Cognitive impairment (CI) is a frequent and disabling symptom in Multiple Sclerosis (MS). Axonal damage may contribute to CI development from early stages. Nevertheless, no biomarkers are at the ...moment available to track CI in MS patients. We aimed to explore the correlation of cerebrospinal fluid (CSF) axonal biomarkers, in particular: light-chain neurofilaments (NFL), Tau, and Beta-amyloid protein (Abeta) in MS patients with CI at the diagnosis. 62 newly diagnosed MS patients were enrolled, and cognition was evaluated using the Brief International Cognitive Assessment for MS (BICAMS) battery. CSF NFL, Abeta, and Tau levels were determined with commercial ELISA. Patients with CI (45.1%) did not differ for demographic, clinical, and MRI characteristics (except for lower educational level), but they displayed greater neurodegeneration, exhibiting higher mean CSF Tau protein (162.1 ± 52.96 pg/ml versus 132.2 ± 63.86 pg/ml
p
:0.03). No differences were observed for Abeta and NFL. The number of impaired tests and Tau were significantly correlated (
r
:0.32
p
:0.01). Tau was higher in particular in patients with slowed information processing speed (IPS) (
p
:0.006) and a linear regression analysis accounting for EDSS, MRI, and MS subtype confirmed Tau as a weak predictor of IPS and cognitive impairment. In conclusion, CI has an important burden on the quality of life of MS patients and should be looked for even at diagnosis. Axonal damage biomarkers, and in particular Tau, seem to reflect cognition impairment in the early stages.
Multiple sclerosis (MS) is a debilitating autoimmune condition primarily affecting young adults, and its rise is evident globally. Despite this, its precise etiology remains elusive. Both genetic and ...environmental factors contribute to MS susceptibility; however, the link between diet and MS lacks substantial evidence due to limited large-scale studies. We exploited the UK Biobank resources to explore the nexus between diet, lifestyle, and MS risk. The dietary and lifestyle habits of MS incident cases, derived from a general food frequency questionnaire (FFQ) completed by all participants at study enrollment, were compared to those of subjects who did not develop MS during the follow-up. Our findings suggest the protective role of moderate oily fish consumption and weekly alcohol intake. Furthermore, by analyzing food intake data obtained through 24 h recall, completed by a subset of participants, we found a protective, though non-significant, trend of an increased adherence to the Mediterranean diet (MD). These findings, derived from the analysis of the UK Biobank and representing an unprecedented approach for this inquiry, warrant further exploration and integration in future research.
A 35-year-old Caucasian woman presented an abrupt onset of bilateral impaired vision, and arrived to our attention two weeks later. She had a previous episode of mild dizziness. She underwent a ...fluorescein angiography showing branch retinal artery occlusions and a brain magnetic resonance imaging (MRI) revealing several supraand infratentorial FLAIR-hyperintense white matter lesions, two with contrast enhancement. Thrombophilic, autoimmune and infective (including Human Immunodeficiency Virus, Borrelia burgdorferi, Hepatitis B Virus, Hepatitis C Virus, Herpes Simplex Virus 1-2, Varicella Zoster Virus) screening was negative. Cerebrospinal fluid analysis showed intrathecal IgG synthesis. We suspected a Primary Central Nervous System Vasculitis, and intravenous steroids were started. Three months later a second brain MRI showed seven new lesions without contrast enhancement, and she revealed a cognitive impairment and bilateral hearing loss. Reviewing the clinical history and MRI, she fulfilled diagnostic criteria for Susac syndrome. She had two cycles of cyclophosphamide, and recovered in 6 months and then remained stable with metotrexate.
Aquaporin-4 antibody (AQP4-IgG) neuromyelitis optica spectrum disorders (NMOSD) are rare idiopathic autoimmune diseases, presenting with optic neuritis (ON), longitudinally extensive transverse ...myelitis (LETM), and brainstem syndromes and a prevalence range between 0.5 and 4/100,000. Only 3% to 25% of NMOSD have been described as a paraneoplastic (PN) syndrome (PNNMOSD). Both idiopathic NMOSD (INMOSD) and PNNMOSD cases mostly affect females, but PNNMOSD usually presents with a spinal cord or brainstem involvement in elderly patients. Few cases of both malignancies (for the majority breast or lung cancer) and benign tumors (monoclonal gammopathy) were previously reported. Currently, there is no consensus on treatment approach for PNNMOSD (only surgical removal or surgery combined with chronic immunosuppression). Here, we present a series of three newly diagnosed PNNMOSD cases, who differ from each other for demographic and clinical features, tumor association, long-term treatment, and outcome. We propose that a PN etiology should be considered always whenever a new diagnosis of NMOSD is made, not only in patients over 50 years old or in spinal cord/brainstem lesions presentations. Our findings add to existing evidence and raise awareness on PNNMOSD. We enhance the importance for the clinicians of recognizing tumor symptoms and signs whenever a NMOSD is newly diagnosed.
