Cognitive, behavioral, and psychological phenotypes in small fiber neuropathy: A case-control study.

OBJECTIVE: Small fiber neuropathy (SFN) is a well-defined chronic painful condition causing severe individual and societal burden. While mood disorders have been described, cognitive and behavioral profiles of SFN patients has not been investigated. METHODS: Thirty-four painful SFN patients underwent comprehensive cognitive, behavioral, psychological, quality of life (QoL), and personality assessment using validated questionnaires. As control samples, we enrolled 36 patients with painful peripheral neuropathy (PPN) of mixed etiology and 30 healthy controls (HC). Clinical measures of neuropathic pain, duration, frequency, and intensity of pain at the time of assessment were recorded. Between-group and correlation analyses were performed and corrected for multiple comparisons. RESULTS: No differences in clinical measures were found between SFN and PPN, and all groups had similar cognitive profiles. SFN patients showed higher levels of anxiety and alexithymia (p < .005) compared to PPN and HC, considering also pain intensity. Maladaptive coping strategies characterized both patient groups, but only SFN revealed higher levels of acceptance of pain (p < .05). Pain intensity and neuropathic symptoms were associated with mood, low QoL and catastrophism (p < .001), particularly, the higher the perceived pain intensity, the higher the use of maladaptive coping strategies (p < .001). The personality assessment revealed significant feelings of worthlessness and somatization traits both in SFN and PPN (p < .002 vs HC). DISCUSSIONS: our results suggest that SFN patients had a normal-like cognitive profile, while their behavioral profile is characterized by mood disorders, alexithymia, maladaptive coping strategies, and poor QoL, as other chronic pain conditions, possibly related to pain intensity. Personality assessment suggests that somatization and feelings of worthlessness, which may worsen the neuropsychological profile, deserve clinical attention when considering patients' therapeutic approaches. At the same time, the high level of acceptance of pain is promising for therapeutic approaches based on psychological support.

Prognostic impact of pretreatment cell-free DNA concentration in newly diagnosed peripheral T-cell lymphomas.

Peripheral T-cell lymphomas (PTCLs) have a poor prognosis and, to date, there are no reliable predictive biomarkers of response. In this work we explored the prognostic impact of cell-free DNA (cfDNA) concentration in 75 newly diagnosed patients enrolled in a prospective multicenter study. Pre-treatment cfDNA was strongly associated with clinical risk factors and was identified as a superior predictor for shorter progression-free survival in multivariable analysis, outweighing canonical risk parameters. Furthermore, we identified a cfDNA value above which survival worsens. In conclusion, pre-treatment cfDNA concentration represents an easily usable predictive biomarker that is highly associated with survival of PTCL patients.

Inguinal hernia repair in day surgery: the role of MAC (Monitored Anesthesia Care) with remifentanil.

BACKGROUND: The extension of indications for procedures in a Day Surgery (DS) setting has led to changes in the anesthetic and surgical treatment of Inguinal Hernias (IH). According to the recommendations of the European Hernia Society, the treatment of IH in DS units should be performed under Monitored Anesthesia Care (MAC). PATIENTS AND METHODS: 960 patients underwent IH repairs over a period of 24 months. The patients were randomly divided into two groups: R (remifentanil) and F (fentanyl); the group F was considered as a control group. The exclusion criteria in both group were: morbid obesity (BMI>40 or BMI>35 in association with high blood pressure or diabetes); coagulopathy; OSAS (obstructive sleep apnea syndrome) with AHI >10; cardiovascular, respiratory, renal, hepatic or metabolic disease; history of substances abuse; GERD-related esophagitis (gastro-esophageal reflux disease); chronic analgesic use; allergy to local anesthetic and ASA>III. Patients reported their level of pain on a verbal numeric scale (VNS), with scores ranging from 0 to 10. For each patient systolic and diastolic blood pressure (SBP and DBP), mean arterial pressure (MAP), heart rate (HR) and peripheral oxygen saturation (SpO2) were recorded. The results are presented as the mean value ± standard deviations; statistical analysis was performed using Student's t-test. RESULTS: Amongst the 960 procedures, complications or side effects related to the anesthetic techniques didn't occur; no procedure-related complications requiring mechanical ventilation support were reported. Our research focused on evaluating remifentanil effectiveness in pain control and its impact on hemodynamic stability and respiratory function. There was a significant difference between the two groups with regard to the VNS. CONCLUSIONS: Remifentanil, is an excellent drug for pain control during intra-operative procedures, that allows an optimal hemodynamic stability for IH repairs in a DS setting, due to its pharmacokinetic and pharmacodynamic properties and few adverse effects.

