Paola Di Fiore

The neuropsychiatric profile of Parkinson’s disease subjects with and without mild cognitive impairment

Neuropsychiatric symptoms (NPS) are common clinical features of Parkinson’s disease (PD). However, NPS profiles in PD subjects with mild cognitive impairment (MCI) have scarcely been investigated. We aimed to describe the NPS profiles of non-demented PD subjects with and without MCI. A total of 410 non-demented PD subjects were included. Of these, 164 were cognitively normal PD subjects (PD-cn), 142 PD had amnestic MCI (PD-aMCI), and 104 had PD with non-amnestic MCI (PD-naMCI). NPS were evaluated in accordance with the Neuropsychiatric Inventory (NPI). PD-aMCI subjects revealed the highest NPS burden, followed by PD-naMCI and then PD-cn. Overall, the most common NPS in PD-MCI were in order: depression, sleep disturbance, anxiety and apathy. Irritability was significantly associated with PD-aMCI and PD-naMCI. Prospective studies are required to evaluate the significance, clinical correlates and prognostic role of NPS in subject with PD-MCI.

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.

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

PurposeThe 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).MethodsPatients were enroled 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.ResultsThe 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.ConclusionsOur 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.

Prevalence and Profile of Mild Cognitive Impairment in Parkinson’s Disease

Background/Aims: The frequency of mild cognitive impairment (MCI) in Parkinson’s disease (PD) ranges from 19 to 40%, and this is probably due to methodological differences between the studies. The aim of this study was to evaluate the frequency and profile of MCI in a large sample of nondemented PD subjects and neurologically healthy subjects (NHS). Methods: A total of 872 subjects (582 controls and 290 PD) were included. The association between MCI and PD was tested, using logistic regression models; odds ratios (OR) with 95% confidence intervals (CI) were calculated. Results: Fifty-three percent of PD subjects and 45% NHS met the criteria for MCI (p = 0.001). The PD subjects showed a higher frequency of nonamnestic MCI (naMCI), compared to NHS (23.8 vs. 14.4%, p ≤ 0.0001). In comparison to NHS, PD was associated with a univariate OR of 1.9 (95% CI = 1.3–2.8) for naMCI, and this association was marginally significant after multiple comparisons (multivariate OR = 1.5, 95% CI = 0.96–2.3, p = 0.077). Conclusion: The association between PD and the impairment of nonmemory domains is probably due to frontal-subcortical involvement, which characterizes the disease.

Abnormal tyrosine metabolism in chronic cluster headache

Objective Episodic cluster headache is characterized by abnormalities in tyrosine metabolism (i.e. elevated levels of dopamine, tyramine, octopamine and synephrine and low levels of noradrenalin in plasma and platelets.) It is unknown, however, if such biochemical anomalies are present and/or constitute a predisposing factor in chronic cluster headache. To test this hypothesis, we measured the levels of dopamine and noradrenaline together with those of elusive amines, such as tyramine, octopamine and synephrine, in plasma of chronic cluster patients and control individuals. Methods Plasma levels of dopamine, noradrenaline and trace amines, including tyramine, octopamine and synephrine, were measured in a group of 23 chronic cluster headache patients (10 chronic cluster ab initio and 13 transformed from episodic cluster), and 16 control participants. Results The plasma levels of dopamine, noradrenaline and tyramine were several times higher in chronic cluster headache patients compared with controls. The levels of octopamine and synephrine were significantly lower in plasma of these patients with respect to control individuals. Conclusions These results suggest that anomalies in tyrosine metabolism play a role in the pathogenesis of chronic cluster headache and constitute a predisposing factor for the transformation of the episodic into a chronic form of this primary headache.

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

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.

Comorbidity between depressive symptoms and migraine: preliminary data from the Zabút Aging Project.

We evaluated the association between depressive symptoms and migraine using cross-sectional data from the Zabút Aging Project, a population-based study including subjects aged ≥50 years. A total of 1285 nonmigraineurs and 151 migraineurs were included. Diagnosis of migraine was carried out using the criteria of the International Headache Society. The Center for Epidemiologic Studies Depression scale (CES-D) was used to score depressive symptoms. Depressive symptoms were clustered in four groups: depressed and positive affects, somatic activity and intrapersonal feelings. Migraineurs showed higher total and specific depressive symptoms than controls (p from 0.005 to <0.0001). Mild-to-moderate depressive symptoms (CES-D score of ≥16) were present in 47.2% of migraineurs compared to 15.8% of controls (p<0.0001). After adjustment for demographics, mild-to-moderate depressive symptoms were strongly associated with migraine (OR [95% CI]=4.7 [3.1–7.0]). This association significantly increased in males (OR [95% CI]=6.2 [2.8–14.6]). Depressive features represent highly frequent comorbid symptoms of adult-to-elderly migraineurs.