Background:
Cerebrospinal fluid (CSF) free light chains (FLCs) can be an alternative assay to oligoclonal bands (OCBs) in inflammatory neurological disorders, but threshold has no consensus.
...Objective:
To assess the diagnostic accuracy of CSF FLCs in multiple sclerosis (MS) and other neurological diseases.
Methods:
A total of 406 patients from five Italian centers. FLCs were measured in CSF and serum using Freelite MX assays on Optilite.
Results:
A total of 171 patients were diagnosed as MS, 154 non-inflammatory neurological diseases, 48 inflammatory central nervous system (CNS) diseases, and 33 peripheral neurological diseases. Both kFLC and λFLC indices were significantly higher in patients with MS compared to other groups (p < 0.0001). The kFLC index ⩾ 6.4 is comparable to OCB for MS diagnosis (area under the receiver operating characteristic curve (AUC) = 0.876; sensitivity 83.6% vs 84.2%; specificity 88.5% vs 90.6%). λFLC index ⩾ 5 showed an AUC of 0.616, sensitivity of 33.3% and specificity of 90.6%. In all, 12/27 (44.4%) MS patients with negative OCB had kFLC index ⩾ 6.4. Interestingly, 37.5% of 24 patients with a single CSF IgG band showed high kFLC index and 12.5% positive λFLC index.
Conclusion:
Our findings support the diagnostic utility of FLC indices in MS and other CNS inflammatory disorders, suggesting a combined use of FLC and OCB to help clinicians with complementary information.
Chronic, intractable neuropathic pain is a common and debilitating consequence of neuromyelitis optica spectrum disorder (NMOSD) myelitis, with no satisfactory treatment; few studies have yet to ...explore its aetiology.
To establish if myelitis-associated chronic pain in NMOSD is related to the craniocaudal location of spinal cord lesions.
(1) Retrospective cohort of 76 aquaporin 4-antibody (AQP4-Ab)-positive patients from Oxford and Liverpool's national NMOSD clinics, assessing current pain and craniocaudal location of cord lesion contemporary to pain onset. (2) Focused prospective study of 26 AQP4-Ab-positive Oxford patients, a subset of the retrospective cohort, assessing current craniocaudal lesion location and current pain.
Patients with isolated thoracic cord myelitis at the time of pain onset were significantly more disabled and suffered more pain. Cervical and thoracic lesions that persisted from pain onset to 'out of relapse' follow-up (current MRI) had highly significant (p<0.01) opposing effects on pain scores (std. β=-0.46 and 0.48, respectively). Lesion length, total lesion burden and number of transverse myelitis relapses did not correlate with pain.
Persistent, caudally located (ie, thoracic) cord lesions in AQP4-Ab-positive patients associate with high postmyelitis chronic pain scores, irrespective of number of myelitis relapses, lesion length and lesion burden. Although disability correlated with pain in isolation, it became an insignificant predictor of pain when analysed alongside craniocaudal location of lesions.
Background
The pandemic implied dramatic changes in public health assets. In Italy, some Stroke Units were transformed into sub-intensive COVID-19 Units, making the management of neurological ...patients demanding. We described how the flow of neurological emergencies was affected by the pandemic impact.
Methods
We analyzed accesses to the Emergency Department (ED) of the “Maggiore della Carità” Hospital, Piedmont, Italy, during a period of 8 months (COVID time; March to May 2020 and October 2020 to February 2021) and analyzed the admissions to the Neurology Unit and the underlying diagnosis. We also evaluated potential changes in the treatment of acute ischemic stroke in the same period. These variables were compared with two equivalent periods of time (2019–2020; 2018–2019).
Results
During the COVID time, there was a clear-cut reduction of the total ED accesses compared to NoCOVID times. However, admissions for acute neurological conditions showed a mild but non-significant decrease (6.3%vs.7.3%). The same applied to acute ischemic stroke, which represented the most common condition (47.7%). The proportion of patients who underwent emergent reperfusion therapies remained unchanged. Furthermore, no difference was found in door-to-needle and door-to-groin intervals between COVID time and NoCOVID times. On the contrary, the onset-to-door interval was significantly longer during the COVID time (
p
value: 0.001).
Discussion
While the percentage of admissions following an ED access grew dramatically, those to the Neurology Unit showed overall only a slight non-significant decrease. This finding implicitly reflects the serious and urgent nature of many neurological diseases, compelling people to access EDs at any time.
