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Immunological Disorders of CNS, Refences Aicardi's Diseases of the…
Immunological Disorders of CNS
Acute Demyelinating Syndromes (ADS)
acute demyelinating encephalomyelitis (ADEM)
<10 y
typical course: infectious illness, few days fever, malaise, headache, nausea, vomiting, then drowsiness, counfusion, seasures, multifocal neurologic signs
prominent encephalopathy triggered by infections or vaccination
International
Paediatric Multiple Sclerosis Study Group criteria (IPMSSG)
monophasic ADEM
First polyfocal clinical event affecting the central nervous system
Encephalopathy defined as alteration in consciousness not due to fever, systemic illness or a postictal phase
Abnormal brain MRI within the first 3 months of clinical symptoms. A. diffuse, poorly demarcated (>1–2 cm) lesions predominantly affecting the white matter. B. lesions in the thalamus, basal ganglia, deep grey matter or spinal cord (typically longitudinally extensive)
After the first 3 months from symptom onset no new clinical symptoms or MRI abnormalities are found.
multiphasic ADEM
Two clinical events meeting criteria for acute disseminated encephalomyelitis, separated in time by greater than 3 months
No evidence for clinically-silent new lesion formation on MRI between acute disseminated encephalomyelitis episodes
examinations
cranial MRI
restricted diffusion that reflect vasogenic oedema
prominent asymmetrical bilateral T2 and fluid inversion recovery (FLAIR) enhancing lesions that reflect pathology in myelin
Scattered enhancing lesions in subcortical, cortical grey matter, spinal cord. May show inhancement with gadolinium. Correspond to infiltrates of T-cells and macrophages
CSF: pleocytosis, oligoclonal bands
EEG: slowing - encephalopathy
acute hemorrhagic leukoencephalitis (AHL): more fulminant and aggressive form
severe increased intracranial pressure
H1N1, enterovirus infection, diperte vaccination, mutations in complement factor ' pathway, RANBP2 - tunesia
prognosis
45% second episode
20% later multiple sclerosis
50-70% full recovery in 1-6 mo
20-30% minor disability
mortality 5%
therapy
iv. methylprednisolon 10-30 mg/kg/day maximum 2 g/day followed by steroid taper of prednisone over 4-6 weeks
iv. IgG
plasma exchange
clinically isolated syndromes (CIS)
optic neuritis (ON)
clinical findings
relative afferent pupil defect
visual field restriction
painful eye movements
11 y
etiology: MS, viral/bacterial infections, lyme disease, cat scratch, sarcoid, sinusitis, vaccination, inherited white matter disorres, B12 deficiency, vasculitis, diabetes, medications, SLE, Sjorgren, NMO
prognosis
recovery 1 y 77%
34% NMO, MS
therapy: iv methylprednisolon, oral prednisolon taper
acut transverse myelitis (ATM)
definition: acute onset of sensory, motor or autonomic dysfunction attributable to spinal cord dysfunction with a defined sensory level and MRI rules out extra-axial compression but shows gadolinium enhancement
CSF: pleocytosis, elevated IgG index, oligoclonal band
differeintial diagnosis: arterial stroke, AVM, SLE, HIV, HSV, Guillan-Barré sy, NMO, ADEM
Kutzke Expanded Disability Status Scale
(EDSS), American Spinal Injury Association
impairment (ASIA)
treatment
high dose corticosteroid: iv 1g/1.73 m2/d methylprednisolon 3-5 d
plasmapheresis (adult)
rituximab (adult)
brainstem encephalitis
clinical presentation: external opthalmoplegia, ataxia, multiple cranial nerve involvement, tremor, myoclonic jerks, swallowing, speech problems
Miller-Fisher: ophtalmoplegia, ataxia, areflexia - GBS variant, anti-GQ1b IgG (ganglioside)
abnormal MRI findings: 23%
EEG: 70% abnormal
mycoplasma pneumoniae, EBV, H1N1, streptococcus, cat scratch, enterovirus 71, Japanese encephalitis virus (antibodies: anti-GABA B-receptor, anti-glycine receptor)
treatment: Ivig, alemtuzumab
polyfocal clinically isolated sysndrome
definition
A first monofocal or polyfocal clinical event affecting the central nervous system.
