Validation of the Italian version of a new coma scale: the FOUR score

The Glasgow Coma Scale (GCS) is the most widely accepted tool for the evaluation of consciousness, despite several reported shortcomings. A new coma scale, named Full Outline of UnResponsiveness (FOUR) score, is now available. The aim of the present study is to provide and validate the Italian version of the FOUR score. The Italian version of the FOUR score was developed according to a standardized protocol, and thereafter validated in a series of patients with acute neurological illness. For each patient, the FOUR and the GCS scores were recorded by two physicians randomly selected. The inter-rater agreement for the FOUR and the GCS scores was evaluated using the weighted kappa (kappa(w)). The receiving operating characteristic curve was also calculated to determine the ability of the scales to predict outcome. Eighty-seven consecutive patients with an acute brain injury were enrolled. The inter-rater agreement was excellent both for the FOUR (kappa(w) = 0.953; P < 0.0001) and the GCS (kappa(w) = 0.943; P < 0.01). The area under the curve for mortality was 0.935 for the FOUR and 0.953 for the GCS. The FOUR score provides greater neurological details than the GCS. Our data indicate that the Italian version of the FOUR score is a valid predictor of outcome, yielding reproducible findings across raters independent of their expertise

The First Historically Reported Italian Family with FTD/ALS Teaches a Lesson on C9orf72 RE: Clinical Heterogeneity and Oligogenic Inheritance

Background: In 1969, Dazzi and Finizio reported the second observation of frontotemporal dementia (FTD) - amyotrophic lateral sclerosis (ALS) association in a large Italian kindred affected by an autosomal dominant form of ALS with high penetrance, frequent bulbar onset, and frequent cognitive decline. Objective:To expand the original characterization of this family and report the link with the C9orf72 repeat expansion (RE).Methods: We followed or reviewed the medical records of thirteen patients belonging to the original family and performed genetic analyses in four individuals. Results: Eight patients presented with ALS, four with FTD, and one with schizophrenia. The C9orf72RE was found in three patients but not in the healthy survivor. Additionally, we found a novel possible pathogenic variant in the ITM2B gene in one patient with a complex phenotype, associating movement disorders, psychiatric and cognitive features, deafness, and optic atrophy. The neuropathological examination of this patient did not show the classical features of ITM2B mutation related dementias suggesting that the putative pathogenic mechanism does not involve cellular mislocalization of the protein or the formation of amyloid plaques. Conclusion: We showed that the original Italian pedigree described with FTD/ALS carries the C9orf72 RE. Moreover, the finding of an additional mutation in another dementia causing gene in a patient with a more complex phenotype suggests a possible role of genetic modifiers in the disease.Together with other reports showing the coexistence of mutations in multiple ALS/FTD causative genes in the same family, our study supports an oligogenic etiology of ALS/FTD

The Comorbidities Coma Scale (CoCoS): Psychometric Properties and Clinical Usefulness in Patients With Disorders of Consciousness.

Although comorbidities have a well-known impact on the functional recovery of patients with disorders of consciousness, including coma, vegetative state (VS), and minimally conscious state (MCS), a specific tool for their assessment in this challenging group of patients is lacking. For this aim, a multistep process was used to develop and validate the Comorbidities Coma Scale (CoCoS) in a sample of 162 patients with a diagnosis of coma, VS or MCS admitted to four Acute Inpatient Rehabilitation Units. To establish the psychometric properties of the scale, content validity, and internal consistency were investigated through Exploratory Factor Analysis in the whole sample (n = 162). Interrater reliability, assessed by the weighted Cohen's kappa (Kw), and concurrent validity of the scale as compared to the Greenfield Scale, assessed by ρ Spearman's correlation coefficient, were investigated in a subsample of patients (n = 52) within two of the above units. Our findings provided evidence of a good content validity of the scale, with the identification of a 12-factor structure representing the different comorbid dimensions of the target population. Inter-rater reliability was excellent in both the rehabilitation units where the assessment was made [Kw 0.98 (95% CI 0.96-0.99)]. CoCoS total scores correlated significantly with total scores of the Greenfield Scale (ρ = 0.932, 95% CI 0.89-0.96; P &lt; 0.0001) indicating that CoCoS has concurrent validity while being more informative about the specific pattern of comorbidities of these challenging patients. The CoCos is a new tool which standardizes the approach to assessment of comorbid conditions and reliably identifies the category and severity of each comorbidity detected. It may be used for both clinical and research applications

The Comorbidities Coma Scale (CoCoS): Psychometric Properties and Clinical Usefulness in Patients With Disorders of Consciousness.

