Revue neurologique最新文献

Introduction

This paper aims to provide a literature overview on multiple system atrophy (MSA) prevalence in European and other pan-European populations.

Methods

A literature search (PubMed, EMBASE) was performed through 2022 to identify published studies on MSA prevalence in European countries. Of these search results, titles and abstracts were screened for relevance. A standardized assessment tool was used for systematically data extraction and comparison. For studies where only the incidence rate was reported, MSA prevalence was derived based on the incidence and duration of disease.

Results

A total of 24 studies conducted in 14 countries and published between 1995 and 2022 were identified. The prevalence of MSA was reported in 18 (75%) studies and was derived from six (25%) incidence studies. These studies were mainly prospective population-based studies or multi-center studies from specific regions or specialty clinical settings. Two earlier studies in Germany and the Netherlands were conducted using door-to-door design. The time period of evaluation of prevalence ranged from 1990 to 2018. The crude prevalence of MSA ranged from 0.5/100,000 in Spain to 17/100,000 in Japan. Age-specific prevalence rates were provided in five studies, and the reported age ranges varied. The gender-specific crude prevalence was estimated as 2.75/100,000 for men and 1.19/100.000 for women. The derived prevalence was higher (ranging from 0.7–18.9/100,000) than studies where the prevalence was reported.

Conclusion

The variations observed in MSA prevalence may result from differences in age distributions of the study populations, study methodology, diagnostic criteria and case assessment strategies of MSA. Thus, the comparability of these studies is limited.

Objective

We aimed to describe characteristics of patients with ATTR variant polyneuropathy (ATTRv-PN) and ATTRv-mixed and assess the real-world use and safety profile of tafamidis meglumine 20 mg.

Methods

Thirty-eight French hospitals were invited. Patient files were reviewed to identify clinical manifestations, diagnostic methods, and treatment compliance.

Results

Four hundred and thirteen patients (296 ATTRv-PN, 117 ATTRv-mixed) were analyzed. Patients were predominantly male (68.0%) with a mean age of 57.2 ± 17.2 years. Interval between first symptom(s) and diagnosis was 3.4 ± 4.3 years. First symptoms included sensory complaints (85.9%), dysautonomia (38.5%), motor deficits (26.4%), carpal tunnel syndrome (31.5%), shortness of breath (13.3%), and unexplained weight loss (16.0%). Mini-invasive accessory salivary gland or punch skin and nerve biopsies were most common, with a performance of 78.8–100%. TTR genetic sequencing, performed in all patients, revealed 31 TTR variants. Tafamidis meglumine was initiated in 156/214 (72.9%) ATTRv-PN patients at an early disease stage. Median treatment duration was 6.00 years in ATTRv-PN and 3.42 years in ATTRv-mixed patients. Tafamidis was well tolerated, with 20 adverse events likely related to study drug among the 336 patients.

Conclusion

In France, ATTRv patients are usually identified early thanks to the national network and the help of diagnosis combining genetic testing and mini-invasive biopsies.

The ILAE's Task Force on Nosology and Definitions revised in 2022 its definition of juvenile myoclonic epilepsy (JME), the most common idiopathic generalized epilepsy disorder, but this definition may well change again in the future. Although good drug response could almost be a diagnostic criterion for JME, drug resistance (DR) is observed in up to a third of patients. It is important to distinguish this from pseudoresistance, which is often linked to psychosocial problems or psychiatric comorbidities. After summarizing these aspects and the various definitions applied to JME, the present review lists the risk factors for DR-JME that have been identified in numerous studies and meta-analyses. The factors most often cited are absence seizures, young age at onset, and catamenial seizures. By contrast, photosensitivity seems to favor good treatment response, at least in female patients. Current hypotheses on DR mechanisms in JME are based on studies of either simple (e.g., cortical excitability) or more complex (e.g., anatomical and functional connectivity) neurophysiological markers, bearing in mind that JME is regarded as a neural network disease. This research has revealed correlations between the intensity of some markers and DR, and above all shed light on the role of these markers in associated neurocognitive and neuropsychiatric disorders in both patients and their siblings. Studies of neurotransmission have mainly pointed to impaired GABAergic inhibition. Genetic studies have generally been inconclusive. Increasing restrictions have been placed on the use of valproate, the standard antiseizure medication for this syndrome, owing to its teratogenic and developmental risks. Levetiracetam and lamotrigine are prescribed as alternatives, as is vagal nerve stimulation, and there are several other promising antiseizure drugs and neuromodulation methods. The development of better alternative treatments is continuing to take place alongside advances in our knowledge of JME, as we still have much to learn and understand.

