Cracking code of theory: Hypotonic infant

by Ranjith Kumar CS
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 :

1. Determine age of onset (it may distinguish between congenital and aquired aetiologies), mode of
onset, presenting complaints, rapidity of progression.

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


Antenatal History:

1. Decreased fetal movements and polyhydramnios (due to intrauterine swallowing
difficulty) seen in SMA.

2. Breech presentation (The incidence of breech presentation is higher in fetuses with
neuromuscular disorders as turning requires adequate fetal mobility).

Perinatal History: 

1. Birth weight, hypoxia, sepsis
2. 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
3. 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

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 180 degree 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:

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:
Hypotonia
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









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.

SMA TYPE II

·         Achieve normal milestones upto 6-8 months of age.
·         Legs tend to be more involved than arms à failure to walk.
·         Able to sit without support when placed in position.
·         Sitting, standing, walking is delayed. Walking is always temporary.
·         Many survive to 3rd or 4th decade.sma ii
·         Scoliosis is the major complication
·         Nasal speech and swallowing problems develop later

SMA TYPE III : mildest form of SMA.

·         Onset any time after 18 months of age.
·         Between 12months to 3 yrs of age- SMA type 3a
·         3 years of age – SMA 3 b.
·  Proximal muscle weakness involving the shoulder girdle (25% have muscular hypertrophy).
·         Fasciculations in deltoid, biceps brachii and quadriceps femoris.
·         Affected children have h/o normal motor milestones and walking until they begin to fall.
·         Some may appear very thin like ‘stick man’.

LABORATORY DIAGNOSIS

1)      GENETIC TESTING: Sensitivity is 96%, 94% &82% in SMA 1, 2 and 3.
2)      SERUM CREATININE KINASE: Normal in SMA 1 &2, Increased in SMA 3.
3)  NERVE CONDUCTION STUDIES – Mildly reduced compared muscle action potential amplitudes and velocities. Normal distal latencies.
4)  MUSCLE BIOPSY: neurogenic large group atrophy with evidence of type group. Characteristic pattern of perinatal denervation.

COMPLICATIONS:

1) Restrictive lung disease, Respiratory Insufficiency may occur during sleep; responds to ventilation.
2) Failure to thrive – in infants; exacerbates weakness, fatigue, decreases reserve.
3) Constipation
4) Orthopedic deformities – club foot, kyphoscoliosis, flexion contractures.
5) Psychosocial dysfunction.

MANAGEMENT
No effective therapy.

Motor neurotrophic agents – Recently, Gabapentin – glutamate inhibitor used.

Other drugs – riluzole, Calpase inhibitor
Survival in  SMA 1: 80% die by 1 year; remaining by 2 year
                      SMA 2: 68.5% survives to 25 years.
                      SMA 3: 70% of them are still walking at 10 years of age.

Prevention and treatment of complications

o   Poor Nutrition and FTT complicates due to weak sucking reflex, aspiration, easy fatiguability
o   Feeding evaluation should be done.
o   Barium Swallow radiography using modified approach or Video fluoroscopy is useful in ascertaining need for gastrostomy feeding.
o   Orthopedic problems should be corrected by scoliosis, club foot deficits and contractures.

Genetic Counselling

Once diagnosis is made by genetic testing, do Genetic counselling 98% parents will be carriers with 25% chance for the next sibling to be symptomatic and 50% chance for the carrier state.

Clinical feature
Atonic CP
Werdning Hoffman disease
Antenatal history
Perinatal hypoxia
Polyhydromnios,decreased fetal movements
Developmental delay
global
Motor only
posture
Fisted hands
Frog like
Fasciculations
absent
Present
DTR
Exaggerated
Absent
Superficial reflexes
absent
Present
Microcephaly , MR,Seizures
May be present
absent
Respiratory muscle involvment
rare
Common
Primitive reflex
Present
Absent
Voice
Normal
Feeble ( Dysphonic)
Cardiomegaly
Rare
Often
Autonomic nervous system
Not pronounced
More pronounced

Principles of management:

      Physiotherapy - stretches aimed at prevention of contractures
      Occupational therapy - appliances, improvement of posture and function, facilitating activities of daily living
      Prevention and correction of scoliosis
      Evaluation and treatment of associated cardiac dysfunction
      Respiratory support - assessment of requirement for invasive or non-invasive ventilation and/or tracheostomy
      Feeding - nasogastric feeding, caloric supplementation, gastrostomy
      Management of gastro-oesophageal reflux - medical or fundoplication
      Orthopaedic intervention in setting of established or evolving joint contractures
      Encouragement of overall development and stimulation of learning
      Prevention (influenza and pneumococcal vaccination) and prompt treatment of respiratory infections

About Dr Ranjith kumar CS

He is Currently persuing DM in medical oncology from JIPMER, completed DNB  from  Kanchi Kamakoti Child Trust Hospital with a GOLD MEDAL in his hand, has great academic
interests and contributed  about 9 chapters in  scott  pediatriks clinical methods in 3rd edition as author and is one of the co-author at dnbpediatrics.com
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