Primary disorders of muscle are a more common cause of neonatal hypotonia. One series reported that myopathies comprised 20% of all causes of neonatal hypotonia as well as 75% of causes of ‘peripheral’ hypotonia [21]. Muscle disorders can include the following groups of disorders which can be grouped into the following large categories: congenital myopathies, congenital muscular dystrophies, congenital myotonic disorders, and metabolic myopathies. Electrophysiological testing will reveal normal sensory responses as well as normal or reduced CMAP amplitudes and EMG evidence of myopathic units. Muscle disorders are covered in detail in Chap. 22.

Critical illness polyneuropathy (CIP) and critical illness myopathy (CIM) are neuromuscular disorders that develop during the course of a critical illness. This is one of the key features that allow patients with CIP to be differentiated from patients presenting with an acute motor sensory axonal neuropathy (AMSAN), namely the axonal variant of Guillain-Barré syndrome [50]. In CIP, patients do not show a preceding history of sensory or motor deficits. Moreover, they must have an associated critical illness that seems to trigger the underlying neuromuscular disease [51] with onset of weakness in the 1–2 weeks following the critical illness [52].

Critical illness polyneuropathy (CIP) and CIM can be difficult to differentiate on clinical and electrophysiological testing [26]. However there are some distinguishing features (Table 23.2). Since CIP and CIM can co-exist in the same patient, some authors have grouped them together as critical illness polyneuromyopathy (CIPNM) or critical illness myopathy and neuropathy (CRIMYNE) [53].

In adults, CIP and CIM are the most common neuromuscular conditions that develop during an ICU admission and diagnostic criteria have been created to permit them to be distinguished from other diseases as well as, whenever possible, from each other [51]. One center reviewed all patients admitted to ICU over 15 years who had neuromuscular disease confirmed by neurophysiological testing. Of this group, 13% patients had CIP and 41% had CIM [26]. The incidence of CIP/CIM in children is less clear. A prospective study of all children (3 months to 17 years old) admitted to the PICU of a pediatric tertiary care hospital identified generalized muscle weakness in 1.7% (14/830) patients [54]. Children with pre-existing neuromuscular diseases and Guillain-Barré syndrome were excluded from this cohort. Of the remaining children showing weakness who underwent electrophysiological testing, about half (4 out of 7) showed low CMAP amplitudes and most (4 out of 5) had myopathic units evident upon EMG analysis. When one considers the difference in study design of the adult [26] and pediatric [54] studies (including versus excluding patients GBS) the overall incidence of CIPM appears similar in the two groups, accounting for about half of all patients with confirmed neuromuscular disease in this setting.

Many adult and pediatric patients who develop CIPM have undergone a solid organ or bone marrow transplant, suffered a traumatic injury (e.g., head injury, burns) and/or have had one or more episodes of bacterial sepsis [26, 54]. The use of corticosteroids and neuromuscular blocking agents is also common. Although the precise mechanism of CIPM is not known, it is believed to result from a systemic inflammatory response syndrome (SIRS) provoked by a severe systemic infection or trauma [51]. Patients exhibit profound changes in cellular and humoral immune responses altering the microcirculation throughout the body. At the microscopic level, mitochondrial dysfunction occurs with the loss of normal ATPase staining in type 1 fibers of a muscle biopsy [51, 54]. Endothelial damage may result in the disruption of the vasa nervorum with resulting ischemia of axons. In muscles this can cause disruption of the function and structure of the basic contractile unit and, in more severe cases, areas of necrosis and vacuolar changes [51]. This evidence of microstructural damage and mitochondrial dysfunction seen on biopsy is congruent with the high rate of long-term morbidity seen in adult patients who have suffered CIM [55, 56]. Prospective studies of adult ICU patients indicate that CIPM occurs in about 50-70% of patients suffering from systemic inflammatory response syndrome [57, 58]. As such, milder cases of CIPM may even be more prevalent than that reported by Lacomis [26] and Banwell [54]. Phrenic nerve conduction studies and needle EMG of the diaphragm and chest wall muscles have been recommended in adult patients with suspected CIPM [51]; however, these particular studies are not commonly performed in pediatric EMG.

Medications or toxins can exacerbate underlying disorders of nerve, muscle and neuromuscular transmission.

Chemotherapeutic agents such as vincristine have been reported to cause significant toxicity in patients with Charcot-Marie-Tooth disease.

Most individuals will not report symptoms of a vincristine-induced sensorimotor neuropathy until after a minimum cumulative dose of vincristine 5–8 mg has been administered [59]. However patients with Charcot-Marie-Tooth disease will show marked sensitivity to this chemotherapeutic agent with dramatic sensory symptoms or even a Guillain-Barré-like phenotype apparent after a cumulative dose of only 2 mg [59, 60]. On rare occasions CMT has presented in previously asymptomatic patients after receiving vincristine to treat lymphoma [61, 62]. Reports exist of adults with no prior neurological symptoms progressing to quadriplegia and bulbar palsy after vincristine therapy [62]. As such, hereditary neuropathies must be considered among individuals showing extreme sensitivity to this drug.