Pediatric Neuromuscular Diseases

Question 1

Duchenne Muscular Dystrophy

Answer 1

• X-linked, recessive, myogenic disorder characterized by:
• Progressive muscle wasting and
• Weakness
• Pseudohypertrophy
• Absence of dystrophin

Question 2

What is Dystrophin?

Answer 2

• Protein inside surface of the sarcolema
• Links actin and other support proteins
• Supports muscle fiber strength
• Reduces stiffness
• Increases sarcolemmal deformability
• Prevents muscle fiber injury

Question 3

Signs and Symptoms of Duchenne Muscular Dystrophy

Answer 3

• Variable phenotypic presentation
• Progressive weakness (pseudohypertrophy)
• Cardiomyopathy
• Respiratory insufficiency
• Gower’s Sign/Maneuver
• Loss of independent ambulation

Question 4

Pseudohypertrophy

Answer 4

As muscle breaks down it is replaced by adipose and fibrotic tissue

Question 5

Cardiomyopathy

Answer 5

• Cell membrane degradation
• Interstitial inflammation
• Edema
• Fatty replacement
• Fibrosis

Question 6

Respiratory Insufficiency

Answer 6

•Absolute forced vital capacity (FVC) values peaked around the age of 13–14 years of age: ~ 1 L

Question 7

Diagnosing Duchenne Muscular Dystrophy

Answer 7

• Combination of testing and clinical presentation
• Creatine Kinase
• Muscle Biopsy –Staining to ID presence of dystrophin
• Dystrophindeletion/duplication (genetic)

Question 8

DMD Stage 1: Presymptomatic

Answer 8

• Can be diagnosed at this stage if creatine kinase found to be raised or if positive family history
• Might show developmental delay but no gait disturbances

Question 9

DMD Stage 2: Early Ambulatory

Answer 9

• Gowers’ Sign
• Waddling Gait
• Might be toe walking
• Can climb stairs

Question 10

DMD Stage 3: Late Ambulatory

Answer 10

• Increasingly labored gait

- Losing ability to climb stairs and rise from floor

Question 11

DMD Stage 4: Early Non-Ambulatory

Answer 11

• 11, 12, maybe 13 yo
• Might be able to self propel for some time
• Able to maintain posture
• Might develop scoliosis

Question 12

DMD Stage 5: Late Non-Ambulatory

Answer 12

Upper limb function and postural maintenance is increasingly limited

Question 13

Management of Individuals with DMD

Answer 13

Multidisciplinary

Assessments: systematic, objective, routine

Question 14

Goals of Rehab- Stage 1 and 2

Answer 14

• Education and support
• Preventative measures to maintain muscle
• Contracture prevention
• Appropriate exercise/activity
• Support for function and participation
• Provision of assistive devices

Question 15

Goals of Rehab- Stages 3, 4, 5

Answer 15

• Provision of assistive technology to maximize function, activity, and independence
• Positioning
• Mobility

Question 16

Medical Management of DMD

Answer 16

• Glucocorticoids
• Orthopaedic Surgery
• Experimental Interventions

Question 17

Glucocorticoids for management of DMD

Answer 17

•Slow Decline in Strength
•Prolonged Ambulation
•Decreased Risk of Scoliosis
•Stabilized Pulmonary 
Function

Question 18

Side Effects of Glucocorticoids

Answer 18

•Cushingoid
•Growth Retardation
•Delayed Puberty
•Behavioral Changes
•Immune/Adrenal 
Suppression
•Hypertension
•Glucose Intolerance
•GERD
•Hirsutism

Question 19

Hallmark of scoliosis

Answer 19

restrictive airway disease –> mechanical defect due to scoliosis

Question 20

Gene Therapies for DMD

Answer 20

• Nonsense Suppression
• Exon Skipping
• Gene Transfer

Question 21

Other Myelopathies

Answer 21

• Becker MD
• Limb-Girdle MD
• Fascioscapulohumeral MD
• Spinal Muscular Atrophy:
• SMI 1
• SMA2
• SMA3

Question 22

Spinal Muscular Atrophies

Answer 22

• Primarily autosomal recessive; Characterized by lower motor neuron
disorder:
• Progressive muscle weakness
• Atrophy
• Hypotonia/areflexia
• Loss of anterior horn cells in the spinal cord

Question 23

Survival Motor Neurons

Answer 23

• Gene creates SMN protein essential to maintain the integrity of motor neurons
• Deletions or mutations in both copies of SMN1
• An exonicsplicing suppressor (ESS) at position 6 of SMN2 leads to skipping of exon 7
• Results in a trunkated, non-functional SMN protein

Question 24

Effect of SMN2 on Severity

Answer 24

• Most patients with Type I SMA had 1 or 2 copies of SMN2
• Most patients with Type II SMA had 3 copies of SMN2
• Most patients with Type III SMA had 3 or 4 copies of SMN2

Question 25

SMA I Chart

Answer 25

Onset: 0-6 mo Death: < 2 years Motor Limits: No sitting

Question 26

SMA II Chart

Answer 26

Onset: 7-18 mo Death: >2 years Motor Limits: Usually does not stand

Question 27

SMA III Chart

Answer 27

Onset: > 18 mo Death: Adult Motor Limits: Stands and Walks

Question 28

SMA I- Infantile Werdnig-Hoffmann

Answer 28

``` •60% of children with SMA Features: • Severe weakness at birth • Profound hypotonia • Frog legged posture • Hyporeflexia/Areflexia • Joint contractures • Suck-swallow difficulties • Poor head control • Respiratory Failure • Belly breathing • Tongue fasciculations ```

Question 29

Type II- Intermediate - Dubowitz

Answer 29

``` •27% of children with SMA Features: • Progressive proximal weakness/hypotonia • LE’s > UE’s • Postural hand tremor • Hyporeflexia • Average/Above average intellect • Joint contractures • Scoliosis and restrictive airway disease ```

Question 30

Type III - Kugelberg-Welander

Answer 30

``` •12% of children with SMA Features: •May have hand tremor •Mild progressive weakness •LE’s > UE’s •Resembles Becker Muscular Dystrophy ```

Question 31

Diagnosis of SMA

Answer 31

``` •Carrier testing •Genetic testing •Polymerase chain reaction (PCR) •Multiplex ligation probe amplification (MPLA) •Chromosome microarray (CMA) •Serum creatine kinase •Nerve conduction velocity ```

Question 32

Medical Management of SMA

Answer 32

* Physical Medicine and Rehabilitation * Neurology * Orthopaedics * Physical Therapy * Occupational Therapy * Pulmonology * Nutrition * Gasteroenterology

Question 33

Restrictive Lung Disease

Answer 33

``` •Intercostal weakness/spinal deformity •Progressive because of recurrent microatelectasis causing failure of lung development •Recurrent aspiration and infection •Sleep hypoventilation ```

Question 34

Restrictive Lung Disease Management

Answer 34

* Assisted ventilation – bilevel positive airway pressure (BiPAP) * Secretion management * Antibiotics/infection management

Question 35

Gastrointestinal/Nutrition Deficits of SMA

Answer 35

``` •Weakness can result in failure to thrive and aspiration pneumonia •Dysphagia and fatigue •Constipation •Adiposity/overweight •Percutaneous gastrostomy •Nissen fundoplication •Nutritionist/dietician consultation ```

Question 36

Orthopedic Changes of SMA

Answer 36

* Spinal deformity * Pectus excavatum * Joint contractures * Fractures * Hip subluxation