COEXISTENCE OF TWO CHRONIC NEUROPATHIES IN A YOUNG CHILD: CHARCOT-MARIE-TOOTH DISEASE TYPE 1A AND CHRONIC INFLAMMATORY DEMYELINATING POLYNEUROPATHY

We report an 18-month-old Charcot-Marie-Tooth type 1A (CMT1A) patient who developed a rapid-onset neuropathy, with proximal and distal weakness, and non-uniform nerve conduction studies. The neuropathy responded well to immunomodulation, confirming the coexistence of an inherited and an inflammatory neuropathy. Unexpected clinical and/ or electrophysiological manifestations in CMT1A patients should alert clinicians to concomitant inflammatory neuropathy. In addition, this association raises reflections about disease mechanism in CMT1A. Muscle Nerve 42: 598-600, 2010

Dorsal root ganglionectomy for the diagnosis of sensory neuropathies. Surgical technique and results

Background: Inflammatory diseases stand out among sensory neuronopathies because, in their active phase, they can be treated with immunosuppressive agents. Immunosuppressive therapy may present severe adverse effects and requires previous inflammatory activity confirmation. Sensory neuronopathies are diagnosed based on clinical and EMG findings. Diagnostic confirmation and identification of inflammatory activity are based on sensory ganglion histopathological examination. We describe the surgical technique used for dorsal root ganglionectomy in patients with clinical/EMG diagnosis of sensory neuronopathies. Methods: The sensory ganglion was obtained from 15 patients through a small T7-T8 hemilaminectomy and foraminotomy to expose the C7 root from its origin to the spinal nerve bifurcation. In 6 patients, the dural cuff supposed to contain the ganglion was resected en bloc; and in 9 patients, the ganglion was obtained through a longitudinal incision of the dural cuff and microsurgical dissection from the ventral and dorsal roots and radicular arteries. All ganglia were histopathologically examined. Results: No ganglion was found in the dural cuff in 2 patients submitted to en bloc removal, and the ganglion was removed in all patients who underwent microsurgical dissection. All but 2 patients that had ganglion examination presented a neuronopathy of nerve cell loss, 3 with mononuclear inflammatory infiltrate. These patients underwent immunosuppressive therapy, and 2 of them presented clinical improvement. No surgical complications were observed. Conclusions: Microsurgical dorsal root ganglionectomy for diagnosing inflammatory sensory ganglionopathies was effective and safe. Although safe, en bloc resection of the proximal dural cuff was not effective for this purpose. (c) 2008 Published by Elsevier Inc.

Neuropatías asociadas a anticuerpos anti-GM1. Anti-GM1 antibodies associated neuropathies.

Durante varios años estudiamos los anticuerpos presentes en pacientes con neuropatías e individuos normales. Recientemente hemos implementado un modelo animal de neuropatía inducido por inmunización con GM1, y nos proponemos confirmar en este modelo las observaciones realizadas en pacientes. Se caracterizará la respuesta inmune humoral durante la inducción de la enfermedad, y la posible existencia de un mecanismo regulatorio mediado por anticuerpos bloqueantes de anticuerpos anti-GM1. Además, el modelo nos permitirá ensayar diferentes estrategias terapéutica tales como plasmaféresis específica, bloqueo de anticuerpos por antígenos solubles e inducción de anticuerpos bloqueantes.

Exploring Parallels Between Molecular Changes Induced in PNS by Aging and Demyelinating Neuropathies