Approaches to treatments of chronic migraine associated with medication overuse: a comparison between different intensity regimens.

Treatment of chronic migraine with medication overuse requires withdrawal from acute medications. However, guidelines and clear indications for different intensity regimens, i.e., day hospital (DH) vs. inpatient treatment, are not available. Patients completed disability, quality of life (QoL) and depression questionnaires; headaches frequency and overused medications category were collected. Mann-Whitney U test and Chi square were used to assess differences between inpatients and DH patients; Bonferroni correction was applied. 194 patients aged 43.9 ± 12 (160 females) were enrolled (100 from DH, 94 inpatients). Inpatients were older, less educated and with lower employment rates. Inpatients had higher MIDAS scores (P = 0.003) and headache frequency (P = 0.002). They had lower QoL for restrictive (P = 0.002) and preventive components; no difference was found for disability, mood state and QoL emotional component. Patients treated during hospitalization had higher disease severity and lower quality of life, but similar disability and mood state than those treated in DH.

Onabotulinum toxin A (Botox) for chronic migraine treatment: an Italian experience.

Chronic migraine is a common and debilitating headache syndrome. Botulinum neurotoxin, a potent toxin produced by the anaerobic bacterium clostridium botulinum, used largely for treatment of disorders associated with increased muscle tone and hyperhidrosis, is used for patients suffering from chronic migraine. In this study, a group of patients suffering from chronic migraine with medication overuse was treated with onabotulinum toxin A (Botox) to verify its efficacy for chronic migraine. The results confirmed the efficacy of onabotulinum toxin A (Botox) when used at the dosage of 155 UI according to the PREEMPT protocol. Although these results are preliminary, they led to intense efforts to evaluate the analgesic properties of onabotulinum toxin A (Botox) and to assess its use in clinical practice, in particular in migraine field.

Evaluation of immune parameters in chronic migraine with medication overuse.

It has been postulated that chronic pain and chronic migraine in particular, can be connected to immunologic disturbances. Moreover the psychiatric comorbidity is often responsible of migraine chronification, but also of developing of particular immune function alterations. The role of the immune system in migraine precipitation is still under debate also if speculations about the evidence of infections in migraine patients has been performed, but not always corroborated by clinical and scientific explanations. In this report we present an evaluation of specific immune parameters in patients suffering from different forms of migraine respect to controls in order to determine possible alterations in immune function: speculations about the evidenced abnormalities are attempted.

Disability and quality of life in headache: where we are now and where we are heading.

Headache disorders determine relevant personal and societal burden, and thus the use of patient-reported outcome measures (PROMs) investigating the level of disability and health-related quality of life (HRQoL) have been increasingly used in headache research. The aim of this review was to address the status of research on disability and HRQoL, by addressing results from recently published clinical trials as well as in longitudinal observational studies on headache patients. PubMed has been searched for papers in which measures of HRQoL and/or disability were used as primary or secondary outcome on adult subjects with primary headache, and published in 2010-2012. Among the 70 records retrieved, 12 papers were selected for narrative synthesis. They included data on 2,621 patients with episodic migraine with and without aura, chronic daily headache, and/or chronic migraine with and without medication overuse. The selected trials investigated the efficacy of different pharmacological prophylaxis, of some surgical approaches, of education programmes and osteopathic manipulative treatment; two studies reported longitudinal observations of patients currently under treatment. Overall, the results of our review showed that headache frequency as well as HRQoL and disability were positively impacted by treatment interventions; positive outcomes were less evident in two studies, and similar results were found in the two observational studies. Our findings confirmed that the most commonly used PROMs, including disease-specific tools to assess disability and HRQoL and SF-36, are sensitive to the beneficial effects occurring over time in functioning and quality of life domains in headache patients. They also suggest that the personal and societal costs of headache disorders are likely to be reduced when headache patients receive appropriate treatments and when continuity of care is offered. In terms of future directions, we note that the systematic use of appropriate PROMs should be encouraged both in the clinical practice and in the research field, as they offer a valid option to assess the global effect of treatments on patient-perceived sense of well-being and quality of performance.

Psychiatric screening for migraine patients.

