The impact of cerebral vasomotor reactivity on cerebrovascular diseases and cognitive impairment

The regulation of cerebral blood flow (CBF) is a complex and tightly controlled function ensuring delivery of oxygen and nutrients and removal of metabolic wastes from brain tissue. Cerebral vasoreactivity (CVR) refers to the ability of the nervous system to regulate CBF according to metabolic demands or changes in the microenvironment. This can be assessed through a variety of nuclear medicine and imaging techniques and protocols. Several studies have investigated the association of CVR with physiological and pathological conditions, with particular reference to the relationship with cognitive impairment and cerebrovascular disorders (CVD). A better understanding of the interaction between CVR and cognitive dysfunction in chronic and particularly acute CVD could help improving treatment and rehabilitation strategies in these patients. In this paper, we reviewed current knowledge on CVR alterations in the context of acute and chronic CVD and cognitive dysfunction. Alterations in CVR and hemodynamics have been described in patients with both neurodegenerative and vascular cognitive impairment, and the severity of these alterations seems to correlate with CVR derailment. Furthermore, an increased risk of cognitive impairment progression has been associated with alterations in CVR parameters and hemodynamics. Few studies have investigated these associations in acute cerebrovascular disorders and the results are inconsistent; thus, further research on this topic is encouraged

Correlation between Specific Bacterial Groups in the Oral Cavity and the Severity of Halitosis: Any Possible Beneficial Role for Selected Lactobacilli?

Objective: Halitosis is a widespread problem, normally attributable to specific volatile sulphur compounds (VSC) in the breath. The aim of this study was to first relate halitosis with possible gastric infection by Helicobacter pylori and secondly to quantify specific bacterial groups in the oral cavity flora, thus correlating them with VSC concentrations and Proton Pump Inhibitors (PPIs) intake. Four selected lactobacilli were then assessed in the possible reduction of halitosis in subjects with a total salivary bacterial concentration higher than 105 CFU/ml. Methods: Specific bacterial groups, namely total bacteria, total coliforms, sulphite-reducing bacteria (SRB) and lactobacilli, were quantified in samples of saliva from 29 subjects taking PPIs compared with 36 control subjects. The amount of the three VSC hydrogen sulfide (H2S), methyl mercaptan (CH3SH) and dimethyl sulfide (CH3)2S in the breath and the presence of H. pylori were determined. Results: No significant correlation was found between H. pylori and halitosis as well as with PPIs intake. The baseline bacterial groups quantification (log10 CFU/ml of saliva, PPI group vs. control) showed: total bacteria 8.44 vs. 4.47 (p=0.001); total coliforms 4.95 vs. 2.82 (p=0.001); sulfite-reducing bacteria 5.47 vs. 2.58 (p=0.052); total lactobacilli 4.00 vs. 2.36 (p=0.016). After 15 days of lactobacilli supplementation, the same parameters (d15 vs baseline) gave: total bacteria 7.92 vs. 8.44 (p=0.019); total coliforms 3.13 vs. 4.95 (p=0.001); sulfite-reducing bacteria 4.69 vs. 5.47 (p=0.047); total lactobacilli 7.86 vs. 4.00 (p=0.048). No statistically significant differences were noted in VSC concentrations at any time. Conclusions: The intake of PPIs directly correlated with the overgrowth of specific bacterial groups in the oral cavity, but there was no correlation with H. pylori or with VSC concentration. The significant reduction in all the bacterial groups analysed after two weeks suggested the improvement of the overall oral flora in subjects chronically treated with PPIs

Prophylactic Treatment of Pediatric Migraine:Is There Anything New in the Last Decade?

