The Hypotonic Infant

Basic facts:

• TONE IS THE resistance of muscle to stretch / refers to the state of muscle tension or contraction.

• Clinicians test two kinds of tone:

1) Phasic tone

2) Postural tone

• Phasic tone is a rapid contraction in response to a high-intensity stretch.

Ex: Tendon reflexes (Monosynaptic reflex)

• Postural tone :

� Defined as the prolonged contraction of antigravity muscles in response to the low-intensity

stretch of gravity.

� When postural tone is depressed, the trunk and limbs cannot maintain themselves against

gravity, and the infant appears hypotonic

• The maintenance of normal tone requires intact central and peripheral nervous systems.

• Hypotonia is a common symptom of neurological dysfunction and occurs in diseases of the brain,

spinal cord, nerves, and muscles

• motor unit : One anterior horn cell + all the muscle fibers that it innervates .

• Weakness is a symptom of all motor unit disorders.

• Neuronopathy : A primary disorder of the anterior horn cell body

• Neuropathy : primary disorder of the axon or its myelin covering

• Myopathy : a primary disorder of the muscle fiber

• Cerebral hypotonia encompasses all causes of postural hypotonia caused by a cerebral disease or

defect.

• In infancy and childhood, cerebral disorders far outnumber motor unit disorders.

When to suspect:

• Mother feels baby is floppy since birth.

• Slips from hands.

• Less movement of limbs

• Baby is alert, but less motor activity.

• Delayed motor development.

• Able to walk but with frequent falls

History :

• Determine age of onset (it may distinguish between congenital and aquired aetiologies), mode of

onset, presenting complaints, rapidity of progression.

• H/o feeding problems, recurrent pneumonias. (Neuromuscular disorder)

• Antenatal History:

o Decreased fetal movements and polyhydramnios (due to intrauterine swallowing

difficulty) seen in SMA.

o Breech presentation (The incidence of breech presentation is higher in fetuses with

neuromuscular disorders as turning requires adequate fetal mobility).

• Perinatal History: Birth weight, hypoxia, sepsis

o Documentation of birth trauma, birth anoxia, delivery complications, low cord pH and Apgar

scores are crucial as hypoxic-ischaemic encephalopathy remains an important cause of

neonatal hypotonia

o Neonatal seizures and an encephalopathic state offer further proof that the hypotonia is of

central origin

• Developmental history: Delay of motor milestones with normal intellectual development

suggests possible defect in the motor unit.

• Family History: Important to determine the pattern of inheritance, enquire about

consanguinity

• Look at the parents’ face for evidence of myotonic dystrophy.

• If this is suspected, the parent is asked to make a fist and then open hands quickly. This will

detect myotonia.

• Look for evidence of myasthenia in the mother (neonatal myasthenia)

• Look for pes cavus in the mother (Hereditary Neuropathy).

CLINICAL CLUES ON NEUROLOGICAL EXAMINATION:

� There are two approaches to the diagnostic problem

1. The first is based on identifying the neuro-anatomical site of the lesion or insult.

2. The second is to determine whether or not the hypotonia is accompanied by

weakness

General Observation:

� Dysmorphic Features – Downs, Prader Willi syndrome, MPS, Lipidoses, Cong. muscular

dystrophy

1. Common physical findings of dysmorphia • Unusual facies

• Sloping forehead

• High arched and narrow palate (HIE)

• Down-turned corners of the mouth

• Micrognathia

• Abnormal dermatoglyphics

• Dimpling of the elbows and knees

• Congenital hip dislocation

• Joint laxity

• Joint contractures

• Club feet

• Arthrogryposis multiplex congenita

� Head Size – Microcephaly – Cerebral palsy (CP)

� Macrocephaly – Associated myelomeningocele, Cong. Toxoplasmosis.

