62  Neuromuscular Disorders

Neuromuscular disorders (NMDs) encompass a wide range of conditions that affect the motor unit, the functional link between the nervous system and muscles responsible for movement. They are characterized primarily by muscle weakness, hypotonia, and impaired motor development. These disorders may be inherited or acquired, acute or chronic, and involve any level of the motor pathway from the anterior horn cell in the spinal cord to the muscle fiber itself.

In Ghana and other sub-Saharan African countries, neuromuscular disorders are often underdiagnosed or misdiagnosed due to limited access to electrophysiological, genetic, and imaging studies. Nonetheless, careful clinical assessment can identify most cases early and guide appropriate referral and management.

62.1 Common Terminologies

Understanding basic terms is crucial for describing and classifying neuromuscular disorders:

• Motor unit: The combination of a motor neuron, its axon, and all the muscle fibers it innervates.
• Hypotonia: Reduced muscle tone leading to floppiness and poor resistance to passive movement.
• Weakness: Reduction in the ability to generate voluntary muscle force.
• Fatigability: Diminished ability to sustain muscle contraction during repeated or prolonged activity.
• Atrophy: Loss of muscle bulk, usually due to disuse or denervation.
• Fasciculations: Fine, involuntary muscle twitches visible under the skin, often seen in anterior horn cell disease.
• Pseudohypertrophy: Apparent muscle enlargement due to fatty or fibrous replacement, as in Duchenne muscular dystrophy.
• Myopathy: Primary disorder of the muscle fiber.
• Neuropathy: Disease of peripheral nerves.

62.2 Common Presentations

Children with neuromuscular disorders may present in various ways depending on the site and nature of pathology. Typical features include:

• Delayed motor milestones – not sitting, standing, or walking at expected ages.
• Hypotonia – often noted at birth or during infancy (“floppy baby”).
• Muscle weakness – proximal (difficulty rising from sitting) or distal (foot drop).
• Reduced or absent deep tendon reflexes.
• Gait abnormalities – waddling or high-stepping gait.
• Cranial nerve involvement – facial weakness, ptosis, difficulty swallowing.
• Respiratory distress – due to diaphragmatic or intercostal weakness.
• Skeletal deformities – scoliosis, contractures.

A key clinical clue is that cognition and sensation are usually preserved in primary muscle diseases but may be affected in neuropathies or central lesions.

62.3 The Floppy Infant Syndrome

Definition:
The term “floppy infant” describes a neonate or young infant with decreased resistance to passive movement of limbs and trunk due to hypotonia.

62.3.1 Causes

Floppiness may be due to central or peripheral causes:

• Central (CNS): Hypoxic-ischemic encephalopathy, intracranial hemorrhage, metabolic encephalopathy, chromosomal syndromes (e.g., Down syndrome, Prader–Willi).
• Peripheral: Disorders of the motor unit — anterior horn cell (SMA), peripheral nerves, neuromuscular junction (congenital myasthenic syndrome), or muscle (congenital myopathy, muscular dystrophy).

62.3.2 Clinical Features

• Frog-leg posture.
• Head lag on traction.
• Poor spontaneous movement but preserved alertness (suggesting peripheral cause).
• Weak cry and suck.
• Respiratory difficulty in severe cases.

62.3.3 Evaluation

• Assess tone, reflexes, and antigravity movement.
• Presence of brisk reflexes suggests central cause; diminished reflexes indicate peripheral lesion.
• Look for dysmorphic features or systemic illness.

62.4 Site of Lesion

Neuromuscular disorders are localized anatomically by identifying where in the motor unit the pathology lies:

Level of Lesion	Examples	Characteristic Features
Anterior horn cell	Spinal muscular atrophy, poliomyelitis	Flaccid weakness, fasciculations, atrophy, absent reflexes
Peripheral nerve	Guillain–Barré syndrome, Charcot–Marie–Tooth disease	Distal weakness, areflexia, sensory loss
Neuromuscular junction	Myasthenia gravis, botulism	Fatigable weakness, normal reflexes, cranial involvement
Muscle	Muscular dystrophies, congenital myopathies, dermatomyositis	Proximal weakness, preserved sensation, normal or reduced reflexes

Accurate localization is the first step in diagnosis and guides further investigations such as electromyography (EMG) and genetic testing.

62.5 Specific Neuromuscular Disorders

62.5.1 Spinal Muscular Atrophy (SMA)

A genetic disorder caused by homozygous deletion or mutation of the SMN1 gene, leading to degeneration of anterior horn cells.

Clinical Types:

• Type I (Werdnig–Hoffmann): Onset before 6 months, severe hypotonia (“floppy infant”), poor feeding, respiratory distress, early death.

• Type II: Onset 6–18 months; able to sit but not walk unaided. - Type III (Kugelberg–Welander): Late onset; mild weakness, able to walk initially.

Investigations: EMG (denervation), genetic testing.
Management: Supportive care, respiratory support, physiotherapy, new therapies (nusinersen, gene therapy) where available.

62.5.2 Poliomyelitis

A viral infection caused by poliovirus that selectively destroys anterior horn cells. Though now rare due to immunization, sporadic cases or vaccine-derived poliovirus can still occur.

Clinical features: - Fever and malaise followed by asymmetric, flaccid paralysis. - No sensory loss. - Reflexes absent in affected limbs.

