Social cognition abilities in patients with primary and secondary chronic pain.

Previous evidence suggested that chronic pain is characterized by cognitive deficits, particularly in the social cognition domain. Recently, a new chronic pain classification has been proposed distinguishing chronic primary pain (CPP), in which pain is the primary cause of patients' disease, and chronic secondary pain (CSP), in which pain is secondary to an underlying illness. The present study aimed at investigating social cognition profiles in the two disorders. We included 38 CPP, 43 CSP patients, and 41 healthy controls (HC). Social cognition was assessed with the Ekman-60 faces test (Ekman-60F) and the Story-Based Empathy Task (SET), whereas global cognitive functioning was measured with the Montreal Cognitive Assessment (MoCA). Pain and mood symptoms, coping strategies, and alexithymia were also evaluated. Correlations among clinical pain-related measures, cognitive performance, and psychopathological features were investigated. Results suggested that CSP patients were impaired compared to CPP and HC in social cognition abilities, while CPP and HC performance was not statistically different. Pain intensity and illness duration did not correlate with cognitive performance or psychopathological measures. These findings confirmed the presence of social cognition deficits in chronic pain patients, suggesting for the first time that such impairment mainly affects CSP patients, but not CPP. We also highlighted the importance of measuring global cognitive functioning when targeting chronic pain disorders. Future research should further investigate the cognitive and psychopathological profile of CPP and CSP patients to clarify whether present findings can be generalized as disorder characteristics.

Different personality profiles in patients with cluster headache: a data-driven approach.

INTRODUCTION: Cluster headache (CH) is usually comorbid to mood spectrum disorders, but the psychopathological aspects are poorly explored. We aimed at identifying discrete profiles of personality traits and their association with clinical features. METHODS: Based on the personality scales of the Millon Clinical Multiaxial Inventory-III, principal component analysis (PCA) identified psychological patterns of functioning of 56 CH patients. PCA outcomes were used for hierarchical cluster analysis (HCA) for sub-groups classification. RESULTS: Eighty-seven percent of patients had personality dysfunctions. PCA found two bipolar patterns: (i) negativistic, sadic-aggressive, borderline, and compulsive traits were distinctive of the psychological dysregulation (PD) dimension, and (ii) narcissistic, histrionic, avoidant, and schizoid traits loaded under the social engagement (SE) component. PD was associated with disease duration and psychopathology. SE was related to educational level and young age. HCA found three groups of patients, and the one with high PD and low SE had the worst psychological profile. CONCLUSIONS: Personality disorders are common in CH. Our data-driven approach revealed distinct personality patterns which can appear differently among patients. The worst combination arguing against mental health is low SE and high PD. Linking this information with medical history may help clinicians to identify tailored-based therapeutic interventions for CH patients.

Self-administered subcutaneous diclofenac sodium in acute migraine attack: A randomized, double-blind, placebo-controlled dose-finding pilot study.

BACKGROUND: A novel formulation of diclofenac, complexed with hydroxypropyl-ß-cyclodextrin (HPßCD) as a solubility enhancer, in a prefilled syringe for self-administered subcutaneous injection may overcome the limitations of acute migraine treatments administered by oral, rectal, intramuscular, or intravenous routes. METHODS: This multicentre, phase 2, double-blind, randomized, placebo-controlled, dose-finding pilot study evaluated the efficacy, safety and tolerability of three different doses (25/50/75 mg/1 mL) of subcutaneous diclofenac sodium in the treatment of an acute migraine attack in 122 subjects. The primary efficacy endpoint was the percentage of patients pain-free at 2 hours after the study drug injection. RESULTS: A significantly higher percentage of patients in the 50 mg diclofenac group 14 (46.7%) were pain-free at 2 hours when compared with placebo: 9 (29.0%) (p = 0.01). The 50 mg dose proved superior to placebo also in the majority of the secondary endpoints. The overall global impression favoured diclofenac vs placebo. There were no adverse events leading to study withdrawal. The majority of treatment-emergent adverse events were mild. CONCLUSIONS: The 50 mg dose of this novel formulation of diclofenac represents a valuable self-administered option for the acute treatment of migraine attacks.Trial registration: EudraCT Registration No. 2017-004828-29.

