Clinical features, disease progression, and use of healthcare resources in a large sample of 866 patients from 24 headache centers: A real-life perspective from the Italian chROnic migraiNe (IRON) project.

OBJECTIVE: To develop a dedicated Italian chronic migraine (CM) database (IRON project) to overcome disease misconceptions, improve clinical administration, reduce patients' burden, and rationalize economic resource allotment. BACKGROUND: Proper CM management requires a comprehensive appraisal of its full clinical, social, and economic complexity. METHODS: In this cross-sectional study, CM patients were screened in 24 certified headache centers with face-to-face interviews. Information on sociodemographic factors, medical history, characteristics of CM, and of prior episodic migraine (EM), and healthcare resource use was gathered using a semistructured web-based questionnaire. RESULTS: A total of 866 CM patients were enrolled. CM started ~20 years after EM onset (age at EM onset 17.4 ± 9.1 vs. age at CM onset 35.3 ± 12.5 [mean ± SD]). CM prophylaxis, used by 430/866 (49.6%) of the patients, was often ineffective, not tolerated, and prematurely discontinued. Medications and diagnostic workup, frequently inappropriate, were mostly subsidized by the Italian national health service. CM patients with ≥25 headache days/month revealed substantial clinical differences and heavier disability and economic burden compared with those with <25 headache days/month. CONCLUSIONS: CM is a heterogeneous headache disorder deserving more in-depth clinical characterization, sharper diagnostic criteria, and tailored treatments. CM registries are expected to improve clinical management, resulting in increased disease awareness, better healthcare resource allocation, and reduced economic burden.

Isolated, Subtle Neurological Abnormalities in Mild Cognitive Impairment Types.

BACKGROUND: Isolated, subtle neurological abnormalities (ISNA) are commonly seen in aging and have been related to cerebral small vessel disease (SVD) and subcortical atrophy in neurologically and cognitively healthy aging subjects. OBJECTIVE: To investigate the frequency of ISNA in different mild cognitive impairment (MCI) types and to evaluate for each MCI type, the cross-sectional relation between ISNA and white matter hyperintensities (WMH), lacunes, caudate atrophy, and ventricular enlargement. METHODS: One thousand two hundred fifty subjects with different MCI types were included in the analysis and underwent brain magnetic resonance imaging. WMHs were assessed through two visual rating scales. Lacunes were also rated. Atrophy of the caudate nuclei and ventricular enlargement were assessed through the bicaudate ratio (BCr) and the lateral ventricles to brain ratio (LVBr), respectively. Apolipoprotein E (APOE) genotypes were also assessed. The routine neurological examination was used to evaluate ISNAs that were clustered as central-based signs, cerebellar-based signs, and primitive reflexes. The items of Part-III of the Unified Parkinson's Disease Rating Scale were used to evaluate ISNAs that were clustered as mild parkinsonian signs. Associations of ISNAs with imaging findings were determined through logistic regression analysis. RESULTS: The ISNAs increase with the age and are present in all MCI types, particularly in those multiple domains, and carrying the APOE ϵ4 allele, and are associated with WMH, lacunes, BCr, and LVBr. CONCLUSION: This study demonstrates that cortical and subcortical vascular and atrophic processes contribute to ISNAs. Long prospective population-based studies are needed to disentangle the role of ISNAs in the conversion from MCI to dementia.

