Floppy Infant Syndrome - Pathogenesis, Causes, Clinical Features, Diagnosis and Management

Introduction:

Floppy infant syndrome refers to children with generalized hypotonia, most commonly occurring as an insult incurred during the neonatal or fetal period. It affects infants, usually below six months. It is more severe in infants less than two months. It is a potentially fatal disease caused by ingesting food contaminated by Clostridium botulinum spores.

It progresses as paralysis of the cranial nerve, which descends as symmetrical weakness of the trunk and extremities with flaccid paralysis. The disease is typically characterized by constipation, weakness, lethargy, and cranial palsies. The severity of the disease varies from mild illness to fatal diseases.

Clostridium botulinum is an anaerobic gram-positive organism that forms spores. They may survive boiling for several hours at a hundred-degree centigrade. Specific conditions for germination are mild alkalinity, warmth, and anaerobic conditions.

What Are the Prenatal Risk Factors?

Prenatal risk factors include

• History of drug or teratogen exposure.

• Presence of polyhydramnios (excess amniotic fluid around the baby inside the womb).

• Maternal diseases such as diabetes and epilepsy.

• Family history of neuromuscular diseases.

• Consanguinity (descended from same ancestors).

What Is the Pathogenesis of Floppy Infant Syndrome?

Clostridium can produce several toxins from A to G. All are neurotoxins except for C2. Each type affects different species. Toxins A, B, E, and F cause illness in humans. Toxin G has been associated with sudden death but not with neuroparalytic illness. Toxin A produces the most severe syndrome, with a maximum number of patients requiring mechanical ventilation. Toxin B produces mild diseases as compared to toxin A.

These toxins enter the bloodstream from mucosal surfaces or wounds. They bind to the presynaptic cholinergic nerve membrane, which further blocks the release of acetylcholine at the neuromuscular junction preventing muscles from contracting and resulting in symmetrical descending flaccid paralysis. It is characterized by diplopia (double vision), dysphagia (difficulty in swallowing), dry mouth, constipation, respiratory paralysis, and death.

Infants under twelve months of age are particularly susceptible to clostridium botulinum spores as their digestive tracts are not fully developed and, therefore, unable to prevent germination and subsequent toxin production in the intestines. Adults or children more than twelve months rarely develop infant botulism but may be more susceptible if they have pre-existing intestinal conditions.

What Are the Causes of Floppy Infant Syndrome?

The causes of floppy infant syndrome:

Central Nervous System:

• Perinatal asphyxia (lack of exchange of gas immediately after, before, or during birth).

• Neonatal encephalopathy (inflammation of the brain).

• Kernicterus (brain damage that results due to high bilirubin level in the baby's blood).

• Cerebral palsy.

• Intracranial hemorrhage (bleeding inside the brain).

• Chromosome abnormalities such as Down's syndrome.

• Inborn errors of metabolism such as aminoacidurias, mucopolysaccharidosis, and cerebral lipidosis.

Spinal Cord Lesions:

• Anterior cerebral horn cell disease such as Werdnig Hoffman spinal muscle atrophy, SMA 2 and 3, and myelopathies.

• Poliomyelitis (a life-threatening disease that results in physical disability caused by poliovirus).

Peripheral Nervous System:

• Acute polyneuropathy (a group of genetic diseases that causes peripheral nerve dysfunction).

• Familial dysautonomia (autonomic nervous system dysfunction that runs in the family).

• Congenital sensory neuropathy (a condition that affects sensory nerve cells during birth).

Myoneural Junction:

• Neonatal myasthenia gravis (an antibody disorder that is caused by maternal antibodies by transplacental transmission).

• Infantile botulism (an infection caused by the ingestion of the bacterium Clostridium botulinum).

Muscles:

• Muscular dystrophies (a group of diseases that results in progressive muscle weakness).

• Congenital myotonic dystrophies (progressive muscle weakness disease).

• Congenital myopathies, including central core disease and nemaline myopathies.

• Polymyositis (an abnormal inflammatory disease that results in muscle weakness of both sides of the body).

• Glycogen storage disease or Pompe's disease.

