Staged magnetic resonance-guided focused ultrasound thalamotomy for the treatment of bilateral essential tremor and Parkinson's disease related tremor: a systematic review and critical appraisal of current knowledge.

Introduction: Essential tremor (ET) and Parkinson's Disease (PD) are debilitating neurodegenerative disorders characterized by tremor as a predominant symptom, significantly impacting patients' quality of life. Magnetic Resonance-guided Focused Ultrasound (MRgFUS) Thalamotomy is an innovative therapeutic option for the treatment of unilateral medically refractory tremor with fewer adverse effects compared to traditional surgical interventions. A recent CE approval allows appropriate patients to have their second side treated. Objective: The objective of this systematic review was to analyze available current knowledge about the use of MRgFUS for the treatment of bilateral ET and PD related tremor, to identify the effectiveness and the risks associated with bilateral treatment. Methods: Eligible studies were identified by searching published studies in PubMed and Scopus databases from May 2014 to January 2024 and by identifying ongoing studies registered on the clinicaltrials.gov website. Data were summarized by considering the following information topics: the number of patients involved, the selected lesion target, the assessment tool used to evaluate clinical changes, the observed improvement, the reported side effects, and the time interval between the two treatments. The study was registered in PROSPERO (ID: CRD42024513178). Results: Nine studies were eligible for this review, 7 for ET and 2 for PD. The involved population included a variable number of patients, ranging from 1 to 11 subjects for ET and from 10 to 15 subjects for PD. The main lesional targets were the ventral intermediate nucleus of the thalamus, the pallidothalamic tract and the cerebellothalamic tract bilaterally. All studies investigated the tremor relief through the Clinical Rating Scale for Tremor (CRST) in patients with ET, and through the Unified Parkinson's Disease Rating Scale (UPDRS) in patients with PD. A variable degree of improvement was observed, with all patients expressing overall satisfaction with the bilateral treatment. Adverse events were mild and transient, primarily involving gait disturbances, dysarthria, and ataxia. A standardized protocol for administering the two consecutive treatments was not identifiable; typically, the timing of the second treatment was delayed by at least 6 months. Conclusion: Available evidence supports the effectiveness and safety of staged bilateral MRgFUS treatments for ET and PD-related tremor.

Cognitive safety of focused ultrasound thalamotomy for tremor: 1-year follow-up results of the COGNIFUS part 2 study.

Introduction: In the COGNitive in Focused UltraSound (COGNIFUS) study, we examined the 6-month cognitive outcomes of patients undergoing MRgFUS thalamotomy. This study endorsed the safety profile of the procedure in terms of cognitive functions that cannot be evaluated in real-time during the procedure unlike other aspects. The aim of the COGNIFUS Part 2 study was to investigate the cognitive trajectory of MRgFUS patients over a 1-year period, in order to confirm long-term safety and satisfaction. Methods: We prospectively evaluated the cognitive and neurobehavioral profile of patients with essential tremor (ET) or Parkinson's Disease (PD) related tremor undergoing MRgFUS thalamotomy at 1 year-follow-up following the treatment. Results: The sample consists of 50 patients (male 76%; mean age ± SD 69.0 ± 8.56; mean disease duration ± SD 12.13 ± 12.59; ET 28, PD 22 patients). A significant improvement was detected at the 1 year-follow-up assessment in anxiety and mood feelings (Hamilton Anxiety rating scale 5.66 ± 5.02 vs. 2.69 ± 3.76, p ≤ <0.001; Beck depression Inventory II score 3.74 ± 3.80 vs. 1.80 ± 2.78, p = 0.001), memory domains (Rey Auditory Verbal Learning Test, immediate recall 31.76 ± 7.60 vs. 35.38 ± 7.72, p = 0.001 and delayed recall scores 5.57 ± 2 0.75 vs. 6.41 ± 2.48), frontal functions (Frontal Assessment Battery score 14.24 ± 3.04 vs. 15.16 ± 2.74) and in quality of life (Quality of life in Essential Tremor Questionnaire 35.00 ± 12.08 vs. 9.03 ± 10.64, p ≤ 0.001 and PD Questionnaire -8 7.86 ± 3.10 vs. 3.09 ± 2.29, p ≤ 0.001). Conclusion: Our study supports the long-term efficacy and cognitive safety of MRgFUS treatment for ET and PD.

