Lafora disease

It was in 2004 that we noticed the deterioration in Sam, our Dachshund. He stopped playing ball and started to lick his back feet and haunches and asking to be carried up the stairs.

From diary entries I can see that the first note about Sam’s ‘oddness’ and his inability to stand on his hind legs was in November 2007. At times his back legs gave away completely.

In January 2008 I wrote that Sam didn’t seem to know what he wanted. Later, he became very unwell and couldn’t stand. The emergency vet gave him painkillers and Sam went to an orthopaedic vet. Sam was an inpatient for five days. Nothing showed obviously on his X-rays.

At this time concerns were raised over his ataxia, a condition that affects the part of the brain which controls balance and which caused Sam to “high step” with his back legs. We couldn’t remember a time when he hadn’t walked like that; it had come on gradually. Sam came home prescribed prednisolone and gabapentin for nerve pain. We soon realised that he seemed to be “jumping” more often, as if being startled. At first we thought just rapid movements alarmed him; then we realised it happened after any slight move, any sudden noise, flickering from the television, the sunlight. He reacted like he’d been slapped in the face.

I noted that Sam seemed to have no traction in his back legs whatsoever in April 2008. In July, he had two vestibular attacks. He was treated again with prednisolone and recovered very well.

He gradually went blind and deaf and started to have difficulty climbing the stairs. Dementia slowly crept up on him. Somewhere during all this, he developed myoclonus, a medical sign of twitching muscles.

Sometimes he would keel over, as if he had tripped or stepped onto something that threw him off balance.

Early in 2010 I was looking at Dr Clare Rusbridge’s website. I read the Lafora disease page and realised that Clare was describing Sam. Then, I watched a video clip, and I knew that, indeed, Sam had Lafora disease. My vets, who had never heard of Lafora disease before, agreed.

None of Sam’s meds needed to be changed; he was on drugs for older dogs, Vivitonin and Aktivait, and the painkiller gabapentin.

At Sam’s age there was no point in seeing a neurologist because nothing would’ve changed. It would have been expensive, and distressing for Sam, to tell us something we already knew. He sadly passed away on 11 November 2010 and his obituary was printed in the February 2011 issue of Dogs Today.

My own vets had never heard of Lafora disease. I have found out more about it, but wanted to make other people aware of this dreadful condition, in the hope that it could help just one more person reach a diagnosis.

Jean Collinson, by email



Clare Rusbridge, BVMS PhD DipECVN MRCVS RCVS and European Specialist in Veterinary Neurology advises...


What is Lafora?
Lafora disease is a disabling progressive neurological disease characterised by myoclonus (jerking), epilepsy and dementia. It is due to excess storage of a toxic starch-like compound called ‘polyglucosan’ within cells – in particularly in nerve, liver and muscle cells. Latest research suggests that there is a problem with the control of the manufacture of glycogen and/or regulation of insulin sensitivity. Glycogen is a polysaccharide (complex carbohydrate) of glucose, which is stored in the animal cell providing the most important source of short term energy.

Is Lafora genetic?
Yes, in the Minature Wireharied Dachshund and Bassett Hound Lafora’s disease is caused by a mutation in the EPM2B (NHLRC1) a gene that encodes malin E3 ubiquitin ligase, a protein involved with carbohydrate metabolism. It is inherited as an autosomal recessive condition. This means that to have the disease the affected dog will have inherited one copy of the disease gene from each of the parents. Both male and female dogs can be affected.

For the breeder of a Lafora dog this means that both the SIRE and the DAM of an affected dog will be either a CARRIER (one copy of the gene and unaffected) or AFFECTED (two copies of the gene). Also ALL of the puppies of a dog with Laforas disease will be either a CARRIER (one copy of the gene and unaffected) or AFFECTED (two copies of the gene). The puppies will only be affected if the mate of the Lafora’s affected dog was also either a carrier or affected. As Lafora’s is a late onset disease it is not possible to select away from the condition by simple breeding practice, e.g. avoiding using affected individuals, and ideally breeders of susceptible breeds should srceen their dogs prior to mating.

Are there DNA tests available?
The genetic mutation was discovered by a Canadian/UK team led from the The Hospital for Sick Children, Toronto and they offer an ‘affected/unaffected’ test in return for a $300 (Canadian dollars) donation to the hospital.
Unfortunately at the current time a test for carriers is not available.

