Neuropathophysiology

In BRPNI infants, the damaged nerves are usually not completely ruptured in the sense that there is a gap between two stumps. This is most likely caused by the gradual exertion of traction forces over a small distance that acts during a relatively long period and by the changes of direction of these forces during the delivery. The two crucial factors that determine good functional recovery are the number of damaged axons that successfully elongate past the lesion site and their routing. Axonal outgrowth and restoration of connections with their original motor or sensory end organs can only take place when the basal laminal tubes surrounding the axons—which are in this context the crucial anatomic structures—remain intact. The distance from the lesion site, which is in BRPNI almost always at root and trunk level, to the end organ determines the length of the time interval after which recovery will take place. Proximal muscles recover, therefore, at an earlier stage than more distally located ones. Spontaneous recovery of predominantly axonotmetic BRPN injuries is usually seen within the first 3 to 4 months of life.

When the traction lesion is severe the basal laminal tubes are ruptured, but the perineurium and epineurium remain more or less intact. Outgrowing axons then do not end up directly in any tube. Typical for the BRPNI, the stretched and damaged nerve forms a neuroma in continuity, that is, a tangled mass of connective scar tissue and outgrowing, branching axons. The local environment encountered by the axonal growth cone can impede outgrowth and can ultimately block the restoration of axonal continuity. Even in the most severe C5–6 BRPNIs, at least some axons pass through the neuroma in continuity and reach the tubes distal to the lesion site.

The number of axons that do not pass the lesion site depends on the severity of the lesion, which is determined by the magnitude and angle of the exerted traction forces. There is a minimum number of axons that should reconnect with the end organs in order to regain function. In addition, for the regain of useful function there is a minimum of axons that should be properly routed to their original end organ. We presume that those axons in the BRPNI neuroma in continuity are particularly prone to abnormal branching and misrouting. Because the direction of outgrowth after severe lesions is essentially random,²² outgrowing axons growing through a neuroma in continuity are likely to end up in the wrong tube.

Each BRPNI case is unique on an axonal level in the sense that the number of ruptured axons and basal laminal tubes differ for each intraplexal involved nerve element. This subsequently leads to the wide variety in level of functional recovery that can be found in individual cases. Branching and misrouting can also explain co-contraction,²³ a typical feature of BRPNI at a later age, in which shoulder abduction and elbow flexion or elbow flexion and extension become irreversibly linked. Misrouting can even result in the phenomenon of the breathing arm: Clinically, when the proximal arm is at rest, involuntary movements simultaneous with the breathing rhythm can be observed. This can be explained by misrouting of ruptured C4 or C5 axons that were originally connected to the diaphragm through the phrenic nerve and erroneously grow into a superior trunk neuroma-in-continuity to shoulder muscles or the biceps muscle.²⁴

The most severe lesion type, which is specifically related to traction to the spinal nerves that form the brachial plexus, is a root avulsion. The result is a complete discontinuity of the neural connections of the central nervous system to the peripheral nervous system. Outgrow of axons, and thus neuroma formation or misrouting, does not take place in case of a root avulsion.

An additional factor to inadequate number of outgrowing axons and misrouting that can reduce functional regeneration is that improper central motor programming can occur.²⁵ There are various reasons that the formation of motor programs fail in BRPNI. Firstly, BRPNI causes deafferentation as well as weakness; many functions in the central nervous system depend on afferent input in a specific time window or else they are not formed correctly. Secondly, aberrant outgrowth of motor axons can present the central nervous system with conflicting information. A motor command for shoulder abduction can, for instance, cause elbow flexion in addition to abduction through misrouted motor axons. The resulting feedback may well hamper the formation of a selective abduction program, because there is probably no way for the central nervous system to identify the “misbehaving” motor units.^26,27 Thirdly, sensory axons might also be prone to misrouting, compounding the problem. A final hurdle for the central nervous system may be the severity of paresis. In such cases the only way to effect certain movements may be through trick movements (such as scapular rotation instead of glenohumeral rotation), which then represent a functional adaptation.

Natural History

The prognosis of BRPNI is generally considered to be very good, with complete or almost complete spontaneous recovery in more than 90% of patients.^28–33 However, this opinion is based on a limited number of series,^34,35 which are cited indiscriminately, and without considering methodological aspects of these studies. In a systematic literature review, we discussed the methodologic flaws in the available natural history studies.³⁶ We found that no study presented a prospective population-based cohort that was scored with a proper scoring system with adequate follow-up of 3 years. In other words, there is no scientifically sound evidence to support the common perception of complete spontaneous recovery from BRPNI. The often-cited excellent prognosis may be too optimistic.