Network analysis of negative emotions in patients with episodic migraine: need for a multidisciplinary perspective.

Background: Episodic migraine (EM) is the second most prevalent neurological disorder worldwide and is responsible for more disability than all other neurological disorders combined. Triggers for the development of migraine include, stress, emotional burden, low blood sugar levels, tobacco, skipped meals, anxious and depressive feelings. Migraine affects both children and adults, occurring three times more frequently in women than in men. Objective: The aim of this study was to evaluate the psychological profile of EM patients and the relationship among negative emotions in EM patients, analyzing self-efficacy measures in pain management. Design: We performed an observational study in 60 outpatients aged 18-55 years (mean age 33.8; SD ±10.4) with EM. Methods: All patients have been enrolled at the Headache Center of the San Salvatore Hospital of L'Aquila. The assessment comprised five standardized psychological self-assessments investigating relevant emotional dimensions and pain self-efficacy, along with two questionnaires assessing migraine-related disability. A network analysis of negative emotions was performed to evaluate which emotional traits and relationships play a crucial role in pain coping and management. Results: Our findings indicate that migraine significantly impairs the quality of life of patients in their daily lives. Over half of the patients reported experiencing severe disability, with negative emotions significantly influencing their ability to cope with pain and maintain productivity during migraine attacks. Dysphoric variables (irritability, interpersonal resentment, and surrender) were correlated with difficulties in emotion regulation ability and with the capacity of engaging in goal-directed behaviors despite experiencing pain. The ability to regulate one's emotions and manage dysphoria were positively correlated with pain self-efficacy, whereas positive mental health was associated with individuals' confidence in performing activities despite experiencing pain. Conclusion: Negative emotions had a negative correlation with positive mental health and were linked to a lower capacity to carry out daily activities despite experiencing migraine pain. This suggests that psychological interventions could improve mental health and potentially surpassing the effects of pharmacological interventions alone in migraine management. An integrated, patient-centered approach may represent an effective paradigm to address and reduce the burden of migraine, leading to a reduction in healthcare costs.

Facial emotion recognition and judgment of affective scenes in Parkinson's disease.

Emotional dysfunctions in Parkinson's disease (PD) remain a controversial issue. While previous investigations showed compromised recognition of expressive faces in PD, no studies evaluated potential deficits in recognizing the emotional valence of affective scenes. This study aimed to investigate both facial emotion recognition performance and the ability to judge affective scenes in PD patients. Forty PD patients (mean age ± SD: 64.50 ± 8.19 years; 27 men) and forty healthy subjects (64.95 ± 8.25 years; 27 men) were included. Exclusion criteria were previous psychiatric disorders, previous Deep Brain Stimulation, and cognitive impairment. Participants were evaluated through the Ekman 60-Faces test and the International Affective Picture System. The accuracy in recognizing the emotional valence of facial expressions and affective scenes was compared between groups using linear mixed models. Pearson's correlation was performed to test the association between accuracy measures. The groups did not differ in sex, age, education, and Mini-Mental State Examination scores. Patients showed a lower recognition accuracy of facial expressions (68.54 % ± 15.83 %) than healthy participants (78.67 % ± 12.04 %; p < 0.001). Specifically, the PD group was characterized by lower recognition of faces expressing fear, sadness, and anger than the control group (all p < 0.020). No difference was detected for faces expressing disgust, surprise, and happiness (all p ≥ 0.25). Furthermore, patients showed lower accuracy in recognizing the emotional valence of affective scenes (66.75 % ± 14.59 %) than healthy subjects (74.83 % ± 12.65 %; p = 0.010). Pearson's correlations indicated that higher accuracy in recognizing the emotional facial expressions was associated with higher accuracy in classifying the valence of affective scenes in patients (r = 0.57, p < 0.001) and control participants (r = 0.57, p < 0.001). Our study suggested maladaptive affective processing in PD, leading patients to misinterpret both facial expressions and the emotional valence of complex evocative scenes.

