9/5/2022 ‫كلية طب نينوى‬

‫علي عادل الحيالي‬.‫د‬

‫أطفال‬ CNS)5( ‫محاضرة‬

FLOPPY INFANT SYNDROME (HYPOTONIA IN INFANTS)

FLOPPY INFANT

Refers to those children presenting with generalized hypotonia, most often due to an insult
occurred during fetal or neonatal period.

 In early infancy, there is decreased muscular activity, both spontaneous and in

response to passive motion.
 In older infants, there will be delay in motor milestones.

Signs:
1. Frog like posture
2. Marked head lag is characteristic of the floppy infant.
The normal infant attempts to keep the head in the same plane as the body when pulled up from
supine to sitting by the hands (traction response).
3. Slipping during axillary suspension: suspend infant by holding at axilla and lifting; hypotonic
babies will slip through the grasp because of low shoulder girdle tone
4. Inverted U shape on ventral suspension : ventral suspension, infant is prone and supported
under the abdomen by one hand , normally results in the infant's holding its head slightly up (45
degrees or less), the back straight or nearly so, the arms flexed at the elbows and the knees
partly flexed, while the hypotonic infant will assume the Inverted u shape.
5. There is diminished resistance to passive movement of the limbs: pull to sit and look for
flexion of arms to counteract traction.
6. Scarf Sign: Put the child in a supine position and hold one of the infant’s hands. Try to
put it around the neck as far as possible around the opposite shoulder. Observe how far
the elbow goes across the body. In a floppy infant, the elbow easily crosses the midline.

Etiology:

A. Central hypotonia(UMN)
 chromosomal (e.g. Down syndrome, Prader-Willi)
 metabolic (e.g. hypoglycemia, kernicterus)
 perinatal problems (e.g. asphyxia, ICH, Inborn error of metabolism)
 endocrine (e.g. hypothyroidism, hypopituitarism)
 infections (e.g. TORCH, Sepsis)
 CNS malformations
 dysmorphic syndromes
  In central type ,weakness is uncommon except in the acute stages,and usually it is axial
weakness.
 Hyperreflexia may presnt in CNS causes.
 Other clinical features may presnt as: impairment in level of consciousness(Awareness
not intact),
 seizures, apneas, feeding difficulties, abnormalities of ocular movements
 Dysmorphic features suggest a genetic cause
 Persistent fisting of the hands

B. Peripheral hypotonia(LMN)
 Motor neuron (e.g. spinal muscular atrophy, polio)
 Peripheral nerve (e.g. Guillain-Barré)
 Neuromuscular junction (e.g. myasthenia gravis)
 Muscle fibers (e.g. muscular dystrophy, myotonic dystrophy)

 This type is characterized by the presence of profound weakness as well as

hypo/areflexia.
 Infants are visually quite alert
 Involvement of bulbar and occulomotor muscles
 Poor anti-gravity movements

Investigations
A- Evaluation of central CNS disorders
 Brain MRI
 EEG
 Genetic tests
 Infection screen
 CSF neurotransmitters
B- Evaluation of motor unit disorders
 DNA-based testing
 Edrophonium chloride test
 Electrophysiological study
 EMG
 NCS
 Repetitive stimulation
 Muscle biopsy
 Nerve biopsy
 Serum CK

Spinal Muscular Atrophy (SMA)

  Progressive degeneration and loss of the anterior horn cells (i.e., lower motor neurons) in
the spinal cord and sometimes in the brainstem nuclei.
 This disorder is usually autosomal recessive.
 It is the 2nd most common neuromuscular disease, following Duchenne muscular
dystrophy.
 The incidence of SMA is 10–15 per 100,000 live births
 Presentation is with weakness, wasting and absent reflexes
 SMA is classified into :
1) SMA type 1: Severe infantile form, also known as werdnig-Hoffmann disease
2) SMA type 2: Late infantile and more slowly progressive form
3) SMA type 3: More chronic or juvenile form, also called Kugelberg-Welander
disease

Etiology: the survivor motor neuron gene 1 (SMN-1) on chromosome No.5, encodes for SMN
protein which is responsible for arresting apoptosis of motor neuroblasts . Loss or mutation of
the two copies of this gene (homozygous) result in a pathologic continuation of the process of
programmed motor neuroblasts death (apoptosis) that is normal in embryonic life.

Spinal muscular atrophy type 1 (Werdnig-Hoffmann disease)

The cardinal features of SMA type 1 are:

 severe hypotonia
 Generalized weakness, difficulty sucking or swallowing, poor feeding
 Thin muscle mass
 Absent tendon reflexes
 Involvement of the tongue, face, and jaw muscles; and sparing of extraocular muscles
and sphincters.
 Diaphragmatic involvement is late.
 Bell-shaped torso (caused by using only abdominal muscles for respiration).
 Loss of strength of the respiratory muscles: weak cough, weak cry , accumulation of
secretions in the lungs or throat, respiratory distress
 fasciculation of the tongue.
 Infants who are symptomatic at birth may have respiratory distress and are unable to
feed.
 These children never sit unaided. More than ⅔ die by 2 yr of age, and many die early in
infancy.
 The heart is not involved in SMA and they have normal mentality , language &sensation
 Cause of death: respiratory infection , respiratory failure.
 Investigations:
1) Electromyography (EMG) :shows signs of denervation of muscle.
2) Genetic marker for the SMN gene The most definitive diagnostic test is a molecular
DNA probes in blood samples or in muscle biopsy or chorionic villi tissues
3) Muscle biopsy reveals a characteristic pattern of perinatal denervation that is unlike
that of mature muscle.
4) The serum creatine kinase (CK) level may be normal, but more commonly is mildly
elevated

