A Controlled Trial of Riluzole in Amyotrophic Lateral Sclerosis

Bensimon, Gilbert; Lacomblez, Lucette; Meininger, Vincent

doi:10.1056/nejm199403033300901

Cited by 1,942 publications

(1,146 citation statements)

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“…In the phase III trial of riluzole versus placebo in patients with amyotrophic lateral sclerosis (ALS), a statistically significant benefit of riluzole was noted with respect to survival, with a suggestion of a dose-dependent trend toward increased efficacy with higher doses [3,4]. However, MMT strength grading showed no difference from placebo, or any hint of a dose effect.…”

Section: Methods Of Strength Assessment Manual Muscle Testingmentioning

confidence: 99%

Strength Testing in Motor Neuron Diseases

Shefner

2017

Neurotherapeutics

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Loss of muscle strength is a cardinal feature of all motor neuron diseases. Functional loss over time, including respiratory dysfunction, inability to ambulate, loss of ability to perform activities of daily living, and others are due, in large part, to decline in strength. Thus, the accurate measurement of limb muscle strength is essential in therapeutic trials to best understand the impact of therapy on vital function. While qualitative strength measurements show declines over time, the lack of reproducibility and linearity of measurement make qualitative techniques inadequate. A variety of quantitative measures have been developed; all have both positive attributes and limitations. However, with careful training and reliability testing, quantitative measures have proven to be reliable and sensitive indicators of both disease progression and the impact of experimental therapy. Quantitative strength measurements have demonstrated potentially important therapeutic effects in both amyotrophic lateral sclerosis and spinobulbar muscular atrophy, and have been shown feasible in children with spinal muscular atrophy. The spectrum of both qualitative and quantitative strength measurements are reviewed and their utility examined in this review.

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Section: Methods Of Strength Assessment Manual Muscle Testingmentioning

confidence: 99%

Strength Testing in Motor Neuron Diseases

Shefner

2017

Neurotherapeutics

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“…Lamotrigine is a comparatively novel antiepileptic agent used primarily in the treatment of generalized and partial seizures (Bazil, 2002;Kwan and Brodie, 2001); its mechanism of action is considered to be a reduction in glutamate release following inhibition of Na + channels and consequent neurotransmitter glutamate exocytosis (Ahmad et al, 2004;Lees and Leach, 1993). Riluzole (2-amino-6-trifluoromethoxybenzothiazole), an inhibitor of sodium channel and thus glutamate release, is approved by the US Food and Drug Administration for the treatment of amyotrophic lateral sclerosis (Bensimon et al, 1994). Similar to lamotrigine, it also has anticonvulsant and neuroprotective properties.…”

Section: Introductionmentioning

confidence: 99%

The Anticonvulsants Lamotrigine, Riluzole, and Valproate Differentially Regulate AMPA Receptor Membrane Localization: Relationship to Clinical Effects in Mood Disorders

Suzuki

Wei

et al. 2006

Neuropsychopharmacol

194

153

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A growing body of data suggests that the glutamatergic system may be involved in the pathophysiology and treatment of severe mood disorders. Chronic treatment with the antimanic agents, lithium and valproate, resulted in reduced synaptic expression of the AMPA(-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptor subunit GluR1 in the hippocampus, while treatment with an antidepressant (imipramine) enhanced the synaptic expression of GluR1. The anticonvulsants, lamotrigine (6-(2,3-dichlorophenyl)-1,2,4-triazine-3,5-diamine) and riluzole (2-amino-6-trifluoromethoxybenzothiazole), have been demonstrated to have efficacy in the depressive phase of bipolar disorder. We therefore sought to determine the role of these anticonvulsants, compared to that of the predominantly antimanic anticonvulsant valproate, on AMPA receptor localization. We found that the agents with a predominantly antidepressant profile, namely lamotrigine and riluzole, significantly enhanced the surface expression of GluR1 and GluR2 in a time-and dose-dependent manner in cultured hippocampal neurons. By contrast, the predominantly antimanic agent, valproate, significantly reduced surface expression of GluR1 and GluR2. Concomitant with the GluR1 and GluR2 changes, the peak value of depolarized membrane potential evoked by AMPA was significantly higher in lamotrigine-and riluzole-treated neurons, supporting the surface receptor changes. Phosphorylation of GluR1 at the PKA (cAMP-dependent protein kinase) site (S845) was enhanced in both lamotrigine-and riluzoletreated hippocampal neurons, but reduced in valproate-treated neurons. In addition, lamotrigine and riluzole, as well as the traditional antidepressant imipramine, also increased GluR1 phosphorylation at GluR1 (S845) in the hippocampus after chronic in vivo treatment. Our findings suggest that regulation of GluR1/2 surface levels and function may be responsible for the different clinical profile of anticonvulsants (antimanic or antidepressant), and may suggest avenues for the development of novel therapeutics for these illnesses.