Psychiatric disorders in migraine patients have a higher prevalence than general population. The presence of psychiatric comorbidities may influence the complexity of the migraine pictures and be related to medication overuse. Severely impaired chronic migraineurs presenting with medication overuse are a challenge for headache clinics. Psychiatric comorbities, such as dependency-like behaviors, anxiety and mood symptoms, might account for headache-related disability and recurrent relapses into medication overuse after a successful detoxification. Within a sample of 63 chronic migraineurs with medication overuse and severe disability, we investigated to which extent clinical severity, affective states and attitudes about medication impact the overall functioning at time of detoxification. To unravel whether some of these factors could predict their long-term outcome, we followed and retest them 1 year after withdrawal. We hypothesized that the detoxification would have led to a partial improvement and not modified the attitudes toward medication and dependence. Detoxification improves most of the clinical and affective measures, but does not free from significant levels of pain intensity and headache-related disability. The partial benefit from detoxification, the severity bias and the maladaptive cognitive profile led us to believe that subgroups of chronic-relapsing migraineurs deserve a multidisciplinary approach that addresses not only the reduction of clinical severity but also specific cognitive and behavioral impairments.

A 14-month study of change in disability and mood state in patients with chronic migraine associated to medication overuse.

This paper aims to evaluate changes in disease severity, disability and mood state in patients with chronic migraine associated to medication overuse (CM-MO). MIDAS was used for assessing disease activity, WHO-DAS-2 for disability, DBI-2 for mood state. ANOVA was used to test change over time; t-test to assess follow-up differences in WHO-DAS-2 and BDI-2 between patients with MIDAS ≤20 and ≥21. Change in MIDAS, WHO-DAS-2 and BDI-2 scores were computed: Pearson's index was used to assess correlation between them; linear regression to assess change in WHO-DAS-2, using MIDAS and BDI-2 change as predictors. Mean MIDAS decreased significantly (from 101.9 to 52.0). In 26.1 % of the sample, MIDAS fell below 21 at follow-up: these patients had lower WHO-DAS-2 score. WHO-DAS-2 change was little correlated to MIDAS change and strongly correlated to changes in BDI-2 scores. 57.1 % of WHO-DAS-2 change variance is explained by change in BDI-2 and MIDAS scores. There was a clear clinical improvement 14 months after detoxification, and a modest reduction in disability which is explained by reduced disease activity and improved mood state. An appropriate treatment of CM-MO, based on detoxification and prophylaxis, is likely to reduce disease burden: recognition and treatment of mood problems may be a key factor to reduce disability.

Day-hospital withdrawal for chronic migraine with medication overuse: results at 3 years follow-up.

Patients with chronic headache and medication overuse are particularly difficult to treat, with no one approach being universally accepted. Some type of withdrawal program, however, is typically implemented before beginning a pharmacological prophylaxis treatment. Different withdrawal modalities have been performed for managing these patients: at first step, in-patient withdrawal has been confirmed effective in preceding clinical experiences. In recent years, new modalities for withdrawal have been developed as day-hospital setting. Purpose of this study was to determine the clinical course of a sample of chronic migraine patients with medication overuse 3 years after day-hospital withdrawal. A group of 202 patients were treated. Patients were suffering from chronic migraine with medication overuse according with IHS criteria. All patients were submitted to a day-hospital withdrawal and then they were followed with meetings every 3 months until the first year and then every 6 months until the last follow-up 3 years after withdrawal. Eighty patients achieved the last follow-up meeting 3 years after withdrawal. Patients clinically improved, significantly, both for days of headache per month and consumption of medications per month. From these results, the day-hospital setting for withdrawal, followed by periodic clinical meetings, seems to be effective for this category of patients to improve significantly at long-term headache frequency and analgesics intake.

Decision-making deficit in chronic migraine patients with medication overuse.

