Multiple sclerosis: autoimmune disease or autoimmune reaction?

Multiple sclerosis (MS) is traditionally considered an autoimmune inflammatory demyelinating disease of the central nervous system (CNS) with much knowledge available to support this view. However, this characterization implies that the primary event is an aberrant immune response directed at CNS antigens, promoting inflammation and later driving progressive axo-glial degeneration. Trials with potent anti-inflammatory agents and detailed neuropathological studies raise questions about this sequence of events. This hypothetical paper argues that MS may be primarily a "cytodegenerative" disease, possibly first involving the oligodendrocyte/myelin unit. Liberation of autoantigens secondarily recruits an immune response, the force of which heavily depends on the host's immune predisposition. Thus, the spectrum of MS from highly aggressive Marburg type, to primary progressive disease with little inflammatory burden, is governed by a "convolution" between the underlying cytodegeneration and the host's immune predilection. Clinical heterogeneity may be a reflection of a variable immune response, whereas in reality, the "real MS" may be a homogeneous degenerative process analogous to well known primary neurodegenerative diseases.     

Multiple sclerosis - a vascular etiology?

From the earliest pathological studies the perivenular localization of the demyelination in multiple sclerosis (MS) has been observed. It has recently been suggested that obstructions to venous flow or inadequate venous valves in the great veins in the neck, thorax and abdomen can cause damaging backflow into the cerebral and spinal cord circulations. Paolo Zamboni and colleagues have demonstrated abnormal venous circulation in some multiple sclerosis patients using non-invasive sonography and invasive venography. Furthermore, they have obtained apparent clinical improvement or stabilization by endovascular ballooning of points of obstruction in the great veins in some, at least temporarily. If non-invasive observations by others validate their initial observations of a significantly increased prevalence of venous obstructions in MS then trials of angioplasty/stenting would be justified in selected cases in view of the biological plausibility of the concept.     

Multiple sclerosis and non-communicating syringomyelia: a casual association or linked diseases?

Non-communicating syringomyelia (NCS) can be associated with different disease processes such as arachnoidytis, trauma or tumor. Approximately 12 cases, documented radiographically, of the association of non-communicating syringomyelia and multiple sclerosis (MS) have been described but their relationship remains obscure. In 3 patients with laboratory supported MS spinal magnetic resonance imaging (MRI) revealed a central cystic cavity. In 2 patients lesions on the spinal cord above the cavity were demonstrated. At 3-year follow-up in 1 patient, no change in the cavity was detected. Although 3 cases are insufficient for providing a definitive conclusion on the relationship between these two diseases, we suggest that demyelinating lesions have to be regarded as possible causes of spinal, asymptomatic cavities.     

Multiple sclerosis biomarkers: Helping the diagnosis?

Multiple sclerosis (MS) is a complex heterogeneous disease. Diagnostic criteria are based on symptoms, biomarkers, MRI data and exclusion of differential diagnoses. Over the past few years, the usefulness of biomarkers has progressively decreased with the development of new MRI criteria, yet dozens of new biomarkers, especially in cerebrospinal fluid, for MS diagnosis and prognosis have been described. Large-scale studies validating some of these new biomarkers have also provided confirmation of a restricted set of biomarkers (presented here in this review) as having potential value for different stages of the disease, including as early as clinically isolated syndrome and radiologically isolated syndrome. However, differentiating progressive forms of MS from relapsing–remitting MS remains a genuine challenge, and could help to predict future conversion to secondary-progressive MS. In addition, new approaches combining multiple biomarkers might allow us to unravel the complexity of the disease and determine disease stages more precisely. Moreover, recent technological developments allowing analysis of biomarkers in plasma have also provided less invasive analysis of MS, and should serve to predict MS evolution and therapeutic responses during follow-up.     

Multiple sclerosis and amyotrophic lateral sclerosis: is there a link?