Migraine is a frequent and very disabling disease, especially at pediatric age. Despite this, there are few controlled data on the prophylactic treatment of primary headaches in this category of age. Given that the recently introduced calcitonin gene-related peptide (CGRP) inhibitors (CGRP-r) are still limited to adulthood, there is no drug with exclusive indication for migraine treatment in pediatric age. This raises several limitations in terms of adherence and effectiveness of the therapy. Moreover, the scenario is complicated by placebo response, which is larger in children and adolescents than in adults and often leads to an improvement in the attack frequency even in absence of any active pharmacological treatment. Our aim was to investigate the real evidence concerning the prophylactic therapy of pediatric migraine by reviewing the clinical studies published between 2010 and 2019

Opsoclonus-Myoclonus Syndrome in Children and Adolescents:A Therapeutic Challenge

Opsoclonus-myoclonus syndrome (OMS) is a neurological non-fatal disease that usually responds to immunotherapies. However, the real challenge is to counteract the high frequency of relapses and long-term developmental sequelae. Since the OMS is extremely rare, a common consensus regarding therapeutic guidelines is still lacking. The goals of this study were to test whether ACTH was superior to other immunotherapies and to investigate whether an early treatment could improve the outcome. Sixteen children affected by OMS were retrospectively reviewed. Eight children had a neuroblastic tumor. The other eight patients were affected by non-paraneoplastic OMS. Overall, the most commonly used treatment was corticotherapy (n = 11). However, ACTH (n = 10), rituximab (n = 7), immunoglobulins (n = 4), cyclophosphamide (n = 3), and mycophenolate (n = 2) were also administered. ACTH was associated with a high percentage of patients who healed (80%) and, as a first-line therapy, was associated with a lower incidence of relapses. An early treatment was associated with a favorable long-term outcome. Long-term sequelae occurred in 42% of patients who were treated early and in all of those who were treated late. It is advisable for the affected children to be identified at an early time, as they may benefit from an early treatment. ACTH represents an effective treatment with a high probability of recovery and low rate of relapses

Medication Overuse Withdrawal in Children and Adolescents Does Not Always Improve Headache:A Cross-Sectional Study

Background:MOH can be diagnosed in subjects with headache occurring 15 days/month in association with a regular medication overuse, but its existence is not universally accepted. ICHD-3 redefined criteria for MOH, removing the criterion associating drug suspension with headache course. The aim of our study was to compare the rate of patients diagnosed with medication overuse headache (MOH) according to ICHD-2 and ICHD-3 criteria, to verify the degree of concordance. The secondary aim was to verify if drug withdrawal was really associated with pain relief. Methods:In this cross-sectional study, we retrospectively analyzed a sample of 400 patients followed for primary chronic headache at the Headache Center of Bambino Gesu Children's Hospital. We then selected those presenting with a history of medication overuse, and we applied both ICHD-2 and ICHD-3 criteria to verify in which patients the criteria would identify a clinical diagnosis of MOH. Results:We identified 42 subjects (10.5%) with MOH; 23 of them (55%) presented a relief of headache withdrawing drug overuse. Regarding the applicability of the ICHD-2 criteria, 43% of patients (18/42) fulfilled all criteria, while all ICHD-3 diagnostic criteria were satisfied in 76% of patients (32/42). Eighteen patients (43%) satisfied both ICHD-2 and ICHD-3 criteria, while 10 patients (24%) did not satisfy either diagnostic criterion. Conclusions:Our study suggests that in children and adolescents, withdrawing medication overuse is not always associated with a clinical benefit. Therefore, though allowing a MOH diagnosis in a higher rate of patients as compared to ICHD-2, the application of ICHD-3 criteria does not guarantee a true a causal relationship between medication overuse and headache worsening

Case report:A pediatric case of Bickerstaff brainstem encephalitis after COVID-19 vaccination and Mycoplasma pneumoniae infection: Looking for the culprit

