Multiple Sclerosis and other inflammatory Demyelinating Diseases Flashcards
generally accepted pathologic criteria of a DEMYELINATING DISEASE (3)
- destruction of myelin sheaths of nerve fibers with relative sparing of other elements 2. infiltration of inflammatory cells, perivenous distribution 3. lesions that are primarily in white matter
topography of lesions in MS
periventricular optic nerves and chiasm spinal cord
histologic appearance of MS in the ACUTE phase
partial or complete destruction of myelin, perivenous axons are relatively spared slight degeneration of oligodendroglia variable astrocytic reaction perivascular and para-adventitial infiltration of mononuclear cells and lymphocytes
histologic appearance of CHRONIC lesions in MS
thickly matter, acellular glial tissue occasional perivascuar lymphocytes and macrophages descending and ascending wallerian degeneration partial remyelination
4 histologic subgroups in MS
pattern I inflammatory lesions made up of T cells and macophages pattern II autoantibody lesion mediated by immunoglobulin and complement pattern III apoptosis of oligodendrocytes, absence of IG, complement and partial remyelination pattern IV oligodendrocyte dystrophy, no remyelination
T/F MS has a uni-modal age specific onset curve, similar to that of infectious and connective tissue diseases.
True p 917
T/F There is an increased risk of developing MS with higher and lower latitude.
True p918
T/F Approximately 15% of MS patients have an affected relative, with the highest risk of concurrence being observed in the patient’s siblings.
True p918
T/F In MS, the concordance rate in dizygotic pairs is similar to that of nontwin siblings.
True p918
Certain histocompatibility locus antigens (HLAs) are more frequent in patients with MS than in control subjects The strongest association is
DR locus on chromosome 6
Presence of markers or HLAs increases the risk of an individual to develop MS by
3-5x
other alleles (aside from HLA loci) identified as heritable risk factors
IL - 2Ra IL - 7Ra
MS is mediated by ____cell sensitization to some component of _____
T cell myelin
typical feature of MS , temporary induction by heat or exercise of symptoms such as unilateral BOV, tinging and weakness of limb
Uhtfoff phenomenon
other situations that can briefly worsen neurologic functioning in MS, and may be confused with relapses of disease
smoking, fatigue, hyperventilation, rise in environmental temp
syndromes typical of MS (4)
optic neuritis transverse myelitis cerebellar ataxia brainstem syndromes
Lhermitte sign
flexion of the neck may induce a tingling, electric -lie feeling down the shoulders and back and less commonly down the anterior thighs
T/F In optic neuritis, there is pain within the orbit, worsened by eye movement or palpation of the globe.
True p921
T/F In optic neuritis, both optic nerves are sometimes involved either simultaneously or more commonly within a few days or weeks of one another.
True p921
percentage of patients with optic neuritis who will develop other signs of MS
50% p921
T/F Recurrent optic neuritis increases the chances of developing MS.
True p922
Charcot Triad
nystagmus scanning speech intention tremor
inernuclear ophthalmoplegia
involvement of MLF paresis of MR on lateral gaze, with coarse nystagmus in the abducting eye
True or False The presence of bilateral INO in a young adult is virtually diagnostic of MS.
True p924
common precipitating factors in MS but was not really proven
infection trauma pregnancy
variant of MS rapidly progressive, highly malignant form combination of cerebral, brainstem and manifestations evolve over a few weeks may render the patient stuporous, comatose, or decerebrate with prominent cranial nerve and CST abnormalities death may end illness CSF shows cellular response but no oligoclonal bands
Acute and Tumor-Like (Tumefactive) MS Marburg Variant
occurrence of alternating bands of destruction and preservation of myelin in a series of concentric rings that represent alternating areas of myelin loss and preservation
concentric sclerosis of Balo
CSF findings in typical MS
slight mononuclear pleocytosis - usually in the range of 6-10, less than 50 cells in cases of severe demyelinating disease of brainstem - up to 100 presence of gamma globulins, seen as oligoclonal bands in electrophoresis increased total protein content more than 100mg/dL is unusual IgG and IgG index positive test >12% concentration of MBP, elevated - not particularly useful in diagnosis, but reflects destruction of myelin
define IgG index
proportion of gamma globulin in reference to total protein of CSF
how many percent of MS cases show several bands in determination for oligoclonal IgG
90%
other conditions which show demonstrate bands
syphilis, Lyme, subacute sclerosing panencephalitis but can be distinguished from MS clinically
True or False The presence of bands in a first attack of MS is predictive of a chronic relapsing course.