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“…Nossa opção de administrar aciclovir para o paciente foi embasada na mais singela prática da medicina: devemos sempre tratar, algumas vezes diagnosticar e jamais prognosticar. O tratamento da ELA com o riluzole é apenas mais uma possibilidade que parece não ser das mais animadoras 2,19 . O uso de ceftriaxona, como era de se esperar, mostrou-se absolutamente desprovido de benefícios 20 .…”

Section: Discussionunclassified

Esclerose lateral amiotrófica e herpes vírus. Relato de um caso curioso: uma associação casual ou causal?

Ferri-de-Barros¹,

Moreira

1998

Arq. Neuro-Psiquiatr.

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RESUMO -Objetivo: Apresentar o relato de um caso curioso de esclerose lateral amiotrófica (ELA). Caso: Homem de 47 anos que apresentava déficit de força nos membros superiores evoluindo há 4 anos. A eletroneuromiografia era compatível a ELA, forma de Vulpian-Bernardt. O estudo do líquido cefalorraqueano (LCR) mostrava processo inflamatório e positividade das reações para Herpes vírus I e II. O estudo do LCR, do soro sanguíneo e da barreira hemato-encefálica sugeria imunoprodução local para Herpes vírus tipo I. A ressonância nuclear magnética sugeria mielopatia cística ou seringomielia em medula cervical estendendo-se nos espaços C2 a C4. O paciente foi tratado com aciclovir endovenoso por 21 dias. Até dois meses após, o paciente não foi submetido a novos exames subsidiários para controle. Discussão: Até o momento atual, a doença ELA não tem tratamento medicamentoso específico. A noção da existência de "síndrome esclerose lateral amiotrófica" associada a etiologias diversas pode contribuir para o tratamento de alguns doentes.PALAVRAS-CHAVE: esclerose lateral amiotrófica, herpes vírus, tratamento medicamentoso. Amyotrophic lateral sclerosis and herpes virus. A curious case report: a cause or casual association?ABSTRACT -Objective: To present a curious case of amyotrophic lateral sclerosis (ALS). Case: A forty-seven year old man claimed of paresis in the arms since four years. The electrical study of the muscles and nerves diagnosis was ALS, type Vulpian-Bernardt. The cerebrospinal fluid study revealed an inflammatory process and the positivity of immulogical reactions for Herpes simplex I. The blood-brain barrier study showed the possibility that immulogical response for Herpes simplex I was produced in the spinal fluid space. A magnetic resonance suggested cystic myelopathy of cervical spinal cord expanding from C2 to C4. The patient received endovenous acyclovir for 21 days. Until two months after the medication we did not submit the patient to other subsidiary examinations. Discussion: Until now there is no specific drug treatment for ALS. The notion that there is a "syndrome of ALS" related with various causes may help to treat some patients.

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A Controlled Trial of Riluzole in Amyotrophic Lateral Sclerosis

Abstract: The antiglutamate agent riluzole appears to slow the progression of amyotrophic lateral sclerosis, and it may improve survival in patients with disease of bulbar onset.

Cited by 1,942 publications

References 18 publications

Strength Testing in Motor Neuron Diseases

Strength Testing in Motor Neuron Diseases

The Anticonvulsants Lamotrigine, Riluzole, and Valproate Differentially Regulate AMPA Receptor Membrane Localization: Relationship to Clinical Effects in Mood Disorders

Esclerose lateral amiotrófica e herpes vírus. Relato de um caso curioso: uma associação casual ou causal?

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