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Migraine

Criteria voor migraine
Aanvallen van hoofdpijn die, zonder behandeling, tussen de vier uur en drie dagen duren.
De hoofdpijn moet minstens twee van de volgende vier karakteristieken hebben:
de pijn zit aan één zijde van het hoofd;
de pijn is kloppend of bonkend van aard;
de pijn is matig tot ernstig, zodanig dat de dagelijkse activiteiten ernstig belemmerd worden en/of de patiënt naar bed gaat;
de pijn verergert reeds bij geringe lichamelijke activiteiten.

Naast de hoofdpijn moet er tevens minstens één van  de volgende drie  bijverschijnselen zijn:
misselijkheid en/of braken;overgevoeligheid voor licht;
overgevoeligheid voor geluid.

Migrainepatiënten hebben een verlaagde prikkeldrempel die gemakkelijk overschreden kan worden.De migraineprikkels zijn sterker dan normaal of de prikkeldrempel is nog verder verlaagd door drempelverlagende factoren. De gevoeligheid voor migraineprikkels is waarschijnlijk voor een groot deel erfelijk bepaald. Op dit moment wordt veel onderzoek naar deze erfelijke factoren gedaan. Hoe een migraineaanval precies begint is nog onbekend. 

Wat wel duidelijk is dat door prikkeling van bepaalde delen van de hersenen een tijdelijke ontregeling in de hersenstam ontstaat. Dit leidt, via het zenuwstelsel, tot een ontregeling van bepaalde andere delen van de hersenen en uiteindelijk ook van de bloedvaten en zenuwen in de hersenvliezen. De bloedvaten in de hersenvliezen verwijden zich. Dit heeft hoofdpijn tot gevolg. De auraverschijnselen ontstaan door een ontregeling in de hersenschors. 

Prikkeldrempelverlagende factoren zijn:
  • bij vrouwen de menstruatie
  • verder extreme vermoeidheid
  • ontspanning na stress
  • te hoog gebruik van pijnstillers
  • te hoog gebruik van antimigrainemiddelen ergotamine
  • te hoog gebruik van cafeïne (pijnstillers, koffie, cola, guarana, thee en cacao).
Bij het ontstaan van migraine speelt de neurotransmitter serotonine een centrale rol. Serotonine zorgt dat de bloedvaten samentrekken. Mogelijk is de primaire oorzaak van migraine een verstoorde calcium-balans in de hersencellen, als gevolg van bepaalde defecten aan het calcium-ionkanaal in de celmembraan waardoor calciumionen de hersencel binnengaan. De instroom van calcium in de hersencellen is een voorwaarde voor de uitscheiding van serotonine, en een defect aan het calcium-kanaal veroorzaakt een verstoring van dit proces, waardoor een migraineaanval optreedt. Veranderingen in de calcium-kanalen van de hersencellen resulteren mogelijk in verlaging van de prikkeldrempel. 

Mogelijk is dat ook een verklaring waarom magnesium kan helpen bij migraine. Magnesium en calcium zijn chemisch verwante elementen en maken beiden gebruik van de calcium-kanalen. Magnesium kan bepaalde calcium-kanalen "blokkeren" en wellicht werkt magnesium daarom tegen migraine. 

Stikstofoxide, een bloedvatverwijdende stof, speelt mogelijk ook een rol bij het ontstaan van migraine. Het is één van de schadelijke uitlaatgassen die bijdraagt aan de zure regen. Dit gas wordt echter ook geproduceerd in het lichaam en vervult daar tal van belangrijke biologische functies. Eén daarvan is het doen verslappen van de spiertjes in de wanden van bloedvaten, waardoor deze wijder worden. Stikstofoxide wordt in het lichaam gemaakt met behulp van het enzym NO-synthase. Stoffen die de werking van dit enzym blokkeren zouden daarom in aanmerking kunnen komen als medicijn tegen migraine.Op dit moment wordt nog veel onderzoek gedaan om de oorzaak of oorzaken van migraine te ontmaskeren. Hoe het ook zij: de migraineklachten houden rechtstreeks verband met een sterke verwijding van bloedvaten in de hersenen.

Natuurlijke adviezen bij migraine
  • Magnesium***
  • Vitamin B2 
  • 5-HTP **  
  • Calcium*
  • visolie(EPA/DHA)
  • Melatonine
  • SAMe
  • Vitamin D 
  • Moederkruid / Tanacethum parhenium
  • Groot hoefblad / Petasitus
  • Cayenne
  • Gember
  • Ginkgo biloba 
Neurol Sci. 2014 May;35 Suppl 1:135-40. doi: 10.1007/s10072-014-1757-x. Herbal therapy in migraine.
D'Andrea G1, Cevoli S, Cologno D.
The use of herbal therapies is ancient and increasing worldwide. There is a growing body of evidence supporting the efficacy of various "complementary" and alternative medicine approaches in the management of headache disorders. Promising tools to treat migraine patients are herbal products. In particular constituents of Petasites hybridus, Tanacetum Parthenium and Ginkgo Biloba have shown antimigraine action in clinical studies. A miscellaneous of recreational drugs and other herbal remedies have been supposed to have a role in headache treatment but quality of clinical studies in this field is low and inconclusive. Further research is warranted in this area.



Anti-migraine herbs
Treatment of vascular headache involves not only relief of the intense pain of an acute attack but also the prevention (prophylaxis) of additional
attacks. During the past decade, research has demonstrated the prophylactic value in the following herbs in treating migraine.

