N-Methyl-D-Aspartate Receptor-Antibody Encephalitis Impairs Maintenance of Attention to Items in Working Memory.

NMDA receptors (NMDARs) may be crucial to working memory (WM). Computational models predict that they sustain neural firing and produce associative memory, which may underpin maintaining and binding information, respectively. We test this in patients with antibodies to NMDAR (n = 10, female) and compare them with healthy control participants (n = 55, 20 male, 35 female). Patients were tested after recovery with a task that separates two aspects of WM: sustaining attention and feature binding. Participants had to remember two colored arrows. Then attention was directed to one of them. After a variable delay, they reported the direction of either the same arrow (congruent cue) or of the other arrow (incongruent cue). We asked how congruency affected recall precision and measured types of error. Patients had difficulty in both sustaining attention to an item over time and feature binding. Controls were less precise after longer delays and incongruent cues. In contrast, patients did not benefit from congruent cues at longer delays [group × congruency (long condition); p = 0.041], indicating they could not sustain attention. Additionally, patients reported the wrong item (misbinding errors) more than controls after congruent cues [group × delay (congruent condition), main effect of group; p ≤ 0.001]. Our results suggest NMDARs are critical for both maintaining attention and feature binding.

Pharmacological interventions for prophylaxis of vestibular migraine.

BACKGROUND: Vestibular migraine is a form of migraine where one of the main features is recurrent attacks of vertigo. These episodes are often associated with other features of migraine, including headache and sensitivity to light or sound. These unpredictable and severe attacks of vertigo can lead to a considerable reduction in quality of life. The condition is estimated to affect just under 1% of the population, although many people remain undiagnosed. A number of pharmacological interventions have been used or proposed to be used as prophylaxis for this condition, to help reduce the frequency of the attacks. These are predominantly based on treatments that are in use for headache migraine, with the belief that the underlying pathophysiology of these conditions is similar. OBJECTIVES: To assess the benefits and harms of pharmacological treatments used for prophylaxis of vestibular migraine. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 23 September 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs in adults with definite or probable vestibular migraine comparing beta-blockers, calcium channel blockers, antiepileptics, antidepressants, diuretics, monoclonal antibodies against calcitonin gene-related peptide (or its receptor), botulinum toxin or hormonal modification with either placebo or no treatment. We excluded studies with a cross-over design, unless data from the first phase of the study could be identified. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were: 1) improvement in vertigo (assessed as a dichotomous outcome - improved or not improved), 2) change in vertigo (assessed as a continuous outcome, with a score on a numerical scale) and 3) serious adverse events. Our secondary outcomes were: 4) disease-specific health-related quality of life, 5) improvement in headache, 6) improvement in other migrainous symptoms and 7) other adverse effects. We considered outcomes reported at three time points: < 3 months, 3 to < 6 months, > 6 to 12 months. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We included three studies with a total of 209 participants. One evaluated beta-blockers and the other two evaluated calcium channel blockers. We did not identify any evidence for the remaining interventions of interest. Beta-blockers versus placebo One study (including 130 participants, 61% female) evaluated the use of 95 mg metoprolol once daily for six months, compared to placebo. The proportion of people who reported improvement in vertigo was not assessed in this study. Some data were reported on the frequency of vertigo attacks at six months and the occurrence of serious adverse effects. However, this is a single, small study and for all outcomes the certainty of evidence was low or very low. We are unable to draw meaningful conclusions from the numerical results. Calcium channel blockers versus no treatment Two studies, which included a total of 79 participants (72% female), assessed the use of 10 mg flunarizine once daily for three months, compared to no intervention. All of the evidence for this comparison was of very low certainty. Most of our outcomes were only reported by a single study, therefore we were unable to conduct any meta-analysis. Some data were reported on improvement in vertigo and change in vertigo, but no information was available regarding serious adverse events. We are unable to draw meaningful conclusions from the numerical results, as these data come from single, small studies and the certainty of the evidence was very low. AUTHORS CONCLUSIONS: There is very limited evidence from placebo-controlled randomised trials regarding the efficacy and potential harms of pharmacological interventions for prophylaxis of vestibular migraine. We only identified evidence for two of our interventions of interest (beta-blockers and calcium channel blockers) and all evidence was of low or very low certainty. Further research is necessary to identify whether these treatments are effective at improving symptoms and whether there are any harms associated with their use.

Non-pharmacological interventions for prophylaxis of vestibular migraine.

