Fatigue in Multiple Sclerosis: A Resting-State EEG Microstate Study.

Fatigue affects approximately 80% of people with Multiple Sclerosis (PwMS) and can impact several domains of daily life. However, the neural underpinnings of fatigue in MS are still not completely clear. The aim of our study was to investigate the spontaneous large-scale networks functioning associated with fatigue in PwMS using the EEG microstate approach with a spectral decomposition. Forty-three relapsing-remitting MS patients and twenty-four healthy controls (HCs) were recruited. All participants underwent an administration of Modified Fatigue Impact scale (MFIS) and a 15-min resting-state high-density EEG recording. We compared the microstates of healthy subjects, fatigued (F-MS) and non-fatigued (nF-MS) patients with MS; correlations with clinical and behavioral fatigue scores were also analyzed. Microstates analysis showed six templates across groups and frequencies. We found that in the F-MS emerged a significant decrease of microstate F, associated to the salience network, in the broadband and in the beta band. Moreover, the microstate B, associated to the visual network, showed a significant increase in fatigued patients than healthy subjects in broadband and beta bands. The multiple linear regression showed that the high cognitive fatigue was predicted by both an increase and decrease, respectively, in delta band microstate B and beta band microstate F. On the other hand, higher physical fatigue was predicted with lower occurrence microstate F in beta band. The current findings suggest that in MS the higher level of fatigue might be related to a maladaptive functioning of the salience and visual network.

Sars-CoV2 infection in pregnant women with multiple sclerosis.

BACKGROUND: In the general population, maternal SARS-CoV-2 infection during pregnancy is associated with worse maternal outcomes; however, only one study so far has evaluated COVID-19 clinical outcomes in pregnant and postpartum women with multiple sclerosis, showing no higher risk for poor COVID-19 outcomes in these patients. OBJECTIVE: In this multicenter study, we aimed to evaluate COVID-19 clinical outcomes in pregnant patients with multiple sclerosis. METHODS: We recruited 85 pregnant patients with multiple sclerosis who contracted COVID-19 after conception and were prospectively followed-up in Italian and Turkish Centers, in the period 2020-2022. A control group of 1354 women was extracted from the database of the Multiple Sclerosis and COVID-19 (MuSC-19). Univariate and subsequent logistic regression models were fitted to search for risk factors associated with severe COVID-19 course (at least one outcome among hospitalization, intensive care unit [ICU] admission and death). RESULTS: In the multivariable analysis, independent predictors of severe COVID-19 were age, body mass index ⩾ 30, treatment with anti-CD20 and recent use of methylprednisolone. Vaccination before infection was a protective factor. Vaccination before infection was a protective factor. Pregnancy was not a risk nor a protective factor for severe COVID-19 course. CONCLUSION: Our data show no significant increase of severe COVID-19 outcomes in patients with multiple sclerosis who contracted the infection during pregnancy.

Switch from sequestering to anti-CD20 depleting treatment: disease activity outcomes during wash-out and in the first 6 months of ocrelizumab therapy.

OBJECTIVES: Switching between treatments is an opportunity for patients with multiple sclerosis (MS) to ameliorate disease control or safety. The aim of this study was to investigate the impact of switching from fingolimod (FTY) or natalizumab (NTZ) to ocrelizumab (OCR) on disease activity. METHODS: We retrospectively enrolled 165 patients treated with OCR from 11 MS centres. We assessed the association of demographic and clinical characteristics on relapse rate (RR) and activity on magnetic resonance imaging (MRI) during wash-out and after 6 months of treatment with OCR through univariable and multivariable negative binomial regression models. RESULTS: We registered a total of 35 relapses during the wash-out period. Previous treatment with FTY, relapses in the previous year, and relapsing-remitting course were associated with higher RR. In the first 6 months of OCR, 12 patients had clinical or MRI disease activity. Higher Expanded Disability Status Scale (EDSS) and higher lymphocyte count at OCR start were associated with a reduced probability of relapse. DISCUSSION AND CONCLUSION: This study confirms that withdrawal from sequestering agents as FTY increases the risk of relapses in the wash-out period. Nevertheless, starting OCR before achieving complete immune reconstitution could limit its effectiveness in the first 6 months probably because trapped lymphocytes escape the CD20-mediated depletion.

