In cases with partial visual field loss there may be a particularly dense central scotoma.Swelling of the optic nerve head papillitis is morecommon in children than it is in adults with
Trang 1presence of red blood cells (Leake and Billman,2002) Imaging studies disclose fairly symmetricallydistributed hemorrhages in deep white matter, some
of which may coalesce into large somewhat metrical hemorrhagic areas Thalami, hypothalamus,brainstem, cerebellum, and spinal cord may also
asym-be involved, while cerebral cortex and basal gangliatend to be spared Involved tissues may be quite edematous
The disease is fulminant with death usually ing within hours to days A number of reports offavorable response to high doses of intravenous corticosteroids (Seales and Greer, 1991) and appro-priate additional treatments of increased intracra-nial pressure suggest that AHLE may be treatable ifrecognized quickly Plasmapheresis and cyclophos-phamide have also been employed with apparenteffectiveness in a few cases Rapid and effective treat-ment requires recognition of the presence of AHLE, adiagnosis that has been confirmed in some instances
ensu-by urgent brain biopsy, followed ensu-by successful ment (McLeod, 2001) Craniectomy appears to havebeen beneficial in some cases with severe elevation ofintracranial pressure
treat-Severe cases have become rarer due to the ability and increased safety of vaccines, permittingchildren to be effectively vaccinated against manyillnesses associated with the possibility of AHLE How-
that are often found in lumbar CSF of children withADEM suggests the possibility that milder degrees
of AHLE, falling below the resolution of scan niques, continue to occur Moreover, it has beencompellingly suggested that cerebral malaria is theresult of a hyperergic host response with the pro-duction of AHLE (Toro and Roman, 1978)
tech-Concentric sclerosis, Balò type (CSBT; encephalitis periaxialis concentrica)
This illness, which may be a peculiar hyperacutevariant of MS, may in addition be influenced bygenetic factors that may admix features of both MSand ADEM (Caracciolo et al., 2001; Itoyama et al.,1985; Kira et al., 1996; Moore et al., 1985; Sotgiu
et al., 2001) The rarity of this illness appears to be
on the order of Schilder disease and its etiologicalbasis similarly uncertain Peak incidence is in thethird decade of life, although cases may arise as early
as the second and as late as the sixth decade The male
to female ratio is about 1:2 CSBT appears to havehigher incidence in Taiwan, Japan, or the Philippines(Tabira and Nishizawa, 1990; Tabira, 1994).Mild prodromal fever, malaise, and headache arenoted in approximately half of CSBT cases, followed
by behavioral withdrawal The acute behavioralchange is associated with weakness and numbness,initially on one side of the body (face, limb, or trunk)that then worsens in extent and degree Develop-ment of pyramidal or cerebellar signs and deteriora-tion of higher cortical and oropharyngeal functionsensue A Dévic syndrome phenotype is occasionallyfound (Currie et al., 1970) Generalized convulsionsoccur in approximately 25% of cases The clinicalcourse may suggest ADEM, especially in youngerindividuals with this condition Blood and CSF testsreveal little information of diagnostic importance;mild CSF pleocytosis may be found (Tabira, 1994).Historically, diagnosis was ascertained in severecases by postmortem or brain biopsy Pathologicalstudy of the concentric layers of greater or lesserdegrees of demyelinative and remyelinative inflamma-tion suggest similarities with the appearance of the
• Para-infectious (e.g Influenza A, RSV,mycoplasma, varicella, measles and other exanthematous illnesses)
• Postvaccination (especially Pasteur rabies vaccine; hepatitis B)
• Asthma
Box 5.13 Etiological association of acute hemorrhagic leukoencephalitis.
