BACKGROUND:Neuralgic amyotrophy (NA) causes acute episodes of neuropathic pain in the upper limbs, followed by weakness and atrophy. NA can be idiopathic (INA) or hereditary (HNA). The SEPTIN9 gene has been linked to HNA. This study aimed to characterize the clinical and prognostic features of patients with SEPTIN9-related HNA. METHODS:This retrospective multicenter study included all adult patients diagnosed with SEPTIN9-related HNA in France from January 2012-June 2025. INA patients were included as controls. RESULTS:Twelve patients with SEPTIN9-related HNA and 25 with INA were included. A family history of NA (75%) and dysmorphic features (50%) were reported exclusively in the SEPTIN9 group. The median age at neurological episode was significantly lower in the SEPTIN9 group (26.0 years) than in the INA group (38.5 years; p < 0.01). Multiple episodes were more frequent in the SEPTIN9 group (75%) than in the INA group (24%; p < 0.01). Distal upper-limb nerves were more frequently affected in SEPTIN9-related HNA episodes than in INA episodes. Sensory symptoms were significantly more frequent in SEPTIN9-related HNA episodes (57%) than in INA episodes (22%; p < 0.01). A higher proportion of SEPTIN9-related HNA patients had a modified Rankin Scale score ≥ 2 (42%) compared with INA patients (16%), although this difference did not reach statistical significance (p = 0.12). CONCLUSIONS:While not completely sensitive or specific, certain features may prompt clinicians to suspect a SEPTIN9-related form when assessing a patient with NA: young age, dysmorphic features, a family history of NA, repeated episodes, sensory symptoms, and distal nerve involvement affecting the upper limbs.

INTRODUCTION/AIMS:Identifying factors associated with short-term relapse is essential for tailoring maintenance treatment on a case-by-case basis in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We sought to determine whether changes in demyelinating electrophysiological features during treatment could predict relapse after treatment discontinuation in a cohort of CIDP patients. METHODS:We conducted a retrospective study of patients with CIDP treated with intravenous immunoglobulin (IVIg), all of whom had a first nerve conduction study (NCS) at treatment initiation or during treatment, while the disease was in a stable phase, followed by a second study at the time of treatment discontinuation. Demyelinating features and the degree of axonal loss were determined during each NCS and compared between the two examinations. RESULTS:Thirty-one consecutive IVIg-responsive CIDP patients were included, with a mean age of 59.1 ± 14.6 years. Twenty (65%) were males. Sixteen patients (52%) relapsed after a mean of 6 months. Most patients demonstrated a reduced total number and type of demyelinating features between the two assessments, but overall, these changes were not different between the relapse and relapse-free groups. Similarly, axonal loss at our first assessment and the progression of axonal loss between our two assessments were not different in the relapse group compared to the relapse-free group. DISCUSSION:In our population of IVIg responsive CIDP patients, we were unable to demonstrate the predictive value of follow-up nerve conduction studies alone for the risk of relapse. Looking at other biomarkers alone or in combination with NCS is necessary.

Current guidelines for immune-related neurotoxicities recommend discontinuation of immune checkpoint inhibitors (ICIs) and steroid therapy in severe cases. However, the management of ICI-related neuropathies remains less standardised, with intravenous immunoglobulin (IVIg) frequently combined with steroids despite limited evidence. This study aims to evaluate the treatment responses to immune-modulatory treatments in a multicenter French cohort of patients with ICI-related neuropathies. We conducted a retrospective analysis of patients with ICI-related neuropathies from six French centers. Clinical, biological and electrophysiological data were collected at baseline, 3 months, and 6 months. Patients were classified into three groups based on neuropathy type: demyelinating, axonal, or multiradiculopathic. The outcome was defined by changes in the modified Rankin Scale (mRS) and the Inflammatory Neuropathy Cause and Treatment (INCAT) disability scores between baseline and follow-up visits. Forty-eight patients with ICI-related neuropathies were identified including 24 demyelinating neuropathies, 18 axonal neuropathies, and 6 multifocal radiculopathies. Most presented with subacute onset and predominant sensory symptoms. ICIs were discontinued in all patients, and immunomodulatory therapy was initiated for severe cases, primarily steroids alone (n = 25) or steroids combined with IVIg (n = 14). Overall, 90% of patients achieved a favourable and rapid outcome: 11 experienced complete recovery, while 32 showed partial or subtotal improvement. No significant advantage was observed in adding IVIg to steroids when comparing the two treatment groups. In the analysis of other variables, a higher baseline disability score (INCAT) was the only factor significantly associated with poorer outcomes. The following variables did not significantly impact outcomes: neuropathy type, ICI class, treatment type, presence of antiganglioside antibodies, or time to ICI discontinuation and steroid initiation. ICIs were reintroduced in eleven patients, with good tolerance observed. Although limited by its retrospective design, this study did not demonstrate a clear added benefit of IVIg when combined with steroids as first-line treatment for ICI-related neuropathies. Reintroduction of ICIs after resolution of neurological impairment appears safe and feasible.