 There are milder forms of the disorder with a later onset. Children with type 2 spinal
muscular atrophy can sit, but never walk independently. Those with type 3 (Kugelberg-
Welander) do walk and can present later in life.

 Treatment :

 Supportive therapy includes respiratory care, orthopedic care with particular

attention to scoliosis and joint contractures, mild physiotherapy, and mechanical aids
for assisting the child to eat and to be as functionally independent as possible.
 Prenatal diagnosis should be offered to families with an index patient in the family
(recurrence risk is 25%), and antenatal screening by chorionic villus sampling
between the 10th and 12th gestational week of pregnancy may serve for SMN1
deletion/mutation analysis.
 Pharmacotherapy: it is proved that these drugs can improve survival rate and
promotes motor functioning
a) Nusinersen (Spinraza ™ )(SMN-antisense oligonucleotide (ASO)): administered
intrathecally and it is approved for all types of SMA patients. It modifies the
splicing of SMN2 gene.
Treatment with Nusinersen begins with 4 loading doses. The first 3 doses are
administered at 14-day intervals. The fourth dose should be administered 30 days
after the third dose. After the starting dose period, a dose should be administered
once every 4 months.
b) Zolgensma™ (onasemnogene abeparvovec-xioi): it is the second approved drug
for treating SMA; it is given as a single dose IV infusion for patients who are under
2 years of age at the time of dosing. It is highly expensive gene therapy work by
infecting the patient with adeno virus (vector) which carry a functioning SMN1
gene.
Duchenne muscular dystrophy
Is the most common hereditary neuromuscular disease. The incidence is 1 : 3,600 liveborn
infant boys.

Etiology :

 X-linked recessive
 The disease results from absence of a large protein called dystrophin

Clinical Manifestations :

 Infant boys are rarely symptomatic at birth or in early infancy.

 Early gross motor skills, such as rolling over, sitting, and standing, are usually achieved
at the appropriate ages or may be mildly delayed
 Walking is often accomplished at the normal age of about 12 mo
 Poor head control in infancy may be the 1st sign of weakness
 Most clinical features starts at 2-3yr with abnormality of the gait and running , Toddlers
may assume a lordotic posture when standing to compensate for gluteal weakness.
 Cardiomyopathy, including persistent tachycardia and myocardiac failure, is seen in 50–
80% of patients with this disease.
 mild Intellectual impairment and learning disabilities occurs in all patients
 Death occurs usually at about 18–20 yr of age. The causes of death are:-

 respiratory failure in sleep

 intractable heart failure
 pneumonia
 occasionally aspiration and airway obstruction.

 Examination shows:
– Calf hypertrophy.
– waddling gait and lordotic posture
– Early Gowers sign is often evident by age 3 yr and is fully expressed by age 5 or 6
yr(The child typically arises from a lying position on the floor by using his arms to
"climb up" his legs and body )
– Weakness progress to involve the arm and the child become confined to wheelchair
at 10-12 yrs

Laboratory and Diagnostic Studies :

  the serum CK level is greatly elevated in DMD , 15000-35000IU/L (normal <160
IU/L).
 Blood PCR for the dystrophin gene is the primary test.
 Muscle biopsy specimen shows muscle fiber degeneration and regeneration.
 Cardiac assessment by echocardiography, ECG, and CXR is essential and should be
repeated periodically.

Treatment :

 Supportive care includes physical therapy, bracing, proper wheelchairs, and

prevention of scoliosis.
 Cardiac decompression often respods well to digoxin
 Glucocorticoids decrease the rate of apoptosis or programmed cell death of
myotubes ,prednisone (0.75 mg/kg/day) for the 1st 10 days of each month to avoid
chronic complications.
 Pulmonary infections should be promptly treated.
 Immunization for influenza virus and other routine vaccination are indicated.

 Becker muscular dystrophy: is the same fundamental disease as Duchenne

dystrophy, with a genetic defect at the same locus, but clinically it follows a milder
and more protracted course

Myasthenia Gravis
Etiology:

The classical juvenile myasthenia gravis occurs in late infancy and childhood is an acquired
autoimmune condition in which antibodies directed to the acetylcholine receptors at the
neuromuscular junction which leads to damage to the neuromuscular junction.