Des anomalies neurologiques subtiles et isolées associées à différents types de déficience cognitive légère. Contexte: Des anomalies neurologiques à la fois subtiles et isolées sont fréquemment observées chez les personnes vieillissantes. Elles ont été associées à la maladie des petits vaisseaux du cerveau (cerebral small vessel disease) et à une atrophie des structures sous-corticales chez des sujets âgés en santé sur les plans neurologique et cognitif. Objectif: Étudier la fréquence de ces anomalies dans le cas de différents types de déficience cognitive légère ; évaluer, pour chaque type de déficience, la relation transversale entre ces anomalies et des hyper-signaux de la substance blanche, des lacunes cérébrales, l'atrophie du noyau caudé et l'élargissement des ventricules. Méthodes: Au total, 1250 sujets atteints de différents types de déficience cognitive légère ont été inclus dans notre analyse et ont passé un examen d'IRM du cerveau. On a évalué les hyper-signaux de la substance blanche à l'aide de deux échelles d'évaluation visuelle. À noter que les lacunes cérébrales ont également été évaluées. Du côté de l'atrophie du noyau caudé et de l'élargissement des ventricules, ces anomalies ont été mesurées respectivement au moyen de l'index bicaudé (bicaudate ratio) et du ratio volumique ventricule-cerveau (lateral ventricles to brain ratio). Enfin, les génotypes associés à l'apolipoprotéine E (ApoE) ont été examinés. Fait à souligner, des examens neurologiques de routine portant sur les signes du système nerveux central, sur les signes du cervelet et sur les réflexes archaïques ont été utilisés pour tenter de cerner les anomalies évoquées ci-dessus. Des éléments de la partie III de l'échelle UPDRS (Unified Parkinson's Disease Rating Scale) ont été par ailleurs mis à profit pour évaluer les anomalies regroupées au sein de la catégorie des signes bénins de la maladie de Parkinson. Les liens entre ces anomalies et les résultats aux examens d'IRM ont été déterminés à l'aide d'une analyse de régression logistique. Résultats: Ces anomalies neurologiques à la fois subtiles et isolées augmentent en fonction de l'âge et sont présentes parmi tous les types de déficience cognitive légère, en particulier dans ces domaines multiples et chez les sujets porteurs de l'allèle ϵ4 du gène de l'ApoE. On a vu également qu'elles sont associées à des hyper-signaux de la substance blanche, à des lacunes cérébrales, à l'atrophie du noyau caudé et à l'élargissement des ventricules. Conclusion: Cette étude démontre que les processus vasculaires et atrophiques des structures corticales et sous-corticales contribuent à l'apparition d'anomalies neurologiques à la fois subtiles et isolées. Des études prospectives de longue haleine basées sur la population sont toutefois nécessaires pour mieux comprendre le rôle de ces anomalies dans l'évolution des cas de déficience cognitive légère vers la démence.

Nociceptive Primitive Reflexes in Neurologically and Cognitively Healthy Aging Subjects.

BACKGROUND: To assess the prevalence of three nociceptive primitive reflexes (nPR), i.e., glabellar tap, snout reflex, and palmomental reflex, in neurologically and cognitively healthy (NCH) aging subjects. OBJECTIVE: To investigate whether nPR are cross-sectionally associated with white matter hyperintensities (WMH), lacunes, atrophy of the caudate nuclei, and global brain atrophy. METHODS: A total of 1246 NCH subjects aged 45-91 years were included in the study and underwent standard brain MRI. Atrophy of the caudate nuclei and global brain atrophy were assessed through the bicaudate ratio (BCr) and lateral ventricles to brain ratio (LVBr), respectively. WMH were assessed through visual rating scales. Lacunes were also rated. Association of nPR with vascular risk factors/diseases and imaging findings was evaluated using logistic regression analysis. RESULTS: nPR were exhibited by 33.1% of subjects and increased with age. Subjects with nPR performed less than subjects without nPR in tests evaluating global cognition, executive functions, attention, and language. Snout reflex was the most common nPR, followed by glabellar tap and palmomental reflex. Glabellar tap was associated with parieto-temporal WMH, BCr, and LVBr; snout reflex was associated with frontal lacunes, temporal WMH, BCr, and LVBr; palmomental reflex was associated with parieto-occipital WMH, basal ganglia lacunes, BCr, and LVBr. CONCLUSIONS: This study demonstrates that in NCH aging individuals, nPR are associated with WMH, lacunes, BCr, and LVBr and are probably a warning sign of incipient cognitive decline. Therefore, NCH subjects presenting nPR should manage their vascular risk factors/vascular diseases rigorously in order to prevent or delay progression of small vessel disease, and future neurological and cognitive disabilities.

