An n-of-one RCT for intravenous immunoglobulin G for inflammation in hereditary neuropathy with liability to pressure palsy (HNPP).
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ABSTRACT:
SUBMITTER: Vrinten C
PROVIDER: S-EPMC4941134 | biostudies-literature | 2016 Jul
REPOSITORIES: biostudies-literature
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An n-of-one RCT for intravenous immunoglobulin G for inflammation in hereditary neuropathy with liability to pressure palsy (HNPP).
Vrinten Charlotte C Gu Xin X Weinreich Stephanie S SS Schipper Mirjam H MH Wessels Judith J Ferrari Michel D MD Hoijtink Herbert H Verschuuren Jan J G M JJ
Journal of neurology, neurosurgery, and psychiatry 20150717 7
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Project description:BackgroundHereditary neuropathy with liability to pressure palsy (HNPP) is an autosomal dominant disorder most commonly presenting with acute-onset, non-painful focal sensory and motor mononeuropathy. Approximately 80% of patients carry a 1.5 Mb deletion of chromosome 17p11.2 involving the peripheral myelin protein 22 gene (PMP22), the same duplicated in Charcot-Marie-Tooth 1A patients. In a small proportion of patients the disease is caused by PMP22 point mutations.Case presentationWe report on a familial case harbouring a new point mutation in the PMP22 gene. The proband is a 4-years-old girl with acute onset of focal numbness and weakness in her right hand. Electroneurography demonstrated transient sensory and motor radial nerves involvement. In her father, reporting chronic symptoms (cramps and exercise-induced myalgia), we uncovered mild atrophy and areflexia on clinical examination and a mixed (predominantly demyelinating) polyneuropathy with sensory-motor involvement on electrophysiological study. Both carried a nucleotidic substitution c.178 + 2 T > C on intron 3 of the PMP22 gene, involving the splicing donor site, not reported on databases but predicted to be likely pathogenic.ConclusionsWe described a previously unreported point mutation in PMP22 gene, which led to the development of a HNPP phenotype in a child and her father. In children evaluated for a sensory and motor transient episode, HNPP disorder due to PMP22 mutations should be suspected. Clinical and electrophysiological studies should be extended to all family members even in the absence of previous episodes suggestive for HNPP.
| S-EPMC5658948 | biostudies-literature
Project description:ABSTRACT Hereditary neuropathy with liability to pressure palsy (HNPP) is a rare autosomal dominant disease characterized by focal, recurrent, demyelinating peripheral neuropathies. It is caused by deletions of the gene encoding for peripheral myelin protein 22 (PMP22) on chromosome 17. While it may range widely, the most common clinical presentation is an acute, focal mononeuropathy with numbness or muscle weakness after trauma or compression. Diagnostic tools include electrophysiological studies, genetic tests and nerve biopsies. There is no standard surgical or pharmacological treatment. The course of the disease is usually benign, with spontaneous improvement after most episodes of peripheral nerve palsy. HNPP is best managed by early detection, preventative measures, and subsequent treatment of symptoms. According to the medical literature, operative treatment was undertaken in few cases and limited to decompression of the nerve at the classic entrapment sites of the carpal or cubital tunnels. We present a case of multiple tendon transfer (pronator teres to extensor carpi radialis brevis and flexor carpi radialis to extensor digitorum communis) with a two-year follow-up in a 24-year-old woman with HNPP who was affected by irreversible radial nerve palsy, and conclude with a review of the medical literature related to the disease.
| S-EPMC10009638 | biostudies-literature
Project description:This review summarizes the clinical and electromyography (EMG) characteristics and peripheral myelin protein 22 (PMP22) gene-related diseases of hereditary neuropathy with liability to pressure palsies (HNPP). Clinical, EMG, and laboratory data of patients diagnosed with HNPP at our institution from 2022 to 2023 were retrospectively reviewed. Relevant literature from January 2003 to June 2024 was retrieved from PubMed using the keywords "hereditary neuropathy with liability to pressure palsies" and "HNPP." Clinical manifestations, EMG characteristics, and gene detection results of HNPP were summarized. All patients exhibited transient neurological symptoms and tested positive for the PMP22 deletion. EMG revealed multiple peripheral nerve abnormalities. Sixty-eight studies meeting the inclusion and exclusion criteria were included, comprising 124 HNPP cases (including six from our study), with 67 males and 57 females. The mean age of onset and diagnosis for the 124 cases were 26.5 ± 18 years and 32.7 ± 18.9 years, respectively, with a maximum onset-to-diagnosis interval of 40 years. Typical weakness and numbness in vulnerable areas were observed in 63.7% of cases, with 62% experiencing recurrent episodes. Atypical symptoms were present in 29.8%, while 6.5% were asymptomatic. Patients exhibited pain and muscular dystrophy (17.7%), pes cavus (12.1%), and a family history of HNPP (64.5%). Among symptomatic patients, triggers were traction or compression (57.8%), temperature changes (3.4%), or unclear (38.8%). Heterozygous PMP22 deletions and other PMP22 gene mutations were found in 77.4% and 22.6% of cases, respectively.
