First I would like to thank ALLAH for his care and blessing .<br /> I would like to express my feelings of gratitude to Prof. Dr. Mohamed yassermetwallywho was a kind great supportive teacher, I will be forever grateful to him . <br /> Words cannot express gratitude to my Prof.Dr. NevineElnahasfor her kind support during this work<br /> I would like to express my deepest gratitude to Dr. HalaElkhawasfor her willing help, guidance and support throughout this work. <br />
Post infectious monophasicdemyelinatingdisorders of CNS<br />By<br />Mohamed El sayedabd El aziz<br />M.B.B.Ch<br />
<ul><li>Discuss post infectious demyelinating disorders and its clinical subtypes.
Review pathology, pathogenesis ,immunology and neuroimaging of these disorders.
Discuss prognosis of these disorders and how to manage them.</li></li></ul><li>INTRODUCTION<br />
Encephalitis/myelitis is an acute inflammatory process that affects brain or spinal cord tissue and is almost always accompanied by inflammation of the adjacent meninges. The disease is most commonly caused by viral infection<br />
Encephalitis manifests either as :<br /><ul><li>Acute viral encephalitis.
Post infectious encephalomyelitis. </li></li></ul><li>Acute viral encephalitis (infective)is adirect viral infection of the brain and spinal cord affects mainly the gray matter. <br />Post infectious encephalomyelitisis simply a white matter disease in which there is immune mediated demyelination of the white matter long tracts and the association fibers in the CNS.<br />
In acute viral encephalitis The viral antigens is present in the neural tissue<br />In post infectious encephalomyelitis the viral antigens is absent <br />
The distinction between infective (neuronal) and post infectious immune -mediated demyelinative white matter disease might be difficult or even impossible on clinical background<br />
The spectrum of post infectious demylinating disorders comprise:<br /><ul><li>Acute disseminated encephalomyelitis
Guillain-Barre syndrome (GBS). </li></li></ul><li><ul><li>These disorders are commonly post infectious or post vaccination in origin
They are white matter diseases characterized by autoimmune demyelination, breakdown of blood brain barrier with the development of vasogenic edema and contrast enhancement in the acute stage.
The MRI signal changes (mainly MRI T2 hyperintensities) observed in these disorders are mainly due to the development of vasogenic edema.
They commonly have an acute onset and a regressive course.
They commonly have a benign course with good prognosis and full functional recovery should be expected in most cases. </li></li></ul><li>Pathogenesis<br />
Post infectious demyelinating white matter diseases represent an autoimmune response to proteins, most probably myelin- basic proteins, in the CNS with perivenous inflammation and demyelination<br />
The immune mechanisms include antibody-mediated complement dependant myelinolysis, T-cell mediated lysis of Schwann cells and T -cell mediated induction of an immune reaction with release of cytokines and recruitment of inflammatory cells including macrophages.<br />
The spectrum of neuroinflammatory CNS conditions varies based on regional involvement of the CNS, ranging from monofocalinvolvement (TM , ON) to multifocal involvement (ADEM involving the brain and spinal cord and NMO involving the optic nerve and spinal cord) <br />
What accounts for this regional specificity is a subject of considerable research interest, for which there is no current explanation. <br />
It may be explained by<br />Different inherents in CNS tissue at different sites (such as varying threshold for injury) <br />Differential access to distinct regions of the CNS by exogenous pathogenic mechanisms<br />Difference in the antigenic properties of the myelin basic protein in the nervous system <br />
This might explain why the demyelinating process may preferentially involve some parts of the CNS and spare other parts in different patients resulting in a protean clinical presentations of the same disease in different patients.<br />
ADEM is a collective pathological terminology that can involve <br />The cerebrum only (acute disseminated cerebritis). <br />the spinal cord only (acute post infectious transverse myelitis).<br /> The cerebellum only (acute post infectious cerebellitis).<br />The optic nerves and the spinal cord (neuromyelitis optic).<br /> The optic nerves only (optic neuritis in children).<br />
The disease is better termed<br />Cerebral ADEM (Acute disseminated encephalitis).<br />Spinal ADEM (acute post infectious transverse myelitis).<br />Cerebellar ADEM (acute post infectious cerebellitis).<br />Optic ADEM (Optic neuritis in children)...etc. <br />
