I set off, leaving my work in the UK, my body arriving in Seattle and my suprachiasmatic nucleus staying stubbornly in mid-Atlantic, waiting to be collected on the way home. In the North West USA I found that we are two nations separated by a common pharmaceutical industry.
The drugs clobazam and vigabatrin arriving with much fanfare in the USA at glacial pace after decades in Europe. On the other hand, slow release preparations of oxcarbazepine and topiramate (for epilepsy only, not migraine) being launched in the USA, hopefully the Gulf Stream will get them to us more quickly. The annual course was on the subject of status epilepticus and the key question of the morning was should every single patient in the neuro intensive care have EEG monitoring. Of course they should and there should be an end to all war, poverty and illness too – so I skipped that as being redundant in the real world. I take some consolation that the presentations are from centres of excellence and in Armpitsville Arizona, practice is more what I am used to, with EEG monitoring a wish more than a reality. The science of status epilepticus is becoming evermore interesting – I have reported before that GABA receptors are internalised and stop working after a short time, explaining the failure of benzodiazepines after the initial stages. But NMDA receptors become upregulated and may be responsible both for seizures and neurotoxicity. There was discussion around the use of ketamine in the ITU, as a neuroprotective agent and it was felt that there was some rationale but no evidence. A trial of therapy is just starting in the USA, comparing Phenytoin, Levetiracetam and Valproate. The latest kid on the block with anecdotal successes is IV lacosamide but it will not be included. There was also debate around whether we treat non-convulsive status too aggressively and that in less severe forms of status, the prognosis depends on the cause and the toxicity of drugs is a significant factor.
A year ago, CNN released a documentary called Charlotte’s web about Charlotte Figi with Dravet’s syndrome (severe myoclonic epilepsy of infancy, often due to a sodium channel mutation) whose treatment failed until she tried “medical marijuana” with miraculous results – see youtube. Since it is only licensed in few states, notably Colorado, this has lead to a migration of hopeful families to said states on the hemp road and not insignificant pressure on the medical profession, which they have responded to in a commendably balanced fashion by doing some science. There were two sessions, including an excellent one featuring researchers from our very own University of Reading, with not a ponytail or a diaphanous scarf in sight. Endocannabinoids are released post-synaptically and feed back on presynaptic neurotransmitter release, producing alterations in temporal and spatial patterns of neuronal excitation. They are implicated in modulating responses to stress and as stress is suggested to be a seizure trigger that may be important. As well as effects on neuronal firing, there are probably trophic effects too, which could be of significance in epileptogenesis. The psychoactive THC moiety can be separated from a potentially anti-epileptic moiety, within the hundreds of cannabinoids that make up Cannabis sativa. There is no doubt that cannabinoids have a useful action on a range of laboratory models of epilepsy. One poster at the conference reported some efficacy in Dravet syndrome but as was wisely quoted to us: “the plural of anecdote is not data”. It seems highly likely that trials of the drug will be taken forward and I shall watch this space with interest.
Dravet syndrome also figured in another major theme of this conference, as of all others – genetics. The array of genes is bewildering, to me at least, but we are just starting to see the first tentative steps to personalised medicine. Drugs to avoid in Dravet syndrome are those which block sodium channels, such as lamotrigine and carbamazepine, which are known to make it worse and the logic is clear, given the gene. If this also applies to those cases due to different genes, is not yet clear – whether we shall be treating the phenotype or the genotype is an intriguing question. Prof Anne Berg gave the Lennox and Lombroso lecture pointing out that in these malignant paediatric epilepsy syndromes, data clearly show that very early control of seizures can prevent long term intellectual and social disability, She contrasted the success of the coordination of childhood clinicians in improving cancer outcomes with the lack of anything similar for epilepsy and gave a call to arms to develop systems that allowed these unfortunate children to access tertiary services within days of presentation.
The AES should also be congratulated for setting up a cloud-based resource for researchers to share their information which must be valuable in accelerating the pace of new research and disseminating knowledge, especially in the area of rare genetic conditions.
What have I heard that will change my practice? There is now a large volume of evidence to suggest that the psychosocial morbidity of epilepsy is not just about having a bad time from seizures. It may precede the onset of seizures and long outlast them, even in syndromes where patients may have very few seizures in their lives, such as epilepsy with tonic clonic seizures on waking. Increasingly, I am thinking of epilepsy as a syndrome causing psychosocial dysfunction, in which seizures are just one symptom. I shall be screening my patients for anxiety and depression at each clinic appointment, as it has been demonstrated that my usual: “do they look sad or fidgety?” assessment might not cut the mustard. The Hospital Anxiety and Depression Scale was shown by Hannah Cock and others to be a useful tool and alternatives (which I prefer) are the NIID-E, which they also consider, and GAD-7 assessments. I commend them to you – available on the web. Looking forward to being home again from a slightly lonely and UK depleted AES.
Memorable statistic from the conference: The second commonest cause, after stroke, of days of life lost from neurological disease is from SUDEP. Not as common but strikes young. We need to ensure that our patients are informed sensitively of these risks to help their decision making.
ACNR 2015;14(6);24. Online 22/01/15