Neurofeedback is a brain-computer interface tool enabling the user to self-regulate their neuronal activity, and ultimately, induce long-term brain plasticity, making it an interesting instrument to cure brain disorders. Although this method has been used successfully in the past as an adjunctive therapy in drug-resistant epilepsy, this approach remains under-explored and deserves more rigorous scientific inquiry. In this review, we present early neurofeedback protocols employed in epilepsy and provide a critical overview of the main clinical studies. We also describe the potential neurophysiological mechanisms through which neurofeedback may produce its therapeutic effects. Finally, we discuss how to innovate and standardize future neurofeedback clinical trials in epilepsy based on evidence from recent research studies.

In childhood absence epilepsy, pharmaco-resistance occurs in 20–30% of patients. In that situation, glucose transporter type 1 deficiency has to be ruled out, especially if absences started before the age of four years and if neurological signs are present. If ethosuximide, valproate and lamotrigine have failed in monotherapy or in association, there are currently no valuable therapeutic options. The same rules apply for epilepsy with myoclonic absences. Importantly, arguments supporting that making the patient seizure-free will improve eventual associated cognitive deficits such as attention deficit are very weak. Therefore, limiting the cognitive side effects of the anti-epileptic drugs has always to be a priority when faced with typical refractory absences in childhood. In epilepsy with eyelid myoclonia, the majority of patients are pharmaco-resistant. However, absence seizures, if present, tend to be very brief, and seizures are limited in many patients to eyelid myoclonia that eventually do not affect their quality of life and are well attenuated by wearing blue lenses. Atypical absences occurring in the course a developmental and/or epileptic encephalopathy are often pharmaco-resistant. In that situation, characterizing the type of epilepsy syndrome and searching for a specific genetic or structural etiology are needed to offer the best therapeutic options to the patient.

Psychotic disorders are eight times more frequent in epilepsy than in the general population. The various clinical syndromes are classified according to their chronology of onset in relation to epileptic seizures: ictal psychoses (during epileptic discharge), post-ictal psychoses (PIP, after a seizure), interictal psychoses (IIP, with no chronological link) and those related to complete seizure control. Antiepileptic drugs can cause psychotic disorders in all these situations. Post-ictal psychoses (PIP) are affective psychoses that occur after a lucid interval lasting 12 to 120 hours following a cluster of seizures. They last an average of 10 days, with an abrupt beginning and end. PIP are directly linked to epileptic seizures, and disappear when the epilepsy is controlled. Interictal psychoses are schizophrenias. The management of psychotic disorders in epilepsy is neuropsychiatric, and requires close collaboration between epileptologists and psychiatrists. Antipsychotics can be prescribed in persons with epilepsy. Even today, psychotic disorders in epilepsy are poorly understood, under-diagnosed and under-treated.

The 2017 International League Against Epilepsy (ILAE) classification suggested that the term “genetic generalized epilepsies” (GGEs) should be used for the broad group of epilepsies with so-called “generalized” seizure types and “generalized” spike-wave activity on EEG, based on a presumed genetic etiology. Within this framework, idiopathic generalized epilepsies (IGEs) are described as a subset of GGEs and include only four epileptic syndromes: childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, and epilepsy with generalized tonic-clonic seizures alone. The recent 2022 ILAE definition of IGEs is based on the current state of knowledge and reflects a community consensus and is designed to evolve as knowledge advances. The term “frontiers of IGEs” refers to the actual limits of our understanding of these four syndromes. Indeed, among patients presenting with a syndrome compatible with the 2022 definition of IGEs, we still observe a significant proportion of patients presenting with specific clinical features, refractory seizures, or drug-resistant epilepsies. This leads to the discussion of the boundaries of IGEs and GGEs, or what is accepted within a clinical spectrum of a definite IGE. Here, we discuss several entities that have been described in the literature for many years and that may either constitute rare features of IGEs or a distinct differential diagnosis. Their recognition by clinicians may allow a more individualized approach and improve the management of patients presenting with such entities.