The Pre-Lumbar puncture Intracranial Hypertension Scale (PLIHS): A practical scale to identify subjects with normal cerebrospinal fluid pressure in the management of idiopathic intracranial hypertension.

BACKGROUND: Idiopathic Intracranial Hypertension (IIH) diagnosis requires lumbar puncture to measure cerebrospinal fluid (CSF) pressure. The Pre-Lumbar puncture Intracranial Hypertension Scale (PLIHS) is aimed to detect cases that will show raised or normal CSF opening pressure. METHODS: Retrospective analysis of records of patients who underwent lumbar puncture for suspect IIH. The target was CSF opening pressure ≥ 250 mmH2O, whereas a set of known neurological, neuro-ophthalmological and neuro-radiological parameters, plus obesity, were used as predictors in a logistic regression model. The PLIHS was based on significant predictors and a cut-off was validated using chi-squared test around CSF opening pressure ≥ 250 and < 200 mmH2O. RESULTS: Records of 162 patients were included: CSF opening pressure was <200 mmH2O in 40 and ≥ 250 mmH2O in 95 patients; 85 fulfilled IIH diagnosis. PLIHS is based on Frisén grade 2 or higher papilledema, tinnitus, empty sella, perioptic subarachnoid space distension, and obesity. Score range is 0-7: correlation with CSF opening pressure is 0.508 (p < .001), and PLIHS score is different between subjects not diagnosed with IIH, and those diagnosed with IIH both with and without papilledema (p < .001). PLIHS score ≤ 2 identifies cerebrospinal fluid pressure < 200 mmH2O; PLIHS score ≥ 3 identifies CSF opening pressure ≥ 250 mmH2O, IIH diagnosis, visual acuity ≤0.7, and optic nerve atrophy. CONCLUSIONS: The PLIHS, can be used to identify patients who will particularly need LP, thus helping with the organization of the diagnostic work-up by optimising healthcare resources and potentially limit the likelihood to incur in LP-related adverse events.

SARS-COV-2 comorbidity network and outcome in hospitalized patients in Crema, Italy.

We report onset, course, correlations with comorbidities, and diagnostic accuracy of nasopharyngeal swab in 539 individuals suspected to carry SARS-COV-2 admitted to the hospital of Crema, Italy. All individuals underwent clinical and laboratory exams, SARS-COV-2 reverse transcriptase-polymerase chain reaction on nasopharyngeal swab, and chest X-ray and/or computed tomography (CT). Data on onset, course, comorbidities, number of drugs including angiotensin converting enzyme (ACE) inhibitors and angiotensin-II-receptor antagonists (sartans), follow-up swab, pharmacological treatments, non-invasive respiratory support, ICU admission, and deaths were recorded. Among 411 SARS-COV-2 patients (67.7% males) median age was 70.8 years (range 5-99). Chest CT was performed in 317 (77.2%) and showed interstitial pneumonia in 304 (96%). Fatality rate was 17.5% (74% males), with 6.6% in 60-69 years old, 21.1% in 70-79 years old, 38.8% in 80-89 years old, and 83.3% above 90 years. No death occurred below 60 years. Non-invasive respiratory support rate was 27.2% and ICU admission 6.8%. Charlson comorbidity index and high C-reactive protein at admission were significantly associated with death. Use of ACE inhibitors or sartans was not associated with outcomes. Among 128 swab negative patients at admission (63.3% males) median age was 67.7 years (range 1-98). Chest CT was performed in 87 (68%) and showed interstitial pneumonia in 76 (87.3%). Follow-up swab turned positive in 13 of 32 patients. Using chest CT at admission as gold standard on the entire study population of 539 patients, nasopharyngeal swab had 80% accuracy. Comorbidity network analysis revealed a more homogenous distribution 60-40 aged SARS-COV-2 patients across diseases and a crucial different interplay of diseases in the networks of deceased and survived patients. SARS-CoV-2 caused high mortality among patients older than 60 years and correlated with pre-existing multiorgan impairment.

Headache in spontaneous intracranial hypotension: an overview with indications for differential diagnosis in the clinical practice.