Patients with chronic migraine developing medication-overuse headache (MOH) show dependency-like behaviors such as loss of control over analgesics despite adverse consequences on headaches, high rates of relapse after withdrawal from symptomatic medications, and compromised social functioning. Neuroimaging research suggests a common pathophysiology between substance-use disorders and MOH, which involves functional alterations in fronto-striatal networks, particularly in the orbitofrontal region of prefrontal cortex. These findings could explain the impaired decision-making observed in substance-use disorders. We hypothesize that MOH could share fronto-striatal circuit dysfunction and relative decision-making deficit with addiction. We further examine whether this deficit is a persistent cognitive trait or a reversible consequence of medication overuse. This study shows a dataset of 50 patients with MOH before the detoxification. All patients underwent a complete neurological and psychiatric examination. Psychiatric examination consisted of a clinical interview, Structured Clinical Interview for DSM-IV TR Axis II Personality Disorders, Anxiety and Depression Hamilton Scales, Severity of Dependence Scale. The neurological examination included the migraine disability assessment questionnaire. Neuropsychological assessment of fronto-striatal circuits was investigated using the Iowa gambling task (IGT). Twenty patients monitored for any relapse into medication overuse had 12 months of follow-up. Our sample, characterized by high rates of disability and dependency-like behaviors, exhibited a deficit in IGT performance, indicating an overall impairment in decision-making. All the 20 patients showed neurological and psychiatric improvement at 12-month follow-up, notwithstanding the overuse relapse, but a persistent IGT deficit was found. To our knowledge this is the first study that assesses this cognitive function in patients with MOH. Medication-overuse headache seems to share a persistent decision-making deficit with substance abuse that confirms the orbitofrontal cortex hypometabolism described in literature from a neuropsychological perspective. Looking at these shared neurocognitive features, our results suggest that MOH could belong to the addiction spectrum. Fronto-striatal dysfunction could be a premorbid psychobiological condition of vulnerability explaining the clinical onset of medication overuse and recurrent relapses. We propose that IGT could be used to identify chronic migraine patients with higher risk for medication overuse and relapse.

Disability and mood state in patients with episodic and chronic migraine associated to medication overuse.

This study aims to compare disability and mood state in patients with episodic (EM) and chronic migraine associated to medication overuse (CM-MO), and to assess the relationships between the two outcomes. Patients, matched for age and gender, were administered the MIDAS, the WHO-DAS-2 and BDI-2. Difference between EM and CM-MO was assessed with the Kolmogorov-Smirnov Test; difference in distribution of patients with severe disability and low mood was tested with contingency coefficient; the correlation between MIDAS, WHO-DAS-2 and BDI-2 was tested with Spearman's index. Seventy patients were enrolled: CM-MO patients reported higher BDI-2 scores and higher MIDAS and WHO-DAS-2 scores, and were more likely to have severe disability and low mood state than those with EM; BDI-2 scores were correlated with disability scores, particularly with WHO-DAS-2. The study shows that disability and mood state are negatively impacted by the presence of more frequent headaches and by the overuse of acute medications.

Disability in chronic daily headache: state of the art and future directions.

Aim of this literature review is to summarize the most relevant research findings on disability in subjects with chronic daily headache (CDH) and chronic migraine (CM) measured with the MIDAS and the HIT-6, and to address issues for further research in the field. Research strategy aimed to find papers published after 2001 that focused on disability in patients with CDH, CM and transformed migraine. Both, general population surveys or clinical series were included if they reported total scores, or distribution of the different disability levels, derived from the MIDAS and/or from the HIT-6. Fifteen papers were selected. Studies demonstrated that these subjects report a remarkable impact on functioning, with high disability scores, and reduced ability in work and non-work activities. Modern definitions of disability conceptualize it as the result of the interaction between a health condition and environmental factors. Research strategies should therefore recognize that disability may represent a global evaluation which should be added to more specific endpoints, using instruments that measure disability in a multi-dimensional way, such as the WHO-DAS II.

Restless legs syndrome is not associated with migraine with aura: a clinical study.

Based on recent data about the association between restless legs syndrome (RLS) and migraine, we performed an observational study on the occurrence of RLS in patients affected by "pure" migraine with aura (pMA). We recruited 63 patients (33 females and 30 males) affected by MA without other types of primary headache among all patients referred in five Italian headache centers in a 1-year period. The prevalence of RLS in pMA patients (9.5%) is similar to that observed in Italian headache-free subjects (8.3%). No significant differences were found between pMA patients with and without RLS about clinical features of MA attacks and systemic and psychiatric diseases were investigated. Moreover, no association appeared between RLS and familial cases of MA. Differently from migraine without aura, our data do not confirm the existence of an association between RLS and MA, not even when a genetic factor is involved.

Evolution of headache in a population of young Italian headache sufferers: a brief report.

Headache is a common symptom in children and adolescence. In this retrospective analysis, we interviewed a population of young patients who were arrived to our observation 10 years before, in order to: (1) determine if the first diagnosis was still adequate and (2) which percentage of these young patients developed chronic forms (more than 15 days/month) from episodic forms. One hundred and seventy-seven patients suffering from different forms of headache were contacted and interviewed. The original diagnosis was confirmed in all the population of patients and the percentage of chronic forms developed from episodic forms was not significant. From this retrospective study, it does not seem the evolution of episodic forms in young age is necessarily a chronic form in adult as this depends from other behavioural or biological or environmental factors.

