Combining early lower eyelid surgery with neuromuscular retraining for synkinesis prevention after facial palsy: the role of the eye in aberrant facial nerve regeneration.

Background: Facial synkinesis (FS) is a distressing sequela of facial palsy (FP) characterized by involuntary, simultaneous movements of facial muscles occurring during voluntary facial expressions. Treatment of synkinesis is challenging, and preventive methods are needed. Aim: This study evaluated the efficacy of physical facial nerve rehabilitation (PFNR) therapy alone vs. PNFR with eyelid surgery to correct lagophthalmos and prevent the onset of synkinesis. Methods: Twenty five outpatients were randomized to receive either PFNR alone (neuromuscular retraining and Kabat proprioceptive neuromuscular facilitation) or PNFR and early (90 days after FP onset) eyelid surgery (involving a conservative oculoplastic correction for lagophthalmos with epiphora or ectropion). Comprehensive otolaryngological assessments and Magnetic Resonance Imaging (MRI) were conducted. Synkinesis progression was measured using Another Disease Scale (ADS) at baseline, 3-, 6-, 12-, and 24-months post-treatment. The data were analyzed with ANOVA, τ-test, Chi-Square analyses. Results: Patients undergoing eyelid surgery with PFNR showed faster (p < 0.001) and better recovery of facial movements (p < 0.05) than patients receiving PFNR alone comparing T0 and T12 (p < 0.0001). No synkinesis were observed in the PFNR plus surgery group while 37% of patients in PFNR alone had synkinesis (p = 0.03). At 24 months, none of the patients in the surgery group presented synkinesis. Conclusion: Combining early surgical treatment of paralytic lagophthalmos or epiphora with PFNR accelerated functional recovery and reduced synkinesis in patients with FP compared to facial rehabilitation alone. Further investigations in larger populations with long-term follow-up are needed. Clinical trial registration: https://clinicaltrials.gov/study/NCT06538103, NCT06538103.

Proteomic profile of extracellular vesicles from plasma and CSF of multiple sclerosis patients reveals disease activity-associated EAAT2.

BACKGROUND AND OBJECTIVES: There is an urgent need to discover blood-based biomarkers of multiple sclerosis (MS) to better define the underlying biology of relapses and monitor disease progression. The main goal of this study is to search for candidate biomarkers of MS relapses associated with circulating extracellular vesicles (EVs), an emerging tool for biomarker discovery. METHODS: EVs, purified from unpaired plasma and CSF samples of RRMS patients by size-exclusion chromatography (SEC), underwent proteomic analysis to discover novel biomarkers associated with MS relapses. The candidate biomarkers of disease activity were detected by comparison approach between plasma- and CSF-EV proteomes associated with relapses. Among them, a selected potential biomarker was evaluated in a cohort of MS patients, using a novel and highly reproducible flow cytometry-based approach in order to detect low abundant EV subsets in a complex body fluid such as plasma. RESULTS: The proteomic profiles of both SEC-purified plasma EVs (from 6 patients in relapse and 5 patients in remission) and SEC-purified CSF EVs (from 4 patients in relapse and 3 patients in remission) revealed a set of proteins associated with MS relapses significant enriched in the synaptic transmission pathway. Among common proteins, excitatory amino-acid transporter 2, EAAT2, responsible for the majority of the glutamate uptake in CNS, was worthy of further investigation. By screening plasma samples from 110 MS patients, we found a significant association of plasma EV-carried EAAT2 protein (EV-EAAT2) with MS relapses, regardless of disease-modifying therapies. This finding was confirmed by investigating the presence of EV-EAAT2 in plasma samples collected longitudinally from 10 RRMS patients, during relapse and remission. Moreover, plasma EV-EAAT2 levels correlated positively with Expanded Disability Status Scale (EDSS) score in remitting MS patients but showed a negative correlation with age in patients with secondary progressive (SPMS). CONCLUSION: Our results emphaticize the usefulness of plasma EVs as a source of accessible biomarkers to remotely analyse the CNS status. Plasma EV-EAAT2 showed to be a promising biomarker for MS relapses. Further studies are required to assess the clinical relevance of this biomarker also for disability progression independent of relapse activity and transition from RRMS towards SPMS.

SUNCT syndrome secondary to multiple sclerosis: Not only trigeminal neuralgia.

