Assessment of diagnostic criteria for multifocal motor neuropathy in patients included in the Italian database.

BACKGROUND AND PURPOSE: This study aimed to assess the diagnostic criteria, ancillary investigations and treatment response using real-life data in multifocal motor neuropathy (MMN) patients. METHODS: Clinical and laboratory data were collected from 110 patients enrolled in the Italian MMN database through a structured questionnaire. Twenty-six patients were excluded due to the unavailability of nerve conduction studies or the presence of clinical signs and symptoms and electrodiagnostic abnormalities inconsistent with the MMN diagnosis. Analyses were conducted on 73 patients with a confirmed MMN diagnosis and 11 patients who did not meet the diagnostic criteria. RESULTS: The European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) diagnostic criteria were variably applied. AUTHOR: When applying the American Association of Electrodiagnostic Medicine criteria, an additional 17% of patients fulfilled the criteria for probable/definite diagnosis whilst a further 9.5% missed the diagnosis. In 17% of the patients only compound muscle action potential amplitude, but not area, was measured and subsequently recorded in the database by the treating physician. Additional investigations, including anti-GM1 immunoglobulin M antibodies, cerebrospinal fluid analysis, nerve ultrasound and magnetic resonance imaging, supported the diagnosis in 46%-83% of the patients. Anti-GM1 immunoglobulin M antibodies and nerve ultrasound demonstrated the highest sensitivity. Additional tests were frequently performed outside the EFNS/PNS guideline recommendations. CONCLUSIONS: This study provides insights into the real-world diagnostic and management strategies for MMN, highlighting the challenges in applying diagnostic criteria.

Impact of 2021 European Academy of Neurology/Peripheral Nerve Society diagnostic criteria on diagnosis and therapy of chronic inflammatory demyelinating polyradiculoneuropathy variants.

BACKGROUND AND PURPOSE: There are different criteria for the diagnosis of different variants of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). The 2021 European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) guidelines provide specific clinical criteria for each CIDP variant even if their therapeutical impact has not been investigated. METHODS: We applied the clinical criteria for CIDP variants of the 2021 EAN/PNS guidelines to 369 patients included in the Italian CIDP database who fulfilled the 2021 EAN/PNS electrodiagnostic criteria for CIDP. RESULTS: According to the 2021 EAN/PNS clinical criteria, 245 patients achieved a clinical diagnosis of typical CIDP or CIDP variant (66%). We identified 106 patients with typical CIDP (29%), 62 distal CIDP (17%), 28 multifocal or focal CIDP (7%), four sensory CIDP (1%), 27 sensory-predominant CIDP (7%), 10 motor CIDP (3%), and eight motor-predominant CIDP (2%). Patients with multifocal, distal, and sensory CIDP had milder impairment and symptoms. Patients with multifocal CIDP had less frequently reduced conduction velocity and prolonged F-wave latency and had lower levels of cerebrospinal fluid protein. Patients with distal CIDP more frequently had reduced distal compound muscle action potentials. Patients with motor CIDP did not improve after steroid therapy, whereas those with motor-predominant CIDP did. None of the patients with sensory CIDP responded to steroids, whereas most of those with sensory-predominant CIDP did. CONCLUSIONS: The 2021 EAN/PNS criteria for CIDP allow a better characterization of CIDP variants, permitting their distinction from typical CIDP and more appropriate treatment for patients.

Topographical Correlation between Structural and Functional Impairment of the Macular Inner Retinal Layers in Multiple Sclerosis Eyes with a History of Optic Neuropathy.

We investigated the potential correlation between morphological and functional parameters describing the rarefaction and dysfunction of retinal ganglion cells (RGCs), located in the macula, in multiple sclerosis eyes with a history of optic neuritis (MS-ON). A total of 19 MS-ON eyes from 19 MS patients (mean age: 44.16 ± 4.66 years; 11 females and 8 males), with a mean disease duration of 10.06 ± 6.12 years and full recovery of visual acuity, and 30 age-similar (mean age: 45.09 ± 5.08 years) healthy eyes were submitted for ophthalmological evaluation using swept-source optical coherence tomography (SS-OCT) and multifocal photopic negative response (mfPhNR) to study the structural and functional features of localized RGCs. Both GCL+ thickness (via SS-OCT) and response amplitude density (RAD) (via mfPhNR) measurements were obtained from annular regions and ETDRS sectors. Morphological and electrophysiological data from the control and MS groups were compared by using an ANOVA test. GCL+ values were correlated with the corresponding RADs derived from almost superimposable areas using Pearson's tests (p < 0.01). In MS-ON eyes, the mean values of macular GCL+-T and mfPhNR RAD detected in all rings and ETDRS sectors were significantly reduced (p < 0.01) when compared with control ones. In addition, when plotting the GCL+-T and mfPhNR RAD individual data from MS-ON eyes, we found statistically significant linear correlations (p < 0.01) when considering responses from both rings and sectors. In conclusion, in MS-ON eyes, a topographical correlation between structural and functional impairment of macular RGCs occurs.