� Facial features

1. Alert: SMA.

2. Expressionless (Myopathic facies) - Congenital myopathies (CM), myotonic

dystrophies (MD), myasthenia gravis (MG)

� Ptosis, ophthalmoplegia - Congenital myopathies, MD, MG

� Nasogastric tube- Hypotonic CP, CM, MD

� Fish (triangular) mouth – CM, MD

� Tongue fasciculation – SMA.

� Oxygen Catheter – Hypotonic CP, SMA, some congenital myopathies, MD, MG.

Posture:

� Frog legged lower limb posture – SMA, Congenital myopathies

� Rag doll position on ventral suspension - SMA

� Fisted hands – CP

� Arthrogryposis – congenital muscular dystrophy, myotonic dystrophy

Weakness: � Weakness is uncommon in UMN hypotonia except in the acute stages.

� Hypotonia with profound weakness therefore suggests involvement of the LMN.

� Assessment of muscle power of infants is generally limited to inspection

� Proportionate to hypotonia – muscle/nerve etiology

� Disproportionate to hypotonia – CNS, Systemic illness, metabolic or connective tissue

disorders

� Useful indicators of weakness are:

� Ability to cough and clear airway secretions (‘cough test’). Apply pressure to the

trachea and wait for a single cough that clears secretions. If more than one cough is

needed to clear secretions, this is indicative of weakness.

� Poor swallowing ability as indicated by drooling and oropharyngeal pooling of

secretions.

� The character of the cry — infants with consistent respiratory weakness have a

weak cry.

� Paradoxical breathing pattern — intercostal muscles paralysed with intact

diaphragm

A distinct pattern of weakness may favour certain aetiologies:

• Axial weakness is a significant feature in central hypotonia.

• Generalised weakness with sparing of the diaphragm, facial muscles,pelvis and

sphincters suggests anterior horn cell involvement.

• With myasthenic syndromes, the bulbar and oculomotor muscles exhibit a greater

degree of involvement.

• Progressive proximal symmetrical weakness suggests a dystrophinopathy. Signs of

proximal weakness in the older infant include a lordotic posture, Trendelenburg gait

and Gower sign.

• A striking distribution of weakness of the face, upper arms and shoulders suggests

fascioscapulohumeral muscular dystrophy.

• Distal muscle groups are predominantly affected with peripheral neuropathies.

Signs suggesting distal weakness in an older infant would include weakness of hand

grip, foot drop and a high stepping,slapping gait

Main Areas Affected

� FACE: Congenital myopathies, Myotonic dystrophies, myasthenia gravis

� The presence of a facial diplegia (myopathic facies) suggests either a congenital structural

myopathy or myasthenia gravis.

� Respiratory and bulbar weakness can accompany both conditions.

� Fluctuation in strength would favour myasthenic syndromes

� Lower Limbs: Myelomeningocele.

� Proximal Limb: SMA

� Distal limb: Congenital myotonic dystrophy.

� Fasciculations Eg: SMA.

� Previous intervention: Tracheostomy/scar – infantile botulism.

� Gastrostomy/scar – Hypotonic CP, congenital myotonic dystrophy

� Examine the tongue :

� for size and fasciculations.

� Fasciculations, irregular twitching movements, generally indicate an abnormality of the

anterior horn cells.

� Do not examine the tongue while the infant is crying.

� The co-existence of atrophy would strongly favour a denervative aetiology.

� Enlargement of the tongue may suggest a storage disorder such as Pompe’s disease

� fasciculations –

1) spontaneous contractions of portions of individual motor units - may occur.

2) Occur due to a motor nerve or motor neuron lesion,

3) Fasciculations are more typical of motor neuron disease and root lesions than of distal

motor neuropathies.

Respiratory Difficulties:

• Upper airway noise – CP

• Weak cry/weak cough – Hypotonic CP, SMA, Cong. Myopathies, myasthenia gravis.

• Tachypnea – Aspiration with SMA, CP, Congenital myasthenia, Pompe disease.

• Paradoxical breathing (Diaphragmatic see saw breathing)– SMA.

• Bell shaped chest – SMA

• Splayed lower ribs – SMA.