Encephalopathy is not present (unless transient and caused by fever).
For patients between 12–18 years the 2010 McDonald MRI criteria for dissemination in space and time as applied to the baseline MRI are not met
multiple sclerosis (MS)
clinical definition
Two clinical events without encephalopathy consistent with multiple sclerosis separated by more than 30 days and affecting more than one area of the brain, optic nerves or spinal cord.
A first clinical event consistent with multiple sclerosis in a patient between 12–18 who fulfills 2010 McDonald MRI dissemination in space in two of four locations, periventricular, juxtacortical, infratentorial or spinal cord, as well as dissemination in time (clinically silent enhancing or non-enhancing on T1-weighted images) criteria on baseline MRI.
One clinical event without encephallpathy typical of multiple sclerosis and MRI demonstrating at least one new T2 lesion on a scan more than 30 days after the incident attack.
An event that fulfills criteria initially for acute disseminated encephalomyelitis followed by a second non-acute disseminated encephalomyelitis event (>3 months from symptom onset) associated with new MRI lesions demonstrated 2010 McDonald disseminated in space criteria.
chronic remitting, relapsing inflammatory demyelinating disorder in which lesions are disseminatedover space and time in the nervous system
differential diagnosis
Endocrine thyroid disorder, diabetes mellitus
Inflammatory systemic lupus erythematosus, neurosarcoidosis, antiphospholipid antibody syndrome
Mitochondrial MERRF, MELAS, LHON
Leukodystrophy metachromatic leukodystrophy, adrenoleukodystrophy
Genetic/metabolic inborn errors of metabolism, amino acidurias
Infectious disorders neuroborreliosis, herpes simplex encephalitis, HIV, neurocysticercosis
Post streptococcal infection, abscess
Vascular disorders CADASIL, Moyamoya disease, carotid dissection
Demyelinating ADEM, ON, TM, NMO
Nutritional B12 or folate deficiency
Neoplastic lymphoma, astrocytoma
MERRF–myoclonic epilepsy with ragged red fibers; MELAS–mitochondrial encephalopathy with lactic acidosis and stroke-like episodes
LHON–Leber hereditary optic neuropathy; CADASIL–cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy
diagnosis
based on the history and neurological examination as well as MRI and the exclusion of alternative diagnose:
DIAGNOSIS OF EXCLUSION
IPMSSG diagnostic criteria 1/4
Two or more non-encephalopathic (non-ADEM) clinical inflammatory CNS events separated by more than 30 days and involving more than one area of the CNS;
One nonencephalopathic event typical of multiple sclerosis with magnetic resonance findings consistent with the 2010 Revised McDonald Criteria for dissemination in space and in which the MRI shows at least one new enhancing or nonenhancing lesion consistent with dissemination in time;
One ADEM episode followed by a nonencephalopathic clinical event, 3 or more months after symptom onset, that is associated with new MRI lesions that fulfill 2010 McDonald criteria for dissemination in space;
A first, single, acute event that does not meet ADEM criteria and whose MRI findings are consistent with the 2010 McDonald criteria for dissemination in space and time, applying only to children >12 years.
