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.

Evaluation of Cerebral Volume Changes in Patients with Tremor Treated by MRgFUS Thalamotomy.

The purpose of the study is to quantify volumetric variations of cortical and subcortical brain structures after Vim ablation using MRgFUS, and correlate them with the patients' clinical features and treatment outcomes. For this pilot retrospective study we enrolled 31 patients with a mean age of 70.86 years who were eligible for unilateral Vim thalamotomy. Clinical evaluation included tremor severity assessment using the FTM scale and cognitive assessment using the MoCA score. MRI data were acquired with a 3T scanner, using a dedicated 32-channel coil and acquiring a volumetric sequence of T1 3D IR FSPGR (BRAVO), before treatment and one year after MRgFUS thalamotomy. Image processing and volume data extraction were conducted with dedicated software. A volumetric analysis showed a significant reduction (p < 0.05) of the left thalamus 1 year after the treatment in patients with ET. Other significant results were found on the same side in the other nuclei of the basal ganglia and in the cerebellar cortex. In confronting the two groups (ET, PD), no significant differences were found in terms of age, FTM, MoCA scores, or brain volumes. Similarly, no significant correlations were found between the FTM and MoCA scores and the brain volumes before the treatment.

Comprehensive Evaluation of Factors Affecting Tremor Relapse after MRgFUS Thalamotomy: A Case-Control Study.

OBJECTIVE: To identify possible relevant factors contributing to tremor relapse after MRgFUS thalamotomy in patients with essential tremor (ET) and Parkinson's disease (PD). METHODS: We identified patients with tremor relapse from a series of 79 treatments in a single institution. The demographic and clinical characteristics of the study group patients were compared to those of patients who did not relapse in the same follow-up period. Imaging and procedural factors were compared using a control group matched for clinical and demographic characteristics. RESULTS: Concerning clinical and demographic characteristics, we did not find statistically significant differences in gender and age. Seventy-three percent of patients with tremor relapse were Parkinson's disease patients. Using MRI, we found larger thalamotomy lesions at the 1-year follow-up in the control group with stable outcomes, compared to patients with tremor relapse. In the tractography evaluation, we found a more frequent eccentric position of the DRTt in patients with tremor relapse. CONCLUSIONS: The most relevant determining factors for tremor relapse after MRgFUS thalamotomy appear to be tremor from Parkinson's disease and inaccurate thalamic targeting. Size of the thalamotomy lesion can also influence the outcome of treatment.

Comparative evaluation of tractography-based direct targeting and atlas-based indirect targeting of the ventral intermediate (Vim) nucleus in MRgFUS thalamotomy.

To analyze and compare direct and indirect targeting of the Vim for MRgFUS thalamotomy. We retrospectively evaluated 21 patients who underwent unilateral MRgFUS Vim ablation and required targeting repositioning during the procedures. For each patient, in the three spatial coordinates, we recorded: (i) indirect coordinates; (ii) the coordinates where we clinically observed tremor reduction during the verification stage sonications; (iii) direct coordinates, measured on the dentatorubrothalamic tract (DRTT) at the after postprocessing of DTI data. The agreement between direct and indirect coordinates compared to clinically effective coordinates was evaluated through the Bland-Altman test and intraclass correlation coefficient. The median absolute percentage error was also calculated. Compared to indirect targeting, direct targeting showed inferior error values on the RL and AP coordinates (0.019 vs. 0.079 and 0.207 vs. 0.221, respectively) and higher error values on the SI coordinates (0.263 vs. 0.021). The agreement between measurements was higher for tractography along the AP and SI planes and lower along the RL planes. Indirect atlas-based targeting represents a valid approach for MRgFUS thalamotomy. The direct tractography approach is a valuable aid in assessing the possible deviation of the error in cases where no immediate clinical response is achieved.

Association between response to triptans and response to erenumab: real-life data.

