Antonio Carotenuto

Cognitive impairment at diagnosis predicts 10-year multiple sclerosis progression:

Background: Cognitive impairment occurs from the early phases of multiple sclerosis (MS), and more frequently affects secondary progressive (SP) subjects than relapsing–remitting (RR). Objective: To investigate relationships between cognitive dysfunctions in newly diagnosed RRMS, and long-term MS-related outcomes. Methods: The present 10-year retrospective longitudinal study included 155 RRMS subjects, tested with the Rao Brief Repeatable Battery at MS diagnosis. The reaching of Expanded Disability Status Scale (EDSS) 4.0, and the SP conversion were recorded. Results: 67 subjects (43.2%) reached EDSS 4.0, and 34 subjects (21.9%) converted to SP during a follow-up period of 10.0±1.8 years. Subjects with cognitive impairment at diagnosis had a rate of reaching EDSS 4.0 more than three times greater (p<0.001; HR=3.183), and a rate of SP conversion more than two times greater, as compared to cognitively preserved subjects (p=0.008; HR=2.535). In particular, better scores in the Selective Reminding Test-Delayed Recall and in the Symbol Digit Modalities Test at baseline were associated with lower SP conversion rates during the follow-up period (p=0.018; HR=0.835; and p=0.001; HR=0.941, respectively). Conclusion: Cognitive impairment, with particular involvement of processing speed and memory, predicts disability progression and SP conversion in newly diagnosed RRMS, highlighting the importance of cognitive assessment from the beginning of MS.

The Framingham cardiovascular risk score in multiple sclerosis.

Cardiovascular risk factors can increase the risk of multiple sclerosis (MS) and modify its course. However, such factors possibly interact, determining a global cardiovascular risk. Our aim was to compare the global cardiovascular risk of subjects with and without MS with the simplified 10‐year Framingham General Cardiovascular Disease Risk Score (FR) and to evaluate its importance on MS‐related outcomes.

Epilepsy in ring 14 chromosome syndrome

Ring chromosome 14 [r(14)] is a rare disorder. The aim of this study was to describe two new cases of r(14) drug-resistant epilepsy, and, through an extensive review of literature, highlight those epileptological features which are more commonly found and which may help in early diagnosis, genetic counseling, and treatment. Epilepsy onset in r(14) syndrome takes place during the first year of life; seizures are generalized or focal and less frequently myoclonic. Seizures might be induced by fever. Focal seizures are characterized by staring, eye or head deviation, respiratory arrest, swallowing, and hypertonia/hypotonia or clonic movements. Ictal EEG might show both focal and diffuse discharges. Interictal EEG reveals mainly focal abnormalities. Mental retardation represents a constant feature. Neurological assessment yields a delay in motor skill acquisition and less frequently both pyramidal and cerebellar signs. Dysmorphic features are evident in the majority of cases. Epilepsy associated with r(14) has many features that entail a challenging diagnostic process. The reported cases of r(14)-related epilepsy seem to highlight a series of common elements which may be helpful in pointing the clinician towards a correct diagnosis.

Uric acid: a potential biomarker of multiple sclerosis and of its disability

Abstract Background: Uric acid (UA) is a strong natural scavenger of reactive oxygen and nitrogen species, with evidence of possible use in the treatment of animal models of multiple sclerosis (MS). Consequently, serum UA has gained much attention as a possible biomarker of MS. We aim to investigate differences in serum UA levels between MS subjects and controls and evaluate possible relationships of UA with MS clinical features. Methods: We recruited relapsing-remitting and secondary progressive MS subjects and healthy controls and measured their serum UA levels. We excluded subjects presenting concomitant conditions affecting UA levels. Results: MS subjects (n=362) and controls (n=181) were recruited by propensity score matching (PSM). Statistical analyses were corrected for age, gender, and renal function. MS subjects presented significantly lower serum UA levels than controls (analysis of variance, p=0.014, adjusted r2=0.3036). Linear regression analysis showed a relationship between UA levels and disease duration (p<0.001, adjusted r2=0.3158, coefficient –0.00039), time from diagnosis (p<0.001, adjusted r2=0.3100, coefficient –0.0012), and Expanded Disability Status Scale (EDSS) (p<0.001, adjusted r2=0.3230, coefficient –0.1). Conclusions: Our findings support the importance of serum UA as a biomarker of MS disability and progression. Further studies with longitudinal design should be specifically designed to evaluate the importance of UA in the different stages of MS and in relation to distinct therapeutic strategies.

Can people with multiple sclerosis actually understand what they read in the Internet age

People with multiple sclerosis (MS) frequently report difficulties in finding personally relevant information on the Internet. With this in mind, the Google top-ten patient-oriented results were analysed for their overall level of readability. The most commonly visited websites required an average grade level of 11.74 ± 1.54, and an average number of years of formal education of 12.78 ± 1.82, to be easily understood. The average Flesch Reading Ease readability index is 45.26 ± 7.35, a difficult-to-read score. The high educational level required to easily understand most websites worsens health inequalities, not allowing a full participation in health information and decision making.

A longitudinal real-life comparison study of natalizumab and fingolimod.

Different retrospective studies compared natalizumab and fingolimod in relapsing‐remitting multiple sclerosis (RRMS), with conflicting results. We aimed to explore the prescriptive attitude and the clinical outcome of the two therapies.

