CDKl5 Epilepsy

Epilepsy is a primary symptom of CDKL5 Deficiency Disorder and can have a huge impact on the lives of our children. Currently there are a number of clinical trials aimed at finding ways to treat seizures in children with CDKL5.

CDKl5 Epilepsy

Although it is relatively rare for children with CDKL5 disorder to experience status epilepticus, it can happen by the very nature of the severe seizure disorder which is generally the most prominent symptom of the disorder.

However, non-convulsive status is more common amongst this population of children.  The following article has been written as a guideline.

Status epilepticus is defined as a seizure lasting for thirty minutes or longer, or multiple seizures spaced so close together within thirty minutes that the patient does not recover between them. Status epilepticus – regardless of its cause – is associated with increased morbidity and mortality in all age and remains the most common neurological medical emergency in the UK.

At the onset of a seizure, it is first important to ensure that the patient is not in a potentially harmful position, and assess their airway, breathing and circulation. Help should be called for immediately – whether it is an ambulance or medical staff, depending on where the seizures begin. As soon as the proper equipment is available, the patient’s blood glucose concentration should be checked and high flow oxygen administered.

As is outlined in Figure 1, if intravenous (IV) access has not yet been established, then 0.5 mg/kg of buccal midazolam should be given. IV access should be gained rapidly such that 0.1 mg/kg of lorazepam can be administered if the convulsions persist for ten minutes following the first line oral treatment.

On the occasion that IV access cannot be obtained, a second dose of buccal midazolam can be given or, alternatively, a rectal dose of paraldehyde could be administered.

The patient should be carefully monitored after the first dose of lorazepam and, if their seizures continue for ten minutes, a second dose of lorazepam should be given. If the patient still does not recover, they are said to have entered the second phase of status epilepticus – established status epilepticus.

This phase of the condition is first treated by setting up an IV infusion of 20 mg/kg of phenytoin to be administered over 20 minutes. As an adjuvant to phenytoin, a 0.8ml/kg mixture of paraldehyde can also be infused at the discretion of senior medical staff. Alternatively, 20 mg/kg of phenobarbital can be infused over five minutes.

It is at this point that the staff of the intensive care unit should be notified of the impending transfer of the patient for intensive treatment; the patient is now entering refractory status epilepticus.

Figure 1: A flow chart outlining the treatment of status epilepticus in children.

Freilich ER, Schreiber JM, Zelleke T, Gaillard WD (2014). Pediatric status epilepticus: identification and evaluation. Curr Opin Pediatr 26(6): 655-661.

Nair PP, Kalita J, Misra UK (2011). Status epilepticus: why, what, and how. J Postgrad Med 57(3): 242-252.

Neubauer BA, Hahn A (2014). Syndromes at risk of status epilepticus in children: genetic and pathophysiological issues. Epileptic Disord 16 Suppl 1: 89-95.

Scott RC, Surtees RA, Neville BG (1998). Status epilepticus: pathophysiology, epidemiology, and outcomes. Arch Dis Child 79(1): 73-77.

There are a number of dietary treatments which are used to help with the management of epilepsy.
The ketogenic diet, a high fat diet designed to mimic starvation and has been used for the treatment of epilepsy for over eighty years.

Many children with CDKL5 have tried the ketogenic diet, some has had very good responses, although the prevalence of those that have achieved seizure free has been relatively small.

However, having said that parents have reported few seizures, increase in awareness and a better quality of life.  CDKL5 UK have worked closely over the years with Matthews Friends, the Ketogenic Diet Therapies charity in the UK.  There are a number of dietaries which are currently in use:

Classical Ketogenic and MCT Diet
Modified Atkins Diet
Low Glycaemic Index
Tube feeding the Ketogenic Diet 
A comparison of Dietary Treatments

For more detailed information about dietary therapies for epilepsy visit the Matthews Friends website here.

Personal Experience of the Ketogenic Diet

Before Evie started on the ketogenic diet I had my doubts. It all sounded very complicated and thought it would just take over and going out and away would be a nightmare. In the build up to starting the diet the information came in fast and the papers built up and I talked myself into not being able to do it.

