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Background Subjective complaints of cognitive deficits are not necessarily consistent with objective evidence of cognitive impairment in Parkinson’s disease (PD). Here we examined the factors associated with the objective-subjective cognitive discrepancy. Methods We consecutively enrolled 90 non-demented patients with PD who completed the Parkinson’s Disease Cognitive Functional Rating Scale (subjective cognitive measure) and the Montreal Cognitive Assessment (MoCA; objective cognitive measure). The patients were classified as “Overestimators”, “Accurate estimators”, and “Underestimators” on the basis of the discrepancy between the objective vs. subjective cognitive measures. To identify the factors distinguishing these groups from each other, we used chi-square tests or one-way analyses of variance, completed by logistic and linear regression analyses. Results Forty-nine patients (54.45%) were classified as “Accurate estimators”, 29 (32.22%) as “Underestimators”, and 12 (13.33%) as “Overestimators”. Relative to the other groups, the “Underestimators” scored higher on the Fatigue Severity Scale (FSS), Beck Depression Inventory (BDI), and Parkinson Anxiety Scale (p p p p Conclusion In more than 45% of consecutive non-demented patients with PD, we found a ‘mismatch’ between objective and subjective measures of cognitive functioning. Such discrepancy, which was related to the presence of fatigue and depressive symptoms and frontal executive impairments, should be carefully evaluated in clinical setting.

Introduction Caring for a person with Parkinson’s disease (PD) is associated with an increased risk of psychiatric morbidity and persistent distress. The objective of this study was to describe the burden and the related factors of caregivers of advanced PD (APD) patients either treated with continuous dopaminergic delivery systems or standard therapy. Methods This cross-sectional, epidemiologic study conducted in 13 Italian sites enrolled PD patients treated with continuous dopaminergic delivering systems [either levodopa/carbidopa intestinal gel (LCIG) infusion or continuous subcutaneous apomorphine infusion (CSAI)] or continuation of standard of care (SOC) with a caregiver. Patient quality of life (QoL) and caregiver burden were assessed using the Parkinson’s Disease Questionnaire (PDQ-8) and Zarit Burden Inventory (ZBI), respectively. Results 126 patients (mean age 69.3 ± 8 years) and their caregivers (mean age 57.9 ± 12.9) were enrolled. Most caregivers were spouses. Fifty-three patients were treated with LCIG, 19 with CSAI, and 54 with SOC. Mean ZBI scores were 29.6 ± 14.4 for LCIG, 35.8 ± 20.2 for CSAI, and 31.4 ± 16.0 for SOC. Caregivers of LCIG, CSAI, and SOC patients showed no burden or mild/moderate burden in 74, 53, and 63% of the cases, respectively. Mean PDQ-8 scores were 11.25 ± 5.67, 11.26 ± 5.55, and 14.22 ± 6.51 in LCIG, CSAI, and SOC patients. Neurologists considered patients “very much or much improved” in 89, 58, and 13% of the LCIG, CSAI, and SOC groups using the Clinical Global Impression–Global Improvement Scale. Predictors significantly associated with caregiver burden were patients and caregivers’ judgment of QoL and caregivers’ need to change work. Conclusions Caregiver burden showed a tendency to be lower when patients are treated with LCIG than with CSAI or SOC.

To investigate the reliability of a new in-house automatic algorithm for calculating the Magnetic Resonance Parkinsonism Index (MRPI), in a large multicentre study population of patients affected by progressive supranuclear palsy (PSP) or Parkinson’s disease (PD), and healthy controls (HC), and to compare the diagnostic accuracy of the automatic and manual MRPI values. The study included 88 PSP patients, 234 PD patients and 117 controls. MRI was performed using both 3T and 1.5T scanners. Automatic and manual MRPI values were evaluated, and accuracy of both methods in distinguishing PSP from PD and controls was calculated. No statistical differences were found between automated and manual MRPI values in all groups. The automatic MRPI values differentiated PSP from PD with an accuracy of 95 % (manual MRPI accuracy 96 %) and 97 % (manual MRPI accuracy 100 %) for 1.5T and 3T scanners, respectively. Our study showed that the new in-house automated method for MRPI calculation was highly accurate in distinguishing PSP from PD. Our automatic approach allows a widespread use of MRPI in clinical practice and in longitudinal research studies. • A new automatic method for calculating the MRPI is presented. • Automatic MRPI values are in good agreement with manual values. • Automatic MRPI can distinguish patients with PSP from patients with PD. • The automatic method overcomes MRPI application limitations in routine practice. • The automatic method may allow a more widespread use of MRPI.