ADEM is probably the clinico-pathological category under which all other subtypes are filed<br />
The acute lesions are characterized by perivenous cuffing with inflammatory cells, especially lymphocytes and macrophages, and loss of myelin. This may be in the form of a well-demarcated area of demyelination, although in the acute situation, the edges of the demyelinated lesions often are less well defined, and the demyelination and attendant cellular processes extend into the surrounding rim<br />
Accompanying the myelin loss is a large infiltrate of foamy or debris- filled macrophages lying in sheets that appear to have replaced the normal neutrophil. They also may be around the blood vessels, or infiltrating the more preserved areas of tissue as single cells<br />
Thinly myelinated fibers may be seen within the lesion, suggesting partially demyelinated or remyelinated fibers.The presence of oligodendrocytes showing the re-expression of myelination proteins suggests the latter event is occurring in a least a significant number of these fibers.<br />
Demyelination of the white matter is associated with breakdown of the blood brain barrier which leads to extravasation of protein-rich filtrate of plasma into the interstitial space, with subsequent accumulation of vascular fluid and the development of Vasogenic edema. <br />
Post infectious demyelinating disorders must be differentiated from the more malignant and progressive post infectious neurological disorders such as SSPE (sub acute sclerosing pan encephalomyelitis) and other viral encephalitis<br />
Distinguishing between ADEM and MS is a diagnostic challenge and has important therapeutic and prognostic implications. There are several clinical, imaging, and laboratory parameters that may be useful to distinguish between the two<br />
In general ADEM is an autoimmune meningo-encephalitic process that is associated with disturbed level of consciousness, seizures and meningeal irritation signs (multiple sclerosis is not an encephalitic process)<br />
The clinical history, aided by MRI is the most reliable means of differantiation between ADEM and the initial bout of MS, or between recurrent DEM and relapsing– remitting multiple sclerosis (RRMS). <br />
The Treatment aims to counter autoimmune-mediated inflammation (immunomodulation ( Though spontaneous resolution has been described, recovery is usually incomplete and hence patients presenting in the acute stage with significant, progressive neurological deficits should receive treatment<br />
CorticosteroidIn addition to immunosuppression, steroids also have anti-inflammatory and anti edema actions, and the immediate improvement following administration of steroids is likely to be due to reduction in cerebral edema. The role of corticosteroids in patients presenting late in the course of the disease is questionable <br />
Plasmapharesisits role in the management of demyelinating disorders that are nonresponsive to corticosteroids has been established in one randomized control trial. In most studies, 1-1.4 plasma volumes were exchanged by continuous flow centrifugation and 70% of volume was replaced by 5% serum albumin, fresh-frozen plasma, or hydroxyethylstarch<br />
Immunoglobulin(IVIG) The use of IVIg has proven effective with particular subgroups of patients showing both CNS and peripheral nervous system (PNS) involvement The usual total dose of IVIG is 1–2g/kg, administered over 2–5 days<br />
<ul><li>Post infectious demyelinating disorders comprises a group of poorly understood inflammatory/demyelinating white matter disorders of CNS that is characteristically post infectious or post vaccination in nature. </li></li></ul><li><ul><li>The spectrum of these neuro inflammatory disorders comprise acute disseminated encephalomyelitis (ADEM), Neuromyelitis Optica (NMO), optic neuritis, transverse myelitis, post infectious cerebellitis and Guillain-Barre syndrome (GBS). </li></li></ul><li><ul><li>Each of these disorders differs in the spatial and temporal restriction of inflammation within the nervous system. However, clinical and pathologic studies support that there are many common features of the inflammation and white matter demyelination that is post infectious or post vaccinal in nature.</li></li></ul><li><ul><li>They are monophasic pathological process that has a regressive, benign and self-limiting course in most cases.
These disorders simply represent a single disease with different clinical presentations.</li>