Management of SMA type 1 History Examination Investigation Treatment Prognosis

History & Examination Prenatal Hx – decreased fetal movement Neonatal Hx – asphyxia, kernicterus, IVH etc Hx of suspected aetiology Muscle bulk Tone Strength Distribution of weakness and muscle wasting Proximal - Myopathy Distal - Neuropathy Myotonia is specific for a few myopathies

Tendon stretch reflexes Lost - in neuropathies and in motor neuron diseases Diminished but preserved - in myopathy Fasciculations of muscle – tongue Present Absent Sensory abnormalities - neuropathy Involvement of the face, tongue, palate, and extra ocular muscles

Muscle pain or myalgias Present - A cute disease of either myopathic or neurogenic origin. Acute dermatomyositis Acute polyneuropathy (Guillain-Barré syndrome) etc Several metabolic diseases of muscle and in ischemic myopathy Absent Muscular dystrophies and spinal muscular atrophies Contractures of muscles – at birth or developing later Myopathic and neurogenic diseases.

Descent of testes Undescended - Gubernaculum is weakened Spinal muscular atrophy Myotonic muscular dystrophy Many congenital myopathies. Shape of thorax funnel shape – IUGR Infantile spinal muscular atrophy Myotubular myopathy Neonatal myotonic dystrophy etc

Spinal Muscular Atrophies Degenerative diseases of motor neurons 2nd most common neuromuscular disease Most cases are inherited as an autosomal recessive trait. Incidence of SMA is 10–15 per 100,000 live births No racial predilection Genetic locus for all 3 of the common forms of SMA is on chromosome 5

Onset In fetal life Continue to be progressive in infancy and childhood Upper motor neurons remain normal. Classification based on clinical manifestations Age at onset Severity of weakness Clinical course

SMA type 1 - Werdnig-Hoffmann Dx Severe infantile form 25% of cases SMA type 2 - Dubowitz disease Late infantile and more slowly progressive form 50% of cases SMA type 3 - Kugelberg-Welander disease More chronic or juvenile form 25% of cases.

SMA type O Severe fetal form that is usually lethal in the perinatal period Rare and accounts for <1%. A variant of SMA - Fazio-Londe disease Motor neuron degeneration more in the brainstem than the spinal cord. Progressive bulbar palsy Some patients are transitional between types 1 and 2 or between types 2 and 3 in terms of clinical function

SMA type 1 – Werdnig-Hoffmann disease Johann Hoffmann and Guido Werdnig Johann HoffmannGuido Werdnig A genetic disorder Inheritance is autosomal recessive Results from destruction & degeneration of motor neurones in the spinal cord and the brain stem in utero following prolongation of the normal process of programmed cell death It is the most severe form of SMA Starts at birth or within 6 mo of age Incidence is 0.4 per 1000 births.

Clinical Features Reduced foetal movements in utero Infant is severely hypotonic at birth with a frog-like posture Triad of symptoms Severe hypotonia Absent reflexes Fasciculation - tongue & fingers Severe weakness in a proximal > distal distribution is seen Thin muscle mass

Absent tendon stretch reflexes Involvement of the tongue, face, and jaw muscles Tongue fasciculation – diagnostic Respiratory muscles are weak, and intercostal muscles are usually affected more than diaphragm, leading to paradoxical abdominal movement and pectus excavatum Difficulty with swallowing & accumulation of secretions in the mouth because of weak masticatory and pharyngeal muscles Inability to feed Aspiration pneumonitis

Congenital contractures Simple clubfoot Generalized arthrogryposis 10% of severely involved neonates Unable to overcome gravity Neck control grossly delayed Weak cry Unusual delay in achieving developmental milestones Infants usually not strong enough to sit or sit late

No sphincteric or sensory impairment Extra-ocular muscles are unaffected Facial muscles are not weak The alert state is not affected Mental development is normal Normal IQ Children often appear brighter than their normal peers Myalgias are not a feature of SMA. The heart is not involved in SMA. About 70% die either in early infancy or before the age of 2 yrs

Investigation Molecular Genetic Studies Genetic marker in blood for the SMN gene Simplest, Highly sensitive and specific By DNA probes in blood samples or in muscle biopsy or chorionic villi tissues Serum CK level Isoenzymes MM for skeletal muscle MB for cardiac muscle BB for brain Normal Mild elevation

Nerve conduction velocity (NCV) 80% of the total nerve fibers must be involved before slowing in conduction is detected. Motor Normal - usually Mild slowing in terminal stages of the disease Sensory may be slowed Electromyography (EMG) Shows fasciculations and fibrillations Muscle Biopsy Classic finding is grouped atrophy

Treatment No medical treatment delays the progression Supportive therapy Orthopedic care - scoliosis and joint contractures Mild physiotherapy Spine fusion Respiratory care Non-invasive ventilation Tracheostomy Nutritional care Tube feeding

Mechanical aids for assisting the child to eat and to be as functionally independent as possible Respiratory depression is the most serious complication and the most common cause of mortality. Aggressive and early respiratory toilet and treatment is required. Most Type 1 patients will have severe respiratory compromise and may eventually mechanical ventilation

Prognosis Poor Many Type 1 and Type 2 patients do not survive childhood without mechanical ventilation Do not survive beyond 3yrs 7months to 7yrs for milder forms

Pull to Sit

Scalf sign

Shoulder suspension

Ventral suspension

Conclusion

References Asindi AA. Muscular dystrophies and the floppy infant. In: Azubuike JC, Nkanginieme KEO, ed(s). Paediatrics and child health in the tropics. Owerri: African Educational services; p Sarnat HB. Neuromuscular Disorders. In: Kleigman RM, Behrman RE, Jenson HB, Stanton BF, ed(s). Nelson textbook of Pediatrics. Philadelphia: WB Saunder Company; p. Bodensteiner JB. The evaluation of hypotonic infant. Semin Paediatr Neurol 2008; 15:10-20