Headache is the most common symptom of spontaneous intracranial hypotension (SIH). The present review focuses on data regarding headache features reported in the most relevant published articles and summarizes the main SIH headache features, namely, orthostatic headache, headache triggered by Valsalva maneuver, pattern of onset of headache, and location and quality of headache. Published data indicate that the clinical suspect of this disorder may be challenging, due to its protean presentation. Among the main implications for clinical practice, we suggest to suspect SIH in all patients with a new onset headache, as different forms of primary and secondary headache should be considered in the differential diagnosis of SIH, particularly cervicogenic headache, new daily persistent headache, and headaches precipitated by Valsalva maneuver. The clinical interview must include specific questions on the possible orthostatic feature of headache, although its absence should not make clinicians to reject the SIH hypothesis as headache cannot be orthostatic in each patient and in all periods of the natural history of the disease. Other disorders with orthostatic symptoms, such as in postural tachycardia syndrome (POTS) and persistent postural-perceptual dizziness (PPPD), should be considered in the differential diagnosis. Awareness that SIH can present with acute, sudden onset requires that clinicians working in the emergency settings should consider SIH in the range of diagnoses of thunderclap headache.

Syncope at SARS-CoV-2 onset.

We describe clinical and laboratory findings in 35 patients tested positive for SARS-CoV-2 by reverse transcriptase-polymerase chain reaction on nasopharyngeal swab experiencing one or multiple syncope at disease onset. Clinical neurologic and cardiologic examination, and electrocardiographic findings were normal. Chest computed tomography showed findings consistent with interstitial pneumonia. Arterial blood gas analysis showed low pO2, pCO2, and ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) indicating hypocapnic hypoxemia. Patients who presented with syncope showed significantly lower heart rate as compared to 68 SARS-CoV-2 positive that did not. Such poorer than expected compensatory heart rate increase may have led to syncope based on individual susceptibility. We speculate that SARS-CoV-2 could have caused angiotensin-converting enzyme-2 (ACE2) receptor internalization in the nucleus of the solitary tract and other midbrain nuclei, impairing baroreflex and chemoreceptor response, and inhibiting the compensatory tachycardia during acute hypocapnic hypoxemia.

No efficacy of transcranial direct current stimulation on chronic migraine with medication overuse: A double blind, randomised clinical trial.

BACKGROUND: Transcranial direct current stimulation was suggested to provide beneficial effects in chronic migraine, a condition often associated with medication overuse for which no long-term therapy is available. METHODS: We conducted a randomised controlled trial to assess long-term efficacy of transcranial direct current stimulation. Adults diagnosed with chronic migraine and medication overuse were assigned to receive in a 1:1:1 ratio anodal, cathodal, or sham transcranial direct current stimulation daily for five consecutive days, along with standardised drug withdrawal protocol. Primary outcome was 50% reduction of days of headache per month at 12 months. Co-secondary outcomes were 50% reduction of days of headache per month at 6 months, reduction of analgesic intake per month, and change in disability and quality of life, catastrophising, depression, state and trait anxiety, dependence attitude and allodynia intensity. Patients were not allowed to take any migraine prophylaxis drug for the entire study period. RESULTS: We randomly allocated 135 patients to anodal (44), cathodal (45), and sham (46) transcranial direct current stimulation. At 6 and 12 months, the percentage of reduction of days of headache and number of analgesics per month ranged between 48.5% and 64.7%, without differences between transcranial direct current stimulation (cathodal, anodal, or the results obtained from the two arms of treatment, anodal plus cathodal) and sham. Catastrophising attitude significantly reduced at 12 months in all groups. There was no difference for the other secondary outcomes. CONCLUSIONS: Transcranial direct current stimulation did not influence the short and long-term course of chronic migraine with medication overuse after acute drug withdrawal. Behavioral and educational measures and support for patients' pain management could provide long-term improvement and low relapse rate.Trial registration number NCT04228809.

Clinical and psychosocial features of frequent relapsers (FR) among patients with chronic migraine and medication overuse.

The objective was to characterize frequent relapsers (FR)-i.e. those requiring two or more withdrawals in a 3-year period-in a sample of 188 patients with chronic migraine with medication overuse (CM-MO). We tested differences between FR and non-FR for age, gender, employment status, days with headache, headache severity, type of overused medication, BDI-II, WHODAS 2.0 and MSQ. 30.8% of participants were FR: they were more frequently treated as inpatients and living alone, had a lower education, higher disability and lower QoL, higher frequency and intensity of headaches, and higher depression scores. Clinicians should address whether CM-MO patients submitted to withdrawal had recently underwent other similar interventions.

