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.     

Autoimmune hepatitis and multiple sclerosis: a coincidental association?

In the present study we report, as part of a large multiple sclerosis (MS) cohort (1800 patients), three cases of untreated patients who developed autoimmune hepatitis (AIH). The prevalence of AIH in the general population is about 0.0169% and seems to be higher in our MS cohort (0.17%). We suggest that a liver biopsy should systematically be performed in untreated MS patients with a sustained increase of liver enzyme.     

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.     

Lumbar puncture and dural sinus thrombosis--a causal or casual association?

BACKGROUND: A few cases of cerebral venous thrombosis (CVT) were reported after a lumbar puncture (LP), suggesting a causal association. The purpose of our study was to document that LP might predispose to CVT by decreasing blood flow velocities (BFV) in veins or dural sinus. METHODS: We performed a transcranial Doppler ultrasound study to register the mean BFV of the straight sinus (SS) before, during and after LP. RESULTS: Thirteen patients were studied. LP induced a decrease of 47% of mean BFV in the SS. The mean decrease of BFV was significant immediately at the end (p = 0.003), 30 min after (p = 0.015) and more than 6 h after LP (p = 0.008). CONCLUSIONS: LP induced a sustained decrease of mean BFV in the SS. The decrease of venous blood flow is a possible mechanism contributing to the occurrence of CVT.     

Amyotrophic lateral sclerosis and myasthenia gravis: association or chance occurrence?

Very few cases of patients with myasthenia gravis (MG) who later developed amyotrophic lateral sclerosis (ALS) have been described, although some studies showed that significantly more cases than expected have ALS associated with a prior diagnosis of autoimmune diseases. Our aim was to investigate whether the association of ALS and MG was higher than expected in a population-based study and to describe the clinical features characterizing these patients. In Emilia Romagna Region of Italy, a prospective registry has been collecting all incident ALS cases since 1.1.2009. For each patient, detailed clinical information is collected by caring physicians, including comorbidities. From 1.1.2009 to 31.12.2014, 671 patients were diagnosed with ALS; five patients (0.75%) were also affected by MG. Considering Western Countries incidence rates the occurrence of both the diseases should be a really exceptional event (7.5/10⁹), compared to our findings (1.87/10⁷) (p < 0.01). Patients with ALS and MG had more frequently a bulbar onset and a fast progressive course. These cases of ALS after MG raise the possibility of potential shared immunological dysfunctions, which may be expression of common pathogenic mechanisms, as well as of shared disease-course modulating events.     

COVID-19 and Parkinson’s disease: a casual association or a possible second hit in neurodegeneration?

Journal of Neurology -     

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.     

Limbic encephalitis with anti‐GAD antibodies and Thomsen myotonia: a casual or causal association?

The association between hereditary myotonic disorders and epilepsy is seldom described in the literature. To date, few reports have dealt with dystrophic myotonias, whereas a single case demonstrating an association between sporadic congenital myotonia and epilepsy was recently reported in a patient carrying a de novo mutation of the CLCN1 gene. Additional evidence for a role of CLCN1 in the pathogenesis of epilepsy is derived from large‐scale exome analysis of ion channel variants and expression studies. Here, we describe the first case of association between familial Thomsen myotonia and epilepsy. All the affected members of a two‐generation family presented myotonia and disclosed a pathogenic mutation in CLCN1. In addition, one individual experienced epileptic seizures due to limbic encephalitis (LE) with anti‐GAD antibodies. The occurrence of the two diseases in this patient could be a chance association, however, CLCN1 mutation, as a susceptibility factor for epilepsy through dysfunction of GABA_a inhibitory signalling, cannot be ruled out as a possible influence.     

Acute axonal form of Guillain–Barré syndrome in a multiple sclerosis patient: chance association or linked disorders?

Multiple sclerosis (MS) is characterized by inflammation, demyelination and gliosis, involving the central nervous system (CNS) and commonly sparing the peripheral nervous system (PNS). Coexistence of CNS and PNS chronic demyelination has been rarely demonstrated in chronic inflammatory demyelinating polyradiculoneuropathies (CIDP) and in MS, but the occurrence of acute polyradiculoneuropathy in a patient with MS is even more unusual. We describe the case of a woman with relapsing-remitting MS who presented with an acute severe tetraparesis. Cerebrospinal fluid (CSF) examination together with neurophysiological data and sural nerve biopsy study demonstrated an axonal form of Guillain-Barré Syndrome (GBS). It remains unresolved if the association of an axonal form of GBS and MS is fortuitous or, on the contrary, is indicative of the coexistence in some individuals of common pathogenetic mechanisms.     

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.