RESEARCH

"All truths are easy to understand once they are discovered;

the point is to discover them"

-Galileo Galilei

Gliacin^TMfor the Prophylactic Treatment of Migraine: Review of an Initial Case Series

Eric J. Eross, D.O., Scottsdale Headache Center (Scottsdale, AZ)

OBJECTIVE: Review the cases of ten patients who responded to Gliacin^TM for the prophylactic treatment of migraine

BACKGROUND: Migraine is a common primary headache disorder that is often associated with a high level of personal disability and socio-economic impact. A reduction of headache days, severity and associated disability are common goals of migraine prophylaxis. Clinical evidence, safety, potential side effects, cost and patient preference should all be considered in selecting a prophylactic agent. The use of various herbal preparations such as butterbur and feverfew are backed by the 2012 AHS/AAN guidelines for their use in the prophylactic treatment of episodic migraine. Although used in Ayurvedic medicine for thousands of years, forms of Boswellia serrata are relatively new to the headache arena. Gliacin^TM is a unique, patent-pending, heavy-metal free derivative of Boswellia serrata first shown to have promise for the treatment of indomethacin responsive headache syndromes.

METHODS: Ten Gliacin^TM responders (>50% reduction in headache frequency), were followed for a period of three to 24 months. These migraineurs included children, adolescents and adults who had either episodic or chronic migraine based on the ICHD (2nd edition) criteria. Only migraineurs using Gliacin^TM as prophylactic monotherapy were used in this analysis. Doses of Gliacin^TM were adjusted based on side effects and efficacy. Patients kept daily headache logs and completed monthly HIT-6, MIDAS and Headache Related Quality of Life (HQL) scores for analysis.

RESULTS: Of the Gliacin^TM responders, eight were female and two were male. Their ages ranged from 10 to 58 years (average of 38 years); they included one child, two adolescents and seven adults. Duration of migraine condition ranged from 0.5 to 34 years (average of 19 years). Two patients had a diagnosis of episodic migraine and eight had chronic migraine. Gliacin^TM doses ranged from 750 mg to 3,375 mg per day divided in either BID (n=4) or TID (n=6) dosing. While on Gliacin^TM, the responders’ headache frequency dropped from an average of 21 to 2.4 days per month (89% reduction) and their average pain level dropped by 46% (7.6 to 4.1). Their average HIT-6 score dropped from 70 to 49 (30% reduction). Likewise, their MIDAS and HQL sores dropped by 96% (from 81 to 3.4) and 68% (60 to 19) respectively. While on Gliacin^TMthe group of migraineurs reported a 95% reduction in headache related visits to the emergency department. The average responder satisfaction score (0 to 10) was an 8.7. Only one patient reported side effects (mild dyspepsia). All patients have elected to continue Gliacin^TM and would recommend its use to others. The average commercial cost of Gliacin^TM for responders was approximately a dollar per day.

CONCLUSIONS: In this case series, all migraineurs experienced a reduction in headache frequency, severity and related disability while on Gliacin^TM. Gliacin^TM was well tolerated without any serious side effects or adverse reactions. Likewise, it was highly satisfactory and cost effective to patients. Although the scope of this work is limited and can not be applied to all migraineurs, Gliacin^TM represents a novel herbal preparation that warrants further investigation as a potential migraine prophylactic agent.

Study presented at the Scientific Meeting of the American Headache Society (Los Angeles, U.S.A., June 2014)

Headache 2014. 54 (8): pages 1418-1434.

The Efficacy of Gliacin^TM, a Specialized Boswellia Serrata Extract,

on Indomethacin Responsive Headache Syndromes (IRHS)

Eric J. Eross, D.O., Scottsdale Headache Center (Scottsdale, AZ)

OBJECTIVE: The objective of this study was to determine the efficacy and tolerability of the nutraceutical Gliacin^TM, a specialized Boswellia serrata extract, in the treatment of a series of subjects with confirmed indomethacin responsive headache syndromes (IRHS).

