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Case: Six-Year-Old Girl with CAE
Sometime in January 2016, six-year-old Victoria was having episodes where she would space out for several seconds at a time during the day. From January to March the parents simply thought their daughter was not paying attention, and often they would talk loudly to capture her attention once again. The mother noticed that in March the frequency where Victoria would space out became observably more numerous, and these spacing-out spells were happening upwards of five times each hour. Because the spacing out became more pronounced the mother inquired if Victoria's teachers at school noticed anything similar. The teachers did not report on anything unusual, but Victoria's good friend did tell the mother that she had noticed Victoria spacing out a lot. The mother and father did their own research and were convinced that Victoria had CAE. The mother tested their concern by yelling into Victoria's ear during one of the episodes to see if this would startle her, but there was no startle response. This more or less confirmed their suspicion that Victoria had CAE.
Shortly after, on April 8th, they took Victoria to see their family physician who could not confirm the diagnosis until a video EEG was done. They estimated at the appointment that Victoria was likely having upwards of five seizures each hour (sometimes less and sometimes more). Thus, Victoria was having approximately 40 seizures each day. Sometimes during a seizure she would just blink or lick her lips, and other times she might also walk a little or speak incoherently.
The video EEG done on April 16th confirmed the presences of seizures. The pediatric neurologist who interpreted the EEG stated the following in the "Impression" section of the report:
This routine awake video EEG is mildly abnormal with several paroxysms recorded of generalized 3/s spike and slow wave activity which were enhanced during hyperventilation and accompanied clinically by staring and unresponsiveness. There was also a prolonged event which could have been triggered by photic stimulation at 8 Hz. The overall findings are in keeping with primary generalized epilepsy and the more prolonged events recorded, with absence seizures. Clinical correlation is indicated.
On April 21st they had their first visit with the pediatric neurologist who correlated the video EEG with the history that the parents' reported and agreed that Victoria's primary diagnosis was CAE. Prior to the appointment, the father had done research and began giving Victoria GABA (3,000 mg/day) on April 17. He believed that there was a reduction (but not complete cessation) in her seizure activity. The wife, on the other hand, was not sure if the GABA lessened the frequency of seizures. The father brought the information about GABA to show the physician, but he dismissed the information and would not agree to even review it. The father stated that given the possible adverse effects of ES, why not combine it with GABA and even PS so that a smaller daily dose might be used? The physician again expressed no interest in the information and told the parents to begin with 3 ml (150 mg) twice daily, increasing over a 14-day period to 5 ml (250 mg) twice daily.
On April 22nd Victoria began the ES at the 3 ml twice daily dosage along with 1,500 mg GABA twice daily, and a liquid fish oil product - that contained 100 mg PS, 350 mg docosahexaenoic acid (DHA), 150 mg eicosapentaenoic acid (EPA), 1,000 IU vitamin D3, 2 mg lutein, and 1 mg zeaxanthin per 5 ml - given twice daily with the GABA. She also continued with a chewable multiple vitamin/mineral supplement that she had taken since she was a toddler, along with 500 mg or more of vitamin C several times each week. Prior to using the liquid fish oil that contained PS, Victoria had taken a teaspoon daily of a different product that provided 320 mg EPA, 200 DHA, and 50 mg gamma-linolenic acid (GLA).
Victoria has been on 300 mg ES, 3,000 mg GABA, and 200 mg PS for more than seven months. The parents have not seen even one absence seizure or a hint a seizure activity since commencing treatment with this combination. Victoria has not had any problems tolerating the treatments, is now seven years old, and thankfully there has not been any need to increase the daily dose of ES thus far. Compliance has not been much of an issue. At first, Victoria consumed the GABA mixed in applesauce, but has since learned how to swallow pills, and now swallows the GABA (2 x 750 mg) twice daily without any problems. She has become much more engaged and focused since receiving treatment, and she has been less shy and more sociable at school. She is thriving and doing well overall. Victoria will be getting another video EEG when she has been seizure-free for two years, at which point the ES will be gradually discontinued to ascertain if she still needs it.
It should be noted that in the study cited earlier (Glauser et al, 2010) that involved patients with new onset CAE, the mean dose of ES at final evaluation was 33.5±15.3 mg/kg of body weight, with 17.5% of the group requiring the maximal dose of medication (2,000 mg/day). The trial duration was 16 to 20 weeks, and only 53% of patients taking ES became seizure-free. Victoria, on the other hand, had an immediate remission in all seizure activity with this combination, and has maintained the same daily dose of ES for more than seven months (300 mg) without needing an increase. According to the mean daily dose from the study, Victoria should be taking approximately 670 mg (based on her 20 kg weight) to be free from seizures. It is possible that she has only responded to the ES and not the other treatments. However, given how common and usually necessary it is for doses of anti-seizure medication to be increased - including the fact that the father noticed a reduction in seizure activity while taking GABA prior to instituting anti-seizure medication - it does seem possible and likely that the combination of ES, GABA, and PS has produced the very favourable outcome to date. This combination approach has kept Victoria's daily dose of ES low, and she has not experienced any concerning adverse effects.
