Background and AimNeurolymphomatosis is defined as an infiltration of the peripheral nervous system (PNS) by malignant lymphoma cells. It is a rare entity and diagnosis is complicated especially when PNS involvement is the initial and leading symptom. To improve knowledge of the disorder and shorten the time to diagnosis, we report a series of nine patients without a history of hematologic malignancy, who were diagnosed with neurolymphomatosis after evaluation and workup of peripheral neuropathy. MethodsThe patients were included from the Department of Clinical Neurophysiology at Pitie Salpetriere and Nancy Hospitals over a period of 15 years. Diagnosis of neurolymphomatosis was confirmed by histopathologic examination for each patient. We characterized their clinical, electrophysiological, biological, imaging, and histopathologic features. ResultsThe neuropathy was characterized by pain (78%), proximal involvement (44%) or of all four limbs (67%), asymmetrical or with multifocal distribution (78%), abundant fibrillation (78%), a tendency to worsen rapidly, and significant associated weight loss (67%). Neurolymphomatosis was diagnosed principally on nerve biopsy (89%) identifying infiltration of lymphoid cells, atypical cells (78%), a monoclonal population (78%), and supported by fluorodeoxyglucose-positron emission tomography, spine or plexus MRI, cerebrospinal fluid analysis, and blood lymphocyte immunophenotyping. Six patients had systemic disease and three impairment limited to the PNS. In the latter case, progression could be unpredictable and may be diffuse and explosive, sometimes occurring years after a seemingly indolent course. InterpretationThis study provides better knowledge and understanding of neurolymphomatosis when neuropathy is the initial presentation.

Patient de 29 ans, réfugié d'origine afghane, né de parents consanguins, antécédent d'hépatite B active, présentant un tableau de polyradiculonévrite inflammatoire démyélinisante chronique (PIDC) juvénile, évoluant progressivement depuis l'âge de 16 ans. Le tableau clinique est celui d'une atteinte à prédominance motrice, symétrique et distale, ayant débuté aux membres inférieurs, avec une extension après quatre ans aux membres supérieurs. Il ne présente pas de déformation des pieds. L'ENMG est en faveur du diagnostic de PIDC, avec de multiples blocs de conduction sévères, essentiellement aux membres inférieurs et sur les nerfs ulnaires et des ralentissements marqués, surtout tronculaires et proximaux, touchant les quatre membres. La ponction lombaire retrouve une protéinorachie peu augmentée à 0,58 g/L. Les anticorps anti-gangliosides sont négatifs et les CPK s'élèvent à cinq fois la normale. L'IRM plexique montre une augmentation de calibre, associée à des hypersignaux des plexus brachiaux et lombo-sacrés. Le patient présente un bénéfice fonctionnel net des cures d'immunoglobulines intraveineuses (allongement du périmètre de marche par trois). Cependant, l'examen clinique reste inchangé et l'ENMG stable. Cette évolution atypique, ainsi que le contexte familial, nous obligent à reconsidérer le diagnostic princeps et à rechercher des causes de neuropathies héréditaires.

Objective: To investigate the clinical relevance of individual profiles of cortical and white matter lesion myelin content changes combining magnetisation transfer imaging (MTI) and 11C-PiB-positron emission tomography (PET) in patients with multiple sclerosis (MS). Methods: MTI and [ 11 C]PiB-PET acquired in 19 patients with MS followed up over 2–4 months and in seven healthy controls (HCs), were employed to generate individual maps of cortical and white matter (WM) lesion myelin content changes, respectively. These maps were used to calculate individual indices of demyelination and remyelination, and to investigate their association with clinical scores. Results: Cortical remyelination ranged between 1% and 5% of the total cortical volume (17%–45% of the cortical volume demyelinated at baseline). WM lesion remyelination ranged between 8% and 22% of the lesional volume. An extensive cortical remyelination was associated with a shorter disease duration (rho = −0.63, p = 0.01) and, in combination with WM lesion remyelination, explained 68%–70% of the variance of clinical scores ( p < 0.01). Conclusion: Our multimodal and multicompartment approach allows us to explore single-patient cortical and WM lesion demyelination and remyelination, and to generate clinically relevant indices of myelin repair. These indices may be used as outcome measures in clinical trials, thus increasing the chance to identify successful promyelinating treatments in patients with MS.