BACKGROUND: Triptans and erenumab are both migraine-specific agents acting on the calcitonin gene-related peptide pathway. Therefore, response to triptans might be associated with response to erenumab. MAIN BODY: In our study, consecutive patients referring to the Headache Centers of the Abruzzo region from January 2019 to March 2020 and treated with erenumab were interviewed about past use and efficacy of triptans. Triptan users were classified as 'triptan responders' if they were headache-free 2 h after treating ≥3 migraine attacks with ≥1 triptan. We considered patients as 'erenumab responders', if they had a ≥ 50% mean reduction in monthly migraine days between the 4th and the 6th month from treatment start compared with baseline. Of 91 triptan users, 73 (80.2%) were triptan responders and 58 (63.7%) were erenumab responders. The odds ratio of being erenumab responder was 3.64 (95% CI, 1.25-10.64) for triptan users as compared to non-users. (P = 0.014). Besides, starting erenumab improved triptan response in both erenumab responders and non-responders. CONCLUSIONS: Our data of an association between response to triptans and response to erenumab can be useful for patient advice and to improve the understanding of migraine pathophysiology and treatment.

Conversion from chronic to episodic migraine in patients treated with erenumab: real-life data from an Italian region.

BACKGROUND: Most patients treated with erenumab in clinical practice have chronic migraine (CM). We assessed the rate and possible predictors of conversion from CM to episodic migraine (EM) in a real-life study. MAIN BODY: We performed a subgroup analysis of patients treated with erenumab from January 2019 to February 2020 in the Abruzzo region, central Italy. Treatment was provided according to current clinical practice. For the purpose of the present study, we included patients fulfilling the definition of CM for the three months preceding erenumab treatment and with at least 6 months of follow-up after treatment. We assessed the rate of conversion to EM from baseline to Months 4-6 of treatment and during each month of treatment. To test the clinical validity of conversion to EM, we also assessed the decrease in monthly headache days (MHDs), acute medication days, and median headache intensity on a Numerical Rating Scale (NRS). We included in our study 91 patients with CM. At Months 4-6, 62 patients (68.1%) converted from CM to EM; the proportion of converters increased from Month 1 to Month 5. In the overall group of patients, median MHDs decreased from 26.5 (IQR 20-30) to 7.5 (IQR 5-16; P < 0.001) compared with baseline, while median acute medication days decreased from 21 (IQR 16-30) to 6 (IQR 3-10; P < 0.001) and median NRS scores decreased from 8 (IQR 7-9) to 6 (IQR 4-7; P < 0.001). Significant decreases were found both in converters and in non-converters. We found no significant predictors of conversion to EM among the patients' baseline characteristics. CONCLUSIONS: In our study, two thirds of patients with CM converted to EM during 6 months of treatment with erenumab. MHDs, acute medication use, and headache intensity decreased regardless of conversion from CM to EM.

An experience-based review of HIFU in functional interventional neuroradiology: transcranial MRgFUS thalamotomy for treatment of tremor.

Tremor is a common and very disabling symptom in patients with essential tremor and Parkinson's disease. In the recent years, transcranial ablation of thalamic nuclei using magnetic resonance guided high-intensity focused ultrasound has emerged as a minimally invasive treatment for tremor. The aim of this review is to discuss, in the light of our single-center experience, the technique, current applications, results, and future perspectives of this novel technology.

Real-life data on the efficacy and safety of erenumab in the Abruzzo region, central Italy.

BACKGROUND: We aimed to assess the efficacy and safety of erenumab, a fully human monoclonal antibody inhibiting the calcitonin gene-related peptide receptor (CGRPr), for the prevention of migraine in a real-life setting. MAIN BODY: We included in our observational study all patients with episodic or chronic migraine treated with erenumab during the year 2019 in the Abruzzo region, central Italy, and with a 6-month follow-up. We included 89 patients; 76 (85.4%) received 6 doses of erenumab, 11 (12.4%) autonomously withdrew the drug due to perceived inefficacy, and 2 (2.2%) due to adverse events. Seventy-eight patients (87.6%) were female, with a mean age of 46.8 ± 11.2 years; 84 (94.4%) had chronic migraine, and 64 (71.9%) medication overuse. All patients had ≥2 prior preventive treatment failures. Fifty-three patients (69.7%) had a 50% decrease in monthly migraine days (MMDs) within the first three doses; 46 (71.9%) of 64 patients withdrew medication overuse. In the 76 patients who completed a 6-dose treatment, erenumab decreased median MMDs from 19 (interquartile range [IQR] 12-27.5) to 4 (IQR 2-9.5; P < 0.001), median monthly days of analgesic use from 10 (IQR 4.5-20) to 2 IQR 0-5; P < 0.001), and median monthly days of triptan use from 5 (IQR 0-15.5) to 1 (IQR 0-4; P < 0.001). We recorded 27 adverse events in 20 (22.5%) patients, the most common being constipation (13.5%). One adverse event, i.e. allergic reaction, led to treatment discontinuation in one patient. CONCLUSIONS: Our real-life data confirm the efficacy and tolerability of erenumab for the prevention of migraine in a difficult-to-treat population of patients with a high prevalence of chronic migraine and medication overuse.

