What are the types of Anterior Horn Cell (AHC) disorders?

Types of Anterior Horn Cell Disorders

Anterior horn cell (AHC) disorders are characterized by degeneration of motor neurons in the anterior horn of the spinal cord, leading to progressive muscle weakness, atrophy, and significant impacts on morbidity and mortality.

Major Categories of Anterior Horn Cell Disorders

Amyotrophic Lateral Sclerosis (ALS)

• ALS is the most common motor neuron disease, representing approximately 85% of all cases with an annual incidence of 1-2/100,000 and median survival of 3-4 years after symptom onset 1
• Characterized by degeneration of both upper and lower motor neurons, resulting in hypertonicity and hyperreflexia (upper motor neuron signs) along with muscle fasciculations, weakness, and atrophy (lower motor neuron signs) 1
• Riluzole is FDA-approved for treatment of ALS with a recommended dosage of 50 mg taken orally twice daily 2

Spinal Muscular Atrophy (SMA)

• Classified into several types based on age of onset and severity:
  • SMA Type I (Werdnig-Hoffmann disease): Severe infantile form with onset before 6 months 3
  • SMA Type II: Intermediate form with onset between 6-18 months 1
  • SMA Type III (Kugelberg-Welander disease): Mild juvenile form 1
  • SMA Type IV: Adult-onset form 1
• Risdiplam is an FDA-approved treatment for SMA that has shown significant improvement in motor function and survival without permanent ventilation in infantile-onset SMA patients 4
• Pre-symptomatic treatment with risdiplam in genetically diagnosed infants has shown promising results 4

Progressive Muscular Atrophy (PMA)

• A variant of ALS affecting only lower motor neurons 1
• Characterized by progressive muscle weakness and atrophy without upper motor neuron signs 1

Primary Lateral Sclerosis (PLS)

• A variant of ALS affecting only upper motor neurons 1
• Characterized by progressive spasticity and hyperreflexia without lower motor neuron signs 1

Progressive Bulbar Palsy (PBP)

• A variant of ALS primarily affecting bulbar muscles 1
• Characterized by dysarthria, dysphagia, and tongue fasciculations 1

Kennedy's Disease (Spinal and Bulbar Muscular Atrophy)

• X-linked recessive disorder characterized by slowly progressive weakness and atrophy of bulbar and limb muscles 1
• Distinguished from other AHC disorders by sensory nerve conduction abnormalities 1

Poliomyelitis

• Viral infection affecting anterior horn cells 1
• Unlike other AHC disorders, it is not progressive after the acute phase 1

Anterior Horn Cell Disease with Olivopontocerebellar Hypoplasia

• Rare disorder with fewer than 30 reported cases 3
• Characterized by progressive spinal muscular atrophy similar to Werdnig-Hoffmann disease, with hypoplasia of olivary nuclei, pons, and cerebellum 3
• May present with additional features such as dysmorphism, abnormal eye movements, stridor, congenital joint contractures, and enlarged kidneys 3

Diagnostic Features

Electrodiagnostic Findings

• Motor nerve conduction studies may be normal or show low compound muscle action potential (CMAP) amplitudes with relatively normal conduction velocities 1
• Sensory nerve conduction studies are typically normal (except in Kennedy's disease) 1
• Needle electromyography (EMG) shows:
  • Abnormal spontaneous activity including fibrillation potentials and positive sharp waves 1
  • Fasciculation potentials and complex repetitive discharges 1
  • Abnormal motor unit morphology with polyphasic motor units and large amplitude/duration motor unit action potentials (MUAPs) in slowly progressive disease 1
  • Reduced recruitment with abnormally rapidly firing motor units 1

Imaging Findings

• MRI of the head without IV contrast is usually appropriate for the initial imaging of patients with suspected motor neuron disease 5
• MRI of the spine without IV contrast may be appropriate for certain patients with suspected motor neuron disease 5
• The most common MRI finding in the spine in ALS is abnormal T2/STIR signal in the anterior horns ("snake eyes" appearance), corresponding to lateral corticospinal tracts 5

Pathological Features

Synaptic Pathology

• Decreased synaptophysin immunoreactivity in the neuropil of the spinal anterior horn in ALS patients 6
• Synaptophysin expression in the perikarya and dendrites of remaining neurons may be normal or even increased 6
• Similar alterations occur in other lower motor neuron diseases 6

Morphometric Changes

• Studies of cervical anterior horn cells in patients with cerebrovascular disease show decreased cross-sectional area of anterior horn cells contralateral to hemispheric lesions 7
• Severe stenosis in cervical spondylotic myelopathy may ultimately result in necrosis of both gray and white matter 5
• Abnormal accumulation of 10 nm filaments appearing as argyrophilic spheroids in the perikarya and axons of motor neurons has been observed in some cases 8

Treatment Considerations

Pharmacological Treatments

• Riluzole (50 mg twice daily) is indicated for ALS treatment 2
  • Monitor liver function as cases of drug-induced liver injury have been reported 2
  • Watch for neutropenia and interstitial lung disease as potential adverse effects 2
• Risdiplam has shown efficacy in SMA patients:
  • Improved motor milestone achievement in infantile-onset SMA 4
  • 84% event-free survival (alive without permanent ventilation) at 24 months in infantile-onset SMA 4
  • Clinically meaningful improvement in motor function in later-onset SMA 4

Physical Therapy Considerations

• For progressive muscle diseases, guidelines recommend:
  • Submaximal, functional, and aerobic exercise 5
  • Avoiding excessive resistive and eccentric exercise 5
  • Avoiding overwork weakness and disuse atrophy 5
  • Allowing compensatory movements necessary for function while preventing contractures and deformity 5

Clinical Monitoring

• Regular assessment of musculoskeletal impairments, functional deficits, and disability levels 5
• Motor and functional assessments at 3-6 month intervals for children under five years, and annually in older children and adults 5
• Perform needle EMG in initial evaluation to determine presence of denervation as evidence of anterior horn cell involvement 5
• Perform nerve conduction studies at initial evaluation 5
• Motor unit number evaluation (MUNE) may be considered as an adjunctive assessment of anterior horn cell function 5