CSF: oligoclonal bands might be present
McDonald Criteria 2010
dissemination in space (multifocal)
The McDonald criteria for dissemination in space are fulfilled if ne of the following is present in a patient with a clinically isolated syndrome or typical MS attack:
An MRI with one or more hyperintense T2 lesions that are characteristic of multiple sclerosis in at least two of four MS-typical regions of the central nervous system: Periventricular / Cortical or juxtacortical / Infratentorial / Spinal cord
Development of an additional clinical attack characteristic of multiple sclerosis, supported by objective clinical evidence, that implicates a different central nervous system site
dissemination in time
The McDonald criteria for dissemination in time are fulfilled if one of the following is present in a patient with a clinically isolated syndrome or a characteristic MS attack:
The development of an additional clinical attack, supported by objective clinical evidence, that is characteristic of multiple sclerosis
An MRI of the brain and/or spinal cord with the simultaneous presence of gadolinium-enhancing and nonenhancing lesions at any time, or by a new hyperintense T2 and/or gadolinium-enhancing lesion(s) on follow-up MRI, irrespective of its timing with reference to a baseline scan
Finding of cerebrospinal fluid-specific oligoclonal bands (as a substitute for dissemination in time)
treatment
Methylprednisolone Used in high doses for acute episodes and those affecting vision
Interferon β-1a First line disease modifying interferon (im, sc)
Interferon β-1b First line disease modifying interferon (sc)
Glatiramer acetate First line disease modifying, synthetic polypeptide (sc)
Cyclophosphamide Alkylating agent second line for aggressive multiple sclerosis (IV)
Teriflunomide Pyrimidine synthase inhibitor (oral)
Fingolimode Sphingosine-1-PO4, inhibits T and B cells (oral)
Dimethyl fumarate Inhibits immune cells (oral)
Natalizumab Antibody blocks white cell entry into brain (Tysabri®, IV)
Mitoxantrone Immunosuppressant with considerable heart toxicity
Rituximab Monoclonal antibody against pan-B cell marker CD20
KIDMUS criteria 2008
IPMSSG International Pediatric Multiple Sclerosis Study Group
fatigue, depression, cognitive impairment
Antibody-mediated encephalopathy
neuromyelitis optica (NMO) = Devic disease
bilateral optic atrophy
A spinal cord lesion extending over three or more vertebral
segments on MRI (t2 hyperintens, T1 hxpointens, gadolinium inhancement
A brain MRI that does not meet the criteria for multiple
sclerosis - optic chiasma, area postrema
The presence of the NMO-AQP4- IgG antibody in
plasma - suitable for monitoring treatment success
oligoclonal bands 18%
antibodies against myelin ologodendrocyte
glycoprotein (MOG-Ig)
treatment
acute episode
line: methylprednisolon 1 g/d for 5 d
line: plasma exchange every other day for 2 weeks
interval
cyclophosphamid, azathioprine, mycophenolate (mofetil), rituximab, ivig
CAVE: interferon beta increases the level of NMO antibody!
anti-glutamate receptor encephalopathies and related disorders
streptococcal infection-related disorders
Hashimoto encephalopathy and anti-thyroperoxidase antibodies
anti--myelin oligodendrocyte glycoprotein encephalitis: anti-MOG antybody serum: ADEM, CIS 40%, viral encephalitis, favourable outcome
Mimics
vasculitis
systemic lupus eryhtematosus (SLE)
Bechet disease
primary central nervous system vasculitis
immunogenetic diseases: primary and secondary hemophagocytic lymphohistiocytosis
tumours
primary cerebral lymphoma
Langerhans cell histiocytosis
oligodendroglioma, low grade astrocytoma
genetic diseases
disease of the RNA metabolism, Aicardi.Goutieres sy
mitochondrial respiratory chain defects (Leigh, Leber, OPA)
X-ALD, lysosomal diseases
angiopathies: CADASIL, Coats+ sy
inflammatory diseases
granulomatous disorders
sarcoidosis
polyarteritis nodosa
Wegener
anti-ANCA related disorders
autoinflammatory disorders
Neonatal onset multisystem inflammatory disease (NOMID) or Chronic inflammatory
neurological cutaneous articular syndrome (CINCA
cryptopyrin-associated periodic syndromes
SUSAC syndrome
infections: cat scratch disease, Lyme disease, Chikungunya
migraine
para-neoplastic disorders
opsoclonus-myoclonus syndrome = dancing eye syndrome = Kinsbourne's syndrome
rapid onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation
examinations
MRI
LP - WBC, WBC, protein, sugar, IgG index, oligoclonal band, lactate/pyruvate ratio for the detection of respiratory chain dysfunction, particularly in patients with MRI lesions restricted to the brainstem and basal ganglia
blood formula, CRP, ESR
complement activity
anti-thyroid, anti-neuronal antibody
vasculitis: auto-antibodies: antinuclear antibodies, anti-double-stranded DNA, anti-SSA, anti-SSB, antiSm, anti-RNP antibodies
ANCA
Refences Aicardi's Diseases of the Nervous System in Childhood (2018)