Brain Benefits Of CAVM For Epilepsy

Which of the most popular CAVM treatments demonstrate rational, plausible neuromodulatory mechanisms and, even better, value in clinical applications?


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The popularity of complementary and alternative medicine (CAM) continues to surge; this extends to epilepsy patients, wherein nearly half of patients partake of one or more CAM treatments to control seizures.1 Why does interest remain high, despite there being no proven alternative with as much evidential support as medication?2

The problem is that even with drugs, epilepsy can be tough to treat. About a third of human and canine patients with epilepsy become refractory to medications.3,4 Bouts of status epilepticus worsen the condition by increasing the expression of permeability-glycoprotein (P-gp) in the brain and escalating drug resistance.

Epilepsy has been called the most common chronic neurologic illness in dogs.5 To make matters worse, over a dozen breeds, including beagles, boxers and border collies, have genetic predispositions for epilepsy.6,7

To benefit the brain, antiepileptic treatments from CAVM need to improve brain chemistry, regulate neuronal excitability and/or revamp their firing patterns.8 In other words, a treatment needs to “neuromodulate” brain activity.9 Which of the most popular CAVM treatments demonstrate rational, plausible neuromodulatory mechanisms and, even better, value in clinical applications?

Homepathy and Herbs

Not homeopathy. Even though a recent survey of veterinary homeopaths in the United Kingdom ranked epilepsy as one of the most frequently addressed chronic conditions,10 homeopathy lacks a biologically plausible mechanism of action and evidence of effectiveness for epilepsy. While homeopathic remedies contain virtually nothing but milk sugar, their risk pertains less to intrinsic toxicity and more to the potential delay of meaningful treatment. Currently promoted standards of practice by the veterinary homeopathic community11 advise against patients ingesting medications while receiving homeopathy. This suggests that a veterinary homeopath might forgo prescribing antiepileptic agents for a new canine epileptic patient while testing the effects of what is essentially a sugar pill week after week, after week.

Herbs, on the other hand, do possess active ingredients and display measurable mechanisms of action. The ready availability of herbs on the Internet catches the bleary eye of many desperate caregivers who lose sleep over their epileptic companions. Dr. Google offers consultations 24 hours a day; the online herbal marketplace never shuts its virtual doors. Botanical blends beckon and testimonials tempt. Fearful of ridicule or criticism, veterinary clients may dose their dogs with one or more extracts, outside of the watchful eye of their regular veterinarians, unaware of the risk of interactions and duplicative effects.

Herbs

Which herbs can benefit the seizure-prone brain? Many plants have had strong folkloric appeal, including American hellebore (Veratrum viride), Kava (Piper methysticum), skull cap (Scutellaria and S Baicalensis) and blue cohosh (Caulophyllum thalictroides). However, each poses risks. As pharmacologically active agents, herbs may interact with drugs; some, such as American hellebore and skullcap, may deliver both pro- and anticonvulsive effects.12

Valerian root (Valeriana officinalis), in contrast, boasts a strong safety and long historic record; at one point, valerian served as a first-line treatment for epilepsy.13,14 Neurophysiologists are now asking questions about why ancient Eastern peoples smelled shoes to arrest seizures.15 One whiff of valerian extract, however, provides the answer. Its aroma of “old smelly gym socks” resembles well-worn shoes. By depositing volatilized molecules on the olfactory epithelium through inhalation, both odors may alter olfactory lobe activity and prevent the spread of synchronous activity and the seizures it spells.

In addition to the smell of fetid footwear, other, more pleasant forms of aromatherapy may prevent or lessen the severity of an impending seizure by means of a similarly desynchronizing effect. Sweet basil and oil of bergamot suppress seizures. Oils should be gently inhaled. Vigorous sniffing, in contrast, may precipitate an attack, as with nutmeg or anise.16 Rosemary, sage, hyssop, wormwood and fennel can arouse brain activity and are thus considered epileptogenic.17

Nutrition

Diet serves as another vehicle through which to change cerebral states. The ketogenic diet (KD) shifts the brain’s energy substrate from glucose to ketone bodies, making it less reactive to external stimuli.18 The classic KD was developed for human children with epilepsy that does not respond to drugs.19 It required that 90 percent of the total calories consumed in a day come from fat with only 10 percent from protein and carbohydrate (CHO) combined.

Early indications for KD were for children with deficiencies in glucose transporter protein 1 and pyruvate dehydrogenase, which both disturb brain energy metabolism through enzymatic defects. Supplying ketones instead of glucose transfers the brain’s energy mainstay to a less problematic source than sugar. Additional indications for KD therapy have since expanded, now including severe myoclonic epilepsy of infancy, medically refractory epilepsy, and extreme intolerance to antiepileptic drugs (AED).