I didn’t really understand it and I didn’t know anyone else who had tried it. It turned out I was making it seem a lot worse than it actually is.

When we went for the first appointment my mind was put at ease. The dieticians for me were great, explaining things well so I can could understand it and so could my family who I took with me, I thought in the case the more ears the better and also for when they would look after Evie they would have more of an understanding.

I just told myself it would be like getting up to prep bottles like I did when Evie was born except  I would be getting up and weighing out her meals for the day, it would soon become way of life which it has. I am a very organised person, which I think with this kind of diet really helps.

Evie has never been a fussy eater and would always try new things which helped, in the lead up to starting I tried a few meals out on Evie to see what she would and wouldn’t like.

When we started the diet GOSH where great, they were always at the end of the phone or email. For the first 2 months I think I spoke to them nearly every day one way or another!

They initially said to give the diet a go for 3 months, check her blood keto levels every day with a finger prick test (which I hated, still do) and we will find a ratio which suits her best. 3+ months went past and there was no change, she was still having tonic-clonic seizures, they said to give it another few months but I said I would give it another month and that would be it.

I remember being out shopping with Evie and she suddenly had a really bad seizure, luckily before rescue meds was needed she came out of it. That was it for me; I was ringing the hospital and coming up with a new plan. But after that seizure there were no more tonic-clonics, so we monitored her and things did improve, yes she has absences and spasms but to me that is better than the tonic-clonics.

So we continued on with the diet, regular checks at GOSH, regular weighs in and blood checks and it became way of life pretty quickly. She does pretty much have the same meals everyday but she doesn’t complain and she always eats them.

As I said before I am organised, once you are established on the diet you can cook and freeze meals and I prep what I can for the week ahead especially with Evie being at school now. School are also extremely good and only give her what I take in and they keep her own squash at school.

There are things that seem extreme, like certain toothpastes, squashes and certain double creams but you soon get used it. And then there’s the pots! You will have more plastic pots than you could ever imagine!

Evie has now been on the diet for 2 ½ years and I feel it’s time to wean her off. Why? Because over the last 2 ½ Evie has changed so much and I want to see that the diet I still the right way forward for her. Yes there is a chance of some bad seizures coming back and she has had the odd one here and there but if they come back then the diet will also come back in play. I feel she is missing out on different textures, flavours and the opportunity to try and chew.

She will be weaned off the diet like she was weaned on, gradually, slowly and will be monitored by weight and keto blood levels. We are currently on the first stages on coming off so fingers crossed it goes smoothly.

If you are thinking of trying the ketogenic diet but you are unsure then I personally would say give it a go but that’s because it worked for us. At least you would have tried it and if doesn’t work you can cross it off, like any of the epileptic drugs out there, they don’t work for everyone. Its finding what’s best for your little fighter.

Vagus Nerve Stimulation

For most children and adults with CDKL5 their epilepsy does not respond to medication.  This is known as refractory or intractable epilepsy.  It is becoming more common for these patients with CDKL5 to have a Vagus Nerve Stimulator. The youngest patient our support groups have known to have the procedure is 9 months of age.  The average age of children that are currently undergoing the surgery is between 3-5.

Vagus Nerve Stimulator therapy uses a pulse generator to send mild electrical stimulations to the vagus nerve with the aim of reducing the number, length and severity of seizures. NICE guidelines state that “VNS is indicated for use as an adjunctive therapy to reduce the frequency of seizures in patients whose epileptic disorder is dominated by partial or generalised seizures that are refractory to anti-epileptic medication.”

VNS surgery is carried out, in full consultation with parents and the child’s Neurology team, by a neurosurgeon. The operation normally takes around one hour and is usually day surgery, recovery will depend on whether the child will be released the same day or the next.

The neurosurgeon makes two small cuts, one in a natural crease on the left of the neck, and one in the left-hand side of the chest, below the collarbone. The generator is placed under the skin in the chest. A thin, flexible wire connects the generator to the left vagus nerve in the neck. The small scars from the two cuts fade over time.

The generator is checked during the surgery but is usually left switched off for two weeks after surgery. This is to help the body heal. After that, it is usually switched on by a epilepsy nurse specialist in a clinic.

