Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive disorder that involves the degenerative loss of motor neurons in the spinal cord, brainstem, and corticospinal tracts.
The reason for the degenerative loss is not well understood. But, it may be related to a series of genetic mutations that are found in all patients with ALS.
The negative effects of these mutations preferentially affect motor neurons while sensory neurons remain unaffected. But, not all motor neurons are vulnerable in patients with ALS. For some reason, motor neurons innervating the eyes and bladder are resistant. As a result, eye and bladder function are usually spared.
A final common pathway of degenerative motor neuron loss is the accumulation of the neurotransmitter glutamate. Glutamate is particularly cytotoxic to neurons in specific concentrations and is a target for ALS treatment.
What is the pattern of disease in ALS?
Due to the selective but diffuse motor neuron loss in the central nervous system, ALS presents with a mixture of upper and lower motor neuron findings. However, keep in mind that multilevel cervical spondylotic myelopathy (CSM) presents with similar findings. In fact, the most common differential diagnosis for ALS is CSM!
While ALS and CSM both present with upper and lower motor neuron findings, patients with ALS will often show cranial nerve signs and symptoms. Cranial nerves are not affected in CSM. As well, patients with CSM typically present with sensory symptoms (such as early loss of proprioception) whereas patients with ALS don’t typically show sensory symptoms.
Upper motor neuron findings in ALS may include six signs and symptoms:
- Abnormal reflexes (e.g., Babinski and Hoffmann’s reflex)
- Late progression of weakness
Lower motor neuron findings in ALS may include five signs and symptoms:
- Early weakness
- Decreased muscle tone
- Fasciculations in the affected muscles
Some patients with ALS may have a predominance of upper motor neuron findings, some may present with mostly lower motor neuron findings, and some may have predominantly brainstem (e.g., cranial nerve) findings. Typically, most patients will have a mix of all three findings.
What to do if you suspect ALS?
If you suspect ALS, start by performing an extensive neurological exam:
- Perform a sensory exam
- Perform a motor exam
- Assess cognition and sacral function
- Evaluate the cranial nerves
- Test deep tendon reflexes
Perform a sensory exam
With ALS, the patient’s sensory function should be relatively unaffected. For example, proprioception (which is often lost in CSM) should be well preserved.
Perform a motor exam
An extensive motor exam of all extremities should be performed on a patient when you suspect ALS. Early weakness tends to center on the hands while lower extremities are affected later in the disease progression.
When observing the patient, look for diffuse muscular atrophy and fasciculations in the extremities. In patients with ALS, atrophy becomes quite pronounced over time and the fasciculations are more plentiful and dramatic than those seen in CSM.
Also, check the patient’s muscle tone. Lower extremity tone is often increased in patients with ALS—sometimes to the point of spasticity.
Assess cognition and sacral function
When performing a neurological exam, also evaluate cognition, which should be well preserved.
Assess the sacral function as well. In ALS, urinary dysfunction should be absent, whereas in severe spinal cord myelopathy, urinary function may be affected.
Evaluate the cranial nerves
During your assessment, you’ll also want to evaluate the cranial nerves extensively. Facial movement and lower cranial nerves may be particularly affected while extraocular nerves tend to be preserved.
Test deep tendon reflexes
Test the patient’s major deep tendon reflexes. Early in the disease, they tend to be hyperreflexic in the lower extremities and hyporeflexic in the upper extremities (although they can also be diffusely hyperreflexic).
How to make the diagnosis of ALS
Look for motor neuron dysfunction
The diagnosis of ALS involves looking for motor findings such as weakness, changes in tone, atrophy, and fasciculations in four regions of the body. Finding evidence of motor neuron dysfunction in three of the four regions secures the diagnosis.
Look for evidence of motor neuron dysfunctions in each of the following four body areas:
- Cranial-bulbar region
- Upper extremities
- Lower extremities
In the cranial nerve exam, extraocular muscle function is generally intact in patients with ALS. But, other facial muscles may be affected. Pay particular attention to the lower cranial nerves. Speech is often slurred, decreased in volume, hoarse, or dysarthric. Swallowing may be compromised. Notably, speech and swallowing difficulties tend to intensify over time.
When assessing the upper extremities for motor neuron dysfunction, look for a loss of finger dexterity or loss of hand and wrist strength (most often in the dominant arm). Initially, the muscle tone is often decreased. Over time, the tone may increase, and atrophy and fasciculations become prominent.
In the trunk, look for weakness and instability. These show as the tendency to start to slump over and a need to support oneself. Note that in patients with ALS, this tendency to slump over is not due to proprioceptive loss (as it is in patients with CSM). You should also scan the muscles for atrophy and fasciculations.
Early signs of motor neuron dysfunction often occur in the legs. Look for increased tone, hyperreflexia, stumbling, and a foot drop. Over time, the legs may become quite spastic and dysfunctional. Atrophy will eventually be seen in the legs as well.
Perform additional testing as necessary
Initially, a definitive diagnosis of ALS may not be straightforward. Oftentimes there is a period of watchful waiting. Unfortunately, there are no definitive biomarkers or imaging findings for ALS. But, extensive bloodwork and imaging should still be performed to rule out other differential diagnoses. Anatomic and specialized magnetic resonance imaging (MRI) may show evidence of thinning of the corticospinal tracts, but this is not considered diagnostic.
Most cases of ALS are sporadic. However, about 5% of the cases are familial. If the patient has a family history of ALS, genetic testing may be indicated. However, without definitive lab tests, the diagnosis is secured if there is evidence of upper and lower motor neuron findings in at least three of the four key body areas.
It is important to order electromyography (EMG) testing. It may not be definitive, but the testing will help define three or four regions of motor neuron involvement. Fibrillations and fasciculations in the tongue and lower extremities can strengthen the diagnosis and help rule out CSM (since neither of these should be seen with CSM). As well, nerve conduction velocities should be normal.
If the diagnosis is still in question, and there are no cranial nerve or brainstem findings, the patient may have CSM. This should be evaluated with MRI of the cervical spine. However, be careful of overinterpretation as many people will have some degree of cervical stenosis (especially older patients).
Other cervical spinal cord pathologies can also mimic ALS such as intrinsic spinal cord tumors or syrinx. Magnetic resonance imaging will quickly eliminate these possibilities.
When the diagnosis is in question (and CSM is suspected), consult neurosurgery and neurology specialists. They may need to confer. There are times where ALS is strongly suspected in a patient, but cervical decompression may be tried to see if it was contributing to the patient’s disability.
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