The Italian Registry of Endovascular Treatment in Acute Stroke: rationale, design and baseline features of patients.

Endovascular treatment (ET) showed to be safe in acute stroke, but its superiority over intravenous thrombolysis is debated. As ET is rapidly evolving, it is not clear which role it may deserve in the future of stoke treatments. Based on an observational design, a treatment registry allows to study a broad range of patients, turning into a powerful tool for patients' selection. We report the methodology and a descriptive analysis of patients from a national registry of ET for stroke. The Italian Registry of Endovascular Treatment in Acute Stroke is a multicenter, observational registry running in Italy from 2010. All patients treated with ET in the participating centers were consecutively recorded. Safety measures were symptomatic intracranial hemorrhage, procedural adverse events and death rate. Efficacy measures were arterial recanalization and 3-month good functional outcome. From 2008 to 2012, 960 patients were treated in 25 centers. Median age was 67 years, male gender 57 %. Median baseline NIHSS was 17. The most frequent occlusion site was Middle cerebral artery (46.9 %). Intra-arterial thrombolytics were used in 165 (17.9 %) patients, in 531 (57.5 %) thrombectomy was employed, and 228 (24.7 %) patients received both treatments. Baseline features of this cohort are in line with data from large clinical series and recent trials. This registry allows to collect data from a real practice scenario and to highlight time trends in treatment modalities. It can address unsolved safety and efficacy issues on ET of stroke, providing a useful tool for the planning of new trials.

Epidemiology of stroke in Italy.

This study reviews available data on stroke epidemiology in Italy. Data were identified through Medline/PubMed, Embase, and from reference lists, related articles, and citation lists of each of the retrieved papers. Nineteen papers were considered, referring to selected stroke-registers performed in seven different geographical areas: Acquaviva-Casamassima county, Aeolian Islands, Aosta district, Belluno district, L'Aquila district, Trasimeno area, and Vibo Valentia district. Registers covered a total population of 2 262 940 people, with a hospitalization rate from 82% to 98%. The mean age at stroke onset was 74·6 ± 1·1 years, 72·3 years in men and 76·6 years in women. Among all strokes: • 67·3-82·6% were classified ischemic • 9·9-19·6% as primary intracerebral hemorrhage • 1·6-4·0% as sub-arachnoid hemorrhage, and • 1·2-17·7% as undetermined. Annual incidence rates standardized to the Italian population ranged from 175/1 00 000 to 360/1 00 000 in men and from 130/1 00 000 to 273/1 00 000 in women. Thirty-day case-fatality rates for all strokes ranged from 18·1% to 33·0% while one-year case-fatality rates ranged from 37·9% to 40·2%. Data from selected Italian registers on stroke incidence and case-fatality indicate the great burden of the disease on our national healthcare system. The continuous implementation of preventive strategies, either population-based or addressed to the single patient at a high risk of stroke, is important to reduce the burden of the disease.

Validation of the Italian version of the Coma Recovery Scale-Revised (CRS-R).