BACKGROUND: Facial pain in multiple sclerosis is often due to trigeminal neuralgia but atypical pictures can be observed. CASE PRESENTATION: A man with primary progressive multiple sclerosis developed severe unilateral facial pain in the right orbital region. Spontaneous and triggered attacks were associated with ipsilateral conjunctival injection and lacrimation. A diagnosis of short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing was made, and symptoms significantly improved with lamotrigine. CONCLUSION: Pain is poorly investigated in multiple sclerosis, with a dramatic impact on patients' life quality. In this light, standardized evaluation of pain is needed to improve patient management.

Treatment modifiers across different regimens of natalizumab treatment in MS: An Italian real-world experience.

Despite its widespread use in clinical practice, the effectiveness of natalizumab extended interval dosing (EID) adopted from treatment start across different treatment intervals and individual modifiers (body mass index - BMI) is still under-investigated. Here, seven-hundred and forty-five multiple sclerosis (MS) patients, exposed to natalizumab for 3.30 â€‹± â€‹1.34 years, were retrospectively enrolled in an observational multicenter study. After stratifying patients in EID or standard interval dosing (SID), we assessed differences in time to relapse, MRI activity and Expanded Disability Status Scale (EDSS) progression. The primary analysis was conducted on patients exposed to EID interval from 5 weeks and 1 day to 7 weeks, while a secondary analysis included also EID periods up to 8 weeks. An additional analysis explored the impact of BMI. No differences in time to first relapse, time to radiological activity, time to EDSS progression or time to EDA (evidence of disease activity) were detected between SID and EID group (EID interval from 5 weeks to 1 day to 7 weeks). When including EID periods from 7 weeks and 1 day to 8 weeks, the EID group showed a trend towards higher risk of experience clinical relapses than the SID group. A higher EDA risk was also identified in EID patients with BMI above median. In conclusion, a higher risk of relapses seems to occur for EID above 7 weeks. Independently from the EID scheme adopted, higher BMI increases the risk of EDA in these patients.

Neuroinflammatory disorders of the brain and inner ear: a systematic review of auditory function in patients with migraine, multiple sclerosis, and neurodegeneration to support the idea of an innovative 'window of discovery'.

Background: Hearing can be impaired in many neurological conditions and can even represent a forme fruste of specific disorders. Auditory function can be measured by either subjective or objective tests. Objective tests are more useful in identifying which auditory pathway (superior or inferior) is most affected by disease. The inner ear's perilymphatic fluid communicates with the cerebrospinal fluid (CSF) via the cochlear aqueduct representing a window from which pathological changes in the contents of the CSF due to brain inflammation could, therefore, spread to and cause inflammation in the inner ear, damaging inner hair cells and leading to hearing impairment identifiable on tests of auditory function. Methods: A systematic review of the literature was performed, searching for papers with case-control studies that analyzed the hearing and migraine function in patients with neuro-inflammatory, neurodegenerative disorders. With data extracted from these papers, the risk of patients with neurological distortion product otoacoustic emission (DPOAE) was then calculated. Results: Patients with neurological disorders (headache, Parkinson's disease, and multiple sclerosis) had a higher risk of having peripheral auditory deficits when compared to healthy individuals. Conclusion: Existing data lend credence to the hypothesis that inflammatory mediators transmitted via fluid exchange across this communication window, thereby represents a key pathobiological mechanism capable of culminating in hearing disturbances associated with neuroimmunological and neuroinflammatory disorders of the nervous system.

Assessing 'no evidence of disease activity' status in patients with relapsing-remitting multiple sclerosis: a long-term follow-up.

Introduction: Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the CNS with an autoimmune pathogenesis. Over the years, numerous disease-modifying therapies (DMTs) have proven effective in disease control; to date, there is a need to identify a personalized treatment effective in ensuring disease-free status or no evidence of disease activity (NEDA). Objective: identify clinical, demographic and treatment approach characteristics that affect the maintenance of NEDA-3 and the occurrence of clinical relapses during a 6-years follow-up. Materials and method: a retrospective study was conducted on a cohort of MS patients followed up with six-year period. All participants were treated with first- or second-line MS drugs.Clinical relapse, NEDA-3 at 6 years and sustained EDSS were assessed as disease activity outcomes. Patients with follow-up of less than 6 years and insufficient clinical and radiological data were excluded from the study. Results: Two-hundred-eighty naive patients (mean age was 49.8 years, SD ± 11.35 years, 23-76, F/M 182/98), with MS were followed up for 6 years.The mean age at diagnosis was 34.3 years (SD ±11.5, 14-62 years), the mean EDSS score at the onset was 1.9 (±1.3), 76.8% of patients had an EDSS below or equal to 2.5 at diagnosis.In the cohort 37 (13.2%) directly received second-line treatment, 243 (86.8%) received first-line drugs.The analysis showed that second-line treatment from beginning had a protective effect for the achievement of NEDA-3 (p = 0.029), on the prevention of clinical relapse (p = 0.018) and on number of relapses (p = 0.010); this finding was confirmed by logistic regression analysis (p = 0.04) and Kaplan-Meier analysis (p = 0.034). Conclusion: The results of this study demonstrate the efficacy of targeted and early intervention so as to act in the right time window, ensuring a favorable outcome in both clinical and radiological terms; this could be decisive in reducing clinical relapse, disease progression and related disability. Therefore, prescribing highly effective drug in the early stages of the disease represents a leading strategy with the most favorable cost-benefit ratio.