LIMBS:

INSPECTION

� Decreased muscle bulk (Egs:- SMA, Undernutrition.)

� Fasciculation (SMA)

� Muscle biopsy site.

PALPATE:

� Confirm hypotonia – muscles appear flabby

� Decreased resistance to passive movements of the limbs

� Increased range of movements of peripheral joints.

� Contractures.

� Joint hyper extensibility (connective tissue disorders).

REFLEXES:

� Absent �SMA

� Decreased � Neuropathies or later myopathies

� Normal � Connective tissue disorders

� Increased � CP

PRIMITIVE REFLEXES

� Test for suck, grasp, stepping, placing, ATNR, Moro reflex

HEAD: Inspect, Palpate, Auscultate, Transilluminate

EYES: Full examination for evidence of intrauterine infection. CP, ROP

HEARING: Test with bell and rattle for deafness from kernicterus, intrauterine infection, CP

ABDOMEN:

� Examine for hepatosplenomegaly due to ToRCH infections, MPS Glycogen and lipid

storage myopathies

PRECORDIUM:

� Cardiomegaly – GSD type 2 and 3.

� PDA- Rubella.

GENITALIA: Hypoplastic in Prader Willi.

MANOEUVERS IN EXAMINATION OF A FLOPPY INFANT:

THE 1800

EXAMINATION

To quantify degree of hypotonicity

� TRACTION RESPONSE:

o Initiated by grasping hands and pulling the child to sitting position.

o It is not elicited in premature infants less than 33 weeks of gestation.

o After 33 weeks, there is considerable head lag, but neck flexors respond to traction

by lifting head.

o At term, only minimal head lag is present.

o Presence of more than minimal head lag and failure to counter traction by flexion of

limb is abnormal and indicates postural hypotonia in full term newborn.

VERTICAL SUSPENSION:

o Examiner places both hands in axilla and with out grasping thorax, lifts straight up.

o With weakness, infant needs to be grasped around trunk to prevent falling.

HORIZONTAL SUSPENSION: Normal infant suspended horizontally in prone keeps head erect,

maintains straight back demonstrates flexion at elbows, hips, knees, and ankles. Hypotonic

infant drape over examiners hands with head and limbs hanging limply.

VENTRAL SUSPENSION:

o Rag Doll Position.

Note:

Where clinical evaluation suggests complex multisystem involvement (i.e. hypotonia plus) inborn errors

of metabolism should be excluded.

Normal development of muscle strength :

• 28 weeks :minimal resistance to passive manipulation in all limbs

• 32 weeks: distinct flexor tone in the lower extremities

• 36 weeks: flexor tone is present in lower extremities and palpable in the upper extremities

• Term: flexor tone is present in all extremities

Clinical clues on neurological examination

Floppy strong • Increased tendon reflexes • Extensor plantar response • Sustained ankle clonus • Global developmental delay • Microcephaly or suboptimal head

growth • Obtundation convulsions • Axial weakness a significant feature

Floppy weak: • Hypo- to areflexia • Selective motor delay • Normal head circumference and growth • Preserved social interaction • Weakness of antigravitational limb

muscles • Low pitched weak cry • Tongue fasciculations • Paradoxical chest wall movement

Upper motor neuron disorder Central hypotonia

Lower motor neuron disorder Peripheral hypotonia

• Genetic studies • Karotyping • FISH methylation studies

• VLCFA

CT/MRI

DNA-based mutation analysis if available

Muscle or nerve biopsy

Triosomy 21 Prader-Willi syndrome Zellweger syndrome

Hypoxic ischaemic encephalopathy Cerabral malformations

Spinal muscular dystrophy Congenital myotonic dystrophy Congenital muscular dystrophies

Congenital structural myopathies

Creatine kinase assay EMG Nerve conduction studies

PRACTICAL MEASURES OF STRENGTH in infants & young children:

Head and Trunk

o Upright head stability

o Traction response.

o Independent sitting with/without hand popping.

o Ability to reach overhead without lateral popping and tilting head back.