BACKGROUND: Indomethacin responsive headache syndromes are a group of heterogeneous primary headache disorders which promptly and completely respond to indomethacin often to the exclusion of other treatments. Indomethacin is a powerful NSAID and its effects may in part come from its ability to block cyclooxygenase (COX) enzymes. Prototypical examples of IRHS include both hemicrania continua (HC) [4.7] and the paroxysmal hemicranias (PH) [3.2]; each requires an absolute response to indomethacin to confirm their diagnosis based on the ICHD-II criteria. Although an absolute response to indomethacin is not required for diagnosis, there are several other conditions generally accepted to be IRHS which include: primary stabbing headache (PSH) [4.1], primary cough headache (PCH) [4.2], primary exertional headache (PEH) [4.3], primary headache associated with sexual activity (PHASA) [4.4] and hypnic headache (HH) [4.5]. Unfortunately, responders often can't tolerate indomethacin long term because of its numerous side effects and potential serious adverse reactions. In such situations, a significant therapeutic dilemma ensues often leaving the clinician with few to no alternative treatments. In fact, there is a paucity of information in the literature regarding effective alternative treatments for IRHS. The author's research suggests that blocking the lipoxygenase (LOX) enzyme may be an effective alternative approach to treating IRHS. Such therapeutic candidates thus include boswellic acids which are pentacyclic triterpenes shown to inhibit prostaglandin synthesis by inhibiting the LOX pathway. Boswellic acids are found in high concentrations in the plant Boswellia serrata which has been used in Ayurvedic medicine for hundreds of years and is well known for its long term tolerability and safety. Boswellia serrata contains other phytochemicals which may mimic the physiologic effects seen with indomethacin. In this study, the effects of Gliacin^TM are investigated in subjects with confirmed IRHS.

METHODS: A total of 592 consecutive patients / potential subjects presenting to a headache subspecialty clinic for initial consultation were evaluated for the possibility of an IRHS. Of these potential subjects, 12% (n=73) were suspected of having an IRHS. All 73 subjects were placed on indomethacin and titrated based on tolerability up to doses as high as 75 mg PO TID. Those with over a 90% response (n=32, 5.4%) were classified as having an IRHS. These included subjects with HC (n=16), PH (n=4), PCH (n=4), PEH (n=2), PHASA (n=4), PSH (n=1) and HH (n=1). These 32 subjects were asked to stay on the lowest effective dose of indomethacin for 90 days if possible. They maintained headache diaries and captured information such as headache frequency, headache severity, MIDAS, HIT-6, Headache-Related Quality of Life scores and side effects experienced. After completing their indomethacin trial, subjects went through a washout period until confirmed they resorted back to their baseline headache status. Next, subjects were given the option to start Gliacin^TM or return to indomethacin use. Twenty-seven of the 32 subjects (84%) elected to proceed with the Gliacin^TM trial. These subjects were started on 250 mg PO TID of Gliacin^TM and titrated upwards based on tolerability and effectiveness. As with the previous trial of indomethacin, subjects took Gliacin^TM for 90 days and recorded key outcome measures. At the end of the Gliacin^TM trial, all 27 subjects completed an exit interview and an analysis comparing the two therapies was conducted.

RESULTS: A total of 27 subjects with a confirmed IRHS went on to undergo a trial of Gliacin^TM. Subjects who rated their overall benefit from Gliacin^TM above 70% were considered Gliacin^TM responders. The Gliacin^TM responder rate was 78% (21 of 27 subjects). These subjects included those with HC (n=9), PH (n=3), PCH (n=2), PEH (n=2), PHASA (n=3), PSH (n=1) and HH (n=1). For these 21 Gliacin^TM responders, a comparison was made between their headaches prior to indomethacin, while on indomethacin and while on Gliacin^TM. The group's average headache days per month were 28 prior to indomethacin, 2.3 while on indomethacin and 1.8 while on Gliacin^TM. The average pain levels (0-10) were 8.2, 2.0 and 2.3 respectively. The average HIT-6 scores were 67, 46 and 43 respectively. The average Headache Related Quality of Life scores were 56, 25 and 20 respectively. The average MIDAS scores were 80, 9, and 3 respectively. Sixty-seven percent of subjects rated their overall satisfaction level with Gliacin^TM superior to indomethacin. Likewise, 67% of subjects stated that they experienced significantly fewer side effects with the Gliacin^TM as compared to indomethacin. In fact, only 38% of subjects reported side effects with Gliacin^TMas compared to 81% while on indomethacin. The only side effect experienced by greater than 5% of subjects taking Gliacin^TM was diarrhea (n=2). Upon completion of the study, 86% of the subjects elected to continue the Gliacin^TM as compared to only 14% wanting to continue indomethacin. All of the non-Gliacin^TM responders (n=6) noticed that they required less indomethacin while concurrently taking Gliacin^TM.