Vestibular migraine (VM) has been increasingly recognized as a frequent cause of episodic vertigo, affecting up to 1 % of the general population, with female preponderance. Recently, both the Bárány Society and the Migraine Classification Subcommittee of the International Headache Society have proposed original diagnostic criteria for VM, which have been included in the recent edition of the ICHD-3 beta version. VM diagnosis implies that vestibular symptoms are present during a migraine attack, with or without headache, in the absence of objectively demonstrated interictal vestibulopathy. Nevertheless, despite a growing body of literature, there is still an ongoing debate regarding whether VM origin is principally central or peripheral. However, during the past few years, the extensive application of advanced MRI techniques has contributed to significantly improve the understanding VM pathophysiology. Functional and structural abnormalities have been detected in brain areas involved in multisensory vestibular control and central vestibular processing in patients with VM. In this brief review, we will focus on these recent neuroimaging findings.

Purpose of Review: This review aims to provide an overview of the most recent and significant functional neuroimaging studies which have clarified the complex mechanisms underlying migraine pathophysiology. Recent Findings: The recent data allow us to overcome the concept of a migraine generator suggesting that functional networks abnormalities may lead to changes in different brain area activities and consequent reduced migraine thresholds susceptibility, likely associated with higher migraine severity and burden. Summary: Although functional magnetic resonance imaging studies have allowed recognition of several migraine mechanisms, its pathophysiology is not completely understood and is still a matter of research. Nevertheless, in recent years, functional magnetic resonance imaging studies have allowed us to implement our knowledge of migraine pathophysiology. The pivotal role of both the brainstem and the hippocampus in the first phase of a migraine attack, the involvement of limbic pathway in the constitution of a migrainous pain network, the disrupted functional connectivity in cognitive brain networks, as well as the abnormal function of the visual network in patients with migraine with aura are the main milestones in migraine imaging achieved through functional imaging advances. We believe that further studies based on combined functional and structural techniques and the investigation of the different phases of migraine cycle may represent an efficient methodological approach for comprehensively looking into the migrainous brain secrets.

Migraine is a neurologic disorder characterized by disabling attacks of throbbing headache with specific features and associated symptoms. Despite the recent discoveries in basic neurosciences, migraine pathophysiology is not completely understood. Nevertheless, in the last decades, advances in functional magnetic resonance imaging (fMRI) have significantly provided new insights into migraine mechanisms. Blood oxygen level dependent (BOLD) fMRI technique is the most commonly used method to explore brain function and connectivity due to high temporal and spatial resolution. The purpose of this review is to present a synthesis of recent BOLD-fMRI studies which have allowed us to elucidate the complex process involved in migraine pathophysiology.

BACKGROUND: The occurrence of cognitive dysfunctions and psychological symptoms, as well as their mutual relationships, in migraine patients are still debated. The aim of the study was to characterize the cognitive profile and psychological symptoms (i.e. depression, anxiety and apathy) in drug-naïve migraine without aura (MwoA) patients. METHODS: Seventy-two consecutive MwoA patients, referred to the Italian University Headache Clinic and 72 healthy subjects (HCs) were enrolled. Patients, during an attack-free period, and HCs completed Montreal Cognitive Assessment (MoCA), Beck Depression Inventory-II (BDI-II), Self-version of Apathy Evaluation Scale (AES-S) and State and Trait Anxiety Inventory (STAI-Y-1 and 2). Clinical parameters of disease severity (i.e. disease duration, migraine attacks per month, mean pain intensity during migraine attacks, migraine disability and impact on daily life) were recorded. RESULTS: Although performance of MwoA patients on MoCA was above Italian cut-off threshold (