Unclassified clinical presentations of chronic inflammatory demyelinating polyradiculoneuropathy.

BACKGROUND: To assess the ability of the 2021 European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) clinical criteria for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) to include within their classification the whole spectrum of clinical heterogeneity of the disease and to define the clinical characteristics of the unclassifiable clinical forms. METHODS: The 2021 EAN/PNS clinical criteria for CIDP were applied to 329 patients fulfilling the electrodiagnostic (and in some cases also the supportive) criteria for the diagnosis of CIDP. Clinical characteristics were reviewed for each patient not strictly fulfilling the clinical criteria ('unclassifiable'). RESULTS: At study inclusion, 124 (37.5%) patients had an unclassifiable clinical presentation, including 110 (89%) with a typical CIDP-like clinical phenotype in whom some segments of the four limbs were unaffected by weakness ('incomplete typical CIDP'), 10 (8%) with a mild distal, symmetric, sensory or sensorimotor polyneuropathy confined to the lower limbs with cranial nerve involvement ('cranial nerve predominant CIDP') and 4 (1%) with a symmetric sensorimotor polyneuropathy limited to the proximal and distal areas of the lower limbs ('paraparetic CIDP'). Eighty-one (65%) patients maintained an unclassifiable presentation during the entire disease follow-up while 13 patients progressed to typical CIDP. Patients with the unclassifiable clinical forms compared with patients with typical CIDP had a milder form of CIDP, while there was no difference in the distribution patterns of demyelination. CONCLUSIONS: A proportion of patients with CIDP do not strictly fulfil the 2021 EAN/PNS clinical criteria for diagnosis. These unclassifiable clinical phenotypes may pose diagnostic challenges and thus deserve more attention in clinical practice and research.

Risk of disease relapse, safety and tolerability of SARS-CoV-2 vaccination in patients with chronic inflammatory neuropathies.

BACKGROUND AND PURPOSE: The aim was to evaluate the risk of relapse after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, and its safety and tolerability, in patients with chronic inflammatory neuropathies. METHODS: In this multicenter, cohort and case-crossover study, the risk of relapse associated with SARS-CoV-2 vaccination was assessed by comparing the frequency of relapse in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) patients who underwent or did not undergo vaccination. Frequency of relapse in the 3 months prior to and after vaccination, and safety and tolerability of SARS-CoV-2 vaccination, were also assessed. RESULTS: In all, 336 patients were included (278 CIDP, 58 MMN). Three hundred and seven (91%) patients underwent SARS-CoV-2 vaccination. Twenty-nine patients (9%) did not undergo vaccination. Mild and transient relapses were observed in 16 (5%) patients (13 CIDP, 3 MMN) after SARS-CoV-2 vaccination and in none of the patients who did not undergo vaccination (relative risk [RR] 3.21, 95% confidence interval [CI] 0.19-52.25). There was no increase in the specific risk of relapse associated with type of vaccine or diagnosis. Comparison with the 3-month control period preceding vaccination revealed an increased risk of relapse after vaccination (RR 4.00, 95% CI 1.35-11.82), which was restricted to CIDP patients (RR 3.25, 95% CI 1.07-9.84). The safety profile of SARS-CoV-2 vaccination was characterized by short-term, mild-to-moderate local and systemic adverse events. CONCLUSIONS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in CIDP and MMN patients does not seem to be associated with an increased risk of relapse at the primary end-point, although a slightly increased risk in CIDP patients was found compared to the 3 months before vaccination.

COVID-19 vaccine hesitancy among Italian people with multiple sclerosis.