Case report: Recurrent nocturnal awakenings in cluster headache: a different type of ghost attack.

Introduction: Cluster headache (CH) is a trigeminal autonomic cephalalgia characterized by attacks of severe unilateral pain associated with ipsilateral autonomic symptoms. Cluster headache attacks exhibit nocturnal predilection, and sleep disorders could be the first manifestation of an incipient cluster period. Sleep alterations in cluster headache patients may reflect the pivotal role of the hypothalamus, which is crucially involved in the pathophysiology of this primary headache. We describe the case of a patient affected by episodic cluster headache who experienced a sleep disorder after starting therapy with verapamil. Case presentation: A 47-year-old man was affected by episodic cluster headache, characterized by attacks of excruciating pain in the left orbital and temporal regions, associated with prominent ipsilateral vegetative symptoms. Headaches occurred during the night, with one or two nocturnal attacks appearing at 11.30-12 p.m. and 4-4.30 a.m. Preventive treatment with verapamil was started, with immediate pain relief. Later, he experienced consecutive nocturnal awakenings for a couple of weeks, always at the same time, without any pain or autonomic symptoms. He was not agitated and did not need to get out of bed; after the awakenings, he reported sleep disturbances with vivid dreams. Discussion and conclusion: This case represents the first description of recurrent cyclic nocturnal awakenings, without pain and autonomic symptoms, in a patient with episodic cluster headache during the active phase of a cluster bout. Nocturnal awakenings, started after the introduction of effective preventive therapy, might be an unusual form of "ghost attacks." After the beginning of prophylactic therapy, patients often describe mild pain or localized pressure in the same localization of CH attack. Similarly, the appearance of sleep disturbances, without any pain or vegetative symptoms, should be regarded as a warning sign of a still active cluster bout. Since these manifestations may influence therapeutic management, they should be carefully investigated.

Habituation deficit of visual evoked potentials in migraine patients with hypermobile Ehlers-Danlos syndrome.

Objectives: Migraine is one of the most frequent clinical manifestations of hypermobile Ehlers-Danlos syndrome (hEDS). The comorbidity between these two diseases has been only partially investigated. We aimed to observe whether neurophysiological alterations described in migraineurs in visual evoked potentials (VEPs) were present in hEDS patients with migraine. Methods: We enrolled 22 hEDS patients with migraine (hEDS) and 22 non-hEDS patients with migraine (MIG), with and without aura (according to ICHD-3), as well as 22 healthy controls (HC). Repetitive pattern reversal (PR)-VEPs were recorded in basal conditions in all participants. During uninterrupted stimulation, 250 cortical responses were recorded (4,000 Hz sample rate) and divided into epochs of 300 ms after the stimulus. Cerebral responses were divided into five blocks. The habituation was calculated as the slope interpolating the amplitudes in each block, for both the N75-P100 and P100-N145 components of PR-VEP. Results: We observed a significant habituation deficit of the P100-N145 component of PR-VEP in hEDS compared to HC (p = 0.002), unexpectedly more pronounced than in MIG. We observed only a slight habituation deficit of N75-P100 in hEDS, with a slope degree that was intermediate between MIG and HC. Discussion: hEDS patients with migraine presented an interictal habituation deficit of both VEPs components like MIG. Pathophysiological aspects underlying the pathology could account for the peculiar pattern of habituation in hEDS patients with migraine characterized by a pronounced habituation deficit in the P100-N145 component and a less clear-cut habituation deficit in the N75-P100 component with respect to MIG.

