Clinical Constellations

Amyotrophic Lateral Sclerosis lies on the spectrum of disorders known as motor neuron diseases.  ALS is not just one presentation or group of symptoms; in fact, it can manifest so differently from patient to patient, that it can often look like an entirely different disease early on.  I want to take you through a brief and cursory breakdown of the different ways ALS can present or appear. 

For reference:

UMN signs = upper motor neuron = spasticity, brisk or hyperactive reflexes

LMN signs = lower motor neuron = decreased tone, twitching also known as fasciculations and atrophy (wasting)

Bulbar signs = trouble speaking (dysarthria), trouble swallowing (dysphagia), facial weakness

PBA = pseudobulbar affect = emotional disturbances such as excessive or inappropriate laughing or crying

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Typical/classic ALS

• Simultaneous UMN/LMN signs
• Weakness starts focally in one limb and then spreads to all four
• Weakness, atrophy, spasticity, fasciculations, cramps, +/- bulbar features and respiratory compromise as disease progresses

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Upper motor neuron predominant ALS

• Weakness (without atrophy), cramps, spasticity, PBA, bulbar symptoms
• Lower motor neuron signs absent or restricted to one level (bulbar = face, cervical = neck/arms, thoracic = mid-back, lumbar = low back/legs… to keep it simple
• Minimal respiratory involvement early on
• Can differentiate from PLS (see below) as UMN ALS typically has faster progression, bulbar features at onset, reduced respiratory capacity and is limb weakness predominant

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 Lower motor neuron predominant ALS (Progressive muscular atrophy)

• A pure LMN presentation most commonly considered a variant of ALS and not a necessarily a separate disease entity
• Slower progression of weakness with atrophy, decreased muscle tone and fasciculations
• Can start in any body region but hands are usually involved first
• Slightly later age of onset
• Males are more often affected than females

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Lower extremity predominant ALS 

• Isolated LE weakness at onset which may remain isolated for a time or eventually spread to the arms.  May have UMN features, LMN features or both
• Note the separate, more benign disease entity of Flail Limb Syndrome: also known as leg amyotrophic diplegia which may look like early ALS. A duration less than 14 mos to the second involved region typically go on to have LE onset ALS and greater than 14 mos tends to remain FLS. Median disease duration of FLS 80 mos.

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Upper extremity predominant ALS

• Isolated UE weakness at onset which may remain isolated or may spread to the legs in time. May have UMN features, LMN features or both
• Note the separate, more benign disease entity of Flail Arm Syndrome: also known as brachial amyotrophic diplegia which may look like ALS early on. There is a male preponderance in this condition, predominantly proximal weakness of the arms (think man in a barrel), diagnosed when symptoms are confined to arms for at least 12 mo. 
• Those who progress to LE or bulbar within 12 mos classified as UE predominant ALS

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Bulbar onset ALS

• Disease onset with either dysarthria or dysphagia (may be of UMN or LMN type). May be followed by facial weakness, increased saliva production, cough, shortness of breath, pseudobulbar affect
• 29 months median survival is reduced compared to limb onset ALS 
• 25% of ALS
• Pseudobulbar onset variant is indicative of UMN involvement
• Females are more commonly affected

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PLS

• Sporadic, pure UMN but there is debate as to how much LMN is “allowed” on exam and on EMG (NOTE! EMGs detect LMN disease and not UMN). While on the motor neuron disease spectrum, this is considered a discrete entity by most, unlike PMA (described above)
• Slowly progressing symmetric ascending weakness in the LEs with associated cramps, spasticity +/- FTD picture +/- bowel/bladder dysfunction. Rare respiratory involvement.
• Typically starts in the LE and ascends symmetrically upward
• Patients with an UMN syndrome, without EMG findings for 4 yrs have the diagnosis of PLS - and not UMN variant ALS. Can live for decades
• FTD and other cognitive impairment is similar to that in ALS

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Mill’s variant

• Hemiplegic ALS meaning purely lateralized weakness at onset (one side of the body is affected and the other is normal)
• Starts in leg and ascends or starts in arm and descends
• Exceedingly rare

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Respiratory onset ALS

• Respiratory weakness as presenting symptom +/- neck flexion/extension or shoulder girdle weakness.
• Rare, about 2% of all ALS
• Mean survival time from symptom onset to death or ventilator dependency is 27 months which is similar to that of bulbar onset ALS
• Most patients go on to meet El Escorial criteria
• 90% will have some shoulder girdle weakness so these are patients with primary cervical involvement

Since no two patients with ALS are identical in their symptoms and progression of the disease, personalized care plans are crucial in the treatment of the disease. Our team at Synapticure strongly believes in this individualized and patient centric approach to the development of these care plans including: medication regimens, rehabilitation and physical therapy programs, supplement and nutraceutical plans and access to trials or experimental treatment . Click below if you would like to meet with one of our care coordinators to learn more.