Disseminated encephalomyelitis in adults.

Disseminated encephalomyelitis (DEM) is an inflammatory demyelinating disease that is common in children, but also appears in adults. It is often misdiagnosed as multiple sclerosis (MS) from which it differs in its clinical presentation, course of disease and prognosis. Some aspects of DEM overlap with neuromyelitis optica (NMO), another demyelination disease of CNS that was for a long time regarded as part of the MS spectrum, until discovery of the aquaporin-4 antibodies, claimed to be specific for NMO. The clinical symptoms of both may be similar, and their clinical courses may be monophasic or multiphasic, mild but also very aggressive. Neuroimaging in both diseases is characterized by large demyelinating lesions in the spinal cord extending over several segments, and/or in the brain often involving the locations of astrocytes water channels. Our cases of monophasic, multiphasic and recurrent DEM, invoking possible causative triggers, point to the conclusion that DEM has to be regarded as a separate disease; its similarities with NMO raise the expectations that other specific autoantibodies will be identified to explain DEM and its variations.

The accuracy of prevalence rates of multiple sclerosis: a critical review.

Review of the recent medical literature raises doubts about the reliability of reported prevalence rates of multiple sclerosis (MS). Many published prevalence rates are inflated. Some studies have shown that relying on clinical information and MRI interpretation leads to one third of incorrect MS diagnoses. The most important error is failing to distinguish between the clinical and MRI characteristics of MS and of disseminated encephalomyelitis (DEM) in both their acute and relapsing forms. The diagnostic criteria in current usage, including those relating to imaging, do not differentiate between MS and other recurrent inflammatory demyelinating diseases of the central nervous system. Considering a second demyelinating episode following a clinically isolated symptom or acute DEM, as confirming MS, is another major source of error. Another is including cases with onset before they entered the study group or moved to the geographic area. Neuromyelitis optica (NMO) has long been considered an MS variant and in Far Eastern countries it is counted as the 'oriental' form of MS, falsely inflating prevalence rates of MS in those areas. Recent immunologic and radiologic evidence shows that at least some NMO cases represent instances of DEM.

The environment and the nervous system.

Multiple sclerosis (MS) is used as the best example to illustrate the interplay between genetic endowment and environmental effects. The former is widely considered as being the more important one, although there is mounting evidence that environmental factors influence genetic predisposition. The vast majority of environmental epidemiological studies have failed for two major reasons: they have lacked biological plausibility, and they have not considered possible environmental factors operative during the putative period of acquisition of the disease. Lack of diagnostic precision in distinguishing among the inflammatory demyelinating diseases has caused confusion. The role of infectious agents remains controversial: there is little evidence in favor of MS resulting from a specific infection, but the effect of viral infections and vaccinations on the immune system of a genetically vulnerable person remains unresolved.

The multiple sclerosis trait and the development of multiple sclerosis: genetic vulnerability and environmental effect.

The remarkably low rate of concordance of multiple sclerosis (MS) in monozygotic twins has never been fully explained but it implies the possibility of a systemic condition called the multiple sclerosis trait (MST), which is quite different from asymptomatic MS. It results from the action of an antigenic challenge on the immune system of a genetically vulnerable person that does not cause damage to the nervous parenchyma; it may never evolve into the disease MS. A subsequent environmental viral-antigenic event in some MST-carriers can change the trait into the disease. This event could be an infection, which need not be symptomatic, or a vaccination. The MS may become symptomatic, remain asymptomatic, or manifested only by lesions visible by MRI. It is likely that the development of the MST, called activation, occurs early in life, while the transition from MST to MS, called acquisition, takes place at puberty in most patients. Differences in prevalence between pre-puberal migrants, and the locally born children of migrants, and their population of origin may also be explained by the MST.

Psychiatric manifestations of multiple sclerosis and acute disseminated encephalomyelitis.

It is unusual for acute disseminated encephalomyelitis and multiple sclerosis to present as purely psychiatric disorders. We report five patients with such demyelinating diseases and symptoms of psychosis, depression or anxiety. The importance of excluding demyelination as the basis for these psychiatric disturbances is emphasized, especially in the presence of unexplained neurologic findings. The possible relationship between psychiatric symptoms and demyelinating disorders is explored.

Enlargement of the spinal cord: inflammation or neoplasm?

Intramedullary spinal tumours are uncommon lesions that can cause significant difficulties in the differential diagnosis between inflammatory diseases such as multiple sclerosis and acute disseminated encephalomyelitis, and vascular malformations or neoplasms. We report five cases in which the history and the clinical symptoms suggested an inflammatory process of the spinal cord but the MRI characteristics were those of neoplastic lesions. Both non-neoplastic and neoplastic intramedullary lesion may have very similar symptoms, and even CSF abnormalities, but in every one of our cases, a more detailed history and longer observation of the clinical course would have led to the correct diagnosis; in such problem cases, empirical treatment and a follow-up MRI after a month's observation would be a more prudent approach providing that the patient is not rapidly deteriorating.

Diagnostic criteria for multiple sclerosis: an historical review.

Starting with Charcot, diagnostic criteria for multiple sclerosis (MS) have evolved to reflect advances in our understanding of the disease and the development of new diagnostic techniques, and from purely clinical considerations to increasing dependency upon imaging of the central nervous system. The MS diagnostic process was revolutionized by the 1981 introduction of magnetic resonance imaging (MRI), but the increasing reliance upon this technique has led to a surge in erroneous diagnoses, mostly because of the failure to distinguish between MS and disseminated encephalomyelitis (DEM), as well as mounting disregard for the data obtained from the traditional history and physical examination. The most recent scheme of McDonald et al. incorporated quantitative MRI criteria of dubious origin and reliability, but failed to provide qualitative, illustrative ones that would help differentiate between MS and DEM. The choice will have to be made by the neurological community between basing the diagnosis of MS on the MRI alone, or to use it as one aspect of a comprehensive clinical diagnostic algorithm. There will never be a substitute for the experienced and astute clinician's 'feel' for the patient.