Analysis of the most methodologically sound studies led us to estimate the percentage of children with residual deficits at 20% to 30%. This analysis was subsequently confirmed by two other studies, which prospectively investigated a population-based cohort. In the first, the British Paediatric Surveillance Unit notification system performed a nationwide registration of BRPNI injuries. Although follow-up was restricted to 6 months only, in this period only half of the infants showed full recovery.⁵ A prospective population-based study from a Swedish region revealed that 18% of the children had residual deficits at 18 months of age.³⁷

Electromyography and Prognosis

Ancillary testing, in particular electromyography (EMG), is not considered reliable enough for prognostication of BRPNI.^26,38 A needle EMG might seem a useful tool in this respect, but at present its role is debated. A main reason for this is that EMG findings may be discordant with clinical findings at 3 months of age, at which the biceps test is performed.³⁹ In a paralytic biceps brachii muscle, the expected findings are an absence of motor unit potentials (MUPs) and the presence of positive sharp waves and/or fibrillation potentials (denervation activity). But in a typical BRPNI case, MUPs are present and denervation is absent in a paralytic biceps muscle at 3 months of age. This confusing finding has been noted by others^40,41 and might have contributed to the opinion that the EMG is not useful in BRPNI.^32,42,43 We previously outlined several possible explanations for inactive MUPs, that is, MUPs in a paralytic muscle.²⁶ These explanations suggest that the presence of inactive MUPs might depend on time after injury, because they reflect incomplete outgrowth of damaged axons and the hampered formation of motor programs in the central nervous system.

Spontaneous recovery of useful extremity function has been observed in subsets of patients without elbow flexion at 3 months of age.⁴⁴ In one study, even 20 of 28 infants who had no biceps function at 3 months had developed biceps contraction at 6 months.⁴⁵ Together with our findings⁴⁶ that MUPs can almost always be found in the biceps muscle at 3 months, this strongly suggests that the age of 3 months does not represent a stable state in BRPNI. In fact, the outgrowing axons might well have only just arrived in the various muscles, and the central nervous system might not yet have learned to cope with the situation. In nerve lesions in adults, one may expect all motor programs to be ready and waiting for the restoration of peripheral connections. In BRPNI, axonal outgrowth may only be the starting point for restoration of function, as formation of central nervous system motor programs might only commence after enough axons have arrived to start exerting force. At the same time, forming such central motor programs may be more difficult and thus take longer than in healthy children, because the central nervous system must somehow take aberrant outgrowth and the confusing feedback it causes into account. Faced with a degree of inescapable co-contraction, it might not be easy to program effective elbow flexion, abduction, or rotation. In this hypothetical view, the age of 3 months may well be the very worst period imaginable to correlate the EMG with clinical findings: it is late enough to show evidence of axonal outgrowth but too early for the brain to control contraction efficiently. This leaves the role of the EMG for prognosis at 3 months undetermined at present; we showed that severe cases of BRPNI can be identified reliably at 1 month of age based on clinical findings and needle EMG of the biceps.⁴⁶ These findings will be reported in full after validation, which is currently in progress.

For less-extreme cases, that is, the majority of BRPNI cases, the challenge lies in predicting whether function will be best after spontaneous outgrowth through a neuroma in continuity, resulting in reinnervation through tangled paths, or after nerve grafting, in which the grafts serve as a straight path that can be targeted. Results achieved by surgery are claimed to be superior to the outcome in conservatively treated subjects with equally severe lesions.^39,47,48 However, this comparison relies on historical controls⁴⁹; no randomized study has been performed.^50,51 The best way to answer this question may be a controlled trial comparing nerve surgery to spontaneous recovery. In view of the current standard of treatment practice, it seems extremely difficult to perform such a prospective randomized trial.

Conservative Treatment the First Few Months of Life

In the past there has been a tendency to immobilize the arm directly after birth to prevent secondary damage to the injured nerve elements of the brachial plexus. It is, however, highly unlikely that secondary damage to the brachial plexus can occur during the passive movements of the arm in a physiologic range of motion during exercises or caregiving. We recommend frequent mobilization of the joints from the beginning to prevent formation of joint contractures. Additionally, there is no scientific proof that immobilization might be of any benefit to accelerate or improve the nerve-regeneration process. Joint contracture formation, however, might be detrimental to final functional outcome when contractures limit the effective contraction of reinnervated muscles. It can also lead to improper modeling of the joints, of which the glenohumeral joint is most commonly affected.²⁰ Contractures can start to form as early as 2 to 3 weeks after birth. The type of joint contractures that we most often see are those resulting in a fixed internal rotation, flexion, and pronation position of the upper limb.

Exercises that focus on preventing this type of contracture from forming and that optimize joint mobility consist of passive external rotation in adduction and supination with the elbow flexed to 90 degrees, rotating and adducting just to the point where a certain tension can be felt. The arm should then be held in this position for a few seconds and then released. This passive movement should be frequently repeated during one session. We advise the parents to mobilize the affected arm as frequently as possible during the day, but at least every time the diaper is changed. In addition, we recommend that the parents move both arms in a symmetrical fashion. In this way, the parents can use the unaffected arm’s range of motion as a reference value and therapy target of reach for the affected arm. The joint mobility should initially be evaluated every week by a specialized child physiotherapist.

Surgical Treatment