Trang 2edge of MS plaques (Courville and Cooper, 1970;
Moore et al., 1985; Yao et al., 1994)
MRI scans have proven useful in identification ofmilder cases of CSBT Between 3 – 5 fairly symmet-rical lesions 1.5 – 5 centimeters in diameter are typic-ally found, more commonly in the deep cerebral
than in other rarer locations, such as spinal cord(Currie et al., 1970) During the early acute stage ofCSBT gadolinium enhancement may clearly delin-eate alternating concentric zones of greater or lesserinflammation, quite distinct from what is seen in typical ADEM or MS In the late acute stage only asingle ring of enhancement at the outer margin oflesions may be found more closely resembling MS(which the age at presentation usually suggests) orADEM (which the febrile prodrome may suggest)
The concentric rings may reappear during the ing subacute phase of illness (Caracciolo et al., 2001;
ensu-Chen et al., 1999; ensu-Chen, 2001; Ghatak et al., 1989)
MR spectroscopic abnormalities of CSBT resemblethose found in MS plaques, although similar changesare found in other diseases, including mitochondrialcytopathies (Chen, 2001) In addition to ADEM and
MS, tumor, vasculitis, or infection may resemble CSBT(Caracciolo et al., 2001) Caution is especially import-ant where the pattern of alternating enhancement isless centrifugal and more irregular in arrangement
Biopsy may sometimes prove misleading
Reported CSBT cases, chiefly from the pre-MRIera, have generally proved fatal within 2–60 weeks
Early deaths are due to herniation, late deaths to inanition and secondary infections (Courville andCooper, 1970; Tabira, 1994) Milder cases identified
by MRI and increased availability of supportive apies have modestly improved the overall outlook forthis condition Early provision of immunosuppressivetreatments may ameliorate clinical and imagingabnormalities Some cases arising in fourth–sixthdecades have longer survival and more prominentgliosis of demyelinated layers
ther-Optic neuritis (ON)
Optic neuritis is considered in detail elsewhere in this
volume In this section childhood ON and its
rela-tionship to ADEM and MS will briefly be reviewed
ON may also occur in association with variousinflammatory illnesses other than ADEM or MS(Kazarian and Gager, 1978; O’Halloran et al., 1998;
Riedel et al., 1998) ON is rare prior to six years of ageand more common from six years of age to puberty
Prior to puberty it usually occurs in association with ADEM or NMO In approximately 70% of cases,acute visual loss occurs days to weeks after a non-specific viral illness (especially measles, mumps, andvaricella) or immunization (Kazarian and Gager, 1978;Kline et al., 1982; Purvin et al., 1988; Riikonen,1989) After puberty, it may occur in isolation or inassociation with NMO or MS and the associationwith a prodromal illness is less common In isolatedpostpubertal cases the risk for subsequent diagnosis
of MS is approximately 50%
Visual loss of childhood ON may be preceded
by headache (frontal or ocular), scintillating omata, or painful eye movements Visual loss may be unilateral or bilateral Three-quarters of prepubertalcases develop bilateral changes either simultaneously
scot-or sequentially, the changes in the second eye laggingbehind the first by weeks to months Degree of visualloss is usually fairly symmetrical in bilateral cases,however, in a significant minority of cases it is asym-metrical (Riikonen et al., 1988) Initially the visualdisturbance may be limited to visual blurring withprogression over several days to partial to completevisual loss In cases with partial visual field loss there may be a particularly dense central scotoma.Swelling of the optic nerve head (papillitis) is morecommon in children than it is in adults with ON,occurring in at least two-thirds of cases (Kriss et al.,1988; Parkin et al., 1984) Quite striking abnormal-ities, including fiber layer hemorrhages at the opticnerve margin, vascular tortuosity, or sheathing ofveins, are readily observable on funduscopy in manycases (Riikonen et al., 1988)
These changes may suggest papilledema, ever, the visual loss of ON can, in most cases, readily
how-be distinguished from that due to malignantlyincreased intracranial pressure (ICP) Increased ICP
is usually associated with additional neurological signs(e.g sixth nerve palsy, meningismus) It manifestsslower onset and as it usually provokes less profounddegree of visual loss is less frequently associated with
