Cognitive outcomes after focused ultrasound thalamotomy for tremor: Results from the COGNIFUS (COGNitive in Focused UltraSound) study.

INTRODUCTION: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is an innovative method for the unilateral treatment of essential tremor (ET) and Parkinson's disease (PD) related tremor. Our aim was to assess cognitive changes following MRgFUS thalamotomy to better investigate its safety profile. METHODS: We prospectively investigated the cognitive and neurobehavioral profile of patients consecutively undergoing MRgFUS within a 2-year period. Patients had a comprehensive clinical and neuropsychological assessment before and six months after MRgFUS thalamotomy. RESULTS: The final sample consisted of 40 patients (males 38; mean age±SD 67.7 ± 10.7; mean disease duration±SD 9.3 ± 5.6; ET 22, PD 18 patients). For the whole sample, improvements were detected in tremor (Fahn-Tolosa-Marin Clinical Rating Scale for tremor 35.79 ± 14.39 vs 23.03 ± 10.95; p < 0.001), anxiety feelings (Hamilton Anxiety rating scale 5.36 ± 3.80 vs 2.54 ± 3.28, p < 0.001), in the overall cognitive status (MMSE 25.93 ± 3.76 vs 27.54 ± 2.46, p 0.003; MOCA 22.80 ± 4.08 vs 24.48 ± 3.13, p < 0.001), and in quality of life (Quality of life in Essential Tremor Questionnaire 36.14 ± 12.91 vs 5.14 ± 6.90, p < 0.001 and PD Questionnaire-8 5.61 ± 4.65 vs 1.39 ± 2.33, p 0.001). No changes were detected in frontal and executive functions, verbal fluency and memory, abstract reasoning and problem-solving abilities. CONCLUSION: Our study moves a step forward in establishing the cognitive sequelae of MRgFUS thalamotomy and in endorsing effectiveness and safety.

Use of Non-pharmacological Therapies in Individuals With Migraine Eligible for Treatment With Monoclonal Antibodies Targeting Calcitonin Gene-Related Peptide (CGRP)-Signaling: A Single-Center Cross-Sectional Observational Study.

Introduction: Accessibility of treatment with monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) signaling pathway is impeded by regulatory restrictions. Affected individuals may seek out other services including non-pharmacological therapies. Thus, we found it timely to ascertain the use of non-pharmacological therapies in individuals with treatment-resistant migraine eligible for and naïve to treatment with CGRP-signaling targeting monoclonal antibodies. Methods: We conducted a single-center cross-sectional observational study of patients eligible for and naïve to treatment with monoclonal antibodies targeting CGRP or its receptor. We recorded demographical information (gender, age, educational level, employment status, and income), disease burden (frequency of headache days and migraine days), previous use of preventive pharmacological medications for migraine, and use of non-pharmacological therapies over the past 3 months including frequency of interventions, costs, and patient-reported assessment of efficacy on a 6-point scale (0: no efficacy, 5: best possible efficacy). Results: We included 122 patients between 17 June 2019 and 6 January 2020; 101 (83%) were women and the mean age was 45.2 ± 13.3 years. One-third (n = 41 [34%]) had used non-pharmacological therapy within the past 3 months. Among these participants, the median frequency of different interventions was 1 (IQR: 1-2), the median number of monthly visits was 2.3 (IQR: 1.3-4), mean and median monthly costs were 1,086 ± 1471, and 600 (IQR: 0-1200) DKK (1 EUR = ~7.5 DKK), respectively, and median patient-reported assessment of the efficacy of interventions was 2 (IQR: 0-3). Conclusion: Even in a high-income country with freely accessible headache services and universal healthcare coverage, there was a non-negligible direct cost in parallel with low satisfaction for non-pharmacological therapies among patients at a tertiary headache center.

Gut-brain Axis and migraine headache: a comprehensive review.