A real-world study of alemtuzumab in a cohort of Italian patients.

BACKGROUND AND PURPOSE: Real-world data on alemtuzumab are limited and do not provide evidence of its effectiveness after various disease-modifying therapies (DMTs). Our aim was to provide real-world data on the impact of clinical variables and previous DMTs on clinical response to alemtuzumab. METHODS: Sixteen Italian multiple sclerosis centers retrospectively included patients who started alemtuzumab from January 2015 to December 2018, and recorded demographics, previous therapies, washout duration, relapses, Expanded Disability Status Scale (EDSS) score, and magnetic resonance imaging data. Negative binomial regression models were used to assess the effect of factors on annualized relapse (ARR) after alemtuzumab initiation. RESULTS: We studied 322 patients (mean age 36.8 years, median EDSS score 3, median follow-up 1.94 years). Previous treatments were: fingolimod (106), natalizumab (80), first-line oral agents (56), first-line injectables (interferon/glatiramer acetate; 30), and other drugs (15). Thirty-five patients were treatment-naïve. The pre-alemtuzumab ARR was 0.99 and decreased to 0.13 during alemtuzumab treatment (p < 0.001). The number of previous-year relapses was associated with alemtuzumab ARR (adjusted risk ratio [RR] 1.38, p = 0.009). Progression-free survival was 94.5% after 1 year, and 89.2% after 2 years of alemtuzumab treatment. EDSS score improvement occurred in 13.5% after 1 year, and 20.6% after 2 years. Re-baselining patients after 6 months of alemtuzumab treatment, led to no evidence of disease activity status in 71.6% after 1 year and 58.9% after 2 years. CONCLUSIONS: Alemtuzumab decreases ARR independent of previous therapy, including patients with disease activity during natalizumab treatment. Overall, 90% of patients showed no disease progression, and 20% an improvement after 2 years of alemtuzumab.

Paraneoplastic neurological syndromes associated with non-Hodgkin lymphoma: a case series.

BACKGROUND: Paraneoplastic neurological syndromes (PNS) associated with lymphoma are rare diseases that usually have different peculiar features when compared to PNS associated with solid neoplasms. METHODS: We retrospectively identified patients with NHL-associated PNS. Clinical and demographic data are reported. RESULTS: We report two cases of NHL-associated PNS: a 72-years old female that presented with rapidly progressive cerebellar syndrome (RCPS) and a 65-years old male that presented with encephalomyelitis (confusion, sensory neuropathy, lower motor neuron involvement). Both PNS were associated with a NHL, small lymphocytic lymphoma and nodal marginal zone lymphoma respectively, and onconeural antibodies tested negative. All patients received first-line immunotherapy with absent or minimal benefit and died of intercurrent infection before cancer or immunosuppressive treatment. DISCUSSION: RCPS and encephalomyelitis rarely present in association with NHL. In our cases, those syndromes took place in the setting of non-aggressive advanced hematological disorders, had an unfavorable prognosis with minimal benefit from immunotherapy, and were seronegative for onconeural antibodies. Our patients fulfilled the criteria for "definite PNS" in the 2004 PNS criteria, but they would be classified as "probable", in the new 2021 PNS criteria. The newest criteria rely on onconeural antibodies testing and on the evidence of antigen expression in cancer cells, features that are usually absent in NHL-associated PNS. New antibodies are being discovered but are still not available to promptly test yet. CONCLUSION: NHL-associated PNS are rare and bear unfavorable prognosis. The diagnosis should not be overlooked even in seronegative patients.

Clinical neurophysiology and cerebrospinal liquor analysis to detect Guillain-Barré syndrome and polyneuritis cranialis in COVID-19 patients: A case series.