an afferent pupillary defect As in many cases ofadult ON, childhood ON may occur without observ-able funduscopic changes, in which case the termretrobulbar ON is applied
The diagnosis of ON is made on the basis of a bination of clinical and laboratory findings In subtlecases, diagnosis can be clinically supported by loss ofred vision (“red desaturation”), or by loss of duration
com-or variety of the “flight of colcom-ors” that are hended in a dark room immediately after 60 seconds
appre-of stimulation appre-of a retina with bright light Greater
Trang 3degrees of visual loss are signified by the presence
of an afferent papillary defect (APD – loss of thereflexive constriction of the contralateral pupil whenthe retina of the affected eye is illuminated) Visualevoked responses (VER) are particularly usefulwhere visual loss is mild enough to be uncertain
ON results in increased latency of the positive ponent of this cortical response (Feinsod et al.,1975) Delayed VER may persist for several years inpatients who have shown excellent clinical recovery(Aicardi, 1992)
com-Abnormalities of other portions of the nervoussystem should be sought and if found a more generaldiagnosis (e.g ADEM, Dévic syndrome, Guillain–
Barré syndrome (GBS), MS) should be applied on thebasis of clinical features and history Positivity of theCSF immune profile studies noted above (exceptingmyelin basic protein) or of other studies such as CSF free kappa chains (Rudick et al., 1986; Riikonen
et al., 1988a) favors the diagnosis of MS but does notexclude the diagnosis of ADEM MRI scanning ofbrain and brainstem with appropriate weighting(T1, T2, balanced, and with gadolinium admin-istrations) and special orbital views is important
MRI demonstrates swelling of the optic nerve in most cases; the extent of optic nerve enlargementmay be alarming in some children who neverthelessexperience good recovery
MRI is the most important tool in excluding ative diagnoses such as lesions compressing the opticnerve Disseminated T2 bright lesions may be found
altern-by MRI elsewhere in the brain in as many as 70% ofpatients (Riikonen et al., 1988), interpretation ofsuch changes in children is difficult and may notindicate MS Where such abnormalities are at thegray–white junction and the patients are younger,ADEM is suggested Periventricular plaques (espe-cially if perpendicular to the ventricular surface) aremore suggestive of MS (Ormerod et al., 1986) SSPE,intoxications (e.g methanol), leukodystrophies, andstroke must occasionally be considered Malingeringmay be excluded on the basis of inconsistencies onexamination or with VER testing
Generally, recovery from idiopathic childhood ON
is excellent, although the rate of recovery may beslow (Good et al., 1992) The most common residuainclude optic nerve atrophy and impairments of colorand stereoscopic vision (Parkin et al., 1984; Purvin
et al., 1988) Permanent severe visual loss is quiteexceptional Bilateral presentation after an ante-cedent illness or immunization usually (although notalways) implies good prognosis for visual recovery
(Parkin et al., 1984; Riikonen et al., 1988b; Good
et al., 1992) Postpubertal ON is more likely to haveresidual deficits
In adults, treatment with intravenous high-dosemethylprednisolone of first bout of ON hastens
recovery and may prolong the time to diagnostic
recurrence of MS Oral prednisone provides no benefitand may heighten odds of early recurrence of a boutdiagnostic of MS (Beck et al., 1992; Beck et al., 1993;Silberberg, 1993) These cases were chiefly firstbouts of MS and the relevance of this data to children, many of whom do not go on to develop
MS, is unclear Recovery occurs with or withoutanti-inflammatory therapy in most children andthere is little evidence that final recovery is favorablyinfluenced by treatment High-dose intravenoustreatment for 3 –5 days in cases of quite profoundoptic nerve swelling may prevent ischemic injuryand other childhood ON may manifest more rapidrecovery with such treatment Limited data sug-gests treatment may reduce chances for ultimatediagnosis of MS ( Jacobs et al., 1994)
ON may recur Various studies, following up for
2 –18 years, have estimated a 0 – 60% risk for MS if about of ON occurs before 18 years of age (Kriss et al.,1988; Parkin et al., 1984; Riikonen et al., 1988) Amore refined estimate suggests 15 – 30% overall risk(ON Study Group, 1997), chiefly sustained by thoseover 12 years of age, in whom there is about a 50%risk Poor or incomplete visual recovery, itself chiefly
