Trans 052: Demyelinating Diseases and Multiple Sclerosis

Question 1

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

Answer 1

Demyelinating Diseases

Question 2

Lesions that are primarily in white matter, either in multiple small, disseminated foci or in larger foci spreading from one or more centers

Answer 2

Demyelinating diseases

Question 3

What are demyelinating diseases in the CNS? (4)

Answer 3

• Multiple sclerosis
• Progressive multifocal leukoencephalopathy
• Acute disseminated encephalomyelitis
• Adrenoleukodystrophy

Question 4

What are the demyelinating diseases in the PNS? (2)

Answer 4

• Guillain Barre Syndrome (AIDP1)

- Chronic Inflammatory Demyelinating Polyneuropathy (CIDP2)

Question 5

When there are patients w/ demyelinating disorders especially the atypical ones, there is always a possibility of primary neoplastic disease. T or F

Answer 5

T

Question 6

these are associated w/ neoplastic diseases. (2)

Answer 6

ADEM & paraneoplastic encephalomyelitis: these are associated w/ neoplastic diseases.

Question 7

The most common and important inflammatory demyelinating disease is

Answer 7

MS

Question 8

What is the pathogenesis of MS?

Answer 8

• 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)

Question 9

Symptomatology of MS?

Answer 9

• Fatigue - Numbness - Weakness - Dizziness and vertigo - Spasticity - Gait disturbances - Blurring of vision - Pain - Cognitive decline - Incontinence - Depression - Mood disturbances

Question 10

Risk Factors for MS: Age?

Answer 10

MS can occur at any age, but most commonly affects people between the ages 15 and 60

Question 11

Risk Factors for MS: sex?

Answer 11

Women are about twice as likely as men are to develop MS

Question 12

Risk Factors for MS: Family History?

Answer 12

If one of your parents or siblings has had MS, you are higher risk of developing the disease

Question 13

Risk Factors for MS: Race

Answer 13

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

Question 14

Risk Factors for MS:Climate?

Answer 14

MS is far more common on countries w/ temperate climates, including Canada, the northern United States, New Zealand, southeastern Australia and Europe

Question 15

Risk Factors for MS:: certain autoimmune disease?

Answer 15

You have a slightly higher risk of developing MS if you have thyroid disease, type 1 diabetes, or inflammatory bowel disease

Question 16

Risk Factors for MS: Smoking?

Answer 16

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

Question 17

Risk Factors for MS: Certain infections?

Answer 17

A variety of viruses have been linked to MS, including Epstein – Barr, the virus that causes infectious mononucleosis

Question 18

in mcdonalds criteria, if there are

≥ 2 clinical attacks and objective clinical evidence of ≥ 2 lesions

what additional data are needed?

Answer 18

none. MS na yan

Question 19

According to mcdonalds, if there is

≥ 2 clinical attacks and objective evidence of 1 lesion

what additional criteria is needed?

Answer 19

DIS – an additional clinical attack implicating a different CNS site or by MRI

dissemination in space

Question 20

1 clinical attack and objective clinical evidence of ≥ 2 lesions

what additional data is needed?

Answer 20

DIT – an additional clinical attack or by MRI or demonstration of CSF – specific oligoclonal bands

dissemination in time

Question 21

If there is

1 clinical attack and objective clinical evidence of 1 lesion

what additional data needed?

Answer 21

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

Question 22

Describe an attack in MS?

Answer 22

• 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

Question 23

what is the usual time between attacks in MS?

Answer 23

• 30 days between onset of event 1 and onset of event 2

Question 24

Clearly defined relapses with worsening symptoms and disease activity on subsequent attacks. Symptoms may improve or disappear during remittance . what type of MS?

Answer 24

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.

Question 25

Steady decline after having RRMS

Answer 25

Secondary Progressive MS (SPMS)

Question 26

Steady decline and progression of the disease with no clear remittance

Answer 26

Primary Progressive MS (PPMS)

Question 27

o Steady decline with clear relapses or worsening of symptoms over time

Answer 27

• Progressive Remitting MS (PRMS)

Question 28

what does dissemination in time mean?

Answer 28

• 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

Question 29

What does positive CSf in MS mean?

Answer 29

Oligoclonal IgG bands in CSF (and not serum) or elevated IgG index

Question 30

what are the radiologic findings in MS? Distinct areas of involvement which helps differentiate from other diseases, what are the location usuallt?