We report a case series of five patients affected by SARS-CoV-2 who developed neurological symptoms, mainly expressing as polyradiculoneuritis and cranial polyneuritis in the 2 months of COVID-19 pandemic in a city in the northeast of Italy. A diagnosis of Guillain-Barré syndrome was made on the basis of clinical presentation, cerebrospinal fluid analysis, and electroneurography. In four of them, the therapeutic approach included the administration of intravenous immunoglobulin (0.4 g/kg for 5 days), which resulted in the improvement of neurological symptoms. Clinical neurophysiology revealed the presence of conduction block, absence of F waves, and in two cases a significant decrease in amplitude of compound motor action potential compound muscle action potential (cMAP). Four patients presented a mild facial nerve involvement limited to the muscles of the lower face, with sparing of the forehead muscles associated to ageusia. In one patient, taste assessment showed right-sided ageusia of the tongue, ipsilateral to the mild facial palsy. In three patients we observed albuminocytological dissociation in the cerebrospinal fluid, and notably, we found an increase of inflammatory mediators such as the interleukin-8. Peripheral nervous system involvement after infection with COVID-19 is possible and may include several signs that may be successfully treated with immunoglobulin therapy.

Cerebrospinal fluid and serum interleukins 6 and 8 during the acute and recovery phase in COVID-19 neuropathy patients.

This case series describes three patients affected by severe acute respiratory syndrome coronavirus 2, who developed polyradiculoneuritis as a probable neurological complication of coronavirus disease 2019 (COVID-19). A diagnosis of Guillain Barré syndrome was made on the basis of clinical symptoms, cerebrospinal fluid analysis, and electroneurography. In all of them, the therapeutic approach included the administration of intravenous immunoglobulin (0.4 gr/kg for 5 days), which resulted in the improvement of neurological symptoms. Clinical neurophysiology revealed the presence of conduction block, absence of F waves, and in two cases, a significant decrease in amplitude of compound motor action potential cMAP. Due to the potential role of inflammation on symptoms development and prognosis, interleukin-6 (IL-6) and IL-8 levels were measured in serum and cerebrospinal fluid during the acute phase, while only serum was tested after recovery. Both IL-6 and IL-8 were found increased during the acute phase, both in the serum and cerebrospinal fluid, whereas 4 months after admission (at complete recovery), only IL-8 remained elevated in the serum. These results confirm the inflammatory response that might be linked to peripheral nervous system complications and encourage the use of IL-6 and IL-8 as prognostic biomarkers in COVID-19.

ASL MRI and 18F-FDG-PET in autoimmune limbic encephalitis: clues from two paradigmatic cases.

BACKGROUND: Autoimmune limbic encephalitis (LE) is a neurological condition characterized by seizures and cognitive dysfunction. Fluorine-18 fluorodeoxyglucose (18F-FDG-PET) has recently proved to be an important diagnostic tool in this condition since it may highlight brain metabolism abnormalities in a very early stage of the disease. Two main 18F-FDG-PET patterns have been described: the mixed hypermetabolic/hypometabolic and the neurodegenerative one. Arterial spin labeling (ASL) is an MRI technique showing brain perfusion, rarely used in autoimmune neurological conditions. The aim of the present study was to study patients with LE with both techniques, in order to compare their results. METHODS: Two patients with LE underwent to 18F-FDG-PET and ASL MRI scans using the pseudo-continuous arterial spin labeling (PCASL) technique. Areas of altered perfusion and metabolism were analyzed by visual inspection, and findings were compared between the two techniques. RESULTS: In the first patient, a relapsing LGI-1 LE, right hippocampal hypermetabolism was detected by 18F-FDG-PET (mixed hypermetabolic/hypometabolic pattern), while ASL MRI showed right hippocampal increased perfusion. In the second patient, a seronegative LE, 18F-FDG-PET scan detected a left hemispheric hypoperfusion (neurodegenerative pattern) and ASL MRI yielded similar results. The two 18F-FDG-PET patterns of altered metabolism were similarly detected by ASL imaging. CONCLUSION: ASL and 18F-FDG-PET findings are strongly concordant in LE. ASL imaging was able to detect the two main 18F-FDG-PET patterns previously described in patients with LE.