Migraine with aura and white matter lesions: an MRI study

Several studies report the presence of white matter lesions on brain magnetic resonance imaging in patients with migraine. The aim of our study was to detect the entity of white matter T2-hyperintensities in 90 high selected patients affected by migraine with aura, compared to a group of 90 healthy controls. We found no significant difference of incidence of white matter alterations comparing these two groups.

Cluster headache: what has changed since 1999?

The peripheral and central origin of pain in cluster headache (CH) and trigeminal autonomic cephalgias (TACs) has been matter of debate. In the last decade, a number of information came from both animal and human studies. This paper briefly highlights main data from these studies. Taken together, there is now sufficient body of evidence indicating that CH and TACs can be regarded as a unique headache spectrum–syndrome, due to involvement of specific brain areas.

High dosage of methylprednisolone in cluster headache

Cluster headache (CH) is a primary headache characterized by an extremely intense, lancinating pain, strictly one-sided, of relatively short duration, and with associated autonomic signs, such as lacrimation, conjunctival injection, rhinorrhea, nasal congestion, ptosis, eyelid edema, miosis, redness, and facial sweating. During the attack, the patient is particularly restless and agitated. CH affects about 0.05–0.3% of the general population, predominantly male. It is distinguished in episodic (ECH) and chronic form (CCH), secondary or ab initio. The first is characterized by active periods (clusters), with a duration from 7 to 365 days, with an attacks-free period of at least 1 month; the second one has attacks that occur for over 1 year and periods of remission that last less than 30 days. According to the International Classification of Headache Disorders 3rd edition beta version (ICHD-3), the frequency of attacks ranges from a minimum of 1 every 2 days to a maximum of 8 a day, often with onset at fixed times. Attacks may last from 15 to 180 min. Although several studies have been performed to investigate CH pathogenesis, there is not a univocal interpretation about the origin of this primary headache. Currently, the involvement of the hypothalamus is well documented, but the exact mechanism by which it contributes to the clinical manifestations of the disease remains to be clarified. Several drugs are used as CH therapy, either for the attack or for prophylaxis, for both the episodic and chronic forms. The efficacy of the use of triptans (sumatriptan sc and zolmitriptan nasal spray) and oxygen (12–15 l per minute for about 10 min) is well documented in acute therapy, both by studies and clinical practice. Prophylactic therapies are more challenging: only verapamil has demonstrated to be useful in both ECH and CCH; lithium carbonate seems to be more indicated for CCH, and many other drugs has been employed (carbamazepine, valproic acid, topiramate, etc.), but clinical efficacy is not so satisfying. There is a consensus in literature on the efficacy of steroids, such as prednisone per os and dexamethasone i.m. [1]. Regarding the use of intravenous (iv) steroids, on the other hand, there are no randomized double-blind or prospective studies, and its use is supported only by aneddotic cases or very exiguous groups of patients [2, 3]. In the few studies available, however, homogeneous data are missing, especially concerning the dose and the duration of treatments. In this study, we reviewed the data of 23 patients (20 males and 3 females), suffering from ECH (14 pts) or CCH (9 pts), according to ICHD-3 criteria. All patients were treated in our Headache Center, in the period 2010–2017, for a recurring cluster, using high-dose iv methylprednisolone (MP). We reviewed a total of 37 treatments. At the time of treatment, the mean age of the patients was 43.9 years (range 21–61), the mean duration of the disease was 14.0 years (range 2–33), and all patients had daily attacks, from 1 to 12 (average 3.75). All patients had previously taken prophylactic therapies (verapamil, carbolithium, os steroid, carbamazepine, valproic acid, topiramate, rotigotine, OCS, botox A, pizotifen, melatonin, and flunarizine). On admission, 5 patients were free of prophylactic therapies. In the other 32 cases, verapamil was assumed in 30 patients, steroids in 6, lithium in 3, topiramate in 2, in different combinations among them, 1 patient was on therapy with fentanyl, duloxetine other than steroids and lithium. All patients received daily iv MP; 12 patients only one time, 8 patients in two occasions, and 3 pts repeated the treatment three times; 22 treatments were administered to ECH pts, 15 to CCH pts. Dosages of MP and number of days of treatments depended by the therapeutic response. We used MP 500 mg for 5 days only one time, MP 1 g for 3 days in 9 treatments,MP 1 g for 4 days in 3 occasions,MP 1 g for 5 days in 17 treatments, and MP 1 g for 6 days one time; in 6 patients that went to a second treatment, we used MP 2 g the first day, tapering the dose in the next 6–10 days. After 32/37 therapies (86.5%), patients were discharged pain-free (18 ECH, 14 CCH). In 5/37 treatments, we obtained a partial benefit with several pain-free days and with a clear reduction of intensity of the remaining attacks. In 32 occasions, steroid therapy did not cause side effects (SE); 1 patient reported cardiopalmos, 1 * Giacomo D’Arrigo giacomo.darrigo@asst–santipaolocarlo.it