Safety and efficacy of cerliponase alfa in children with neuronal ceroid lipofuscinosis type 2 (CLN2 disease): an open-label extension study

Background: Cerliponase alfa is a recombinant human tripeptidyl peptidase 1 (TPP1) enzyme replacement therapy for the treatment of neuronal ceroid lipofuscinosis type 2 (CLN2 disease), which is caused by mutations in the TPP1 gene. We aimed to determine the long-term safety and efficacy of intracerebroventricular cerliponase alfa in children with CLN2 disease. Methods: This analysis includes cumulative data from a primary 48-week, single-arm, open-label, multicentre, dose-escalation study (NCT01907087) and the 240-week open-label extension with 6-month safety follow-up, conducted at five hospitals in Germany, Italy, the UK, and the USA. Children aged 3–16 years with CLN2 disease confirmed by genetic analysis and enzyme testing were eligible for inclusion. Treatment was intracerebroventricular infusion of 300 mg cerliponase alfa every 2 weeks. Historical controls with untreated CLN2 disease in the DEM-CHILD database were used as a comparator group. The primary efficacy outcome was time to an unreversed 2-point decline or score of 0 in the combined motor and language domains of the CLN2 Clinical Rating Scale. This extension study is registered with ClinicalTrials.gov, NCT02485899, and is complete. Findings: Between Sept 13, 2013, and Dec 22, 2014, 24 participants were enrolled in the primary study (15 female and 9 male). Of those, 23 participants were enrolled in the extension study, conducted between Feb 2, 2015, and Dec 10, 2020, and received 300 mg cerliponase alfa for a mean of 272·1 (range 162·1–300·1) weeks. 17 participants completed the extension and six discontinued prematurely. Treated patients were significantly less likely than historical untreated controls to have an unreversed 2-point decline or score of 0 in the combined motor and language domains (hazard ratio 0·14, 95% CI 0·06 to 0·33; p<0·0001). All participants experienced at least one adverse event and 21 (88%) experienced a serious adverse event; nine participants experienced intracerebroventricular device-related infections, with nine events in six participants resulting in device replacement. There were no study discontinuations because of an adverse event and no deaths. Interpretation: Cerliponase alfa over a mean treatment period of more than 5 years was seen to confer a clinically meaningful slowing of decline of motor and language function in children with CLN2 disease. Although our study does not have a contemporaneous control group, the results provide crucial insights into the effects of long-term treatment. Funding: BioMarin Pharmaceutical

Stopping Antiepileptic Drugs: When and Why?

After a patient has initiated an antiepileptic drug (AED) and achieved a sustained period of seizure freedom, the bias towards continuing therapy indefinitely can be substantial. Studies show that the rate of seizure recurrence after AED withdrawal is about two to three times the rate in patients who continue AEDs, but there are many benefits to AED withdrawal that should be evaluated on an individualized basis. AED discontinuation may be considered in patients whose seizures have been completely controlled for a prolonged period, typically 1 to 2 years for children and 2 to 5 years for adults. For children, symptomatic epilepsy, adolescent onset, and a longer time to achieve seizure control are associated with a worse prognosis. In adults, factors such as a longer duration of epilepsy, an abnormal neurologic examination, an abnormal EEG, and certain epilepsy syndromes are known to increase the risk of recurrence. Even in patients with a favorable prognosis, however, the risk of relapse can be as high as 20% to 25%. Before withdrawing AEDs, patients should be counseled about their individual risk for relapse and the potential implications of a recurrent seizure, particularly for safety and driving

Epilepsy and Psychiatric Comorbidities: Drug Selection.

Purpose of review The pharmacological treatment of patients with epilepsy and psychiatric comorbidities may sometimes represent a therapeutic challenge. This review is focused on the pharmacological management of patients with epilepsy and psychiatric problems in terms of rationalization of the antiepileptic drug (AED) treatment and the pharmacological management of the most clinically relevant psychiatric comorbidities, namely mood and anxiety disorders, psychoses, and attention deficit hyperactivity disorder (ADHD). Recent findings Up to 8% of patients with drug-resistant epilepsy develop treatment-emergent psychiatric adverse events of AED regardless of the mechanism of action of the drug and this is usually related to an underlying predisposition given by the previous psychiatric history and the involvement of mesolimbic structures. Careful history taking, periodic screening for mood and anxiety disorders, low starting doses, and slow titration schedules can reduce the possibility of AED-related problems. A pragmatic checklist for the pharmacological management of patients with epilepsy and psychiatric disorders is presented. Summary patients should be informed of potential behavioral effects of AEDs but no drugs should be excluded a priori. Any psychiatric comorbidity should be addressed in the appropriate setting and full remission and recovery should always represent the first goal of any therapeutic intervention. Neurologists should be aware of the side effects of major psychotropic drug classes in order to fully counsel their patients and other health professionals involved

Rilievi sull'effetto della I-adamantil-ammina cloridrato e della L-DOPA+Ro 4-4602 nella catatonia umana

Valutazione degli effetti della l-admantil-ammina cloridrato e della L-DOPA in associazioine ad inibitore della decarbossilari periferica nei confronti della sintomatologia di 5 schizofrenici catatonici. Effetti favorevoli sono osservati sullo stupore catatonico e catalessia, nessun vantaggio su negativismo, automatismi stereotipi

EYE TRACKING NELLE COREE CRONICHE

In 8 cases of chronic chorea, 5 of which were of familial nature, the 'smooth pursuit' ocular movements were recorded by means of 'eye tracking', comparing them with those of a group of normal subjects of the same age devoid of neuropsychiatric pathology. The recording of the ocular movements of choreic subjects turned out to be quite different from the normal recordings in which the oculogram (EOG) is a continuous and regular sinusoid. In choreics the EOG was an irregular tracing with changes that affected the entire test, or part of it. The recording of the first of the EOG, which expresses the velocity of the movement, showed in choreics 'arrests' and 'positive errors' of velocity in a significantly higher number than in normal subjects

Enquete sur les connaissances des patients et des aidants sur l'épilepsie

Le laboratoire Éducations et Pratiques de Santé de l’Université Paris XIII, Sorbonne Paris Cité a organisé, du 19 au 21 juin 2014 sur le campus de l’Université à Bobigny, le 5ème Congrès International de la Société d’Education Thérapeutique Européenne. Ce congrès scientifique a accueilli 311 participants et 120 communications d’experts, mettant en valeur les recherches et les expériences multi professionnelles qui, par-delà les frontières et les barrières pouvant exister, aident les patients et leurs familles à apprendre comment gérer au mieux leur maladie. Il a abordé également les champs de l’Education pour la Santé et de l’Education Familiale. Consacré à la diversité de l’éducation thérapeutique du patient et à son accessibilité, l’édition 2014 du congrès avait pour thème : « éducation thérapeutique, quelles frontières ? ». Ce congrès a mis en en valeur, par des communications orales et affichées, les recherches qui ont rassemblé plusieurs éclairages disciplinaires et des expériences multi professionnelles. Nous avons choisi de publier ici les actes de ce congrès SETE 2014, soit les résumés des 42 communications orales qui y ont été présentées

Aspects of motor and cognitive patterns related to functional capacity in Huntington's disease.

Results of this study confirm that impairment of voluntary movements tested by RT and FT are impotant signs of motor pattern of HD, even in early stages. The significant correlation found between multiple choice reaction times tests and TFC seems to suggest that early in the disease a reduction of ability in complex motor planning is associated with functional decline and marks HD evolution more than hyperkinesias and psychic impairment