2. OBJECTIVES
Define tone and how it is maintained
Distinguish b/w hypotonia and muscle weakness
Differences between central and peripheral causes of
hypotonia.
Differential diagnosis of hypotonia in infants
Appropriate medical and genetic evaluation
3. MUSCLE TONE AND TYPES
Muscle tone is usually defined as the resistance to passive movement.
Muscle tone is most easily shown as movement of an extremity but certainly including the trunk, neck,
back and the shoulder and pelvic girdles.
In the clinical setting we speak of 2 types of tone: phasic tone and postural tone
Phasic tone is passive resistance to movement of the extremities (appendicular structures)
Postural tone may be thought of as the resistance to passive movement of the axial muscles (neck,
back, trunk )
There may be a discrepancy between phasic tone and postural tone in a given patient.
Best example is in the 3- or 4-month-old infant who has suffered an hypoxic-ischemic insult at birth
and now has poor head and trunk control (postural hypotonia) but is beginning to become stiff
(hypertonic) in the extremities (phasic tone) and will eventually develop increased reflexes and tone
(spasticity) in the appendicular and axial muscles.
5. Motor signals are transmitted directly from
cortex to spinal cord through cortico spinal tract
Indirectly from multiple accessory pathway
involving basal ganglia, cerebelum and various
nuclei of brain stem.
Direct pathways are more concerned with
discrete and detailed movement, specially of
distal segment of limbs.
6. MOTOR UNIT
Muscle tone is maintained at the peripheral level by
participation of the fusimotor system
pathways involves the muscle spindles that promote
muscle contraction in response to stretch
inverse myotactic reflex involving the Golgi tendon
organ that provides a braking mechanism to the
contraction of muscle.
A lesion interrupting the stretch reflexes at any level in
the lower motor neuron (LMN) will result in a loss of
muscle tone and stretch reflexes i.e. flaccidity
7.
8. Hypotonia vs Weakness
Hypotonia
Is decresed resistance to passive movement around a joint
Also defined as an impairment, of the ability to sustain postural control,
and movement against gravity
Hypotonic infant may not have weakness
Central origin hypotonia – may or may not be associated with weakness
Hypotonia with pofound weakness suggest LMN cause
Weakness
has reduction in maximum power that can be generated
Weak infant many times have hypotonia
9. Because dysfunction at any level of the nervous system can cause hypotonia so D/D
is extnsive
central causes account for 60% to 70% cases
peripheral causes occur in up to 30% cases.
Central conditions include hypoxic-ischemic encephalopathy, other
encephalopathies, brain insult, intracranial hemorrhage, chromosomal disorders,
congenital syndromes, inborn errors of metabolism, and neurometabolic diseases.
Peripheral disorders include abnormalities in the motor unit, specifically in the
anterior horn cell (ie spinal muscular atrophy),
peripheral nerve (ie, myasthenia)
neuromuscular junction (ie botulism)
muscle (ie, myopathy).
Both central and peripheral manifestations such as acid maltase deficiency
(Pompe disease).
16. Differentiating Central Versus Peripheral Causes
Central
Hypotonia and do not track visually, fail to
imitate facial gestures or appear lethargic
Dysmorphic
Motor delay +Social + cognitive delay
Hypotonia with normal strength
N to brisk DTR
h/s/o HIE or birth trauma
Seizure, abn eye movement, depressed level of
consciousness
Predominant axial weakness
Fisting of hand
Persistent neonatal reflexes
brisk jaw jerk
crossed adductors / scissoring on ventral suspension
Infants who have experienced central injury usually
develop increased tone and DTR but infants who
have central developmental disorders do not
Peripheral
Alert, respond well to surrounding &
normal sleep wake cycle
Hypotonia + profound weakness
& hyporeflexia DTR / areflexia
Motor delay
Normal social & cognitive
Family history of NMD or maternal
myotonia
Reduced or absent antigravity
movement with increased range of
movement
Frogged leg posture
Fasciculations (SMA )
Muscle atrophy / pseudohypertrophy
Respiratory & feeding impairement
17.
18.