Although comorbidities have a well-known impact on the functional recovery of patients with disorders of consciousness, including coma, vegetative state (VS), and minimally conscious state (MCS), a specific tool for their assessment in this challenging group of patients is lacking. For this aim, a multistep process was used to develop and validate the Comorbidities Coma Scale (CoCoS) in a sample of 162 patients with a diagnosis of coma, VS or MCS admitted to four Acute Inpatient Rehabilitation Units. To establish the psychometric properties of the scale, content validity, and internal consistency were investigated through Exploratory Factor Analysis in the whole sample (n = 162). Interrater reliability, assessed by the weighted Cohen's kappa (Kw), and concurrent validity of the scale as compared to the Greenfield Scale, assessed by ρ Spearman's correlation coefficient, were investigated in a subsample of patients (n = 52) within two of the above units. Our findings provided evidence of a good content validity of the scale, with the identification of a 12-factor structure representing the different comorbid dimensions of the target population. Inter-rater reliability was excellent in both the rehabilitation units where the assessment was made [Kw 0.98 (95% CI 0.96-0.99)]. CoCoS total scores correlated significantly with total scores of the Greenfield Scale (ρ = 0.932, 95% CI 0.89-0.96; P &lt; 0.0001) indicating that CoCoS has concurrent validity while being more informative about the specific pattern of comorbidities of these challenging patients. The CoCos is a new tool which standardizes the approach to assessment of comorbid conditions and reliably identifies the category and severity of each comorbidity detected. It may be used for both clinical and research applications

Data_Sheet_1_Cranial autonomic symptoms and response to monoclonal antibodies targeting the Calcitonin gene-related peptide pathway: A real-world study.docx

ObjectiveCranial 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.MethodsWe 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.ResultsOut 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.ConclusionsIn 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.</p

Long-Term Treatment Over 52 Weeks with Monthly Fremanezumab in Drug-Resistant Migraine: A Prospective Multicenter Cohort Study

Background: Real-world studies on fremanezumab, an anti-calcitonin gene-related peptide monoclonal antibody for migraine prevention, are few and with limited follow-up. Objective: We aimed to evaluate the long-term (up to 52 weeks) effectiveness and tolerability of fremanezumab in high-frequency episodic migraine and chronic migraine. Methods: This s an independent, prospective, multicenter cohort study enrolling outpatients in 17 Italian Headache Centers with high-frequency episodic migraine or chronic migraine and multiple preventive treatment failures. Patients were treated with fremanezumab 225 mg monthly. The primary outcomes included changes from baseline (1 month before treatment) in monthly headache days, response rates (reduction in monthly headache days from baseline), and persistence in medication overuse at months 3, 6, and 12 (all outcome timeframes refer to the stated month). Secondary outcomes included changes from baseline in acute medication intake and disability questionnaires scores at the same timepoints. A last observation carried forward analysis was also performed. Results: A total of 90 patients who received at least one dose of fremanezumab and with a potential 12-month follow-up were included. Among them, 15 (18.0%) patients discontinued treatment for the entire population, a reduction in monthly headache days compared with baseline was reported at month 3, with a significant median [interquartile range] reduction in monthly headache days (- 9.0 [11.5], p < 0.001). A statistically different reduction was also reported at month 6 compared with baseline (- 10.0 [12.0]; p < 0.001) and at 12 months of treatment (- 10.0 [14.0]; p < 0.001). The percentage of patients with medication overuse was significantly reduced compared with baseline from 68.7% (57/83) to 29.6% (24/81), 25.3% (19/75), and 14.7% (10/68) at 3, 6, and 12 months of treatment, respectively (p < 0.001). Acute medication use (days and total number) and disability scores were also significantly reduced (p < 0.001). A ≥ 50% response rate was achieved for 51.9, 67.9, and 76.5% of all patients at 3, 6, and 12 months, respectively. Last observation carried forward analyses confirmed these findings. Fremanezumab was well tolerated, with just one patient discontinuing treatment because of adverse events. Conclusions: This study provides evidence for the real-world effectiveness of fremanezumab in treating both high-frequency episodic migraine and chronic migraine, with meaningful and sustained improvements in multiple migraine-related variables. No new safety issue was identified

