The Diabetic Radiculoplexus Neuropathies

Most diabetic neuropathies are associated with prolonged glucose exposure and are not due to inflammatory causes. The diabetic radiculoplexus neuropathies are different in that they are likely inflammatory neuropathies. They are a group of disorders that involve the lumbosacral, thoracic and cervical myotomes in a multifocal pattern. They are due to inflammatory damage to roots, plexuses and peripheral nerve from ischemic injury from microvasculitis. Varieties include diabetic lumbosacral radiculoplexus neuropathy (DLRPN), painless motor predominant diabetic neuropathy, diabetic thoracic radiculopathy and diabetic cervical radiculoplexus neuropathy. These conditions are associated with weight loss and can be triggered by rapid glycemic correction, exercise and surgical procedures. They are one of the most common forms of inflammatory neuropathy. Controlled studies with intravenous corticosteroids failed to show efficacy of the primary endpoint but the pain was markedly improved.

P. James B. Dyck is a professor of Neurology, Mayo Clinic and head of the peripheral nerve section. Jim did medical school at University of Minnesota, residency at Washington University and fellowship at Mayo Clinic. He has been head of the UCNS clinical neuromuscular pathology certification, chair of the ICNMD and past chair of the IDNC of the PNS.

The Multiple Dimensions of Peripheral Nerve Immunology

When autoimmunity affects peripheral nerves in inflammatory neuropathies, this can result in considerable morbidity and diagnostic and therapeutic challenges. Novel multi-omic technologies can help to address these challenges, by broadening our understanding of underlying mechanisms and identifying targetable pathways. We previously found widespread transcriptional changes, supporting a view of inflammatory neuropathies as ‚pan-nerve diseases‘. The presentation will outline how endoneurial lipid release and clearance may link myelin damage with extra-endoneurial nerve remodelling including perineurial hyperplasia. This may be generalizeable across conditions with tissue damage and immune-triggered local lipid excess could be diagnostically and therapeutically exploited. Multi-dimensional analyses of cerebrospinal fluid solutes and cells add additional diagnostic and mechanistic tools in inflammatory neuropathies. Together, these approaches reframe available resources for mechanistic discovery and for diagnostic biomarkers in inflammatory neuropathies.

Gerd Meyer zu Hörste leads a translational neuroimmunology group with focus on immune mechanisms at nervous-system interfaces including inflammatory neuropathies. His work combines clinical cohorts with multi-omics and cellular immunology. His expertise bridges basic and translational neuroimmunology with the inflammatory neuropathy field.

Glial Modulation of Sensory Function and Nerve Repair

Peripheral nerves relay sensory information from the body to the central nervous system and have a remarkable, yet incomplete, capacity for repair after injury. Work from our laboratory investigates the cellular and molecular mechanisms that enable nerve regeneration and shape sensory function. A major focus is satellite glial cells, the glial cells that fully envelop sensory neuron cell bodies in dorsal root ganglia. Our studies show that these cells actively regulate both axon regeneration and neuronal excitability. I will discuss recent findings identifying satellite glial cell-derived extracellular matrix proteins, including members of the Fibulin family, as modulators of potassium channel function, sensory neuron activity, and pain sensitivity. I will also describe ongoing translational studies using human dorsal root ganglia tissue from donors with and without chronic pain disorders. Together, these studies highlight the contribution of multiple non-neuronal cell types to sensory dysfunction after injury, in disease, and with aging.

Dr. Valeria Cavalli is the Robert E. and Louise F. Dunn Professor of Biomedical Research and Neuroscience at Washington University in St. Louis. Her laboratory investigates the molecular and cellular mechanisms that repair damaged axons and regulate sensory functions in multiple conditions, including injury, neurodevelopmental disorders and aging. By integrating experimental models with studies of human tissue, her work aims to identify translational therapeutic targets to improve neuronal function in the injured, diseased and aging peripheral nervous system. Dr. Cavalli earned her PhD degrees from the University of Geneva, Switzerland, where she studied the membrane trafficking in cells. She continued with postdoctoral training at the University of California, San Diego, where she studied how information about injury is conveyed from the lesion site in the axon back to the soma. A post-doctoral fellowship from the Christopher and Dana Reeve Foundation was influential in how she pursued her career.

