McAlpine's Multiple Sclerosis

Should Spinal MRI Be Routinely Performed in Patients With Clinically Isolated Optic Neuritis?

In this paper, we reviewed scientific sources on multiple sclerosis, analyzed the latest data on the peculiarities of cognitive dysfunction and comorbid pain syndrome in patients with multiple sclerosis. Multiple sclerosis belongs to the group of chronic progressive demyelinating diseases with a predominant lesion of the central nervous system. It affects over 2.5 million people worldwide and is considered as one of the most disabling neurological disorders. Symptoms range from physical ones including loss of vision, spasticity, bladder and bowel dysfunction, problems with walking and balance, fatigue and pain, to mental problems such as cognitive impairment, depression, and anxiety. Comorbid conditions have a significant impact on the quality of life of patients with multiple sclerosis. This evokes considerable scientific interest, since their presence can cause a delay in diagnosis, change the progression of neurological deficits, reduce physical activity and increase the severity of symptoms of the underlying disease. One of the most common comorbid conditions associated with multiple sclerosis is pain. The prevalence of pain syndrome ranges from 29% to 86%. Patients can consider pain as one of the first symptoms of multiple sclerosis. Moreover, in the treatment and diagnosis of multiple sclerosis, in most cases, the state of cognition is missed or neglected, but it always accompanies the patients in the form of cognitive disorders of varying severity. Cognitive function is understood as the most complex mechanism by which the process of rational cognition of the environment and interaction with it is carried out. Both a series of cognitive tests for multiple sclerosis and an MRI evaluation of gray matter atrophy can help to assess the state of cognition. Also, an additional diagnostic method is transcranial magnetic stimulation, with which it is possible to create a model for mapping the cerebral cortex using evoked motor potentials. Thus, the analysis of the literature has shown that the issues of the influence of comorbidity and cognitive dysfunction on the course of multiple sclerosis, the relationship of the onset of multiple sclerosis with comorbid conditions, and the correlation of neurological deficit with the cognitive ability of patients are not studied completely yet.

Relevance of antinuclear antibody in diagnosis and characteristics of multiple sclerosis

Comorbidity is one of the factors determining the course of multiple sclerosis. Cardiovascular pathology is one of the most common in the population as a whole, especially in age groups over 50. Several studies showed that arterial hypotension and dyslipidemia affected the course, progression rate, and neuroimaging characteristics of patients with multiple sclerosis. An important issue is the effect of disease modifying therapy on the course of concomitant diseases in patients with multiple sclerosis and the effect of concomitant diseases on the effectiveness and safety of disease modifying therapy. The question of the use of statins in multiple sclerosis remains controversial. This review presents data on vascular comorbidity in multiple sclerosis, including the prevalence of risk factors for cardiovascular pathology and concomitant vascular diseases in the population of patients with multiple sclerosis. Data on the effect of cardiovascular pathology on the course and treatment of multiple sclerosis were also analyzed.

The COVID-19 pandemic and the use of MS disease-modifying therapies

Introduction. One of the newest methods that could facilitate the diagnosis and treatment of multiple sclerosis is the measurement of neurofilament levels in the blood and spinal fluid. Neurofilament chains can be found not only in multiple sclerosis but also in other neurodegenerative diseases. Latest research findings have revealed that neurofilament levels in serum along with magnetic resonance imaging and clinical evaluation could help evaluate disease relapses and prognosis. No research on neurofilament levels in multiple sclerosis patients has been done in Lithuania so far.Methods. Permit No. BE-2-73 was obtained from Kaunas Regional Biomedical Research Ethics Committee. Using random sampling we examined 28 patients with relapsing-remitting multiple sclerosis who were treated for relapse in the Multiple Sclerosis Centre of Klaipėda University Hospital. Demographic and clinical data and disease modifying therapies were evaluated. Neurofilament heavy chains levels in the blood were measured using ELISA immunoenzyme assay.Results. The research involved 28 patients: 64.3% women and 25.7% men. Neurofilament heavy chains levels in the blood were higher in patients with 3 or more functional systems affected, compared with patients with only pyramidal or cerebellar systems damaged but the difference was not statistically significant. Significantly higher neurofilament heavy chains levels were found in patients with hyperintense magnetic resonance imaging T2 lesions in both brain and spinal cord areas and with contrast-enhanced lesions. Higher neurofilament heavy chains levels were associated with positive oligoclonal bands and prolonged visual evoked potentials. No significant correlation between disease duration, age, disability, and neurofilament heavy chains levels was found. Patients with no disease modifying treatment had higher serum neurofilament heavy chains levels but the difference was not statistically significant.Conclusion. We found higher serum neurofilament heavy chains levels in patients with 3 and more functional systems affected, radiological disease activity, positive oligoclonal bands, and prolonged visual evoked potentials. These results support the hypothesis that neurofilaments could be a promising biomarker for evaluation of multiple sclerosis relapse and disease prognosis in clinical practice.