True p928
most widely used CSF test for MS
oligoclonal bands
most helpful ancillary examination in the diagnosis of MS
MRI
describe acute lesions of MS in T1 and T2 sequences
Acute lesions tend to demonstrate tissue expansion diue to edema that is evident as T1 hypointensity and T2 hyperintensity Chronic lesions - T2 hyperintense
relation of T1 hypointensity and remyelination
T1 hypointensity is inversely proportional to the degreee of remyelination if there is no or scant remyelination, the center of teh chronic lesion gives the appearance of a “black hole”
MRI findings of multifocal, well-demarcated, oval or linear, radially oriented lesions adjacent to the ventricular surface usually denotes the typical RRMS when viewed on sagittal form what patter can be seen?
Dawsons fingers the lesions extend from the corpus callosum filliform pattern
disruption of BBB in early MS can be seen in T1 as _________ after gadolinium
hyperintensity one characteristic pattern: C-shaped partial or open ring of abnormal enhancement
True or False Spinal lesions of MS occupy only a portion of the transverse surface. They extend longitudinally beyond three contiguous vertebral segments.
False DO NOT extend beyond 3 contiguous vertebral segments
Diagnostic Criteria for MS
- 2 or mote typical attacks with objective evidence for both lesions
- 2 clinical attacks, 1 objective evidence, laboratory: lesions located in at least 2 of 4 typical locations
- 1 attack with objective evidence of 2 or more lesions, laboratory: dissemination over time: simultaneous enhancing and non-enhancing lesions in the said locations, or interval development of new T2 hyperintense lesions
- 1 attack with objective evidence on examination for only 1 lesion (CIS), laboratory: dissemination in space, lesions or T2 hyperintensity located in at least 2 of 4, dissemination time demonstrated by simultaneous enhancing and non-enhancing lesions in the above locations, or interval development of new T2 hyperintense lesions
- progressive, nonrelapsing deficits suggestive of MS, one year disease progression and dissemination in space as above an doligoclonal bands or elevated IgG index in teh CSF
average relapse rate in MS
0.3 - 0.4 attacks per year
in 1 yr 30% of patients
in 2nd yr 20% of patients
True or False
In MS, pregnancy is typically associated with clinical relapse.
False
It is associated with clinical stability and even with improvement (as it is in a number of autoimmune diseases).
p 930
True or False
There is an increased risk of exacerbations up to twofold in MS patients, in the first few months postpartum.
True
p930
True or False
ADEM is an acute illness with widely scattered small demyelinating lesions that is self-limited and monophasic.
True
p931
why should the neurologists be cautious in initiating treatment regimens for MS in patients with systemic autoimmune and inflammatory diseases?
B-interferon may worsen systemic autoimmune illness
True or Fasle
CSF in cervical spondylosis is often elevated.
True
p932
but with absent oligoclonal bands
and absent elevated IgG
Dosing of IV methylprednisolone and oral prednisone in the treatment of acute exacerbations (aborting or shortening an acute attack) of MS or of optic neuritis
500-1000mg of methylprednisolone daily for 3-5 days followed by oral prednisone 60-80mg/day and tapering to a lower dosage over a 12-20 day period
If it is impractical to administer parenteral methylprednisolone, one may substitute for oral methylpred with the ffg dosing:
48 mg in a single daily dose for 1 week
followed by 24mg daily for 1 week and
finally 12g daily for 1 week
OR the equivalent amount of prednisone
Dosing for IV Ig in relapsing-remitting MS
IV Ig 0.2g/kg for 2 years
results of the ONTT
use of IV methylprednisolone followed by orla prednisolone sped the recovery from visual loss although at 6 months, little difference between pts treated vs placebo
those treated with orel pred alone, had slightly increased risk of new episoded of ON
What two drugs alterthe natural history of RRMS
glatiramer
interferon
True or False
Interferon B
Trials have shown that subcutaneous injection of this agent every second day for up to 5 years decreases frequency and severity of relapses by almost one-third and also the number of new or enlarging lesions.