Diagnosis: Isolation of poliovirus from stool or throat swabs.
Prevention: Oral and inactivated polio vaccines (OPV and IPV).
Public health relevance: Surveillance is vital as Ghana remains part of the global polio eradication initiative.

62.5.3 Guillain–Barré Syndrome (GBS)

An acute, immune-mediated demyelinating polyneuropathy, often post-infectious.

Presentation:

• Rapidly progressive, symmetrical ascending weakness.
• Areflexia.
• May involve respiratory and autonomic dysfunction.

Investigations:

• CSF: High protein, normal cells (albuminocytologic dissociation).
• Nerve conduction studies: Demyelination.

Management:

• Supportive care and monitoring for respiratory failure.
• IV immunoglobulin (IVIG) or plasmapheresis.

Prognosis: Good in children; most recover fully.

62.5.4 Charcot–Marie–Tooth Disease (CMT)

A hereditary motor and sensory neuropathy caused by demyelination or axonal degeneration.

Features:

• Distal weakness (especially peroneal muscles).
• Foot drop and high-arched feet (pes cavus).
• Reduced reflexes and distal sensory loss.
• Slowly progressive.

Diagnosis: Nerve conduction studies, genetic testing.
Management: Supportive — physiotherapy, orthotics, and counseling.

62.5.5 Myasthenia Gravis

An autoimmune disorder affecting the neuromuscular junction, where antibodies attack acetylcholine receptors.

Features: - Fluctuating weakness, worsening with exertion. - Ptosis, diplopia, facial weakness. - Bulbar symptoms (dysphagia, dysarthria). - Normal sensation and reflexes.

Diagnosis: Edrophonium test, AChR antibodies, EMG.
Treatment: Pyridostigmine, corticosteroids, thymectomy in selected cases.

62.5.6 Duchenne Muscular Dystrophy (DMD)

An X-linked recessive myopathy due to absence of dystrophin protein.

Features:

• Onset at 2–5 years.
• Progressive proximal weakness, calf pseudohypertrophy.
• Gowers’ sign (using hands to “walk up” thighs).
• Wheelchair-bound by early teens.
• Cardiomyopathy and respiratory failure later.

Investigations: Markedly elevated CK, genetic confirmation.
Management: Corticosteroids, physiotherapy, cardiac and respiratory care.

62.5.7 Congenital Myopathies

A group of inherited disorders characterized by structural defects in muscle fibers (e.g., nemaline, central core, myotubular myopathy).

Features:

• Neonatal hypotonia (“floppy infant”).

• Delayed motor milestones.

• Facial and ocular weakness.

Usually non-progressive or slowly progressive. Diagnosis is confirmed by muscle biopsy and genetic analysis.

62.5.8 Metabolic Myopathies

Caused by enzyme defects in muscle metabolism (e.g., glycogen storage diseases, fatty acid oxidation defects).

Features:

• Exercise intolerance.
• Recurrent rhabdomyolysis or myoglobinuria.
• Hypoglycemia in systemic types.

Management focuses on dietary modification and avoiding fasting or strenuous exercise.

62.5.9 Dermatomyositis

An autoimmune inflammatory myopathy affecting both skin and muscle.

Features:

• Symmetrical proximal weakness.
• Heliotrope rash (purple discolouration of eyelids).
• Gottron’s papules (over knuckles).
• May involve myocardium and lungs.

Investigations: Elevated CK, EMG, muscle biopsy, autoantibody screen.
Treatment: Corticosteroids, immunosuppressants, physiotherapy.

62.6 Acute Flaccid Paralysis (AFP)

62.6.1 Case Definition

Acute flaccid paralysis is defined as sudden onset of weakness or paralysis in a child under 15 years, with reduced or absent muscle tone and reflexes. It includes poliomyelitis and non-polio causes such as Guillain–Barré syndrome and transverse myelitis.

62.6.2 Differential Diagnosis

• Poliomyelitis
• Guillain–Barré syndrome
• Transverse myelitis
• Traumatic neuritis
• Myasthenia gravis
• Botulism

62.6.3 Public Health Importance

AFP surveillance is central to polio eradication efforts.

• Every case of AFP must be reported within 24 hours to health authorities.
• Stool specimens (two within 14 days of onset) are collected for viral isolation.
• Early detection enables rapid outbreak response and immunization campaigns.

In Ghana, AFP surveillance has been instrumental in maintaining polio-free certification and detecting vaccine-derived strains.

62.7 Summary and Key Points

• Neuromuscular disorders affect any part of the motor unit, causing weakness and hypotonia.
• Careful clinical localisation is essential since advanced diagnostics are often unavailable.
• Common disorders in children include SMA, DMD, GBS, and myasthenia gravis.
• The floppy infant syndrome is a key early presentation of several NMDs.
• Acute flaccid paralysis remains a notifiable condition due to its link with polio surveillance.
• Multidisciplinary care, physiotherapy, respiratory and nutritional support—is crucial to improving outcomes.

62.8 References

1. Mah JK. Overview of neuromuscular disorders in children. Paediatr Child Health. 2017.
2. Pearn J. Neuromuscular disorders in childhood. J Child Neurol. 2003.
3. WHO. Acute Flaccid Paralysis Surveillance and Polio Eradication Guidelines. 2022.
4. Bushby K et al. Diagnosis and management of Duchenne muscular dystrophy. Lancet Neurol. 2010.
5. Ghana Health Service. Guidelines on Child Neurology and Disability Care, 2022.