a postpubertal phenomenon, also implies a 50% risk for ultimate diagnosis of MS (Good et al., 1992) The presence of lesions consistent with MS plaques
in typical locations (periventricular, forceps majorand minor) on MRI increases the risk for subsequentdiagnosis of CD-MS to at least 75–80% The presence
of oligoclonal bands in the CSF also increases the risk for diagnosis of MS within five years, althoughnot so decisively as the MRI features just noted.Oligoclonality increases risk even where the MRI
is normal (Cole et al., 1998) Risk of MS is high inunilateral ON (which is mostly postpubertal) andtrivial in bilateral prepubertal cases (Parkin et al.,1984) In cases where ON is associated with ADEM,GBS, or Dévic syndrome, the prognosis should bedetermined on the basis of the more disseminated illness, but visual recovery is usually good
Acute transverse myelitis (ATM)
Various causes for acute childhood/adolescent opathy are listed in Box 5.14 The most common
Trang 4myel-causes are inflammatory, traumatic, or vascular
In children, post-infectious/post-vaccination matory myelitis is a particularly important category
inflam-These cases are often a form of ADEM, including Lymemyelitis (Kerr and Ayetey, 2002; Rousseau et al.,1986; Tyler et al., 1986) Infections precede ATM bydays to several weeks in 60% of cases (Paine andByers, 1953) The additional history of blunt trauma
to the spine is not infrequently recalled The cervicallocation is a common one as is thoracic Many morelevels of the spine may be involved than is typical of
MS In some instances the entire spine is involved
as well as some of the brainstem In some instancesthe inflammatory sensitization involves both centraland peripheral (e.g spinal root) myelin (Abramskyand Teitelbaum, 1977) The irreversible injury withmyeloclasia that complicates severe ATM is likely
to be vascular: due to the ischemia induced by cord swelling within the confined space of the spinalcanal ATM that occurs in the first few years of lifemay be particularly malignant, but most cases occur
in children more than five years of age (Aicardi,1992; Berman et al., 1981)
Pain and dysaesthesiae in the region of the oping ATM are the most common early symptoms
devel-Fever and meningismus may then follow Paraplegia,sensory loss, and sphincter dysfunction may developslowly over days to many weeks or paroxysmallywithin several hours The rate of onset is often pro-portional to the intensity of the initial discomfort
Intense pain in neck presaging hyperacute cervicalATM is a medical emergency that may have a fataloutcome due to cardiorespiratory compromise Inmost instances bilateral flaccid areflexic paraparesiswith a sensory level and sphincter dysfunction develop,followed in a few days by spastic weakness in thesame distribution Superficial reflexes (abdominal,cremasteric, bulbocavernosus) are usually absent.Partial spinal cord syndromes (e.g Brown–Sequardsyndrome) or Dévic syndrome may be found RarelyATM presents with the isolated complaint of urinaryretention (Ropper and Poskanzer, 1978) ATM withfebrile infectious prodrome and associated constitu-tional symptoms is more common in prepubertalpatients and suggests ADEM ATM without theseassociated features is more common in adolescentsand is suggestive of MS MS tends to provoke a lesscomplete form of myelitis than ADEM The MRI ofpatients with MS-related myelitis typically demon-strates T2 bright signal abnormality of some, but notall, areas of the cord that are enriched with myelinatedfibers The outlook for recovery may be poorer andthat for severity of MS may be greater in adolescentsthat are found to have signal abnormality throughmany rather than few levels of the spinal cord.Adolescent patients with purely spinal manifesta-tions suggesting MS should be screened for tropicalspastic paraparesis/HTLV-1 associated myelopathy(TSP/HAM), while men should be evaluated foradrenomyeloneuropathy (Walther and Cutler, 1997)
• Isolated ATM– Abscess*
– Hemorrhage– Stroke (vascular malformation,compressive, embolic*)– Radiation
– Tumor (spinal,* spinal root, meningeal, vascular, bone)– Trauma*
• More widespread neurological disease– Dévic syndrome (see below)***
– Encephalomyeloradiculoneuropathy***
– Multiple sclerosis***
– ADEM***
– Guillain–Barré syndrome– Neurosarcoidosis**
– Tropical spastic paraparesis**
(Link et al., 1989)
• In association with systemic disease– AIDS vascular myelopathy*,**
(Rosenblum et al., 1989)– Chronic progressive (third stage) Lyme neuroborreliosis**,***
– Systemic lupus erythematosus**
Box 5.14 Causes of acute transverse myelitis.