Cluster headache in relation to different age groups.

Cluster headache (CH) has always been considered a type of primary headache affecting predominantly male subjects in early and medium adulthood. However, recent studies carried out in large case series of patients with CH show that not infrequently it may set in also after age 50; by contrast, onset before adolescence is very rare. Additionally, when onset occurs before age 14 or from the sixth decade of life onward, male predominance decreases to the point that in chronic forms CH predominantly affects the female sex. This particular pattern of the gender ratio in relation to onset in different age groups suggests that hormonal factors may actually play a role in the genesis of CH. In particular, future studies should be aimed at investigating the possible protective role of estrogen.

The Clinical Relevance of Artificial Intelligence in Migraine.

Migraine is a burdensome neurological disorder that still lacks clear and easily accessible diagnostic biomarkers. Furthermore, a straightforward pathway is hard to find for migraineurs' management, so the search for response predictors has become urgent. Nowadays, artificial intelligence (AI) has pervaded almost every aspect of our lives, and medicine has not been missed. Its applications are nearly limitless, and the ability to use machine learning approaches has given researchers a chance to give huge amounts of data new insights. When it comes to migraine, AI may play a fundamental role, helping clinicians and patients in many ways. For example, AI-based models can increase diagnostic accuracy, especially for non-headache specialists, and may help in correctly classifying the different groups of patients. Moreover, AI models analysing brain imaging studies reveal promising results in identifying disease biomarkers. Regarding migraine management, AI applications showed value in identifying outcome measures, the best treatment choices, and therapy response prediction. In the present review, the authors introduce the various and most recent clinical applications of AI regarding migraine.

Beyond Pain: The Effects of OnabotulinumtoxinA Therapy on Sensitization and Interictal Symptoms in Chronic Migraine.

Chronic migraine is a disease with a high burden on patients from both a working and quality of life point of view. The pathophysiology of this subtype of migraine is due to several factors, such as medication overuse. Nevertheless, the detrimental recurring of headache attacks with central and peripheral sensitization plays a central role and explains some additional symptoms complained about by these patients even in the interictal phase. OnabotulinumtoxinA is a therapy indicated for chronic migraine since it has proven to reduce peripheral sensitization, showing even efficacy on central symptoms. The aim of this narrative review is to present the current evidence regarding the effect of OnabotulinumtoxinA on sensitization and interictal symptoms.

Insomnia and Migraine: A Missed Call?

Migraine is one of the most prevalent and disabling neurological conditions, presenting episodes of throbbing headache that limit activities of daily living. Several factors may influence migraine frequency, such as lifestyle or alcohol consumption. Among the most recognised ones, sleep plays a biunivocal role, since poor sleep quality may worsen migraine frequency, and a high migraine frequency may affect sleep quality. In this paper, the authors evaluate the relationship between migraine and insomnia by exploring a cohort of patients affected by episodic or chronic migraine. To do so, a phone interview was performed, asking patients about their migraine frequency and mean pain intensity, in addition to the questions of the Insomnia Severity Index. The last one explores several symptoms impairing sleep that focus on insomnia. Patients complaining of insomnia showed an increased migraine frequency, and a weak but significant correlation was found between headache days per month and insomnia scores. Such results were particularly evident in patients affected by chronic migraine. Such results suggest how insomnia, in the presented data, seems to be associated with migraine frequency but not with pain intensity.

Assessing the Long-Term (48-Week) Effectiveness, Safety, and Tolerability of Fremanezumab in Migraine in Real Life: Insights from the Multicenter, Prospective, FRIEND3 Study.