Proximal arm strength

o Arms over head, reaching to defined height.

o Length of ball throw

o Combat crawling.

Distal arm strength ability to grasp and elevate defined objects of various size and weight.

Proximal leg strength

o Movement of leg against gravity while supine

o Kneeling and crawl.

o Gower’s manouvre

o Gait – Trendelenberg’s, waddle.

Distal leg strength

o Motion against gravity.

o Steppage gait with slapping feet.

Pattern of muscle involvement:

Proximal and axial Indicates primary muscle disease.

Pyramidal (unilateral or bilateral) Worse in the leg flexors than leg extensors. In the arm, shoulder abduction and small hand muscles may be weaker than other muscles. Found in stroke and other focal CNS disease

Distal Indicates a polyneuropathy.

Focal In the distribution of a single peripheral nerve or nerve root

Global or random Suggests non-organic illness. Try to describe the pattern and check it for consistency in repeated examinations. Consider additional clinical evidence, such as reflex or sensory findings. Often a rather random pattern actually reflects multiple nerve root involvement

Clinical features suggestive of hypotonia of central origin: • Social and cognitive impairment in addition to motor

delay

• Dysmorphic features implying a syndrome or other

organ

• malformations sometimes implying a syndrome

• Fisting of hands

• Normal or brisk tendon reflexes

• Features of pseudobulbar palsy, brisk jaw jerk,

crossed

• adductor response or scissoring on vertical

suspension

• Features that may suggest an underlying spinal

dysraphism

• History suggestive of hypoxic-ischaemic

encephalopathy, birth

• trauma or symptomatic hypoglycaemia

• Seizures

Indicators of peripheral hypotonia: • Delay in motor milestones with relative normality of

social and cognitive development • Family history of neuromuscular disorders/maternal

myotonia • Reduced or absent spontaneous antigravity

movements, reduced or absent deep tendon jerks and increased range of joint mobility

• Frog-leg posture or ‘jug-handle’ posture of arms in • association with marked paucity of spontaneous

movement • M yopathic facies (open mouth with tented upper lip,

poor lip seal when sucking, lack of facial expression, ptosis and restricted ocular movements)

• M uscle fasciculation (rarely seen but of diagnostic importance when recognized)

• Other corroborative evidence including muscle atrophy,

• muscle hypertrophy and absent or depressed deep tendon reflexes

Conditions associated with central (non-paralytic) hypotonia

Acute encephalopathies

• Birth trauma

• Hypoxic-ischaemic encephalopathy

• Hypoglycaemia

Chronic encephalopathies

• Cerebral malformations

• Inborn errors of metabolism (mucopolysaccharidoses,

aminoacidurias, organic acidurias, lipidoses, glycogen

storage diseases, Menkes syndrome)

• Chromosomal disorders (Prader-Willi syndrome,

trisomy 21)

• Genetic disorders (familial dysautonomia, Lowe

syndrome)

• Peroxisomal disorders (neonatal

adrenoleukodystrophy,

• Zellweger syndrome)

• Endocrine (hypothyroidism)

• Metabolic (rickets, renal tubular acidosis)

Investigations in cases where a central cause for hypotonia is suspected • Serum electrolytes, including calcium and phosphate,

serum

• alkaline phosphatase, venous blood gas, thyroid

function tests

• Plasma copper/caeruloplasmin assay (as screening test

for Menkes syndrome)

• Chromosomal analysis (trisomy), testing for Prader-Willi

syndrome(15q11–13)

• Plasma amino acids and urine organic acids

• Urine mucopolysaccharide screen (GAG)

• Molecular/biochemical diagnosis of pro-collagen

disorders

• Very long chain fatty acids

• Medical genetics opinion

• Ophthalmology opinion

• Brain imaging (CT/MRI)

Causes of paralytic/neuromuscular hypotonia Spinal muscular atrophy Paralytic poliomyelitis Neuropathies