Trang 5Some combination of history, examination, ing studies, and CSF and serum tests discloses an etiological diagnosis (from among those listed in Box 5.14) for ATM in approximately two-thirds ofthe cases encountered in children and adolescents.
imag-MS-associated ATM is almost entirely confined topostpubertal individuals, ADEM-related ATM to pre-pubertal individuals Imaging studies of brain andspinal cord are important in order to disclose dis-tribution and in some instances cause of disease, aswell as lesions or edema that require urgent therapy
in order to prevent irreversible ischemic injury
Unsuspected brain lesions may be found in MS, ADEM,neurosarcoidosis, and other diagnoses (Miller et al.,1987; Sanders et al., 1990) Myelography is some-times helpful (Narciso et al., 2001) CSF pleocytosis
is present in 25%, increased CSF protein in 50% ofpresumed ATM cases (Aicardi, 1992)
No therapy, including corticosteroids, has beenrigorously proven to be efficacious in the treatment
of ATM Management is largely symptomatic, withparticular attention to careful management of suchassociated problems as urinary retention and impairedbreathing Pain and dysaesthesiae may be trouble-some and vigorous attempts should be made to treat these symptoms, particularly where they inter-fere with sleep Some degree of recovery occurs in
80 – 90% of children, requiring weeks to months
Approximately half of children with ATM will showexcellent recovery; 10 – 20% develop cord necrosisand do not recover Most of the remainder have vari-able residua (Ropper and Poskanzer, 1978; Berman
et al., 1981) The most important prognostic factor isacuteness of onset; recovery is poor after hyperacuteonset (Dunne et al., 1986)
A very small number of children with cervicalATM die from cardiorespiratory arrest or upwardsherniation Despite the lack of established efficacy,very high doses of anti-inflammatory agents may
be tried in cases of progressive cervical ATM, ticularly those with hyperacute and potentially life-threatening presentation Ultimate diagnosis of MS
par-is made in only about 10% of adults who experienceATM; the diagnosis of MS after isolated childhoodATM is probably even more exceptional (Aicardi,1992)
Neuromyelitis optica (NMO, Dévic syndrome)
In children with NMO the signs of ATM and ONmay develop simultaneously or in rapid succession
Most prepubertal cases develop within days to weeks
after a viral illness or immunization The transversemyelitis is typically sudden and severe, producingparaplegia ON often develops in both eyes bilateral,onset in the second eye occurring days to monthsafter the first Funduscopic changes of papillitis areusually, but not always, present The prodromal illness is less commonly discerned in postpubertalcases, the myelitis less complete, and there is a greatertendency for the ON to be unilateral More detaileddescription of this entity and recent advances inunderstanding of pathogenesis, classification, dif-ferential considerations and diagnostic testing are considered elsewhere in this volume There is nogenerally accepted therapy for DS However, veryhigh doses of intravenous corticosteroids may beconsidered where optic nerve or spinal cord swelling
is particularly alarming, in order not only to attenuatethe inflammatory process, but also to close blood–brain barrier and prevent swelling that may lead totissue ischemia
Encephalomyeloradiculoneuropathy (Miller–Fisher/Bickerstaff encephalitis)
Some cases of ADEM with prominent myelitis willhave peripheral nerve signs, representing clinicaloverlap with GBS This overlap is particularly pro-minent in patients with AIDS Tumors with involve-ment of the cauda equina or nerve roots must also beconsidered The anti-Hu-associated paraneoplasticsyndromes that should also be considered in adultshave not yet been shown to occur in children(Dalmau et al., 1992)
Acute necrotic encephalitis (ANE)
The pathogenesis of this early childhood illness thathas chiefly been reported in Japanese and Taiwanese(Mizuguchi et al., 1995; Voudris et al., 2001) remainsobscure Although some type of inflammatory en-cephaloclasia is a likely explanation, it is unclearwhether this might be due to a primary infectiousprocess As with ADEM, there is a male predom-
between 6 – 24 months of age, although cases haveoccurred in children as old as five years The onset istypically marked by fever and rapid deterioration ofmental status in association with convulsive seizuresand brainstem signs Abnormalities of liver enzymetesting may be found
MRI scans of severely affected children disclosesymmetrical bright lesions on T2 weighting that