The peripheral nervous system (PNS) is involved in many age-dependent neurological deficits, including numbness, pain, restless legs, trouble with walking and balance that are commonly found in the elderly. These symptoms generally result from demyelination and/or loss of axonal integrity. However, the precise identity of age-regulated molecular changes in either neuronal or glial compartments of the nerve is unclear. Interestingly, these deficiencies are also present in inherited neuropathies, where the expressivity of the rapid and early onset phenotypes is undeniably more severe than in normal aging. Nevertheless, especially the molecular changes underlying loss of axonal integrity in neuropathy condition are also poorly understood. To unravel molecular mechanisms affected by PNS aging, we used wildtype mice at 17 time-points from day of birth until senescence (28 months-old). For the neuropathy study, we focused on 56 day-old Schwann cell-specific neuropathy-inducing mutants, MPZCre/1/ LpinfE2-3/fE2-3 and MPZCre/1/ScapfE1/fE1 mice, that have, at this age, already developed neuropathic symptoms. Transcriptomes of dissected Schwann cell-containing endoneurium or sensory neuron-containing dorsal root ganglia have been analyzed throughout time or genotypes, using Illumina Bead Chips. Following data validation, we identified groups of differentially expressed genes in the development, aging and in the neuropathic mutants, in both glial and neuronal compartments. We detected substantial differences in the dynamics of changes in gene expression during development and aging between these two compartments. Furthermore, considering the above-mentioned phenotypic similarities, we integrated aging and mutant data. Interestingly, we observed that there are some parallels at the molecular level between processes involved in aging, which leads to less severe and more progressive PNS alterations, and in the rapid onset peripheral neuropathies. Apart from helping the understanding of molecular alterations underlying age-related PNS phenotypes, this data should also contribute to the identification of pathways that could be used as targets for therapeutical approaches to prevent complications associated with both aging and inherited forms of neuropathies.

Toxic and drug-induced peripheral neuropathies: updates on causes, mechanisms and management.

PURPOSE OF REVIEW: This review discusses publications highlighting current research on toxic, chemotherapy-induced peripheral neuropathies (CIPNs), and drug-induced peripheral neuropathies (DIPNs). RECENT FINDINGS: The emphasis in clinical studies is on the early detection and grading of peripheral neuropathies, whereas recent studies in animal models have given insights into molecular mechanisms, with the discovery of novel neuronal, axonal, and Schwann cell targets. Some substances trigger inflammatory changes in the peripheral nerves. Pharmacogenetic techniques are underway to identify genes that may help to predict individuals at higher risk of developing DIPNs. Several papers have been published on chemoprotectants; however, to date, this approach has not been shown effective in clinical trials. SUMMARY: Both length and nonlength-dependent neuropathies are encountered, including small-fiber involvement. The introduction of new diagnostic techniques, such as excitability studies, skin laser Doppler flowmetry, and pharmacogenetics, holds promise for early detection and to elucidate underlying mechanisms. New approaches to improve functions and quality of life in CIPN patients are discussed. Apart from developing less neurotoxic anticancer therapies, there is still hope to identify chemoprotective agents (erythropoietin and substances involved in the endocannabinoid system are promising) able to prevent or correct painful CIPNs.

Chemotherapy-induced peripheral neuropathies: an integrative review of the literature

OBJECTIVE: To identify scientific studies and to deepen the knowledge of peripheral neuropathies induced by chemotherapy antineoplastic, seeking evidence for assistance to cancer patients. METHOD: Integrative review of the literature conducted in the databases Latin American and Caribbean Health Sciences (LILACS), Scientific Electronic Library Online (SciELO), Medical Literature Analysis (PubMed/MEDLINE), the Cochrane Library and the Spanish Bibliographic Index Health Sciences (IBECS). RESULTS: The sample consisted of 15 studies published between 2005-2014 that met the inclusion criteria. Studies showed aspects related to advanced age, main symptoms of neuropathy and chemotherapy agents as important adverse effect of neuropathy. CONCLUSION: We identified a small number of studies that addressed the topic, as well as low production of evidence related to interventions with positive results. It is considered important to develop new studies proposed for the prevention and/or treatment, enabling adjustment of the patient's cancer chemotherapy and consequently better service.

Neuropathies diabétiques: tableaux cliniques, détection précoce et appel au spécialiste [Diabetic neuropathies: clinical sub-types, early detection and asking help from the specialist].