The article provides a literature review on contemporary aspects of etiopathogenesis, clinical picture, diagnosis and treatment of multiple sclerosis (MS). MS is one of the most socially significant problems of modern neurology. MS has been proven to be a multifactorial disease, which develops as a result of both internal and external factors. In the early stages of this disease there is damage to the axons, therefore MS is not only considered an autoimmune demyelinating disease, but also neurodegenerative. The disease is characterized by a variety of clinical manifestations. The variety of neurological symptoms is due to a multiplicity of foci of demyelination and their localization in brain and spinal cord. Neuroimaging methods play an important role in the modern diagnosis of MS. Management of patients with a diagnosis of MS involves compulsory and long-term basic therapy with immunomodulatory drugs that change the course of multiple sclerosis.

A growing body of literature suggests the presence of a prodromal period with nonspecific signs and symptoms before onset of multiple sclerosis (MS). To systematically assess diseases and symptoms diagnosed in the 5 years before a first MS- or central nervous system (CNS) demyelinating disease-related diagnostic code in pediatric patients compared with controls without MS and controls with another immune-mediated disorder, juvenile idiopathic arthritis (JIA). This population-based, matched case-control study included children and adolescents (aged <18 years) in Germany with statutory health insurance from January 2010 to December 2020. The study population consisted of 3 groups: case individuals with MS, control individuals without MS, and control individuals with JIA. Data were analyzed from November 2023 to April 2024. Diagnoses coded according to the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, German Modification (ICD-10-GM). The main outcome was incident cases of MS, defined as the first confirmed diagnosis of MS (ICD-10-GM code G35) in 1 quarter between 2013 and 2020 and at least 1 additional diagnosis in the following quarters. In total, 163 ICD-10-GM codes before a first MS diagnosis were assessed using univariable and multivariable logistic regression analyses. The study population consisted of 1091 children and adolescents with MS, 10 910 without MS, and 1068 with JIA. Of the children and adolescents with MS, 788 (72.2%) were female. Mean (SD) age at disease diagnosis was 15.7 (1.7) years. Nine ICD-10-GM codes were present more frequently among children and adolescents with MS in the 5 years before their first MS diagnosis than among controls without MS: obesity (adjusted odds ratio [AOR], 1.70; 95% CI, 1.42-2.02), disorders of eye refraction and accommodation (AOR, 1.26; 95% CI, 1.09-1.47), visual disturbances (AOR, 1.31; 95% CI, 1.10-1.55), gastritis and duodenitis (AOR, 1.35; 95% CI, 1.08-1.70), patella disorders (AOR, 1.47; 95% CI, 1.13-1.90), heartbeat abnormalities (AOR, 1.94; 95% CI, 1.27-2.96), flatulence (AOR, 1.43; 95% CI, 1.01-2.01), skin sensation disturbances (AOR, 12.93; 95% CI, 8.98-18.62), as well as dizziness and giddiness (AOR, 1.52; 95% CI, 1.22-1.89). Four of these ICD-10-GM codes were significantly more prevalent in children and adolescents with MS than in controls with JIA: obesity (AOR, 3.19; 95% CI, 2.03-5.02), refraction and accommodation disorders (AOR, 3.08; 95% CI, 2.33-4.08), visual disturbances (AOR, 1.62; 95% CI, 1.13-2.33), and skin sensation disturbances (AOR, 27.70; 95% CI, 6.52-117.64). In this population-based, matched case-control study, children and adolescents with MS had diverse metabolic, ocular, musculoskeletal, gastrointestinal, and cardiovascular symptoms, signs, or diagnoses within 5 years before their first MS diagnosis. Better characterization of early symptoms and/or risk factors, comorbid disorders, and possible prodromal features of MS may have considerable implications for early recognition and subsequent progression of the disease.