Unveiling the relationship between autonomic involvement, fatigue, and cognitive dysfunction in early relapsing-remitting multiple sclerosis.

BACKGROUND: Fatigue is a common, yet disabling, symptom in patients with multiple sclerosis (PwMS). Fatigue has shown to be associated with self-reported autonomic nervous system (ANS) symptoms, particularly for cognitive fatigue; however, the question whether ANS involvement is related to cognitive impairment has never been addressed. We performed a study to unveil the complex relationship between fatigue, ANS symptoms, and cognitive impairment. METHODS: We prospectively recruited early PwMS that were tested with Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS), State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI), Modified Fatigue Impact Scale (MFIS) and Composite Autonomic Symptoms Scale-31 (COMPASS-31) scale. We performed a comparison between fatigued and non-fatigued patients and between cognitive unimpaired and impaired patients. We evaluated the association of COMPASS-31, MFIS, BDI, STAI, and BICAMS scores, and the analysis was repeated for each scale's sub-scores. A multivariable analysis was performed to elucidate predictors of fatigue. RESULTS: Forty-four patients were recruited. Fatigued patients had higher COMPASS-31 total, orthostatic intolerance, secretomotor, and pupillomotor scores. No differences in fatigue and ANS symptoms were found between cognitive impaired and unimpaired patients. MFIS total score correlated with STAI state (p = 0.002) and trait (p < 0.001), BDI (p < 0.001), COMPASS-31 total (p < 0.001), orthostatic intolerance (p < 0.001), pupillomotor scores (p = 0.006). Multivariable analysis showed that BDI (p < 0.001) and COMPASS-31 (p = 0.021) predicted MFIS score. Sub-scores analysis showed that orthostatic intolerance has a relevant role in fatigue. CONCLUSION: ANS symptoms are closely related with fatigue. Orthostatic intolerance may have a predominant role. Cognitive impairment seems not to be associated with ANS symptoms.

Nabiximols and botulinum toxin injections for patients with multiple sclerosis: efficacy on spasticity and spasms in a single-centre experience.

BACKGROUND: Spasticity is a common and disabling symptom in patients with multiple sclerosis (PwMS): as highlighted by many epidemiological studies, it is often a severe and not well treated. Despite the availability of evidence-based spasticity management guidelines, there is still great variability in everyday therapeutic approach, especially for the most complex cases. METHODS: In our single-centre study, we retrospectively evaluated PwMS-treated nabiximols and botulinum toxin injections (BTI) from July 2015 to April 2019. Clinical and demographic data were collected. The severity of spasticity and spasms was recorded by modified Ashworth Scale (mAS) and Penn Spasm Frequency Scale (PSFS) at baseline and after 1 month of treatment. RESULTS: We evaluated 64 treatments for MS-related spasticity: 28 patients were treated with BTI and 36 patients with nabiximols. We found that both BTI and nabiximols are effective in reducing mAS (nabiximols, BTI: p < 0.001), PSFS frequency (nabiximols: p = 0.001, BTI: p = 0.008) and intensity (nabiximols: p = 0.001, BTI p = 0.016). No differences were found when directly comparing the efficacy of the two treatments, except for a statistical trend favouring BTI on spasms intensity (p = 0.091). Eleven patients were treated with both BTI and nabiximols, and only four patients continued both treatments. All dropouts were due to inefficacy of at least one of the two therapies. CONCLUSIONS: Our single-centre experience highlights that both BTI and nabiximols are effective in treating multiple sclerosis-related spasticity; however, BTI treatment may be more effective on spasms intensity. Combined nabiximols and BTI treatment could represent a therapeutic option for severe spasticity.

Early putamen hypertrophy and ongoing hippocampus atrophy predict cognitive performance in the first ten years of relapsing-remitting multiple sclerosis.