Association of the careggi collateral score with radiological outcomes after thrombectomy for stroke with an occlusion of the middle cerebral artery

: We aimed to examine the association between Careggi Collateral Score (CCS) and radiological outcomes in a large multicenter cohort of patients receiving thrombectomy for stroke with occlusion of middle cerebral artery (MCA). We conducted a study on prospectively collected data from 1785 patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke. According to the extension of the retrograde reperfusion in the cortical anterior cerebral artery-MCA territories, CCS ranges from 0 (absence of retrograde filling) to 4 (visualization of collaterals until the alar segment of the MCA). Radiological outcomes at 24&nbsp;h were the presence and severity of infarct growth defined by the absolute change in ASPECTS from baseline to 24&nbsp;h; presence and severity of cerebral bleeding defined as no ICH, HI-1, HI-2, PH-1, or PH-2; presence and severity of cerebral edema (CED) defined as no CED, CED-1, CED-2, or CED-3. Using CCS = 0 as reference, ORs of CCS grades were significantly associated in the direction of better radiological outcome on infarct growth (0.517 for CCS = 1, 0.413 for CCS = 2, 0.358 for CCS = 3, 0.236 for CCS = 4), cerebral bleeding grading (0.485 for CCS = 1, 0.445 for CCS = 2, 0.400 for CCS = 3, 0.379 for CCS = 4), and CED grading (0.734 for CCS = 1, 0.301 for CCS = 2, 0.295 for CCS = 3, 0.255 for CSS = 4) shift in ordinal regression analysis after adjustment for pre-defined variables (age, NIHSS score, ASPECTS, occlusion site, onset-to-groin puncture time, procedure time, and TICI score). Using CCS = 4 as reference, ORs of CCS grades were significantly associated in the direction of worse radiological outcome on infarct growth (1.521 for CCS = 3, 1.754 for CCS = 2, 2.193 for CCS = 1, 4.244 for CCS = 0), cerebral bleeding grading (2.498 for CCS = 0), and CED grading (1.365 for CCS = 2, 2.876 for CCS = 1, 3.916 for CCS = 0) shift. The CCS could improve the prognostic estimate of radiological outcomes in patients receiving thrombectomy for stroke with MCA occlusion

IER-START nomogram for prediction of three-month unfavorable outcome after thrombectomy for stroke

BACKGROUND: The applicability of the current models for predicting functional outcome after thrombectomy in strokes with large vessel occlusion (LVO) is affected by a moderate predictive performance. AIMS: We aimed to develop and validate a nomogram with pre- and post-treatment factors for prediction of the probability of unfavorable outcome in patients with anterior and posterior LVO who received bridging therapy or direct thrombectomy <6 h of stroke onset. METHODS: We conducted a cohort study on patients data collected prospectively in the Italian Endovascular Registry (IER). Unfavorable outcome was defined as three-month modified Rankin Scale (mRS) score 3-6. Six predictors, including NIH Stroke Scale (NIHSS) score, age, pre-stroke mRS score, bridging therapy or direct thrombectomy, grade of recanalization according to the thrombolysis in cerebral ischemia (TICI) grading system, and onset-to-end procedure time were identified a priori by three stroke experts. To generate the IER-START, the pre-established predictors were entered into a logistic regression model. The discriminative performance of the model was assessed by using the area under the receiver operating characteristic curve (AUC-ROC). RESULTS: A total of 1802 patients with complete data for generating the IER-START was randomly dichotomized into training ( n = 1219) and test ( n = 583) sets. The AUC-ROC of IER-START was 0.838 (95% confidence interval [CI]): 0.816-0.869) in the training set, and 0.820 (95% CI: 0.786-0.854) in the test set. CONCLUSIONS: The IER-START nomogram is the first prognostic model developed and validated in the largest population of stroke patients currently candidates to thrombectomy which reliably calculates the probability of three-month unfavorable outcome