19. APPROACH
Name
Age of presentation :-
SMA type 1- 0 to 6 mth
SMA type 2 - 6 to 18 month
SMA type 3 - after 18 month
neonatal myasthenia soon after birth
juvenile myasthenia - > 6 month
Term infant who born healthy but develops
floppiness after 12 to 24 hours may have IEM
20. Chief complaints
INFANT
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
Difficult sucking, weak cry
Recurrent respiratory infection
21. Sudden onset – IVH in preterm infants
Course – progressive ( SMA )
static
fluctuating
Severity
Apnea, aspiration ( gag reflex lost )
Respiratory difficulty ( inv of resp muscles )
h/o fatigue on continious sucking – myasthenia
h/o constipation – botulinum
Distribution of weakness –
Proximal ( unable to stand from sitting ) - myopathy
Distal ( unable to hold things ) – neuropathy
Associate atrophy of muscle – myopathy, neuropathy
Muscle pain :-
Myositis
Metabolic cause
22. Joint deformity –
Arthrogyropsis
zellwegar syndrome
chromosomal disorder
CMD
transitory neonatal myasthenia
Congenital dislocation of hip – frequent finding
CNS Cause –
Seizure , abnormal movement
Lack of response to visual, auditory stimuli
MR , learning disability
Poor state of alertness
23. Antenatal history
h/o decreased fetal movements
Polyhydramnios
Drug exposure ( lithium, phenytoin, carbamzepine )
Breech delivery / prolonged labour
Post natal history
h/o birth asphyxia
Weak cry at birth
Resp distress with prolonged ventilatory support
Feeding difficulty
Convulsion
Neonatal hyperbillirubinemia
h/o honey consumption
h/o umbilical hernia, contractures , joint dislocation
Low Apgar scores may suggest floppiness from birth
24. Family History
History of consanginity – for inheritence
AD- myotonic dystrophic
AR – LGMD & metabolic myopathy
Maternal transmission – mitochondrial myopathy
Family H/O wheelchair dependent, spinal /
skeletal deformity, functional limitation, early
death, cardiac disease
25. DEVELOPMENTAL HISTORY
Assesed in all four domains
Gross motor
Fine motor
Cognitive domain
Language domain
Preserved cognition / language with Isolated motor delay –
s/o NMD
Cognitive delay / language/ speech delay with vision or
hearing impairement with seizure – s/o CNS involvement
27. Head TO Toe EXAMINATION
Assessment for dysmorphic features
Dysmorphic facies- Prader Willi syndrome
Doll like facies – Pompes disease
Downy facies – trisomy 21, Zelleweger syndrome
Anterior fontenalle - hypothyroidism
Eyes – cataract ( lowe syndrome )
Eye lid - drooping of lid ( myasthenia )
Tongue – fasciculation ( SMA )
large tongue – storage disorders ( acid maltase / pompes disease )
High arched Palate – Neuromuscular disorders
Neurocutaneous markers / facial dysmorphism – CNS involvement
Genitelia – hypogonadism ( prader willi syndrome )
undescended testis ( weakness of gubernaculum)
Limbs examination – contractures ( arthrogyropsis ).seen in both neurogenic and
myopathic disorders.
28. TONE ASSESEMENT
INSPECTION
Observe of posture of child in bed
Floppy child – frog like position ( hip abd, knee flex )
PALPATION
Feel the muscle
Normal muscle feels rubbery
Hypotonic muscle feels soft and flabby
29. Movement at joint
Freely moving joints suggest hypotonia
Examine all4 limbs, assymetry
Check trunk tone
RAG DOLL PHENOMENON
Shake limbs to & fro and observe movement of distal joint
Hypotonia – ease of movement at joint incresed
Distal limb have wooble around a joint like as ragged doll
35. DTR
Central conditions :-
DTR hyperactive
clonus and primitive reflexes persist
Peripheral disorders
DTRs are normal decreased or absent
Other pertinent findings
poor trunk extension
Astasias (inability to stand due to muscular incoordination) in supported standing
Decreased resistance to flexion and extension of the extremities.
Exaggerated hip abduction and exaggerated ankle dorsiflexion.
Abnormalities in stability and movement may manifest in an older infant as W-sitting
a wide-based gait, genu recurvatum, and hyper pronation of the feet
36. ASSESEMENT OF WEAKNESS
Assessment for weakness includes evaluating for cry, suck, facial expressions, antigravity
movements, resistance to strength testing, and respiratory effort.
1. cough test :- Ability to cough and clear airway secretions. 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.
2. Poor swallowing ability as indicated by drooling and oropharyngeal pooling of secretions.
3. Character of the cry — infants with consistent respiratory weakness have a weak cry
4. Paradoxical breathing pattern — intercostal muscles paralysed with intact diaphragm.
5. Frog-like posture and quality of spontaneous movements — poor spontaneous movements and the
frog-like posture are characteristic of LMN conditions.
Infants who can generate a full motor response when aroused are more likely to be hypotonic than
weak.
37. Spinal muscular atrophies
are a heterogeneous group of disorders, usually genetic in origin, characterized by
the degeneration of anterior horn cells in the spinal cord and motor nuclei of the
brainstem.
