Axonal loss at time of diagnosis as biomarker for long‐term disability in chronic inflammatory demyelinating polyneuropathy

Abstract

Introduction/Aims: We hypothesized that early, pretreatment axonal loss would predict long-term disability, supported by a pilot study of selected patients with chronic inflammatory demyelinating polyneuropathy (CIDP). To further test this hypothesis, we examined a larger consecutive group of CIDP patients.Methods: Needle electromyography and motor and sensory nerve conduction studies were carried out in 30 CIDP patients at pretreatment and follow-up 5 to 28 years later. Changes in amplitudes were expressed as axonal Z scores and changes in conduction as demyelination Z scores and correlated with findings of the Inflammatory Rasch-built Overall Disability Scale (I-RODS), the Neuropathy Impairment Score (NIS), and isokinetic dynamometry (IKS).Results: At follow-up, the median I-RODS score was 73, the NIS was 23, and the IKS was 56%. The median axonal Z score was unchanged at follow-up. Conversely, the corresponding demyelination Z scores improved. The initial axonal loss was correlated with the clinical outcome and was an independent predictor of outcome by multivariate regression analysis. Axonal loss at follow-up was also correlated with the clinical outcome. Only the follow-up demyelination Z score was correlated with the clinical outcomes. Furthermore, the latency until treatment initiation was predictive of all three clinical outcome scores at follow-up, and of axonal loss and demyelination at follow-up.Discussion: The present study findings indicate that pretreatment axonal loss at diagnosis in CIDP is predictive of long-term disability, neurological impairment, and strength. A delay in treatment is associated with more pronounced axonal loss and a worse clinical outcome.

Prevention of axonal loss after immediate dosage titration of immunoglobulin in multifocal motor neuropathy

“…An explanation for this finding could be that weakness in MMN predominantly affects the hands, whereas most assessment scales such as NIS and MMN‐RODS encompass the neurological functions more widely. In previous reports by our group on patients with chronic inflammatory demyelinating polyneuropathy, strong associations between initial axonal loss and long‐term clinical performance scores were observed [15, 16].…”

“…Motor fibers were activated by supramaximal stimulation at the wrist and elbow in the median nerve, at the ankle and fibular head of the fibular nerve, and at the medial malleolus and popliteal fossa of the tibial nerve. As previously described, the compound motor action potentials (CMAPs) were recorded using surface electrodes in a belly-tendon montage over the abductor pollicis brevis, extensor digitorum brevis, and abductor hallucis muscles, respectively [15,16]. In addition, the median nerve was stimulated in the axilla and at Erb's point to detect any motor conduction block.…”

Neurophysiological Hallmarks of Axonal Degeneration in CIDP Patients: A Pilot Analysis

“…Long-term prognosis of treated CIDP patients depends on the therapeutic response and the occurrence of disability, mainly characterized by weakness and muscular atrophy [ 28 ]. Although CIDP is an acquired demyelinating disease, secondary axonal degeneration is commonly observed [ 8 ] and mainly related to therapeutic unresponsiveness [ 29 , 30 ]. Mechanisms of axonal damage are largely unknown; in the acute phase of the disease, demyelination and node/paranodal dysfunction may lead to Wallerian degeneration phenomena, while in the chronic phase the persistence of inflammatory and immune attack may lead to progressive degeneration of nerve fibers [ 31 ].…”