BACKGROUND:Primary neurolymphomatosis (PNL) is a rare clinical entity resulting from direct lymphomatous infiltration into the peripheral nervous system. Its diagnosis is challenging as the hematological condition is unknown at the onset of neurological symptoms. METHODS:We report two of our own cases and the first extensive review of published cases of PNL to delineate its clinical features, paraclinical investigation results, progression, and treatment response more precisely. We extracted demographic data, clinical presentation, results of the investigations performed, type and number of treatments, overall survival, and progression-free survival. RESULTS:We describe 301 cases of PNL in patients with a mean age of 57.9 years, 61% of whom were men. The most common clinical presentation was an often painless asymmetric neuropathy. Other presentations included multifocal neuropathy preferentially affecting the sciatic and peroneal nerves, radiculopathy, brachial plexus lesions, cauda equina syndrome, and cranial nerve palsy. Systemic signs and deterioration of clinical status were uncommon. Diagnosis was established after a median of 8 months, based on histological results (76%) or a cluster of elements in cases of positive PET findings. A B-cell lymphoma was diagnosed in 73% of cases. Systemic chemotherapy (90%) and rituximab (60%) were the most common treatments, with a response rate of 45%. Relapse occurred in 24% of patients, and 55% ultimately died from PNL. Overall survival was 28 months. Type of treatment was not associated with survival. CONCLUSIONS:This literature review provides an overview of the available data concerning PNL presentation and progression.

BACKGROUND:Autosomal recessive mutations in the SH3TC2 gene cause Charcot-Marie-Tooth type 4C (CMT4C) demyelinating peripheral neuropathy. METHODS:In this nationwide observational retrospective study involving 27 French University Hospitals, we analyzed the clinical, electrophysiological, and genetic features of 103 patients from 89 families with homozygous and compound heterozygous SH3TC2 gene mutations identified between 2003 and 2023. RESULTS:Mean age was 42 years (2-80), and 49% of patients were female. Mean age at disease onset was 14 years (0-52), 60% of patients started the disease before age 10 years, and 24% after age 20 years. Patients presented with distal motor weakness (93% of cases), sensory loss (86%), foot deformities (83%), scoliosis (73%), proximal limb weakness (40%), cranial nerve involvement (48%), hearing loss (37%), scoliosis-related respiratory insufficiency (14%), and genitourinary disorders (6%). Half the patients (48%) walked independently before age 50 years, in contrast with only 13% after age 50 years. After age 50 years, 23% of patients were wheelchair-bound. Nerve conduction studies showed sensorimotor abnormalities within the demyelinating range in all cases. We identified 56 different pathogenic variants in the SH3TC2 gene, including 22 previously undescribed. Patients with two SH3TC2 gene truncating variants had more severe symptoms than patients with one or zero truncating variants. INTERPRETATION:This study shows CMT4C is a severe childhood- and adult-onset demyelinating peripheral neuropathy often associated with scoliosis, hearing loss, and ambulation loss in a significant proportion of patients after age 50 years. Genotype-phenotype correlations suggest two truncating SH3TC2 gene variants cause a more severe phenotype.