Decoding Skin-Nerve Crosstalk in Painful Peripheral Neuropathy: Omics Insights Toward Precision Medicine

Peripheral neuropathic pain, particularly painful diabetic neuropathy (PDN), remains a major clinical challenge. Patients vary widely in their symptoms, patterns of sensory loss, and disease progression, yet current treatments rarely account for this heterogeneity. Understanding the mechanisms behind these differences is essential to developing more precise therapies. In this plenary lecture, Dr. Menichella will present a framework in which the skin is an active participant in peripheral neuropathy. Sensory nerve endings interact with keratinocytes and immune cells in the epidermis, creating a dynamic skin-nerve unit that can influence neuropathic pain, axonal integrity, and disease progression. Drawing on single-cell and spatial omics, advanced proteomics, experimental models, and human tissues, she will highlight findings that implicate epidermal Langerhans cells and keratinocytes in nociceptor sensitization and axonal remodeling. She will also briefly discuss extracellular vesicles as one route of communication between keratinocytes and sensory neurons. The lecture will then turn to the central translational challenge: connecting these molecular discoveries to the experiences of individual patients. Dr. Menichella will discuss how studies of human skin and sensory neurons, deep clinical phenotyping, and integrated multi-omic analyses across well-characterized patient cohorts can reveal mechanisms underlying distinct clinical presentations. By identifying molecular signatures that track with pain, sensory dysfunction, and disease progression, this approach aims to uncover actionable biomarkers and guide the development of localized, mechanism-based treatments. Together, these studies offer a path from discoveries in the skin-nerve unit to precision medicine for people living with peripheral neuropathy.

Daniela Maria Menichella, MD, PhD, is an Associate Professor of Neurology and Pharmacology at Northwestern University Feinberg School of Medicine. She received her medical and doctoral degrees from the University of Milan, completed postdoctoral training at Wayne State University and Harvard Medical School, and completed her neurology residency at Northwestern. Dr. Menichella directs Northwestern’s Peripheral Neuropathy Multidisciplinary Clinic and Charcot-Marie-Tooth Association Center of Excellence. She is active in NIH NeuroNEXT and serves as Principal Investigator of the Northwestern clinical hub within the NIH-funded Early Phase Pain Investigation Clinical Network (EPPIC-Net). Her NIH-funded research investigates how interactions among sensory neurons, skin cells, and immune cells contribute to neuropathic pain and axonal degeneration, particularly in painful diabetic neuropathy. Her laboratory combines experimental models, imaging, electrophysiology, and single-cell approaches with studies of human dorsal root ganglia and skin biopsies. By linking these mechanistic studies with detailed clinical phenotyping, she aims to explain why peripheral neuropathies affect patients differently and to identify targets for more precise treatments. Dr. Menichella’s honors include the Peripheral Nerve Society’s Peter James Dyck Award (2013), the American Neurological Association’s Wolfe Neuropathy Research Prize (2019), and election as a Fellow of the United States Association for the Study of Pain (2025).

Understanding Sensory Neuron Resilience Over a Lifetime

Neurons are post-mitotic and thus the consequences of death are dire compared with proliferative cells. At the same time, primary afferent nociceptors are subject to noxious stimuli that can provoke hyper-excitation, chronic pain, afferent degeneration, or death – especially under maladaptive conditions associated with diabetes or other metabolic challenges. This presentation will discuss recent studies asking how distinct classes of sensory neurons deal with such challenges over a lifetime.

David Julius is a native of Brooklyn, NY. He received his undergraduate degree from MIT, where he worked with Alexander Rich studying mechanisms of tRNA aminoacylation. He then moved to UC Berkeley for graduate studies with Jeremy Thorner and Randy Schekman, elucidating mechanisms of peptide hormone processing and secretion, followed by postdoctoral studies with Richard Axel at Columbia University, where he identified genes encoding members of the serotonin receptor family. David then joined the faculty at UC San Francisco, where his research is focused on understanding molecular mechanisms of pain and sensory adaptation. David is a member of the US National Academies of Science and Medicine and the American Academy of Arts and Sciences. He has received numerous awards, including the Shaw Prize in Life Sciences and Medicine, the Canada Gairdner International Award, the Breakthrough Prize in Life Sciences, and the Nobel Prize in Physiology or Medicine.

From Genes to Treatments: Strategic Considerations for Inherited Neuropathies

We are now in the era of therapies for inherited neuropathies with multiple therapies in either pre-clinical or clinical development. This presentation will cover a range of strategic considerations in therapy development including the causative genes, phenotype pathogenesis, natural history, outcome measures, biomarkers and what we have learned from inherited neuropathies that we have treated.