Disability in chronic migraine with medication overuse: treatment effects through 5 years.

Chronic migraine accompanied by medication overuse is particularly difficult to treat. The number of treatment investigations is limited, few have included follow-up beyond 6 months and almost none has examined whether treatment leads to concurrent improvements in disability and functional impairment. This open-label study addresses these limitations. We have been prospectively following an initial cohort of 84 chronic migraine patients with medication overuse, who at the time of this evaluation had been reduced to 58, for an extended period to assess longer-term maintenance of effects, using measurement procedures identical to those in the original investigation. Thus, the specific aim was to determine the clinical status, with respect to pain indices and disability level, of chronic migraine patients with medication overuse who were treated and followed prospectively for 5 years. All patients completed a brief inpatient treatment programme, in which they were withdrawn from their offending medications and subsequently placed on more appropriate preventive antimigraine medications. Both end-point, wherein missing data points were estimated, and continuer analyses, wherein data analysis was limited to the 58 individuals with complete datasets, revealed significant improvement on all measures studied-headache days per month, analgesic consumption and Migraine Disability Assessment (MIDAS) total score. The percentage reduction from baseline to 5 years for the MIDAS total score was 76.0%, while the percentage of individuals revealing improvements of clinically significant magnitude (≥ 50%) on the MIDAS was 91.9%. MIDAS total scores were lower at 5 years than at some of the intervening follow-up intervals. Comparisons of those who completed the 5-year follow-up (n = 58) with those who did not revealed no differences at baseline. This finding, coupled with the nearly identical results for the end-point and continuers analyses, suggests that attrition did not have a bearing on outcome. None of the patients completing the 5-year follow-up had relapsed since the prior 3-year follow-up assessment. High levels of maintenance were revealed at 5 years, with disability scores showing some continued improvement over time. The implications of these findings and the limitations of the study are discussed.

Functional-MRI evaluation of pain processing in chronic migraine with medication overuse.

Withdrawal is the first step for treating patients with chronic migraine and medication overuse. Recent studies confirmed common elements in personality between these patients and subjects addicted; some neuroimaging researches showed that abnormalities revealed are related to a specific cerebral pattern and that they can return to the normal state after withdrawal. Aim of the study was to submit a group of patients suffering from chronic migraine and medication overuse (the diagnosis was made according to Silberstein-Lipton criteria) to a withdrawal, to evaluate by f-MRI the presence of specific cerebral patterns before treatment and their possible changes after withdrawal. f-MRI seems to be a useful technique to obtain information on particular neuronal changes of the pain network involved in this type of patients. The activated areas are congruent with some data of the literature and the data emerged are discussed according to preceding reports.

Non-pharmacological approaches to treating chronic migraine with medication overuse.

Medication overuse headache (MOH) is now recognized as a biobehavioral disorder, a condition wherein emotion and pain are intermingled. This review discusses the steps to consider when treating this condition. The first step involves educating patients about MOH and the pathways to chronicity. The second step concerns working with patients to identify risk factors and behaviors that are present and contributing to the condition. The final step involves behavioral intervention. Examples for accomplishing each step are provided.

Prevalence and characteristics of right-to-left shunt in migraine with aura: a survey on 120 Italian patients.

Many lines of research have suggested a relationship between migraine with aura (MA) and patent foramen ovale. Right-to-left shunt (RLS) of blood might explain both the occurrence of MA attacks, as well as the increased risk of ischaemic stroke in these patients. We evaluated the prevalence and the characteristics of RLS in a series of 120 MA patients, who were studied with contrast-enhanced Transcranial Doppler examination. We found RLS in 61 of them. A latent RLS was found in 28%, a permanent RLS in 72%, a shower-curtain pattern was detected in 52% of the studied patients.

Isolated intraorbital schwannoma arising from the abducens nerve.

CASE REPORT: A case of isolated schwannoma of the orbit, arising from the terminal branches of the abducens nerve to the lateral rectus muscle, is reported. The patient presented with a painless proptosis of the left eye. DISCUSSION: Preoperative diagnosis of benign intraorbital neoplasm was made by means of CT and MR scans; the mass was radically excised through a microsurgical lateral orbitotomy and the pathological examination revealed a schwannoma. Features of orbital schwannoma are described, together with some details concerning the surgical strategy and the history of the evolution of the lateral orbitotomy.