Experimental allergic encephalomyelitis (EAE) is the commonest, readily induced, organspecific, autoimmune disorder of laboratory animals of its kind. It is an artificial disorder brought about by the immunisation of susceptible animals with brain antigens in complete Freund׳s adjuvant (CFA). Variations can be induced by altering the nature of the antigen and the conditions involving immunisation. Whilst it is often described as a demyelinating disease, in strict terms it is not, since the primary pathologic process is not demyelination but rather an encephalomyelitis that is immunologically induced. Rather, the prototype demyelinating disease is multiple sclerosis and its variants. In this paper, the central question we ask is whether the data gleaned from the EAE model contributes to our understanding of the pathological events in MS. Towards answering this, we describe the historical development of EAE and its hyperacute form, and discuss the findings studied extensively in the non-human primate which show that ordinary EAE is an exact model for ADEM in the human, and that the hyperacute form of EAE is represented by AHLE in the human. Additionally, we shall comment on the latest research on new variants of EAE, and explain our opinion regarding the use of EAE models in research aiming to understand the pathogenesis of multiple sclerosis.

An important legal question is the role of acute trauma on the central nervous system with stress in precipitating or worsening multiple sclerosis (MS). At present, the prevailing view in neurology is that there is no relationship. We show here that this opinion needs to be reappraised. Medicolegal decisions for compensation in court have hinged on this question, as do the future research and treatment. A critical analysis of highly important but hitherto neglected articles shows the prevailing view to be gravely mistaken. Modern molecular medicine has shown conclusively that trauma and stress (either alone or together) to the central nervous system cause disruption of the blood–brain barrier (BBB). Disruption of this BBB, a complex molecular process, is the basic pathological feature of MS and is affected in both trauma and stress. Its further study should lead to a rational mode of therapy and resolve the legal quagmire.

Experimental allergic encephalomyelitis is ... a true autoimmune disorder. It has been accepted as an animal model of multiple sclerosis ... However, a false orthodoxy claiming that multiple sclerosis is an autoimmune disorder has developed and formed the present basis of treatment, drug trials and research. The outcome of this misplaced creed has been truly catastrophic..

Acute disseminated encephalomyelitis is not an uncommon disorder and affects both children and adults, being more frequent in the younger group. It is said to constitute one third of all encephalidities and usually follows in the wake of a banal viral infection, but may occur after immunizations and as a complication of diseases affecting the cerebral endothelial cells. There is no specific diagnostic test but a good clinical history, attention to clinical findings along with MRI scan often help to make the diagnosis. Treatment with high dose steroids clearly helps as do immunosuppressives and plasma exchange. Whilst the prognosis is generally good, some series have shown 20% mortality, often with high morbidity.

Myasthenic crisis is a life-threatening medical emergency requiring early diagnosis and respiratory assistance. It can affect between one-fifth and one-third of all patients with generalized autoimmune myasthenia gravis. Myasthenic crisis is to be distinguished from other causes of acute neuromuscular paralysis which in most cases, can be achieved clinically. High dose corticosteroids in combination with plasma exchange or immunoglobulin are the cornerstone of treatment for this fully reversible cause of neuromuscular paralysis.

Die Multiple Sklerose (MS) ist eine chronische neurologische Erkrankung des Zentralen Nervensystems (ZNS, Gehirn und Rückenmark), die bei meist jüngeren Betroffenen zu zunehmenden Behinderungen führt. Die genaue Ursache und Pathogenese der MS sind unbekannt, aber es ist allgemein anerkannt, dass komplexe Wechselbeziehungen zwischen genetisch vorbelasteten Personen und Umweltfaktoren die Krankheit auslösen. Diese führt dann zur Bildung von multi-fokalen Bereichen der Demyelinisierung um Blutgefäße herum ("Plaques"), zur Degeneration von Nervenzellen und ihren Fortsätzen und zur Wucherung ("Sklerose") von gliazellen, die normalerweise strukturelle Komponenten des ZNS sind und zur Ernährung der Nervenzellen beitragen.