INTRODUCTION: Long-term (1-year) fremanezumab treatment proved to be effective, safe, and well tolerated in individuals with migraine and < 2 medication clusters in a randomized controlled trial (RCT). We aimed to assess real-world evidence (RWE), long-term effectiveness, tolerability, and safety of fremanezumab in people with high-frequency episodic migraine (HFEM) or chronic migraine (CM) with > 3 treatment failures and various comorbidities. METHODS: A 48-week, prospective, multicenter (n = 26), cohort study assessed fremanezumab's effectiveness, safety, and tolerability in consecutive adults with HFEM or CM with > 3 treatment failures. Primary endpoint was variation from baseline in monthly migraine days (MMD) in HFEM and monthly headache days (MHD) in CM at weeks 45-48. Secondary endpoints were changes in monthly analgesic medications, Numerical Rating Scale (NRS), Headache Impact Test (HIT-6), and the Migraine Disability Assessment Scale (MIDAS) scores and ≥ 50%, ≥ 75%, and 100% responder rates. RESULTS: Of 533 participants who had received ≥ 1 fremanezumab dose, 130 were treated for ≥ 48 weeks and considered for effectiveness analysis. No participant missed any treatment dosage every other consecutive month during the 12-month period. PRIMARY ENDPOINT: fremanezumab significantly (p < 0.001) reduced both MMD (- 6.4) in HFEM and MHD (- 14.5) in CM. Secondary endpoints: a significant reduction (p < 0.001) was observed in monthly analgesic medications (HFEM - 6.0; CM -16.5), NRS (HFEM - 3.4; CM - 3.4), HIT-6 (HFEM - 16.9; CM - 17.9) and MIDAS score (HFEM - 50.4; CM - 76.6). The ≥ 50%, ≥ 75%, and 100% response rates to fremanezumab were 75.5%, 36.7%, and 2% in HFEM and 71.6%, 44.4%, and 3.7% in CM. Corresponding response rates were 60.5%, 37.2%, and 2.3% in individuals with psychiatric comorbidities, 74.2%, 50%, and 4.8% in CM with medication overuse, and 60.9%, 39.1%, and 4.3% in CM with medication overuse and psychiatric comorbidities. Mild and transient treatment-emergent adverse events occurred in 7.8% of the participants. No subject discontinued the treatment for any reason. CONCLUSION: This RWE study documents that long-term fremanezumab treatment is highly effective and remarkably well tolerated in subjects with HFEM or CM with multiple (> 3) therapeutic failures, even in the presence of concomitant medication overuse, psychiatric comorbidities, or both. The effectiveness-to-tolerability ratio appears to be better in RWE than in RCTs.

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.

Erenumab and Possible CGRP Effect on Chronotype in Chronic Migraine: A Real-Life Study of 12 Months Treatment.

The introduction of monoclonal antibodies (mAbs) directed against the calcitonin gene-related peptide (CGRP), or its receptor (CGRPr), revolutionized migraine management due to their high efficacy and few side effects. Data suggest that the CGRP may even be implicated in circadian rhythm, but studies about the effect of anti-CGRP treatments on sleep are still lacking. The aim of the present study was to assess the effect of erenumab (70 and 140 mg per month), a human mAb directed against CGRPr, on chronotype in chronic migraineurs; secondly, we assessed its efficacy, safety, and the effects on anxiety and depression. Sleep was evaluated using self-administrable questionnaires investigating chronotype, sleep quality, and daytime sleepiness. Migraine diaries and several self-administrable questionnaires regarding headache impact and psychological correlates were evaluated every 3 months during 12 months of treatment. Eighty-eight patients were included; most of them showed a significant reduction in headache frequency and an improvement in psychological symptoms. Moreover, an initial change in chronotype was observed at the three-month assessment from a morning chronotype to an intermediate one; a similar trend remained in the other evaluations, even if it did not reach a statistical significance. Lastly, patients who responded to the treatment showed a progressive sleep efficiency reduction. The present real-life study hypothesized the influence of erenumab on chronotype, representing a link between circadian rhythm, CGRP, and migraine.

Sleep and Chronobiology as a Key to Understand Cluster Headache.

