Developmental milestones in type I spinal muscular atrophy

Abstract

The aim of this retrospective multicentric study was to assess developmental milestones longitudinally in type I SMA infants using the Hammersmith Infant Neurological Examination. Thirty-three type I SMA infants, who classically do not achieve the ability to sit unsupported, were included in the study. Our results confirmed that all patients had a score of 0 out of a scale of 4 on items assessing sitting, rolling, crawling, standing or walking. A score of more than 0 was only achieved in three items: head control (n = 13), kicking (n = 15) and hand grasp (n = 18). In these items, the maximal score achieved was 1 out of a scale of 4, indicating only partial achievement of the milestone. Infants with symptom onset after 6 months of age had longer preservation of a score of 1 when compared to those with onset before 6 months of age. Our results suggest that even when current standards of care are applied, developmental milestones are rarely even partially achieved as part of natural history in type I SMA infants. No infants in this study achieved a major milestone such as rolling over, or sitting independently, which would therefore represent robust outcomes in future interventional trials.

Keywords: Hammersmith Infant Neurological Examination; Motor milestones; Outcome measures; Spinal muscular atrophy.

Fig. 1

HINE scoring module illustrating the motor developmental milestones.

Fig. 2

Longitudinal data of the item assessing the ability to control the head in 24 typical type I SMA infants (from number 1 to 24) and in 2 stronger type I infants with late onset (25–26, shaded). Each line represents the different assessments in the same patient linked by a dotted line. ● = score 0, ○ = score 1, V = ventilation; G = gastrostomy; T = tracheostomy). The seven weakest patients with onset within the first week (type IA or 1.1 according to Dubowitz) were not added to the figure as they all had a score of 0 in all assessments.

Fig. 3

Longitudinal data of the item assessing voluntary grasp in 24 typical type I SMA infants (from number 1 to 24) and in 2 type I infants with late onset (25–26, shaded). Each line represents the different assessments in the same patient linked by a dotted line. ● = score 0, ○ = score 1, V = ventilation; G = gastrostomy; T = tracheostomy). The seven patients with onset within the first week (type IA or 1.1 according to Dubowitz) were not added to the figure as they all had a score of 0 in all assessments.

Fig. 4

Longitudinal data of the item assessing ability to kick in 24 typical type I SMA infants (from number 1 to 24) and in 2 type I infants with late onset (25–26, shaded). Each line represents the different assessments in the same patient linked by a dotted line. ● = score 0, ○ = score 1, V = ventilation; G = gastrostomy; T = tracheostomy). The seven patients with onset within the first week (type IA or 1.1 according to Dubowitz) were not added to the figure as they all had a score of 0 in all assessments.