We read the paper “Steroid-responsive encephalopathy associated with autoimmune thyroiditis and primary CNS demyelination” by D.J. Mahad et al. [ [1] Mahad D.J. Staugaitis A. Ruggieri P. Parisi J. Kleinschmidt-Demasters B.K. Lassman H. et al. Steroid-responsive encephalopathy associated with autoimmune thyroiditis and primary CNS demyelination. J Neurol Sci. 2005; 228: 3-5 Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar ]. We were disappointed that the authors [ [1] Mahad D.J. Staugaitis A. Ruggieri P. Parisi J. Kleinschmidt-Demasters B.K. Lassman H. et al. Steroid-responsive encephalopathy associated with autoimmune thyroiditis and primary CNS demyelination. J Neurol Sci. 2005; 228: 3-5 Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar ] and the commentator [ [2] Doherty C.P. Possibly, probably definitely, Hashimoto encephalopathy. J Neurol Sci. 2005; 228: 1-2 Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar ] of the accompanying editorial did not review the existing literature of Hashimoto's encephalopathy and acute disseminated encephalomyelitis (ADEM). We published two comprehensive papers on this unique form of relapsing encephalopathy and were first to propose that Hashimoto's encephalopathy is a relapsing form of recurrent ADEM [ 3 Behan P.O. Henderson L.M. Morrison L. Behan W.M.H. Aarli J. Recurrent acute disseminated encephalomyelitis in association with Hashimoto's thyroiditis. in: Confavreux C. Aimard G. Devic M. Trends in European multiple sclerosis research. Elsevier Science Publishers, Amsterdam1988: 161-171 Google Scholar , 4 Chaudhuri A. Behan P.O. The clinical spectrum, diagnosis, pathogenesis and treatment of Hashimoto's encephalopathy (Recurrent acute disseminated encephalomyelitis). Curr Med Chem. 2003; 10: 1645-1653 Google Scholar ]. ADEM is, usually, in the majority of patients a monophasic illness, but recurrent cases have been described [ 5 Van Bogaert L. Post-infectious encephalomyelitis and multiple sclerosis. The significance of perivenous encephalomyelitis. J Neuropathol Exp Neurol. 1950; 9: 219-249 Crossref PubMed Scopus (65) Google Scholar , 6 Miller M.S. Evans M.J. Prognosis in acute disseminated encephalomyelitis; with a note on neuromyelitis optica. QJM. 1953; 22: 347-379 PubMed Google Scholar , 7 Durston J.HJ. Milnes J.N. Relapsing encephalomyelitis. Brain. 1970; 93: 715-730 Crossref PubMed Scopus (24) Google Scholar ]. ADEM is the human counterpart of experimental allergic encephalomyelitis (EAE) and there is compelling data to show that it is a true organ-specific autoimmune disease [ 8 Behan P.O. Geschwind N. Lamarche J.B. Lisak R.P. Kies M.W. Delayed hypersensitivity to encephalitogenic protein in disseminated encephalomyelitis. Lancet. 1968; ii: 1009-1012 Abstract Google Scholar , 9 Cohen J.A. Lisak R.P. Acute disseminated encephalomyelitis (Chapter 15). in: Aarli J.A. Behan W.M.H. Behan P.O. Clinical Neuroimmunology. Blackwell Scientific Publications, London1987: 192-213 Google Scholar , 10 Johnson R.T. Griffin D.E. Hirsch R.L. Wolinsky R.S. Roedenbeck S. Lindo de Soriano I. et al. Measles encephalomyelitis—clinical and immunological studies. N Engl J Med. 1984; 310: 137-141 Crossref PubMed Scopus (332) Google Scholar ].