The cluster headache is a primary headache characterized by attacks of unilateral pain associated with ipsilateral cranial autonomic features. These attacks recur in clusters during the years alternating with periods of complete remission, and their onset is often during the night. This annual and nocturnal periodicity hides a strong and mysterious link among CH, sleep, chronobiology and circadian rhythm. Behind this relationship, there may be the influence of genetic components or of anatomical structures such as the hypothalamus, which are both involved in regulating the biological clock and contributing even to the periodicity of cluster headaches. The bidirectional relationship manifests itself also with the presence of sleep disturbances in patients affected by cluster headaches. What if the key to studying the physiopathology of such disease could rely on the mechanisms of chronobiology? The purpose of this review is to analyze this link in order to interpret the pathophysiology of cluster headaches and the possible therapeutic implications.

Effects of a Single Session of OnabotulinumtoxinA Therapy on Sleep Quality and Psychological Measures: Preliminary Findings in a Population of Chronic Migraineurs.

Chronic migraine is a burdensome condition, and onabotulinumtoxinA is revealed to be an effective therapy. Migraine shows a bidirectional relationship with sleep, but the effects of preventive therapies on sleep quality are poorly studied. This study aims to evaluate the effects of a single session of onabotulinumtoxinA on patients' sleep quality and correlates the results with measures of comorbid anxiety/depression. Patients completed self-administrable questionnaires about sleep quality (Pittsburgh Sleep Quality Index-PSQI) and psychological symptoms (Beck Depression Inventory, 2nd edition-BDI-II-and Hospital Anxiety and Depression Scale-HADS-subscales "a" and "d" for anxiety and depression, respectively), and reported migraine frequency at baseline and after 12 weeks. The 42 included patients showed a significant reduction in migraine days (from 20.6 ± 6.0 to 13.6 ± 6.2, p < 0.001), while no changes were observed in sleep quality (PSQI score from 11.0 ± 5.0 to 9.8 ± 4.6, p = 0.277) or psychological measures (BDI-II from 16.7 ± 10.2 to 15.7 ± 10.3, p = 0.678; HADS-a from 10.3 ± 4.8 to 9.3 ± 5.5, p = 0.492; and HADS-d from 7.2 ± 3.9 to 7.1 ± 5.0, p = 0.901). On the other hand, a strong correlation among PSQI, BDI-II, HADS-a, and HADS-d scores (p < 0.001, rho > 0.7) was found. Despite its efficacy in migraine prevention, a single session of onabotulinumtoxinA was not able to affect patients' sleep quality or their psychological symptoms.

New-onset headache following COVID-19: An Italian multicentre case series.

OBJECTIVE: To describe the characteristics of patients with new-onset headache following SARS-CoV-2 infection. BACKGROUND: SARS-CoV-2 infection leads to several neurological manifestations, and headache is a frequent and disabling symptom, both exacerbating pre-existing headache syndromes and causing new-onset ones. METHODS: Patients with new-onset headache after SARS-CoV-2 infection with consent to participate were included, while those ones with previous headaches were excluded. The temporal latency of headache after infection, pain characteristics, and concomitant symptoms were analysed. Moreover, the efficacy of acute and preventive medications was explored. RESULTS: Eleven females (median age 37.0 [10.0-60.0] years old) were included. In most cases, headache onset occurred with the infection, the location of pain varied, and the quality was either pulsating or tightening. Headache was persistent and daily in 8 patients (72.7%), while it occurred in episodes in the remaining subjects. Baseline diagnoses were new daily persistent headache (36.4%), probable new daily persistent headache (36.4%), probable migraine (9.1%), and migraine-like headache secondary to COVID-19 (18.2%). Ten patients received one or more preventive treatments and six of them showed an improvement. CONCLUSION: New-onset headache following COVID-19 is a heterogenous condition with uncertain pathogenesis. This type of headache can become persistent and severe, with a wide spectrum of manifestations (new daily persistent headache being the most represented one) and variable response to treatment.

The PACE study: past-year prevalence of migraine in Parma's adult general population.