Clinical Manifestations :

– Classic myasthenia gravis may begin in the teenage years with the onset of ptosis,
diplopia, ophthalmoplegia, and weakness of extremities, neck, face, and jaw.
– The symptoms are less prominent on awakening in the morning and worsen in the end
of the day or with exercise.
 – In some children, the disease never advances beyond ophthalmoplegia and ptosis
(ocular myasthenia).
– Others have a progressive and potentially life-threatening illness that involves all
musculature, including that of respiration and swallowing (systemic myasthenia)

Diagnostic Studies:

1) The diagnosis is confirmed with IV Edrophonium Chloride (Tensilon test), which

transiently improves strength and decreases fatigability.
2) Antiacetylcholine receptor antibodies often can be detected in the serum.
3) Repetitive nerve stimulation shows a decremental response.

Treatment:

 Acetylcholine esterase inhibitors (pyridostigmine).

 Thymectomy.
 Prednisone & immunosuppressive agents.
 Plasmapheresis & intravenous immune globulin (IVIG).
 When respiration is compromised, immediate intubation and admission to an ICU are
indicated.

NEONATAL TRANSITORY MYASTHENIA GRAVIS

 A transitory myasthenic syndrome develops in 10% to 20% of neonates born to mothers
with myasthenia gravis.
 Symptoms persist for 1 to 10 weeks (mean, 3 weeks).
 Almost all infants born to mothers with myasthenia have antiacetylcholine receptor
antibody
 Symptoms and signs include ptosis, ophthalmoplegia, weak facial movements, poor
sucking and feeding, hypotonia, and variable extremity weakness.
 The diagnosis is made by showing clinical improvement lasting approximately 45 minutes
after intramuscular (IM) administration of neostigmine methylsulfate, 0.04 mg/kg.
Treatment with oral pyridostigmine or neostigmine 30 minutes before feeding is
continued until spontaneous resolution occurs.

Juvenile Dermatomyositis (JDM)

JDM is the most common pediatric inflammatory myopathies.

Etiology:

 inflammatory pathway may be driven by the interaction of genetic predisposition with

antigen stimulation and other environmental factors leading to disease.
  A history of infection in the 3 mo before disease onset is obtained in most affected
children upper respiratory symptoms predominate, but ⅓ may have had
gastrointestinal symptoms.

Epidemiology:

– JDM can occur in all age groups with a peak incidence between 4 to 10 years.
– The disease is more common in girls than boys (girls to boys ratio is 2:1)

Clinical Manifestations:

 Dermatomyositis tends to present in a slow, progressive fashion, with insidious onset of

fatigue, malaise, and progressive muscle weakness, accompanied by low-grade fevers
and rash.
 The muscle disease of JDM primarily affects the proximal muscles, particularly the hip
and shoulder girdles, and the abdominal and neck muscles. Children have difficulty
climbing steps, combing hair,getting out of chairs, and getting off the floor. The patient
may have a positive Gower sign. In severe cases, the patient is not able to sit up from a
supine position.
 A classic JDM rash occurs on the face and across the cheeks Patients may have
heliotrope (violaceous) discoloration of the eyelids. Scaly, red plaques (Gottron
papules) classically are found across the knuckles but can be found on the extensor
surfaces of any joint .

Clinical Manifestations:

 If muscles of the upper airway and pharynx are involved, the patient's voice will sound
nasal and the patient may have difficulty swallowing.
 15% of patients with JDM develop arthritis, commonly affecting small joints
 Cardiac involvement with conduction abnormality is frequent at diagnosis.
 Dystrophic calcification can occur in the skin and soft tissues in any area of the body.

Laboratory and imaging studies:

 Elevated serum levels of muscle enzymes as creatine kinase (CK)

 ESR is usually normal and the rheumatoid factor is negative.
 Muscle biopsy often demonstrates evidence of disease activity and chronicity.
 Electromyogram (EMG)
 MRI :localizes the active site of disease for diagnostic muscle biopsy and
electromyogram. Sometimes X-ray can show the calcifications sites in chronic cases.
Treatment:

– Initial treatment with pulse intravenous methylprednisolone is followed by several

months of tapering doses of oral prednisone
– Early institution of methotrexate significantly decreases the duration of corticosteroid
use and its associated toxicities
– In severe or refractory cases, it may be necessary to use cyclosporine or
cyclophosphamide.
– All children with JDM should avoid exposure to sun and also use a sunscreen, even in
the winter.

Prognosis

 The outcome of JDM depends greatly on the extent of muscle disease and the time
between disease onset and initiation of therapy. JDM follows one of three clinical
courses:
1. A monophasic course, in which patients are treated and improve without significant
sequelae
2. A chronic recurrent course
3. chronic progressive course marked by poor response to therapy and resulting loss of
function.

Metabolic Myopathies

 Glycogen storage disease type II (Pompe disease) and muscle carnitine deficiency
 Mitochondrial myopathies: Typical symptoms include hypotonia, ophthalmoplegia, and
progressive weakness.
 Endocrine myopathies: including hyperthyroidism, hypothyroidism,
hyperparathyroidism, and Cushing syndrome, are associated with proximal muscle
weakness
 Hypokalemia and hyperkalemia produce fluctuating weakness (periodic paralysis) and
loss of tendon jerks.

Congenital Myopathies

 Nemaline myopathy
 Central core disease
 Myotubular myopathy
 Congenital fiber type disproportion myopathy
 Multicore myopathy