Background: Multiple sclerosis (MS) is a common chronic autoimmune disease of the central nervous system. In MS, disability progresses unpredictably. Dopamine (DA) is a modulator of immune functions, ...and compelling evidence supports its involvement in both pathogenesis and treatment of MS. Although single nucleotide polymorphisms (SNPs) in dopaminergic receptor (DR) genes have been extensively studied, their role in MS progression remains unexplored. Therefore, the aim of this explorative study is to investigate the potential association between functional SNPs in DR genes and MS progression. Methods: Caucasian patients with relapsing–remitting (RR) MS were enrolled, and disease progression assessed by the Multiple Sclerosis Severity Score (MSSS). Results: Out of the 59 RRMS patients enrolled, those with the G/G genotype for rs6280 and rs1800828 SNPs in DRD3 showed significantly higher MSSSs compared to those with ancestral and heterozygous genotypes. Conclusions: If confirmed in a larger prospective study, the reported findings could contribute to a better understanding of MS pathophysiological mechanisms, opening the way for the identification of marker(s) for assessing MS progression as well as novel therapeutic strategies. A personalized approach to MS management has the potential to improve the overall well-being of MS patients and alleviate the burden on their caregivers.
The protein growth arrest-specific 6 (Gas6) and its tyrosine kinase receptors Tyro-3, Axl, and Mer (TAM) are ubiquitous proteins involved in regulating inflammation and apoptotic body clearance. ...Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous system leading to progressive and irreversible disability if not diagnosed and treated promptly. Gas6 and TAM receptors have been associated with neuronal remyelination and stimulation of oligodendrocyte survival. However, few data are available regarding clinical correlation in MS patients. We aimed to evaluate soluble levels of these molecules in the cerebrospinal fluid (CSF) and serum at MS diagnosis and correlate them with short-term disease severity.
In a prospective cohort study, we enrolled 64 patients with a diagnosis of clinical isolated syndrome (CIS), radiological isolated syndrome (RIS) and relapsing-remitting (RR) MS according to the McDonald 2017 Criteria. Before any treatment initiation, we sampled the serum and CSF, and collected clinical data: disease course, presence of gadolinium-enhancing lesions, and expanded disability status score (EDSS). At the last clinical follow-up, we assessed EDSS and calculated MS severity score (MSSS) and age-related MS severity (ARMSS). Gas6 and TAM receptors were determined using an ELISA kit (R&D Systems) and compared to neurofilament (NFLs) levels evaluated with SimplePlex™ fluorescence-based immunoassay.
At diagnosis, serum sAxl was higher in patients receiving none or low-efficacy disease-modifying treatments (DMTs)
patients with high-efficacy DMTs (
= 0.04). Higher CSF Gas6 and serum sAXL were associated with an EDSS <3 at diagnosis (
= 0.04;
= 0.037). Serum Gas6 correlates to a lower MSSS (r
= -0.32,
= 0.01). Serum and CSF NFLs were confirmed as disability biomarkers in our cohort according to EDSS (
= 0.005;
= 0.002) and MSSS (r
= 0.27,
= 0.03; r
= 0.39,
= 0.001). Results were corroborated using multivariate analysis.
Our data suggest a protective role of Gas6 and its receptors in patients with MS and suitable severity disease biomarkers.
We conducted a retrospective analysis on multiple sclerosis (MS) patients with perceived cognitive decline and long disease duration to investigate early predictors of future cognitive impairment ...(CI) and motor disability. Sixty-five patients complaining of cognitive decline were assessed with an extensive neuropsychological battery at the last clinical follow-up and classified as mildly impaired, severely impaired, and cognitively spared based on the results. Motor disability was assessed with EDSS, MSSS, and ARMSS. Baseline demographic, clinical, and imaging parameters were retrospectively collected and inserted in separate multivariate regression models to investigate the predictive power of future impairment. Twenty-one patients (32.3%) showed no CI, seventeen (26.2%) showed mild CI, and twenty-seven (41.5%) showed severe CI. Older and less educated patients with higher EDSS, longer disease duration, and higher white matter lesion load (WMLL) at diagnosis (particularly with cerebellar involvement) were more likely to develop CI after a mean follow-up from diagnosis of 16.5 ± 6.9 years. DMT exposure was protective. The multivariate regression analyses confirmed WMLL, disease duration, and educational levels as the parameters with significant predictive value for future CI (R2 adjusted: 0.338
: 0.001). Older patients with progressive phenotype both at diagnosis and T1 were more likely to be not fully ambulatory at T1 (R2 adjusted: 0.796
: 0.0001). Our results further expand knowledge on early predictors of cognitive decline and evolution over time.
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