Answer 30

``` o Typical areas of involvement  White matter fibers are involved ▪ Corpus callosum ▪ U fibers (juxtacortical lesions) ▪ Temporal lobe ▪ Brainstem ▪ Cerebellum ▪ Spinal cord ` ```

Question 31

What provides evidence for dissemination in space?

Answer 31

• ≥ 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

Question 32

Demyelinating plaques that are perpendicular to the corpus callosum, arranged at right angles along medullary veins

Answer 32

Dawson Fingers Request for an MRI, then the T2 sequence and DWI

Question 33

Represent involvement of the U fibers (short association fibers) Must touch the cortex

Answer 33

JUXTACORTICAL LESIONS

Question 34

association, projection vs commisural?

Answer 34

association - same hemisphere commisural - different hemishpere projection - brain to spinal cord

Question 35

- Demyelination appears as a mass lesion producing edema - Behaves similar to a tumor yung parang may rose sa MRI

Answer 35

TUMEFACTIVE MULTIPLE SCLEROSIS

Question 36

what are the CSF Findings in MS?

Answer 36

CSF protein maybe elevated with mild mononuclear pleocytosis • IgG fraction elevated (>11%) • IgG / albumin index is elevated • Presence of Oligoclonal Bands

Question 37

management of MS is divided in 2 components:

Answer 37

o Treatment during flare or acute attacks | o Immunomodulation for prevention of flare

Question 38

what are used in the acute exacerbation of MS?

Answer 38

• 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.

Question 39

what are immunomodulation management for MS?

Answer 39

interferon beta 1a Glatiramer Acetate Fingolimod Teriflunomide

Question 40

mimics myelin basic protein (MBP) and competes with myelin antigens when presented to T cells, induces T helper suppressor cells

Answer 40

Glatiramer

Question 41

modulates sphingosine-1-phosphate receptors altering lymphocyte migration

Answer 41

Fingolimod

Question 42

inhibits pyrimidine biosynthesis and disrupts interaction of T cells with antigen presenting cells

Answer 42

Teriflunomide

Question 43

WRONG FC

Answer 43

immunomodulation

Question 44

waht are the sources of stem cells in MS?

Answer 44

o Embryonic stem cells o Fetal stem cells o Umbilical cord stem cells o Adult stem cells

Question 45

sources of adult stem cells?

Answer 45

Bone Marrow ( hematopoietic stem cells and Mesenchymal stem cells) peripheral blood

Question 46

is an inflammatory CNS syndrome distinct from multiple sclerosis (MS) that is associated with serum aquaporin-4 immunoglobulin G antibodies (AQP4-IgG)

Answer 46

Neuromyelitis optica

Question 47

neuromyelitis optica aka?

Answer 47

Devic's Disease

Question 48

principal feature of neuromyelitis optica?

Answer 48

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)

Question 49

Core characteristics required for patients with NMOSD with AQP4-IgG:

Answer 49

Clinical syndromes of MRI findings related to optic nerve, spinal cord, area postrema, other brainstem, diencephalic, or cerebral presentations

Question 50

Criteria in the diagnosis of NMO : Core clinical symptoms?

Answer 50

* 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

Question 51

NMOSD with AQP4 - IgG Positive

Answer 51

* At least 1 core clinical symptom * Positive AQP4-Ab-IgG test * Exclusion of any other diagnosis

Question 52

NMOSD with AQP4-IgG Negative or Unmarked

Answer 52

• 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

Question 53

first line drug in NMO?

Answer 53

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.

Question 54

For the preventive treatment, it’s usually the immunosuppressive drugs. Lately, what is being used is

Answer 54

Rituximab

Question 55

__________is a chimeric monoclonal antibody anti-CD20, but this is very expensive so in the Philippines, so we just use ____________

Answer 55

Rituximab azathiopryne

Question 56

is an immune-mediated demyelinating CNS disorder, characterized clinically by new-onset polyfocal neurologic symptoms including encephalopathy, coupled with neuroimaging evidence of multifocal demyelination.

Answer 56

Acute disseminated encephalomyelitis

Question 57

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.

Answer 57

Acute disseminated encephalomyelitis

Question 58

Criteria for diagnosis in in ADEM

Answer 58

1. A first polyfocal clinical CNS event with presumed inflammatory demyelinating cause 2. Encephalopathy (alteration in consciousness or behavior unexplained by fever, systemic illness, or postictal symptoms) 3. Brain MRI abnormalities consistent with demyelination during the acute (3 months) phase 4. No new clinical or MRI findings 3 months or more after the clinical onset  The condition can be resolved and they do not recur.

Question 59

What is distinguishing in patients with ADEM, ________is a relatively common feature in ADEM which is not seen in patients with MS.

Answer 59

Seizure

Question 60

First line management of ADEM?

Answer 60

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.

Question 61

a rare disorder where the body’s immune system damages nerve causing lower motor neuron type of paralysis.

Answer 61

Guillain Barre Syndrome

Question 62

assolciated bacteria/virus in GBS?

Answer 62

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.

Question 63

Classic weakness in GBS?

Answer 63

The classic weakness if ascending and symmetrical in nature. galing baba symmetrical

Question 64

Signs and symptoms of GBS?

Answer 64

• 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.

Question 65

Laboratory Diagnosis in GBS: CSF Diagnosis

Answer 65

``` CSF STUDIES • Cyto-albumin dissociation (normal WBC count and elevated protein) • Normal WBC count • Normal sugar • Negative bacterial and viral culture ```

Question 66

ELECTRODIAGNOSTIC STUDIES in GBS

Answer 66

• 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

Question 67

We do right away_____________________ in our patients to determine if they have possibility of developing respiratory involvement such as in AMAN and AMSAN

Answer 67

EMG NCV (Electromyography and Nerve Conduction Velocity)

Question 68

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

Answer 68

Miller Fisher Syndrome

Question 69

TYPE OF GBS THAT autonomic dysfunction  Worse prognosis because they can have sudden cardiac arrest, hypotension, hypertension, and signs of increased ICP

Answer 69

Acute pandysautonomic neuropathy

Question 70

Type of GBS Most common variant (85% of cases); primarily motor inflammatory demyelination ± secondary axonal damage max of 4 wk of progression

Answer 70

AIDP: acute inflammatory demyelinating polyradiculoneuropathy;

Question 71

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

Answer 71

AMAN: acute motor axonal neuropathy

Question 72

Type of GBS that: Motor and sensory involvement with severe course of respiratory and bulbar involvement; primary axonal degeneration with poorer prognosis

Answer 72

AMSAN: acute motor-sensory axonal neuropathy

Question 73

management for GBS?

Answer 73

Management – Intravenous immunoglobulin