Electrodiagnostic Evaluation of the Floppy Infant

The most common referral for an electrodiagnostic examination in the infant is generalized hypotonia. The most common etiology for infantile hypotonia is central, accounting for approximately 80% of cases.

Neurogenic causes of generalized weakness in infants are more accurately diagnosed with electrodi­agnostic studies than are myogenic causes (36-38). A study of the predicted value of the electrodiagnostic examination in the hypotonic infant showed that elec­trodiagnostic studies accurately predicted the diag­nosis in 65% of infants with spinal muscular atrophy and only 10% of infants with myopathy. Seventy-five percent of the electrodiagnostic studies performed on infants with documented myopathies were considered normal (39). The sensitivity of EMG improves after age 2 (38).

In arthrogryposis multiplex congenita and hypotonia, neither muscle biopsy nor NCS/EMG alone had consistently high sensitivities, positive

7.8

Differential Diagnosis of Infantile Hypotonia

Cerebral hypotonia

Chromosome disorders

Trisomy

Prader-Willi syndrome

Static encephalopathy

Cerebral malformation

Perinatal CNS insult

Postnatal CNS insult

Peroxisomal disorders

Cerebrohepatorenal syndrome (Zellweger syndrome)

Neonatal adrenoleukodystrophy

Inborn errors of metabolism

Glycogen storage disease type II (Pompe disease)

Infantile GM1 gangliosidosis

Tay-Sachs disease (infantile GM2 gangliosidosis)

Vitamin-dependency disorders

Amino acid and organic acid disorders

Maple syrup disease

Hyperlysinemia

Nonketotic hyperglycinemia

Propionyl-CoA carboxylase deficiency

Other genetic disorders

Familial dysautonomia

Cohen syndrome

Oculocerebrorenal syndrome (Lowe)

Benign congenital hypotonia

Spinal cord

Trauma (obstetrical, postnatal)

Hypotonia early with acute paraplegia

Hypertonia

Tumor or AVM

Hypertonia may occur later or with slow-growing tumor

Anterior horn cell

Spinal muscular atrophy type I (Werdnig-Hoffman)

Spinal muscular atrophy type II

Distal SMA with vocal cord paralysis and diaphragm weakness Poliomyelitis

Neurogenic arthrogryposis

Polyneuropathies

Congenital hypomyelinating neuropathy

Chronic inflammatory demyelinating polyneuropathy

Acute inflammatory demyelinating polyradiculoneuropathy

(Guillain-Barre syndrome)

Hereditary motor-sensory neuropathies

Dejerine Sottas

Congenital hypomyelinating neuropathy

Toxic polyneuropathy

Leukodystrophies (Krabbe's, Nieman-Pick)

Leigh's syndrome

Giant axonal neuropathy

Dysmaturation neuropathy

Neuromuscular junction

Presynaptic

Infantile botulism

Hypermagnesemia—eclampsia

Aminoglycoside antibiotics

Congenital myasthenia

Choline acetyltransferase (CHAT) deficiency

Paucity of acetylcholine synaptic vesicles

Congenital Lambert-Eaton-like syndrome

Decreased quantal release

Synaptic basal lamina defects

Congenital myasthenic syndrome

Endplate acetylcholinesterase (AChE) deficiency

Postsynaptic

Neonatal (autoimmune)

Congenital myasthenia

AChR disorders involving α, β, δ, º receptor subunits

AChR deficiency causing kinetic abnormalities in function

AChR slow-channel syndromes

AChR fast-channel syndromes

Endplate rapsyn deficiency

Myopathies

Congenital myopathies

Nemaline rod

Central core

Myotubular (centronuclear)

Mini-core (multi-core)

Congenital fiber type disproportion

Congenital myotonic dystrophy (DM1)

Congenital muscular dystrophy

Fukuyama type (CNS involvement)

Merosin deficiency (with or without CNS involvement)

Ullrich'e congenital muscular dystrophy (collagen VI deficiency, scleroatonic)

Congenital muscular dystrophy with early spine rigidity Muscle-eye-brain di sease

Walker-Warburg syndrome

Undifferentiated

Inflammatory myopathies

Infantile polymyositis

Metabolic myopathies

Acid maltase deficiency (type II)

Muscle phosphorylase deficiency (type V)

Phosphofructokinase deficiency (type VII)

Cytochrome c oxidase

Carnitine deficiency

Endocrine myopathies

Hypothyroidism

Hypoparathyroidism

AVM, arteriovenous malformation; CNS, central nervous system; SMA, spinal muscular atrophy.

7.9

Infant Hypotonia: Electrodiagnostic Abnormalities

predictive values, or specificities (40). When the clinical evaluation indicates a specific syndromic, developmental, or exogenous cause, NCS/EMG and muscle biopsy are not helpful and may not need to be performed.

In the evaluation of hypotonia, a complete elec­trodiagnostic evaluation is useful, including motor and sensory nerve conduction studies and appro­priate needle examination with the highest yield muscles examined initially, and, if necessary, repet­itive nerve stimulation. It should be emphasized that nerve conduction studies and electromyography are an extension of the clinician’s physical examination. Electrodiagnostic findings need to be interpreted in light of clinical examination findings. Care should be taken not to overinterpret subtle findings on needle electromyography. Low-amplitude, short-duration, polyphasic motor unit action potentials, which would be considered myopathic in adults, may be normal in young children. Motor unit amplitudes and dura­tions may be reduced in the normal young child and mistaken for myopathic MUAPs. End-plate noise, abundant in the small intrinsic muscles of the hand and foot, may be difficult to distinguish from fibrilla­tion potentials. Thus, borderline findings on needle EMG should not be overinterpreted in the infant and young child.

Parents should be cautioned prior to an electrodi­agnostic evaluation that definitive diagnostic infor­mation is often not obtained and the results may help guide further diagnostic studies. For example, results from EMG may help to guide further stud­ies such as muscle biopsy by providing information about the most appropriate muscle site for the biopsy. With spinal muscular atrophy, an electrodiagnostic evaluation can allow the clinician to defer a muscle biopsy and proceed with molecular genetic studies of the survival motor neuron (SMN) gene. Often, the SMN gene test is ordered prior to any electrodiagnos­tic studies being performed, so fewer studies have been performed on this population over the past decade. Electrodiagnostic studies in patients with hereditary motor sensory neuropathy help to catego­rize the neuropathy as either primarily demyelinat­ing or axonal, and such information may help focus subsequent molecular genetic analyses. In general, nerve conduction and electromyography still provide a useful tool for the localization of lesions within the lower motor neuron, but fewer studies have been required as genetic studies have become commer­cially available.