Il glucosio è la principale fonte di energia per i neuroni periferici. Nel corso del diabete, l’esistenza di episodi di ipoglicemia è associata al rischio di neuropatia periferica. Le neuropatie delle ipoglicemie sono un’entità separata, segnalata essenzialmente dopo diversi anni di evoluzione di un insulinoma. Il coinvolgimento periferico segue episodi neurologici centrali. Esso si presenta come una neuropatia a predominanza motoria con interessamento preferenziale degli arti superiori. Associa un’amiotrofia, che colpisce soprattutto i piccoli muscoli delle mani, e un deficit motorio distale degli arti superiori e sia distale che prossimale degli arti inferiori. L’elettromiografia evidenzia una neuropatia assonale a predominanza motoria con, all’inizio dell’evoluzione, la presenza di un’attività spontanea in rilevazione. Dopo la rimozione del tumore, si osserva un recupero in pochi mesi, con possibili sequele motorie.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare immune-mediated neuropathy for which there is no clearly identified risk factor. The present study identified rare variants in the FBXO38 gene in three familial cases of CIDP with response to corticosteroids in three generations with incomplete penetrance, and in an unrelated fourth case with diffuse nerve hypertrophy. FBXO38 may be involved in the regulation of the immunity mediated by CD8 T cells, which have an important role in CIDP pathophysiology, through PD1 degradation. Considering these findings, FBXO38 should be investigated as a potential genetic factor in larger cohorts of patients with CIDP.

ObjectivesAcute confusional state (ACS) is a common cause of admission to the emergency department (ED). It can be related to numerous etiologies. Electroencephalography (EEG) can show specific abnormalities in cases of non-convulsive status epilepticus (NCSE), or metabolic or toxic encephalopathy. However, up to 80% of patients with a final diagnosis of NCSE have an ACS initially attributed to another cause. The exact place of EEG in the diagnostic work-up remains unclear.MethodsData of consecutive patients admitted to the ED for an ACS in a two-year period and who were referred for an EEG were collected. The initial working diagnosis was based on medical history, clinical, biological and imaging investigations allowing classification into four diagnostic categories. Comparison to the final diagnosis was performed after EEG recordings (and sometimes additional tests) were performed, which allowed the reclassification of some patients from one category to another.ResultsSeventy-five patients (mean age: 71.1 years) were included with the following suspected diagnoses: seizures for 8 (11%), encephalopathy for 14 (19%), other cause for 34 (45%) and unknown for 19 (25%). EEG was recorded after a mean of 1.5 days after symptom onset, and resulted in the reclassification of patients as follows: seizure for 15 (20%), encephalopathy for 15 (20%), other cause for 29 (39%) and unknown cause for 16 (21%). Moreover, ongoing epileptic activity (NCSE or seizure) and interictal epileptiform activity were found in eight (11%) patients initially diagnosed in another category.DiscussionIn our cohort, EEG was a key examination in the management strategy of ACS in 11% of patients admitted to the ED. It resulted in a diagnosis of epilepsy in these patients admitted with unusual confounding presentations.

Il diabete è la principale causa di neuropatia nel mondo. La forma più classica è la polineuropatia distale simmetrica che colpisce il 50% dei diabetici. Essa deriva da meccanismi metabolici e vascolari. Si tratta di un disturbo sensitivo cronico che inizia e che rimane predominante ai piedi. Può essere asintomatica, scoperta durante un esame clinico sistematico o in occasione della comparsa di un’ulcera indolore al piede. Può anche causare parestesie, dolori o intorpidimento. Può essere associata una compromissione del sistema nervoso autonomo che può portare a segni cardiovascolari, in particolare un’ipotensione ortostatica e una tachicardia a riposo, o a segni digestivi o urogenitali. È favorita essenzialmente dall’iperglicemia cronica e dalla durata di evoluzione del diabete, ma anche dai diversi fattori della sindrome metabolica. La diagnosi è clinica, ma realizzare un bilancio di laboratorio permette di escludere le altre cause di neuropatia. L’elettroneuromiografia è giustificata solo in presenza di atipie cliniche. La neuropatia può portare a due gravi complicanze: le ulcere ai piedi, che comportano un rischio significativo di amputazione, e la neuroartropatia. Il trattamento mira a un buon controllo glicemico, alla prevenzione delle complicanze e al trattamento sintomatico dei dolori o dei disturbi disautonomici. Oltre alle sindromi canalicolari, nel diabete si possono incontrare altre forme di neuropatie. Neuropatie sensitive molto dolorose associate a segni di disautonomia possono essere innescate dal rapido controllo della glicemia. Più raramente, infine, si riscontrano varie forme di neuropatie multifocali degli arti o dei nervi toracoaddominali di origine microvascolare infiammatoria. Esse giustificano una consulenza e una gestione specialistica.