Mary M. Reilly graduated from University College Dublin in 1986, received her MD in 1996, FRCP in 2002 and FRCPI in 2003. She was appointed consultant neurologist at the National Hospital for Neurology and Neurosurgery in 1998 and a Professor of Clinical Neurology at UCL in 2010. She leads the peripheral nerve clinical and research group and is head of the Division of Clinical Neurology in UCL Queen Square Institute of Neurology. She runs a research program in the inherited neuropathies especially in Charcot Marie Tooth disease and Transthyretin amyloidosis. She is Past President of the Peripheral Nerve Society (PNS), the Association of British Neurologists (ABN) and the British Peripheral Nerve Society. She was elected a Fellow of the Academy of Medical Sciences in 2020 and made a Fellow of the European Academy of Neurology in 2023. She was awarded an honorary MBE for her services to medicine 2025.

Glia Teach Neurons to Fire: Schwann Cell Regulation of Sensory Excitability

While neuronal excitability is often considered an intrinsic property of neurons, sensory neurons are surprisingly dependent on their surrounding glia to function. In this lecture, I will discuss our discovery that Schwann cells actively instruct the developmental excitability of peripheral sensory neurons. Through biochemical and genetic analyses, we identified that Schwann cells synthesize and secrete prostaglandin E₂ (PGE₂). Schwann cell-derived PGE₂ acts on sensory neurons to transcriptionally drive the expression of key voltage-gated sodium channels. Mice lacking Schwann cell PGE₂ fail to properly upregulate these channels, resulting in dampened sensory excitability and profound deficits in pain and mechanosensation. In the spirit of Richard and Mary Bunge’s pioneering work on Schwann cell–axon interactions, this talk highlights how peripheral glia do far more than insulate axons—they program the fundamental electrical properties of the peripheral nervous system.

 Dr. J. Bradley Zuchero is an Associate Professor of Neurosurgery at the Stanford University School of Medicine. The Zuchero Lab investigates how cell-cell interactions between glia and neurons build, regulate, and repair a functional nervous system. By combining novel genetic tools, advanced imaging, and biochemistry, his research group explores the cellular mechanisms driving central nervous system myelination, as well as how myelinating glia instruct the functional development and excitability of peripheral sensory circuitries. Ultimately, his lab aims to leverage these discoveries to identify therapeutic targets for diseases like multiple sclerosis and neurodegeneration. Dr. Zuchero’s contributions to glial biology have been recognized by numerous prestigious honors, including the Beckman Young Investigator Award, the McKnight Scholar Award, the Harry Weaver Neuroscience Scholar Award, and his selection as the Covert-Matera Families Endowed Faculty Scholar.

Fixing the Fold: From Gene Identification to Gene Therapy for CMT4B neuropathies

CMT4 (Charcot-Marie-Tooth) type 4 encompasses a group of severe, autosomal recessive demyelinating motor and sensory neuropathies that typically present in infancy or childhood. Within this group, CMT4B forms a distinct subgroup made up of three genetically separate entities: CMT4B1 results from mutations in MTMR2 (Myotubularin-related protein 2), while CMT4B2 and CMT4B3 arise from mutations in MTMR13/SBF2 and MTMR5/SBF1, respectively. A hallmark feature of CMT4B1 and CMT4B2 in particular is the presence of myelin outfoldings in the peripheral nerve. The proteins encoded by these three genes are structurally related to protein tyrosine phosphatases, but with a key functional distinction: rather than acting on phosphoproteins, the catalytically active members of this family dephosphorylate phosphoinositide lipids, placing them at the center of lipid signaling regulation and its downstream effects on cell function. Beyond CMT4B, mutations across the broader MTMR gene family are linked to other neuromuscular conditions, including congenital myopathies, and variants in several MTMR genes have additionally been implicated in more common, multifactorial conditions such as cancer and obesity. Having outlined this broader context, this lecture will focus specifically on CMT4B1 and MTMR2, reviewing the clinical and genetic features of the disease and tracing how research has informed the development of gene therapy strategies.

Alessandra Bolino is a Professor of Cell Biology at the Vita-Salute San Raffaele University in Milan, Italy, and Group Leader of the Human Inherited Neuropathies Unit at the San Raffaele Hospital. She has served as the President of the Peripheral Nerve Society since 2025.