L’encéphalite limbique auto-immune (EL) est une entité rare qui se manifeste par une épilepsie temporale, des troubles du comportement ou des troubles cognitifs. Elle peut être associée à des anticorps dirigés contre le glutamate décarboxylase-65 (GAD-65), même si le processus physiopathologique reste inconnu. Nous rapportons le cas d’une jeune femme développant une EL avec anti-GAD-65 en post-partum. Elle présenta une épilepsie temporale, de novo, et une légère plainte de mémoire, sans anomalie au bilan neuropsychologique. Son IRM, initialement normale, révéla un hypersignal temporal interne un mois plus tard. Elle fut traitée par des doses élevées d’antiépileptiques et des immunoglobulines intraveineuses.

Focal chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is defined as involving the brachial or lumbosacral plexus, or one or more peripheral nerves in one upper or one lower limb (monomelic distribution). However, other auto-immune neuropathies such as Lewis-Sumner syndrome (LSS) and multifocal motor neuropathy (MMN) can also have a focal onset. From a retrospective cohort of 30 focal CIDP patients with a monomelic onset dating back at least 2 years, we distinguished patients with plexus involvement (focal demyelinating plexus neuropathy [F-PN], n = 18) from those with sensory or sensorimotor (F-SMN, n = 7), or purely motor (F-MN, n = 5) impairment located in one or several peripheral nerves. Few (39%) F-PN patients had motor nerve conduction abnormalities, but the majority showed proximal conduction abnormalities in somatosensory evoked potentials (80%), and all had focal hypertrophy and/or increased short tau inversion recovery image signal intensity on plexus MRI. Impairment remained monomelic in most (94%) F-PN patients, whereas abnormalities developed in other limbs in 57% of F-SMN, and 40% of F-MN patients (P = .015). The prognosis of F-PN patients was significantly better: none had an ONLS score > 2 at the final follow-up visit, vs 43% of F-SMN patients and 40% of F-MN patients (P = .026). Our findings from a large cohort of focal CIDP patients confirm the existence of different entities that are typically categorized under this one term: on the one hand, patients with a focal plexus neuropathy and on the other, patients with monomelic sensori-motor or motor involvement of peripheral nerves. These two last subgroups appeared to be more likely to evolve to LSS or MMN phenotype, when F-PN patients have a more distinctive long-term, focal, benign course.

Objectives To explore in vivo innate immune cell activation as a function of the distance from ventricular CSF in patients with multiple sclerosis (MS) using [F-18]-DPA714 PET and to investigate its relationship with periventricular microstructural damage, evaluated by magnetization transfer ratio (MTR), and with trajectories of disability worsening. Methods Thirty-seven patients with MS and 19 healthy controls underwent MRI and [F-18]-DPA714 TSPO dynamic PET, from which individual maps of voxels characterized by innate immune cell activation (DPA+) were generated. White matter (WM) was divided in 3-mm-thick concentric rings radiating from the ventricular surface toward the cortex, and the percentage of DPA+ voxels and mean MTR were extracted from each ring. Two-year trajectories of disability worsening were collected to identify patients with and without recent disability worsening. Results The percentage of DPA+ voxels was higher in patients compared to controls in the periventricularWM(p = 6.10e-6) and declined with increasing distance from ventricular surface, with a steeper gradient in patients compared to controls (p = 0.001). This gradient was found in both periventricular lesions and normal-appearing WM. In the total WM, it correlated with a gradient of microstructural tissue damage measured byMTR(r(s) = -0.65, p = 1.0e-3). Compared to clinically stable patients, patients with disability worsening were characterized by a higher percentage of DPA+ voxels in the periventricular normal-appearing WM (p = 0.025). Conclusions Our results demonstrate that in MS the innate immune cell activation predominates in periventricular regions and is associated with microstructural damage and disability worsening. This could result from the diffusion of proinflammatory CSF-derived factors into surrounding tissues.