BACKGROUND: In the literature there are few data about the prevalence of primary headaches, including migraine, in the Italian general population. The PACE study (PArma CEfalea, or 'Headache in Parma') is an observational study aimed at detecting the prevalence and clinical features of primary headaches in the city of Parma's adult general population. MATERIALS AND METHODS: A total of 904 subjects representative of Parma's adult general population were interviewed face-to-face by a physician from the Parma Headache Centre. They were given a specially designed and validated questionnaire for the diagnosis of primary headaches according to the ICHD-II criteria. RESULTS: Past-year adjusted prevalence of definite migraine, including migraine with and without aura and chronic migraine, was 24.7% (95% CI 21.9 to 27.5); 13% (95% CI 9.7 to 16.4) were men and 32.9% (95% CI 28.8 to 37.0) were women. Past-year prevalence of probable migraine was 5.1% (95% CI 3.6 to 6.5): 5.2% (95% CI 3.0 to 7.4) in men and 5% (95% CI 3.1 to 6.9) in women. CONCLUSIONS: The high prevalence of definite migraine is the major difference between our results and the literature data. Such a difference in results may be due to the use of a different investigational approach compared with the other epidemiological studies. However, an actual higher frequency of migraine in the Italian general population cannot be excluded given the lack of studies on this topic.

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.

OnabotulinumtoxinA Modulates Visual Cortical Excitability in Chronic Migraine: Effects of 12-Week Treatment.

Chronic migraine is a burdensome disease presenting with episodic pain and several symptoms that may persist even among headache attacks. Multisensory integration is modified in migraine, as assessed by the level of the perception of sound-induced flash illusions, a simple paradigm reflecting changes in cortical excitability which reveals to be altered in migraineurs. OnabotulinumtoxinA is an effective preventive therapy for chronic migraineurs, reducing peripheral and central sensitization, and may influence cortical excitability. Patients affected by chronic migraine who started onabotulinumtoxinA preventive therapy were included. Clinical effects (headache diaries and migraine related questionnaires) were assessed at the beginning of the therapy and after 12 weeks. Contextually, patients underwent the evaluation of multisensory perception by means of the sound-induced flash illusions. OnabotulinumtoxinA showed effectiveness both in migraine prevention and in reducing headache burden. Even one session of therapy was able to restore, at least partially, multisensory processing, as shown by patients' susceptibility to the sound-induced flash illusion. OnabotulinumtoxinA could influence migraineurs cortical excitability concurrently to the beneficial effects in headache prevention.

Activation-Induced Rigidity in Neurologically and Cognitively Healthy Individuals Aged 18-90 Years: A Cross-Sectional Study.

BACKGROUND: Rigidity is a key clinical feature of Parkinson's disease (PD), but in a very early phase of the disease it may be absent and can be enhanced through active movements of the arm contralateral to the one being tested. OBJECTIVE: To evaluate in a large cohort of neurologically and cognitively healthy (NCH) subjects aged 18-90 years if activation-induced rigidity (AR) is present in all age classes, and if there are biological differences between subjects showing AR (AR+) and not showing AR (AR-). METHODS: 2,228 NCH subjects categorized as young adult (18-44 years), adult (45-64 years), elderly (65-74 years), and old/oldest-old (75-90 years) were included in the analysis, and underwent brain MRI. White matter hyperintensities were assessed through two visual rating scales. Lacunes were also rated. Atrophy of the caudate nuclei and ventricular enlargement were assessed through the bicaudate ratio and the lateral ventricles to brain ratio. To elicit AR, the Froment's maneuver (FM) and the instructions of the UPDRS-ME were used. RESULTS: Among the sample, 1,689 (75.81%) subjects showed AR, of which 1,270 (57.00%) subjects showed AR by using FM, and 419 (18.81%) showed AR by using UPDRS-ME instructions. The latter subjects also showed AR by using FM. The number of AR+ subjects significantly increased with increasing age, regardless of the activation maneuver used. In each age class, the number of AR+ subjects was significantly higher by using the FM than the UPDRS-ME instructions. CONCLUSION: Our findings suggest that AR is likely to be one of the signs of the prodromal phase of PD.

APOE Genotypes and Brain Imaging Classes in Normal Cognition, Mild Cognitive Impairment, and Alzheimer's Disease: A Longitudinal Study.