&lt;p dir="ltr"&gt;Multiple sclerosis is a neuroinflammatory condition in which cells of the immune system invade and attack the central nervous system. This results in widespread inflammation, demyelination, and neurodegeneration leading to a host of neurological symptoms. People with multiple sclerosis commonly experience relapses in symptoms due to new waves of immune cells entering the central nervous system. &lt;/p&gt;&lt;p dir="ltr"&gt;As such, treatment is aimed at global immune suppression or inhibition of the migration of immune cells into the central nervous system. In healthy individuals, the brain and spinal cord are normally protected from the immune system by the blood brain barrier. This highly organised structure utilises many mechanisms to prevent unrestricted access to the central nervous system by circulating immune cells. One specialisation of the blood brain barrier is the double basement membrane formed by central nervous system endothelial cells and the glia limitans of astrocytic endfeet. This dense glycocalyx provides both a physical barrier to immune cell entry and is critical in maintaining blood brain barrier organisation through sequestered of trophic factors and signalling molecules.&lt;/p&gt;&lt;p dir="ltr"&gt; The final step in immune cell diapedesis across the blood brain barrier is the enzymatic breakdown of basement membrane components such as heparan sulfate proteoglycans. One such enzyme is heparanase, which is released from activated antigen specific T cells in animal models of multiple sclerosis. By cleaving heparan sulfate proteoglycans, heparanase facilitates the migration of autoreactive immune cells into the central nervous system. Therefore, inhibition of heparanase is an attractive treatment strategy for multiple sclerosis. Heparanase can be inhibited by small heparan sulfate-mimicking, sugar-based compounds. Multiple iterations of heparan sulfate-mimetics have been developed over the years but so far most of these have not progressed to clinical trials due to high anticoagulant effects and complexity in synthesis. Tet-29 is a novel dendrimer-based heparan sulfate-mimetic that exhibits high heparanase inhibiting abilities without the associated anticoagulant effects. &lt;/p&gt;&lt;p dir="ltr"&gt;This thesis investigated the disease modifying capability of Tet-29 in experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis. Treatment with Tet-29 both before and after established disease ameliorated physical symptoms of paralysis. This disease modifying effect was due to a significant reduction in infiltration of T lymphocytes into the central nervous system of Tet-29 treated mice. Further investigation found that this reduction in central nervous system trafficking was due to a rescue of disease-induced blood brain barrier permeability by Tet-29, rather than peripheral immune depletion. Moreover, Tet-29 did not disrupt homeostatic trafficking into the central nervous system, suggesting it does not interfere with surveillance. Disrupted immune surveillance of the central nervous system is a major drawback of other multiple sclerosis treatments on the market. &lt;/p&gt;&lt;p dir="ltr"&gt;The collective findings of this thesis provide evidence that Tet-29 could have a promising therapeutic benefit in multiple sclerosis. By targeting blood brain barrier breakdown rather peripheral immune responses, Tet-29 exhibits not only a novel mechanism of action, but also potentially avoids many of abhorrent side effects associated with immunosuppressant therapies. The work presented in this thesis presents clear evidence that further preclinical investigation into the suitability of Tet-29 as a therapeutic agent for multiple sclerosis is warranted.&lt;/p&gt;

Multiple sclerosis: New insights and trends

Multiple sclerosis (MS) is an inflammatory demyelinating disease, which is considered as a common autoimmune disorder in young adults. A growing number of evidences indicated that the impairment in non-neural tissues plays a significant role in pathology of MS disease. There are bidirectional relationship, metabolic activities and functional similarity between central nervous system (CNS) and kidneys which suggest that kidney tissue may exert remarkable effects on some aspects of MS disorder and CNS impairment in these patients compels the kidney to respond to central inflammation. Recently, it has been well documented that hormonal secretion possesses the important role on CNS abnormalities. In this regard, due to the functional similarity and significant hormonal and non-hormonal relationship between CNS and kidneys, we hypothesized that kidneys exert significant effect on initiation, progression or amelioration of MS disease which might be regarded as potential therapeutic approach in the treatment of MS patients in the future.

The current approach to the use of interferon (IFN) beta in the treatment of multiple sclerosis (MS) is, in general, conservative. However, recent findings about early events in MS and data on dose-response relationships with IFN beta indicate that such an approach may be suboptimal. Four lines of evidence suggest that delays in the initiation of therapy with IFN beta may be detrimental: I) axonal damage secondary to inflammation starts very early in the course of MS; 2) pathological events occurring early in MS are predictive of the future course of the disease; 3) inflammatory activity in relapsing MS is not confined to episodes of clinical impairment, but often starts before the first such episode and generally continues during remissions; and 4) the immune-mediated activity that underlies MS may become more difficult to control as the disease progresses. An early treatment strategy is also supported by data from two recently published clinical studies. In addition, preclinical and clinical results suggest that the beneficial effects of IFN may be dose- and frequency-dependent Taken together, these findings indicate that treatment with IFN beta should be started as early as possible in the course of MS, and suggest that, in order to maximize patient benefit, the highest possible dose of IFN beta should be chosen. Multiple Sclerosis (2002) 8, 2-9

Multiple sclerosis (MS) is a chronic neurodegenerative autoimmune disease with a complex clinical course characterized by inflammation, demyelination, and axonal degeneration. Diagnosis of MS most commonly includes finding lesions in at least two separate areas of the central nervous system (CNS), including the brain, spinal cord, and optic nerves. In recent years, there has been a remarkable increase in the number of available treatments for MS. An optimal treatment is usually based on a personalized approach determined by an individual patient's prognosis and treatment risks. Biomarkers that can predict disability progression, monitor ongoing disease activity, and assess treatment response are integral in making important decisions regarding MS treatment. This review describes MS biomarkers that are currently being used in clinical practice; it also reviews and consolidates published findings from clinically relevant potential MS biomarkers in recent years. The work also discusses the challenges of validating and application of biomarkers in MS clinical practice.

