To assess the role of body mass index (BMI) and of the rate of weight loss as prognostic factors in amyotrophic lateral sclerosis (ALS) and to explore the clinical correlates of weight loss in the ...early phases of the disease.
The study cohort included all ALS patients in Piemonte/Valle d'Aosta in the 2007-2011 period. Overall survival and the probability of death/tracheostomy at 18 months (logistic regression model) were calculated.
Of the 712 patients, 620 (87.1%) were included in the study. Patients ' survival was related to the mean monthly percentage of weight loss at diagnosis (p<0.0001), but not to pre-morbid BMI or BMI at diagnosis. Spinal onset patients with dysphagia at diagnosis had a median survival similar to bulbar onset patients. About 20% of spinal onset patients without dysphagia at diagnosis had severe weight loss and initial respiratory impairment, and had a median survival time similar to bulbar onset patients.
The rate of weight loss from onset to diagnosis was found to be a strong and independent prognostic factor in ALS. Weight loss was mainly due to the reduction of nutritional intake related to dysphagia, but a subgroup of spinal onset patients without dysphagia at diagnosis had a severe weight loss and an outcome similar to bulbar patients. According to our findings, we recommend that in clinical trials patients should be stratified according to the presence of dysphagia at the time of enrolment and not by site of onset of symptoms.
Background:
The MuSC-19 project is an Italian cohort study open to international partners that collects data on multiple sclerosis (MS) patients with COVID-19. During the second wave of the pandemic, ...serological tests became routinely available.
Objective:
To evaluate the seroprevalence of anti-SARS-CoV-2 antibodies according to the use of disease-modifying therapy (DMT) in a subset of patients included in the MuSC-19 data set who had undergone a serological test.
Methods:
We evaluated the association between positive serological test results and time elapsed since infection onset, age, sex, Expanded Disability Status Scale score, comorbidities and DMT exposure using a multivariable logistic model.
Results:
Data were collected from 423 patients (345 from Italy, 61 from Turkey and 17 from Brazil) with a serological test performed during follow-up. Overall, 325 out of 423 tested patients (76.8%) had a positive serological test. At multivariate analysis, therapy with anti-CD20 was significantly associated with a reduced probability of developing antibodies after COVID-19 (odds ratio (OR) = 0.20, p = 0.002).
Conclusion:
Patients with MS maintain the capacity to develop humoral immune response against SARS-COV-2, although to a lesser extent when treated with anti-CD20 drugs. Overall, our results are reassuring with respect to the possibility to achieve sufficient immunization with vaccination.
It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the ...outcomes expected in the age- and sex-matched Italian population.
Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale EDSS score > 3 or at least 1 comorbidity, lower risk: EDSS score ≤ 3 and no comorbidities) by the χ
test, and the risk excess was quantified by risk ratios (RRs).
The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (
< 0.001), RR = 2.19 for ICU admission (
< 0.001), and RR = 2.43 for death (
< 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03,
= 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events,
= 0.04).
Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon.
Background and purpose
Clinical outcomes of multiple sclerosis (MS) patients affected by coronavirus disease 2019 (COVID‐19) have been thoroughly investigated, but a further analysis on main signs ...and symptoms and their risk factors still needs attention. The objective of this study was to group together and describe based on similarity the most common signs and symptoms of COVID‐19 in MS patients and identify all factors associated with their manifestation.
Method
Logistic and linear regression models were run to recognize factors associated with each pooled group of symptoms and their total number.
Results
From March 2020 to November 2021, data were collected from 1354 MS patients with confirmed infection of COVID‐19. Ageusia and anosmia was less frequent in older people (odds ratio OR 0.98; p = 0.005) and more in smoker patients (OR 1.39; p = 0.049). Smoke was also associated with an incremental number of symptoms (OR 1.24; p = 0.031), substance abuse (drugs or alcohol), conjunctivitis and rash (OR 5.20; p = 0.042) and the presence of at least one comorbidity with shortness of breath, tachycardia or chest pain (OR 1.24; p = 0.008). Some disease‐modifying therapies were associated with greater frequencies of certain COVID‐19 symptoms (association between anti‐CD20 therapies and increment in the number of concomitant symptoms: OR 1.29; p = 0.05). Differences in frequencies between the three waves were found for flu‐like symptoms (G1, p = 0.024), joint or muscle pain (G2, p = 0.013) and ageusia and anosmia (G5, p < 0.001). All cases should be referred to variants up to Delta.
Conclusion
Several factors along with the choice of specific therapeutic approaches might have a different impact on the occurrence of some COVID‐19 symptoms.
OBJECTIVE:To analyze the frequency and clinical characteristics of patients with amyotrophic lateral sclerosis (ALS) with intermediate-length (CAG) expansion (encoding 27–33 glutamines, polyQ) in the ...ATXN2 gene, in a population-based cohort of Italian patients with ALS (discovery cohort), and to replicate the findings in an independent cohort of consecutive patients from an ALS tertiary center (validation cohort).