The nature of multiple sclerosis.

Multiple sclerosis (MS) has recently been classified according to its clinical course. Despite relapses and remissions, its course is invariably progressive, and the observed progression from the remitting-relapsing to the secondary progressive form represents the accumulation of permanent damage to the nervous system. Discussions of the nomenclatural position of Schilder's, Marburg's, and Baló's diseases, ignore the fact that the unique, pathognomonic, sharp-edged plaque of MS, is also the pathologic end-result in the three variants. Devic's disease or neuromyelitis optica (NMO) is quite different and with some exceptions, is a particular form of disseminated encephalomyelitis (DEM). There is no evidence that the 'oriental form of MS' is anything but NMO. The suggestion that MS and DEM are variants of the same condition is contradicted by the fact that the pathological characteristics of the two are quite different. While it is probable that the two share aspects of pathogenesis, the patients differ because of their genetic endowment. This was dramatically demonstrated in a group of Japanese patients who died after anti-rabies vaccination and were found to have the typical sharp-edged lesions of MS. The genetic determinant was also crucial in the marmoset in which EAE uniquely resulted in a chronic relapsing-remitting (RR) disease characterized by the classic sharp-edged lesions of MS. The question 'ADEM: distinct disease or part of the MS spectrum?' can be answered with a resounding no. A new classification is proposed separating the different forms of MS from the various types of DEM.

Sudden onset aphasic hemiplegia: an unusual manifestation of disseminated encephalomyelitis.

The association of the sudden onset of aphasia with hemiplegia, hemisenosry defect, and facial palsy, with MRI evidence of white matter lesions, requires differentiation between multiple sclerosis (MS) and acute disseminated encephalomyelitis (ADEM). We have observed eight patients with such a syndrome, all of whom were originally diagnosed as multiple sclerosis, but who, on closer examination, turned out to be instances of disseminated encephalomyelitis. The patterns of demyelination seen in T2-weighted MRI are quite different in both conditions. In two of our patients, MRI reverted to normal after the treatment; in others, the images remained unchanged. A review of the reported cases of multiple sclerosis presenting with the acute onset of aphasia, reveals that the majority of them are, in reality, instances of acute disseminated encephalomyelitis with a much better prognosis. Most of these cases are monophasic and immunomodulatory treatment is inappropriate.

Cerebral demyelination in Wegener's granulomatosis.

A 38-year-old woman with a history of a granulomatous lesion of the nose, developed blurred vision, ataxic gait, and spastic tetraparesis. The presence of demyelination on the brain MRI led to the diagnosis of cerebral demyelination associated with Wegener's granulomatosis. Pulse cyclophosphamide administration resulted in some clinical of improvement of her condition. Demyelinating lesions seen in Wegener's have been ascribed to multiple sclerosis, but in this case, they are much more reminiscent of disseminated encephalomyelitis (DEM). The immunological challenge of the underlying disease, may, in the genetically susceptible person, presumably trigger the appearance of MS lesions. Wegener's granulomatosis must be considered in the differential diagnosis of MS.

Multiple sclerosis in Northern Sardinia, Italy: a methodological approach for genetic epidemiological studies.

The etiopathogenesis of multiple sclerosis (MS) remains unclear. However, genetic factors are believed to be important in disease susceptibility. A methodological approach is presented for a population-based study aimed at investigating MS familial incidence and patterns of familial clustering in Northern Sardinia, Italy, with a reported MS prevalence of 150/100,000 population. Patients with MS since 1965 to the present and known to the MS Register for the province of Sassari will be asked to provide genealogical, comorbid and demographic information. Statistical analyses of the familial risk for MS will depend on the completeness of MS 'age at onset' data for affected individuals and age at the time family history is obtained (or age at death) for unaffected family members.

Epilepsy and multiple sclerosis.

A review of 29 published clinical series of adult patients who had epileptic seizures and multiple sclerosis (MS) yielded a prevalence of 2.3%, about three to six times that in the general adult population. The probable anatomic basis for the seizures is areas of inflammation, edema, and/or demyelination in the cerebral cortex and the juxtacortical white matter generated by a mechanism that is not completely understood; the fact that these plaques are very common suggests that other factors must operate in view of the rarity of seizures in MS. Seizures have been observed before and presumably marking the clinical onset of the disease, and during acute bouts. In some instances convulsions appear to be the only manifestations of an attack of MS, but there is no general acceptance of seizures as the first and only symptoms of the disease. The coincidental occurrence of both diseases, the nonspecific triggering effect of MS on latent epilepsy, and actual causation by MS are all possible explanations, but the last named is, in our opinion, extremely unusual.

Highlights of the Second International Conference on MS, May 2003, Dubrovnik, Croatia.

The conference was organized by Professors Vesna Brinar of the Faculty of Medicine, University of Zagreb, Croatia and Charles Poser of the Harvard Medical School, Boston, USA. It was attended by almost 200 neurologists from as far afield as South Africa and Russia. The major topics to be explored were: the natural history of multiple sclerosis (MS); development of diagnostic criteria; genetics with special emphasis on the 'MS trait'; pathogenesis with emphasis on repair; nomenclature of MS and its 'variants'; differentiation between MS and disseminated encephalomyelitis; diagnostic and therapeutic dilemmas resulting from MRI abnormalities in asymptomatic people; various treatments; and a general critique of therapeutic trials.