Targeting Neuroinflammation to Alleviate Chronic Olfactory Dysfunction in Long COVID: A Role for Investigating Disease-Modifying Therapy (DMT)?

Chronic olfactory dysfunction after SARS-CoV-2 infection occurs in approximately 10% of patients with COVID-19-induced anosmia, and it is a growing public health concern. A regimen of olfactory training and anti-neuroinflammatory therapy with co-ultramicronized palmitoylethanolamide with luteolin (um-PEA-LUT) has shown promising results in clinical trials; however, approximately 15% of treated patients do not achieve full recovery of a normal olfactory threshold, and almost 5% have no recovery. Disease-modifying therapies (DMTs), which are used to treat autoimmune neuroinflammation in multiple sclerosis (MS), have not been studied for treating persistent inflammation in refractory post-COVID-19 smell disorder. This study evaluated COVID-19-related smell loss and MS-related smell loss, comparing the responses to different therapies. Forty patients with MS and 45 reporting post-COVID-19 olfactory disorders were included in the study. All patients underwent nasal endoscopy and were evaluated by using validated Sniffin' Sticks testing. The patients with long COVID were treated for three months with um-PEA-LUT plus olfactory training. The patients with MS were treated with DMTs. Olfactory functions before and after treatment were analyzed in both groups. At the experimental endpoint, 13 patients in the COVID-19 group treated with um-PEA-LUT had residual olfactory impairment versus 10 patients in the MS group treated with DMTs. The severity of the persistent olfactory loss was lower in the MS group, and the patients with MS treated with IFN-beta and glatiramer acetate had the preservation of olfactory function. These data provide a rationale for considering prospective trials investigating the efficacy of DMTs for post-COVID-19 olfactory disorders that are refractory to um-PEA-LUT with olfactory training. This study is the first to consider the role of DMT in treating refractory post-viral olfactory loss in patients with long COVID.

No Changes in Functional Connectivity After Dimethyl Fumarate Treatment in Multiple Sclerosis.

INTRODUCTION: Despite the increased availability of disease-modifying therapies (DMTs) for treating relapsing-remitting multiple sclerosis (RR-MS), only a few studies have evaluated DMT-associated brain functional changes. METHODS: We investigated whether significant resting-state functional connectivity (FC) changes occurred in RR-MS patients after 6 and 12 months of dimethyl fumarate (DMF) treatment using both a seed-based and data-driven approach. RESULTS: Thirty patients were followed up after 6 months of therapy, and 27 of them reached a 12-month follow-up. Three patients at baseline and only one after 12 months showed gadolinium-enhancing lesions. We did not find any significant FC changes after therapy at either time point. After 12 months of DMF, we observed relatively modest brain volume loss and a significant improvement in Paced Auditory Serial Addition Test 3 s and 25-Foot Walk Test scores. CONCLUSION: The absence of FC changes could be due to the low degree of baseline inflammation in our patients, though we cannot exclude that more time may be required to observe such changes. No FC changes may reflect a beneficial effect of DMF therapy, as supported by conventional MRI findings and clinical improvement.

Infectious risk in multiple sclerosis patients treated with disease-modifying therapies: A three-year observational cohort study.

BACKGROUND: The disease-modifying therapies (DMTs) largely used in multiple sclerosis (MS) may result in higher infectious risk. OBJECTIVE: We aimed to investigate the infectious risk in DMT-treated MS patients. METHODS: MS patients were evaluated for infectious risk before starting, switching or during DMT. RESULTS: In this three-year observational cohort study 174 MS patients were enrolled. Among them, 18 patients were anti-HBc + and 19 patients were QuantiFERON®-TB Gold In-Tube (QFT) + . No patients with anti-HBc + showed a detectable HBV-DNA and all started DMT. Among QTB + patients, 17 latent TB infections (LTBIs) and 2 active TB infections (TBIs) were identified. After one month of LTBI prophylaxis or TB treatment, respectively, all patients started DMTs.Overall, 149 started DMTs. During DMTs, one ocrelizumab-treated patient with anti-HBc + developed HBV reactivation and six patients (3 on natalizumab, 2 on ocrelizumab and 1 on IFN-ß) showed reactivation of HSV-1, with detectable plasma DNA. Finally, 1 cladribine-treated patient experienced VZV reactivation. All the reactivations of latent infections have been successfully treated. CONCLUSION: Screening of infectious diseases in DMT candidate MS patients helps to mitigate the infectious risk. During DMTs, a regular assessment of infectious risk allows to avoid discontinuing MS therapy and guarantees a higher degree of safety.