METHODS:PolyQ repeats were assessed in 672 patients with incident ALS in Piemonte and Valle dʼAosta regions, Italy, in the 2007–2012 period (discovery cohort); controls were 509 neurologically healthy age- and sex-matched subjects resident in the study area. The validation cohort included 661 patients with ALS consecutively seen between 2001 and 2013 in the ALS Clinic Center of the Catholic University in Rome, Italy.
RESULTS:In the discovery cohort, the frequency of ≥31 polyQ ATNX2 repeats was significantly more common in ALS cases (19 patients vs 1 control, p = 0.0001; odds ratio 14.8, 95% confidence interval 1.9–110.8). Patients with an increased number of polyQ repeats had a shorter survival than those with <31 repeats (median survival, polyQ ≥31, 1.8 years, interquartile range IQR 1.3–2.2; polyQ <31, 2.7 years, IQR 1.6–5.1; p = 0.001). An increased number of polyQ repeats remained independently significant at multivariable analysis. In the validation cohort, patients with ≥31 polyQ repeats had a shorter survival than those with <31 repeats (median survival, polyQ ≥31, 2.0 years, IQR 1.5–3.4; polyQ <31, 3.2 years, IQR 2.0–6.4; p = 0.007).
CONCLUSIONS:ATXN2 polyQ intermediate-length repeat is a modifier of ALS survival. Disease-modifying therapies targeted to ATXN2 represent a promising therapeutic approach for ALS.
Abstract Objectives To evaluate the presence of chronic cerebrospinal venous insufficiency (CCSVI) and cerebral venous anomalies in a consecutive series of patients with multiple sclerosis (MS), ...other neurologic diseases (NEU) and healthy controls (HC). Methods A consecutive series of 80 MS patients, 41 HC and 26 NEU cases underwent a transcranial and extracranial echo-color Doppler (ECD) evaluation of cerebrospinal venous return in a sonographer-blinded fashion. According to the original Dr. Zamboni's protocol, CCSVI was diagnosed in presence of ≥2 ECD venous criteria. Results We did not observe any association between CCSVI and MS. CCSVI was detected in 17.5% of MS cases, 7.3% of HC and 11.5% of NEU patients ( p = 0.333). The prevalence of internal jugular vein stenosis (IJV) and the proportion of patients with any positive ECD criterion differed significantly among groups, being higher in MS cases versus HC (67.5% and 76.2% versus 48.8% and 41.5%, respectively; p = 0.005 and p = 0.006). No relationship between CCSVI and MS type and severity was evidenced. Conclusions The present study argues against a positive link between CCSVI and MS risk or severity. Interestingly, a weak association between venous ECD anomalies (in particular IJV stenosis) and MS was observed in our population. This finding should be interpreted with caution due to the possible confounders and needs to be confirmed in large controlled studies.
To assess the frequency and clinical characteristics of patients with mutations of major amyotrophic lateral sclerosis (ALS) genes in a prospectively ascertained, population-based epidemiologic ...series of cases.
The study population includes all ALS cases diagnosed in Piemonte, Italy, from January 2007 to June 2011. Mutations of SOD1, TARDBP, ANG, FUS, OPTN, and C9ORF72 have been assessed.
Out of the 475 patients included in the study, 51 (10.7%) carried a mutation of an ALS-related gene (C9ORF72, 32; SOD1, 10; TARDBP, 7; FUS, 1; OPTN, 1; ANG, none). A positive family history for ALS or frontotemporal dementia (FTD) was found in 46 (9.7%) patients. Thirty-one (67.4%) of the 46 familial cases and 20 (4.7%) of the 429 sporadic cases had a genetic mutation. According to logistic regression modeling, besides a positive family history for ALS or FTD, the chance to carry a genetic mutation was related to the presence of comorbid FTD (odds ratio 3.5; p = 0.001), and age at onset ≤54 years (odds ratio 1.79; p = 0.012).
We have found that ∼11% of patients with ALS carry a genetic mutation, with C9ORF72 being the commonest genetic alteration. Comorbid FTD or a young age at onset are strong indicators of a possible genetic origin of the disease.
An investigation of the polar glycosidic fraction from the leaves of myrtle afforded four galloylated nonprenylated phloroglucinol glucosides (3a−d) related to the endoperoxide hormone G3 (4) in ...terms of structure and biogenesis. Despite their close similarity, significant antibacterial activity was shown only by one of these compounds (3b, gallomyrtucommulone B), while the G3 hormone (4) was inactive.
Investigation of an acetone extract from asafetida afforded two drimane sesquiterpene dienones (fetidones A and B, 1a,b) and several known sesquiterpene coumarin ethers, one of which ...(8-acetoxy-5-hydroxyumbelliprenin, 2a) showed potent and specific NF-κB-inhibiting properties. This, coupled to a negligible cytotoxicity, qualifies 2a as a new anti-inflammatory chemotype, and its occurrence in asafetida might rationalize the use of this gum resin to alleviate and prevent colon inflammatory disturbances.
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