Seizures, convulsions and epilepsy

Authors:

Professor Sarah Wolfensohn

Dr Penny Hawkins

Dr Elliot Lilley

Professor Daniel Anthony

Charles Chambers

Sarah Lane

Dr Martin Lawton

Dr Sally Robinson

Dr Hanna-Marja Voipio

Dr Gavin Woodhall

Publication:

Journal of Pharmacological & Toxicological Methods 67, 9-15

Publish Date:

13 September 2012

Background

Animal procedures that can result in seizures, convulsions or epilepsy are used in the development of therapies and treatment regimes for epilepsy and to investigate the underlying mechanisms of this and related conditions. The procedures used to induce seizures, convulsions or epilepsy, and the conditions themselves, are all recognised to have the potential to cause high levels of suffering in animals and are therefore a priority area for implementing all of the 3Rs (Replacement, Reduction, Refinement).

Summary

This report addresses specific welfare issues associated with procedures that result in seizures, convulsions and epilepsy. It includes specific welfare and ethical issues associated with each of these conditions, including induction, translational validity, experimental design, severity assessment, humane endpoints, and housing and care. The report also provides practical measures to reduce animal suffering through the refinement of procedures for each of these conditions.

Key Actions

Provide appropriate housing and care that meet the needs of the animals.
Identify and refine adverse effects resulting from seizures, convulsions and epilepsy, taking into consideration the different phases.
Develop a detailed scoring system taking into account the type, intensity, frequency, and duration of the seizures, as well as the Racine score.
Define early humane endpoints.
Communicate and disseminate good practice.

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Further questions

Animals may experience little to no suffering during a seizure due to loss of consciousness. However, the procedures to induce them (chemical or electrical) are significant sources of suffering. Animals can also experience distress from post-ictal neurological disturbances like drowsiness, confusion, nausea, and headache, similar to human patients. Convulsions can also lead to post-convulsion muscle pain and injury. Chronic epilepsy models are associated with the highest levels of suffering and mortality.
Implement continuous, vigilant monitoring of animals immediately post-seizure and during chronic epilepsy models. Combine this with pre-defined, clear humane endpoints that trigger immediate intervention or removal from the study. These measures ensure timely provision of supportive care, such as warmth and fluids, and minimise prolonged suffering by preventing animals from enduring severe or untreatable seizure activity and its debilitating after-effects.

Authors

Professor Sarah Wolfensohn - University of Surrey

Dr Penny Hawkins - RSPCA Animals in Science Department

Dr Elliot Lilley - RSPCA Animals in Science Department

Professor Daniel Anthony - University of Oxford

Charles Chambers - University of Bristol

Sarah Lane - Novartis

Dr Martin Lawton - Lawton and Stoakes Veterinary Surgeons

Dr Sally Robinson - Astrazeneca Safety Assessment

Dr Hanna-Marja Voipio - University of Oulu

Dr Gavin Woodhall - Aston University