Early re-emerging tremor after MRgFUS thalamotomy: case-control analysis of procedural and imaging features.

Purpose: This study aimed to identify possible prognostic factors determining early tremor relapse after Magnetic Resonance guided Focused Ultrasound Surgery (MRgFUS) thalamotomy in patients with essential tremor (ET) and Parkinson's disease (PD). Methods: Nine patients (six ET and three PD) who underwent Vim MRgFUS thalamotomy in a single institution and developed early re-emergent tremor were analyzed. A control group of patients matched pairwise for sex, pathology, age, disease duration, and skull density ratio (SDR) was selected to compare the technical-procedural data and MR imaging evidence. MR imaging findings compared between groups included lesion shape and volume in multiparametric sequences, as well as Fractiona Anisotropy (FA) and Apparent Diffusion Coefficient (ADC) values derived from Diffusion Tensor Imaging Diffusion Weighted Imaging (DTI) and Diffusion Weighted Imaging (DWI) sequences. Results: We did not find statistically significant differences in gender and age between the two groups. Technical and procedural parameters were also similar in both treatment groups. In MRI analysis, we found lesions of similar size but with greater caudal extension in the control group with stable outcomes compared to patients with tremor relapse. Conclusion: In our analysis of early recurrences after thalamotomy with focused ultrasound, there were neither technical and procedural differences nor prognostic factors related to lesion size or ablation temperatures. Greater caudal extension of the lesion in patients without recurrence might suggest the importance of spatial consolidation during treatment.

Emotional atypical arousal ratings for unpleasant stimuli in patients with Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms, including alteration in emotional processing and recognition of emotions. We explored the effects of PD on the emotional behavioral ratings using a battery of affective visual stimuli selected from the International Affective Picture System (IAPS). METHODS: Twenty-two patients diagnosed with idiopathic PD and 22 healthy controls (HC), matched by age, gender, and education, were enrolled in the study. Following a clinical assessment, each participant was asked to evaluate the arousal and valence of affective visual stimuli, and response time was recorded. Disease-specific measures including the MDS Unified Parkinson's Disease Rating Scale (MDS UPDRS) and the Non-Motor Symptom Scale (NMSS) were also collected. RESULTS: PD patients exhibited higher arousal responses compared to HC for negative/unpleasant pictures (scoring 7.32 ± 0.88 vs 5.43 ± 2.06, p < 0.001). The arousal response to negative/unpleasant pictures was correlated with measures of non-motor burden in PD (MDS UPDRS I and NMSS, rho = 0.480 and p = 0.023, rho = 0.533 and p = 0.010, respectively). CONCLUSION: Impaired emotional processing characterizes PD patients with mild disease and is related to the non-motor symptom burden. Given the importance of emotional processing for the development and maintenance of close interpersonal relationship and for coping with specific medical situations, it is crucial to direct PD patients towards therapeutic interventions focused on the recognition and processing of emotions.

Assessment of Frequency and Predictive Value of Comorbidities in Patients With Disorders of Consciousness in the Acute Setting.