INTRODUCTION: Vaccine hesitancy promotes the spread of infectious diseases including COVID-19 virus, limiting the herd immunity. Complications caused by COVID-19 in people with multiple sclerosis forced governments to ensure them prior access to vaccinations. Their propensity to be vaccinated needs to be assessed to promote adhesion to vaccination programs. The aim of this study was to explore the COVID-19 vaccine hesitancy rate in pwMS. METHODS: We conducted an observational study recruiting patients affected by multiple sclerosis followed at MS Clinical and Research Unit of Tor Vergata University, Rome. We invited them to fill in an online survey about their intent to get COVID-19 vaccination. Fisher's exact test and Kruskal-Wallis test were performed to explore differences in sociodemographic, clinical, and emotional variables relative to the opinions about vaccinations. An exploratory factor analysis (EFA) was performed to assess the factorial structure of the questionnaire; Pearson's correlations between the factors and Big Five personality dimensions were also calculated. RESULTS: Of 276 respondents, 90% was willing to get vaccinated, while only 1.4% was sure to refuse the vaccination. Education level, opinions on safety and efficacy of vaccines, and emotional status were found to be associated to the propensity of getting the COVID-19 vaccination (respectively: p = 0.012, p < 0.001, and p = 0.0001). Moreover, general opinions on healthcare system were related to the intention to get vaccinated. CONCLUSION: Our results reinforce the importance of a good relationship between doctor and patient and the need to adapt doctors' communication strategy to patients' personalities and beliefs.

Exposure to natalizumab throughout pregnancy: effectiveness and safety in an Italian cohort of women with multiple sclerosis.

OBJECTIVE: Assessing the risk of clinical and radiological reactivation during pregnancy and post partum in women with multiple sclerosis (MS) treated with natalizumab (NTZ) throughout pregnancy (LONG_EXP) compared with women interrupting treatment before (NO_EXP) and within >-30 days and ≤90 days from conception (SHORT_EXP), and describing newborns' outcomes. METHODS: Maternal clinical and radiological outcomes and obstetric and fetal outcomes were retrospectively collected and compared among groups (NO_EXP, SHORT_EXP, LONG_EXP). Predictors of clinical and radiological reactivation were investigated through univariable and multivariable analysis. RESULTS: 170 eligible pregnancies from 163 women referring to 29 Italian MS centres were included. Annualised relapse rate (ARR) was significantly lower in LONG_EXP (n=66, 0.02 (0.001-0.09)) compared with NO_EXP (n=31, 0.43 (0.21-0.75), p=0.002) and SHORT_EXP (n=73, 0.46 (0.30-0.66), p=0.0004) during pregnancy, and in LONG_EXP (0.12 (0.05-0.24)) compared with SHORT_EXP (0.30 (0.17-0.50), p=0.008) during post partum. Gadolinium-enhancing (Gd+) lesions were less frequent in LONG_EXP (n=6/50, 2.00%) compared with NO_EXP (n=9/21, 42.86%) and SHORT_EXP after delivery (n=17/49, 34.69%, p=0.010).Delaying NTZ resumption after delivery significantly increased the risk of relapses (OR=1.29 (95% CI 1.07 to 1.57), p=0.009) and Gd+ lesions (OR=1.49 (95% CI 1.17 to 1.89, p=0.001). Newborns' weight, length, head circumference and gestational age did not differ among groups after adjusting for confounders. Anaemia was tracked in 4/69 LONG_EXP newborns. Congenital anomaly rate was within the expected range for the untreated MS population. CONCLUSIONS: Our findings indicate that in women with MS treated with NTZ before conception, continuation of NTZ throughout pregnancy and its early resumption after delivery mitigate the risk of clinical and radiological reactivation. This approach has no major impact on newborns' outcomes.

Multifocal Electroretinogram Photopic Negative Response: A Reliable Paradigm to Detect Localized Retinal Ganglion Cells' Impairment in Retrobulbar Optic Neuritis Due to Multiple Sclerosis as a Model of Retinal Neurodegeneration.