In diabetes mellitus, it is expected to see a common, mainly sensitive, distal symmetrical polyneuropathy (DPN) involving a large proportion of diabetic patients according to known risk factors. Several other diabetic peripheral neuropathies are recognized, such as dysautonomia and multifocal neuropathies including lumbosacral radiculoplexus and oculomotor palsies. In this review, general aspects of diabetic neuropathies are examined, and it is discussed why and how the general practionner has to perform a yearly examination. At the present time, some consensuses emerge to ask help from the specialist when faced to other forms of peripheral neuropathies than distal symmetrical DPN.

Revue de la littérature 2011 : neuropathies dysimmunitaires [2011: What's new in dysimmune neuropathies].

There are strong research activities in the field of dysimmune neuropathies. In Guillain-Barré syndrome, new pathophysiological mechanisms have been demonstrated with the potential development of new therapies, a clinical prediction model is applicable early in the course of disease, and under investigation are new treatment strategies with adapted intravenous Ig dosages. In chronic inflammatory demyelinating polyneuropathies, current diagnostic tests are discussed but biomarkers are needed, such as histological changes or differential gene expression in nerve or skin biopsies. The exploration of novel therapeutic approaches including monoclonal antibodies and oral immunosuppressants, known from multiple sclerosis studies, suggests new approaches to treatment. Changes of the peripheral nerves on MR imaging are better known and the usefulness of serum antibodies is reviewed.

Neuropathies périphériques d'origine médicamenteuse [Drug-induced peripheral neuropathy].

Drug-induced peripheral neuropathies are common, secondary to multiple drug classes, in particular chemotherapeutic agents. They have an important impact on patients' quality of life. In recent years, significant progress has been made in the understanding of some pathophysiological mechanisms. The use of more objective assessment tools should allow the development of individualized and more effective therapeutic strategies.

Diabetische Neuropathien: Klinische Manifestationsformen, Früherkennung und Zuweisung zu einem Neurologen [Diabetic Neuropathies: Clinical sub-Types, Early Detection, and Asking Help from Neurologist].

In diabetes mellitus, it is expected to see a common, mainly sensitive, distal symmetrical polyneuropathy (DPN) involving a large proportion of diabetic patients according to known risk factors. Several other diabetic peripheral neuropathies are recognized, such as dysautonomia and multifocal neuropathies including lumbosacral radiculoplexus and oculomotor palsies. In this review, general aspects of DPN and other diabetic neuropathies are examined, and it is discussed why and how the general practionner has to perform a yearly examination. At the present time, some consensuses emerge to ask help from neurologist when faced to other forms of peripheral neuropathies than distal symmetrical DPN.

Revue de la littérature 2013--les neuropathies inflammatoires [2013: what's new in inflammatory neuropathies].

Several high-quality publications were published in 2013 and some major trials studies were started. In Guillain-Barré syndrome, events included the launch of IGOS and a better understanding of diagnostic limits, the effect of influenza vaccination, and better care, but uncertainty remains about analgesics. A new mouse model was also described. In chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), diagnostic pitfalls can be recalled. Our knowledge of underlying pathophysiological processes has improved, and the value of monitoring with function and deficit scores has been demonstrated. IVIG can sometimes be effective longer than expected, but CIDP remains sensitive to corticosteroids, particularly with the long-term beneficial effects of megadose dexamethasone. The impact of fingolimod remains to be demonstrated in an ongoing trial. Advances concerning multifocal motor neuropathy, inflammatory plexopathy, and neuropathy with anti -MAG activity are discussed but treatments already recognized as effective should not be changed. Imaging of peripheral nerve progresses.

Cranial neuropathies in granulomatosis with polyangiitis (Wegener's): a case-based review.

The purpose of this case-based review is to highlight cranial nerve involvement in granulomatosis with polyangiitis (Wegener's). In this disease, cranial nerve involvement may be less frequent than other neurological manifestations, but often goes unrecognized by physicians as a sign of the disease, and its prevalence and importance is likely underestimated. Awareness of this aspect of the disease is necessary to make the proper diagnosis rapidly, as it can be a major feature of a patient's presentation. We also briefly discuss the known pathogenic mechanisms, which could be important when selecting the best therapeutic option.