| S-EPMC11638277 | biostudies-literature
Project description:Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal neuropathy that is commonly caused by a reciprocal 1.5 Mb deletion on chromosome 17p11.2, at the site of the peripheral myelin protein 22 (PMP22) gene. Other patients with similar phenotypes have been shown to harbor point mutations or small deletions, although there is some clinical variation across these patients. In this report, we describe a case of HNPP with copy number changes in exon or promoter regions of PMP22. Multiplex ligation-dependent probe analysis revealed an exon 1b deletion in the patient, who had been diagnosed with HNPP in the first decade of life using molecular analysis.
| S-EPMC4258352 | biostudies-literature
Project description:Peripheral myelin protein 22 (PMP22) is a component of compact myelin in the peripheral nervous system. The amount of PMP22 in myelin is tightly regulated, and PMP22 over or under-expression cause Charcot-Marie-Tooth 1A (CMT1A) and Hereditary Neuropathy with Pressure Palsies (HNPP). Despite the importance of PMP22, its function remains largely unknown. It was reported that PMP22 interacts with the β4 subunit of the laminin receptor α6β4 integrin, suggesting that α6β4 integrin and laminins may contribute to the pathogenesis of CMT1A or HNPP. Here we asked if the lack of α6β4 integrin in Schwann cells influences myelin stability in the HNPP mouse model. Our data indicate that PMP22 and β4 integrin may not interact directly in myelinating Schwann cells, however, ablating β4 integrin delays the formation of tomacula, a characteristic feature of HNPP. In contrast, ablation of integrin β4 worsens nerve conduction velocities and non-compact myelin organization in HNPP animals. This study demonstrates that indirect interactions between an extracellular matrix receptor and a myelin protein influence the stability and function of myelinated fibers.
| S-EPMC5924464 | biostudies-literature
Project description:Trigeminal sensory neuropathy can be caused by a variety of conditions, including local, traumatic, iatrogenic, or systemic causes. Diagnosis and management remain a challenge for maxillofacial surgeons and neurologists. Therefore, a good clinical examination and objective tests and imaging are needed when diagnosing patients who present with facial numbness. We present a case with spontaneous episodes of facial paresthesia. He was diagnosed with hereditary neuropathy with liability to pressure palsies (HNPP), a rare condition that affects the peripheral nerves. Only a few case reports that describe involvement of the cranial nerves in patients with HNPP were found in the literature, and facial paresthesia has not been previously reported.
| S-EPMC8635109 | biostudies-literature
Project description:RationaleHereditary neuropathy with liability to pressure palsy (HNPP) is an episodic, multifocal neuropathy, with a typical clinical presentation of recurrent transient pressure palsies, which is induced by a PMP22 deletion. Another neuropathy caused by a PMP22 duplication is Charcot-Marie-Tooth disease type 1A (CMT1A). PMP22 is a gene coding a protein called peripheral myelin protein 22 (PMP22), which plays an essential role in the formation and maintenance of compact myelin. Coexistence of type 2 diabetes mellitus (T2DM) and CMT1A has been reported in many work, however HNPP patients with T2DM are rare, and comorbidity of HNPP and psoriasis has not been reported previously. Electrophysiological features of HNPP has been found progressing with aging. Patient concerns: Here we present a 20-year-old man who exhibited lower extremity weakness and foot drop as the initial manifestation.DiagnosesHNPP was diagnosed on the basis of clinical features, positive sural nerve biopsy findings, and genetic testing results. Moreover, physical examination, blood/urine glucose test, and diabetes-related autoantibodies investigations demonstrated that he had psoriasis and T2DM. The electrophysiological manifestations revealed profound demyelinating injuries and axonal injuries in distal peripheral nerves and facial nerves, which were more severe than general HNPP cases.InterventionsThe young patient was treated with continuous subcutaneous insulin infusion and blood glucose monitoring, and then transferred to oral acarbose therapy. The psoriatic lesions were treated with calcipotriol ointment.OutcomesIn the follow-up, the right leg weakness was alleviated, and his gait was improved.LessonsThe findings indicate that diabetes mellitus may have an impact on the severity of HNPP. Physicians should consider that worsening of symptoms might result from newly diagnosed diabetes mellitus while treating patients with HNPP.