No evidence supports feeding dogs with epilepsy a ketogenic diet. That said, the KD in kids has helped up to half of all patients but can lead to side effects severe enough to halt therapy.20 A less extreme option is to review a canine epileptic patient’s diet for presence of excessive carbohydrates and antigenic additives.21 For example, KD modifications have eased the restrictions in CHO and protein intake, changing children’s food to either a modified Atkins diet, limiting daily CHO consumption to between 10g and 20g, or a low-glycemic diet. Recent research from Denmark revealed that a modified Atkins diet produced similar effects as the KD in reducing seizure frequency in children with medically resistant epilepsy.22

While difficult to confirm conclusively, sensitivity to certain foods has been associated with precipitation of seizures.23-26 As such, another avenue to investigate in dog diets is the amount of allergens and additives they contain.

Acupuncture

In contrast to exogenously supplied, biochemically active antiepilepsy aids, physical medicine modalities neuromodulate endogenously. By far, the most well studied CAVM approach for epilepsy is acupuncture.27,28 Vagal nerve stimulation and electroacupuncture (EA) share mechanistic pathways and clinical value as neuroprotective approaches for patients with seizures.29,30

Even manual methods can augment vagal tone, as through ocular pressure, which limits seizure intensity.31 While chiropractors have claimed that neck manipulation neuromodulates as well, evidence consists only of case reports in epileptic children,32 and none in dogs. High velocity upper cervical manipulation also carries the risk of injury, such as stroke and death.33

As indicated above, CAVM often helps, but not always.34 For example, whereas the benefits of acupuncture for dogs with spinal cord injury, pain or impaired gastrointestinal motility are observable, the impact of acupuncture on seizures may be delayed, depending on seizure frequency. As such, feedback is not immediately available.

To assess the value of any CAVM treatment, one needs to keep close tabs on seizure frequency, quality and intensity. Most clients prefer CAVM to lifelong medications, and would like to see their dogs off of drugs. However, this is not necessarily realistic, and even if a dog is responding well, caution advises against a too abrupt withdrawal from antiepileptic medications. If, indeed, the CAVM options do show effectiveness, and if clients are so motivated, then a gradual, veterinarian-supervised withdrawal may be in order, with instructions given about what to do if the seizures recur.

Dr. Robinson, DVM, DO, Dipl. ABMA, FAAMA, oversees complementary veterinary education at Colorado State University.

FOOTNOTES

1. McElroy-Cox C. Alternative approaches to epilepsy treatment. Current Neurology and Neuroscience Reports. 2009;9(4):313-318.

2. Taylor J. Holistic treatments for epilepsy in dogs. The Bark. 2006; Issue 36. Accessed at http://www.thebark.com/print/134?page=show on 01-05-12.

3. McElroy-Cox C. Alternative approaches to epilepsy treatment. Current Neurology and Neuroscience Reports. 2009;9(4):313-38.

4. Weissl J, Hulsmeyer V, Brauer C, et al. Disease progression and treatment response of idiopathic epilepsy in Australian Shepherd dogs. J Vet Intern Med. 2011; Dec 19. doi: 10.1111/j.1939-1676.2011.00853.x. [Epub ahead of print]

5. Ekenstedt KJ, Patterson EE, Minor KM, et al. Candidate genes for idiopathic epilepsy in four dog breeds. BMC Genetics. 2011;12:38.
 
6. Weissl J, Hulsmeyer V, Brauer C, et al. Disease progression and treatment response of idiopathic epilepsy in Australian Shepherd dogs. J Vet Intern Med. 2011; Dec 19. doi: 10.1111/j.1939-1676.2011.00853.x. [Epub ahead of print]

7. Ekenstedt KJ, Patterson EE, Minor KM, et al. Candidate genes for idiopathic epilepsy in four dog breeds. BMC Genetics. 2011;12:38. 

8. McElroy-Cox C. Alternative approaches to epilepsy treatment. Current Neurology and Neuroscience Reports. 2009;9(4):313-318.

9. Chang EF and Barbaro NM. Epilepsy surgery: the emerging field of neuromodulation. Neurosurgery Clinics of North America. 2011;22(4):ix-x.
 
10. Mathie RT, Baitson ES, Hansen L, et al. Homeopathic prescribing for chronic conditions in feline and canine veterinary practice. Homeopathy: the Journal of the Faculty of Homeopathy. 2010;99(4):243-248.

