Trans 052: Demyelinating Diseases and Multiple Sclerosis Flashcards
Destruction of the myelin sheaths of nerve fibers with relative sparing of the other elements of nervous tissue, that is, of axons, nerve cells, and supporting structures, which are less affected
Infiltration of inflammatory cells, particularly in a previous distribution
Demyelinating Diseases
Lesions that are primarily in white matter, either in multiple small, disseminated foci or in larger foci spreading from one or more centers
Demyelinating diseases
What are demyelinating diseases in the CNS? (4)
- Multiple sclerosis
- Progressive multifocal leukoencephalopathy
- Acute disseminated encephalomyelitis
- Adrenoleukodystrophy
What are the demyelinating diseases in the PNS? (2)
- Guillain Barre Syndrome (AIDP1)
- Chronic Inflammatory Demyelinating Polyneuropathy (CIDP2)
When there are patients w/ demyelinating disorders especially the atypical ones, there is always a possibility of primary neoplastic disease. T or F
T
these are associated w/ neoplastic diseases. (2)
ADEM & paraneoplastic encephalomyelitis: these are associated w/ neoplastic diseases.
The most common and important inflammatory demyelinating disease is
MS
What is the pathogenesis of MS?
- A T cell immune mediated attack directed towards myelin
- Damaged myelin produces scars or sclerosis
- Affected areas produce reduction in conduction of nerve impulses producing the symptoms
- Dissemination of the symptoms over space (refers to the different location thus different symptoms) and time (refers to different attack periods, maybe progressive or relapsing and remitting)
Symptomatology of MS?
- Fatigue - Numbness - Weakness - Dizziness and vertigo - Spasticity - Gait disturbances - Blurring of vision - Pain - Cognitive decline - Incontinence - Depression - Mood disturbances
Risk Factors for MS: Age?
MS can occur at any age, but most commonly affects people between the ages 15 and 60
Risk Factors for MS: sex?
Women are about twice as likely as men are to develop MS
Risk Factors for MS: Family History?
If one of your parents or siblings has had MS, you are higher risk of developing the disease
Risk Factors for MS: Race
White people, particularly those of Northern European descent, are at highest risk of developing MS. People of Asian, African, or Native American descent have the lowest risk
Risk Factors for MS:Climate?
MS is far more common on countries w/ temperate climates, including Canada, the northern United States, New Zealand, southeastern Australia and Europe
Risk Factors for MS:: certain autoimmune disease?
You have a slightly higher risk of developing MS if you have thyroid disease, type 1 diabetes, or inflammatory bowel disease
Risk Factors for MS: Smoking?
Smokers who experience an initial event of symptoms that may signal MS are more likely than nonsmokers to develop a second event that confirms relapsing
Risk Factors for MS: Certain infections?
A variety of viruses have been linked to MS, including Epstein – Barr, the virus that causes infectious mononucleosis
in mcdonalds criteria, if there are
≥ 2 clinical attacks and objective clinical evidence of ≥ 2 lesions
what additional data are needed?
none. MS na yan
According to mcdonalds, if there is
≥ 2 clinical attacks and objective evidence of 1 lesion
what additional criteria is needed?
DIS – an additional clinical attack implicating a different CNS site or by MRI
dissemination in space
1 clinical attack and objective clinical evidence of ≥ 2 lesions
what additional data is needed?
DIT – an additional clinical attack or by MRI or demonstration of CSF – specific oligoclonal bands
dissemination in time
If there is
1 clinical attack and objective clinical evidence of 1 lesion
what additional data needed?
DIS - an additional clinical attack implicating a different CNS site or by MRI
AND
DIT – an additional clinical attack or by MRI or demonstration of CSF – specific oligoclonal bands
Describe an attack in MS?
• Neurological disturbance of kind seen in MS • Subjective report or objective observation • At least 24 hours duration in absence of fever or infection • Excludes pseudo attacks, single paroxysmal symptoms (multiple episodes of paroxysmal symptoms occurring over 24 hours or more are acceptable as evidence) • Some historical events w/ symptoms and pattern typical for MS can provide reasonable evidence of previous demyelinating event(s), even in the absence of objective findings
what is the usual time between attacks in MS?
• 30 days between onset of event 1 and onset of event 2
Clearly defined relapses with worsening symptoms and disease activity on subsequent attacks. Symptoms may improve or disappear during remittance . what type of MS?
Relapsing - Remitting
Most of the patients. They would initially have symptoms then nawawala then babalik ulit. They are monitored and have targeted treatments to prevent this and its progression.
Steady decline after having RRMS
Secondary Progressive MS (SPMS)
Steady decline and progression of the disease with no clear remittance
Primary Progressive MS (PPMS)
o Steady decline with clear relapses or worsening of symptoms over time
• Progressive Remitting MS (PRMS)
what does dissemination in time mean?