Addendum to an Earlier Report
Previously, I reported on the integration of several orthomolecules - i.e., chromium, GABA, magnesium, manganese, taurine, vitamins B3 and B6, and zinc - with anti-seizure medication, and suggested that this approach facilities "noteworthy quality of life enhancements" by reducing the frequency and intensity of seizure activity (Prousky, 2014, p. 168). I also presented several cases documenting the putative efficacy of this approach.
One of the cases involved a pediatric patient with MRI results suggestive of focal cortical dysplasia, which results from some type of malformation of cortical development causing symptomatic focal epilepsy in childhood and even adulthood (Fauser, 2006). The patient was initially seen in my private clinical practice on November 2012, when she was having nighttime seizures with a seizure frequency of approximately one every two months. She was not on anti-seizure medication when I began working with her. She was put on a plan that involved the following regimen: vitamin C (500 mg twice daily); omega-3 essential fatty acids (1 teaspoon daily providing 320 mg of EPA, 200 mg of DHA, and 50 mg of GLA); vitamin B6 (100 mg twice daily); magnesium-taurine (providing 200 mg of magnesium and 600 mg of taurine daily); and GABA (200 mg at bedtime). At subsequent visits the daily dose of GABA was increased to 400 mg at bedtime, and the magnesium-taurine was increased such that the daily intake provided 300 mg of magnesium and 900 mg of taurine. The patient experienced approximately 13 seizures in total as documented in a report from her pediatric neurologist (dated: July 8, 2014) who identified that the patient had remained clinically free of seizures since September 2013. The most recent video EEG (dated: June 18, 2014) showed an absence of seizure activity during the awake and sleep period. I have continued to follow this patient's progress closely. She has remained seizure-free on the orthomolecular approach for approximately 26 months (last update with patient's father: November 11, 2016) and has not needed any anti-seizure medication. She has a video EEG planned sometime in December 2016. Her current treatment plan has remained essentially the same during this duration, except that the magnesium-taurine compound changed, and now provides less magnesium (195 mg/day) but the same amount of taurine (900 mg/day).
Given the favourable response as described in this case, as well as other positive responses documented in my 2014 paper, I believe that all patients with epilepsy would potentially benefit from a regimen of orthomolecules in combination with anti-seizure medication. Thus, it makes sense to consider a transdiagnostic approach to epilepsy that would encompass many of the micronutrients that appear to lessen seizure frequency and intensity, and promote a better quality of life. Table 3 lists the therapeutic dose ranges - based on published sources (for more specific references, see Prousky, 2014) and my clinical experience - of all the orthomolecules that could be given to patients with epilepsy to improve outcomes, especially because it can be difficult to control the activity of seizures among medicated patients that have remained treatment resistant. PS was added to the list based on the information presented in this report.
Vitamin D3 was also added because a pilot study by Holló, Clemens, Kamondi, Lakatos, and Szűcs (2012) demonstrated a median seizure reduction of 40% in 10 of 13 patients with various types of epilepsy from supplementation. All the patients in the study were adults with a disease duration ranging from 10 to 42 years, and all were considered to be pharmacoresistant. When the deficient 25(OH)D levels (defined as <30 ng/mL or <75 nmol/L) were normalized from vitamin D3 supplementation, 10 patients experienced decreased seizure frequency during the 90-day observation period, with five having a marked seizure reduction of ≥50%. The precise mechanism of action for vitamin D3 and how it moderates seizure frequency is not well known, but vitamin D receptors and the enzyme that produces its active form are widely found in the brain (Eyles et al, 2005). Vitamin D might also exert its effect in the central nervous system via calcemic and non-calcemic actions (Stewart et al, 2010). Gene expression from vitamin D is also altered when activated by the binding of 1,25(OH)D to the nuclear vitamin D receptor (Ramagopalan et al, 2010).
With respect to vitamin B3, here I have included details that were not reported in my prior publication (Prousky, 2014). Hoffer (1962) reported that niacin (nicotinic acid) can reduce the amount of anti-seizure medication needed while still affording adequate seizure control. Here is a passage from Hoffer's report noting the beneficial effects from 3 g of niacin:
I have given nicotinic acid at this dosage to six epileptics who were having difficulty with control. When they were given sufficient anticonvulsants to control the convulsions they were much too sedated and were ineffective at their jobs, etc. When they were given 3 grams nicotinic acid per day the amount of anticonvulsant could as a rule be halved. One male epileptic needed 800 mg of mesantoin daily to be free of fits, but this large dose made him too sluggish and dopey to do his work. Three grams of nicotinic acid daily allowed me to reduce his dose of mesantoin to 200 mg, yet remain free of seizures, be normally alert and keep his job. He remained on this combination for years (p. 25).