Presence of wasting, areflexia and fasciculation differentiates from primary muscle
disease.
Diagnosis by (PCR RFLP )- exon 7 deletion
Muscle biopsy – group atrophy with small angulated fiber
38. Congenital Myasthenia syndromes
PRESYNAPTIC ( 6 % ) SYNAPTIC (14 % ) POST SYNAPTIC ( 70 % )
Defect in ChAT
-Floppy and weak
-extraocular bulbar and
respiratory muscle affected
Episodic apnea is cardinal
feature
AR INHERITANCE
AR INHERITANCE Primary AchR defeciency
Slow channel/ fast channeL
Group of disorders arise due to genetic mutation causing critical changes in presynaptic,
synaptic or post synaptic proteins.
These disorders are non immunologic so don’t respond with immune therapy as in MG
39. Transient neonatal myasthenic syndrome
is due to the passive placental transfer of antibodies against the
acetylcholine receptor protein from the mother who has
myasthenia to her unaffected fetus.
The severity of symptoms correlates with the newborn’s
antibody concentration.
Ptosis, facial weakness, poor feeding, weak and respiratory
insufficiency since birth.
Symptoms usually occur within hours of birth or up to 3 days
later.
Although weakness initially worsens, dramatic resolution
subsequently occurs.
The duration of symptoms averages 18 days and recovery is
complete.
The transitory disorder is diagnosed by the presence of
antibodies in the infant’s blood.
40. Congenital Myotonic dystrophy
Autosomal Dominant inheritance
caused by an unstable DNA trinucleotide repeat on chromosome 19 that can expand in successive generations.
Symptoms usually begin in young adult life and include weakness of the face and distal limb muscles, cataracts,
multiple endocrinopathies, frontal baldness in males, and myotonia.
Congenital myotonic dystrophy (Steinert disease) can afflict infants born to affected mothers.
Polyhydramnios is common, labor is prolonged, and delivery usually requires mechanical assistance.
Severely affected infants have inadequate diaphragm and intercostal muscle function and require assisted
mechanical ventilation.
Perinatal asphyxia can be a consequence of a prolonged and difficult delivery and resuscitation.
Facial paralysis, generalized muscular hypotonia, joint deformities, gastrointestinal dysfunction, and oral motor
dysfunction can occur.
Affected infants have a characteristic facial appearance, with tenting of the upper lip, thin cheeks, and wasting of
the temporalis muscles. They also tend to have dislocated hips, arthrogryposis, and club feet.
Limb weakness is proximal, tendon reflexes usually are absent and myotonia may not be elicited on
electromyography (EMG).
The patients tend to have intellectual deficits.
Cardiomyopathy contributes to early death, and the long-term prognosis is poor.
Respiratory failure and an increased risk of aspiration also lead to early death.
If the infant survives the first 3 postnatal weeks, motor function may improve, although facial diplegia usually persists.
41. Severe weakness of face, jaw and elevated diaphragm with
thin ribs on chest xray clues to diagnosis
42. - myotonia examined in mother during physical examination, myotonia may be demonstrated by asking
the patient to make tight fists and then to quickly open the hands.
- It may be induced by striking the thenar eminence with a rubber percussion hammer (percussion myotonia)
and it may be detected by watching the involuntary drawing of the thumb across the palm.
-Myotonia can also be demonstrated in the tongue by pressing the edge of a wooden tongue blade against
its dorsal surface and by observing a deep furrow that disappears slowly.
45. Prader-Willi syndrome
is characterized by hypotonia, hypogonadism, intellectual disability, short stature, and obesity.
Affected patients present at birth with profound hypotonia and feeding problems until 8 to 11
months of age, when they develop low-normal muscle tone and insatiable appetites.
Prominent physical features during childhood include a narrow bifrontal diameter, strabismus,
almond-shaped eyes, enamel hypoplasia, and small hands and feet.
The genetic abnormality in 75% of patients is a deletion of the long arm of chromosome 15 at
q11-q13.
Mostly the paternally derived chromosome has been deleted.
46.
47. botulinum
Infantile botulism is an age-limited disorder in which C botulinum is ingested, colonizes the intestinal
tract, and produces toxin in situ.
h/o ingestion of honey or corn syrup is present.
Historically, infants afflicted with botulism are between 2 and 26 weeks of age.
usually live in a dusty environment adjacent to construction or agricultural soil disruption, and become
symptomatic between March and October.
A prodrome of constipation, lethargy, and poor feeding is followed in 4 to 5 days by progressive
bulbar and skeletal muscle weakness and loss of DTRs.
Progressive muscle paralysis can lead to respiratory failure.