Background and purposes: Stroke knowledge, awareness of risk factors and stroke warning symptoms is very poor among stroke survivors. We investigated whether a pre-discharge education intervention in the stroke unit could improve stroke knowledge in patients with TIA or minor stroke. Methods: We performed a prospective single-center, randomized controlled trial (2013-2016) in patients with TIA or minor stroke. The intervention consisted in an interactive group session focused on stroke education, within the stroke unit before hospital discharge. Primary outcome was the 3-month change in stroke knowledge score (SKS) from randomization. Secondary outcomes were the 12-month change in SKS, the number of risk factors and warning signs named, control of risk factors and self-reported adherence. Results: A total of 199 patients (mean [SD] age, 63.5 [12.4] years; 67 [33.7%] women) were randomized (99 in stroke education session). Intervention was associated with a greater improvement in SKS than in the control group (baseline-adjusted mean between group difference, 1.6 point [95%CI, 1.4 to 1.9]; p=0.001). This difference was significantly maintained at 12 months. The number of risk factors and warning signs named were significantly increased in the intervention group at 3 months. Control of risk factors and self-reported adherence did not differ significantly between the two groups. Conclusions: An interactive education session in the stroke unit significantly improved stroke knowledge at 3 months and 12 months in patients with TIA or minor stroke.

ObjectiveRiboflavin transporter deficiencies (RTDs), involving SLC52A3 and SLC52A2 genes, have recently been related to Brown-Vialetto-Van Laere (BVVL) syndrome, a hereditary paediatric condition associating motor neuropathy (MN) and deafness. BVVL/RTD has rarely been reported in adult patients, but is probably underdiagnosed due to poor knowledge and lack of awareness of this form of disease among neurologists. In this study, we aimed to investigate the phenotype and prognosis of RTD patients with late-onset MN.MethodsWe retrospectively collected clinical, biological and electrophysiological data from all French RTD patients with MN onset after 10 years of age (n=6) and extracted data from 19 other similar RTD patients from the literature.ResultsAdult RTD patients with MN had heterogeneous clinical presentations, potentially mimicking amyotrophic lateral sclerosis or distal hereditary motor neuropathy (56%), multinevritis with cranial nerve involvement (16%), Guillain-Barré syndrome (8%) and mixed motor and sensory neuronopathy syndromes (20%, only in SLC52A2 patients). Deafness was often diagnosed before MN (in 44%), but in some patients, onset began only with MN (16%). The pattern of weakness varied widely, and the classic pontobulbar palsy described in BVVL was not constant. Biochemical tests were often normal. The majority of patients improved under riboflavin supplementation (86%).InterpretationWhereas late-onset RTD may mimic different acquired or genetic causes of motor neuropathies, it is a diagnosis not to be missed since high-dose riboflavin per oral supplementation is often highly efficient.

