Briefly, hypotonia and weakness are not synonymous. All babies with weakness have hypotonia, but not all babies with hypotonia have weakness.
For a complete discussion of the causes of weakness in childhood, see Evaluation of a Child With Muscle Weakness.
Epidemiology
- Most common disorder of neuromuscular transmission
- Prevalence 5-15 / 100,000 in adults, 1.1 / 1 Million in childhood
- Related to HLA-DR3, -A1, -B8 and DQw2
Pathophysiology
Neuromuscular junction: 1. Axon 2. Muscle cell membrane 3. Synaptic vesicle 4. Nicotinic acetylcholine receptor 5. Mitochondrion https://en.wikipedia.org/wiki/Myasthenia_gravis
Autoimmune myasthenia gravis - Autoantibodies against acetylcholine receptor (AchR). Antibodies block synaptic transmission and fix complement.
- Transient neonatal myasthenia - Placental transfer of IgG from mother with myasthenia gravis. Neonate will have symptoms for several weeks. Treat with anticholinergics (see below).
Congenital myasthenic syndrome - Hereditary disorder of the neuromuscular junction. Positive family history, usually recessive. Treatment is patient-specific based on genetic testing.
Pathology
Biopsy is rarely done, however should show same results as adult MG – early deposition of antibody and complement on motor endplate and subsequent loss of motor endplate folds.
Clinical Features
Perinatal
Reduced fetal movements
Polyhydramnios
Arthrogryposis (congenital contractures)
Infancy
Hypotonia
Muscle weakness
Weak cry
Feeding difficulties
Recurrent choking or apneic episodes
Childhood
Muscle fatiguability
Respiratory failure
Ophthalmoplegia*
Diplopia*
Ptosis*
Strabismus
Dysarthria
Dysphonia
Dysphagia
*Ocular findings are often the first symptoms, and are the sole symptom in 15%
This table adapted from Parr and Jayawant 2007, Table I
Evaluation
Objective measures of fatigueability
Gross motor, e.g. squats, walking, stairs
Time to swallow a given amount of liquid
PFTs
Bedside testing (80-90% sensitive):
Tensilon (edrophonium test): Inject increasing doses of edrophonium, a short-acting cholinesterase inhibitor. Observe the eyelids after each dose. In patients with ptosis as a symptom of their MG, the lids will lift as Ach concentrations increase.
Ice pack test: Place an icepack on patient's eyelids for 2 minutes, then observe the effect on ptosis. Used when there are contraindications to cholinergics, e.g. cardiac disease, bronchial asthma.
Other muscles can be examined but are dependent on consistent effort
Serologic testing for autoantibodies
Acetylcholine receptor (AchR-Ab): binding antibodies are present in 80-90% with generalized disease, 40-50% with ocular only. False positive rate <5%.
Muscle specific tyrosine kinase (MuSK-Ab): present in 38-50% of those negative for AchR-Ab.
8-12% of patients are 'seronegative' and have a better prognosis.
Electromyogram (EMG)
Single fiber electromyography (SFEMG) is preferred, but repetitive nerve stimulation (RNS) is most widely available.
Diagnosis
There are no formal diagnostic criteria. AchR-Ab or altered EMG are considered confirmatory with appropriate symptoms.
Differential diagnosis:
Generalized fatigue – Rule out anemia; do symptoms worsen over the day?
Motor neuron disease – Ptosis and diplopia are not symptoms of ALS, MG is not progressive, does not show upper or lower motor neuron signs
Brainstem tumors – MRI is useful if bulbar symptoms are present
Compressive cranial neuropathies – MRI can help distinguish
Lambert-Eaton myasthenic syndrome - LEMS improves with recurrent use. EMG will differentiate.
Recent general anesthesia – Rule out by history
Polymyositis
Botulism – History, rapid progression. EMG shows improvement with RNS.
Intrinsic muscle defect (e.g. Kearns-Sayre syndrome) - non-responsive to treatment, progressive, ragged red fibers on muscle biopsy
Management
- Cholinesterase inhibitors (pydridostigmine) increase ACh concentration at NMJ
- Immunosuppressants (corticosteroids etc.) - suppress antibody production
- Plasmapheresis and IVIG - rapidly decrease antibodies in a crisis. No evidence from RCTs.
- Thymectomy for those with thymoma (15%) - generally avoided as T-cells are still developing in pediatric patients.
- Best done within 12 months after diagnosis. 60% rate of remission (vs 30% if untreated). Better results if plasmapheresis before thymectomy.
- Ventilation and other supportive care until symptoms resolve
Prognosis
30% chance of remission, higher than in adults.
References
1.Patterson M.C. and Gomez M.R. Muscle Disease in Children a Practical Approach. Peds in Review 1990
2.Parr J.R. and Jayawant S. Childhood myasthenia: clinical subtypes and practical management. Developmental Medicine & Child Neurology 2007
3. Gadient P. Bolton J. and Puri V. Juvenile Myasthenia Gravis: Three Case Reports and a Literature Review. J Child Neurol 2009
4. Cortese I. Chaudhry V. So Y.T. Cantor F. Cornblath D.R. and Rae-Grant A. Evidence-based guideline update: Plasmapheresis in neurologic disorders. Neurology 2011