Symmetric bulbar nerve palsies manifested as ptosis, sluggish pupillary response to light,
ophthalmoplegia, poor suck, difficulty swallowing, decreased gag reflex, and an expressionless face
are primary features of infantile botulism.
Differential diagnosis includes sepsis, intoxication, dehydration, electrolyte imbalance, encephalitis,
myasthenia gravis.
Spinal muscular atrophy type I and metabolic disorders can mimic infantile botulism. Patients who
have spinal muscular atrophy type I generally have a longer history of generalized weakness,
do not typically have ophthalmoplegia and have normal anal sphincter tone.
Treatment for infantile botulism should be instituted promptly with intravenous human botulism
immune globulin, which neutralizes all circulating botulinum toxin, and supportive therapy for airway
maintenance, ventilation, and nutrition.
Infantile botulism usually is a self-limited disease lasting 2 to 6 weeks, and recovery recovery
generally is complete,although relapse can occur in up to 5% of infants.
48. benign congenital hypotonia
The most common clinical condition, although a diagnosis of exclusion.
presents with delays in achieving developmental milestones.
Benign congenital hypotonia improves with the maturity of the central
nervous system.
Characteristics include generalized symmetric flaccidity of muscles and
hypermobile joints.
Because this is a diagnosis of exclusion, the history does not suggest any
neurologic or metabolic disorders.
Muscle stretch reflexes are normal or only slightly exaggerated and routine
laboratory test results are within normal limits.
Patients must be counseled about the possibility of joint dislocations in the
future.
An increased incidence of intellectual disability, learning disability, or other
sequelae of cerebral abnormality often is evident later in life despite the
recovery of normal muscle tone.
A high familial incidence also is reported.
49. Lab Evaluation
Rule out sepsis Full blood count , C reactive protein, Erythrocyte
sedimentation rate, Blood culture, Urine culture Cerebrospinal fluid
culture and analysis
Serum electrolytes, calcium, magnesium
Serum glucose
Liver functions / Ammonia
Thyroid function test
TORCH titre & urine C/S for CMV(organomegaly & brain calcification)
Blood Gases
If acidosis is present, plasma amino acids and urine organic acids
(aminoacidopathies and organic acidemias)
serum lactate (disorders of carbohydrate metabolism, mitochondrial
disease)
Pyruvate & ammonia (urea cycle defects)
Acyl carnitine profile (organic acidemia, fatty acid oxidation disorder )
50. If central hypotonia is suspected
MRI brain/CT brain :- structural malformations, neuronal migrational defects
Abnormal signals in the basal ganglia (mitochondrial abnormalities)
Brain stem defects (Joubert syndrome)
Deep white matter changes can be seen in Lowe syndrome
Abnormalities in the corpus callosum may occur in Smith-Lemli-Opitz synd
Karyotyping
Molecular genetics
Very long chain fatty acids (VLCFA) – peroxisomal disorders
Serum/Urine amino acids
Urine organic acids
Blood/CSF lactate
Carnitine/acylcarnitine levels
Serum Ammonia
51. If peripheral hypotonia is suspected
Creatine kinase level :- elvated in MD not in SMA
Electromyography (EMG)/Nerve conduction studies (NCS) –
may be delayd till 6 months b’se neonatal results are difficult to
interpret
Muscle biopsy – to diff b/w myopathy from muscle dystrophy,
myopathy from neuropathy
Molecular genetics – CTG repeats, SMN deletion
Toxin assay i.e. Botulism
Auto antibody level
Specific DNA testing for myoyonic dystrophy & SMA (SMN
gene )
52. Treatment
Treatment of the infant who has hypotonia must be tailored to the specific responsible condition.
In general therapy is supportive.
Rehabilitation with the aid of physical and occupational therapists.
Nutrition is of primary importance to maintain ideal body weight for the age and sex which is often
achieved through the nasogastric route or percutaneous gastrostomy.
maximize muscle function and minimize secondary crippling anatomic deformities.
Regular orthopaedic review for scoliosis and hip subluxation / dislocation is an important aspect of
management.
Vigorous therapy for respiratory tract infections and annual flu vaccinations are advised in affected
patients.
In certain conditions (muscular dystrophies, central core disease) anaesthetic complications such as
malignant hyperthermia and difficulty in reversing muscle paralysis may be an issue hence if these
patients are undergoing anaesthesia, it is imperative that the anaesthetist is informed in advance.
Genetic counselling is an important adjunct for the family.
Once a definitive diagnosis is available discussing among professionals is of paramount importance
and discussing with parents and family members about the disease and prognosis is an
important step.
Weaning off the ventilator may be an issue as there may be social and ethical considerations
involved.