Predictors of 12-Months Relapse After Withdrawal Treatment in Hospitalized Patients With Chronic Migraine Associated With Medication Overuse: A Longitudinal Observational Study.

BACKGROUND: Studies addressing relapse rates conflate relapse into chronic migraine (CM) and medication overuse (MO), and the consequent need to repeat withdrawal. We aim to identify 12-months predictors of relapse into CM (based on headaches frequency) separately from occurrence of another structured withdrawal. METHODS: Hospitalized patients with CM-MO under withdrawal were enrolled. Candidate predictors included demographic, disability, quality of life, depression scores, general self-efficacy, social support, headaches frequency and intensity, class of overused medications, history of withdrawal treatment in the three years prior to enrollment, attendance to emergency room (ER) between enrollment and follow-up, nonattendance to outpatient neurological examinations. Logistic regressions was used to address the significant predictors for the two outcomes. RESULTS: Complete data were available for 177 patients: 60 (33.9%) relapsed into CM, 38 (21.5%) underwent another withdrawal treatment. Recent history of withdrawal treatments, ER admission after discharge and high baseline BDI-II scores were significant predictors in both models. In addition to this, high baseline headache frequency predicted relapse into another withdrawal treatment. CONCLUSIONS: Predictors or relapse into CM and of occurrence of another withdrawal by 12-months are somehow similar. It is important to assess presence of recent previous withdrawal treatments and to plan regular follow-up afterwards, in particular for patients with high headache frequency and relevant mood disturbances: in this way, it will be more likely that situations requiring further structured withdrawal treatments can be identified before patients have to refer to ER.

Are depressive symptomatology, self-efficacy, and perceived social support related to disability and quality of life in patients with chronic migraine associated to medication overuse? Data from a cross-sectional study.

BACKGROUND: Chronic migraine with medication overuse (CM-MO) impairs quality of life (QoL) and causes disability. Psychosocial variables such as depressive symptomatology, self-efficacy, and social support have been sparingly investigated, and their impact on disability and QoL is unknown. METHODS: Patients with CM-MO under withdrawal were consecutively enrolled. Standardized measures of disability and QoL were used as outcomes; psychosocial (ie, mood state, self-efficacy, social support) and clinical (ie, headache frequency and intensity) variables were considered as associated variables. Associations between these variables, disability, and QoL were tested with Pearson's correlations. Hierarchical multiple regression was used to assess the cumulative contribution of psychosocial variables on disability and QoL variation when added to clinical variables. RESULTS: One hundred ninety-four patients were enrolled; 82.5% were females and mean age was 43.9. Disability and QoL were moderately or little correlated to clinical and psychosocial variables. Models based on clinical variables explained 7.5-14.3% of disability and QoL variation, with pain intensity being the only significant predictor; when psychosocial variables were added, the explained variation increased to 21.5-35.2%, with depressive symptomatology always having independent predictive power and perceived social support having independent predictive power in the regression model over role-prevention component of QoL. CONCLUSIONS: Adding information on psychosocial variables to headache features improved our ability to understand disability and QoL of CM-MO patients. We deem that the inclusion of psychosocial variables in standard evaluation protocols may contribute to the global assessment of CM-MO patients, and eventually to their success in reducing the personal and social impact of this condition. Future longitudinal studies are needed to confirm this hypothesis.

Chronic migraine with medication overuse: association between disability and quality of life measures, and impact of disease on patients' lives.