The measure of the full-field photopic negative response (ff-PhNR) of light-adapted full-field electroretinogram (ff-ERG) allows to evaluate the function of the innermost retinal layers (IRL) containing primarily retinal ganglion cells (RGCs) and other non-neuronal elements of the entire retina. The aim of this study was to acquire functional information of localized IRL by measuring the PhNR in response to multifocal stimuli (mfPhNR). In this case-control observational and retrospective study, we assessed mfPhNR responses from 25 healthy controls and from 20 patients with multiple sclerosis with previous history of optic neuritis (MS-ON), with full recovery of visual acuity, IRL morphological impairment, and absence of morpho-functional involvement of outer retinal layers (ORL). MfPhNR response amplitude densities (RADs) were measured from concentric rings (R) with increasing foveal eccentricity: 0−5° (R1), 5−10° (R2), 10−15° (R3), 15−20° (R4), and 20−25° (R5) from retinal sectors (superior-temporal (ST), superior-nasal (SN), inferior-nasal (IN), and inferior-temporal (IT)); between 5° and 20° and from retinal sectors (superior (S), temporal (T), inferior (I), and nasal (N)); and within 5° to 10° and within 10° and 20° from the fovea. The mfPhNR RAD values observed in all rings or sectors in MS-ON eyes were significantly reduced (p < 0.01) with respect to control ones. Our results suggest that mfPhNR recordings may detect localized IRL dysfunction in the pathologic condition of selective RGCs neurodegeneration.

Influence of Previous Disease-Modifying Drug Exposure on T-Lymphocyte Dynamic in Patients With Multiple Sclerosis Treated With Ocrelizumab.

BACKGROUND AND OBJECTIVES: To investigate the longitudinal dynamic of lymphocyte subsets during treatment with ocrelizumab (OCR) in patients with multiple sclerosis (PwMS). METHODS: A multicenter retrospective study was conducted in 161 PwMS starting treatment with OCR grouped in naive (naive, n = 40), switching from fingolimod (FTY, n = 52), and switching from other immunomodulating drugs (other, n = 69). Mean lymphocyte subset (total, CD3+, CD4+, CD8+, CD20+, and natural killer) counts were analyzed at baseline, 6 months, and 12 months. Rate of lymphocytopenia for each subset was calculated at all time points in all groups. RESULTS: Mean total, CD3+, and CD4+ counts were significantly different among groups (p < 0.001) at all time points, whereas CD8+ and CD20+ counts only at baseline (p = 0.0157; p < 0.001), consistently lower in FTY. After adjustment for baseline values, interaction time*group was not statistically significant (p > 0.05 for each subset). The odds of lymphopenia were significantly higher among FTY patients compared with naive for total, CD3+, CD4+, and CD20+ cells at baseline, for total and CD4+ cells at the sixth month, and for total cells at the 12th month. DISCUSSION: OCR per se exerts a modest depleting effect on T cells that seems rather due to a carryover phenomenon of previous therapies, particularly FTY. These data may help in the overall evaluation of the risk/benefit profile of treatment sequencing.

Anti-HBs titers are not decreased after treatment with oral Cladribine in patients with Multiple Sclerosis vaccinated against Hepatitis B virus.

BACKGROUND: Oral cladribine is a novel treatment for Multiple Sclerosis (MS). It is a purine nucleoside antimetabolite analogue that is incorporated into the DNA, resulting in single-strand breaks in DNA and apoptosis of replicating lymphocytes. Specifically, Cladribine induces limited depletion of CD4 and CD8 T cell subsets and more marked depletion of memory B cell subsets. Therefore, natural and acquired humoral responses against pathogens may be potentially reduced. The aim of this study was to assess longitudinal variation of antiHBs titers in patients with MS treated with Cladribine. METHODS: Patients with MS treated with 1 cycle of Cladribine (3,5 mg/kg) and previously vaccinated against Hepatitis B virus (HBV) were enrolled. Anti-HBs titers were compared before and after 12 months from Cladribine treatment. Total lymphocyte count was also analysed. RESULTS: Among the 13 RMS patients (10 F, 3 M, mean age 33,8, SD 5,9) enrolled, all had anti-HBs titers >10 mg/dl at baseline. Anti-HBs titer dropped below the reference value at 12 months after Cladribine only in 1 case. Pre-post Cladribine mean anti-HBs values were not significantly different considering the whole cohort (Wilcoxon-Mann-Whitney Test p = 0,762). Four patients had grade 1 and 1 patient grade 2 lymphocytopenia at 12 months. CONCLUSIONS: Cladribine does not seem to reduce humoral immune responses in subjects previously vaccinated against HBV, even in case of lymphocytopenia. These results, if confirmed in larger populations, appear reassuring also for other vaccinations (i.e. COVID19). The low impact of Cladribine on plasma cells may explain such findings.