• A new T2 and/or gadolinium- enhancing lesion(s) on follow – up MRI, with reference to a baseline scan, irrespective of the timing of the baseline MRI
OR
• Simultaneous presence of asymptomatic gadolinium – enhancing and non – enhancing lesions at any time
What does positive CSf in MS mean?
Oligoclonal IgG bands in CSF (and not serum) or elevated IgG index
what are the radiologic findings in MS? Distinct areas of involvement which helps differentiate from other diseases, what are the location usuallt?
o Typical areas of involvement White matter fibers are involved ▪ Corpus callosum ▪ U fibers (juxtacortical lesions) ▪ Temporal lobe ▪ Brainstem ▪ Cerebellum ▪ Spinal cord `
What provides evidence for dissemination in space?
• ≥ 1 T2 lesion in at least two out of four areas of CNS: periventricular, juxtacortical, infratentorial, or spinal cord
o Gadolinium enhancement of lesions is not required for DIS
o If a subject has a brainstem or spinal cord syndrome, the symptomatic lesions are excluded and do not contribute to lesion count
Demyelinating plaques that are perpendicular to the corpus callosum, arranged at right angles along medullary veins
Dawson Fingers
Request for an MRI, then the T2 sequence and DWI
Represent involvement of the U fibers (short association fibers)
Must touch the cortex
JUXTACORTICAL LESIONS
association, projection vs commisural?
association - same hemisphere
commisural - different hemishpere
projection - brain to spinal cord
- Demyelination appears as a mass lesion producing edema
- Behaves similar to a tumor
yung parang may rose sa MRI
TUMEFACTIVE MULTIPLE SCLEROSIS
what are the CSF Findings in MS?
CSF protein maybe elevated with mild mononuclear pleocytosis
• IgG fraction elevated (>11%)
• IgG / albumin index is elevated
• Presence of Oligoclonal Bands
management of MS is divided in 2 components:
o Treatment during flare or acute attacks
o Immunomodulation for prevention of flare
what are used in the acute exacerbation of MS?
• Steroids (methylprednisolone or its equivalent)
First step is the use of steroids
• ACTH (adrenocorticotrophic hormone)
• Plasmapheresis
In cases wherein steroid is unresponsive, plasmapheresis is done. But for a better outcome, there should be immediate diagnosis.
what are immunomodulation management for MS?
interferon beta 1a
Glatiramer Acetate
Fingolimod
Teriflunomide
mimics myelin basic protein (MBP) and competes with myelin antigens when presented to T cells, induces T helper suppressor cells
Glatiramer
modulates sphingosine-1-phosphate receptors altering lymphocyte migration
Fingolimod
inhibits pyrimidine biosynthesis and disrupts interaction of T cells with antigen presenting cells
Teriflunomide
WRONG FC
immunomodulation
waht are the sources of stem cells in MS?
o Embryonic stem cells
o Fetal stem cells
o Umbilical cord stem cells
o Adult stem cells
sources of adult stem cells?
Bone Marrow ( hematopoietic stem cells and Mesenchymal stem cells)
peripheral blood
is an inflammatory CNS syndrome distinct from multiple sclerosis (MS) that is associated with serum aquaporin-4 immunoglobulin G antibodies (AQP4-IgG)
Neuromyelitis optica
neuromyelitis optica aka?
Devic’s Disease
principal feature of neuromyelitis optica?
acute to subacute onset of blindness in one or both eyes, preceded or followed within days or weeks by a severe transverse or ascending myelitis
is an inflammatory CNS syndrome distinct from multiple sclerosis (MS) that is associated with serum aquaporin-4 immunoglobulin G antibodies (AQP4-IgG)
Core characteristics required for patients with NMOSD with AQP4-IgG:
Clinical syndromes of MRI findings related to optic nerve, spinal cord, area postrema, other brainstem, diencephalic, or cerebral presentations
Criteria in the diagnosis of NMO : Core clinical symptoms?
- Optic neuritis
- Acute myelitis
- Area postrema syndrome – unexplained hiccups, nausea or vomiting
- Acute brainstem syndrome (oculomotor disturbances, bulbar syndrome, respiratory failure)
- Symptomatic narcolepsy or acute diencephalic syndrome (apathy or agitation, hypersomnia, obesity, autonomic dysfunction) with NMOSD-typical changes in MRI
- Symptomatic cerebral syndrome (confusion, seizures) with NMOSD-typical brain lesions
NMOSD with AQP4 - IgG Positive
- At least 1 core clinical symptom
- Positive AQP4-Ab-IgG test
- Exclusion of any other diagnosis
NMOSD with AQP4-IgG Negative or Unmarked
• At least 2 core clinical symptoms present as a result 1 or more clinical attacks of the following:
o At least 1 core clinical symptom must be optic neuritis, acute myelitis with LETM or area postrema syndrome
o Disseination in space (2 or more core clinical symptoms)
o Fulfillment of additional MRI criteria
- AQP4-IgG negative or test unavailable
- Exclusion of any other diagnosis
first line drug in NMO?
steroids (methylprednisolone)
If they do not respond, then we do plasma exchange. However, in some cases, they proceed to IVIg (intravenous immunoglobulin) among the non-responders to methylprednisolone.