Patients with chronic migraine with medication overuse (CM-MO) have decreased quality of life (QoL) and increased disability: the degree to which these outcomes are connected to disease severity and the pattern of MO towards disease severity are unclear. Patients under withdrawal were administered the Migraine Disability Assessment (MIDAS), the WHO Disability Assessment Schedule (WHODAS), and the Migraine-Specific Quality of Life Questionnaire (MSQ). They overused NSAIDs, triptans, NSAIDs and triptans, and other drugs (ergotamine, caffeine, opioids/barbiturates). We calculated the correlations between MIDAS, WHODAS, and MSQ; compared WHODAS to normative scores; compared MIDAS, WHODAS, and MSQ in patients with different CM-MO severity; and run a logistic regression to predict CM-MO severity based on overused drugs. One hundred ninety-four patients were enrolled: correlations between WHODAS, MSQ, and MIDAS were moderate; wide differences on WHODAS against normative were found; and no trend was found across severity groups. Compared to triptans overusers, patients overusing NSAID and other drugs had higher odds of severe CM-MO. Coupling different disability measures with QoL assessment offered different insights on the lived experience of CM-MO. Future studies are needed to clarify the relationship between overused drugs and CM-MO severity: we added evidence that NSAIDs do not have protective effect in high-frequency CM-MO.

Dependency-like behaviors and pain coping styles in subjects with chronic migraine and medication overuse: results from a 1-year follow-up study.

BACKGROUND: Even after successful detoxification, 20-40% of subjects presenting chronic migraine with symptomatic medication overuse (CMwMO) relapse into medication overuse within one year. In this restrospective analysis on subjects referred to our center for detoxification, we investigated whether personality traits, dependency-like behaviors and pain coping styles predicted those who relapsed into medication overuse within the 12 months following the detoxification and those who did not. METHODS: 63 patients with CMwMO were assessed for personality traits, mood and anxiety, pain coping styles and dependency-like behaviors prior-to and one year after a detoxification program. RESULTS: Of the 42 subjects who attended 1-year follow-up interviews, 11 relapsed into medication overuse despite a temporary benefit from detoxification and did not show clinical or psychological improvement, instead reporting increased anxiety and unmodified perpetuation of severe dependency-like behaviors. In contrast, subjects who did not relapse into medication overuse had clinical improvements that generalized to untreated domains, including decreased depressive symptoms and dependency-like behaviors, although showing unmodified low internal control over pain. CONCLUSIONS: Subjects who did not fall into medication overuse throughout the 12 months following the detoxification showed improved clinical, affective and dependence-related outcomes, but not pain coping strategies. Conversely, subjects who relapsed within one year into CMwMO continued to experience significant disability, pain intensity, and dependency-like behaviors. We believe that the persistence of maladaptive pain coping strategies and residual symptomatology increase the risk for recurrent relapses, against which pharmacological interventions are only partially effective. Further studies investigating predictors of relapse are needed to inform multi-disciplinary interventions for CMwMO.

Botulinum toxin A: a new option for treatment of chronic migraine with medication overuse.

The application of Botulinum toxin for several pathological conditions has been largely debated in the last decades and its use has been definitively consolidated for disorders related to increased muscle tone and hyperidrosis. Botulinum neurotoxin (BoNT-A) is a potent toxin produced by an anaerobic bacterium, Clostridium botulinum, which presents several pharmacological proprieties, but also different and serious contraindications. As chronic migraine (CM) is commonly reported as a serious and debilitating condition and a big challenge from the therapeutic point of view, in the last decades, after isolated observations, BoNT-A has been applied as preventive treatment for CM patients and, after randomized and rigorous studies, it has been accepted among the most effective pharmacological treatments for these problematic patients. In the present report, a group of patients suffering from CM with medication overuse was treated with BoNT-A to verify its efficacy for CM. The results confirmed the efficacy of BoNT-A when used at the dosage of 155 UI, according with the PREEMPT study protocol. Although these results are preliminary, in a limited group of patients, they led to intense efforts to enforce the use of BoNT-A for CM and to assess its clinical applicability.

Validating the Migraine-Specific Quality of Life Questionnaire v2.1 (MSQ) in Italian inpatients with chronic migraine with a history of medication overuse.

PURPOSE: The purpose of the study is to assess validity, reliability and factor structure of the Italian version of Migraine-Specific Quality of Life Questionnaire v2.1 (MSQ) in patients suffering from chronic migraine (CM) with a history of medication overuse (MO). METHODS: Patients were enrolled at hospital admission for withdrawal from MO. Factor analysis was used to confirm the latent structure of the MSQ. Reliability was measured with Cronbach's alpha coefficient, item-total correlation and inter-item correlation. Construct validity was assessed with Pearson's coefficient and known-group analysis. RESULTS: The three-factor structure is basically confirmed. Cronbach's alpha varied between 0.85 and 0.92; item-total correlations were on average higher than 0.70; average inter-item correlation ranged between 0.63 and 0.65. Correlations were all significant; known-group analysis shows that MSQ score was lower consistently with disease severity. CONCLUSIONS: Our findings confirm the factor structure, reliability and validity of the MSQ and expand results of previous validation studies to the Italian language and to a group of patients with severe CM requiring withdrawal treatment for MO.