Diagnostic Value of JC Polyomavirus Viruria, Viremia, Serostatus and microRNA Expression in Multiple Sclerosis Patients Undergoing Immunosuppressive Treatment.

Markers of JC polyomavirus (JCPyV) activity can be used to evaluate the risk of progressive multifocal leukoencephalopathy (PML) in treated multiple sclerosis (MS) patients. The presence of JCPyV DNA and microRNA (miR-J1-5p), the anti-JCV index and the sequence of the non-coding control region (NCCR) in urine and plasma were determined in 42 MS subjects before treatment (T0), 6 months (T6) and 12 months (T12) after natalizumab, ocrelizumab, fingolimod or dimethyl-fumarate administration and in 25 healthy controls (HC). The number of MS patients with viruria increased from 43% at T0 to 100% at T12, whereas it remained similar for the HC group (35-40%). Viremia first occurred 6 months after treatment in MS patients and increased after 12 months, whereas it was absent in HC. The viral load in urine and plasma from the MS cohort increased over time, mostly pronounced in natalizumab-treated patients, whereas it persisted in HC. The archetypal NCCR was detected in all positive urine, whereas mutations were observed in plasma-derived NCCRs resulting in a more neurotropic variant. The prevalence and miR-J1-5p copy number in MS urine and plasma dropped after treatment, whereas they remained similar in HC specimens. Viruria and miR-J1-5p expression did not correlate with anti-JCV index. In conclusion, analyzing JCPyV DNA and miR-J1-5p levels may allow monitoring JCPyV activity and predicting MS patients at risk of developing PML.

Efficacy of interoceptive and embodied rehabilitative training protocol in patients with mild multiple sclerosis: A randomized controlled trial.

Introduction: The aim of this randomized controlled trial was to evaluate the effect of an embodied rehabilitative protocol, in improving interoceptive awareness respect balance and motor performance in patients with mild multiple sclerosis (pwMS). Methods: In this study patients with relapsing-remitting multiple sclerosis were enrolled. The rehabilitative treatment group (TG) participated in an embodied physiotherapy program consisting of 8 one-hour sessions in groups of 4 patients at a time, 1 per week and 2 one-hour sessions of neuro-cognitive exercise in single session during the rehabilitation program. All pwMS underwent a clinical assessment to measure the interoception sense for the Multidimensional Assessment of Interoceptive Awareness scale, balance for the Tinetti Mobility test and stabilometry, quality of life for the Short Form Health Survey-12 and body image perception for Trunk Appearance Perception Scale and Body Image Scale. All previous scales and tests were performed at baseline (T0), at the end of treatment (T1) and after 2 months of follow up (T2). Results: Sixty patients were enrolled and randomized into two groups: TG (n = 30), aged 43.0 ± 10.2 years, and a control/waiting list (WLG) group (n = 30), aged 40.7 ± 10.4 years. Statistically significant improvements in interoceptive awareness, body image perception, balance and quality of life were reported in TG versus WLG (p < 0.05). Discussion: This study suggests that enhancing interoceptive awareness could improve postural balance. Future studies with a larger sample of patients will be needed to better quantify the effects of an embodied rehabilitation.

Chronic Migraine Preventive Treatment by Prefrontal-Occipital Transcranial Direct Current Stimulation (tDCS): A Proof-of-Concept Study on the Effect of Psychiatric Comorbidities.

Chronic migraine (CM) is often complicated by medication overuse headache (MOH) and psychiatric comorbidities that may influence the clinical outcome. This study aimed to investigate the relationship between psychiatric comorbidities and the effect of transcranial direct current stimulation (tDCS) in patients with CM with or without MOH. We recruited 16 consecutive CM patients who had an unsatisfactory response to at least three pharmacological preventive therapies. They were treated with anodal right-prefrontal and cathodal occipital tDCS (intensity: 2 mA, time: 20 min) three times per week for 4 weeks. All patients underwent a psychopathological assessment before and after treatment, and five of them were diagnosed with bipolar disorder (BD). After treatment, all the patients showed a significant decrease of severe and overall headache days per month. Despite having a higher migraine burden at baseline, patients with CM and BD showed a significantly greater reduction of severe headaches and psychiatric symptoms. Overall, tDCS seems to be effective in the treatment of CM patients with a poor response to different classes of pharmacological therapies, whereas BD status positively influences the response of migraineurs to tDCS.