| S-EPMC5428644 | biostudies-literature
Project description:ObjectiveThis is the first double-blind randomized controlled trial evaluating the efficacy and safety of IV immunoglobulin (IVIG) vs placebo in patients with idiopathic small fiber neuropathy (I-SFN).MethodsBetween July 2016 and November 2018, 60 Dutch patients with skin biopsy-proven I-SFN randomly received a starting dose of IVIG (2 g/kg body weight) or matching placebo (0.9% saline). Subsequently, 3 additional infusions of IVIG (1 g/kg) or placebo were administered at 3-week intervals. The primary outcome was a 1-point change in Pain Intensity Numerical Rating Scale score at 12 weeks compared to baseline.ResultsThirty patients received IVIG, and 30 received placebo. In both groups, 29 patients completed the trial. In 40% of patients receiving IVIG, the mean average pain was decreased by at least 1 point compared to 30% of the patients receiving placebo (p = 0.588, odds ratio 1.56, 95% confidence interval 0.53-4.53). No significant differences were found on any of the other prespecified outcomes, including general well-being, autonomic symptoms, and overall functioning and disability.ConclusionsThis randomized controlled trial showed that IVIG treatment had no significant effect on pain in patients with painful I-SFN.Trial registration informationClinicalTrials.gov Identifier: NCT02637700, EudraCT 2015-002624-31.Classification of evidenceThis study provides Class I evidence that for patients with painful I-SFN, IVIG did not significantly reduce pain compared to placebo.
| S-EPMC8205474 | biostudies-literature
Project description:ObjectiveMultifocal motor neuropathy is a rare chronic immune-mediated neuropathy with impaired grip strength representing a common symptom. While intravenous immunoglobulin G is an effective treatment for the disease, significant variation in treatment response has been observed but not well understood. This analysis characterized dose-exposure-response relationships in multifocal motor neuropathy, using grip strength as a clinical efficacy measure.MethodsSerum immunoglobulin G trough concentrations and grip strength data for the more affected hand from a Phase 3, randomized, double-blind, placebo-controlled, crossover trial of intravenous immunoglobulin 10% in 44 patients with multifocal motor neuropathy (NCT00666263) were used to develop a population pharmacokinetic-pharmacodynamic model.ResultsThe model adequately described the observed pharmacokinetic and pharmacodynamic data and relationships between intravenous immunoglobulin 10% dose, serum immunoglobulin G trough levels, grip strength, and inter-patient variabilities in multifocal motor neuropathy. Model-based simulations for various dosing regimens (0.4-2.0 g/kg every 2-4 weeks) indicated that ≥1.6 g/kg/month would achieve clinically meaningful improvements in grip strength (≥4 kg) in ≥70% of patients. More frequent dosing at an equivalent monthly dose led to a more consistent response in grip strength. Furthermore, splitting the dose over multiple days for high doses (>1 g/kg) did not impact grip strength.InterpretationThese findings suggest that the majority of patients with multifocal motor neuropathy would respond rapidly to intravenous immunoglobulin 10% with a range of dosing regimens. Shorter dosing intervals may avoid the diminishing response seen with longer dosing intervals. Dose-splitting provided similar outcomes while offering flexibility and convenience.
| S-EPMC11330225 | biostudies-literature
Project description:IntroductionIntravenous immunoglobulin (IVIG) is the only approved treatment for multifocal motor neuropathy (MMN), a rare, chronic, immune-mediated demyelinating neuropathy. There is a significant gap in understanding of the role of serum immunoglobulin G (IgG) levels in the efficacy of IVIG in affected patients. We aimed to characterize the interplay between dose and exposure of IVIG and the effects of patient factors on individual variabilities.MethodsSerum IgG trough concentration data from a phase 3, randomized, double-blind, placebo-controlled, crossover trial of IVIG 10% in 44 patients with MMN (NCT00666263) were analyzed using fit-for-purpose population PK modeling. Patient factors were tested as covariates, and IgG PK profiles following various dosing regimens were simulated.ResultsSerum IgG levels, with significant inter-patient variability, correlated with dose and treatment interruptions at the individual patient level. Simulated data for various dosing regimens (0.4-2 g/kg once every 1-4 weeks [Q1-4W]) revealed that more frequent dosing provided more stable IgG levels than less frequent dosing, and dose splitting over multiple days had no significant effects on PK.DiscussionIn patients with MMN, stable dosing and consistent serum IgG levels are crucial to avoid negative responses owing to treatment interruptions. Dosing intervals more frequent than Q4W may alleviate periodic symptom deterioration. Dose splitting potentially offers flexibility for patients requiring large volumes of IVIG without negatively affecting serum IgG PK, while maintaining treatment efficacy. Variability in serum IgG levels between patients suggests that individualizing IVIG treatment regimens and target IgG levels may play a key role in managing MMN.
| S-EPMC11580011 | biostudies-literature