• Arthrogryposis multiplex congenita (a condition of multiple joint stiffness).

Miscellaneous:

• Protein-energy malnutrition (deficiency of macronutrients resulting in energy deficit).

• Prader-Willi syndrome (a genetic disorder that causes various physical, mental, and behavioral problems).

• Malabsorption syndrome (a condition that prohibits absorption of nutrients from the small intestine).

• Ehler-Danlos syndrome (a genetic disorder that causes skin, joint, and blood vessel disorders).

• Cutis laxa syndrome (a condition where the skin is saggy but lacks elasticity).

• Cretinism (a condition involving abnormal mental and physical maturity).

What Are the Clinical Manifestations of Floppy Infant Syndrome?

The clinical manifestations of floppy infant syndrome depend upon the severity of the disease, which includes:

• Constipation.

• Dysphagia or inability to swallow.

• Diplopia.

• Dysarthria (speech difficulty due to weakness of the muscle responsible for speech).

• Dysphonia or weakened voice.

• Ptosis (drooping upper eye lids).

• Hypotonia progresses as a generalized flaccidity.

• Respiratory compromise.

• Nausea.

• Vomiting.

• Lethargy.

• Poor feeding.

• Infants with consistent respiratory weakness have a weak cry.

• Bulbar palsies (a group of conditions that develop due damage to lower cranial nerve damage).

• Paradoxical breathing pattern as the intercostal muscles are paralyzed with the intact diaphragm.

A floppy infant's most characteristic clinical signs are

• Frog-Leg Posture: It implies reduced spontaneous movement, with the legs fully abducted and arms lying beside the body either extended or flexed.

• Pull-to-Sit Maneuver: A significant head lags on traction or pull-to-sit maneuver.

• Rag Doll Posture: Rag doll posture on ventral suspension.

• Vertical Suspension Test: It feels like slipping through the hands.

• Others: Various other findings include flat occiput, congenital dislocation of the hips, or arthrogryposis.

What Are the Lab Diagnostic Tests to Be Carried Out?

The diagnosis is confirmed by identifying the neurotoxin in the stool, serum, gastric aspirate, or suspected food. The culture of the stool or gastric aspirate takes about five to seven days. Furthermore, the botulinum toxin can be detected by various techniques, such as

• Enzyme-linked Immunosorbent Assay (ELISA): It has been developed recently to detect neurotoxins rapidly. It allows the detection of toxins within 24 hours. It is far better than the mouse test as it only requires twenty-four hours compared to the four days required for the mouse test.

What Is the Management of Floppy Infant Syndrome?

There is no treatment protocol for the disease, and it has a progressive course. The treatment mainly focuses on providing basic life support with the help of intubation and mechanical ventilation. Infants with mild symptoms require minimal or no care and should be recalled for follow-up. Infants with severe manifestations are at risk for respiratory paralysis, and their progressive loss of neurological functions can identify them.

Critically ill patients may require hospitalization for up to two to three months, and maintenance of sufficient ventilation and calorie intake plays a major role. Respiratory assistance is usually required during the first week of hospitalization. Antibiotics are generally not recommended for floppy infant syndrome as they do not have any role in the course or recovery of the disease.

The present treatment of floppy infant syndrome includes meticulous supportive care, proper nutrition, and nursing care. The prognosis of the disease is generally excellent.

What Are the Differential Diagnosis of Floppy Infant Syndrome?

The differential diagnosis includes

• Guillain-Barre syndrome (the body's immune system damages the nerves).

• Myasthenia Gravis.

• Stroke.

• Tick paralysis.

• Lambert- Eaton syndrome.

• Psychiatric illness.

• Poliomyelitis

• Drug intoxication.

• Diabetic complications.

• Central nervous system infections.

Conclusion:

Floppy infant syndrome refers to children with generalized hypotonia, most commonly occurring during the neonatal or fetal period. The diagnosis is confirmed by identifying the neurotoxin in the stool, serum, gastric aspirate, or suspected food. There is no treatment protocol, and it has a progressive course. The treatment focuses on providing basic life support with the help of intubation and mechanical ventilation.