BACKGROUND: The first years of relapsing-remitting multiple sclerosis (RRMS) constitute the most vulnerable phase for the progression of cognitive impairment (CImp), due to a gradual decrease of compensatory mechanisms. In the first 10 years of RRMS, the temporal volumetric changes of deep gray matter structures must be clarified, since they could constitute reliable cognitive biomarkers for diagnostic, prognostic, and therapeutic purposes. METHODS: Forty-five cognitively asymptomatic patients with RRMS lasting ≤ 10 years, and with a brain MRI performed in a year from the neuropsychological evaluation (Te-MRI), were included. They performed the Brief International Cognitive Assessment battery for MS. Thirty-one brain MRIs performed in the year of diagnosis (Td-MRI) and 13 brain MRIs of age- and sex-matched healthy controls (HCs) were also included in the study. The relationships between clinical features, cognitive performances, and Te- and Td-MRI volumes were statistically analyzed. RESULTS: Cognitively preserved (CP) patients had significantly increased Td-L-putamen (P = 0.035) and Td-R-putamen volume (P = 0.027) with respect to cognitively impaired (CI) ones. CI patients had significantly reduced Te-L-hippocampus (P = 0.019) and Te-R-hippocampus volume (P = 0.042) compared, respectively, with Td-L-hippocampus and Td-R-hippocampus volume. Td-L-putamen volume (P = 0.011) and Te-L-hippocampus volume (P = 0.023) were independent predictors of the Symbol Digit Modalities Test score in all patients (r2 = 0.31, F = 6.175, P = 0.001). CONCLUSION: In the first years of RRMS, putamen hypertrophy and hippocampus atrophy could represent promising indices of cognitive performance and reserve, and become potentially useful tools for diagnostic, prognostic, and therapeutic purposes.

Comfortable walking speed and energy cost of locomotion in patients with multiple sclerosis.

Comfortable walking speed and energy cost of walking are physiological markers of metabolic activity during gait. People with multiple sclerosis are characterized by altered gait biomechanics and energetics, related to the degree of disability and spasticity, which lead to an increased energy cost of walking. Several studies concerning the energy cost of walking in multiple sclerosis have been published. Nevertheless, differences in protocols and characteristics of the sample have led to different outcomes. The aim of the present meta-analysis is to summarize results from studies with specific inclusion characteristics, and to present data about the comfortable walking speed and the energy cost of walking at that speed. Moreover, a detailed discussion of the potential mechanisms involved in the altered metabolic activity during exercise was included. A total of 19 studies were considered, 12 of which were also part of the quantitative analysis. Despite the strict selection process, high between-group heterogeneity was found for both outcomes. Nevertheless, the overall results suggest a pooled mean comfortable walking speed of 1.12 m/s (95% CI 1.05-1.18) and energy cost of 0.19 mLO2/kg/m (95% CI 0.17-0.21). These findings support the results of previous studies suggesting that energy cost of walking may be increased by 2-3 times compared to healthy controls (HC), and encourage the use of this marker in association with other parameters of the disease.

Effects of a cooling vest with sham condition on walking capacity in heat-sensitive people with Multiple Sclerosis.

PURPOSE: Heat sensitivity is a common contraindication in people with Multiple Sclerosis (pwMS), and physical fatigue is one of the most frequently reported symptoms that can affect quality of life. Increases in body temperature may exacerbate fatigue and heat-related symptoms. Decreasing body temperature via cooling devices may mitigate disease symptoms and improve physical abilities and quality of life. This study evaluates the effects of a cooling vest with sham condition on walking capacity using a commercially-available cooling vest specifically designed for pwMS. METHODS: A counter-balanced, cross-over design was used to assess the effects of a cooling vest (CryoVest Comfort, CryoInnov, France) (COLD) from a menthol-induced sham condition (CON) on ground walking time to exhaustion (Tex, s) and distance at exhaustion (Dex, m) in ambulatory pwMS. Secondary outcomes were heart rate (HR, bpm), thermal sensation (Tsens), skin chest (Tchest) and back (Tback) temperature. RESULTS: Ten females with Multiple Sclerosis (59 ± 9 years, EDSS 3.0-5.5) participated to the study. During COLD, pwMS walked significantly longer (1896 ± 602 vs. 1399 ± 404 s, p < 0.001) and farther (1879 ± 539 vs. 1302 ± 318 m, p < 0.001) than CON. Importantly, Tsens and HR at exhaustion were not significantly different between conditions, although Tchest (- 2.7 ± 1.8 °C, p < 0.01) and Tback (- 3.9 ± 1.8 °C, p < 0.001) were lower at volitional fatigue during COLD. CONCLUSION: The lightweight cooling vest improved total walking time and distance in heat-sensitive pwMS. These physiological improvements were likely due to feeling perceptually cooler in the COLD trial, compared to the corresponding point of fatigue in the CON condition.

