CSF sphingomyelin: a new biomarker of demyelination in the diagnosis and management of CIDP and GBS

ObjectiveTo validate sphingomyelin (SM) dosage in the cerebrospinal fluid (CSF) of patients affected by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and Guillain-Barré syndrome (GBS) as a reliably assessable biomarker.MethodsWe prospectively enrolled 184 patients from six Italian referral centres, in whom CSF SM levels were quantified by a fluorescence-based assay optimised and patented in our laboratory.ResultsWe confirmed increased levels of SM in the CSF of patients affected by typical CIDP (n=35), atypical CIDP (n=18) and acute inflammatory demyelinating polyradiculoneuropathy, AIDP (n=12) compared with patients affected by non-demyelinating neurological diseases, used as controls (n=85) (p<0.0001, p=0.0065 and p<0.0001, respectively). In patients with CIDP classified for disease stage, SM was higher in active CIDP compared with both controls and stable CIDP (p<0.0001), applying for a selective tool to treatment tailoring or withdrawal. SM was also increased in AIDP compared with axonal GBS, discerning the demyelinating from axonal variant of the disease. SM did not correlate with CSF protein levels, stratifying patients independently from commonly used CSF indexes, and displaying high specificity to avoid potential misdiagnosis. Finally, SM correlated with the main clinical scores and some neurophysiological parameters in patients with CIDP and AIDP.ConclusionsCSF SM is a diagnostic and staging wet biomarker for acquired demyelinating neuropathies and may effectively improve the management of patients affected by GBS and CIDP.

51-year old man with tingling, burning and progressive limb weakness

Peripheral neuropathy is a common reason for referral to neurology. Chronic acquired demyelinating neuropathies are an important and varied group with overlapping presentations, and may have an immune-mediated cause. Their correct diagnosis is important as they respond to different treatments; timely intervention can prevent irreversible axonal degeneration. We present a case that highlights the approach to an adult presenting with a chronic demyelinating neuropathy.

Polyneuropathy

Typically polyneuropathy will cause the combination of distal limb muscle weakness, loss of tendon reflexes, and reduced distal limb sensation. There is variable involvement of the autonomic innervation, damage to which causes a dry, vasodilated foot or hand. Loss of tendon reflexes is a cardinal sign of polyneuropathy, often restricted to the ankle jerks in axonal degeneration, but involving more proximal reflexes in acquired demyelinating neuropathies which may involve more proximal segments or the nerve roots. Clinical features suggestive of demyelinating or conduction block polyneuropathy include: a relative lack of muscle wasting in relation to the degree of weakness because no denervation has occurred; weakness of proximal muscles as well as distal, because of nerve root involvement; and disproportionate loss of joint position and vibration sensations compared to relative preservation of pain and temperature sensations which are carried by unmyelinated fibres.