Brain derived neurotrophic factor (BDNF) regulates several CNS physiological and pathological processes. To investigate in multiple sclerosis (MS) patients, the relationship between the Val66Met polymorphism of BDNF and clinical markers of disease activity and MRI markers of focal and diffuse brain pathologies. 45 MS patients and 34 healthy controls (HCs) were genotyped and subjected to clinical-MRI examination. Global white matter fraction (gWM-f), gray matter-f (GM-f), cerebrospinal fluid-f (CSF-f), and abnormal WM-f were measured. We studied 26 Val/Val and 19 Val/Met patients and 23 Val/Val and 11 Val/Met HCs. We found that Val/Val patients had lower GM-f and higher CSF-f than Val/Val HCs; such differences were not statistically significant comparing Val/Met patients to HCs. The regression analysis showed that both Val/Met genotype and relapse number were associated with lower CSF-f. Our data suggest that Met allele might be a protective factor against MS as it is associated to a lower brain atrophy.

Background Approximately two thirds of migraine patients complain of cutaneous allodynia (CA) which is defined as a pain perception evoked by ordinary non-nociceptive skin stimulation in cephalic regions during migraine attacks. CA may be underlied by the sensitization of second-order trigeminovascular neurons, belonging to the trigeminalthalamo-cortical pathway. In this context, a crucial role seems to be played by supraspinal mechanisms related to the descending pain modulatory system [1].

Background Migraine is a disabling neurological condition characterized by headache attacks, hypersensitivities to visual, auditory, olfactory and somatosensory stimuli, nausea and vomiting. Peripheral and central sensitization of trigeminovascular neurons seem to play a critical role in different aspects of migraine pathophysiology [1]. In the last years, several studies investigated pain thresholds in patients with migraine during both attacks and interictal periods. However, pain perception in patients with migraine has been poorly explored. Objective To investigate perception intensity of trigeminal heat stimulation (THS) [2] in patients with migraine without (MwoA CA-) and with allodynia (MwoA CA+) compared to healthy controls (HC) and correlation with clinical parameters of migraine severity. Methods We enrolled 80 patients with migraine (40 patients with MwoA CA- and 40 patients with MwoA CA+) and 60 HC. THS was performed using the contact heat evoked potential stimulator (CHEPS) at three different intensities: a low-innocuous stimulus at 41°C and two painful heat stimuli at 51° and 53°C (to provide a moderate-noxious and a high-noxious stimulus). Subjects had to verbally rate the intensity perception of the experimental stimulus by means of a numerical rating scale (NRS) ranging from 0( “no pain” )t o 10 (“worst pain imaginable”). Results NRS of pain perception was not significantly different between patients with MwoA (as a group) and HC at any level of experimental stimuli. The absence of significant differences in pain perception was also found between patient groups defined as patients with MwoA CA- and with MwoA CA+ compared to HC, at any level of experimental stimuli. Conclusions

Sneddon’s syndrome (SS) is a rare condition characterized by the combination of ischemic strokes and cutaneous livedo [1, 2], defined as the ‘‘persistent, not reversible with rewarming, violaceous, reticular or mottled pattern of the skin of trunk, arms or legs, consisting of regular unbroken circles (livedo reticularis) or irregular-broken circles (livedo racemosa)’’. Other well-defined neurological manifestations of SS include headache, seizures, and vascular dementia. Here, we report two cases with clinical and imaging features suggestive of SS. In both patients skin biopsy was performed and sections were stained with hematoxylin and eosin (HE general examination revealed diffused livedo racemosa (Fig. 1a). An extensive cardiological evaluation including an electrocardiogram, an echocardiogram and carotid ultrasound evaluation ruled out cardiovascular causes of stroke. Coagulation parameters (including fibrinogen and D-dimer), inflammatory indexes, syphilis serology, and autoimmune antibody panels including, ANA, ENA, ANCA, lupus anti-coagulants (LAC) and antiphospholipid antibodies (IgM and IgG anti-cardiolipin and anti-b2-microglobulin) were negative. A heterozygous mutation of factor V Leiden was detected. Brain MRI showed cortical atrophy and multiple ischemic lesions involving both the superficial and deep territories of posterior and middle cerebral artery (Fig. 1b). Skin biopsy showed intra-capillary and parietal widespread thrombosis (Fig. 1c). Oral anticoagulants and antipsychotic were added to therapy. A 65-year-old man (Case 2) presented with a 3-year history of progressive lower limbs weakness and mixed dysphagia. He had been having recurrent ischemic strokes since he was 55. He had history of myocardial infarcts, hypertension, and smoking. His neurological examination revealed dysphagia, ataxic and spastic gait, limbs hyperreflexia, right extensor plantar response. General examination revealed diffused livedo racemosa at the trunk and lower limbs (Fig. 1a). A cardiological evaluation and electrocardiogram ruled out the presence of heart arrhythmia; echocardiography demonstrated mild hypokinesia of apical and distal septum of lateral ventricle, as consequence of previous myocardial infarcts. Coagulation parameters and thrombophilic screening were normal. Brain MRI showed diffused cortical atrophy and multiple ischemic lesions (Fig. 1b) in both medium-sized superficial and deep, posterior and middle cerebral artery territories. Skin biopsy revealed intra-capillary and parietal widespread thrombosis (Fig. 1c). As for the first patient, oral anticoagulants were added to therapy. G. Cirillo A. Tessitore (&) F. Salemi S. Liguori S. Esposito G. Tedeschi Department of Neurology, Second University of Naples, 80138 Naples, Italy e-mail: alessandro.tessitore@unina2.it