Counselling on family planning and future pregnancies with appropriate genetic diagnosis would be
helpful.
55. Clinical feature of floopy infant
Frog like posture Abducted leg at hip, flexed at knee
Pull to sit Excessive head lag and rounded back
Vertical suspension Slipping through hand
Ventral suspension Ragged doll like
Drooling of secretions Poor swallowing ability
Weak cry Respiratory weakness
Paradoxical breathing Intercostal muscle paralysis with intact
diaphragm
Plagiocephaly, arthrogyropsis
Seizure, apnea, feeding problem, abnormal
posturing
Decreased fetal movement
f/s/o severe CNS abnormality
56. CLINICAL CLUES AND INVESTIGATIONS
CONDITION CLINICAL CLUES INVESTIGATION
Spinal cord transection
Syringomyelia
Spinal dysraphism
Hemangioma or tuft of hair in midline
Scoliosis
Bowel / bladder dysfunctn
Mixed DTR
(- )abdominal / anal reflex
MRI spinal cord
Spinal Muscular Atrophy Tongue atrophy / fasciculations
Severe proximal muscle weakness
Absent DTR
Preserved social interaction
- EMG/ NCV – anterior
horn cell involvement
- PCR – deletion of
SMN gene
Perpipheral neuropathy Distal weakness
Absent DTR
Pes cavus
- NCV study
- nerve biopsy
- DNA testing for
specific demyelination
disorder
57. CONDITION CLINICAL CLUES INVESTIGATION
Myasthhenia gravis - Bulbar / oculomotor muscle
involvement
- True cong myasthenia is rare
- Exclude transient neonatal from
maternal history
- Single fiber EMG
- Serum antibodies to
acetylcholine receptors
-Response to
acetylcholinesterase
-inhibitors
- Electrodiagnostic studies
Infantile botulism Acute onset descending weakness
Cranial neuropathies
Ptosis
Dysphagia
Constipation
- Isolation of organism from
stool culture
- Toxin in stool
58. CONDITION CLINICAL CLUES INVESTIGATION
Cong myotonic dystrophy - Polyhydramnios
- Decresed fetal movement
- Inverted v apperance of
mouth
- Mother can have myotonia
- Premature cataract surgery
in mother
- Slender stature
Molecular DNA test
( CTG repest )
EMG in mother
Cong muscular dystrophy
( merasinopathy /
Fukuyama MD )
- Hypotonia, weakness,
contracture
- Associated brain / eye
problem
- Brain MRI - str / white
matter abn
- Raised CK
- Muscle biopsy – merosin
stain
59. CONDITION CLINICAL CLUES INVESTIGATIONS
Cong structural myopathy Hypotonia with feeding
problem at birth
Non progressive weakness
Central core – ass with
malignant hyperthermia
Myotubular myopathy –
ptosis with extraocular palsies
Nemaline myopathy – ass
with feeding problem
- Muscle biopsy for definitive
diagnosis
- ECG
- Genetic mutation study
Pompes disease Cardiomegaly
Cardiac failue
Enalrged tongue
- Blood smear – vacuolated
lymphocyte
-Urine oligosacharides
-ECG & ECHO changes
- Acid maltase assay in
cultured fibroblast
61. TAKE HOME MESSAGE
Hypotonia is characterized by reduced resistance to passive range of motion in joints versus
weakness which is a reduction in the maximum muscle power .
(Dubowitz, 1985; Crawford,1992; Martin, 2005)
Central hypotonia accounts for 60% to 80% of cases of hypotonia whereas peripheral
hypotonia is the cause in about 5% to 20% of cases.
Disorders causing central hypotonia often are associated with a depressed level of
consciousness, predominantly axial weakness, normal strength accompanying the hypotonia,
and hyperactive or normal reflexes.
(Martin, 2005;Igarashi, 2004; Richer, 2001; Miller, 1992; Crawford, 1992; Bergen, 1985;
Dubowitz, 1985)
50% of patients who have hypotonia are diagnosed by history and physical examination alone
(Paro-Panjan, 2004)
An appropriate medical and genetic evaluation of hypotonia in infants includes a karyotype,
DNA-based diagnostic tests, and cranial imaging.
(Battaglia, 2008; Laugel, 2008; Birdi, 2005; Paro-Panjan, 2004; Prasad, 2003; Richer, 2001;)
Infant botulism should be suspected in an acute or subacute presentation of hypotonia in an
infant younger than 6 months of age who has signs and symptoms such as constipation,
listlessness, poor feeding, weak cry and a decreased gag reflex.
(Francisco, 2007; Muensterer, 2000)