CONCLUSIONS: The key conclusions from this study include: (1) Nearly 8 out of 10 subjects with an IRHS experienced a significant benefit from Gliacin^TM. (2) At least one of every type of IRHS was shown to respond to Gliacin^TM. (3) Gliacin^TM appears to decrease headache frequency, intensity and related disability in certain subjects experiencing IRHS. (4) Gliacin^TM is well tolerated and with fewer side effects than indomethacin. (5) Because of the side effects and potential serious adverse reactions associated with indomethacin, all indomethacin responders should be offered Gliacin^TM as an alternative treatment. (6) Treatment with Gliacin^TM (as monotherapy or in combination with indomethacin) warrants further investigation and has widespread clinical implications.

Study presented at the Scientific Meeting of the American Headache Society (Washington, D.C., June 2011)

Study presented at the International Headache Congress (Berlin, Germany, May 2011)

Cephalalgia 2011. 31 (suppl. 1): page 47.

Headache 2011. 51 (suppl. 1): pages 75-76.

The Effective Use of Gliacin^TMfor the Treatment of Primary Cough Headache

Eric J. Eross, D.O., Scottsdale Headache Center (Scottsdale, AZ)

OBJECTIVE: Review the cases of nine patients who responded to Gliacin^TM for the treatment of primary cough headache (PCH)

BACKGROUND: Primary cough headache is a rare, often debilitating headache condition associated with the sudden onset of pain as a result of coughing, straining and/or Valsalva maneuver in the absence of any intracranial abnormality. The pain is typically bilateral and occipital in location and lasts anywhere from one second to two hours. Various pharmacologic agents have been used successfully to treat PCH, but indomethacin is generally considered to be the drug of choice. Although indomethacin can be extremely effective, its clinical utility is limited because of its frequent severe side effects such as gastric bleeding. Gliacin^TM has been previously shown/proposed by the author to be a potential safer, better-tolerated substitute for indomethacin in responsive headache syndromes. Gliacin^TM is a novel, patent-pending derivative of Boswellia serrata that may, in part, be effective clinically by blocking interleukins and decreasing intracranial pressure.

METHODS: A case series of nine patients with PCH (based on the ICHD-3 [beta] criteria) who have been successfully treated with Gliacin^TM is reported. Only patients who reported over a 70% : (1) reduction in headache frequency, (2) reduction in headache severity and (3) subjective improvement in their headache condition associated with Gliacin^TM therapy were used in this analysis. These patients were considered "Gliacin^TMresponders."

RESULTS: A total of nine patients (eight men and one woman) with PCH were shown to be Gliacin^TM responders. Their ages ranged from 39 to 60 years (average of 52 years). All patients reported the abrupt onset of headache exclusively with activities such as coughing and Valsalva maneuver. Their pain was moderate/severe in intensity, bilateral/occipital in location and lasted anywhere from one to 90 minutes. All patients had non-focal neurological exams and unremarkable neuroimaging. All of the patients experienced dramatic improvement with indomethacin (average of 100-125 mg per day). One-third of patients were forced to come off indomethacin because of severe side effects (two with severe dyspepsia and one with rectal bleeding). All nine patients, willingly converted to Gliacin^TM and took doses ranging from 1,125 mg to 3,375 mg per day. Within a short timeframe, all nine patients became Gliacin^TM responders as well. Only one of the patients experienced side effects (“mild indigestion”) with Gliacin^TM. All patients preferred Gliacin^TM over indomethacin and all but one (who combines both therapies) were able to entirely discontinue indomethacin. No adverse reactions have been associated thus far with long term (120 total patient months) Gliacin^TM use. The average commercial cost of Gliacin^TM for these responders is less than two dollars per day.