Medical comorbidities are frequent in patients with disorders of consciousness (DoC) and their impact on outcomes is under investigation. The aim of this study was to investigate patients with DoC in the acute stage and the influence of comorbidities. Patients admitted to intensive care units and neurological units with a diagnosis of coma, vegetative state/unresponsive wakefulness syndrome (VS/UWS), and minimally conscious state (MCS) were investigated through the Glasgow Coma Scale (GCS), the Coma Recovery Scale - Revised (CRS-R) and the Comorbidities Coma Scale (CoCos). Forty-three patients (21 men and 22 women; mean age at admission: 60.4 ± 21.0) were included in the study. The most frequent diagnosis at admission was coma (72%) followed by VS/UWS (14%) and MCS (14%). The most frequent brain injury was subarachnoid hemorrhage (46%). At the 6-month follow-up, 19 patients had died (44%), 15 showed a full recovery of consciousness (35%), 7 were in a condition of emergence from MCS (16%), and 2 showed a persistent VS/UWS (5%). Forty-two (98%) patients showed at least one comorbidity: presence of life-support device (92.9%), anemia (76.2%), arterial hypertension (66,7%), hydrocephalus (45.3%), and respiratory infections (45.2%) were those most frequently reported. At the Multivariable Cox regression, the presence of renal disease (hazard ratio [HR] 33.37; p = 0.033) and malnutrition (HR 14.52; p = 0.001) were predictors of missed recovery of full consciousness. Although adverse outcomes are generally predicted by the severity of brain damage, the presence of medical comorbidities in an acute phase could influence outcomes and long-term prognosis.

Effects of deep brain stimulation of the subthalamic nucleus on patients with Parkinson's disease: a machine-learning voice analysis.

Introduction: Deep brain stimulation of the subthalamic nucleus (STN-DBS) can exert relevant effects on the voice of patients with Parkinson's disease (PD). In this study, we used artificial intelligence to objectively analyze the voices of PD patients with STN-DBS. Materials and methods: In a cross-sectional study, we enrolled 108 controls and 101 patients with PD. The cohort of PD was divided into two groups: the first group included 50 patients with STN-DBS, and the second group included 51 patients receiving the best medical treatment. The voices were clinically evaluated using the Unified Parkinson's Disease Rating Scale part-III subitem for voice (UPDRS-III-v). We recorded and then analyzed voices using specific machine-learning algorithms. The likelihood ratio (LR) was also calculated as an objective measure for clinical-instrumental correlations. Results: Clinically, voice impairment was greater in STN-DBS patients than in those who received oral treatment. Using machine learning, we objectively and accurately distinguished between the voices of STN-DBS patients and those under oral treatments. We also found significant clinical-instrumental correlations since the greater the LRs, the higher the UPDRS-III-v scores. Discussion: STN-DBS deteriorates speech in patients with PD, as objectively demonstrated by machine-learning voice analysis.

White matter hyperintensities in migraine are not mediated by a dysfunction of the glymphatic system-A diffusion tensor imaging magnetic resonance imaging study.

OBJECTIVE: We assessed whether brain magnetic resonance imaging (MRI) markers of glymphatic function are altered in patients with migraine and brain white matter hyperintensities (WMHs). BACKGROUND: The glymphatic system is responsible for the outflow of waste products from the brain. An impaired glymphatic system has been associated with WMH; however, this impairment has not been shown in patients with migraine. METHODS: The present cross-sectional study included consecutive patients with migraine from a single tertiary headache center. Glymphatic function was assessed by measuring the diffusion tensor imaging along the perivascular space (DTI-ALPS) technique, resulting in an index value. WMHs were assessed and quantified by using the Scheltens semi-quantitative score. RESULTS: We included 147 patients (120 women [81.6%]) with a median (interquartile range [IQR]) age of 45 (36-50) years. In all, 74 (50.3%) patients had WMHs. The median (IQR) ALPS index was similar in patients with WMHs compared with those without, at 2.658 (2.332-3.199) versus 2.563 (2.222-3.050) (p = 0.344). The Scheltens score did not correlate with ALPS index (rho = 0.112, p = 0.268). CONCLUSIONS: Our results suggest that the presence of WMHs is not associated with an impairment in the glymphatic system in patients with migraine. Although negative and worthy of further confirmation, our finding has implications for the understanding of the nature of WMH in patients with migraine.