Real world experience with teriflunomide in multiple sclerosis: the TER-Italy study.

OBJECTIVE: To identify baseline factors associated with disease activity in patients with relapsing-remitting multiple sclerosis (RRMS) under teriflunomide treatment. METHODS: This was an independent, multi-centre, retrospective post-marketing study. We analysed data of 1,507 patients who started teriflunomide since October 2014 and were regularly followed in 28 Centres in Italy. We reported the proportions of patients who discontinued treatment (after excluding 32 lost to follow-up) and who experienced clinical disease activity, i.e., relapse(s) and/or confirmed disability worsening, as assessed by the Expanded Disability Status Scale (EDSS). Decision tree-based analysis was performed to identify baseline factors associated with clinical disease activity during teriflunomide treatment. RESULTS: At database lock (September 2020), approximately 29% of patients (430 out of 1,475) discontinued teriflunomide because of disease activity (~ 46%), adverse events (~ 37%), poor tolerability (~ 15%), pregnancy planning (~ 2%). Approximately 28% of patients experienced disease activity over a median follow-up of 2.75 years: ~ 9% had relapses but not disability worsening; ~ 13% had isolated disability worsening; ~ 6% had both relapses and disability worsening. The most important baseline factor associated with disease activity (especially disability worsening) was an EDSS > 4.0 (p < 0.001). In patients with moderate disability level (EDSS 2.0-4.0), disease activity occurred more frequently in case of ≥ 1 pre-treatment relapses (p = 0.025). In patients with milder disability level (EDSS < 2.0), disease activity occurred more frequently after previous exposure to ≥ 2 disease-modifying treatments (p = 0.007). CONCLUSIONS: Our study suggests a place-in-therapy for teriflunomide in naïve patients with mild disability level or in those who switched their initial treatment for poor tolerability. Adverse events related with teriflunomide were consistent with literature data, without any new safety concern.

Early diagnosis of secondary progressive multiple sclerosis: focus on fluid and neurophysiological biomarkers.

BACKGROUND AND AIMS: Most patients with multiple sclerosis presenting with a relapsing-remitting disease course at diagnosis transition to secondary progressive multiple sclerosis (SPMS) 1-2 decades after onset. SPMS is characterized by predominant neurodegeneration and atrophy. These pathogenic hallmarks result in unsatisfactory treatment response in SPMS patients. Therefore, early diagnosis of SPMS is necessary for prompt treatment decisions. The aim of this review was to assess neurophysiological and fluid biomarkers that have the potential to monitor disease progression and support early SPMS diagnosis. METHODS: We performed a systematic review of studies that analyzed the role of neurophysiological techniques and fluid biomarkers in supporting SPMS diagnosis using the preferred reporting items for systematic reviews and meta-analyses statement. RESULTS: From our initial search, we selected 24 relevant articles on neurophysiological biomarkers and 55 articles on fluid biomarkers. CONCLUSION: To date, no neurophysiological or fluid biomarker is sufficiently validated to support the early diagnosis of SPMS. Neurophysiological measurements, including short interval intracortical inhibition and somatosensory temporal discrimination threshold, and the neurofilament light chain fluid biomarker seem to be the most promising. Cross-sectional studies on an adequate number of patients followed by longitudinal studies are needed to confirm the diagnostic and prognostic value of these biomarkers. A combination of neurophysiological and fluid biomarkers may be more sensitive in detecting SPMS conversion.

ENT-MS-12 questionnaire: A novel tool to investigate otolaryngology symptoms in patients with relapsing-remitting multiple sclerosis. Results from a pilot study.

