How to differentiate Amyotrophic Lateral Sclerosis (ALS) from a cervical cord syrinx?

Distinguishing ALS from Cervical Cord Syrinx

The key to differentiating ALS (Lou Gehrig disease) from cervical cord syrinx is MRI of the cervical spine combined with electromyography (EMG), where MRI will directly visualize the syrinx cavity while EMG using Awaji criteria demonstrates widespread lower motor neuron involvement characteristic of ALS. 1, 2, 3

Primary Diagnostic Approach

Initial Imaging Strategy

• Obtain MRI of the cervical spine without IV contrast as the first-line imaging test, which has superior soft-tissue resolution for evaluating the spinal cord and can directly identify a syrinx cavity (fluid-filled cavity within the cord) 1
• Look for the characteristic "snake eyes" appearance on T2/STIR sequences in the anterior horns, which may appear in ALS but represents a late finding and is not specific 2
• Identify syrinx-specific features on MRI: a well-defined CSF-intensity cavity within the cord substance, often associated with cord expansion, that follows CSF signal on all sequences 1
• Evaluate for underlying causes of syrinx: Chiari malformation (most common), arachnoid webs, cord tethering, or prior trauma 1, 4

Electromyography: The Definitive Differentiator

• Perform EMG with nerve conduction studies in all patients, as this is the cornerstone test for diagnosing ALS and has excellent accuracy (83.3% positive predictive value, 85.2% negative predictive value) in distinguishing ALS from structural cord lesions 2, 3
• Apply Awaji criteria during EMG interpretation, which requires evidence of lower motor neuron degeneration in multiple spinal segments beyond what a localized syrinx could explain 2, 3
• A syrinx produces focal lower motor neuron signs only at the affected cord levels, whereas ALS demonstrates widespread denervation across multiple non-contiguous myotomes including bulbar, cervical, thoracic, and lumbosacral regions 2, 3

Clinical Features That Distinguish the Two Conditions

Syrinx-Specific Patterns

• Dissociated sensory loss (loss of pain/temperature with preserved light touch and proprioception) in a "cape-like" distribution strongly suggests syrinx, as this pattern does not occur in ALS 1
• Segmental weakness and atrophy restricted to specific myotomes corresponding to the syrinx level (typically C5-T1 for cervical syrinx) 1, 5
• Associated Chiari malformation symptoms: occipital headaches worsened by Valsalva, downbeat nystagmus 4
• Dynamic compression on flexion MRI may be present in cases related to Hirayama disease (cervical flexion myelopathy), which can mimic early ALS 5

ALS-Specific Patterns

• Combination of upper and lower motor neuron signs (hyperreflexia with muscle atrophy, fasciculations with Babinski sign) is pathognomonic for ALS and does not occur with isolated syrinx 2, 3
• Progressive spread of weakness from one body region to others over months (e.g., arm to leg to bulbar) indicates ALS rather than a static structural lesion 2, 3
• Bulbar involvement (tongue fasciculations, dysarthria, dysphagia) strongly favors ALS, as syrinx rarely extends to medullary levels 6, 3
• Absence of sensory symptoms despite motor involvement suggests ALS, whereas syrinx typically causes sensory deficits 2, 3

Advanced MRI Findings in ALS

• T2/FLAIR hyperintensity in the corticospinal tracts, particularly in the posterior limb of internal capsule and cerebral peduncles on brain MRI, supports ALS 2, 7, 8
• Hypointensity on T2/susceptibility-weighted imaging in the precentral gyrus* is highly sensitive and specific for ALS 2
• Cervical cord MRI may show bilateral hyperintensity in the dorsolateral columns (corticospinal tracts) in ALS, which differs from the central cavity of syrinx 8

Laboratory Testing to Exclude ALS Mimics

• Obtain CSF analysis (cell count, protein, oligoclonal bands) to exclude inflammatory/infectious myelopathies that can mimic either condition 2, 7
• Check vitamin B12, copper, and vitamin E levels to rule out metabolic causes of myelopathy 2
• Test anti-ganglioside antibodies (GM1, GD1a, GD1b) to exclude immune-mediated motor neuropathies 2
• Consider genetic testing for ALS-associated genes (C9orf72, SOD1, FUS, TARDBP) if family history is present 2

Critical Pitfalls to Avoid

• Do not assume that cervical spondylosis or syrinx explains all symptoms, as ALS and structural cord lesions can coexist in 2% of cases, making EMG essential for accurate diagnosis 3
• Recognize that a single autopsy case report documented ALS with concurrent cervical syringomyelia, but the syrinx was attributed to spondylotic myelopathy rather than causing the ALS 6
• Dynamic MRI with neck flexion has prognostic significance: patients with progressive upper-limb weakness who lack dynamic cord compression on flexion MRI are more likely to develop generalized ALS 5
• Absence of pyramidal signs does not exclude ALS, as pseudopolyneuritic forms exist, but EMG will still show widespread denervation 8
• Syrinx associated with multiple sclerosis can occur, so if MRI shows both syrinx and periventricular white matter lesions, consider demyelinating disease in the differential 9

When Both Conditions Coexist

• In the 2% of patients with both CSM and ALS, EMG using Awaji criteria has 83.3% positive predictive value for identifying concurrent ALS, which is critical for surgical decision-making 3
• Patients with CSM who fulfill Awaji criteria on EMG have 83.3% likelihood of developing clinically definite ALS during follow-up, making EMG essential before considering decompressive surgery 3
• Surgical decompression will not improve symptoms in patients with concurrent ALS, so accurate preoperative diagnosis prevents unnecessary surgery 3