5-10mls of EDTA blood should be submitted to:

Dr. Berge Minassian
Room 6536B
The Hospital for Sick Children
555 University Ave.
Toronto, ON
M5G 1X8
Canada

Tel: 416-813-7721 berge.minassian@sickkids.ca

The disease may also be confirmed by identification of the abnormal polyglucosan (Lafora bodies) in a liver, muscle or nerve biopsy.

What breeds/types of dog are typically affected? Are any other animals affected?
Lafora disease can occur spontaneously in any breed however the Miniature Wire-haired Dachshund, Bassett hound and Beagle are predisposed. Typically first signs are from the age of six-seven years although some dogs start to show signs much later. The Beagle has a more severe version of the disease and the associated epilepsy can be drug resistant. The mutation causing Lafora’s disease in Beagles is so far undetermined. Disease similar to Lafora’s disease has also been also reported in a six-year-old captive-born female fennec fox, cows and a parakeet. Lafora’s disease is a rare cause of progressive myoclonic epilepsy in children. The human form of the disease is typically severe and fatal with affected children developing dementia and status epilepticus; most do not survive beyond their second decade.

What are the signs to look out for?
The most characteristic feature of Lafora disease is a myoclonus typified by rapid shuddering/jerking the head backwards. The jerking movements occur spontaneously and in response to flickering light (including television), sudden sounds and movement especially that close to the dog’s head. These violent jerks can be so disabling that simple activites such as a car journey or walk in long grass can be extremely difficult or impossible. Hypnic (sleep related) myoclonus may also occur. Generalised or focal seizures may be seen in some dogs. The disease progresses slowly over many years and gradually other neurological deficits such as ataxia (wobbliness), blindness and dementia occur.

What treatments are available?
Drugs
Not all dogs with Lafora’s disease require medication however if they have frequent seizures or if the myoclonic jerking is disabling then therapy is advised. In some cases this can be difficult since some dogs do not respond to traditional anti-epileptic drugs like phenobarbital. If the main problem is seizures then I usually start with the antiepileptic drug potassium bromide adjusting the dose to achieve an optimal blood concentration without adverse effects (such as drowsiness or uncoordinated walking). If the number of seizures is still unacceptable then I add phenobarbital again adjusting the dose to achieve an optimal blood concentration without adverse effects. If the seizures are still not adequately controlled with these licensed dog medications then I switch to unlicensed anti-epileptic drugs such as Levetiracetam or Zonisamide. At this stage it is worth considering referral to a specialist veterinary neurologist as they are likely to be more experienced in prescribing these drugs. These “human” second generation anti-epileptic drugs may also be more effective for treating the myoclonic jerks.

Diet
Anecdotally there is some evidence to suggest that dogs with Lafora’s disease are improved on a low glycemic index (GI) diet - in other words a diet which is low in simple carbohydrates. Simple carbohydrates, e.g. glucose and starch, are easily and quickly digested and release glucose rapidly into the bloodstream. There are many proprietary dog food diets that that have a low GI-index and/or are low in carbohydrates (look for a low grain content) and some owners use homemade diets however, remember that before changing your dog’s diet you should seek the advice of your veterinary surgeon. Starchy/sugary treats may aggravate Lafora’s disease and should be avoided.

Other
Some dogs have a problem walking in sunlight and some owners have found that the jerking significantly improves if the dog wears sunglasses (for example DOGGLES). Signs of Lafora’s disease can be aggravated by stress and anxiety and dogs with Lafora’s disease can be more likely to become anxious. Contact your veterinary surgeon for advice. Simple aids include Dog Appeasing Pheromone (DAP) which is available as a spray, a diffuser or a collar. DAP is the synthetic equivalent of the pheromone secreted by bitches to reassure their pups.

Other links
Lafora dogs http://laforadogs.org/ aims to provide central hub for information for owners who have or think that they might have a dog with Lafora’s disease. There is also information on management based on other owners’ personal experience and what is being done to try to reduce the number of affected dogs in the future. More information about Lafora’s disease, its diagnosis and prevention can also be found at www.veterinary-neurologist.co.uk