Trang 6involve the thalami, hypothalamus, brainstem mentum, and cerebellum Bright signal may also
teg-be found in cerebral white matter Some of theseabnormalities (particularly those representing edema)and clinical status may improve with high doses ofintravenously administered corticosteroids Someparticularly malignant cases appear to have favor-ably responded to heroical treatment with surgicaldecompression of intracranial pressure The graymatter lesions may become cavitary and death hasoccurred in approximately half of recognized cases
This severe disease must be differentiated fromthose cases of presumed ADEM whose imaging manifestations may be confined to or emphasized inwhite matter and thalami The patients with theseADEM-related manifestations tend to be older (0.4 –
6 years of age) and their disease evolution is muchless severe than is observed by the infants with ANE
The outcome is favorable, with resolution of scanchanges once recovery occurs (Cusmai et al., 1994;
Marcu et al., 1979; Suwa et al., 1999; Tenembaum
et al., 2002) It is not entirely clear whether somereports of milder cases of ANE from which infantsrecover without subsequent relapse are cases of mildANE or of ADEM ANE must not be confused withsome cases that fall within the ADEM/childhood MS/“recurrent ADEM” spectrum that manifest largepseudo-cavitary lesions of deep white matter sparingbasal ganglia or thalamus, or with AHLE or Balò disease, all diseases for which high doses of intra-venous corticosteroids may prove beneficial The differential diagnosis also includes tumor, infectious,metabolic, or vascular (e.g sinovenous thrombosis)diseases of brain
Subacute-onset disseminated CNS illnesses that may be forms of ADEM
Considerable recent interest has focused on the sibility that certain complex subacute-onset illnesseswith extra pyramidal, psychiatric, and behavioralmanifestations may represent post-infectious diseasesthat have mechanisms similar to ADEM or mightrespond to therapies advocated for ADEM and relatedillnesses The basis for such speculation derives inpart from the strong evidence that one such illness,Sydenham chorea, is a post-infectious condition that
pos-is known to be provoked by certain strains of Group
attempted to characterize another entity, termedpediatric autoimmune neuropsychiatric disorder(PANDAS) Attention has also been directed to the
study of the neuropsychiatric disturbances that maydevelop in patients with rheumatic fever withoutassociated chorea, observations that some believewill have pertinence to the development of isolatedpsychiatric disturbances (Mercandonte, 2000) or suchcontroversial entities as “chronic fatigue syndrome.”During the past two decades, a number of cases ofindolent psychiatric disturbances associated with
“ADEM-like” MRI abnormalities have been reported,
as has the gradual improvement of images and affectwith corticosteroid treatment Investigators havesuggested that these are examples of “subacute” limbic or disseminated encephalomyelitis ( Johnson
et al., 1985) These cases have tended to have noclear association of deterioration with a precedingfebrile illness or vaccination and CSF immune profilestudies if obtained have been normal
Meningoencephalitic encephalitis and other infections with possible ADEM-related complications
The role that inflammatory dysregulation plays
in the pathogenesis of CNS infectious conditions has received increasing scrutiny in the past decadeand falls outside of the scope of this review Theextent to which mechanisms closely resemble those
of ADEM or MS, the role of genetics, and the tinence of anti-inflammatory therapy for these con-ditions are as yet incompletely understood Theseconditions constitute part of the differential dia-gnosis of ADEM and MS, and may produce similarimaging or CSF abnormalities The presence of pial
per-or cper-ortical gadolinium enhancement on T1-weightedimages is suggestive of encephalitis rather thanADEM The borderland between HSV2 encephalitisand ADEM is especially unclear when there arewidespread lesions, some such cases responding very well to acyclovir treatment (Chu et al., 2002),some apparently benefiting from the addition of anti-inflammatory therapy
Acute or “relapsing” HSV2 encephalitis may beespecially difficult to distinguish from ADEM (Chu
et al., 2002) Some widespread HSV2 “recurrence” is
a form of ADEM, responsive to corticosteroid ment with a good outcome (Tulyapronchote and Rust,1992) Chronic progressive Lyme encephalomyelitis
treat-or third-stage neurobtreat-orreliosis may also be a ftreat-orm
