Recombinant porphobilinogen deaminase targeted to the liver corrects enzymopenia in a mouse model of acute intermittent porphyria

Systemic and subcutaneous rApoAI-PBGD therapy protects against porphyrin precursor accumulation, pain, and motor neuropathy in AIP mice.

Evidence base for investigative and therapeutic modalities in chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy

Chronic inflammatory demyelinating polyneuropathy, its variants and multifocal motor neuropathy belong to a spectrum of peripheral nerve disorders with complex dysimmune disease mechanisms. Awareness of the unique clinical phenotypes but also heterogeneity between patients is vital to arrive at early suspicion and ordering appropriate tests. This includes requirements for optimal electrodiagnostic protocol, aimed to capture sufficient electrophysiologic evidence for relevant abnormalities, a case-based approach on the eventual need to further expand the diagnostic armamentarium and correct reading of their results. Considerable phenotypical variation, diverse combinations of abnormalities found on diagnostic tests and heterogeneity in disease course and treatment response, all contribute to widespread differences in success rates on timely diagnosis and optimal treatment. We aim to provide a practical overview and guidance on relevant diagnostic and management strategies, including pitfalls and present a summary of the relevant novel developments in this field.

Motor Nerve Conduction Block Estimation in Demyelinating Neuropathies by Deconvolution

A deconvolution method is proposed for conduction block (CB) estimation based on two compound muscle action potentials (CMAPs) elicited by stimulating a nerve proximal and distal to the region in which the block is suspected. It estimates the time delay distributions by CMAPs deconvolution, from which CB is computed. The slow afterwave (SAW) is included to describe the motor unit potential, as it gives an important contribution in case of the large temporal dispersion (TD) often found in patients. The method is tested on experimental signals obtained from both healthy subjects and pathological patients, with either Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) or Multifocal Motor Neuropathy (MMN). The new technique outperforms the clinical methods (based on amplitude and area of CMAPs) and a previous state-of-the-art deconvolution approach. It compensates phase cancellations, allowing to discriminate among CB and TD: estimated by the methods of amplitude, area and deconvolution, CB showed a correlation with TD equal to 39.3%, 29.5% and 8.2%, respectively. Moreover, a significant decrease of percentage reconstruction errors of the CMAPs with respect to the previous deconvolution approach is obtained (from a mean/median of 19.1%/16.7% to 11.7%/11.2%). Therefore, the new method is able to discriminate between CB and TD (overcoming the important limitation of clinical approaches) and can approximate patients’ CMAPs better than the previous deconvolution algorithm. Then, it appears to be promising for the diagnosis of demyelinating polyneuropathies, to be further tested in the future in a prospective clinical trial.

Facial onset sensory and motor neuropathy in a pain clinic outpatient: a case report

Background Facial onset sensory and motor neuropathy is a very rare sensorimotor disorder characterized by facial onset and gradual progression, with approximately 100 cases reported worldwide in 2020. We report on our experience with a facial onset sensory and motor neuropathy case in our outpatient pain clinic. Case presentation A 71-year-old Japanese man with a previous diagnosis of trigeminal nerve palsy complained of facial paresthesia, cervical pain, and arm numbness. Cervical facet arthropathy was diagnosed initially, but neither pharmacotherapy nor nerve blocking alleviated his symptoms. We suspected bulbar palsy based on the presence of tongue fasciculation, which prompted referral to a neurologist. Based on a series of neurological examinations, facial onset sensory and motor neuropathy was ultimately diagnosed. Conclusions Pain clinicians must be mindful of rare diseases such as facial onset sensory and motor neuropathy; if they are unable to make a diagnosis, they should consult with other competent specialists.

Cryotherapy for Prevention of Taxane-Induced Peripheral Neuropathy: A Meta-Analysis

PurposeTaxanes are widely used in gynecological cancer therapy, however, taxane-induced peripheral neuropathy (TIPN) limits chemotherapy dose and reduces patients’ quality of life. As a safe and convenient intervention, cryotherapy has been recommended as a promising intervention in the recent clinical guidelines for the prevention of TIPN. Although there are a considerable number of studies which explored the use of cryotherapy in preventing chemotherapy-induced peripheral neuropathy (CIPN), there is insufficient large-scale clinical evidence. We performed a meta-analysis on the current available evidence to examine whether cryotherapy can prevent TIPN in cancer patients receiving taxanes.MethodsWe searched databases including PubMed, Embase, and Cochrane from inception to August 3, 2021 for eligible trials. Clinical trials that examined the efficacy of cryotherapy for prevention of TIPN were included. The primary outcome was the incidence of TIPN, and secondary outcomes were incidence of taxane dose reduction and changes in nerve conduction studies. The meta-analysis software (RevMan 5.3) was used to analyze the data.ResultsWe analyzed 2250 patients from 9 trials. Assessments using the Common Terminology Criteria for Adverse Events (CTCAE) score showed that cryotherapy could significantly reduce the incidence of motor and sensory neuropathy of grade≥2 (sensory: RR 0.65, 95%CI 0.56 to 0.75, p<0.00001; motor: RR 0.18, 95% CI [0.03, 0.94], p=0.04). When evaluated using the Patient Neuropathy Questionnaire (PNQ), cryotherapy demonstrated significant reduction in the incidence of sensory neuropathy (RR 0.11, 95% CI 0.04 to 0.31], p<0.0001), but did not show significant reduction in the incidence of motor neuropathy (RR 0.46, 95% CI 0.11 to 1.88, p=0.28). Cryotherapy was associated with reduced incidences of taxane dose reduction due to TIPN (RR 0.48, 95% CI [0.24, 0.95], p=0.04) and had potential to preserve motor nerves.ConclusionsCryotherapy is likely to prevent TIPN in patients receiving taxanes. High quality and sufficient amount of evidence is warranted.