1. April 18, 2012
Case Conference

2. Patient…
16 year old Male presenting with right sided weakness

3. History of Present Illness
7 days prior to admission
Gradual onset of right sided weakness (clumsy, could not write well)
Complains of poor sensation over the right face.
Brought to an emergency room; Dx: Nerve impingement  Reassurance
No relief of symptoms
Was transferred to another correctional facility
Symptoms got worse
Can’t walk straight
Loss some feeling over the right leg.
Day of admission

4. History PAST MEDICAL HISTORY Previously healthy; no previous episodes
No known allergies to food/medications
FAMILY HISTORY
No known family history of any cardiac, respiratory, rheumatologic or neurologic conditions
PERSONAL-SOCIAL HISTORY
Allen McQueen correctional facility for boys since 9 months ago. Receives all medical care/shots. Now in middle school with no issues and learning disabilities. Denies smoking/alcohol. 1 x illicit drug use. Sexual debut at 15 years old, had only 2 lifetime partners with inconsistent use of protection. Previously tested for STI - negative

5. Physical Examination System Findings Vital signs General Appearance
Awake, alert, very cooperative, not in acute distress
HEENT
NCAT, Pinkish palpebral conjunctiva, anicteric sclerae, moist mucous membranes, nasal septum midline, normal TM’s, no palpable CLAD
Cardiovascular
NSRRR, Normal S1 and S2, no murmurs, no rubs, no gallops
Respiratory
CTA b/l, GAEB, no crackles, no wheezes
Abdomen
Flat abdomen, non-distended, soft, normoactive bowel sounds,
Extremities
No edema, no cyanosis, cap refill <2 s

6. Neurologic Examination
System
Findings
Mental Status
Cooperative patient and oriented to person, time and place; appropriate affect
Cranial Nerves
CN 2-12 intact
Motor/DTR
See diagram 
Sensory
Decreased cold sensation over the right cheek
Cerebellar
No ataxia, dysmetria nor nystagmus
Gait
(+) Antalgic gait on the right
Meningeal
No meningeal signs 2+
4/5 2+
5/5 3+
4/5 2+
5/5

7. Differential Diagnosis
Neurologic
Ischemic vs Hemorrhagic Stroke
Peripheral nerve disease
Demyelinating Disease

8. And so the story goes… Concerned about ischemic stroke
Labs were ordered
IVF started
MRI obtained

9. Laboratory Tests CBC Chemistries Parameter Results WBC count 5.3
Hemoglobin
15.9
Hematocrit
45.1
Platelets
201 N 56 L 32
Parameter
Results
Na+
133 K+
4.4
Cl-
100
CO2 29
BUN 14
Crea
1.0
Glucose 97
Calcium
9.5

10. Laboratory Tests CHEMISTRIES OTHER TESTS Parameter Results ALT 28 AST24
Bilirubin
1.0
Albumin
4.1
Total Protein
6.5
Magnesium 21
Phosphorus
4.9
Parameter
Results
Vitamin B12
557
RPR
Non-reactive
Hepa C Ag
Hepa C Ab
HIV
Negative
ANA
ESR 10

11. Cerebrospinal Fluid Studies
CSF Cell count – normal
CSF Proteins – 23
CSF Glucose – 79
CSF Oligoclonal bands - Negative

12. MRI (1/25/2012)

13. MRI (1/25/2012)

14. MRI (1/25/2012)

15. The Child with A Demyelinating Disease
Vincent Patrick Uy, MD
PGY-1
The Child with A Demyelinating Disease

16. Introduction
No single diagnostic test is specific to particular diagnosis
Must rely on History and PE, clinical features and imaging to arrive at a plausible diagnosis
Uncommon in the pediatric age group
Think of RARE disorders!

17. The Working Diagnosis Acute Disseminated Encephalomyelitis
Multiple Sclerosis
Optic Neuropathy
Transverse Myelitis
Neuromyelitis Optica

18. Pathophysiology

19. Leukodystrophies Adrenoleukodystrophies
Cytoskeletal disorders (Alexander’s disease)
Myelin Basic Protein disorder
Organic acid diseases (Canavan disease)
Disorders of energy metabolism (MELAS)
Krabbe disease
Rare disorders that are typically confused with more common disorders. Symmetric white matter disease is a hallmark of there cases. Imaging will produce a more diffuse picture.