Predictors of long-term interferon discontinuation in newly diagnosed relapsing multiple sclerosis

BACKGROUND Interferon-β has long-term safety and efficacy profiles for Relapsing Remitting Multiple Sclerosis (RRMS). However, the increasing number of available treatments requires to improve patient profiling and to perform individualized clinical decisions. Therefore, the present study investigated predictors of Interferon-β discontinuation. METHODS The present retrospective observational cohort study included 499 newly diagnosed, drug naïve RRMS subjects receiving Interferon-β as first disease modifying treatment (DMT), during a 7.9±3.8 year period, up to treatment discontinuation. Possible markers of interest were recorded at the time of diagnosis (age, gender, disease duration, baseline EDSS) or during follow-up as variables of disease evolution (relapse occurrence, annualized relapse rate -ARR-, 1-point EDSS progression, reaching of EDSS 4.0) or of treatment (high-dose Interferon-β1a, low-dose Interferon-β1a, or Interferon-β1b). RESULTS 217 patients (43.5%) discontinued the treatment during the follow-up period, with an incidence of 5% person-years (95%CI=4.6-5.9%). A multivariate Cox regression model showed an increased rate of Interferon-β discontinuation for female gender (p=0.019; HR=1.428), higher baseline EDSS (p=0.026; HR=1.346), relapse occurrence (p=0.009; HR=1.618), higher ARR (p<0.001; HR=5.269), and Interferon-β1b treatment (p=0.019; HR=1.506); and a reduced rate for occurrence of EDSS progression (p<0.001; HR=0.299). CONCLUSIONS Most of the factors associated with Interferon-β discontinuation are not modifiable, and are part of demographic features (i.e. gender), or of disease characteristics (i.e. disability at diagnosis), but should be taken into account when prescribing the first DMT for MS. Noteworthy, the use of Interferon-β1b is associated with 50% increased risk of discontinuation, compared with high-dose Interferon-β1a, highlighting the importance of drug formulations in treatment persistence.

Lymphocytosis as a response biomarker of natalizumab therapeutic efficacy in multiple sclerosis

Background: Natalizumab is an effective therapy in relapsing–remitting multiple sclerosis (RRMS), as it reduces lymphocyte transmigration through the blood–brain barrier (BBB) and induces lymphocytosis. Objectives: To analyse natalizumab-induced lymphocytosis (NIL) as a biomarker of drug efficacy. Materials and methods: We enrolled 50 relapsing–remitting (RR) and progressive–relapsing (PR) natalizumab-treated patients who had received at least 16 infusions and had been tested for lymphocyte count 24 hours before each administration. Clinical, MRI and hematological data were collected. Patients were divided into responders and sub-optimal responders according to the experience of at least one clinical and/or instrumental relapse during the treatment. Results: In 15 (30%) patients, an instrumental/clinical (14) or only instrumental (one) relapse occurred. We found a statistically significant difference in the mean percentage of the lymphocytes between the two groups over the first ten administrations (p=0.04). The comparison between the time-to-relapse in the groups with high and low levels of lymphocytes showed that the group with a low NIL had a greater risk of relapse (p=0.03). Conclusions: We suggest that NIL could be a biomarker of therapeutic efficacy in patients with RRMS treated with natalizumab, and that the risk of relapse may be higher in patients with a lower-than-expected NIL.

Communication in Multiple Sclerosis: Pragmatic Deficit and its Relation with Cognition and Social Cognition

Objective Cognitive functions have been largely investigated in multiple sclerosis. Less attention has been paid to social communication abilities, despite their presumptive affect on quality of life. We run the first comprehensive assessment of pragmatic skills in multiple sclerosis, evaluating also the relationship between pragmatics and other cognitive domains. Methods Forty-two multiple sclerosis patients and 42 controls were tested for pragmatic abilities, neuro-cognition, social cognition, depression, and fatigue. Results Patients performed poorly in most pragmatic tasks compared to controls. Globally, 55% of patients performed below the 5th percentile in the total pragmatic score. Notably, pragmatic skills did not differ between cognitively impaired and unimpaired patients. However, an association was found between pragmatics and verbal fluency, as measured in the Word List Generation. Finally, we observed an association of pragmatic abilities with social cognition, and a trend with psychosocial functioning. Conclusion Overall, the study shows a diffuse pragmatic impairment in multiple sclerosis, not associated with the patients global neuropsychological profile. By contrast, our findings suggest a close relation between pragmatics and specific cognitive aspects such as executive functions, and between pragmatics and social cognition. This study underlines the need of looking beyond classical cognitive performance, to consider underestimated communicative disturbances of high clinical relevance.

Optical coherence tomography angiography retinal vascular network assessment in multiple sclerosis

Background: Optical coherence tomography (OCT) angiography is a new method to assess the density of the vascular networks. Vascular abnormalities are considered involved in multiple sclerosis (MS) pathology. Objective: To assess the presence of vascular abnormalities in MS and to evaluate their correlation to disease features. Methods: A total of 50 MS patients with and without history of optic neuritis (ON) and 46 healthy subjects were included. All underwent spectral domain (SD)-OCT and OCT angiography. Clinical history, Expanded Disability Status Scale (EDSS), Multiple Sclerosis Severity Score (MSSS) and disease duration were collected. Results: Angio-OCT showed a vessel density reduction in eyes of MS patients when compared to controls. A statistically significant reduction in all SD-OCT and OCT angiography parameters was noticed both in eyes with and without ON when compared with control eyes. We found an inverse correlation between SD-OCT parameters and MSSS (p = 0.003) and between vessel density parameters and EDSS (p = 0.007). Conclusion: We report a vessel density reduction in retina of MS patients. We highlight the clinical correlation between vessel density and EDSS, suggesting that angio-OCT could be a good marker of disease and of disability in MS.