Safety of Natalizumab infusion in multiple sclerosis patients during active SARS-CoV-2 infection.

COVID-19 pandemic represented a challenge in the management of treatments for Multiple Sclerosis (MS), such as Natalizumab (NTZ). NTZ interferes with the homing of lymphocytes into the central nervous system, reducing immune surveillance against opportunistic infection. Although NTZ efficacy starts to decline 8 weeks after the last infusion, increasing the risk of disease reactivation, evidence is lacking on the safety of reinfusion during active SARS-CoV-2 infection. We report clinical outcomes of 18 pwMS receiving NTZ retreatment during confirmed SARS-CoV-2 infection. No worsening of infection or recovery delay was observed. Our data supports the safety of NTZ redosing in these circumstances.

Electrodiagnosis of Guillain-Barre syndrome in the International GBS Outcome Study: Differences in methods and reference values.

OBJECTIVE: To describe the heterogeneity of electrodiagnostic (EDx) studies in Guillain-Barré syndrome (GBS) patients collected as part of the International GBS Outcome Study (IGOS). METHODS: Prospectively collected clinical and EDx data were available in 957 IGOS patients from 115 centers. Only the first EDx study was included in the current analysis. RESULTS: Median timing of the EDx study was 7 days (interquartile range 4-11) from symptom onset. Methodology varied between centers, countries and regions. Reference values from the responding 103 centers were derived locally in 49%, from publications in 37% and from a combination of these in the remaining 15%. Amplitude measurement in the EDx studies (baseline-to-peak or peak-to-peak) differed from the way this was done in the reference values, in 22% of motor and 39% of sensory conduction. There was marked variability in both motor and sensory reference values, although only a few outliers accounted for this. CONCLUSIONS: Our study showed extensive variation in the clinical practice of EDx in GBS patients among IGOS centers across the regions. SIGNIFICANCE: Besides EDx variation in GBS patients participating in IGOS, this diversity is likely to be present in other neuromuscular disorders and centers. This underlines the need for standardization of EDx in future multinational GBS studies.

The neurophysiological lesson from the Italian CIDP database.

INTRODUCTION: Electrophysiological diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) may be challenging. Thus, with the aim ofproviding some practical advice in electrophysiological approach to a patient with suspected CIDP, we analyzed electrophysiological data from 499 patients enrolled inthe Italian CIDP Database. METHODS: We calculated the rate of each demyelinating feature, the rate of demyelinating features per nerve, the diagnostic rate for upper andlower limb nerves, and, using a ROC curve analysis, the diagnostic accuracy of each couple of nerves and each demyelinating feature, for every CIDP subtype.Moreover, we compared the electrophysiological data of definite and probable CIDP patients with those of possible and not-fulfilling CIDP patients, and by a logisticregression analysis, we estimated the odds ratio (OR) to make an electrophysiological diagnosis of definite or probable CIDP. RESULTS: The ulnar nerve had the highestrate of demyelinating features and, when tested bilaterally, had the highest diagnostic accuracy except for DADS in which peroneal nerves were the most informative.In possible and not-fulfilling CIDP patients, a lower number of nerves and proximal temporal dispersion (TD) measurements had been performed compared to definiteand probable CIDP patients. Importantly, OR for each tested motor nerve and each TD measurement was 1.59 and 1.33, respectively. CONCLUSION: Our findingsdemonstrated that the diagnosis of CIDP may be missed due to inadequate or incomplete electrophysiological examination or interpretation. At the same time, thesedata taken together could be useful to draw a thoughtful electrophysiological approach to patients suspected of CIDP.

Patient's point of view on the use of telemedicine in multiple sclerosis: a web-based survey.