For the preventive treatment, it’s usually the immunosuppressive drugs. Lately, what is being used is
Rituximab
__________is a chimeric monoclonal antibody anti-CD20, but this is very expensive so in the Philippines, so we just use ____________
Rituximab
azathiopryne
is an immune-mediated demyelinating CNS disorder, characterized clinically by new-onset polyfocal neurologic symptoms including encephalopathy, coupled with neuroimaging evidence of multifocal demyelination.
Acute disseminated encephalomyelitis
is classically considered a monophasic illness, with highest incidence in early childhood. This is not relapsing.
continues to be among the most frequent demyelinating disorders in childhood.
Acute disseminated encephalomyelitis
Criteria for diagnosis in in ADEM
- A first polyfocal clinical CNS event with presumed inflammatory demyelinating cause
- Encephalopathy (alteration in consciousness or behavior unexplained by fever, systemic illness, or postictal symptoms)
- Brain MRI abnormalities consistent with demyelination during the acute (3 months) phase
- No new clinical or MRI findings 3 months or more after the clinical onset
The condition can be resolved and they do not recur.
What is distinguishing in patients with ADEM, ________is a relatively common feature in ADEM which is not seen in patients with MS.
Seizure
First line management of ADEM?
high dose corticosteroids
A typical treatment regimen consists of IV methylprednisolone at a dose of 30 mg/kg/d (maximally 1,000 mg/d) for 5 days, followed by an oral taper over 4-6 weeks with a starting dose of prednisone of 1-2 mg/kg/d.
o IV immunoglobulin treatment has been described in case reports and small case series, mostly in combination with corticosteroids or as a second-line treatment in steroid-unresponsive ADEM.
a rare disorder where the body’s immune system damages nerve causing lower motor neuron type of paralysis.
Guillain Barre Syndrome
assolciated bacteria/virus in GBS?
While its cause is not fully understood, the syndrome often follows infection with a virus or bacteria, Campylobacter jejuni, which causes gastroenteritis (including symptoms of nausea, vomiting and diarrhea). GBS are also reported after having the flu or other infections such as cytomegalovirus and Epstein-Barr virus.
Recently, GBS has been associated with the ZIKA virus infection.
Classic weakness in GBS?
The classic weakness if ascending and symmetrical in nature.
galing baba symmetrical
Signs and symptoms of GBS?
• Typical patient with GBS, presents 2-4 weeks following a relatively benign respiratory or gastrointestinal illness.
• The weakness may progress over hours to days to involve the arms, truncal muscles, cranial nerves, and muscles of respiration.
These patients are prone to be put under ventilators.
• Most patients complain of paresthesias, numbness, or similar sensory changes.
But when you do the neurological examination, there are no definite sensory findings because this is primarily motor neuron disease.
- Paresthesias generally being in the toes and fingertips, progressing upward but generally not extending beyond the wrists or ankles.
- The classic weakness if ascending and symmetrical in nature.
The LL (lower left extremities) are usually involved before the UL (upper left).
• Proximal muscles involved earlier than the more distal ones.
Laboratory Diagnosis in GBS: CSF Diagnosis
CSF STUDIES • Cyto-albumin dissociation (normal WBC count and elevated protein) • Normal WBC count • Normal sugar • Negative bacterial and viral culture
ELECTRODIAGNOSTIC STUDIES in GBS
• Motor and sensory nerve conduction studies
• Needle electromyography
• Findings:
o Segmental nerve demyelination
o Multifocal conduction blocks
o Slow conduction velocity
o Consistent with a peripheral neuropathy
We do right away_____________________ in our patients to determine if they have possibility of developing respiratory involvement such as in AMAN and AMSAN
EMG NCV (Electromyography and Nerve Conduction Velocity)
is a subgroup of GBS but now they are trying to separate it due to the involvement of mostly the trunk and the extremities
Involves the motor cranial nerves
Miller Fisher Syndrome
TYPE OF GBS THAT
autonomic dysfunction Worse prognosis because they can have sudden cardiac arrest, hypotension, hypertension, and signs of increased ICP
Acute pandysautonomic neuropathy
Type of GBS
Most common variant (85% of cases); primarily motor inflammatory demyelination ± secondary axonal damage max of 4 wk of progression
AIDP: acute inflammatory demyelinating polyradiculoneuropathy;
Type of GBS that:
Motor only with early and severe respiratory involvement; primary axonal degeneration; often affects children, young adults; up to 75% positive Campylobacter jejuni serology; often positive for anti-GM1, anti-GD1a antibodies
AMAN: acute motor axonal neuropathy
Type of GBS that:
Motor and sensory involvement with severe course of respiratory and bulbar involvement; primary axonal degeneration with poorer prognosis
AMSAN: acute motor-sensory axonal neuropathy
management for GBS?
Management – Intravenous immunoglobulin