Bickerstaff brainstem encephalitis (BBE) is a rare, immune-mediated disease characterized by the acute onset of external ophthalmoplegia, ataxia, and consciousness disturbance. It has a complex multifactorial etiology, and a preceding infectious illness is seen in the majority of cases. Immune-mediated neurological syndromes following COVID-19 vaccination have been increasingly described. Here we report the case of a child developing BBE 2 weeks after COVID-19 vaccination. Despite nerve conduction studies and CSF analysis showing normal results, BBE was diagnosed on clinical ground and immunotherapy was started early with a complete recovery. Later, diagnosis was confirmed by positive anti-GQ1b IgG in serum. Even if there was a close temporal relationship between disease onset and COVID-19 vaccination, our patient also had evidence of a recent Mycoplasma pneumoniae infection that is associated with BBE. Indeed, the similarity between bacterial glycolipids and human myelin glycolipids, including gangliosides, could lead to an aberrantly immune activation against self-antigens (i.e., molecular mimicry). We considered the recent Mycoplasma pneumoniae infection a more plausible explanation of the disease onset. Our case report suggests that suspect cases of side effects related to COVID-19 vaccines need a careful evaluation in order to rule out well-known associated factors before claiming for a causal relationship

From the New Diagnostic Criteria to COVID-19 Pandemic Passing Through the Placebo Effect. What Have We Learned in the Management of Pediatric Migrane Over the Past 5 Years?

In 2018, the Food and Drug Administration (FDA) approval of anti-calcitonin gene-related peptide (CGRP) therapies for the treatment of migraine represented a milestone for the management of the disease in adults. On the contrary, the novelties in the field of pediatric migraine are inserted in a different scenario and still concern: (1) diagnostic criteria of the international classification of headache disorders-3 (ICHD-3) that show numerous limits of applicability in the developmental age; (2) the release of the results of the Childhood and Adolescent Migraine Prevention (CHAMP) study that raised doubts about the usefulness of traditional drugs for the treatment of pediatric migraine; (3) the Coronavirus disease 2019 (COVID-19) pandemic has put the spotlight on the importance of managing the psychological factors associated with the disease. In this mini review we discuss the most relevant news in pediatric migraine over the last 5 years

Anxiety, Depression, and Body Weight in Children and Adolescents With Migraine

Background: There is a lack of studies that explore the possible association between body weight, psychological symptoms, and migraine severity in pediatric populations. The purpose of the study was to explore: (1) the association between body weight and the frequency of migraine attacks, (2) the possible differences in anxiety and depression symptoms according to the frequency of attacks and body weight, and (3) the possible mediating role of anxiety and/or depression in the association between body weight and frequency of migraine attacks in children.Methods: One hundred and eleven children/adolescents with migraine were included (47 boys and 64 girls; mean age 11.7; +/- 2.4 years). The patients were classified as: (1) high frequency patients, reporting from weekly to daily episodes and (2) low frequency patients, with <= 3 episodes per month. According to their body mass index percentiles, the patients were divided in "Normal weight" (from >= 5 to <85 percentile), "Overweight" (from >= 85 to <95 percentile), and "Obese" (>= 95 percentile). Given the low number of obese patients, the overweight and obese groups were considered together in the "Overweight" group. Anxiety and depression symptoms were assessed by the Self-Administered Psychiatric Scales for Children and Adolescents (SAFA).Results: Fifty-four patients were normal in weight (49.6%), while 56 patients (50.4%) were overweight. The overweight patients showed a higher frequency of migraine attacks (64.7%; p < 0.05). Patients with a high frequency of attacks reported higher scores in all SAFA-Anxiety subscales (SAFA-A Tot: F = 15.107; p = 0.000). Overweight patients showed a significantly higher score in the "Separation anxiety" subscale (F = 7.855; p = 0.006). We found a mediating role between the overweight and high frequency for total anxiety (z = 2.11 +/- 0.03; p < 0.05) and social anxiety (z = 2.04 +/- 0.03; p < 0.05).Conclusions: Our results suggest that, among the children suffering from migraine, the overweight status is associated with a higher frequency of attacks and separation anxiety symptoms. In particular, our study provides the first evidence of the role of anxiety in linking overweight and the frequency of migraine attacks in children and adolescents