11. The Academy of Veterinary Homeopathy. Standards of Practice and Purpose of the Academy of Veterinary Homeopathy. Accessed at http://www.theavh.org/referral/sop.php on 01-05-12. 

12. Pearl PL, Drillings IM, and Conry JA. Herbs in epilepsy: evidence for efficacy, toxicity, and interactions. Semin Pediatr Neurol. 2011;18:203-208.
 
13. Pearl PL, Drillings IM, and Conry JA. Herbs in epilepsy: evidence for efficacy, toxicity, and interactions. Semin Pediatr Neurol. 2011;18:203-208.

14. Eadie MJ. Could valerian have been the first anticonvulsant? Epilepsia. 2004;45(11):1338-1343.

15. Jaseja H. Review. Scientific basis behind traditional practice of application of “shoe smell” in controlling epileptic seizures in the eastern countries. Clinical Neurology and Neurosurgery. 2008;110:535-538.
 
16. Dobetsberger C and Buchbauer G. Actions of essential oils on the central nervous system: an updated review.  Flavour and Fragrance Journal. 2011;26(5):300-316.

17. Jaseja H. Review. Scientific basis behind traditional practice of application of “shoe smell” in controlling epileptic seizures in the eastern countries. Clinical Neurology and Neurosurgery. 2008;110:535-538. 

18. Swann JW. How does the ketogenic diet work? Epilepsy Curr. 2004;4(1):20-21.
 
19. Veggiotti P, Burlina A, Coppola G, et al. The ketogenic diet for Dravet syndrome and other epileptic encephalopathies: an Italian consensus. Epilepsia. 2011;52(Suppl. 2):83-89.

20. Pluta R and Jabionski M. Editorial. The ketogenic diet for epilepsy therapy in children: Quo vadis? Nutrition. 2011;27:615-616.

21. Symes, J. B.; Food intolerance, epilepsy, and the “G.A.R.D.” Small animal and exotics. Proceedings of the North American Veterinary Conference, Volume 21, Orlando, Florida, USA, 2007; Gainesville: The North American Veterinary Conference, 2007, 66-68
 
22. Miranda MJ, Mortensen M, Povlsen JH, et al. Danish study of a Modified Atkins diet for medically intractable epilepsy in children: Can we achieve the same results as with the classical ketogenic diet? Seizure. 2011;20:151-155.

23. Crayton JW. Epilepsy precipitated by food sensitivity: Report of a case with double-blind placebo controlled assessment. Clinical?Electroencephalography 12:192-198,1981. 

24. Egger J, et al. Oligoantigenic diet treatment of children with epilepsy and migraine. Journal of Pediatrics 114:51-58,1989.
 
25. Collins JR. Seizures and other neurologic manifestations of allergy. Veterinary Clinics of North America: Small Animal Practice?24: 735-48, 1994.

26. Karimzadeh P, Khajeh A, Tabarestani S, et al. Relationship between celiac disease and refractory idiopathic epilepsy in children. Iran J Child Neurology. 2010;4(4):19-24.

27. Van Niekerk J. The use of acupuncture in canine epilepsy. J South African Veterinary Medical Association. 1988;59(1):5-6.
 
28. Zhang J-L, Zhang S-P, and Zhang H-Q. Antiepileptic effects of electroacupuncture vs vagus nerve stimulation on cortical epileptiform activities. J Neurological Sciences. 2008;270:114-121.
 
29. Cakmak YO. Epilepsy, electroacupuncture and the nucleus of the solitary tract. Acupuncture in Medicine. 2006;24(4):164-168.
 
30. Zhang J-L, Zhang S-P, and Zhang H-Q. Antiepileptic effect of electroacupuncture vs. vagus nerve stimulation in the rat thalamus. Neuroscience Letters. 2008;441:183-187.
 
31. Speciale J and Stahlbrodt JE. Use of ocular compression to induce vagal stimulation and aid in controlling seizures in seven dogs. JAVMA. 1999;214(5):663-665.

32  Pistolese RA. Epilepsy and seizure disorders: a review of literature relative to chiropractic care of children. J Manipulative Physiol Ther. 2001;24:199-205.

33. Albuquerque FC, Hu YC, Dashti SR, et al. Craniocervical arterial dissections as sequelae of chiropractic manipulation: patterns of injury and management. J Neurosurg. 2011;115(6):1197-1205.
 
34. Stavem K, Kloster R, Rossberg E, et al. Acupuncture in intractable epilepsy: lack of effect on health-related quality of life. Seizure. 2000;9:422-426.

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