Introduction

Hopkins Syndrome (HS) represents an exceedingly rare neurological disorder characterized by the abrupt onset of acute flaccid paralysis (AFP) typically subsequent to an exacerbation of asthma. The condition predominantly affects the pediatric population and poses significant diagnostic and therapeutic complexities due to its infrequency and an incompletely understood pathophysiology.

Historical Perspective

• Initial Description: First delineated by Hopkins et al. in 1974.
• Initially associated with status asthmaticus, though later cases linked it to milder asthma exacerbations.
• Often conceptualized as a variant of post-viral or post-infectious myelitis, exhibiting distinctive clinical features that set it apart.

Epidemiology

• Age of Onset: Primarily affects children, particularly those under the age of 10.
• Incidence: Extremely rare, with most data derived from isolated case reports or small series.
• Gender Disparity: No significant sex predilection has been established.

Pathophysiology

• Asthmatic Association: A consistent temporal relationship between asthma exacerbations and the onset of paralysis.
• Viral Triggers: Hypothesized involvement of respiratory viruses such as Enterovirus, Coxsackievirus, and Adenovirus, though no definitive causative agent has been identified.
• Autoimmune Hypothesis: Immune-mediated destruction of anterior horn cells in the spinal cord, potentially triggered by asthma-related immune dysregulation.
• Hypoxic Contribution: Hypoxia during severe asthma episodes may exacerbate neuronal injury, although the exact mechanism remains speculative.

Clinical Manifestations

Core Features

1. Acute Flaccid Paralysis (AFP):

   • Typically asymmetric, involving one or more limbs.
   • Predilection for lower limbs.
   • Paralysis characterized by flaccidity and hyporeflexia or areflexia.

2. Temporal Onset:

   • Paralysis generally manifests days to weeks following an episode of asthma exacerbation or respiratory illness.

3. Sensory Integrity:

   • Sensory examination remains normal, distinguishing HS from other forms of transverse myelitis.

4. Autonomic Involvement:

   • Rare instances of bladder or bowel dysfunction, predominantly in cases involving extensive thoracolumbar spinal segments.

Additional Characteristics

• Respiratory Precursor: Frequently preceded by a history of viral respiratory symptoms.
• Chronic Deficits: Residual limb weakness is common, often resulting in long-term disability.
• Non-Recurrence: Paralysis does not recur even with subsequent asthma exacerbations.

Differential Diagnosis

1. Acute Flaccid Myelitis (AFM): Associated with Enterovirus, featuring MRI evidence of anterior horn involvement.
2. Guillain-Barré Syndrome (GBS): Characterized by ascending paralysis, hyporeflexia, and autonomic dysfunction.
3. Transverse Myelitis: Bilateral motor and sensory involvement with MRI evidence of spinal cord inflammation.
4. Spinal Cord Infarction: Acute, asymmetric paralysis often with identifiable vascular risk factors.
5. Poliomyelitis: Rare in vaccinated populations but remains a consideration in endemic regions.

Diagnostic Evaluation

Laboratory Investigations

• Cerebrospinal Fluid (CSF):
  • Often reveals mild pleocytosis or elevated protein concentrations, though findings are non-specific.
• Virological Studies:
  • PCR testing of respiratory swabs, stool, or CSF to identify potential viral pathogens (e.g., Enterovirus).

Neuroimaging

• MRI of the Spine:
  • Variable findings; anterior horn cell involvement may be evident in cervical or thoracic regions.
  • Normal imaging does not exclude the diagnosis.

Electrophysiological Testing

• Nerve Conduction Studies (NCS):
  • Findings consistent with anterior horn cell dysfunction.
• Electromyography (EMG):
  • Evidence of denervation in affected muscle groups.

Management Strategies

Acute Management

1. Supportive Care:

   • Optimize management of respiratory complications associated with asthma.
   • Initiate physical therapy to preserve joint mobility and prevent contractures.

2. Immunomodulatory Therapies:

   • Intravenous Immunoglobulin (IVIG): Anecdotal reports suggest potential benefit.
   • Corticosteroids: Occasionally employed in cases with suspected autoimmune etiology.

3. Antiviral Agents:

   • Not routinely indicated but may be considered if virological studies identify a specific pathogen.

Chronic and Rehabilitative Care

1. Physical and Occupational Therapy:

   • Essential for functional recovery and adaptation to residual motor deficits.
   • Multidisciplinary approach to rehabilitation.

2. Orthotic Interventions:

   • Utilize braces or orthoses to enhance mobility and prevent secondary musculoskeletal deformities.

3. Psychosocial Support:

   • Address psychological and emotional challenges faced by the child and family.

Prognosis

• Motor Recovery: Highly variable, ranging from substantial recovery to significant residual deficits.
• Mortality: Rare, primarily linked to complications of severe asthma or respiratory failure.
• Chronic Disability: Limb weakness and musculoskeletal complications are common in untreated or severe cases.

Key Points

1. Recognize the temporal association between asthma exacerbations and acute flaccid paralysis.
2. Prioritize differential diagnoses that encompass AFP with and without sensory involvement.
3. Emphasize early intervention and a multidisciplinary approach to optimize long-term outcomes.
4. Encourage contributions to research to elucidate the pathophysiological mechanisms and refine therapeutic strategies.

Suggested Readings

Hopkins, I.J.. A new syndrome: Poliomyelitis-like illness associated with acute asthma in childhood. Aust Paediatr J. 1974; 10:273-276