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La main est l’outil complexe du membre supérieur capable de mouvements de grande précision dont la mobilité est assurée par un jeu d’os et d’articulations actionnés par des muscles de l’avant-bras ou de la main elle-même. Les atteintes des muscles de la main sont le plus souvent dues à des atteintes neurogènes au premier rang desquels on retrouve les syndromes canalaires. Cependant, d’autres pathologies neurogènes musculaires ou relevant d’autres pathologies neurologiques dont l’identification est primordiale pour assurer une prise en charge adaptée au patient et le cas échéant, prévenir leurs complications graves.

Recreational use of nitrous oxide (N2O) has dramatically increased in recent years, resulting in numerous cases of acute sensorimotor tetraparesis secondary to nitrous oxide‐induced neuropathy (N2On). Challenging clinical features can mimic Guillain‐Barré syndrome (GBS), the main differential diagnosis upon admission. The most sensitive biomarkers for distinguishing between these two conditions remain to be determined.

BackgroundDespite multimodal assessment (clinical examination, biology, brain MRI, electroencephalography, somatosensory evoked potentials, mismatch negativity at auditory evoked potentials), coma prognostic evaluation remains challenging. MethodsWe present here a method to predict the return to consciousness and good neurological outcome based on classification of auditory evoked potentials obtained during an oddball paradigm. Data from event-related potentials (ERPs) were recorded noninvasively using four surface electroencephalography (EEG) electrodes in a cohort of 29 post-cardiac arrest comatose patients (between day 3 and day 6 following admission). We extracted retrospectively several EEG features (standard deviation and similarity for standard auditory stimulations and number of extrema and oscillations for deviant auditory stimulations) from the time responses in a window of few hundreds of milliseconds. The responses to the standard and the deviant auditory stimulations were thus considered independently. By combining these features, based on machine learning, we built a two-dimensional map to evaluate possible group clustering. ResultsAnalysis in two-dimensions of the present data revealed two separated clusters of patients with good versus bad neurological outcome. When favoring the highest specificity of our mathematical algorithms (0.91), we found a sensitivity of 0.83 and an accuracy of 0.90, maintained when calculation was performed using data from only one central electrode. Using Gaussian, K-neighborhood and SVM classifiers, we could predict the neurological outcome of post-anoxic comatose patients, the validity of the method being tested by a cross-validation procedure. Moreover, the same results were obtained with one single electrode (Cz). Conclusionstatistics of standard and deviant responses considered separately provide complementary and confirmatory predictions of the outcome of anoxic comatose patients, better assessed when combining these features on a two-dimensional statistical map. The benefit of this method compared to classical EEG and ERP predictors should be tested in a large prospective cohort. If validated, this method could provide an alternative tool to intensivists, to better evaluate neurological outcome and improve patient management, without neurophysiologist assistance.

Several disabling symptoms potentially related to dysautonomia have been reported in "long-COVID" patients. Unfortunately, these symptoms are often nonspecific, and autonomic nervous system explorations are rarely performed in these patients. This study aimed to evaluate prospectively a cohort of long-COVID patients presenting severe disabling and non-relapsing symptoms of potential dysautonomia and to identify sensitive tests. Autonomic function was assessed by clinical examination, the Schirmer test; sudomotor evaluation, orthostatic blood pressure (BP) variation, 24-h ambulatory BP monitoring for sympathetic evaluation, and heart rate variation during orthostatism, deep breathing and Valsalva maneuvers for parasympathetic evaluation. Test results were considered abnormal if they reached the lower thresholds defined in publications and in our department. We also compared mean values for autonomic function tests between patients and age-matched controls. Sixteen patients (median age 37 years [31-43 years], 15 women) were included in this study and referred 14.5 months (median) [12.0-16.5 months] after initial infection. Nine had at least one positive SARS-CoV-2 RT-PCR or serology result. Symptoms after SARS-CoV-2 infection were severe, fluctuating and disabling with effort intolerance. Six patients (37.5%) had one or several abnormal test results, affecting the parasympathetic cardiac function in five of them (31%). Mean Valsalva score was significantly lower in patients than in controls. In this cohort of severely disabled long-COVID patients, 37.5% of them had at least one abnormal test result showing a possible contribution of dysautonomia to these nonspecific symptoms. Interestingly, mean values of the Valsalva test were significantly lower in patients than in control subjects, suggesting that normal values thresholds might not be appropriate in this population.