Amphetamine, a potent monoaminergic agonist, has pronounced effects on emotional behavior in humans, including the generation of fear and anxiety. Recent animal studies have demonstrated the importance of monoamines, especially dopamine, in modulating the response of the amygdala, a key brain region involved in the perception of fearful and threatening stimuli, and the generation of appropriate physiological and behavioral responses. We have explored the possibility that the anxiogenic effect of amphetamine in humans reflects the drug's influence on the activity of the amygdala. In a double-blind placebo controlled study, fMRI revealed that dextroamphetamine potentiated the response of the amygdala during the perceptual processing of angry and fearful facial expressions. Our results provide the first evidence of a specific neural substrate for the anxiogenic effects of amphetamine and are consistent with animal models of dopaminergic activation of the amygdala.

The aim of our study was to explore the pain processing network in patients with migraine during trigeminal nociceptive stimulation. Sixteen patients with episodic migraine without aura and 16 healthy controls performed functional magnetic resonance imaging during thermal stimuli (at 41, 51 and 53A degrees C). Patients with migraine showed a greater activation in the perigenual part of anterior cingulate cortex at 51A degrees C and less activation in the bilateral somatosensory cortex at 53A degrees C compared to healthy controls. There were no differences in experimental pain perception between groups. Our findings demonstrate a functional reorganization of cerebral areas known to be involved in pain processing in patients with migraine.

Migraine pathophysiology is not completely understood and is still a matter of ongoing research. However, functional magnetic resonance imaging studies have provided, over the last few decades, notable insights into neuronal mechanisms underlying migraine. Recently, by using an innovative approach based on repetitive trigeminal painful stimulation, researchers have explored pain processing network functional changes associated with migraine and their correlations with specific migraineous clinical features. These functional changes have been demonstrated during different phases of migraine cycle. However, owing to the complexity of its neurobiology, migraine pathophysiology still has many secrets to be discovered.

Mutations in the Cu/Zn superoxide dismutase (Sod1) gene have been reported to cause adult-onset autosomal dominant Amyotrophic Lateral Sclerosis (FALS). In sporadic cases (SALS) de novo mutations in the Sod1 gene have occasionally been observed. The recent finding of a mutation in the VAMP/synaptobrevin-associated membrane protein B (VAPB) gene as the cause of amyotrophic lateral sclerosis (ALS8), prompted us to investigate the entire coding region of this gene in SALS patients. One hundred twenty-five unrelated patients with adult-onset ALS and 150 healthy sex-age-matched subjects with the same genetic background were analyzed. Genetic analysis for all exons of the VAPB gene by DHPLC revealed 5 variant profiles in 83 out of 125 SALS patients. Direct sequencing of these PCR products revealed 3 nucleotide substitutions. Two of these were found within intron 3 of the gene, harbouring 4 variant DHPLC profiles. The third nucleotide variation (Asp130Glu) was the only substitution present in the coding region of the VAPB gene, and it occurred within exon 4. It was found in three patients out of 125. The frequency of the detected exon variation in the VAPB gene was not significantly different between patients and controls. In conclusion, our study suggests that VAPB mutations are not a common cause of adult-onset SALS.