BACKGROUND: Multiple sclerosis (MS) is associated with otolaryngology-related manifestations including vestibular or auditory symptoms; facial motor or sensory disorders; voice or swallowing impairment; and snoring/sleep apnea. Because these symptoms are nonspecific, their significance in MS is seldom recognized by patients with MS and their physicians; yet, presence of these symptoms may be a harbinger of impending relapse or disease progression. We developed and investigated a survey instrument, the ENT-MS-12, to standardize reporting of otolaryngology symptoms in patients with MS, correlating its scoring with disability and lesions. METHODS: The ENT-MS-12 was administered to 40 patients with relapsing-remitting MS in different phases of their disease. We collected data using the Expanded Disability Status Scale (EDSS) and analyzed patient brain MRIs to evaluate the state (active or non-active) of brain lesions based on gadolinium enhancement. Odds ratios for diverse otolaryngology symptoms across the EDSS scores and brain lesions were calculated. RESULTS: Higher EDSS scores were associated with auditory and vestibular symptoms (Odd Ratio (OR): 3.06; p: 0.0003); voice and swallowing symptoms (OR: 6.8; p=0.007); and snoring/sleep apnea (OR: 5.1; p=0.03). Presence of active brain lesions was also associated with auditory and vestibular symptoms (OR: 6.7); voice and swallowing symptoms (OR: 5.7); and snoring/sleep apnea (OR: 5). CONCLUSIONS: The ENT-MS-12 survey instrument standardizes reporting of otolaryngology symptoms in patients with MS and documents association between symptoms and phase of disease in this series. Because ear, nose and throat (ENT)- related symptoms (i.e., sensory symptoms, such as numbness) are under-reported in MS, further investigation is warranted, as such data may improve clinical management of MS.

The role of stress and psychiatric comorbidities as targets of non-pharmacological therapeutic approaches for migraine.

This narrative review addresses the interconnections among stress, mental disorders and migraine with a specific focus on non-pharmacological interventions that may be effective in improving both migraine and the psychiatric comorbidity. Migraine is often comorbid with depression, anxiety, personality disorders, and sleep disorders. Subjective stress and stressors are common triggers for migraine attacks and are risk factors for chronification, whilst mental disorders and stress responses are closely linked in a bidirectional relation. Recent studies show that psychiatric comorbidity is associated with migraine severity, worse outcomes, increased disability and reduce quality of life. Numerous studies on non-pharmacological interventions for migraine were published and behavioural treatments included biofeedback, cognitive-behavioural therapy, relaxation training, stress management and brief psychodynamic psychotherapy. Taken together, psychological interventions proved to be effective in migraine treatment and a combination of pharmacological and psychological treatment appear to be more effective than either medication or psychotherapy alone. Non-pharmacological interventions effectiveness should be due to the improvement of migraine, stress-related vulnerability and mental disorders together and the combined treatment could prevent the chronification circuit of migraine. Well-designed long-term studies are needed to clarify comparative effectiveness of non-pharmacological techniques in the treatment and the prevention of migraine.

Audiovestibular symptoms in patients with multiple sclerosis: A correlation between self-reported symptomatology and MRI findings to monitor disease progression.

BACKGROUNDS: The interest about audiovestibular symptoms in patients with multiple sclerosis (MS) is recently growing. However, these symptoms can be often underestimated by patients. We aim to evaluate the presence of audiovestibular symptoms in patients with MS as reported by themselves and correlate these symptoms with the different phases of MS. Audiovestibular symptoms, if correlated with relapsing phase could be an indicator of disease progression. METHODS: In this prospective study 80 patients with MS were screened for the presence of audiovestibular symptoms, during their first neurological consultation, using a self-administered questionnaire developed by our research team. Magnetic Resonance Imaging (MRI) scans were performed within a week from the consultation and were compared with scan performed 12-month before, looking for the presence of new active lesions or enlargement of the ones already present. Data on the year of diagnosis, symptom onset, treatment history and expanded disability status scale (EDSS) were collected. Statistical analysis was performed to identify a correlation between audiovestibular symptoms and active lesions in MRI scan. Odds ratio were calculated. RESULTS: 75% of patients reported audiovestibular symptoms and 37.5% of them had an active or enlarged (compared with previous MRI) lesion/s in their brain MRI scan when they referred to the symptoms' presence. Active lesion/s in MRI were positively correlated with the presence of audiovestibular symptoms (p = 0.0009). Based on our analysis, patients with active lesions had an increased risk of developing audiovestibular symptoms compared to patients with enlarged but non-active lesions (odds ratio: 4.7). Lesions in the cortex rather than in the medulla (odds ratio: 0.6) or optic nerve (odds ratio:1.6), were more common in patients that developed audiovestibular symptoms. Patients with supratentorial active lesions were more at risk to present audiological symptoms than subjects with the infratentorial lesions (odd ratio: 1.3). CONCLUSIONS: Audio-vestibular symptoms can arise in the relapsing phases of MS and their presence may be correlated with an active lesion in the brain. The self-administered questionnaire can be useful both for patients and physicians, to early identify the presence of audiovestibular symptoms that might be related to the progression of the disease.