20. Malignancies CNS lymphomas High-grade glioma
Large area of tumefactive demyelination
CSF studies show atypical cells

21. Collagen Vascular Diseases
Systemic Lupus Erythomatosus
Behcet’s disease
Neurosarcoidosis
Look for other symptoms
Anti-dsDNA, anti-phospholipids, elevated ACE enzymes

22. Optic Neuritis
May be a clinically isolated syndrome or part of another condition
Monocular in most adults; bilateral in most children years old.
Symptoms can progress from several hours to days
Risk factor for developing frank Multiple Sclerosis
Correlates more if there are lesions developing outside the optic nerve

23. Optic Neuritis Headache Painful eye movements
Partial or complete vision loss
Relative afferent pupillary defect
Papillitis (75% in the acute phase)

24. Optic Neuritis

25. Transverse Myelitis
Spinal cord disease without evidence of compression
Inflammation of the spinal cord
May present as a clinically isolated disorder or part of other conditions.
Most cases are idiopathic
Subset of patients develop TM after vaccination

26. Transverse Myelitis
Weakness, paresthesias, urinary and bladder problems
Hyperacute presentation
MRI shows contrast enhancing lesions on the cord
Swelling of the segments at T2 imaging.

27. Transverse Myelitis Idi0pathic Transverse Myelitis
Spontaneous but partial recovery in 1-3 months
40% will have a persistent disability

28. Neuromyelitis Optica Devic’s Disease Combination of:
Optic neuritis
Transverse Myelitis
Seropositivity to NMO IgG antibodies
>3 contiguous spinal levels involved
Presentation can be primarily progressive with a fulminant course on presentation
Any child with a severe and rapidly progressive clinical course should be investigated for NMO

29. Acute Disseminated Encephalomyelitis
Acute or subacute onset of multifocal neurologic deficits with encephalopathy
Often follows a viral infection or vaccination
Very uncommon illness
Autoimmune disorder of the CNS, triggered by environmental factors, in genetically susceptible individuals
Any vaccine can cause ADEM, but as in most identified cases, the MMR vaccine has been implicated most of the time.

30. Acute Disseminated Encephalomyelitis
CLASSIFICATION
DESCRIPTION
Classic
Monophasic; happens only once
Relapsing
Recurs more than 3 months after recovery - or -
More than 1 month from stopping steroids
Recurrent
Subtype of relapsing ADEM presenting with similar symptoms and MRI lesions
Multiphasic
Subtype of relapsing ADEM presenting with different symptoms and different MRI lesions
The condition is very self-limited in recurrences that generally have no neurologic sequelae after an episode.
Patients with ADEM, no matter what form, should have complete recovery to baseline.

31. Acute Disseminated Encephalomyelitis
Clinical Presentation
Febrile illness occurs in about 50-75% of children a month before neurologic symptoms appear.
Headache and meningeal signs
Encephalopathy (changes in mental status)
Acute hemiparesis, cerebellar ataxia, optic neuritis and spinal cord dysfunction are also common
ADEM typically lasts for about 2-4 weeks

32. Acute Disseminated Encephalomyelitis
The lesions are typically bilateral. As the name implies, the lesions are disseminated in nature and will involve multiple sites, often with no particular pattern. Symptoms noted from large lesions are often related to mass effect.

33. Acute Disseminated Encephalomyelitis

34. Acute Disseminated Encephalomyelitis

35. Acute Disseminated Encephalomyelitis
Treatment
Fever, meningisimus, headaches, change in mental state, etc. Treat for suspected meningitis/encephalitis
Imaging may be obtained
High dose IV Glucocorticoids treatment for 3-5 days + steroid taper for 4-6 weeks
Methylprednisolone (10-30 mg/kg/d)
Dexamethasone (1 mg/kg/d)
Appropriate IV antibiotics and acyclovir are usually considered – change in mental status in the setting of fever; maybe it’s a viral encephalitis?
There is no evidence to support that prolonging steroid taper after IV steroids will result in faster recovery
IVIG may also be used as rescue therapy in patients who do not respond to steroids
Plasma exchange is recommended in patients with very extensive transverse myelitis with failure to respond to conventional treatments

36. Pediatric Multiple Sclerosis
Chronic disease characterized by repeated episodes of demyelination separated by space and time
Pediatric multiple sclerosis  age of onset before 16 years old
2.5/100,000 children

37. Pediatric Multiple Sclerosis
Genetic Susceptibility
Higher risk in monozygotic twins
Certain HLA subtypes are associated with increased risk
Environmental factors
Epstein-Barr Virus infection
Vitamin D deficiency
Any viral or bacterial infection can increase the risk to develop MS. Among the most studied is EBV because of the molecular mimicry phenomenon.
Research has also been geared toward poor sun exposure resulting in deficiency of vitamin D. Viamin D is an immunoregulatory effect by enhancing T-cell activity, up-regulation of anti-inflammatory cytokines and downregulation of pro-inflammatory cytokines. This factor is suggested by the higher incidence of MS in children in Northern hemispheres and among communities where sun exposure is limited.

