The effects of denervation, reinnervation, and muscle imbalance on functional muscle length and elbow flexion contracture following neonatal brachial plexus injury

Abstract

The pathophysiology of paradoxical elbow flexion contractures following neonatal brachial plexus injury (NBPI) is incompletely understood. The current study tests the hypothesis that this contracture occurs by denervation-induced impairment of elbow flexor muscle growth. Unilateral forelimb paralysis was created in mice in four neonatal (5-day-old) BPI groups (C5-6 excision, C5-6 neurotomy, C5-6 neurotomy/repair, and C5-T1 global excision), one non-neonatal BPI group (28-day-old C5-6 excision), and two neonatal muscle imbalance groups (triceps tenotomy AE C5-6 excision). Four weeks post-operatively, motor function, elbow range of motion, and biceps/brachialis functional lengths were assessed. Musculocutaneous nerve (MCN) denervation and reinnervation were assessed immunohistochemically. Elbow flexion motor recovery and elbow flexion contractures varied inversely among the neonatal BPI groups. Contracture severity correlated with biceps/brachialis shortening and MCN denervation (relative axon loss), with no contractures occurring in mice with MCN reinnervation (presence of growth cones). No contractures or biceps/brachialis shortening occurred following non-neonatal BPI, regardless of denervation or reinnervation. Neonatal triceps tenotomy did not cause contractures or biceps/brachialis shortening, nor did it worsen those following neonatal C5-6 excision. Denervation-induced functional shortening of elbow flexor muscles leads to variable elbow flexion contractures depending on the degree, permanence, and timing of denervation, independent of muscle imbalance. Neonatal brachial plexus injury (NBPI) occurs in 1.5 per 1,000 live births. 1 In the 20-30% of children without immediate neurological recovery, 2 secondary contractures occur, most notably shoulder internal rotation contractures and elbow flexion contractures. 3 In contrast to the wealth of literature addressing the shoulder contracture, relatively few studies have addressed the elbow flexion contracture, despite the fact that the latter contracture has been described for over 100 years 4 and affects 62-89% of children following unresolved NBPI. 5,6 These elbow contractures range from mild (10-208) 6,7 to severe (40-908), [8][9][10] limiting the functional range of elbow motion 11 and exacerbating the cosmetic deformity of an already short, malpositioned upper extremity. 9 Recommendations for treatment vary widely, with proponents of no treatment, 12 serial casting, 8 surgical release, 5,13 external fixator distraction, 10 flexor-to-extensor muscle transfers, 14 and humeral osteotomy. 9 Underlying the paucity of literature and lack of treatment consensus is an incomplete understanding of the contracture's etiology. Despite the fact that this paradoxical flexion contracture occurs in the setting of elbow flexor paralysis, 6,15,16 several authors believe muscle imbalance to be the cause, 3,8,10,17 proposing that the imbalance may be caused by earlier 6 or anomalous 1014 reinnervation of the elbow flexors. Additional proposed etiologies of the elbow ...

The natural history and management of brachial plexus birth palsy

“…Nikolaou has shown that functional shortening of denervated muscle plays a primary role in contracture pathogenesis [32]. However, the mechanism of contracture development in denervated muscle remains unanswered [33,34].…”

The Multifactorial Role of Peripheral Nervous System in Bone Growth

“…Clinical studies have also demonstrated the effect of peripheral nerve system on bone growth [44,45]. In 2012 Reading et al [44] retrospectively reviewed children with neonatal brachial plexus palsy who had underwent joint rebalancing with magnetic resonance imaging (MRI).…”

“Popeye muscle” morphology in OBPI elbow flexion contracture

“…The leading explanation is "muscle imbalance", involving preferential flexor action [8], secondary to delayed reinnervation of the elbow extensors vs the flexors [10]. This hypothesis does not account for cases with flexion paralysis [11].…”

“…The historical [8] clinical hypothesis for EFC is delayed elbow extensor reinnervation vs the flexors [10], allowing preferential flexor action for a brief period. However, EFC occurs even in cases without recovery of elbow flexion [11]. Additional hypotheses include: long head of biceps over-activity [12], uncommon C8-T1 pattern injuries [13], presence of shoulder contracture [14], and abnormal posturing [10].…”

“…Using a rat model, they showed diminished longitudinal and cross-sectional growth of the biceps and brachialis and impaired elbow passive range of motion. A second study by the same authors correlated severity of neonatal denervation with elbow flexor shortening [11]. Biceps function is a particular focus of OBPI literature; biceps function is a prognostic indicator [1], and an independent surgical indication [19].…”