The terminology "gut-brain axis "points out a bidirectional relationship between the GI system and the central nervous system (CNS). To date, several researches have shown that migraine is associated with some gastrointestinal (GI) disorders such as Helicobacter pylori (HP) infection, irritable bowel syndrome (IBS), and celiac disease (CD). The present review article aims to discuss the direct and indirect evidence suggesting relationships between migraine and the gut-brain axis. However, the mechanisms explaining how the gut and the brain may interact in patients with migraine are not entirely clear. Studies suggest that this interaction seems to be influenced by multiple factors such as inflammatory mediators (IL-1ß, IL-6, IL-8, and TNF-α), gut microbiota profile, neuropeptides and serotonin pathway, stress hormones and nutritional substances. Neuropeptides including CGRP, SP, VIP, NPY are thought to have antimicrobial impact on a variety of the gut bacterial strains and thus speculated to be involved in the bidirectional relationship between the gut and the brain. According to the current knowledge, migraine headache in patients harboring HP might be improved following the bacteria eradication. Migraineurs with long headache history and high headache frequency have a higher chance of being diagnosed with IBS. IBS and migraine share some similarities and can alter gut microflora composition and thereby may affect the gut-brain axis and inflammatory status. Migraine has been also associated with CD and the condition should be searched particularly in patients with migraine with occipital and parieto-occipital calcification at brain neuroimaging. In those patients, gluten-free diet can also be effective in reducing migraine frequency. It has also been proposed that migraine may be improved by dietary approaches with beneficial effects on gut microbiota and gut-brain axis including appropriate consumption of fiber per day, adhering to a low glycemic index diet, supplementation with vitamin D, omega-3 and probiotics as well as weight loss dietary plans for overweight and obese patients.

Functional connectivity studies in migraine: what have we learned?

BACKGROUND: Resting-state functional connectivity (FC) MRI has widely been used to understand migraine pathophysiology and to identify an imaging marker of the disorder. Here, we review what we have learned from FC studies. METHODS: We performed a literature search on the PubMed website for original articles reporting data obtained from conventional resting-state FC recording in migraine patients compared with healthy controls or during and outside of migraine attacks in the same patients. RESULTS: We found 219 articles and included 28 in this review after screening for inclusion and exclusion criteria. Twenty-five studies compared migraine patients with healthy controls, whereas three studies investigated migraine patients during and outside of attacks. In the studies of interictal migraine more alterations of more than 20 FC networks (including amygdala, caudate nucleus, central executive, cerebellum, cuneus, dorsal attention network, default mode, executive control, fronto-parietal, hypothalamus, insula, neostriatum, nucleus accumbens, occipital lobe, periaqueductal grey, prefrontal cortex, salience, somatosensory cortex I, thalamus and visual) were reported. We found a poor level of reproducibility and no migraine specific pattern across these studies. CONCLUSION: Based on the findings in the present review, it seems very difficult to extract knowledge of migraine pathophysiology or to identify a biomarker of migraine. There is an unmet need of guidelines for resting-state FC studies in migraine, which promote the use of homogenous terminology, public availability of protocol and the a priori hypothesis in line with for instance randomized clinical trial guidelines.

Selective motor imagery defect in patients with locked-in syndrome.

Recent studies indicate that motor imagery is subserved by activation of motor information. However, at present it is not clear whether the sparing of motor efferent pathways is necessary to perform a motor imagery task. To clarify this issue, we required patients with a selective, severe de-efferentation (locked-in syndrome, LIS) to mentally manipulate hands and three-dimensional objects. Compared with normal controls, LIS patients showed a profound impairment on a modified version of the hand-laterality task and a normal performance on mental rotation of abstract items. Moreover, LIS patients did not present visuomotor compatibility effects between anatomical side of hands and spatial location of stimuli on the computer screen. Such findings confirmed that the motor system is involved in mental simulation of action but not in mental manipulation of visual images. To explain LIS patients' inability in manipulating hand representations, we suggested that the pontine lesion, both determined a complete de-efferentation, and affected a component of the motor system, which is crucial for mental representation of body parts, probably the neural connections between parietal lobes and cerebellum.

Management of pathologic laughter and crying in patients with locked-in syndrome: a report of 4 cases.

Emotional lability and pathologic laughter and crying (PLC) have been frequently mentioned in patients with locked-in syndrome (LIS) without giving any detail about the clinical characteristics and possible consequences in terms of symptoms burden, functional impact, and recovery. In the present report, we describe our approach and management of 4 patients with LIS and PLC. PLC caused discomfort to the patients and hindered the different components of their rehabilitation program, limiting communication, the execution of swallowing testing and training, and the improvement of any residual motor function. PLC was unrelated to depression, did not ameliorate after pharmacologic treatment, and improved with cognitive-behavior treatment. Our findings suggest that, in LIS patients, laughter and crying alterations do not represent symptoms of a mood disorder but are the result of the same pontine lesion that causes LIS. In relation to the complex pathway regulating laughter and crying, we hypothesized that, in patients with LIS, PLC may be the result of a direct damage to the pontine center or of an alteration in the ponto-cerebellar pathway linking emotional behavior to contextual information. Presence of PLC in patients with LIS severely affects their intelligent adaptation to the environment. Direct explanation to the patients of the origin of PLC may be helpful as a cognitive-behavior treatment, with resulting benefits to the entire rehabilitation program.