amyotrophic%20lateral%20sclerosis
AMYOTROPHIC LATERAL SCLEROSIS
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with undetermined etiology that primarily involves the motor neurons in the cerebral cortex, brainstem and spinal cord.
There is no cure and the mean duration of survival is 2-5 years without tracheostomy and ventilator support.
Clinical hallmarks of ALS are: presence of upper & lower motor neuron features involving the brainstem and spinal cord and progressive limb weakness, respiratory insufficiency, spasticity, hyperreflexia, and bulbar symptoms such as dysarthria and dysphagia.

Diagnosis

  • Patient should be referred to experienced neurologist for definitive diagnosis
    • Lack of specific biological marker and variability in clinical presentation make definitive diagnosis difficult
  • The El Escorial criteria uses a combination of upper motor neuron (UMN) and lower motor neuron (LMN) signs to establish levels of diagnostic certainty
  • Due to the insidious onset and nature of disease, a long delay is experienced before a definitive diagnosis is reached with a median time of 14 months
  • Common causes of diagnostic uncertainty include unusual clinical presentations, low index of suspicion and misinterpretation of neurophysiological or neuroradiological findings

Diagnostic Requirements Based Upon World Federation of Neurology Research Committee on Motor Neuron Diseases 1998 (Revised El Escorial criteria)

The following must be present:

  • Evidence of lower motor neuron degeneration
  • Evidence of upper motor neuron degeneration
  • There is progression of signs or symptoms within a region or to other regions which is determined by physical exam or history

The following must be absent:

  • Electrophysiological and pathological evidence of other diseases which may cause lower motor neuron and/or upper motor neuron degeneration
  • Neuroimaging evidence of other diseases that might explain the observed clinical and electrophysiological signs

Clinically Definite Amyotrophic Lateral Sclerosis

  • Clinical evidence alone reveals presence of upper motor neuron and lower motor neuron signs in 3 of the 4 regions (brainstem, cervical, thoracic, lumbosacral spinal cord)

Clinically Probable Amyotrophic Lateral Sclerosis

  • Clinical evidence alone reveals presence of upper motor neuron and lower motor neuron signs in 2 regions within some upper motor neuron signs necessarily rostral to (above) the lower motor neuron signs

Clinically Probable Amyotrophic Lateral Sclerosis: Laboratory-supported

  • Clinical signs of  upper motor neuron and lower motor neuron dysfunction are in 1 region only, or when upper motor neuron signs alone are present in one region and lower motor neuron signs defined by EMG criteria are present in at least 2 limbs

Clinically Possible Amyotrophic Lateral Sclerosis

  • Clinical signs of upper motor neuron and lower motor neuron dysfunction are found in 1 region only or upper motor neuron signs are found in ≥2 regions alone; or lower motor neuron signs are found rostral to upper motor neuron signs

Diagnostic Requirements Based Upon Revised Airlie House criteria 1998 (incorporating the Awaji-Shima criteria, 2008):

Definite Amyotrophic Lateral Sclerosis 

  • Clinical or electrophysiological evidence, demonstrated by the presence of upper motor neuron and lower motor neuron signs in the bulbar region and at least 2 spinal regions, or the presence of upper motor neuron and lower motor neuron signs in 3 spinal regions

Probable Amyotrophic Lateral Sclerosis

  • Clinical or electrophysiological evidence, demonstrated by upper motor neuron and lower motor neuron signs in at least 2 spinal regions, with some upper motor neuron signs necessarily rostral to the lower motor neuron signs

Possible Amyotrophic Lateral Sclerosis

  • Clinical or electrophysiological evidence of upper motor neuron and lower motor neuron dysfunction in only 1 region, or upper motor neuron signs alone in 2 or more regions, or lower motor neuron signs rostral to upper motor neuron signs

Laboratory Tests

  • Essential blood tests are erythrocyte sedimentation rate, C-reactive protein, complete blood count, liver function tests, creatinine kinase, electrolytes (Na, K, Cl, Ca), glucose, thyroid function tests, lactase dehydrogenase

Imaging

Neuroimaging Studies

  • Used to exclude other conditions
  • Advances in neuroimaging led to the following findings suggestive but not specific to amyotrophic lateral sclerosis (ALS):
    • Corticospinal tract hyperintensity and cerebral atrophy detected in magnetic resonance imaging (MRI)
    • Reduced primary motor cortex N-acetylaspartate to creatine ratio in magnetic resonance spectroscopy

Radiology

  • Chest X-ray should be done

Screening

Electrophysiological Studies

  • The diagnosis of amyotrophic lateral sclerosis amyotrophic lateral sclerosis is supported by fasciculations in 1 or more regions, neurogenic changes in electromyography (EMG) results, normal motor and sensory nerve conduction and absence of conduction block
  • If diagnosis of amyotrophic lateral sclerosis is considered on clinical grounds, electrophysiological studies should be performed to:
    • Confirm lower motor neuron (LMN) dysfunction in clinically affected regions
    • Detect electrophysiological evidence of lower motor neuron dysfunction in clinically uninvolved regions
    • Exclude other pathophysiological processes

Nerve Conduction Studies

  • May be used to exclude demyelinating motor neuropathies, which mimic amyotrophic lateral sclerosis
  • Motor nerve conduction is normal in the early stages of amyotrophic lateral sclerosis, but in advanced stages, denervation is observed and this reduces the muscle action potential amplitude

Electromyography

  • Findings in amyotrophic lateral sclerosis patients include features of acute and chronic denervation and reinnervation
    • Not pathognomonic for amyotrophic lateral sclerosis, but similar abnormalities in several muscles of proximal and distal limbs suggest a diagnosis of amyotrophic lateral sclerosis when there is no corresponding nerve root compression significant to cause the abnormality
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