5 ± 0.9 doses, and a control group composed of 16 healthy volunteers. Urine proteins were analyzed by mono-dimensional gel electrophoresis and identified by mass spectrometry analysis. Comparing the proteomic profiles of patients and controls, we found a significantly different protein expression, especially in the NSAIDs group, in which seven proteins resulted over-secreted from kidney (OR = 49, 95% CI 2.53–948.67 vs. controls; OR = 11.6, 95% CI 0.92–147.57 vs. triptans and mixtures groups). Six of these proteins (uromodulin, α-1-microglobulin, zinc-α-2-glycoprotein, cystatin C, Ig-kappa-chain, and inter-α-trypsin heavy chain H4) were strongly correlated with various forms of kidney disorders. Otherwise, in mixtures and in triptans abusers, only three proteins were potentially associated to pathological conditions (OR = 4.2, 95% CI 0.33–53.12, vs. controls). In conclusion, this preliminary proteomic study allowed us to define the urinary protein pattern of MOH patients that is related to the abused drug. According with the obtained results, we believe that the risk of nephrotoxicity should be considered particularly in MOH patients who abuse of NSAIDs

Mental turmoil, suicide risk, illness perception, and temperament, and their impact on quality of life in chronic daily headache

To evaluate the relationship among quality of life, temperament, illness perception, and mental turmoil in patients affected by chronic daily headache with concomitant medication overuse headache. Participants were 116 consecutive adult outpatients admitted to the Department of General Medicine of the Sant’Andrea Hospital in Rome, between January 2007 and December 2007 with a diagnosis of chronic daily headache (illness duration >5 years). Patients were administered the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-autoquestionnaire version (TEMPS-A), the Beck Hopelessness Scale (BHS), the Hamilton Rating Scale for Depression (HAM-D), the Mini-International Neuropsychiatric Interview (MINI), the Revised Illness Perception Questionnaire (IPQ), the Suicide Score Scale (SSS), and the Quality of Life Index (QL-Index). Twenty-eight percent of the patients evidenced moderate to severe depression, and 35% evidenced severe hopelessness. Analyses also indicated that quality of life, temperament, illness perception, and psychological turmoil are associated. However, a hierarchical multivariate regression analysis with quality of life as dependent variable indicated that only a model with mental turmoil variables may fit data; further, only the MINI suicidal intent resulted associated with quality of life (standardized regression coefficient = −0.55; t = −3.06; P < 0.01). Suicide risk may play a central role in affecting the quality of life of patients with chronic headache. The investigation of the interplay of factors that precipitate suicide risk should include assessment of chronic headache and its effects on wellbeing

Chronic migraine classification: current knowledge and future perspectives

In the field of so-called chronic daily headache, it is not easy for migraine that worsens progressively until it becomes daily or almost daily to find a precise and universally recognized place within the current international headache classification systems. In line with the 2006 revision of the second edition of the International Classification of Headache Disorders (ICHD-2R), the current prevailing opinion is that this headache type should be named chronic migraine (CM) and be characterized by the presence of at least 15 days of headache per month for at least 3 consecutive months, with headache having the same clinical features of migraine without aura for at least 8 of those 15 days. Based on much evidence, though, a CM with the above characteristics appears to be a heterogeneous entity and the obvious risk is that its definition may be extended to include a variety of different clinical entities. A proposal is advanced to consider CM a subtype of migraine without aura that is characterized by a high frequency of attacks (10–20 days of headache per month for at least 3 months) and is distinct from transformed migraine (TM), which in turn should be included in the classification as a complication of migraine. Therefore, CM should be removed from its current coding position in the ICHD-2 and be replaced by TM, which has more restrictive diagnostic criteria (at least 20 days of headache per month for at least 1 year, with no more than 5 consecutive days free of symptoms; same clinical features of migraine without aura for at least 10 of those 20 days)

Migraine in women: the role of hormones and their impact on vascular diseases

Migraine is a predominantly female disorder. Menarche, menstruation, pregnancy, and menopause, and also the use of hormonal contraceptives and hormone replacement treatment may influence migraine occurrence. Migraine usually starts after menarche, occurs more frequently in the days just before or during menstruation, and ameliorates during pregnancy and menopause. Those variations are mediated by fluctuation of estrogen levels through their influence on cellular excitability or cerebral vasculature. Moreover, administration of exogenous hormones may cause worsening of migraine as may expose migrainous women to an increased risk of vascular disease. In fact, migraine with aura represents a risk factor for stroke, cardiac disease, and vascular mortality. Studies have shown that administration of combined oral contraceptives to migraineurs may further increase the risk for ischemic stroke. Consequently, in women suffering from migraine with aura caution should be deserved when prescribing combined oral contraceptives

The primary headaches: genetics, epigenetics and a behavioural genetic model

The primary headaches, migraine with (MA) and without aura (MO) and cluster headache, all carry a substantial genetic liability. Familial hemiplegic migraine (FHM), an autosomal dominant mendelian disorder classified as a subtype of MA, is due to mutations in genes encoding neural channel subunits. MA/MO are considered multifactorial genetic disorders, and FHM has been proposed as a model for migraine aetiology. However, a review of the genetic studies suggests that the FHM genes are not involved in the typical migraines and that FHM should be considered as a syndromic migraine rather than a subtype of MA. Adopting the concept of syndromic migraine could be useful in understanding migraine pathogenesis. We hypothesise that epigenetic mechanisms play an important role in headache pathogenesis. A behavioural model is proposed, whereby the primary headaches are construed as behaviours, not symptoms, evolutionarily conserved for their adaptive value and engendered out of a genetic repertoire by a network of pattern generators present in the brain and signalling homeostatic imbalance. This behavioural model could be incorporated into migraine genetic research

Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics?

<p>Abstract</p> <p>Background</p> <p>Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics.</p> <p>Discussion</p> <p>In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect.</p> <p>As an example the fixesd-dose combination of acetylsalicylic acid (ASA), paracetamol (acetaminophen) and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy.</p> <p>Summary</p> <p>Multitarget therapeutics like combined analgesics broaden the array of therapeutic options, enable the completeness of the therapeutic effect, and allow doctors (and, in self-medication with OTC medications, the patients themselves) to customize treatment to the patient's specific needs. There is substantial clinical evidence that such a multi-component therapy is more effective than mono-component therapies.</p