True
p933
role of interfero in progressive MS
there was delay in progression by how many months
9-12 months
side effects of interferon agents
flu-like symptoms, sweating, malaise, beginningseveral hrs after injection up yo 14 hrs
(reduced by pre and post treatment with NSAIDs
prednisone 10mg may be taken few hrs before and after)
exacerbation of headaches in migraineurs
mimic actions of MBP
given subcutaneous dily 20mg
glatiramer
side effects of glatiramer
flushing
chest tightness
dyspnea
palpitations
severe anxiety
role of azathioprine in MS
British and Dutch MS Azathioprine Study Group
no significant advantage to treatment with azathioprine
role of oral methotrexate in MS
one trial showed that in patients with progressive MS, weekly low-dose of methotrexate resulted in slight improvement difference and produced some reduction in the volume of cerebral lesions on the MRI compared with control cases
MOA Natalimumab
directed against alpha-integrin in order to block lymphocyte and monocyte adhesion to endothelial cells and their migration through the vessel wall
shown to reduce the number of relapses and slowing of the accumulation of MRI lesions
a monoclonal antibody that targets CD-52 antigen expressed on T and B lymphocytes, reduces the number of circulating cells and for a longer period T cells
Alemruzumb
side effect of Natalimumab
appearance of progressive multifocal leukoencephalopathy (PML)
the risk of developing PML in patients receiving Natalimumab is 11 per 1000 in the presence of these factors
postive anti-JC virus antibodies
long duration of matalimumab use over 24 months
side effecs of alemtuzumab
appearace of Idiopathic Thrombocytopenic Purpura
Autoimmune thyroiditis
B-cell depleting monoclonal antibody that targets CD20 lymphocytes
effective in reducing relapses and accumulation of MRi lesions in RRMS,
long term safety is still being established
Rituximab
oral immunossuppressive drug for MS that interferes with egress of lymphocytes form lymph nodes
has a short-term effect on MRI lesion burden and relapse rate that is comparable or slightly superior to injectable agents in a randomized trial
fingolimod
side effects of fingolimod
lymphophenia
bardycardia, AV block, macular edema, herpes infections, elevations of LFTs
what drug do we give for patients with MS experiencing the ffg symptoms:
fatigue
urinary retention
spastic bladder
sexual dysfunction
fatigue: amantadine, modafinil, pemoine, methylphenidate or dextroamphetamine
urinary retention: bethanechol
spastic bladder: propantheline, oxybutynin
sexual dysfunction: sildenafil
What do we give for the ffg symptoms in MS patients
spasticity
tremors
spasticity: botox, baclofen
tremors: isoniazid with pyridoxine, carbamazepine or clonazepam
monophasic, demyelinating disease with simultaneous or successive and usually sever involvement of optic nerves and spinal cord
Neuromyelitis optica
Devic Disease
Indicate if MS or NMO
- presence of oligoclonal bands in CSF
- higher tendency to pleocytosis
- necrotizing and cavitary nature of teh spinal cord lesion affecting both white and gray matter, centrally located
- involves several contiguous longitudinal segments of spinal cord
- involves less than 3 contiguous vertebral segments of SC
- spinal lesions occupy only a portion of the transverse surface of SC
- clinical effects are likely to be permanent
- MS
- NMO
- NMO
- NMO
- MS
- MS
- NMO
antibody found in serum of patients with Dveic disease
NMO antibody
IgG antineural antibody directed against aquaporin-4 that binds complement
True or False
Devic disease involves humorla process in contrast to the cellular mechanism in MS.
True
p936
acute encephalitix, myelitic, encephalomyelitic process usually following a febrile illness up to 2 weeks, more commonly seen in children
originally, occurred within a few days of onset of the exanthem of measle, rubella, smallpox or chickenpox
Acute disseminated encephalomyelitis
True or False
In ADEM, teh encephalitic form is expressed more fully in children than in adults.
True
p938
as an acute illness is resolving there is an abrupt onset or over a day or two, of confusion, somnolence, convulsions, headache, fever, neck stiffness.
ataxia is common
True or False
The myelitic form of ADEM may simulate a spinal artery occlusion syndrome.
True
p939
CSF findings in ADEM
slight increase in lymphocytes and protein content
MRI in ADEM
bilateral confluent white matter lesions in both cerebral hemispheres early in the course
A postinfectious encephalomeylitis that involves predominantly the cerebellum presents as mild ataxia with variable CST signs
seen in patients with childhood exanthems such as:
EBV
CMV
Mycoplasma
Legionella
most fulminant form of demyelinating disease almost certainly the sever end of the spectrum of ADEM, affects mainly young adults and children
usually preceded by a respiratory infection of variable duration, sometimes caused by M. pneumoniae
headache, fever, stiff neck, confusion
followed by seizures, hemiplegia/quadriplegia, pseudobulbar paralysis, progressive deepening coma
Acute Necrotizing Hemorrhagic Encephalomyelitis
(Acute Hemorrhagic Leukoencephalitis of Weston Hurst)
imaging findings in Acute Necrotizing Hemorrhagic Encephalomyelitis
bilateral, asymmetrical, large, confluent edematous lesions in teh cerebral white matter with a myriad of punctate hemorrhages in gray and white matter
treatment
ADEM and Acute Necrotizing Hemorrhagic Encephalomyelitis
high dose steroids