Models of care in emergency neurology: from the Neuro Fast Track to the emergency neurologist-a position paper of the Italian Association for Emergency Neurology (ANEU).

I n the context of an adequate health care organization, the figure of the neurologist as an emergency operator (in the emergency room-ER-and/or in a dedicated outpatient clinic) is crucial for an effective functional connection with the territory (and therefore with general practitioners), a reduction in inappropriate ER accesses, specific diagnostic and therapeutic approaches to neurological emergencies in the ER and a reduction in nonspecific or even unnecessary instrumental investigations. In this position paper of the Italian Association of Emergency Neurology (ANEU: Associazione Neurologia dell'Emergenza Urgenza), these issues are addressed, and two important organizational solutions are proposed: 1) The Neuro Fast Track, as an outpatient organization approach strongly linked to general practitioners and non-neurological specialists and dedicated to cases with deferrable urgency (to be assessed within 72 h) 2) The identification of an emergency neurologist, who is engaged in ER assessments as a consultant and involved in the management of the semi-intensive care unit of the emergency neurology and the stroke unit according to an appropriate rotation, as well as in consultations for patients with neurological emergencies in inpatient wards The possibility of computerizing the screening of patients with deferrable urgency in the Neuro Fast Track is described. A dedicated app represents an important tool that can facilitate the identification of patients for whom deferred assessment is appropriate, the scheduling of neurological examinations and reductions in the booking time through a more rapid approach to specialist assessment and subsequent investigations.

Magnetic Resonance-guided Focused Ultrasound thalamotomy for refractory neuropathic pain: a systematic review and critical appraisal of current knowledge.

Background: Magnetic Resonance-guided Focused Ultrasound (MRgFUS) is an innovative therapeutical approach for medically refractory tremor. It is currently under investigation for other neurological diseases including refractory neuropathic pain (NP). Objective: The objective of this systematic review is to analyze available evidence about the effectiveness and safety profile of MRgFUS in the treatment of refractory NP. Methods: Eligible studies were identified by searching published studies in PubMed and Scopus databases from inception to December 2022 and by identifying ongoing studies registered on the clinicaltrials.gov website. The study was registered in PROSPERO (ID: CRD42021277154). Results: We found three published observational studies and nine ongoing studies. In published studies, the involved population ranged from 8 to 46 patients with overall 66 patients being included with NP or trigeminal neuralgia. The target lesion was in the posterior part of the central lateral nucleus of the thalamus, bilaterally. Outcomes were assessed at different times through the Visual Analog Scale, showing a variable degree of improvement. Adverse events were rare, mild, and transient (vertigo, paresthesias, and dysesthesias) with intracerebral bleeding being reported as major adverse event in one case only. Among ongoing studies, we found three prospective, randomized, sham-controlled, crossover trials (RCTs) and six observational studies. Inclusion criteria are previous failure of more than three pharmacological treatments and NP duration longer than 6 months. The thalamus is the main proposed target and measured outcomes are accuracy of the procedure and pain relief, with a follow-up period ranging from 1 week to 1 year. Conclusion: This systematic review suggests that, although high-quality studies are lacking, available evidence endorses the effectiveness and safety of MRgFUS in the management of NP. Ongoing RCTs will provide more robust data to understand benefits and risks of the procedure. Registration: PROSPERO (ID: CRD42021277154).

Levodopa Equivalent Dose of Safinamide: A Multicenter, Longitudinal, Case-Control Study.

