Why pediatric MS important

• Treating kids is always important

• Many missed opportunities because diagnosis is delayed, yet early treatment is critical

• Studying pediatric MS may increase our understanding of the pathogenesis of the disease and help all patients with MS

Unique Challenges

•          The diagnosis of pediatric MS is increasingly being considered

 - Wide spread availability of MRI

 - Need for early diagnosis & treatment

•          Demyelination in the presence of ongoing myelination within the brain raises unique issues

•          Rapid diagnosis and treatment is limited by lack of clinical experience

Epidemiology

•          2.5 million people affected world-wide

•          3.5-5%  symptoms before 18 years

–        (100,000-200,000 world-wide)

•          0.2-0.7% onset before 10 years of age

•          MS as young as 2 years is reported but uncommon

Gender Distribution

Age	Female: Male	Ref
< 10 years	0.6: 1	Simone 2002
10 – 14 years	2.6:1	Simone 2002
13 years	3.5:1	Boiko 2002
14 years	7.5:1	Boiko 2002

 Definitions

•          Acute Disseminated Encephalomyelitis  (ADEM)

•          Clinical Isolated Syndrome (CIS)

•          Neuromyelitis Optica (Devic Syndrome)

•          Pediatric Multiple Sclerosis  (Pediatric MS)

ADEM

•          Acute Demyelinating CNS Disorder

•          Usually a one time event

•          Typically Affects Children

•          Monophasic Course

•          Focal or Multi-focal Neurologic S&S 

•           Multi-focal Demyelinating Lesions (MRI),  grey and white matter

•          Behavioral/ or Mental Status Changes

•          Seizure

•          Prodromal Illness (≥70 %)

•          Fever, Headache, Nausea/Vomiting/ ¯ Appetite, Lethargy

 

ADEM   Clinical Characteristics

Signs & Symptoms evolve over time

                                  Maximal deficits reached ~ 1-2 weeks

                                  Resolution

                                                 rapid / or weeks to months

                                                 may / may not be complete

                                   Repeat MRI ® resolution / no new lesions

ADEM:  Laboratory Findings

CSF                         mild pleocytosis(↑wbc)

                                                + ↑ protein       

                                                + OCB (Oligoclonal Bands) / IgG production

(uncommon -    transient)

MRI                        white matter and grey matter lesions

                                                  (bilateral, asymmetric)

                                                Usually spare periventricular areas

                                                + Basal ganglia involved

                                                lesions highly variable size and number

                                                punctate - large & confluent - tumor-like

                                                Usually resolve

ADEM

                      

At onset                                                                     8 wk f/u

FLAIR MRI

 

ADEM Differential Diagnosis

• Encephalitis / Infection

• Vasculitis

• Leukodystrophy

• Mitochondrial Cytopathies

• Sarcoidosis

• Histiocytic lymphangiomatosis

• Tumors / glioblastoma

• Multiple Sclerosis

 

INFECTIOUS ILLNESSES

• Measles -20-30% deaths

• Influenza A or B

• Hepatitis A or B,

• Coxsackie virus

• Vaccinia

• winter/spring respiratory viruses

• Herpes virus infections 

• (HSV,VZV, HHV6, CMV,  EBV)                                    

 

IMMUNIZATIONS / VACCINATIONS

                                Rabies  

                                Diptheria -Tetnus-Pertussis

                                Hepatitis B

                                Smallpox

                                                Vaccines now devoid of neural elements

                                                Successful immunization programs, virtual eradication of                                                                                              small pox disease

ADEM Evaluation

–        CSF –        Lactate-Pyruvate –        Cytology –        IgG Index; OCB –        R/O CNS infection CSF profile, CSF viral & bacterial cultures  PCR- especially for Herpes Simplex Virus  Lyme titer Measles Ab

Blood    CBC/diff, Electrolytes, LFTs, ESR T4/TSH, B12, Biotinase ANA, Anticardiolipin Ab, Antiphospholipid Ab, ACE Lupus Anticoagulant VDRL/RPR CADASIL, LHON mutation Mitochondrial gene mutation Lactate-Pyruvate

 

ADEM treatment

• Corticosteroids

  • Anti-inflammatory and Immunosupressive

  • Anecdotal Reports

• Supportive Care

• Symptomatic Treatment

• Therapy targeted to immune-mediated process

• Currently, no treatment trials or proven protocols for ADEM

 

ADEM- the dilemma

• ADEM considered an acute monophasic illness

• Most clinicians acknowledge ADEM may recur

                           myriad of terms found in the literature

                                        biphasic

                                        multiphasic

                                        relapsing

                                        recurrent

                                        steroid dependent

• Clinicians also acknowledge –

  • some children with ADEM  may go on to develop MS

 

Neuromyelitis Optica  (Devic’s)

• Absolute criteria

  • Hx of ON or recurrent ON

  • Hx spinal cord symptoms

  • Spinal cord lesion(s) extending 3 or more segments

  • Normal brain MRI

  • CSF shows pleocytosis (>50 leukocytes)

  • May show NMO antibodies

 

Disease Courses in MS: Types of MS