To date, there are no reports studying the rate of amyotrophic lateral sclerosis (ALS) in relatives of multiple sclerosis (MS) patients and vice versa. This study was designed to look into this issue using two population-based databases of MS and ALS in Isfahan province of Iran. We have searched for any first, second or third degree familial kinship between the Isfahan MS Society database and Isfahan ALS population. We compared the rate of ALS among the population of first degree relatives of MS patients, with the crude prevalence of ALS in the general population of Isfahan. On the other hand, a reverse analysis was carried out to compare the prevalence of MS in Isfahan with its rate amongst the first degree relatives of ALS patients. We found 10 families among which five had first degree kinship. The rate of the diseases was significantly higher in both comparisons among the family members (p < 0.00001) and an odds ratios of more than 67 in both calculations showed a several-fold increase of ALS occurrence in the first degree relatives of MS patients and vice versa. In our study relatives of MS patients were significantly more prone to ALS and vice versa. This could give clues about the common features that the two disease share. Both diseases have an environmental and genetic component and these results mostly point toward genetic similarities.     

Is multiple sclerosis a sexually transmitted infection?

It is proposed that multiple sclerosis may be transmitted chiefly by sexual contact. Arguments favouring this include: migration studies that suggest a transmissible agent in adolescence; clusters of multiple sclerosis which have occurred in low prevalence areas following entry of young males; the similarity of multiple sclerosis to tropical spastic paraplegia, a known sexually transmitted infection with resemblance to primary progressive multiple sclerosis; an increased rate in drug misusers; a similar age of onset and sex pattern to that found in sexually transmitted disease; increased incidence of multiple sclerosis in those using oral contraceptives; low multiple sclerosis rates in societies with a strict moral code; longitudinal shifts in sex prevalence that show an increase in women after the sexual revolution of the 1960s; and important exceptions to the worldwide distribution corresponding to countries with permissive attitudes to sex. Family, conjugal pair, twin, and adoption studies are compatible with an infectious cause of multiple sclerosis if this is sexually transmitted. It is not proposed that sexual transmission is the only cause but that inherited factors create a susceptibility to a sexually transmitted neurotropic agent. It is hoped this hypothesis might encourage a new direction of neurological research.     

Multiple sclerosis: is there neurodegeneration independent from inflammation?

Clinical and magnetic resonance imaging studies in multiple sclerosis have recently suggested that neurodegenerative events may take place in multiple sclerosis brains, which occur independently from inflammation. Here we summarize the results from recent pathological studies, which show, that inflammation is invariably present at all stages and in all forms of the disease. However, the patterns of inflammation differ between different disease stages. This may in part explain, why anti-inflammatory or immunosuppressive treatments fail in progressive multiple sclerosis.     

Multiple sclerosis and cancer: When two wrongs make a right?

Introduction: Current treatments for multiple sclerosis (MS) remain partially successful, with certain patients remaining treatment resistant. A recent treatment, known as ‘immunoablation’ has been used in severe cases of adult MS with promising results. However, due to its high risk and reservation for severe or refractory cases, its full potential remains unknown.

Methods: We report the case of MM, a 14-year-old boy diagnosed with MS and a concurrent diagnosis of Hodgkin's lymphoma.

Results: After receiving aggressive chemotherapy (immunoablation) for Hodgkin's lymphoma, MM's MS symptoms appear to have remitted, and he has remained progression- and disease activity-free for over six years.

Discussion: This case study will focus on MM's cognitive and behavioural development over this time, but will also discuss treatment implications raised by this rare case.     

Multiple sclerosis and celiac disease: is there an increased risk?

Multiple sclerosis and celiac disease are both considered immune-mediated diseases. Recently, improved serological screening methods provided a higher prevalence of celiac disease (CD) in the general population worldwide and also demonstrated gastrointestinal symptoms may be lacking. The aim of this study was to determine the prevalence of (CD) in an unselected group of 95 adults with multiple sclerosis using transglutaminase antibodies. No patients showed pathological values. Different immune and genetic basis between the two diseases may represent crucial insights to explain our results.     

Relapsing remitting multiple sclerosis or multiphasic disseminated encephalomyelitis?

Introduction: The imaging presentation of some forms of multiple sclerosis may be misleading. In patients with a history of recent infection or vaccination, especially for adolescents or young adults, the differential diagnosis with acute disseminated encephalomyelitis can be difficult. CASE REPORT: We report an unusual clinical and radiological presentation of multiple sclerosis, mimicking acute disseminated encephalomyelitis. We discuss clinical and radiological differential diagnosis, and the outcome after immunosuppressive treatment. CONCLUSION: Distinguishing between acute disseminated encephalomyelitis and the first relapse of multiple sclerosis can be difficult. Brain imaging is a precious tool for differentiating between the two diseases.