Background: Effects of dopaminergic medications used to treat Parkinson's disease (PD) may be compared with each other by using conversion factors, calculated as Levodopa equivalent dose (LED). However, current LED proposals on MAO-B inhibitors (iMAO-B) safinamide and rasagiline are still based on empirical approaches. Objectives: To estimate LED of safinamide 50 and 100 mg. Methods: In this multicenter, longitudinal, case-control study, we retrospectively reviewed clinical charts of 500 consecutive PD patients with motor complications and treated with (i) safinamide 100 mg (N = 130), safinamide 50 mg (N = 144), or rasagiline 1 mg (N = 97) for 9 ± 3 months and a control group of patients never treated with any iMAO-B (N = 129). Results: Major baseline features (age, sex, disease duration and stage, severity of motor signs and motor complications) were similar among the groups. Patients on rasagiline had lower UPDRS-II scores and Levodopa dose than control subjects. After a mean follow-up of 8.8-to-10.1 months, patients on Safinamide 50 mg and 100 mg had lower UPDRS-III and OFF-related UPDRS-IV scores than control subjects, who in turn had larger increase in total LED than the three iMAO-B groups. After adjusting for age, disease duration, duration of follow-up, baseline values and taking change in UPDRS-III scores into account (sensitivity analysis), safinamide 100 mg corresponded to 125 mg LED, whereas safinamide 50 mg and rasagiline 1 mg equally corresponded to 100 mg LED. Conclusions: We used a rigorous approach to calculate LED of safinamide 50 and 100 mg. Large prospective pragmatic trials are needed to replicate our findings.

Divergence Between Clinical Trial Evidence and Actual Practice in Use of Dual Antiplatelet Therapy After Transient Ischemic Attack and Minor Stroke.

BACKGROUND: Randomized controlled trials (RCTs) proved that short-term (21-90 days) dual antiplatelet therapy (DAPT) reduces the risk of early ischemic recurrences after a noncardioembolic minor stroke or high-risk transient ischemic attack (TIA) without substantially increasing the hemorrhagic risk. We aimed at understanding whether and how real-world use of DAPT differs from RCTs. METHODS: READAPT (Real-Life Study on Short-Term Dual Antiplatelet Treatment in Patients With Ischemic Stroke or TIA) is a prospective cohort study including >18-year-old patients treated with DAPT after a noncardioembolic minor ischemic stroke or high-risk TIA from 51 Italian centers. The study comprises a 90-day follow-up from symptom onset. In the present work, we reported descriptive statistics of baseline data of patients recruited up to July 31, 2022, and proportions of patients who would have been excluded from RCTs. We compared categorical data through the χ² test. RESULTS: We evaluated 1070 patients, who had 72 (interquartile range, 62-79) years median age, were mostly Caucasian (1045; 97.7%), and were men (711; 66.4%). Among the 726 (67.9%) patients with ischemic stroke, 226 (31.1%) did not meet the RCT inclusion criteria because of National Institutes of Health Stroke Scale score >3 and 50 (6.9%) because of National Institutes of Health Stroke Scale score >5. Among the 344 (32.1%) patients with TIA, 69 (19.7%) did not meet the RCT criteria because of age, blood pressure, clinical features, duration of TIA, presence of diabetes score <4 and 252 (74.7%) because of age, blood pressure, clinical features, duration of TIA, presence of diabetes score <6 and no symptomatic arterial stenosis. Additionally, 144 (13.5%) patients would have been excluded because of revascularization procedures. Three hundred forty-five patients (32.2%) did not follow the RCT procedures because of late (>24 hours) DAPT initiation; 776 (72.5%) and 676 (63.2%) patients did not take loading doses of aspirin and clopidogrel, respectively. Overall, 84 (7.8%) patients met the RCT inclusion/exclusion criteria. CONCLUSIONS: The real-world use of DAPT is broader than RCTs. Most patients did not meet the RCT criteria because of the severity of ischemic stroke, lower risk of TIA, late DAPT start, or lack of antiplatelet loading dose. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT05476081.

Validation of the Italian version of the Cluster Headache Impact Questionnaire (CHIQ).

