Amyotrophic Lateral Sclerosis Initial Assessment

Clinical Presentation

The clinical hallmarks of amyotrophic lateral sclerosis include the presence of upper motor neuron and lower motor neuron features involving the brainstem and spinal cord, progressive weakness, respiratory insufficiency, spasticity, hyperreflexia, and bulbar symptoms such as dysarthria and dysphagia.  

The main presentation of amyotrophic lateral sclerosis will depend on the type. In the case of limb-onset amyotrophic lateral sclerosis, there is a combination of upper motor neuron and lower motor neuron signs in the limbs. Bulbar-onset amyotrophic lateral sclerosis is characterized by speech and swallowing difficulties with limb features developing later in the course of the disease. Primary lateral sclerosis is characterized by pure upper motor neuron involvement. While pure muscular atrophy is characterized by pure upper motor neuron involvement. 

Signs and Symptoms  

Upper motor neuron dysfunction leads to muscle weakness, spasticity, and brisk tendon reflexes (DTR). While lower motor neuron dysfunction leads to muscle fasciculations, wasting, and weakness. Both upper and lower limb involvements are present at diagnosis in about 30 to 40% of patients. Weakness of the lower extremities may first be noted as frequent tripping, stumbling, or awkwardness when walking or running. Upper limb weakness may first be noticed as difficulty in buttoning clothes, picking up small objects or turning keys. As symptoms worsen, muscle atrophy becomes apparent, and spasticity complicates gait and dexterity. Patients may also experience muscle pain or cramps due to clonus and hyperreflexia. Immobility from weakness and spasticity results in painful joint complications. Bulbar symptoms are present initially in 25% of patients. Among the bulbar symptoms, dysarthria and dysphagia are the most common symptoms in amyotrophic lateral sclerosis and can reduce patient’s life expectancy and quality of life. Bulbar upper motor neuron dysfunction presents as spastic dysarthria characterized by slow, labored, and distorted speech with nasal quality. Pathologically brisk gag and jaw reflexes may also be noted. Bulbar lower motor neuron dysfunction leads to tongue wasting, weakness, fasciculations, flaccid dysarthria, and dysphagia.

Extraocular muscles, bladder, and bowel control, sensory function, visual disturbances, basal ganglia, and skin integrity may remain unaffected in amyotrophic lateral sclerosis patients. Irrespective of the presence or absence of bulbar motor signs, emotional lability occurs in at least half of patients. There is conflicting data regarding its correlation with cognitive impairment. Prominent pseudobulbar features (eg pathological weeping, laughing or yawning) can be socially disabling. A frontotemporal syndrome occurs in up to half of patients with amyotrophic lateral sclerosis and is associated with a poorer prognosis. Symptoms of cognitive dysfunction may appear before or after the onset of motor symptoms. 

Course and Progression  

Amyotrophic lateral sclerosis has no cure and is relentlessly progressive with a mean survival of 3 years after disease onset. Fifty percent of patients die within 30 months of symptom onset, while 20% survive 5 to 10 years after symptom onset. Factors that reduce survival include older age of onset, early respiratory dysfunction, and bulbar-onset disease. Survival is dependent on several factors such as clinical presentation, rate of disease progression, early onset of respiratory failure, and nutritional status. Independent predictors of prolonged survival include limb-onset disease, younger age at presentation, and shorter diagnostic delay. The weakness leads to disability and eventual need for ventilatory assistance. Death in patients is usually caused by respiratory failure.  

Amyotrophic Lateral Sclerosis_Initial Assesment

Diagnosis or Diagnostic Criteria

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

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

The following must be present:

• Evidence of upper motor neuron and lower motor neuron signs to establish levels of diagnostic certainty degeneration
• Evidence of lower motor neuron degeneration
• There is progression of signs and symptoms within a region or to other regions as determined by history or physical examination

The following must be absent:

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

Clinically Definite Amyotrophic Lateral Sclerosis  

Clinically definitive amyotrophic lateral sclerosis is characterized by clinical evidence alone revealing the presence of upper motor neuron and lower neuron signs in 3 of the 4 regions (brainstem, cervical, thoracic, lumbosacral spinal cord). 

Clinically Probable Amyotrophic Lateral Sclerosis  

Clinically probable amyotrophic lateral sclerosis is characterized by clinical evidence alone revealing the presence of upper motor neuron and lower motor neuron signs in 2 regions with 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 one region only, or when upper motor neuron signs alone are present in one region, and lower motor neuron signs defined by electromyography (EMG) criteria are present in at least 2 limbs.  

Clinically Possible Amyotrophic Lateral Sclerosis  

Clinically possible amyotrophic lateral sclerosis is characterized by clinical signs of upper motor neuron and lower motor neuron dysfunction being found in one region only or upper motor neuron signs being found in ≥2 regions alone; or lower motor neuron signs being found rostral to upper motor neuron signs. 

Diagnostic Requirements Based on the Revised Airlie House Criteria 1998 (incorporating Awaji-Shima Criteria, 2008)

Definite Amyotrophic Lateral Sclerosis  

Definite amyotrophic lateral sclerosis is characterized by 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  

Probable amyotrophic lateral sclerosis is characterized by 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  

Possible amyotrophic lateral sclerosis is characterized by clinical or electrophysiological evidence of upper motor neuron and lower motor neuron dysfunction in only one region, or upper motor neuron signs alone in 2 or more regions, or lower motor neuron signs rostral to the upper motor neuron signs.