Management of amyotrophic lateral sclerosis in clinical practice: Results of the expert consensus using the Delphi methodology.

Amyotrophic lateral sclerosis (ALS) is a rare disease characterized by a progressive and irreversible degeneration of upper and lower motor neurons leading to death. In France, limited data exist describing the criteria used in clinical practice for diagnosis and follow-up, and how novel therapies may fit in. The objective of this Delphi panel was to obtain an overview of current French practices in ALS diagnosis, management, and follow-up by determining the scales and criteria used in clinical practice outside of clinical trials, as well as the place of a future treatment like AMX0035, acting on endoplasmic reticulum (ER) stress and mitochondrial dysfunction, in the current therapeutic strategies. A questionnaire was administered to 24 ALS healthcare providers practicing in ALS centers in France. Two rounds of remote voting were organized, before proposition of final consensus statements. Consensus was considered reached when at least 66% of the voters agreed. Consensus were obtained to define the new Gold Coast criteria as the ones used in clinical practice to establish the diagnosis of ALS, thus replacing the revised El Escorial criteria, considered too complex and now mainly used to characterize the patient populations to be included in clinical trials. The clinical factors considered to establish ALS diagnosis are mainly the demonstration of progression of the motor deficit and elimination of differential diagnoses. The ALSFRS-R scale is used in daily clinical practice to assess patient's functional impairment in terms of number of points lost, with the bulbar, respiratory, and fine motor subscores being the most important to evaluate independently. A critical medical need was identified regarding the provision of new therapeutic alternatives in ALS. The panel members would support the earliest management of patients. In this landscape, based on data from a very encouraging phase II (Centaur trial), AMX0035 represents a new tool of choice in current treatment strategies for all patients for whom experts are confident in the diagnosis of ALS, in combination with riluzole. These results will need to be confirmed by the ongoing phase III trial (Phoenix trial).

Efficacy and safety of rituximab in myasthenia gravis: a French multicentre real-life study.

BACKGROUND AND PURPOSE: Fifteen percent of patients with myasthenia gravis (MG) are refractory to conventional treatment. Case reports and a few studies show probable benefit of rituximab in these cases. Our objective was to assess the efficacy and the safety of rituximab in patients with MG, in a multicentric real-life study. METHOD: Inclusion criteria were: age > 18 years; MG with anti-acetylcholine receptor (AChR) antibodies, anti-muscle-specific kinase (MuSk) antibodies or significant decrement after repetitive nerve stimulation; Myasthenia Gravis Foundation of America (MGFA) class >II; refractory or steroid-dependent MG; and treatment with rituximab. Efficacy was assessed at 6 months using the MGFA-post-intervention status (PIS) score, the myasthenic muscle score (MMS) and the number of patients receiving steroids <10 mg/day. Data on adverse events were collected. RESULTS: Twenty-nine patients were included: 20 with anti-AChR MG, five with anti-MuSK MG and four with seronegative MG. MGFA-PIS score was improved or better (improved, minimal manifestations or remission) in 86.2% of patients after 6 months of treatment (P < 0.0001). The mean MMS increased from 68.8 to 83.1 (P < 0.0001). A decrease in steroid dosage (<10 mg/day) was effective in 57.9% of treated patients. In all, 42.8% of patients experienced adverse events: infections (21.4% of patients); infusion reaction (7%); bradycardia (3.7%); and cytopenia (7%). CONCLUSION: The present study demonstrates the efficacy and safety of rituximab in patients with MG. Additional studies remain necessary to determine the role of rituximab in the pharmacopeia of MG treatment and to establish precise recommendations for the infusion protocol.

Autosomal dominant SPG9: intrafamilial variability and onset during pregnancy.

INTRODUCTION: The ALDH18A1 gene, encoding delta-1-pyrroline-5-carboxylate synthase (P5CS), is responsible for an autosomal recessive disease with severe developmental delay; more recently, ALDH18A1 was found to be responsible for SPG9, an autosomal dominant (AD) spastic paraplegia. CASE REPORT: We report a three-generation family with AD SPG9, initially suspected because of low citrulline on fasting plasma amino acid chromatography (AAC). Interestingly, in two patients, the spastic paraplegia appeared during pregnancy. One subject presented a severe childhood-onset form while another subject had a mild late-onset disease. CONCLUSION: The description of this family is of particular interest: it highlights the possibility of transient or permanent aggravation of spastic paraplegia due to SPG9 during pregnancy, suggesting a direct link between neurological symptoms and amino acid defect in a period of higher requirements and the potential benefit of amino acid supplementation; it underscores the value of plasma citrulline on fasting plasma AAC as a biomarker for this disease; it shows the variable expression of the disease.

[Kleine-Levin syndrome: a case report]. / Le syndrome de Kleine-Levin: à propos d'un cas.

The purpose of this article is to report an original clinical case whose symptoms suggest a very peculiar pathology, because of its rarity, symptomatic expression and unclear etiopathogenesis: the Kleine-Levin Syndrome (KLS). During the regression of tonsillitis concomitant with an emotional shock, the 15-year-old patient exhibited a dramatic change in behaviour, at odds with his previous state, and accompanied by hypersomnia and confusion, megaphagia, irritability, hypersexuality and mood disorders. We observed a spontaneous and total regression of the symptoms after 12 days, except for the incomplete amnesia that proved to be persistent. Four months later, further to an ethylic drunkenness, the patient presented with a new and similar episode. The patient benefited from no medicinal treatment, even in the course of hypersomnia episodes and asymptomatic periods. After a clinical presentation of this patient, we will consider this case study from a more psychopathological angle by questioning the existence of a facilitating psychological profile. The discovery of an IQ equal to 86 from the scores of WISC-IV, and the identification of constructive visual difficulties made us suspect neurological disorders, but these abnormalities were not found during the completion of the Rey Complex Figure Test. The personality profile issued from the scores at the MMPI-A assessment was ranked as barely significant (type 2-4): indeed, it showed nothing specific to this patient. Literature data show that most of the patients presenting with a KLS have been seen by a psychiatrist at the time of the disease and diagnosed as suffering from hysteria, or schizophrenia, or bipolar disorders... Because of diagnostic wanderings, some patients have, hence, received inappropriate treatments. One should pay close attention to this very rare syndrome, on the border between neurology and psychiatry, since its diagnosis is essentially based on clinical features, and carefully think about the implementation of a medicinal treatment. This unique case seems unable to support our working hypothesis about the identification of a particular psychological profile in the KLS, but the question of an underlying fragility is still worth considering. We personally think that, even though links between the KLS and bipolar disorders have been suggested, this disease has to be considered as a separate entity.