BACKGROUND: The Cluster Headache Impact Questionnaire (CHIQ) is a specific and easy-to-use questionnaire to assess the current impact of cluster headache (CH). The aim of this study was to validate the Italian version of the CHIQ. METHODS: We included patients diagnosed with episodic CH (eCH) or chronic CH (cCH) according to the ICHD-3 criteria and included in the "Italian Headache Registry" (RICe). The questionnaire was administered to patients through an electronic form in two sessions: at first visit for validation, and after 7 days for test-retest reliability. For internal consistency, Cronbach's alpha was calculated. Convergent validity of the CHIQ with CH features and the results of questionnaires assessing anxiety, depression, stress, and quality of life was evaluated using Spearman's correlation coefficient. RESULTS: We included 181 patients subdivided in 96 patients with active eCH, 14 with cCH, and 71 with eCH in remission. The 110 patients with either active eCH or cCH were included in the validation cohort; only 24 patients with CH were characterized by a stable attack frequency after 7 days, and were included in the test-retest cohort. Internal consistency of the CHIQ was good with a Cronbach alpha value of 0.891. The CHIQ score showed a significant positive correlation with anxiety, depression, and stress scores, while showing a significant negative correlation with quality-of-life scale scores. CONCLUSION: Our data show the validity of the Italian version of the CHIQ, which represents a suitable tool for evaluating the social and psychological impact of CH in clinical practice and research.

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.

Cerebello-Thalamo-Cortical MR Spectroscopy in Patients with Essential Tremor Undergoing MRgFUS Thalamotomy: A Pilot Study.

Previous literature studies explored the association between brain neurometabolic changes detected by MR spectroscopy and symptoms in patients with tremor, as well as the outcome after deep brain stimulation (DBS) treatment. The purpose of our study was to evaluate the possible changes in cerebello-thalamo-cortical neurometabolic findings using MR spectroscopy in patients submitted to MRgFUS thalamotomy. For this pilot study, we enrolled 10 ET patients eligible for MRgFUS thalamotomy. All patients were preoperatively submitted to 3T MR spectroscopy. Single-voxel MRS measurements were performed at the level of the thalamus contralateral to the treated side and the ipsilateral cerebellar dentate nucleus. Multivoxel acquisition was used for MRS at the level of the contralateral motor cortex. At the 6-month follow-up after treatment, we found a statistically significant increase in the Cho/Cr ratio at the level of the thalamus, a significant increase of the NAA/Cr ratio at the level of the dentate nucleus and a significant decrease of the NAA/Cho ratio at the level of the motor cortex. We found a significant positive correlation between cortical NAA/Cr and clinical improvement (i.e., tremor reduction) after treatment. A significant negative correlation was found between clinical improvement and thalamic and cerebellar NAA/Cr. Confirming some previous literature observations, our preliminary results revealed neurometabolic changes and suggest a possible prognostic role of the MRS assessment in patients with ET treated by MRgFUS.

Cranial autonomic symptoms and response to monoclonal antibodies targeting the Calcitonin gene-related peptide pathway: A real-world study.

Objective: Cranial autonomic symptoms (CAS), including conjunctival injection, tearing, nasal congestion or rhinorrhea, eyelid edema, miosis or ptosis, and forehead or facial sweating ipsilateral to headache, are often reported by patients with migraine during headache attacks. CAS is a consequence of the activation of the trigeminovascular system, which is the target of monoclonal antibodies acting on the CGRP pathway. Therefore, we hypothesized that patients with CAS might have higher trigeminovascular activation than those without CAS leading to a better response to anti-CGRP treatments. Methods: We performed a prospective analysis including patients with episodic or chronic migraine treated with anti-CGRP monoclonal antibodies (i.e., erenumab, fremanezumab, and galcanezumab) between 2019 and 2021. The observation period included a 12-week baseline before treatment with anti-CGRP antibodies and a 12-week treatment follow-up. We evaluated the prevalence of CAS in our cohort and compared disease characteristics and treatment response (i.e., 12-week monthly headache days and 0-29, 30-49, 50-74, 75-99, and 100% monthly headache days reduction from baseline) among patients with and without CAS using the χ2 test, Kruskal-Wallis test, and Mann-Whitney U-test. Results: Out of 136 patients, 88 (65%) had CAS. Both patients with and without CAS reported a significant decrease in monthly headache days from baseline. During the 12-week follow-up, the median difference in monthly headache days from baseline was higher in patients with CAS (-10, IQR-15 to-6) than in those without CAS (6, IQR 12 to 3; P = 0.009). However, the proportions of patients with 0 to 29, 30 to 49, 50 to 74, 75 to 99, and 100% response rates did not differ between the two groups. Conclusions: In our cohort, the presence of CAS was associated with a greater response to monoclonal antibodies targeting the CGRP pathway. CAS could be a clinical marker of trigeminovascular activation and thus be related to a better response to CGRP treatments.

