Definition And Epidemiology
- Autonomic neuropathies refer to disorders involving small, lightly myelinated, or unmyelinated autonomic nerve fibers that regulate cardiovascular, gastrointestinal, genitourinary, thermoregulatory, sudomotor, and pupillary functions.
- They are classified as hereditary or acquired and may present as isolated entities or as part of a broader sensorimotor neuropathy.
- These disorders are uncommon in children but serve as important differentials in floppy infants and peripheral neuropathies.
- Hereditary forms, primarily Hereditary Sensory and Autonomic Neuropathies (HSANs), are rare, with Familial dysautonomia being the most common variant.
- Acquired forms are observed in Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), metabolic disorders, and toxic neuropathies.
Classification Of Pediatric Autonomic Disorders
| Etiology | Topography | Frequency |
|---|---|---|
| Acquired | Postural orthostatic tachycardia syndrome | Common |
| Acquired | Orthostatic intolerance without tachycardia | Common |
| Inherited | Hereditary sensory autonomic neuropathies (HSANs) | Variable |
| Inherited | Other metabolic disorders | Rare |
Pathophysiology
- Autonomic neuropathies result from damage to small unmyelinated and thinly myelinated fibers derived from neural crest cells, known as neurocristopathies.
- In hereditary forms, specific gene variants disrupt the development and maturation of peripheral nerves. For example, variants in the IKBKAP/ELP1 gene in Familial dysautonomia affect the transcription of vital neural proteins.
- Acquired forms involve immune-mediated, toxic, metabolic, or infectious damage to the autonomic nervous system.
- The resulting pathology includes a reduced number of small unmyelinated fibers, loss of myelinated fibers, and structural involvement of the dorsal root ganglia, parasympathetic ganglia, and central autonomic centres, leading to widespread autonomic failure.
Clinical Manifestations
Symptoms arise from the widespread involvement of the sympathetic, parasympathetic, and enteric autonomic nervous systems.
Organ System Involvement
| System | Characteristic Clinical Features |
|---|---|
| Cardiovascular | Postural hypotension without compensatory tachycardia, extreme hypertension and tachycardia under stress, cardiac arrhythmias, prolonged QT interval. |
| Gastrointestinal | Feeding difficulties, recurrent vomiting, gastroesophageal reflux, prominent gastric distention, constipation, diarrhoea. |
| Sudomotor And Thermoregulatory | Hyperhidrosis, anhidrosis, recurrent fevers, or hypothermia triggered by infections or environmental stress. |
| Ocular | Alacrima (absence of tears with emotional crying), corneal ulcerations secondary to decreased sensation and xerophthalmia. |
| Respiratory | Reduced physiological responses to hypoxia and hypercapnia, breath-holding spells, recurrent pneumonia, chronic lung disease. |
| Sensory | Profound insensitivity to pain, reduced temperature sensation leading to traumatic injuries and acral mutilation. |
Dysautonomic Crises
- Dysautonomic crises typically begin after 3 years of age, notably in Familial dysautonomia.
- These crises present with attacks of cyclic vomiting lasting 24-72 hours, retching, tachycardia, hypertension, profuse sweating, skin blotching, apprehension, and irritability.
- Severe gastric distention can cause abdominal pain and respiratory distress.
Diagnosis And Investigations
The diagnosis relies on combining clinical features, autonomic tests, and genetic confirmation.
- Clinical Tests: The histamine test demonstrates an absent normal axon flare response. The methacholine eye drop test utilizes 2.5% methacholine to produce miosis, indicating parasympathetic denervation.
- Electrophysiology: Nerve conduction studies and electromyography are often entirely normal because the large myelinated fibers are typically spared.
- Autonomic Testing: Includes tilt table testing, heart rate variability assessments, and sudomotor testing.
- Biopsy: Sural nerve biopsy reveals a characteristic loss of unmyelinated fibers.
- Genetic Testing: Targeted gene testing or next-generation sequencing panels confirm hereditary aetiologies like HSANs.
Management
There is no curative therapy for most hereditary autonomic neuropathies; management requires rigorous multidisciplinary supportive care.
- Systemic Support: Aggressive respiratory and gastrointestinal support is necessary to prevent aspiration and malnutrition. Gastrostomy with or without fundoplication may be required.
- Ocular Care: Continuous use of topical ocular lubricants is required for corneal protection.
- Injury Prevention: Strict protection from injuries due to profound pain insensitivity.
- Dysautonomic Crises Management: Managed utilizing centrally acting medications such as diazepam and clonidine, or carbidopa (a dopa decarboxylase inhibitor).
- Fever Management: Aggressive pharmacological and physical fever management is necessary in patients with anhidrosis.