Restrictions in the access to healthcare facilities during COVID-19 pandemic have raised the need for remote monitoring of chronic medical conditions, including multiple sclerosis (MS). In order to enable the continuity of care in these circumstances, many telemedicine applications are currently tested. While physicians' preferences are commonly investigated, data regarding the patients' point of view are still lacking. We built a 37 items web-based survey exploring patients' propensity, awareness, and opinions on telemedicine with the aim to evaluate the sustainability of this approach in MS. Analysing 613 questionnaires out of 1093 that were sent to persons with MS followed at the Multiple Sclerosis Center of Tor Vergata University, Rome, we found that more than half of respondents (54%) were open to having a televisit. Propensity toward telemedicine significantly depended on having a higher income (p = 0.037), living farther from the center (p = 0.038), using computer and tablet (p = 0.010) and using the Internet for other remote activities (p < 0.001), conversely it was not influenced by any specific disease characteristics (i.e. degree of disability). The main advantages and disadvantages of televisit reported by participants were respectively saving time (70%) and impossibility to measure physical parameters (71%). Although the majority of respondents are in favour of televisit, so far this approach is restricted to those displaying better socioeconomic conditions and higher familiarity with technology. Implications of the study are that telemedicine platforms should be better tailored to patients' demands in order to spread the use of telemedicine, to enhance usability and to increase patients' adherence.

Prolonged distal motor latency of median nerve does not improve diagnostic accuracy for CIDP.

Compression of the median nerve at the carpal tunnel can give demyelinating features and result in distal motor latency (DML) prolongation fulfilling the EFNS/PNS demyelinating criteria for chronic inflammatory demyelinating polyneuropathy (CIDP). Accordingly, being carpal tunnel syndrome (CTS) common in the general population, the EFNS/PNS guidelines recommend excluding the DML of the median nerve when DML prolongation may be consistent with median neuropathy at the wrist from CTS. The main aims of this study were to verify whether the inclusion of DML of the median nerve (when consistent with CTS) could improve electrophysiological diagnostic accuracy for CIDP and if the median nerve at the carpal tunnel was more prone to demyelination. We analyzed electrophysiological data from 499 patients included consecutively into the Italian CIDP Database. According to the EFNS/PNS criteria, 352 patients had a definite, 10 a probable, and 57 a possible diagnosis of CIDP, while 80 were not fulfilling the diagnostic criteria. The inclusion of DML prolongation of median nerve did not improve significantly the diagnostic accuracy for CIDP; overall diagnostic class changed in 6 out of 499 patients (1.2%) and electrodiagnostic class of CIDP changed from not fulfilling to possible in only 2 patients (2.5% of not-fulfilling patients). In conclusion, we can infer that excluding DML prolongation of median nerve does not increase the risk of missing a diagnosis of CIDP thus corroborating the current EFNS/PNS criteria.

Sustained Efficacy, Safety and High Adherence Rate of Onabotulinum Toxin Type A in Chronic Migraine Patients: A Multicentric Prospective Real-Life Study.

Guidelines regarding long-term use with onabotulinumtoxinA (onaBT-A) in chronic migraine (CM) prophylaxis are lacking. This multicentric prospective real-life study aimed to assess the efficacy and safety of a long-term treatment. A total of 195 chronic migraine patients were treated with onaBT-A, every 3 months for 5 cycles (Phase 1). In the Phase 2 of the study, depending on response rate, patients were divided into "responders" (R), "partially responders" (PR) and "non-responders" (NR). Then, we proposed to R and PR patients to continue with an additional 12 months of treatment (additional 4 sessions). Response to treatment and adverse events were collected for the entire duration of the study. Of the 195 patients included (females 82.1%, mean age 47.4 ± 12.4), at the end of Phase 1 there were 52.3% of R patients, 17.9% of PR patients, 15.4% of NR patients and 14.4% drop-outs. During Phase 2 of treatment, R patients presented a maintenance of the improvement achieved during the first year of treatment, as well as PR patients. Except for three serious adverse events not related to treatment, all other adverse events were mild or moderate in severity and resolved without sequelae. In the literature, adherence to oral migraine-preventive medications among patients with CM was found to be less than 25%. The results of this prospective real-life multicenter study show efficacy, safety and adherence to a long-term treatment with onaBT-A.

Complex Rearrangement of the Entire Retinal Posterior Pole in Patients with Relapsing Remitting Multiple Sclerosis.