of ADEM (Braune, 1991; Pavlovic et al., 1993; Reik et al., 1985) Japanese B, measles, and mumpsencephalitides, cerebral malaria, and the CNS manifestations of Dengue all likely entail immuno
Trang 7dysregulation that may involve ADEM-related anisms and may prove responsive to therapies aimed
mech-at this form of pmech-athogenesis The presence of pialenhancement, which is not a finding in ADEM, sug-gests active meningoencephalitis Metazoal parasiticdiseases of brain (e.g cysticercosis) may produceimaging changes that closely resemble ADEM,
although the pathogenic mechanisms of ADEM areprobably not involved
Summary
Box 5.15 includes hypothetical criteria for variousADEM spectrum diagnoses in children
I Tentative ADEM (T-ADEM)
1 Preceding exogenous provocation(required)
a Febrile, likely infectious illness
or vaccination within 28 days
b At least 12 hours afebrileimprovement prior to ADEM-related deterioration
2 Neurological deterioration: required
a At least two separate clinical lesions, otherwise unexplained
b At least three of the following:
(1) Recurrence of fever,irritability, or lethargy
at onset(2) Bilateral optic neuritis(3) MRI typical for ADEM (see text)
(i) Cortical ribbon–
subcortical whitematter junction(ii) Indistinct margins(“smudge”
appearance)(4) Focal or generalized EEGslowing
(5) Elevated myelin basis protein with normal CSF immune profile(6) Clear improvement ≤24hours after high-doseintravenous steroids
3 Other relevant diagnoses, including MS, excluded byappropriate testing
II Probable ADEM (P-ADEM): Meet T-ADEM criteria without recurrence
in 2 years*
III Definite ADEM (D-ADEM): Meet P-ADEM criteria, no recurrence for additional 10 years
IV Tentative Recurrent ADEM (TR-ADEM): Initial bout + ≤ four total bouts* each meeting criteria for diagnosis T-ADEM
V Probable recurrent ADEM (PR-ADEM):Meet TR-ADEM criteria followed by
a hiatus of ≥ 2 years without furtherrecurrence*
Not treated with immunomodulatoryprophylaxis during those 2 years without bouts
VI Definite recurrent ADEM (DR-ADEM):Meet PR-ADEM criteria followed ≥ 10additional years without recurrenceNot treated with immunomodulatoryprophylaxis during those 10 additionalyears
(*Excepting taper-related recurrences)VII Type 1 steroid-dependent idiopathicdemyelinating illness (SDIPI)
1 Recurrent cases not satisfying CD-MS or ADEM diagnosticcategories
2 Unavoidable recurrences provoked
at same approximate threshold
of steroid taper unless replaced
with at least monthly high doseintravenous corticosteroids
3 Excludes alternative diagnosesVIII Type 2 steroid-dependent idiopathicdemyelinating illness (SDIPI)
1 Recurrent cases not satisfying CD-MS
or ADEM diagnostic categories
Box 5.15 Criteria for various suggested diagnostic
groupings of ADEM family.
continued
Trang 8Abramsky, O and Teitelbaum, D 1977 The immune features of acute transverse myelopathy
auto-Ann Neurol, 2, 36 – 40.
Aicardi, J 1992 Diseases of the Nervous System in
Childhood MacKeith Press, London.
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high dose corticosteroid treatment Brain Dev, 21(4),
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Arya, S.C 2001 Acute disseminated
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Deep gray matter involvement in children with
acute disseminated encephalomyelitis AJNR Am J
Neuroradiol, 15(7), 1275 – 83.
Beck, R.W., Cleary, P.A., Anderson, M.M., Jr et al
1992 A randomized, controlled trial of oids in the treatment of acute optic neuritis The
corticoster-Optic Neuritis Study Group (see comments) N Engl J
Med, 326(9), 581– 8.
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The Optic Neuritis Study Group (see comments)
Braune, H.J 1991 Lyme borreliosis – Epidemiology,
etiology, diagnosis and therapy Fortschr Neurol
Psychiatr, 59(11), 456 – 67.
Bye, A.M.E., Kendall, B and Wilson, J 1985 Multiple
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Caracciolo, J.T., Murtagh, R.D., Rojiani, A.M et al 2001.Pathognomonic MR imaging findings in Balo con-
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Chen, C.J 2001 Serial proton magnetic resonancespectroscopy in lesions of Balo concentric sclerosis
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unless replaced with
immunomodulatory interferon therapy
3 Excludes alternative diagnoses
IX Other idiopathic recurrentdemyelinating illness (OIRDI)
1 Recurrent cases not satisfying CD-MS, ADEM, R-ADEM, T-ADEM, or SDIDI criteria
2 Alternative diagnoses excluded
by specific testing
X Idiopathic progressive disseminatedencephalomyelitis
1 Requires exogenous stimulus
2 Excludes cases with identifiable toxic, heritable, infectious condition(e.g heritable leukodystrophy,Aicardi-Goutieres, TORCH infection, AIDS, etc.)