OBJECTIVE: To evaluate in 419 stroke-free cognitively normal subjects (CN) aged 45-82 years covering during a long prospective study (11.54 ± 1.47 years) the preclinical to dementia spectrum: 1) the distribution of small vessel disease (V) and brain atrophy (A) aggregated as following: V-/A-, V-/A+, V+/A-, V+/A+; 2) the relationship of these imaging classes with individual apolipoprotein E (APOE) genotypes; 3) the risk of progression to Alzheimer Disease (AD) of the individual APOE genotypes. METHODS: Participants underwent one baseline (t0), and 4 clinical and neuropsychological assessments (t1,t2,t3, and t4). Brain MRI was performed in all subjects at t0, t2, t3 and t4.. White matter hyperintensities were assessed through two visual rating scales. Lacunes were also rated. Subcortical and global brain atrophy were determined through the bicaudate ratio and the lateral ventricle to brain ratio, respectively. APOE genotypes were determined at t0 in all subjects. Cox proportional hazard model was used to evaluate the risk of progression to AD. RESULTS: The imaging class of mixed type was very common in AD, and in non amnestic mild cognitive impaired APOE ε4 non carriers. In these subjects, frontal and parieto-occipital regions were most affected by small vessel disease. CONCLUSION: Our findings suggest that the APOE ε3 allele is probably linked to the brain vascular pathology.

Mild Parkinsonian Signs in a Hospital-based Cohort of Mild Cognitive Impairment Types: A Cross-sectional Study.

BACKGROUND: Mild Parkinsonian Signs (MPS) have been associated with Mild Cognitive Impairment (MCI) types with conflicting results. OBJECTIVE: To investigate the association of individual MPS with different MCI types using logistic ridge regression analysis, and to evaluate for each MCI type, the association of MPS with caudate atrophy, global cerebral atrophy, and the topographical location of White Matter Hyperintensities (WMH), and lacunes. METHODS: A cross-sectional study was performed among 1,168 subjects with different types of MCI aged 45-97 (70,52 ± 9,41) years, who underwent brain MRI. WMH were assessed through two visual rating scales. The number and location of lacunes were also rated. Atrophy of the caudate nuclei and global cerebral atrophy were assessed through the bicaudate ratio, and the lateral ventricles to brain ratio, respectively. Apolipoprotein E (APOE) genotypes were also assessed. Using the items of the motor section of the Unified Parkinson's Disease Rating Scale, tremor, rigidity, bradykinesia, and gait/balance/axial dysfunction were evaluated. RESULTS: Bradykinesia, and gait/balance/axial dysfunction were the MPS more frequently encountered followed by rigidity, and tremor. MPS were present in both amnestic and non-amnestic MCI types, and were associated with WMH, lacunes, bicaudate ratio, and lateral ventricles to brain ratio. CONCLUSION: MPS are present in both amnestic and non-amnestic MCI types, particularly in those multiple domain, and carrying the APOE ε4 allele. Cortical and subcortical vascular and atrophic processes contribute to MPS. Long prospective studies are needed to disentangle the contribution of MPS to the conversion from MCI to dementia.

Chronic paroxysmal hemicrania and hemicrania continua responding to topiramate: two case reports.

Chronic paroxysmal hemicrania (CPH) is a rare primary headache syndrome, which is classified along with cluster headache and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing as a trigeminal autonomic cephalalgia (TACs). Hemicrania continua (HC) was previously classified as one of the TACs, but in the recent second classification of the International Headache Society this disorder was moved to the group of other primary headaches. Both CPH and HC are characterised by moderate to excruciating pain requiring pharmacological treatment; furthermore, both conditions are characterised by an absolute response to indomethacin, which represents one of the current diagnostic criteria for these two syndromes. Unfortunately, in about one-fourth of cases treatment with indomethacin may cause adverse events, mostly gastrointestinal. We report one subject with CPH and another with HC intolerant to indomethacin, who responded remarkably well to topiramate.