Our objective was to develop a novel approach to generate individual maps of white matter (WM) innate immune cell activation using 18F-DPA-714 translocator protein PET and to explore the relationship between these maps and individual trajectories of worsening disability in patients with multiple sclerosis (MS). Methods: Patients with MS (n = 37), whose trajectories of worsening disability over the 2 y preceding study entry were calculated, and healthy controls (n = 19) underwent MRI and 18F-DPA-714 PET. A threshold for significant activation of 18F-DPA-714 binding was calculated with a voxelwise randomized permutation-based comparison between patients and controls and used to classify each WM voxel in all subjects as characterized by a significant activation of innate immune cells (DPA+) or not. Individual maps of innate immune cell activation in the WM were used to calculate the extent of activation in WM regions of interests and to classify each WM lesion as DPA-active, DPA-inactive, or unclassified. Results: Compared with the WM of healthy controls, patients with MS had a significantly higher percentage of DPA+ voxels in the normal-appearing WM (NAWM) (NAWM in patients, 24.6% ± 1.4%; WM in controls, 14.6% ± 2.0%; P < 0.001). In patients with MS, the percentage of DPA+ voxels increased significantly from the NAWM to the perilesional areas, T2 hyperintense lesions, and T1 hypointense lesions (38.1% ± 2.6%, 45.0% ± 2.6%, 51.8% ± 2.6%, respectively; P < 0.001). Among the 1,379 T2 lesions identified, 512 were defined as DPA-active and 258 as DPA-inactive. A higher number of lesions classified as DPA-active (odds ratio, 1.13; P = 0.009), a higher percentage of DPA+ voxels in the NAWM (odds ratio, 1.16; P = 0.009), and a higher percentage of DPA+ voxels in T1 spin-echo lesions (odds ratio, 1.06; P = 0.036) were significantly associated with a retrospectively more severe clinical trajectory in patients with MS. Conclusion: A more severe trajectory of disability worsening in MS is associated with innate immune cell activation inside and around WM lesions. 18F-DPA-714 PET may provide a promising biomarker to identify patients at risk of a severe clinical trajectory.

A 53-year-old man treated with an angiotensin-converting enzyme (ACE) inhibitor presented with left hemiplegia (NIH Stroke Scale 23). Magnetic resonance angiography revealed a right proximal middle cerebral artery occlusion (figure 1). Thirty minutes after thrombolysis, orolingual swelling was observed. Two hours later, just after mechanical thrombectomy was completed, he developed painful abdominal edema, which improved after icatibant administration (figure 2). Bradykinin-mediated angioedema can be a complication of recombinant tissue plasminogen activator, typically orolingual, with increased risk for patients on ACE inhibitors.1 We speculate that the procedure of thrombectomy, acting as a mechanical stress,2 could have been a triggering factor for the unusual presentation of abdominal edema.

Les PIDC focales (PIDC-F) sont définies comme cliniquement restreintes à un seul membre, qu'elles soient en lien avec une atteinte plexique (PIDC-P) ou d'un ou plusieurs troncs nerveux. Décrire les PIDC-F et mieux situer au sein de ce cadre diagnostic les PIDC-P, les syndromes de Lewis et Sumner et les neuropathies motrices multifocales à début monomélique (SLS-F et NMM-F). À partir de notre base de données PIDC, nous avons étudié rétrospectivement 26 patients répondant initialement aux critères de PIDC-F, avec une atteinte clinique strictement monomélique durant au moins les deux premières années d'évolution. Nous avons distingué les patients ayant une atteinte initiale clinico-électrique de systématisation plexique (PIDC-P), ou une atteinte mono ou multi-tronculaire avec bloc de conduction, classés SLS-F en cas d'atteinte sensitive associée, ou NMM-F en cas d'atteinte motrice pure. Nous avons identifié 16 PIDC-P, 6 SLS-F et 4 NMM-F. Parmi les PIDC-P, les signes électrophysiologiques suggérant une démyélinisation étaient peu fréquent (30 %) ainsi que la dissociation albuminocytologique (25 %), les PES montraient des altérations proximales (65 %) et l'IRM plexique une hypertrophie ou un hypersignal (100 %). L'évolution des PIDC-P est restée monomélique (100 %), tandis que 3 des 6 SLS-F et 1 des 4 NMM-F ont évolué de façon multifocale aux autres membres. Les PIDC-F représentent une forme rare de PIDC, au sein duquel il peut être difficile de distinguer les diagnostics de SLS et NMM à début focal. Cette cohorte, la plus grande jamais rapportée, suggère qu'au sein de ce cadre diagnostic, les PIDC-P représentent une entité distincte, avec une évolution restant focale. Le diagnostic de PIDC-P doit être évoqué devant une atteinte plexique chronique. L'EMG et la PL étant en défaut, l'IRM plexique et les PES doivent être réalisés pour confirmation diagnostique.