There are consolidated data about multiple sclerosis (MS)-dependent retinal neurodegeneration occurring in the optic disk and the macula, although it is unclear whether other retinal regions are affected. Our objective is to evaluate, for the first time, the involvement of the entire retinal posterior pole in patients diagnosed with relapsing remitting multiple sclerosis (RRMS) unaffected by optic neuritis using Spectral Domain-Optical Coherence Tomography (SD-OCT). The study protocol was approved by Tor Vergata Hospital Institutional Ethics Committee (Approval number 107/16), and conforms to the tenets of the Declaration of Helsinki. After a comprehensive neurological and ophthalmological examination, 53 untreated RRMS patients (aged 37.4 ± 10) and 53 matched controls (aged 36.11 ± 12.94) were enrolled. In addition, each patient underwent an examination of the posterior pole using the SD-OCT built-in Spectralis posterior pole scanning protocol. After segmentation, the mean thickness, as well as the thickness of the 64 single regions of interest, were calculated for each retinal layer. No statistically significant difference in terms of average retinal thickness was found between the groups. However, MS patients showed both a significantly thinner ganglion cell layer (p < 0.001), and, although not statistically significant, a thinner inner nuclear layer (p = 0.072) and retinal nerve fiber layer (p = 0.074). In contrast, the retinal pigment epithelium (p = 0.014) and photoreceptor layers p < 0.001) resulted significantly thicker in these patients. Interestingly, the analysis of the region of interest showed that neurodegeneration was non-homogeneously distributed across each layer. This is the first report that suggests a complex rearrangement that affects, layer by layer, the entire retinal posterior pole of RRMS retinas in response to the underlying neurotoxic insult.

Assessment of Macular Function by Multifocal Electroretinogram in Patients with Multiple Sclerosis Treated with Fingolimod.

INTRODUCTION: This study aimed to evaluate whether treatment with fingolimod (FTY) may induce functional changes on the macular pre-ganglionic retinal elements in patients affected by relapsing-remitting multiple sclerosis (RR-MS) without optic neuritis (ON). METHODS: This case-control observational and retrospective study assessed multifocal electroretinogram (mfERG) responses from 35 healthy controls (mean age 43.58 ± 5.76 years), 41 patients with RR-MS without ON (mean age 40.64 ± 4.83 years, MS-noFTY group), and from 21 patients with RR-MS without ON (mean age 42.38 ± 12.34 years) and treated with fingolimod (Gilenya®, Novartis Europharm, 0.5 mg/day) (MS-FTY group). MfERG N1 and P1 implicit times (ITs), and N1-P1 response amplitude densities (RADs) were measured from concentric rings (R) with increasing foveal eccentricity: 0-5° (R1), 5-10° (R2), 10-15° (R3), 15-20° (R4), 20-25° (R5). We considered R1 and R2 as "central macular areas" and R3, R4 and R5 as "more eccentric retinal areas". In the MS-FTY group, mfERG recordings were performed between 6 and 12 months (mean 7.2 ± 1.5 months) from the start of FTY. RESULTS: In the MS-FTY group, the mean values of mfERG N1 and P1 ITs and RADs detected in both central macular areas (R1 and R2) and in more eccentric retinal areas (R3, R4 and R5) were not significantly different (p > 0.01) with respect to those of control and MS-noFTY groups. CONCLUSIONS: Our mfERG results suggest that the chronic use of FTY does not induce a dysfunction of pre-ganglionic retinal elements located in the 0-25° of central retina. Since FTY does not cause any retinal functional abnormality, we suggest that FTY treatment could not produce any toxic effect on pre-ganglionic retinal elements even in the absence of macular oedema.

Validity of the Italian multiple sclerosis neuropsychological screening questionnaire.

The Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) is a brief questionnaire useful for screening patients with multiple sclerosis (MS) at risk for cognitive impairment. It includes a patient self-assessment (MSNQ-p) and a section for the caregiver (informant) (MSNQ-i). This study's aim was to validate the Italian version of MSNQ and to compare MSNQ scores with Symbol Digit Modality Test (SDMT), Beck Depression Inventory (BDI), and Expanded Disability Status Scale (EDSS) score, measuring cognitive skills, mood status, and physical disability respectively. We enrolled 122 MS patients (and related caregivers) at MS center of Tor Vergata University Hospital of Rome. The final study sample consisted of 122 patients with MS (90 relapsing-remitting, 24 secondary progressive, and 8 primary progressive). Our results highlighted that MSNQ has a unidimensional factor structure. Correlational analyses found a good correlation between both versions (MSNQ-p and MSNQ-i) of the questionnaire. Both MSNQ-p and MSNQ-i were correlated with clinical variables, specifically with cognitive impairment, mood disorder, and with disability. The Italian version of MSNQ is reliable and useful as screening tool to identify MS patients at high risk of cognitive impairment.