CONCLUSIONS: In this case series, Gliacin^TM has been used to successfully treat nine patients suffering from PCH. Furthermore, Gliacin^TM was well tolerated, preferred over indomethacin and cost effective. Gliacin^TM represents the first herbal preparation used to successfully treat PCH and its use warrants further investigation.

Study presented at the Scientific Meeting of the American Headache Society (Los Angeles, U.S.A., June 2014)

Headache 2014. 54 (8): pages 1418-1434.

A Case Report of SUNCT Syndrome Responsive to Gliacin^TM

Eric J. Eross, D.O., Scottsdale Headache Center (Scottsdale, AZ)

Fred Freitag, D.O., Medical College of Wisconsin (Milwaukee, WI)

OBJECTIVE: Review the case of a patient who has successfully used Gliacin^TM for the long term treatment of SUNCT syndrome.

BACKGROUND: Short-lasting unilateral neuralgiaform headache attacks with conjunctival injection and tearing (SUNCT) is a rare primary headache disorder which is characterized by very brief (5-240 seconds), stabbing/pulsatile pain in the orbital/supraorbital region. Attacks are unilateral, associated with prominent lacrimation and redness of the ipsilateral eye and occur 3 to 200 times per day. Treatment of SUNCT is challenging with no consistent outcomes being reported with any one therapeutic approach. Case reports have shown benefit from various pharmacologic agents and procedural interventions from occipital nerve blocks to deep brain stimulation. To the authors’ knowledge, the effective use of a herbal preparation for SUNCT has yet to be reported. Gliacin^TM is a novel, patent-pending derivative of Boswellia serrata first shown to have promise for the treatment of indomethacin responsive headache syndromes including various TAC’s.

METHODS: A single case report of a SUNCT patient successfully treated with Gliacin^TM is reported. Details regarding her case were obtained through the personal medical management of her case.

RESULTS: A previously healthy 45 year-old woman experienced the onset of left-sided periorbital pain. The pain was described as “stabbing” and occurred in attacks lasting a few seconds to three to four minutes. Attacks (witnessed in the clinic) were associated with ipsilateral conjuctival injection, prominent tearing and periorbital edema. At their most frequent, attacks would occur up to 125-150 times per day. Ocular etiologies were excluded with ophthalmologic consultation. A MRI of the brain and MRA of the head and neck were normal without evidence of posterior fossa or pituitary abnormalities. After seeking neurological consultation, a diagnosis SUNCT was made. Various pharmacological agents were systematically initiated including methylprednisolone, verapamil, pregabalin and topiramate. Both pregabalin (50 mg TID) and topiramate (50 mg BID) were modestly effective but very poorly tolerated. Ultimately the patient was placed on Gliacin^TM (375 mg PO TID); within 72 hours of initiating therapy attack frequency drastically reduced. Attacks dropped from over 100 per day to a few (<5) per month (>99% reduction). Attack severity also dropped by 30%. HIT-6 and HQL scores dropped by 38% (78 to 48) and 65% (78 to 27) respectively. The patient has continued to use Gliacin^TM effectively for over a year. Missed doses are associated with a steady increase in attack frequency and intensity. The patient reports no side effects or adverse reactions to Gliacin^TMand the commercial cost of her therapy is less than a dollar per day.

CONCLUSIONS: SUNCT is a rare debilitating primary headache disorder with few consistently effective treatment options. Certainly additional therapeutics are welcome considering the potential side effects of pharmacologic agents and serious nature of aggressive surgical intervention. In this case, Gliacin^TM has been highly effective, well tolerated and affordable. Gliacin^TM represents a novel herbal preparation that warrants further consideration for other patients suffering from SUNCT.

Study presented at the Scientific Meeting of the American Headache Society (Los Angeles, U.S.A., June 2014)

Headache 2014. 54 (8): pages 1418-1434.