They will gradually increase the settings (adjustments) over a number of weeks, the frequency of these adjustments will be determined by local policy and also how well the patient seizure control is with each adjustment.  For example if a patient is having good seizure control at a certain level, then they may not need regular adjustments.

It varies from individual to individual to see the positive effects of VNS.  For some there are some immediate benefits as soon as stimulation reaches a therapeutic level however, it can take up to two years before full benefits are seen.  For many parents they report that the magnet is able to either stop or reduce the length and severity of a seizure from the beginning.  Other benefits of having the VNS which parents have noticed is the decrease in seizure activity and severity and increase in the quality of live of the patient.  This in turn have a positive impact on the carers.

With any operation that involves a general anaesthetic there is rick of a reaction to the anaesthetic.  Because the surgery is invasive there is also a small risk of bleeding and infection. The Neurosurgeon will take all the necessary precautions to prevent this and you will be given dressings to ensure that the wound site is kept clean, you will be given a follow-up appointment to ensure that the site is healing well. There can be other rare complications and your surgeon will discuss this before the operation takes place and prior to you signing the medical consent form.  There might be some some pain for a while from the area of the implant after VNS surgery and this can be managed with over the counter pain meds.  For more intense pain then seek advice from the GP.

The magnet is used to add a burst of stimulation for 1 minute in the event of a seizure.  The generator is normally set so that when the magnet activated the generator the amplitude of stimulation is at a high rate.  The magnet can be used anytime during a seizure, but it is most likely to work when it is used towards the beginning of a seizure. You should use the magnet if…

  • You see seizure activity beginning to start.
  • At the start of a seizure.
  • Or when if you notice the patient is having a seizure.

Generally the epilepsy nurse, or community nurse will be able to provide training on the use of the magnet to education and carers for example.  The magnet can be used to also switch off the generator if a MRI is needed for example.
Because the magnet is strong there are some safety tips that you should be aware of.

  • Keep your magnet in a different pocket or on your belt buckle, away from your wallet at it can affect credit/debits cards for example.
  • If you use a computer frequently, don’t wear the magnet on your wrist – it may get too close to the computer. Wear it on your belt buckle or put it on the floor when you are working at the computer.
  • Don’t put magnets on top of a television, stereo, or other electronic device.
  • Don’t enter rooms or places that have strong electronic or magnetic fields or that have warnings for people with pacemakers or other implanted devices.
  • Ask your doctor or nurse to write a letter to use while travelling that explains the VNS device and magnets. Wands used during security checks could affect the VNS device or the magnet could trigger a security alarm.

If in any doubt about the use of the magnet then should can consult the VNS Therapy Patient Manual which should have been supplied at the point of surgery, or alternatively it can be downloaded from Cyberonics website here, or alternatively your epilepsy specialist nurse.

VNS therapy is not a drug, so doesn’t have the same sort of side-effects as epilepsy medicines, and it doesn’t interact with other medicines. However, for some patients that have CDKL5, they may have a “honeymoon” as they do with drugs. The most common side-effects reported from having the VNS implant.

  • Temporary hoarseness/change in voice tone
  • Sore/tickling throat
  • Shortness of breath
  • Coughing

Generally these side-effects happen during stimulation, and usually get less over time. However, If you continue to have side-effects, talk to your epilepsy nurse, to see if they can help.

VNS is not used to replace medications.  However, if there is a positive improvement with the VNS then it is possible that the Neurologist will look to reduce medications over time.

The generator does not last for ever and therefore at some point, it will need replacing.  It usually lasts for around three to six years, depending on the settings used. The higher the frequency and output of the settings, the faster the battery will run down. The epilepsy nurse will ensure that the VNS is checked every 3 months or so and they are able to see when the battery is running low. If seizures increase and your know that the battery is nearing the end of its life it is important that you seek support from the epilepsy nurse so that the generator can be replaced at its earlier convenience so that seizure control is not impacted too greatly.  The surgery for the replacement is similar to the first, however, the wires are kept in situ and are checked to ensure that the are still in tact.

Further information is available from Cyberonics, who make the VNS devices. You can also see the NICE guidelines here.