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. 2022 Jul;181(7):2821-2829.
doi: 10.1007/s00431-022-04470-3. Epub 2022 May 6.

Neurological assessment of newborns with spinal muscular atrophy identified through neonatal screening

Marika Pane #  1   2 , Maria Alice Donati #  3 , Costanza Cutrona #  1   2 , Roberto De Sanctis  1 , Matteo Pirinu  4 , Giorgia Coratti  1   2 , Martina Ricci  1   2 , Concetta Palermo  1 , Beatrice Berti  1 , Daniela Leone  1 , Chiara Ticci  3 , Michele Sacchini  3 , Margherita Cerboneschi  4 , Anna Capasso  1   2 , Gianpaolo Cicala  1   2 , Maria Carmela Pera  1 , Chiara Bravetti  1 , Emanuela Abiusi  5 , Alessandro Vaisfeld  5 , Giovanni Vento  6 , Francesco Danilo Tiziano  5 , Eugenio Mercuri  7   8
Affiliations

Neurological assessment of newborns with spinal muscular atrophy identified through neonatal screening

Marika Pane et al. Eur J Pediatr. 2022 Jul.

Abstract

The possibility to identify patients with spinal muscular atrophy through neonatal screenings has highlighted the need for clinical assessments that may systematically evaluate the possible presence of early neurological signs. The aim of this study was to use the Hammersmith Neonatal Neurological Examination (HNNE) and a module specifically designed for floppy infants to assess the possible variability of neurological findings in infants identified through neonatal screening. The infants included in this study were identified as part of a pilot study exploring neonatal screening in two Italian regions. A neurological examination was performed using the HNNE and an additional module developed for the assessment of floppy infants. Seventeen infants were identified through the screening. One patient had 1 SMN2 copy, 9 had 2 copies, 3 had 3, and 4 had more than 3 copies. Nine of the 17 infants (53%) had completely normal results on both scales, 3 had minimal signs, and the other 5 had more obvious clinical signs. The number of SMN2 copies was related to the presence of abnormal neurological signs (p = 0.036) but two SMN2 copies were associated with variable clinical signs as they were found in some infants with respectively normal examination or obvious severe early signs.

Conclusions: Our results suggest that the combination of both scales increases the possibility to detect neonatal neurological signs and to define different early patterns of involvement also identifying paucisymptomatic patients.

What is known: • The use of new therapeutic options in presymptomatic SMA patients leads to a dramatic reduction of the onset and severity of the diesease. • The already existing tools commonly used in Type I SMA (HINE and CHOP-intend) may not be suitable to identify minor neurological signs in the neonatal period.

What is new: • Combining the HNNE and the floppy infant module, we were able to identify early neurological signs in SMA infants identified through newborn screening and may help to predict the individual therapeutic outcome of these patients. • Iinfants with 2 SMN2 copies identified through the screening had a more variable neonatal examination compared to those with three or more copies, in agreement with similar findings in older infants.

Keywords: Assessment; Neonatal; SMA; Screening.

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Conflict of interest statement

Pane M, Donati MA, De Sanctis R, Coratti G, Tiziano FD, and Mercuri E report personal fees from BIOGEN S.R.L. outside the submitted work; Coratti G, Pera MC, Tiziano FD, and Mercuri E report personal fees from ROCHE outside the submitted work; Pane M, De Sanctis R, Coratti G, and Mercuri E report from personal fees AVEXIS and NOVARTIS outside the submitted work; Tiziano FD report from personal fees NOVARTIS outside the submitted work; Pane M and Mercuri E report personal fees from PTC THERAPEUTICS and SAREPTA outside the submitted work; Coratti G report personal fees from GENESIS PHARMA and Biologix outside the submitted work; Mercuri E report from personal fees SANTHERA outside the submitted work; Cutrona C, Pirinu M, Ricci M, Palermo C, Berti B, Leone D, Ticci C, Sacchini M, Cerboneschi M, Capasso A, Cicala G, Bravetti C, Abiusi E, Vaisfeld A, and Vento G have nothing to disclose.

Figures

Fig. 1
Fig. 1
HNNE tone and posture optimality score. The figure shows details of the frequency of optimality scores in the individual item in the Tone and Posture section. Panel A shows an example of the recurrent pattern of optimality observed in many items, with asymptomatic and presymptomatic infants all having optimal results and symptomatic patients all having suboptimal results. This pattern was found in the items: arm recoil, arm traction, leg traction, popliteal angle, head control (1), head control (2) and head lag. The other panels show items who had different patterns of responses: posture (B); leg recoil (C); ventral suspension (D)
Fig. 2
Fig. 2
HNNE movements and reflexes optimality scores. The figure shows details of the frequency of optimality scores in the individual items assessing: quantity (A) and quality (B) of Spontaneous movements; Head raising (prone) (C). Panel D shows the frequency of optimality scores for tendon reflexes
Fig. 3
Fig. 3
Correlation between SMN2 copies and neurological findings. Key to figure: Dark gray: patients with 1 SMN2 copy; Gray: patients with 2 SMN2 copies; Light Gray: patients with 3 SMN2 copies; Dotted: patients with more than 3 copies
See this image and copyright information in PMC

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