A 26-year-old male patient was admitted to our outpatient clinic with complaints of numbness and weakness in his left arm and leg. These complaints had started about 10 days ago and were continuing. From his personal history, it was found out that he had been followed up with the diagnosis of Ehlers-Danlos syndrome (EDS) hypermobile tip for 10 years, and that he had had low vision in his left eye lasting for 15 days, but he had not consulted a physician for this complaint. After 1 year had passed from the complaint of blurred vision, he had had a weakness in his right arm and loss of balance, but again he had not sought medical advice. From his familial history, it was found out that his paternal grandmother, father, aunt, cousins, and younger sister were being followed up with the diagnosis of EDS. General physical examination revealed no pathological features except for several atrophic cicatrices on the face, back, and arms and hyperflexibility of the joints (Figure 1). No cardiologic or ophthalmologic involvement was detected in terms of EDS. Neurological examination revealed that the patient is conscious, cooperated and oriented. His cranial nerve examinations were normal. His muscle strength was 3/5 in the upper left limb, 4/5 in the lower left limb, and 5/5 in the upper and lower right limbs. Left-sided hemihypoesthesia including the face, and globally hyperactive deep tendon reflexes were seen. The patient had bilateral extensor plantar reflexes and reduced abdominal cutaneous reflex on the left side. His cerebellar tests were normal, and no urinary or fecal incontinence. His cranial magnetic resonance imaging (MRI) revealed several ovoid-shaped periventricular lesions located perpendicular to the ventricle, which is consistent with demyelinating plaques (Figure 2). His cervical MRI revealed several centrally-located, ovoid-shaped lesions aligned with C2-C3-C4 segments, which are consistent with demyelinating plaques. His thoracic MRI was considered to be normal. For the patient, who had blurred vision, a visual evoked potential (VEP) test was performed. p100 wave latency was lengthened for both VEP systems (right: 136, left: 132). Brainstem auditory evoked potential examination was normal. ANA, anti-dsDNA, Anti-cardiolipin IgG and IM, Homocysteine, Lupus Anticoagulant, Protein C, Protein S, Prothrombin II gene mutation, Factor 5 leiden mutation investigations revealed no significant pathologies. The patient was evaluated according to McDonald’s criteria, an acute multiple sclerosis (MS) episode was considered, and pulse steroid therapy was prescribed for 10 days. Following the treatment, his symptoms at admission were recovered. He is now being followed up by our outpatient clinic. Figure 1 General physical examination revealed hyperflexibility of the joints Figure 2 Hyperintense, ovoid-shaped, periventricular lesions located perpendicular to the ventricle EDS is a rare, inherited disease characterized by disturbed collagen synthesis and enzyme dysfunction. Central nervous system involvements are remarkable, mainly in vascular type EDS.1 However, only one study could be identified that examined the potential association with MS, and it was emphasized in this study that MS prevalence is 10 to 11-fold greater in EDS patients compared to general population.2 ECM is a structure that encloses and supports the cells. It has three major components. Structural proteins (mainly collagen), proteoglycan and hyaluronan, and specialized multi-adhesive proteins. ECM proteins were observed to involve in central nervous system inflammation and demyelination.3 It is thought that in EDS, there are mutations in the genes coding ECM proteins. These are cells which ensure cell migration and organization, and EDS is seen when a synthesis defect occurs in their synthesis.4,5 ECM proteins are produced by oligodendrocytes and astrocytes in the central nervous system, and were observed to be associated with the astroglial response in the MS lesions. According to a hypothesis, it can show effects on connective tissues and at the vascular level. Changes in the ECM proteins such as collagen and tenascin which are present in the blood vessel walls can cause myelin destruction by increasing the migration of the immune cells to the central nervous system. According to another hypothesis, MS-EDS association may be due to a suspicious gene. There may be a polygenic effect in MS, and one of these mutations may cause EDS. There are some points to be considered in the treatment of MS and EDS. These patients, who undergo physiotherapy due to MS, strong passive exercises can trigger pain or cause joint dislocations. Neck extension should be avoided to prevent carotid artery dissection.2 In our case, we discuss a rare association in terms of their underlying mechanisms and of the points to be considered in the treatment.

Is breastfeeding in MS harmful or not? An answer from real-world Czech data.