BACKGROUND:The relationship between Health-Related Quality of Life (HRQoL) and MDS-UPDRS has not been fully studied so far. The aim of this study was to evaluate the relationship between all MDS-UPDRS components and HRQoL in a representative international cohort of PD patients.METHODS:We collected demographic and disease-related data as well as MDS-UPDRS and PDQ8 scales. Data were analyzed using correlations between PDQ8 and all MDS-UPDRS items, subsequently two hierarchical multiple regressions were performed, first between the scores of the MDS-UPDRS Parts and PDQ8 and second between individual items from those Parts demonstrating significant relationship to PDQ8 scores in the first regression. LASSO regression analyses were performed to evaluate the relationship between PDQ8 and all individual MDS-UPDRS items.RESULTS:A total of 3206 PD patients were included in the study. In the first regression analysis, PDQ8 was significantly related to MDS-UPDRS parts I and II, but not to III and IV. In the second regression model, significant contributions to PDQ8 were found for Part I items Fatigue, Pain, Depressed mood, Apathy; and Part II items Dressing, Doing hobbies, Freezing, Speech and Tremor. In the LASSO analysis, six Part I, seven Part II, three Part III and one Part IV items contributed to PDQ8 scores. The five items most significantly related to the model were Depressed mood, Dressing, Apathy, Pain and Fatigue.CONCLUSIONS:This is so far the largest study related to HRQoL issues in PD. Restrictions in activities of daily living and non-motor symptoms significantly contribute to HRQoL in PD.

La paraparésie spastique tropicale ou myélopathie associée au virus HTLV-1 (TSP-HAM) est une pathologie associée à l’infection par le virus HTLV-1. Elle fait partie du spectre neurologique des manifestations présumées dysimmunitaires associées à l’infection par ce virus. Elle se traduit par une paraparésie lentement progressive, des troubles vésico-sphinctériens, des signes sensitifs inconstants. L’aspect IRM est fréquemment celui d’une atrophie médullaire dorsale, tandis qu’à l’étage encéphalique des hypersignaux sus-tentoriels aspécifiques ont été souvent décrits. Nous rapportons le cas d’une patiente de 39 ans présentant une paraparésie spastique progressive associée à une leuco-encéphalopathie extensive dans le cadre d’une TSP/HAM, confirmée par la positivité des PCR HTLV-1 dans le sang et le LCS. Les aspects diagnostiques, radiologiques et thérapeutiques de cette pathologie seront décrits.

BackgroundThe Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a newly developed tool to assess Parkinson's disease (PD). Changes in scores on the scale over the course of PD, including increasing disease duration and Hoehn and Yahr (HY) stages, have not been described. The objectives of this study were to analyze MDS-UPDRS scores on Parts I through IV and their differences based on HY stage and disease duration in a large cohort of patients with PD.MethodsFor this cross-sectional study, demographic data and MDS-UPDRS scores were collected, including HY stage. Subscores on MDS-UPDRS Parts I through IV were analyzed using 1-way analyses of variance for each HY stage and in 5-year increments of disease duration. Part III (motor assessment) scores were analyzed separately for on and off states.ResultsThe mean age of the 3206 patients was 65.8 10.6 years, 53.3% were men, the mean disease duration was 11.5 +/- 4.6 years, and the median HY stage was 2 (range, 0-5); 2156 patients were examined in an on state and 987 were examined in an off state. Scores for all MDS-UPDRS parts increased significantly through HY stages 1 through 5, with an average increase of 3.8, 7.7, 14.6, and 2.0 points consecutively for parts I through IV, respectively. For the 5-year increments of disease duration, MDS-UPDRS subscores increased by an average of 1.6, 3.3, 4.2, and 1.4 points consecutively for parts I through IV, respectively. This increase was significant only during the first 15 years of disease for all 4 parts, including part III scores evaluated in both on and off states.ConclusionsMDS-UPDRS scores for all 4 parts increase significantly with every HY stage and also with 5-year increments of disease duration in the first 15 years of the disease.