Hoffer (1962) also cited a case in more detail describing the therapeutic effects of vitamin B3 (as niacinamide) in a 16-year-old female having a history of mixed petit mal and grand mal seizures, taking phenobarbital and dilantin to control them. When she was examined, it was apparent that her daily doses of anti-seizure medication (i.e., 300 mg dilantin and 90 mg phenobarbital) were causing symptoms of over-sedation, which made it likely that she would lose her job because of making too many mistakes. She also exhibited perceptual changes that included laughing frequently and inappropriately. Hoffer commented that the "problem was to provide a balance between freedom from convulsions and freedom from over sedation" (p. 28). He started her on 3 g of niacinamide daily, and reduced the dilantin to 160 mg and the phenobarbital to 60 mg. She was seen a little over 6 months later, did not report any seizures, had no more perceptual changes, and demonstrated good cognition and mood during the examination. A little less than three months later, she continued to be free from seizures, and was looking forward to pursuing a Bachelor of Arts degree at university.
Other data cited by Hoffer (1962) showed that children given doses of niacin as low as 50 mg orally had EEG changes within 5 to 10 minutes whereby the vitamin "produced a dramatic normalization of high voltage alpha activity without spiking" (p. 28). He further remarked that while niacin and niacinamide produce EEG effects similar to that of barbiturates, they do not impair consciousness or awareness, but in fact "they calm and tranquilize without lessening awareness" (p. 29). As I suggested in my prior publication (Prousky, 2014), niacinamide is preferred because the cutaneous flushing seldom happens and because this form of vitamin B3 influences the GABA system and has therapeutic effects similar to that of benzodiazepine medications commonly used to suppress seizure activity.
This approach should be combined with a multiple vitamin/mineral supplement to ensure that the minimum requirements are met for all the essential micronutrients. More study is certainly needed; but given the fact that uncontrolled or treatment-resistant epilepsy is potentially life threatening and definitely life impairing, I cannot think of any justifiable reason to withhold this approach given the potential upside and the relative long-term safety and tolerability of these commonly-consumed orthomolecules.
Table 3. Transdiagnostic Orthomolecular Approach to Epilepsy 1.0 |
Intervention |
Suggested daily therapeutic dose range |
Chromium picolinate |
200-600 mcg (in suspected hypoglycemia-associated seizures) |
GABA |
400-3,000 mg |
Magnesium |
200-600 mg (or more aggressively, 5-30 mg/kg) |
Manganese |
15-30 mg |
Phosphatidylserine |
200-500 mg |
Taurine |
100-1,500 mg (or more aggressively, up to 8,000 mg) |
Vitamin B3 |
500-2,500 mg (as niacinamide) |
Vitamin B6 |
60-200 mg (consider pyridoxal phosphate - the more potent form - at a dose of 7-38 mg/kg) |
Vitamin D3 |
Optimal daily doses to maintain a 25(OH)D level ≥30 ng/mL (≥75 nmol/L) |
Zinc |
10-80 mg (consider adding 1-2 mg of copper if high doses of zinc, i.e., at or above 80 mg are taken long-term) |
Conclusion
This report focused on CAE but also included information relevant to adults with AS as well as other types of seizures. While some children with CAE will grow out of their seizures (i.e., remit) within two to five years of onset (Panayiotopoulos, 1999), some children experience persistent seizures into adulthood, and some have seizures that evolve into the generalized tonic-clonic type. Because pharmacoresistance is a real and known concern - and because some patients with CAE have persistent epilepsy into adulthood - it behooves all clinicians to think outside of the box and consider augmenting anti-seizure medication with dietary interventions (e.g., the KD, MAD, or Paleolithic KD) or with specific orthomolecules, such as GABA and PS. For patients with related or different types of seizures, I also proposed a transdiagnostic orthomolecular approach that could be offered in conjunction with anti-seizure medication to lessen seizure frequency and improve quality of life. Once again, it behooves all clinicians to consider several or all of the transdiagnostic orthomolecular treatments when faced with epilepsy patients that have remained treatment resistant and have experienced repeated seizures with debilitating and potentially life-threatening effects on their quality of life.
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Acknowledgements
I thank Mr. Bob Sealey for his helpful editing suggestions and input on the contents of this paper.
Competing Interests
The author declares that he has no competing interests.
Statement of Informed Consent
Written consent was obtained from the guardians of the patients described in this report.
References .pdf
*Reprinted with permission from: Journal of Orthomolecular Medicine, 2016; 31(2).
Jonathan E. Prousky, ND, MSc, MA
Chief Naturopathic Medical Officer, Professor, Canadian College of Naturopathic Medicine, 1255 Sheppard Avenue East, Toronto, Ontario, M2K 1E2, Tel: 416-498-1255 ext. 235, email: jprousky@ccnm.edu
Editor, Journal of Orthomolecular Medicine, email: jprousky@ccnm.edu
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