Approach to differentiating lesions (motor neuron): Clinical sciences

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Introduction 0:00–0:49

Motor neuron lesions are conditions associated with a loss of strength and movement due to upper or lower motor neuron injuries.
Upper motor neurons originate in the cerebral cortex, with axons that descend through the subcortical white matter and synapse with lower motor neurons in the brainstem and anterior horn cells in the spinal cord.
These lower motor neurons then send axons out of the central nervous system via cranial nerves or spinal nerve roots to reach muscle cells.
Now, some conditions affect only lower motor neurons, such as acute flaccid myelitis and adult-onset spinal muscular atrophy; while other conditions can affect both upper and lower motor neurons, such as amyotrophic lateral sclerosis.
Now, if your patient presents with a chief concern suggesting motor neuron disease, first perform an ABCDE assessment to determine if they are unstable or stable.

Unstable Patient 0:49–1:25

If unstable, stabilize the airway, breathing, and circulation. In some cases, you might even have to intubate the patient and start mechanical ventilation.
Next, obtain IV access and consider starting IV fluids. Finally, put your patient on continuous vital sign monitoring, including heart rate, blood pressure, and pulse oximetry, as well as cardiac telemetry; and if needed, provide supplemental oxygen.
Now, let’s go back to the ABCDE assessment and focus on stable patients. In this case, obtain a focused history and physical examination.

Stable Patient 1:25–2:07

The patient will describe progressive bilateral weakness, which could affect muscles of the face, neck, arms, or legs. Some patients might describe trouble standing up and walking, while others might report trouble speaking, swallowing, or breathing.
On physical exam, you will notice weakness of the facial muscles, neck, trunk, or limbs, which may or may not be symmetric.
Finally, the physical exam will reveal abnormal muscle tone and reflexes, and in some cases, cranial nerve dysfunction and an abnormal gait.
Next, assess for sensory involvement. If the patient reports numbness or tingling, and the exam reveals a loss of sensation, you should consider alternative diagnoses, because motor neuron conditions do not cause sensory deficits.

Consider alternative diagnosis 2:07–2:40

Instead, think about conditions that impair both motor strength and sensation, such as spinal cord lesions, or bilateral brain lesions from a stroke or demyelination.
On the other hand, if the exam reveals pure weakness with normal sensation, consider motor neuron disease. This can be isolated to either upper motor neurons, or lower motor neurons or affect both.

Lower motor neuron lesion 2:40–3:21

In this case, your first step is to assess the pattern of motor neuron injury. If the physical exam reveals muscle atrophy; fasciculations, which are involuntary muscle fiber contractions; decreased tone; and hyporeflexia, it’s likely that your patient has a lower motor neuron lesion.
The next step is to assess the underlying cause. Now, if history reveals a child with weakness that progresses rapidly over hours to days; with a preceding fever and respiratory or gastrointestinal illness; consider acute flaccid myelitis.

Acute flaccid myelitis 3:21–4:35

Then, obtain a CSF analysis and an MRI of the spine. If CSF analysis reveals pleocytosis, usually less than 100 cells per microliter, with a lymphocytic predominance; and the spine MRI shows predominantly gray matter involvement; diagnose acute flaccid myelitis in this case.
Now, here’s a clinical pearl to keep in mind! Acute flaccid myelitis typically occurs after a viral infection, especially enteroviruses D68 and 71, West Nile virus, and poliovirus.
Depending on the underlying infection, you can often identify the causative virus by testing serum, stool, nasopharyngeal, or CSF samples.
Infections from enteroviruses D68 and 71, and West Nile virus are more common in the summer and early fall, while the incidence of poliomyelitis has fallen significantly due to widespread polio vaccination.
Alright, let’s switch gears and discuss the underlying cause of lower motor neuron lesions that are associated with slowly progressive weakness, developing over several years.

SMA 4 4:35–6:18

These patients have weakness that is worse in the shoulders and thighs than in the hands and feet; or in other words, the proximal muscles are more significantly affected.
Despite the weakness, these patients are still able to walk. This clinical picture should make you consider spinal muscular atrophy type 4, or SMA 4.
Now perform a genetic analysis of the survival motor neuron 1, or SMN1, gene. If results reveal deletions or mutations of both copies of the SMN1 gene, diagnose spinal muscular atrophy, specifically type 4.
Here's a high-yield fact! SMA can be subdivided into four main types, which are based on severity.
Type 1, which is also known as Werdnig-Hoffmann disease or infantile-onset SMA, is the most severe phenotype. Affected patients cannot sit independently and have early mortality from respiratory failure.
Those with type 2 SMA can sit independently, while those with type 3 can also walk. Finally, SMA type 4 is the least severe phenotype and usually presents during adulthood.
As far as management goes, there are 3 disease-modifying treatments that have significantly improved motor skill development and survival.
These include the antisense oligonucleotide called nusinersen; the mRNA splicing modifier called risdiplam; and the gene therapy onasemnogene abeparvovec, which delivers a copy of the functioning SMN1 gene.
Now, let’s step back and look at individuals with lower and upper motor neuron signs. Lower motor neuron signs are muscle atrophy, fasciculations, and decreased tone, while upper motor neuron signs are spasticity and hyperreflexia.

Amyotrophic lateral sclerosis 6:18–8:38

In this case, think of conditions associated with both lower and upper motor neuron lesions; more specifically, you should consider amyotrophic lateral sclerosis, or ALS.
Time for a clinical pearl! Patients with acute upper motor neuron injuries resulting from conditions like stroke or spinal cord trauma will first present with signs of lower motor neuron injury, like flaccid paresis, decreased tone, and hyporeflexia.
However, after several hours or even weeks, these patients typically develop spasticity and hyperreflexia. Now back to our patient.
Individuals with ALS might experience episodes of uncontrollable laughter or crying due to emotional lability, known as a pseudobulbar affect.
Some of these patients also develop cognitive impairment as a result of frontotemporal dementia. Finally, there might be a family history of ALS.
In addition to lower and upper motor neuron signs involving multiple body parts, such as the bulbar, cervical, thoracic, and lumbosacral regions; the physical exam might also reveal dysarthria and hoarseness.
These findings are consistent with amyotrophic lateral sclerosis. Here’s your last clinical pearl!
If the clinical presentation is unclear, you can obtain a nerve conduction study and electromyography to confirm a diagnosis of ALS.
Findings suggestive of ALS include low or absent motor responses with intact sensory conduction velocities and signs of active and chronic muscle denervation in different body regions.
Once you diagnose ALS, it’s important to provide well-rounded multidisciplinary care, including physical therapy, speech and swallow therapy, respiratory therapy, dietary management, and social work.
Additionally, there’s pharmacologic therapy, which relies on disease-modifying treatments such as riluzole and edaravone, that can slow the progression of symptoms.
Finally, if your patient has pseudobulbar affect, consider starting the combination of dextromethorphan and quinidine. Alright, as a quick recap… Motor neuron lesions are conditions associated with loss of strength and movement due to upper or lower motor neuron injuries.

Review 8:38–9:10

The hallmark of motor neuron disease is muscle weakness without sensory involvement. Now, once you suspect a motor neuron disease, first, assess the pattern of motor neuron injury.
If your patient presents with signs of an isolated lower motor neuron lesion, consider conditions like acute flaccid myelitis and SMA type 4.
On the flip side, if the patient presents with signs of both lower and upper motor neuron