Abstract BACKGROUND Immune checkpoint inhibitors (ICIs) are associated with a wide range of neurotoxicities. Several types of neuropathies have been associated to immune checkpoint inhibitors (ICIs), from length-dependent sensory neuropathies to radiculoneuropathies similar to Guillain-Barré syndromes, with an overall incidence estimated to be between 0.1-1.2% of patients. Guidelines recommend prompt ICI discontinuation and the INTRODUCTION of steroids depending on the severity of the adverse event. However, the usage of IVIG or plasmapheresis (alternatively or in addition to steroids) has been reported in cases of Guillain-Barré-like syndromes. MATERIAL AND METHODS In this study, we report a retrospective consecutive series of patients with an ICI-related neuropathy referred to our department between 2016 and 2021, with the intent to describe their clinical and para-clinical features and the outcome after ICI discontinuation and steroids. RESULTS We identified 12 cases of acute peripheral nervous system involvement, with a predominant sensory pattern. The median onset of symptoms from ICI initiation was 18 weeks, and the median number of ICIs doses was 3. Electrophysiological studies, done in 11 patients, showed a radiculopathy in 9 cases, associated with an axonal neuropathy in 3, and a demyelinating neuropathy in 2 cases. Altogether, these findings are consistent with Guillain-Barré-like syndrome. ICIs were stopped in all patients and steroids started in 7 patients, leading to a favourable outcome (complete recovery =7, partial recovery =4, stability =1). CONCLUSION This consecutive retrospective series identifies Guillain-Barré-like syndrome as the main clinical pattern of immune related neuropathies. We did not observe any case of length-dependent axonal neuropathy without an associated root involvement. Our systematic management, consisting of ICI discontinuation in all patients and steroids in more severe cases, seems a valid strategy. On the other hand, our results do not support the use of IVIG or other treatments.

We would like to thank you for the opportunity to respond to the remarks presented in the letter “What biological markers could be used for diagnosis and monitoring of nitrous oxide abuse?” We would also like to thank Gernez et al. for their interest and contribution to our article [1]. The authors proposed some suggestions about the different biological biomarkers in nitrous oxide (N2O) intoxication by highlighting the relevance of homocysteine and methylmalonic acid (MMA) over serum vitamin B12 measurement. The primary objective of our study was to help clinicians to rapidly discriminate between N2O-induced neuropathy (N2On) and its main differential diagnosis, namely, Guillain–Barré syndrome [2], by characterizing the most efficient clinical, biological, and electrophysiological biomarkers. As mentioned by the authors, the diagnosis is mainly based on discriminating clinical features, and we tried to describe the typical N2On patient in the first part of the Results section. However, as detailed in the article, the diagnosis can be challenging, with equivocal clinical presentations and hidden N2O misuse at first interview, requiring the analysis of biological and electrophysiological biomarkers. With regard to biological biomarkers, vitamin B12 serum level was reduced in only half of our patients, as reported recently in the literature [3]. Nevertheless, the use of a slightly different threshold presented a good sensitivity and specificity to distinguish between the two groups of patients, which was the purpose of our work. We agree with the authors' observations on the relevance of homocysteine and MMA in N2O intoxication. However, as mentioned in the article, the average time to obtain these results in our three centers was approximately 7 days, making it difficult to use them as differential biomarkers in this context. MMA has been correlated to the clinical severity of N2O intoxication in a previous study [4]. In our cohort, there was no correlation between homocysteine or MMA serum levels and clinical severity. This may be due to some missing data concerning MMA serum levels, resulting in a lack of statistical power. Larger national cohorts will undoubtedly enable us to better assess the correlation between biological and clinical biomarkers in the future. Finally, we agree with the authors in their recommendation to perform a combination of biological tests (at least vitamin B9 and B12, homocysteine, and MMA) as quickly as possible, another issue being the fairly rapid correction of some markers after vitamin supplementation, which is sometimes carried out in emergency departments before any blood testing. Etienne Fortanier: Conceptualization; writing – review and editing; writing – original draft. Edouard Berling: Writing – review and editing. Adrien Zanin: Writing – review and editing. Adrien Le Guillou: Writing – review and editing. Joelle Micaleff: Writing – review and editing; supervision. Guillaume Nicolas: Supervision; writing – review and editing. Pierre Lozeron: Supervision; writing – review and editing. Shahram Attarian: Supervision; writing – review and editing. None of the authors has any conflict of interest to disclose. The data that support the findings of this study are available from the corresponding author upon reasonable request.