Determinants of therapy switch in multiple sclerosis treatment-naïve patients: A real-life study.

BACKGROUND: With many options now available, first therapy choice is challenging in multiple sclerosis (MS) and depends mainly on neurologist and patient preferences. OBJECTIVES: To identify prognostic factors for early switch after first therapy choice. METHODS: Newly diagnosed relapsing-remitting MS patients from 24 Italian centers were included. We evaluated the association of baseline demographics, clinical, and magnetic resonance imaging (MRI) data to the switch probability for lack of efficacy or intolerance/safety with a multivariate Cox analysis and estimated switch rates by competing risks models. RESULTS: We enrolled 3025 patients. The overall switch frequency was 48% after 3 years. Switch risk for lack of efficacy was lower with fingolimod (hazard ratio (HR) = 0.50; p = 0.009), natalizumab (HR = 0.13; p < 0.001), dimethyl-fumarate (HR = 0.60; p = 0.037), teriflunomide (HR = 0.21; p = 0.031) as compared to interferons. Younger age (HR = 0.96; p < 0.001), diagnosis delay (HR = 1.23; p = 0.021), higher baseline Expanded Disability Status Scale (HR = 1.17; p = 0.001), and spinal cord lesions (HR = 1.46; p = 0.001) were independently associated with higher inefficacy switch rates. We found lower switch for intolerance/safety with glatiramer acetate (HR = 0.61; p = 0.001), fingolimod (HR = 0.35; p = 0.002), and dimethyl-fumarate (HR = 0.57; p = 0.022) as compared to interferons, while it increased with natalizumab (HR = 1.43; p = 0.022). Comorbidities were associated with intolerance switch (HR = 1.28; p = 0.047). CONCLUSION: Several factors are associated with higher switch risk in patients starting a first-line therapy and could be integrated in the decision-making process of first treatment choice.

Cerebrospinal Fluid Cytokine Expression Profile in Multiple Sclerosis and Chronic Inflammatory Demyelinating Polyneuropathy.

BACKGROUND: Cerebrospinal fluid (CSF) analysis in patients with particular neurologic disorders is a powerful tool to evaluate specific central nervous system inflammatory markers for diagnostic needs, because CSF represents the specific immune micro-environment to the central nervous system. METHODS: CSF samples from 49 patients with multiple sclerosis (MS), chronic inflammatory demyelinating polyneuropathy (CIDP), and non-inflammatory neurologic disorders (NIND) as controls were submitted to protein expression profiles of 47 inflammatory biomarkers by multiplex Luminex bead assay to investigate possible differences in the inflammatory process for MS and CIDP. RESULTS: Our results showed differences in CSF cytokine levels in MS and CIDP; in particular, IL12 (p40) was significantly highly expressed in MS in comparison with CIDP and NIND, while SDF-1α and SCGF-ß were significantly highly expressed in CIDP cohort when compared to MS and NIND. IL-9, IL-13, and IL-17 had higher expression levels in NIND if compared with the other groups. CONCLUSIONS: Our study showed that, despite some common pathogenic mechanisms, central and peripheral nervous system demyelinating diseases, such as MS and CIDP, differ in some specific inflammatory soluble proteins in CSF, underlining differences in the immune response involved in those autoimmune diseases.

Early Recovery of Aphasia through Thrombolysis: The Significance of Spontaneous Speech.