• Hereditary motor-sensory neuropathy

• Congenital hypomyelinating neuropathy

• Acute demyelinating polyneuropathy Neuromuscular junction problems

• Botulism

• Transient neonatal myasthenia

• Autoimmune myasthenia

• Congenital myasthenic syndromes Muscular disorders

• Congenital myopathies (nemaline rod myopathy,

• myotubular myopathies, central core disease, minicore disease, etc)

• Congenital muscular dystrophies (CMD) (Walker-Warburg,

• Fukuyama, muscle-eye-brain disease, merosin-positive CMD, etc)

• Congenital myasthenic syndromes

• Congenital myotonic dystrophy

• Metabolic myopathies (acid maltase deficiency,

• phosphorylase deficiency, mitochondrial myopathy

• Endocrine myopathies (hypothyroidism)

Investigations of peripheral hypotonia

• Creatinine kinase

• Lactate

• EMG /NCS/repetitive nerve stimulation test

• Muscle biopsy (histology, immunohistochemistry,

electron

• microscopy, respiratory chain enzyme analysis)

• Genetic testing (SMN gene deletion present in 95%

of cases of spinal muscular atrophy type 1,

myotonic dystrophy,congenital myasthenic

syndromes)

• Nerve biopsy (rarely)

• Tensilon test (Edrophonium chloride)

Conditions where central and peripheral hypotonia may coexist • Familial dysautonomia • Hypoxic–ischaemic encephalopathy • Infantile neuroaxonal degeneration • Lipid storage diseases • Lysosomal disorders(Acid maltase deficiency) • Mitochondrial disorders • Perinatal asphyxia secondary to motor unit disease

Useful EMG features in peripheral hypotonia • EMG /NCS studies may distinguish between neurogenic,

myopathic and myasthenic aetiologies for hypotonia

• Neurogenic – large amplitude action potentials, reduced

interference pattern, increased internal instability

• Myopathic – small amplitude action potentials with increased

interference pattern

• Myotonic – increased insertional activity

• Myasthenic – abnormal repetitive and single fibre studies

SPINAL MUSCULAR ATROPHY:

SMA is a common autosommal recessive disorder characterized by muscle weakness due to

degeneration of motor neurons in spinal cord and brain stem nuclei.

Incidence

Infantile SMA – 4-10 per lakh live births.

Childhood and Adult SMA – 1 per 19,420

Genetics: Autosommal recessive can be AD, X linked or sporadic. Chromosome 5

Types:

Type I – Werdnig Hoffman disease. Onset by 6 months of age – Severe infantile form

Type II – Dubowitz disease. Onset 6-18 months – Slowly progressive form

Type III – Kugelberg Welander disease. Onset after 18 months, Chronic/Juvenile form

Variant of SMA – Fazio Londe disease – Progressive bulbar palsy

Etiology:

Pathologic continuation of a process of programmed cell death (Apoptosis), which is normal in

embryologic life. A unique mammalian gene, SMN (Survivor Motor Neuron) gene arrests

apoptosis of motor neuroblasts normally.

SMA TYPE 1

· Severe infantile hypotonia.

· Areflexia (absent DTR)

· Involvement of tongue (fasciculations), face and jaw muscles.

· No disturbance of cognition, sensation, sphincter tone and extra ocular muscles.

· Progressive limb and intercostal muscle weakness.

· Congenital joint contractures – club foot, arthrogryposis.

· Poor sucking reflex, Swallowing difficulty, tires during feeding

· Poor motor milestones of development

· Never sit without support when placed.

· Lie in frog leg position

· Fine tremors of fingers called polyminimyoclonus.

· No spontaneous movements except in hands and feet.

· Level of social interaction is unimpaired.

· Pulmonary insufficiency: intercostal muscle weakness à pectus excavatum, and flaring of lower ribs à

bell shaped deformity.

· Bilateral eventeration/paralysis of diaphragm occurs with abdominal breathing pattern.