Behavioral and psychological factors in individuals with migraine without psychiatric comorbidities.

BACKGROUND: It is well known that the course of migraine is influenced by comorbidities and that individual psychological characteristics may impact on the disease. Proper identification of psychological factors that are relevant to migraine is important to improve non-pharmacological management. This study aimed at investigating the relationship between psychological factors and migraine in subjects free of psychiatric comorbidities. METHODS: A sample of women with episodic (EM) and chronic migraine (CM) without history of psychiatric comorbidities were included in this cross-sectional study. The study also included female healthy controls (HC) without migraine or other primary headaches. We evaluated sleep, anxiety, depression, intolerance of uncertainty, decision making style and tendence to pain catastrophizing by validated self-report questionnaires or scales. Comparisons among groups were performed using ANOVA and Bonferroni post-hoc tests. Statistical significance was set at p < 0.05. RESULTS: A total of 65 women with EM (mean age ± SD, 43.9 ± 7.2), 65 women with CM (47.7 ± 8.5), and 65 HC (43.5 ± 9.0) were evaluated. In sleep domains, CM patients reported poorer overall sleep quality, more severe sleep disturbances, greater sleep medication use, higher daytime dysfunction, and more severe insomnia symptoms than HC. EM group showed better sleep quality, lower sleep disturbances and sleep medication use than CM. On the other hand, the analysis highlighted more severe daytime dysfunction and insomnia symptoms in EM patients compared to HC. In anxiety and mood domains, CM showed greater trait anxiety and a higher level of general anxiety sensitivity than HC. Specifically, CM participants were more afraid of somatic and cognitive anxiety symptoms than HC. No difference in depression severity emerged. Finally, CM reported a higher pain catastrophizing tendency, more severe feeling of helplessness, and more substantial ruminative thinking than EM and HC, whilst EM participants reported higher scores in the three above-mentioned dimensions than HC. The three groups showed similar decision-making styles, intolerance of uncertainty, and strategies for coping with uncertainty. CONCLUSIONS: Even in individuals without psychiatric comorbidities, specific behavioral and psychological factors are associated with migraine, especially in its chronic form. Proper identification of those factors is important to improve management of migraine through non-pharmacological strategies.

Can Stimulus Valence Modulate Task-Switching Ability? A Pilot Study on Primary School Children.

Executive functions and emotional processes follow a time-dependent development that reflects the brain's anatomo-functional maturation. Though the assessment of these cognitive functions is largely examined, in children the role of emotions in the mental set-shifting is still rarely investigated. The aim of this study was to assess how attention shifting can be modulated by the valence of emotional stimuli. To this end, sixty-two primary school children were tested with a new emotional task-switching paradigm obtained by manipulating the emotional valence and physical features of the stimulus pool. Thus, two tasks were alternatively presented: the Valence task and the Color task. Based on executive performance results, we found a lengthening of response times and a lower accuracy in the emotionally connoted task (Valence task), compared to the neutral task (Color task). The data demonstrate that the processing of emotional stimuli modulates the task-switching performance during development. These findings could help in the implementation of teaching strategies that can promote the development of executive functions and, therefore, functionally improve the overall academic performance of children. Finally, a better understanding of the developmental trajectories of executive functions can help neuropsychologists both in the early diagnosis and treatment of potential executive alterations.