XI Special cases
1 Lyme neuroborreliosis
Box 5.15 (Cont’d )
Trang 9Croft, P.B 1969 Para-infectious and post-vaccinal
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Currie, S., Roberts, A.H and Urich, H 1970 The nosological position of concentric lacunar leucoen-
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131– 7
Cusmai, R., Bertini, E., Di Capua, M et al 1994 Bilateral,reversible, selective thalamic involvement demon-strated by brain MR and acute severe neurological
dysfunction with favorable outcome Neuropediatrics,
25(1), 44 – 7.
Dale, J.B and Beachey, E.H 1984 Unique and mon protective epitopes among different serotypes
com-of group A streptococcal M proteins defined with
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Trang 13Guillain–Barré syndrome (GBS) is the most commoncause of nontraumatic acute and subacute general-ized paralysis in adults in the industrialized world It
is an acute acquired inflammatory neuropathy thatusually affects the motor nerve roots or its axons
GBS probably represents several distinct diseasesthat are grouped within a single syndrome TypicallyGBS presents with acroparesthesias or numbness, andevolves to ascending weakness within days to weeks
Areflexia is a hallmark As the weakness progresses,the patient may become completely paralyzed, requir-ing assisted ventilatory support Typically there isnormal cerebrospinal fluid (CSF) cellularity with anincreased CSF protein level Several variants havebeen reported
Epidemiology
Throughout the world, the annual incidence of GBS
is 1.3 cases for 100,000, affecting children and adults
GBS is the most common acute acquired neuropathy
of childhood In adults the prevalence is higher in
affected than women (1.5:1.0) (Kuwabara, 2004)
Recent anteceding infections are frequently associated,
most commonly Campylobacter jejuni, identified in up
to 25% of the cases Viral agents (HIV, EBV, CMV) and
other microbial infections (Mycoplasma pneumoniae)
have also been reported preceding GBS A history ofrecent immunization has also been implicated (e.g
vaccination against swine influenza, 1977) ations with recent surgery, trauma, and puerperiumhave been suggested, though more epidemiologicaldata is needed to confirm these associations with GBS(Cheng et al., 1998)
(LOS) from C jejuni, which causes a diarrheal illness,
and gangliosides of the peripheral nerve Macko et al., 1996b) The genetics of the micro-bial agent associated with the preceding infection may play an important role in the likelihood of itsimmunogenicity and cross-reaction against com-ponents of the peripheral nerve (Koga et al., 1998)
(Hafer-Several C jejuni genes may participate in the genic role of C jejuni infection Mutation of the
patho-C jejuni waaC gene alters both the bacterial LOS and
the capsular polysaccharides (Kanipes et al., 2006)
Gene racR may encode factors necessary for
patho-genicity in humans (Kordinas et al., 2005) Humanhost genetics also play an important role Humanleukocyte antigens (HLA) B54 and Cw1 were signific-antly more frequently present in patients with GBSand Miller–Fisher (MF) syndrome than in normalcontrols (Koga et al., 2005) In Japanese patients,immunoglobulin KM allotypes are associated with
an increased prevalence of anti-GD1a antibodies,but are not a risk factor for developing GBS (Pandey
et al., 2005)
The study of GBS variants like MF syndrome and AMAN has increased the understanding of thepathogenesis of these diseases and the autoimmunenature of GBS The pathogenesis of acute inflammat-ory demyelinating polyradiculoneuropathy (AIDP),which is the most common type of GBS in the USAand Europe, still remains uncertain There is suggest-ive evidence that increased circulating T-cell react-ivity against gangliosides, such as GM1, occurs in GBS.This is probably not related to nonspecific peripheralnerve damage, since hereditary, toxic, and diabeticneuropathy patients did not have increased T-cellreactivity (Csurhes et al., 2005) More recently,characteristics common to both European and Asian
C jejuni strains associated with GBS have been
described (Koga et al., 2006)
Guillain–Barré syndrome
Eduardo A De Sousa and Thomas H Brannagan III