38. Pediatric Multiple Sclerosis
EBV nuclear antigen has similar structure to Myelin Basic Protein. The body will produce antibodies to EBV and these antibodies may gain access to the CNS.

39. Pediatric Multiple Sclerosis
SUBTYPES OF MULTIPLE SCLEROSIS
Description
RELAPSING REMITTING MS
Repeated episodes of MS with partial or complete recovery between episodes
97-99% of children
PRIMARY PROGRESSIVE MS
Continuous and worsening disease activity over time.
Very rare in both adults and children
CLINICAL ISOLATED SYNDROME
Does not fit the diagnostic criteria of MS.
Acute demyelination x 1 episode

40. Pediatric Multiple Sclerosis
Diagnostic Criteria for Diagnosis of MS
Dissemination in Space
Dissemination in Time
Another criteria called the POSER criteria may be useful in areas where MRI is unavailable. Because of the widespread use of MRI, the McDonald criteria has gained popularity.

41. Pediatric Multiple Sclerosis
Dissemination in Space
T2 lesions on MRI in at least two of the four MS-typical regions of the brain:
Periventricular
Juxtacortical
Infratentorial
Spinal Cord
Development of a further clinical attack implicating a different CNS site
The findings of a positive CSF oligoclonal bands was part of the criteria in the 2001 version. However, elevated CSF IgG depends on timing of CSF collection, age of the patient and the laboratory methods for assaying the protein. Thus, it was removed in the 2010 version of disseminatinon in space.

42. Pediatric Multiple Sclerosis
Dissemination in Time
Simultaneous presence of asymptomatic gadolinium-enhancing and non enhancing lesions at anytime or a new T2 lesion on a follow-up MRI (irrespective of timing)
Development of a second clinical attack

43. Pediatric Multiple Sclerosis
Clinically Isolated Syndrome
INCREASED RISK for MS
Age 10 years or older
Optic nerve lesions
MRI pattern very typical for MS
DECREASED RISK for MS
Spinal cord lesions
Acute Mental status change (ADEM)

44. Pediatric Multiple Sclerosis
Treatment strategy (Acute setting)
IV pulse methylprednisolone mg/kg/d x 5 days
Steroid taper 1 mg/kg/day for 4-6 weeks if without complete resolution
May re-treat with IV pulse methylprednisolone if symptoms recur during steroid taper

45. Pediatric Multiple Sclerosis
Treatment strategy (Chronic Therapy)
Glatiramer acetate
Interferons
For patients with recurrent attacks of MS, immunomodulatory agents may be considered. Treatment is based on family preference. However, randomized trials with these agents are lacking, and most studies were conducted in adults. This only shows the rarity of the condition. Alternate conditions should be considered in patients with progressive MS.

46. Pediatric Multiple Sclerosis
Monitoring patients after and ACUTE ATTACK
Completion of steroid taper
Neurologic exam at 1/3/6 months thereafter
For treatment failures, consider switching to immunomodulatory agents after stabilization. Treatment failure with immunomodulatory agents are beynd the scope of this lecture.
Clinically stable
Symptomatic
Send for MRI
Annual Physical Examination

47. Patient Update…
Received 5 day high dose methylprednisolone therapy via IV
Completed steroid taper with prednisone PO
On follow-up 4/3/2012  Complete resolution of symptoms with return to baseline
Dismissed as a case of Acute Demyelination – Clinically Isolated Syndrome

48. Let’s demyelinate YOUR neurons!
A 9 year old girl with anxiety disorder was diagnosed with acute demyelination because of sudden onset of left sided weakness and ataxia. Typical MS lesions which included the cerebellum and spinal cord were discovered after MRI. She comes to the clinic for the first time after completing 6 weeks of steroid taper. On further questioning, mom has missed several doses of her prednisone at home. So far, she never experienced symptoms again. Mom is concerned that the catastrophe might happen again. Which of the following conditions increases her risk to develop frank multiple sclerosis?
Non compliance to steroid taper
Her young age
Typical lesions were seen on MRI
Concomitant anxiety disorder
She doesn’t have risk factors that increase her risk to develop MS.

49. Now let’s give YOU ADEM!
A 17 year old boy was brought to the ER for change in mental status. Ultimately, he was diagnosed with ADEM. He recovered after 5 days in the ICU and is now back to baseline. Which of the following environmental triggers could have increased his risk for developing the condition.
Receiving an unrecalled vaccine from the PMD a month ago during annual visit
Getting daily morning sun exposure for minutes
Blurring of vision without eye pain
Experiencing an exudative sore throat which was negative on rapid strep test
Spider bite 2 weeks ago

50. Thank You!