BACKGROUND: Aphasia is one of the most devastating stroke-related consequences for social interaction and daily activities. Aphasia recovery in acute stroke depends on the degree of reperfusion after thrombolysis or thrombectomy. As aphasia assessment tests are often time-consuming for patients with acute stroke, physicians have been developing rapid and simple tests. The aim of our study is to evaluate the improvement of language functions in the earliest stage in patients treated with thrombolysis and in nontreated patients using our rapid screening test. MATERIALS AND METHODS: Our study is a single-center prospective observational study conducted at the Stroke Unit of the University Medical Hospital of Trieste (January-December 2016). Patients treated with thrombolysis and nontreated patients underwent 3 aphasia assessments through our rapid screening test (at baseline, 24 hours, and 72 hours). The screening test assesses spontaneous speech, oral comprehension of words, reading aloud and comprehension of written words, oral comprehension of sentences, naming, repetition of words and a sentence, and writing words. RESULTS: The study included 40 patients: 18 patients treated with thrombolysis and 22 nontreated patients. Both groups improved over time. Among all language parameters, spontaneous speech was statistically significant between 24 and 72 hours (P value = .012), and between baseline and 72 hours (P value = .017). CONCLUSIONS: Our study demonstrates that patients treated with thrombolysis experience greater improvement in language than the nontreated patients. The difference between the 2 groups is increasingly evident over time. Moreover, spontaneous speech is the parameter marked by the greatest improvement.

The Use of Antidepressant Medication before and after the Diagnosis of Amyotrophic Lateral Sclerosis: A Population-Based Cohort Study.

BACKGROUND: The prevalent use of antidepressants (ATDs) in patients with Amyotrophic Lateral Sclerosis (ALS) varies across cross-sectional and clinic-based published studies. This population-based cohort study assesses the real-world prevalence of the use of ATDs, its trajectory and the association of incident use with clinical characteristics. METHODS: All patients with incident ALS in the Friuli Venezia Giulia region, Italy, from 2002 to 2009, were identified through multiple sources including health databases. Diagnosis was validated through clinical documentation review. ATDs prescriptions from 2000 to 2011 were obtained from regional database. The trajectory was estimated through generalized estimating equations for repeated measures logistic regression and the Hazard ratio (HR) of initiating ATDs through multivariate proportional hazard Cox regression. RESULTS: In this cohort of 261 ALS cases, age-, sex-adjusted prevalence of the use of ATDs was 37.3%, higher than in general population. The trajectory increased by 16% in 1-year period across diagnosis. Age ≤67 years at diagnosis (HR 1.28, 95% CI 0.84-1.95) and bulbar onset (1.43, 95% CI 0.90-2.26) were positively associated with initiating ATDs after diagnosis. CONCLUSIONS: More than one-third of patients used ATDs. Depression may occur more frequently than previously reported. Depression may precede motor alterations and be related to both ALS diagnosis and progression.

The incidence of amyotrophic lateral sclerosis in Friuli Venezia Giulia, Italy, from 2002 to 2009: a retrospective population-based study.

BACKGROUND: We conducted a retrospective population-based study to estimate the incidence of amyotrophic lateral sclerosis (ALS) in Friuli Venezia Giulia, Italy, from 2001 to 2009. METHODS: Multiple sources were used for case ascertainment: Health databases, archives of the neurology departments and of the regional chapter of the Italian ALS Association. The diagnosis was validated through clinical documentation review. Crude and standardized incidence rates (IRs) per 100,000 person-years were calculated. RESULTS: We identified 262 incident ALS cases, 50.4% men, 4.2% familial. Half of the patients had spinal onset (56.8% in men) and 25.2% bulbar (29% in women). Bulbar onset had a similar frequency in women (31.7%) and men (31.5%) aged 67 or above at diagnosis. The crude IR was 2.72 (95% confidence interval, 95% CI, 2.39-3.05) and the male:female ratio 1.08. The IR peaked in the 65-74 age group, with a second increase in men 85 years and older. The IR standardized to the 2001 Italian population was 2.38 (95% CI 2.13-2.63) and to the 2000 European population 2.58 (95% CI 2.34-2.81). CONCLUSIONS: This retrospective study found IRs of ALS in the range of Italian and European prospective population-based registries, suggesting an almost complete case ascertainment.