PRIMARY OBJECTIVE: To validate the Italian version of the Coma Recovery Scale-Revised (CRS-R). METHODS: Two observers applied the Italian version of the CRS-R to selected patients. On day 1, observer A and B independently scored each patient; the comparison of their observations was used to evaluate inter-observer agreement. On day 2, observer A completed a second evaluation and the comparison of this observation with that obtained on day 1 by the same observer was used to evaluate test-re-test agreement. For each evaluation, also diagnostic impression (vegetative state/minimally conscious state) was reported. RESULTS: Thirty-eight patients were evaluated (mean age ± SD, 58.9 ± 13.8 years). Inter-observer (ρ = 0.81; p < 0.001) as well as test-re-test agreement (ρ = 0.97; p < 0.001) for the total score was high. Inter-observer agreement was excellent for the communication sub-scale, good for the auditory, visual and motor sub-scales and moderate for the oromotor/verbal and arousal sub-scales. Test-re-test agreement was excellent for the visual, motor, oromotor/verbal and communication sub-scales, good for the auditory sub-scale and moderate for the arousal sub-scale. When considering the diagnostic impression, inter-observer agreement was good (κ = 0.75; p < 0.001) and test-re-test agreement was excellent (κ = 0.92; p < 0.001). CONCLUSIONS: The Italian version of the CRS-R can be administered reliably and can be also employed to discriminate patients in vegetative and in minimally conscious state.

Incidence, case-fatalities and 10-year survival of subarachnoid hemorrhage in a population-based registry.

OBJECTIVE: To evaluate incidence, case fatalities and prognosis of subarachnoid hemorrhage (SAH). SUBJECTS AND METHODS: Prospective population-based registry (1994-1998) including patients with a first-ever stroke followed up to 10 years. RESULTS: In a 5-year period we included 118 patients (55 men and 63 women; mean age +/- SD 60.7 +/- 15.9 years) with an SAH. The crude annual incidence rate was 7.93 cases per 100,000 inhabitants (95% CI 6.46-9.63), 7.60 per 100,000 when standardized to the 2006 European population and 5.27 per 100,000 when standardized to the 2005 world population. The 7-day case-fatality rate was 16.1% (95% CI 9.5-22.7), 30-day case-fatality rate was 34.7% (95% CI 21.2-43.3), and 1-year case-fatality rate was 44.9% (95% CI 35.9-53.9). At the end of the 1-year follow-up, 53 patients (44.9%) had a good recovery [modified Rankin scale (mRS) 0-2] and 12 (10.2%) had a severe disability (mRS 3-5). The 10-year survival rate was 46.4% (95% CI 36.0-57.8). CONCLUSION: In our district, the SAH incidence rate was similar to what is reported in most European countries. Since more than half of the patients with SAH remained severely disabled or died, results from our population-based study strongly support the notion that the most appropriate treatments should be made available for all patients in comprehensive centers and the call for an urgent implementation of telemedicine in the rural areas of our district.

Gender and stroke: acute phase treatment and prevention.

Stroke is the third most common cause of death in women and a major cause of disability. Many aspects of stroke are similar in men and women, including clinical presentation, main risk factors, and distribution of the main subtypes. There are, however, some gender differences and specificities in stroke including some aspects related to treatment. Women are less likely to receive thrombolysis than men; however, in treated cases, the efficacy of intravenous thrombolysis is higher in women than in men. Hormone replacement therapy has been suggested as a possible strategy to reduce the occurrence of stroke in postmenopausal women but several clinical trials failed to show any benefit in stroke and cardiovascular disease prevention. Also in stroke prevention with antiplatelets there emerge some important gender differences: in primary prevention of stroke, aspirin was effective in women but not in men while in secondary prevention no gender differences were found with any of the available antiplatelet agents.

Comorbid neuropathologies in migraine: an update on cerebrovascular and cardiovascular aspects.

Several conditions are comorbid with migraine; our review is focused on the relation between migraine, and cerebrovascular and cardiovascular diseases. Despite many studies showed an association between migraine and patent foramen ovale, it is still not known whether its presence might be causal for the migraine pathogenesis and currently its closure cannot be recommended for migraine prevention. On the contrary, conflicting epidemiological data link migraine to arterial hypertension and the use of antihypertensive agents acting on the renin-angiotensin system sounds promising in migraine prevention. A complex bidirectional relation exists between migraine and stroke, and new evidences show a clear association between migraine and coronary heart disease. In both conditions, migraine represents a defined risk factor although the magnitude of the risk varies across the different studies. However, since the risk is low in the general population, it is not possible to identify which migraineurs will develop a cardiovascular or a cerebrovascular event making difficult to apply preventive measures.