The Forssman carotid syndrome was induced in guinea pigs to study the mechanism of demyelination-like lesions in this animal model and to compare it with experimental allergic encephalomyelitis (EAE). Acute lesions were studied at 1–3 days after intracarotid injection of rabbit anti-Forssman antibody and chronic lesions at 7–21 days post injection, using routine histological, immunofluorescent, and electron-microscopic techniques. The results were compared to those in a group of guinea pigs with acute or chronic lesions of EAE. The picture was remarkably similar in the two conditions, in regard to localization in the central nervous system (CNS), composition of cellular infiltrates, diameter of lesions produced, myelin loss and axonal degeneration, together with gamma globulin deposition in small vessels in affected areas. The differences were that in the Forssman carotid syndrome, in contrast to EAE, there were no mononuclear cell infiltrates in the acute phase, and no evidence of macrophages invading myelin sheaths was detected. Perivascular lesions consisted of demyelination within infiltrates of mononuclear cell in chronic relapsing EAE, but not in the Forssman carotid syndrome. It is suggested that investigation of the distinction between the two models of the CNS may be of benefit in the pathogenetic study of demyelinating disease.

The pathogenic mechanisms of chronic fatigue syndrome (CFS) are not clearly known. Fatigue, poor short-term memory and muscle pain are the most disabling symptoms in CFS. Research data on magnetic resonance spectroscopy (MRS) of muscles and brain in CFS patients suggest a cellular metabolic abnormality in some cases. 31P MRS of skeletal muscles in a subset of patients indicate early intracellular acidosis in the exercising muscles. 1H MRS of the regional brain areas in CFS have shown increased peaks of choline derived from the cell membrane phospholipids. Cell membrane oxidative stress may offer a common explanation for the observed MRS changes in the muscles and brain of CFS patients and this may have important therapeutic implications. As a research tool, MRS may be used as an objective outcome measure in the intervention studies. In addition, regional brain 1H MRS has the potential for wider use to substantiate a clinical diagnosis of CFS from other disorders of unexplained chronic fatigue.

diagnosticcriteria.TheMSplaquehas a well-defined edge and a scant lymphocyticinfiltratethatisabsentinone third of all plaques. In patients with MS, the normal-appearing gray and whitematterarealwaysinvolvedwith thediseaseprocess,extendingwellbeyondthebordersoftheplaqueasseen in the T2-weighted magnetic resonance (MR) brain images. In the diffusion tensor MR imaging, there is a progressive decline in fractional anisotropyextendingfromthenormalappearingwhitemattertotheplaque withthemostextensivechangesseen at the center of the plaque paralleling the decrease in the magnetization transfer ratio. 4 White matter abnormalities in ADEM are different, however, and do not extend beyond the focal areas of injury. Unlike MS, themagnetizationtransferratioofthe uninvolved brain and spinal cord in ADEM is identical to that of normal tissue. The evolution of the plaques in patients with MS as seen in MR spectroscopyisdifferentfromADEM. Extrapolation of EAE data to MS is guided purely by faith rather than by science. Even the most exhaustiveexperimentshaveyieldedinconclusive results. Autoreactive T-cell

Chronic fatigue is a typical symptom of neurological diseases, and is most disabling in multiple sclerosis, postpoliomyelitis, poststroke, and in chronic fatigue syndrome. Disorders of neuromuscular junction transmission and metabolic diseases cause muscle fatigability, which is characterised by failure to sustain the force of muscle contraction (peripheral fatigue). Fatigue is also seen in diseases that affect the central, peripheral, and autonomic nervous systems (central fatigue). Enhanced perception of effort and limited endurance of sustained physical and mental activities are the main characteristics of central fatigue. Metabolic and structural lesions that disrupt the usual process of activation in pathways interconnecting the basal ganglia, thalamus, limbic system, and higher cortical centre are implicated in the pathophysiological process of central fatigue. A state of pre-existing relative hypocortisolaemia might sensitise the hypothalamic-pituitary-adrenal axis to development of persistent central fatigue after stress. The contributions of physiological, cognitive, and affective changes underlying fatigue are variable, and treatment is largely symptomatic and rehabilitative.

Consideration of the clinical, pathological and immunological features in PM reveals that a variety of immunological processes, both cellular and humoral, are occurring and may produce widespread damage to other organs as well as skeletal muscle. The basis for the disorder appears to be a failure of immune regulation, most likely associated with a genetic susceptibility.