“Werewolf syndrome” in dogs: the search for the causes

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What exactly is this “werewolf syndrome” in dogs?

Andrea Fischer: We describe it as an acute, episodic behavioral disorder with anxiety states and severe neurological symptoms. Affected dogs have symptoms such as panic attacks, spasms, and howling. Epileptic fits can also occur. We find this particularly concerning, as epilepsy has been the most common neurological disease in dogs for many years. We offer epilepsy consultations in the clinic, where we examine and treat dogs with suspicious neurological symptoms. At these consultations, we occasionally see dogs with the symptoms of “werewolf syndrome.”

With similar cases showing up in specialist veterinary practices throughout the continent, European specialists in veterinary neurology (www.ebvs.eu; www.ecvn.org) have been engaged in intensive dialogue and exchange over the past few months. This has been an important element to the response, as networking ensured we could identify the syndrome as such and became aware of the accumulation of cases and the parallels between them.

Dog chews are suspected of triggering the symptoms. What evidence is there for this claim?

At the moment, there is a purely epidemiological link. The proliferation of cases of this new syndrome has been observed since last summer, and in the search for parallels, the feeding of dog chews crystallized as a common characteristic.

In many cases, the dogs were given a comprehensive battery of diagnostic tests, including blood tests and advanced neurological diagnostics like brain imaging, cerebrospinal fluid analysis. This made it possible to rule out many other possible causes of behavioral disorders, such as metabolic disorders, pains, infections, tumors, hemorrhaging, and inflammations.

According to current knowledge, there are some indications that substances that have entered dog chews made of cow hides during processing or through contamination could be responsible for the observed symptoms.

Wide-ranging epidemiological study

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Has a specific substance been identified yet?

No toxicological evidence has yet been presented – neither in testing of the chews themselves nor in samples of body fluids from affected dogs. It’s possible, however, that we’re dealing with volatile substances like solvents, or substances which are too small or present in concentrations that lie below the detection limits of the analyzers. Equally, the substances might work indirectly by triggering metabolic changes in the body of the dog. Another possibility is that the animal’s body rapidly breaks down the substances.

Whether there is actually a causal connection between substances in dog chews and the observed symptoms, however, is something that rigorous scientific demonstration must establish. Initial proofs would take the form of positive toxicological evidence or clear evidence from epidemiological studies.

Just such a wide-ranging epidemiological study has been launched by researchers at LMU’s Small Animal Clinic together with the University of Veterinary Medicine Hannover (TiHo) …

That’s right, we’re carrying out a comprehensive epidemiological study to characterize the dietary behavior of dogs. The target group is the general dog population. In the online questionnaire for the epidemiological study, which we developed and refined in conjunction with TiHo, we ask dog owners about the diets of their pets and about any acute behavioral episodes or seizures. Participation is open to anyone who owns a dog, even if the dog does not have the symptoms. In epidemiological studies, it’s always important to study a large population so that you can make robust conclusions through comparison with control groups and incorporate as many risk factors as possible into the analysis. This is possible only with a large database. After all, if you include more risk factors in the analysis, then its conclusions become less ambiguous.

Supplementary toxicological investigations are being conducted in various toxicological institutes, including the Institute of Pharmacology, Toxicology, and Pharmacy at LMU’s Faculty of Veterinary Medicine and the supervisory authorities at the state testing laboratories.

What data are you collecting in the course of the study?

The questions cover numerous risk factors and aspects: the general health data and characteristics of the individual dogs, such as breed, age, and sex, but also their living conditions, current and former diseases, medication, vaccines, and individual preventative healthcare treatments. On top of this, there is a detailed analysis of diet. When considering the possibility of exposure to toxins through the environment or food, it’s particularly important to investigate many different factors.

By comparing affected dogs with unaffected dogs from the general population, we want to obtain reliable indicators of possible triggers or risk factors for “werewolf syndrome” and potentially also other neurological diseases like epilepsy. We also include data from patients (sick dogs) that have received a detailed neurological diagnosis from specialist animal neurologists (EBVS® European Specialists in Veterinary Neurology; www.ebvs.eu). And so we have data from a large population, for which we can analyze exposure and possible connections with dog chews and other risk factors, and then we have the group of cases where thorough neurological examinations were carried out, along with their detailed exposure and testing data.

Many possible causes for seizures

So research into the causes of “werewolf syndrome” is beginning in earnest …

Yes, I think we’ll learn a lot of new things from the research project. It will certainly give us exciting insights into the connections that can exist between diet and behavioral changes, psychoses, and other neurological symptoms such as epilepsy and dyskinesia in dogs. I’m convinced there should be greater emphasis on diet in research.

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What parallels exist with your main research interest, epilepsy in dogs?

As things stand, we wouldn’t classify “werewolf syndrome” as epilepsy, but as an acute behavioral disorder or psychosis in which epileptic fits can occur in individual cases. According to our current understanding, these dogs recover and do not have lifelong symptoms, as is usually the case for dogs with epilepsy.

Repeated bouts of unusual behavior can have many causes, as can epileptic fits and dyskinesia. The brain itself can be diseased as a result of a tumor, an inflammation, a vascular insult or a past trauma. And there is also canine idiopathic epilepsy, which often has a genetic origin. Furthermore, there are metabolic disorders, poisonings and other disorders that can mimic epileptic fits. In these cases, nothing suspicious shows up on brain scans – neither structural lesions nor centers of inflammation. Just like in the transient neurological symptoms, as is currently the case for “werewolf syndrome.”

Diagnosing chronic epilepsy is complex, and each case entails a certain amount of detective work. Similarly to epilepsy in humans, its canine counterpart is increasingly being viewed as a complex disease involving a combination of genetic risks and external factors. There are also indications that inflammation and diet can modulate the expression of epilepsy and dyskinesia. “Werewolf syndrome” will potentially give us further insights here.

Can human medicine learn anything from research into epilepsy and other neurological disorders in dogs?

There are many parallels, as dogs and humans have very similar basic organisms and biological and genetic backgrounds. I think there’s a rich store of potential here, which research has left largely untapped. We want to exploit this with our animal neurology research. After all, dogs not only often suffer from the same tumors, metabolic disorders, and genetic diseases as people, but also from neurological conditions such as epilepsy, dyskinesia, neurodegenerative diseases, and autoimmune diseases with parallels to ALS and multiple sclerosis. Furthermore, many animal owners have a big interest in contributing to the improvement of diagnosis and therapy with their animals. I ask myself why human medicine does not place more of an emphasis on these spontaneous animal models instead of animal experiments. In my view, there is untapped potential here, especially for gene discoveries and innovative therapeutic approaches. Our team, for example, is collaborating with pediatricians on research into a form of genetic epilepsy in dogs with parallels to epilepsy in children. Similarly, researchers at LMU’s Small Animal Clinic are engaged in pioneering collaborations with Dr. von Hauner Children’s Hospital at LMU on therapies for feline infectious peritonitis (FIP), a coronavirus infection in cats which is generally fatal.

Prof. Dr. med. vet. Andrea Fischer heads the Neurology & Neurosurgery department at LMU’s Small Animal Clinic. She is national representative for Germany at the European Board of Veterinary Specialisation.