Orbitofrontal dysfunction and medication overuse in patients with migraine.

OBJECTIVE: Orbitofrontal cortex (OFC) dysfunction and poor decision making have been described in patients with chronic migraine and medication overuse. These neurobiological underpinnings might explain dependency-like behaviors often described in this condition, such as loss of control over painkillers, high rates of relapse after detoxification, and compromised social functioning. We investigate whether the OFC impairment was a persistent trait in migraine, independent of clinical and affective features, a dynamic result of the need to cope with the increased pain and disability, or a temporary consequence of medication overuse. METHODS: For this purpose, we compared 40 chronic migraineurs with medication overuse, 40 episodic migraineurs, and 40 matched healthy controls. The examination consisted of a clinical interview, Anxiety and Depression Hamilton Scales, Severity of Dependence Scale, and Migraine Disability Assessment questionnaire. A neuropsychological assessment of orbitofrontal function was made through the Iowa Gambling Task (IGT). Chronic migraineurs with medication overuse were followed for a year after detoxification. RESULTS: We found an impaired decision-making performance among chronic and episodic migraineurs that seems independent of the patients' clinical and affective status. Contrary to the psychiatric and clinical improvement shown 1 year after the detox, CM patients exhibited a persistent IGT deficit. No significant differences in OFC functioning were found between the CM patients who relapsed into medication overuse after detox and those who did not. CONCLUSIONS: The present findings suggest the presence of a persistent OFC dysfunction in migraine as a psychobiologic trait that is not influenced by the presence of medication overuse, the clinical severity of the disease, or the patient's affective status. Further studies are needed to elucidate the etiopathological role of OFC in migraine and medication overuse.

The 'nightmare' of wrong level in spine surgery: a critical appraisal.

The recent article published in the Journal by Lindley and colleagues (Patient Saf. Surg. 2011, 5:33) reported the successful surgical treatment of a persistent thoracic pain following a T7-8 microdiscectomy, truly performed at the 'level immediately above'. The wrong level in spine surgery is a multi-factorial matter and several strategies have been designed and adopted to try decreasing its occurrence. We think that three of these factors are crucial: global strategy, attention, precision in level identification; and the actors we identified are the surgeon, the assistant nurse and the (neuro)radiologist respectively. Basing upon our experience, the role of the radiologist pre- and intraoperatively and the importance of the assistant nurse are briefly described.

How to investigate and treat: headache and hyperprolactinemia.

Hyperprolactinemia is a condition characterised by an increase of prolactin blood levels (more than 100-200 ng/ml). It is the most common endocrine disorder of the hypothalamic-pituitary axis. The clinical characteristics of the headache-hyperprolactinemia-hypophyseal-adenoma association are discussed, the various diagnostic and treatment possibilities are explored and the etiology of the headache is considered in the light of several pathogenetic possibilities. We present two cases. (1) A 35-year-old woman suffering from chronic tension-type headache interspersed with occasional episodes of migraine without aura (as defined by the International Headache Society criteria). She had also suffered menstrual cycle alterations since the age of 16. At the age of 30 she developed amenorrhea with hyperprolactinemia. Computed tomography (CT) and magnetic resonance imaging (MRI) scans revealed a median-left intrasellar mass. Treatment with cabergoline resulted in complete resolution of both types of headache and the menstrual cycle and prolactin levels returned to normal. The therapy also reduced the volume of the tumour. (2) The second case relates to a 47-year-old man who had been suffering from tension-type headaches for almost 3 months. The patient had never previously suffered from headaches. CT and MRI scans showed a large sellar and suprasellar lesion with raised serum prolactin levels. Treatment with cabergoline had significantly reduced the prolactin levels and had also improved the patient's headaches. High-resolution CT, with and without contrast, or MRI is necessary to visualise microprolactinomas (and other sellar lesions) and confirm the diagnosis.