Diag/Treat

Genetic testing: best initial and confirmatory test

Further tests

• Muscle biopsy: atrophy of groups of motor units interspersed with normal or hypertrophied motor units

• EMG: spontaneous, large-amplitude, low-frequency electrical activity (rarified interference pattern)

• Laboratory tests: normal or mildly elevated creatine kinase

Congenital myasthenic syndromes: muscle weakness induced by fatigue, ptosis, extraocular muscle palsy

Congenital myopathies: more prominent hypotonia and weakness in proximal muscles

Certain viral infections (polio, coxsackievirus, echovirus, West Nile virus): much more acute onset of flaccid paralysis, ascending paralysis (i.e., starts distally)

Hypotonic cerebral palsy : non-progressive weakness

Muscular dystrophies : ↑↑ creatine kinase, characteristic findings on muscle biopsy

Rare juvenile form of amyotrophic lateral sclerosis: predominantly bulbar weakness with minimal involvement of anterior horn cells

Motor neuron degeneration: associated with severe arthrogryposis

Progressive muscular atrophy: a nonhereditary, adult-onset, progressive lower motor neuron disorder

Nusinersen

• An antisense nucleotide that alters differential splicing of the transcript of the SMN2 gene, so it produces a functional SMN1 protein

• Requires annual intrathecal injections

Onasemnogene abeparvovec

• An agent based on an adeno-associated virus 9-based vector that carries a normal copy of SMN1 to the lower motor neurons of the spinal cord

• Should be administered intravenously once in a lifetime

Risdiplam

• mRNA splicing modulator that improves the efficiency of SMN2 gene transcription → ↑ systemic SMN protein concentration

• Can be given orally, in contrast to nusinersen

Respiratory support

Nutritional support

Physical rehabilitation

Orthotics to prevent joint and spine deformities