BACKGROUND: Vestibular migraine is a form of migraine where one of the main features is recurrent attacks of vertigo. These episodes are often associated with other features of migraine, including headache and sensitivity to light or sound. These unpredictable and severe attacks of vertigo can lead to a considerable reduction in quality of life. The condition is estimated to affect just under 1% of the population, although many people remain undiagnosed. A number of interventions have been used, or proposed to be used, as prophylaxis for this condition, to help reduce the frequency of the attacks. Many of these interventions include dietary, lifestyle or behavioural changes, rather than medication.  OBJECTIVES: To assess the benefits and harms of non-pharmacological treatments used for prophylaxis of vestibular migraine. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 23 September 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs in adults with definite or probable vestibular migraine comparing dietary modifications, sleep improvement techniques, vitamin and mineral supplements, herbal supplements, talking therapies, mind-body interventions or vestibular rehabilitation with either placebo or no treatment. We excluded studies with a cross-over design, unless data from the first phase of the study could be identified.  DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were: 1) improvement in vertigo (assessed as a dichotomous outcome - improved or not improved), 2) change in vertigo (assessed as a continuous outcome, with a score on a numerical scale) and 3) serious adverse events. Our secondary outcomes were: 4) disease-specific health-related quality of life, 5) improvement in headache, 6) improvement in other migrainous symptoms and 7) other adverse effects. We considered outcomes reported at three time points: < 3 months, 3 to < 6 months, > 6 to 12 months. We used GRADE to assess the certainty of evidence for each outcome.  MAIN RESULTS: We included three studies in this review with a total of 319 participants. Each study addressed a different comparison and these are outlined below. We did not identify any evidence for the remaining comparisons of interest in this review.   Dietary interventions (probiotics) versus placebo We identified one study with 218 participants (85% female). The use of a probiotic supplement was compared to a placebo and participants were followed up for two years. Some data were reported on the change in vertigo frequency and severity over the duration of the study. However, there were no data regarding improvement of vertigo or serious adverse events. Cognitive behavioural therapy (CBT) versus no intervention One study compared CBT to no treatment in 61 participants (72% female). Participants were followed up for eight weeks. Data were reported on the change in vertigo over the course of the study, but no information was reported on the proportion of people whose vertigo improved, or on the occurrence of serious adverse events.  Vestibular rehabilitation versus no intervention The third study compared the use of vestibular rehabilitation to no treatment in a group of 40 participants (90% female) and participants were followed up for six months. Again, this study reported some data on change in the frequency of vertigo during the study, but no information on the proportion of participants who experienced an improvement in vertigo or the number who experienced serious adverse events.  We are unable to draw meaningful conclusions from the numerical results of these studies, as the data for each comparison of interest come from single, small studies and the certainty of the evidence was low or very low.  AUTHORS' CONCLUSIONS: There is a paucity of evidence for non-pharmacological interventions that may be used for prophylaxis of vestibular migraine. Only a limited number of interventions have been assessed by comparing them to no intervention or a placebo treatment, and the evidence from these studies is all of low or very low certainty. We are therefore unsure whether any of these interventions may be effective at reducing the symptoms of vestibular migraine and we are also unsure whether they have the potential to cause harm.

Pharmacological interventions for acute attacks of vestibular migraine.

BACKGROUND: Vestibular migraine is a form of migraine where one of the main features is recurrent attacks of vertigo. These episodes are often associated with other features of migraine, including headache and sensitivity to light or sound. The unpredictable and severe attacks of vertigo can lead to a considerable reduction in quality of life. The condition is estimated to affect just under 1% of the population, although many people remain undiagnosed. A number of pharmacological interventions have been used, or proposed to be used, at the time of a vestibular migraine attack to help reduce the severity or resolve the symptoms. These are predominantly based on treatments that are in use for headache migraine, with the belief that the underlying pathophysiology of these conditions is similar.  OBJECTIVES: To assess the benefits and harms of pharmacological interventions used to relieve acute attacks of vestibular migraine. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 23 September 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs in adults with definite or probable vestibular migraine comparing triptans, ergot alkaloids, dopamine antagonists, antihistamines, 5-HT3 receptor antagonists, gepants (CGRP receptor antagonists), magnesium, paracetamol or non-steroidal anti-inflammatory drugs (NSAIDs) with either placebo or no treatment.  DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were: 1) improvement in vertigo (assessed as a dichotomous outcome - improved or not improved), 2) change in vertigo (assessed as a continuous outcome, with a score on a numerical scale) and 3) serious adverse events. Our secondary outcomes were: 4) disease-specific health-related quality of life, 5) improvement in headache, 6) improvement in other migrainous symptoms and 7) other adverse effects. We considered outcomes reported at three time points: < 2 hours, 2 to 12 hours, > 12 to 72 hours. We used GRADE to assess the certainty of evidence for each outcome.  MAIN RESULTS: We included two RCTs with a total of 133 participants, both of which compared the use of triptans to placebo for an acute attack of vestibular migraine. One study was a parallel-group RCT (of 114 participants, 75% female). This compared the use of 10 mg rizatriptan to placebo. The second study was a smaller, cross-over RCT (of 19 participants, 70% female). This compared the use of 2.5 mg zolmitriptan to placebo.  Triptans may result in little or no difference in the proportion of people whose vertigo improves at up to two hours after taking the medication. However, the evidence was very uncertain (risk ratio 0.84, 95% confidence interval 0.66 to 1.07; 2 studies; based on 262 attacks of vestibular migraine treated in 124 participants; very low-certainty evidence). We did not identify any evidence on the change in vertigo using a continuous scale. Only one of the studies assessed serious adverse events. No events were noted in either group, but as the sample size was small we cannot be sure if there are risks associated with taking triptans for this condition (0/75 receiving triptans, 0/39 receiving placebo; 1 study; 114 participants; very low-certainty evidence).  AUTHORS' CONCLUSIONS: The evidence for interventions used to treat acute attacks of vestibular migraine is very sparse. We identified only two studies, both of which assessed the use of triptans. We rated all the evidence as very low-certainty, meaning that we have little confidence in the effect estimates and cannot be sure if triptans have any effect on the symptoms of vestibular migraine. Although we identified sparse information on potential harms of treatment in this review, the use of triptans for other conditions (such as headache migraine) is known to be associated with some adverse effects.  We did not identify any placebo-controlled randomised trials for other interventions that may be used for this condition. Further research is needed to identify whether any interventions help to improve the symptoms of vestibular migraine attacks and to determine if there are side effects associated with their use.