Feverfew
Valued since the time of Dioscorides (a.d. 78) as a febrifuge (antipyretic), the leaves of Tanacetum parthenium (L.) Schultz Bip. syn. Chrysanthemumparthenium (L.) Bernh. have now been shown to be useful in reducing the frequency and severity of migraine as well as the discomfort of the frequently associated nausea and vomiting. A daily dose of 50–250 mg of dried leaf is recommended for prophylaxis.105
Seven randomized double-blind, placebo-controlled clinical trials (RCTs) have been conducted with feverfew monopreparations; five were reported to be successful, three employing dried powdered feverfew leaf.106–108 Two recent German studies used the same proprietary CO2 supercritical fluid extract (SFE).109,110 The first six of these trials have been systematically reviewed.111 

Extracts of both leaves and root/rhizome of Petasites hybridus (L.) Gaertn, Meyer & Scherb. (Asteraceae/Compositae) have been clinically tested asmigraine prophylactic as well as treatment for seasonal allergic rhinitis.
The Swiss company Zeller AG manufactures an extract of butterbur leaves (Ze339), standardized to contain 25–35 percent petasins (sesquiterpene esters). Marketed as Tesalin™, a root extract, Petadolex™ is produced by Weber and Weber in Petaforce™ and is available from Bioforce Ltd., Irvine, United Kingdom. These manufacturers claim that the hepatotoxic and potentially carcinogenic pyrrolizidine alkaloids (PAs) of butterburhave been removed.122 However, preparations from the rhizome of P. hybridus were removed from the market in Switzerland in early 2004.123
Nonetheless, Petadolex was submitted to clinical trials for prophylaxis of migraine.124–126 Both migraine studies noted a significant reduction
in frequency of migraine attacks, as well as excellent tolerability, recommending butterbur as a effective migraine prophylactic.

Ginger
One case history from Denmark in 1990 reported the beneficial effect of ginger in aborting the effects of migraine headache: a forty-two-year-oldfemale migraineur given 1.5–2.0 g of powdered ginger daily at the onset of a migraine attack experienced marked reduction in the frequency and severity of migraine headache.129 Recently, a proprietary product (Gelstat Migraine) has been claimed effective as a sublingually administeredfeverfew and ginger compound for treatment of acute migraine during the mild pain phase.130

Cannabis
Cannabis sativa L., Cannabaceae, was once a widely accepted medical treatment for the prevention and relief of migraine headache, listed in the United States Pharmacopeia from 1860 to 1941.131 Savitex® (GW Pharmaceuticals, Salisbury, UK) is a cannabis-based blend of whole plant extracts that delivers approximately equal amounts of Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC has analgesic activity in both nociceptive and neuropathic pain, and both THC and CBD exert antiinflammatory effects. Savitex has been approved for several medicinal applications in the United Kingdom and is also available by prescription in Canada for symptomatic relief of neuropathic pain in multiple sclerosis (MS). Clinical trials conducted in the United Kingdom support the benefitof the cannabis-based medicine in MS132 and rheumatoid arthritis.133

Caffeine-containing beverages
These CNS-stimulant plant products are most commonly employed simply to overcome drowsiness; in addition, they are used therapeutically
as adjuncts in the treatment of headache. The acute consumption of caffeine in conjunction with OTC analgesics such as aspirin or acetaminophen increases their activity by as much as 40 percent, depending on the specific type of pain involved. This beneficial effect is apparently due to the ability of caffeine to cause constriction of the cerebral blood vessels and, possibly, to facilitate the absorption of other drugs. The enhancement is short-lived, diminishing greatly on repeated (chronic) coadministration.
The principal caffeine beverages are prepared from
• coffee—dried ripe seed of Coffea arabica L. (family Rubiaceae);
• tea—leaves and leaf buds of Camellia sinensis (L.) O. Kuntze (familyTheaceae);
• kola (cola)—dried cotyledons of Cola nitida (Vent.) Schott & Endl.and other Cola spp. (family Sterculiaceae);
• roasted seeds of Theobroma cacao L. (familySterculiaceae);
• guarana—crushed seed of Paullinia cupana Kunth. ex H. B. K. (familySapindaceae); and
• maté—dried leaves of Ilex paraguariensis St.-Hil. (familyAquifoliaceae).
Guarana has the highest caffeine content of all caffeine-containing plants—up to 5 percent.134
Research from Austria’s Medical University of Innsbruck has shown that caffeine boosts short-term memory and task orientation. Using MRI scans, the Innsbruck researchers discovered that subjects who consumed approximately 100 mg of caffeine—about the amount in two cups of coffee—had higher activity levels in the frontal lobe, an important memory center, and the anterior cingulum, which controls attention span. The effect typically lasts for about twenty minutes.135

106. Johnson, E. S., N. P. Kadam, D. M. Hylands, and P. J. Hylands. 1985. BritishMedical Journal 291:569–573.
107. Murphy, J. J., S. Heptinstall, and J. R. A. Mitchell. 1998. Lancet ii:189–192.
108. Palevitch, D., G. Earon, and R. Carasso. 1997. Phytotherapy Research11:508–511.
109. Pfaffenrath, V., H. C. Diener, M. Fisher, M. Friede, and H. H. Heinnecke-vonZepelin. 2002. Cephalalgia 22:523–532.
110. Diener, H. C., V. Pfaffenrath, J. Schnitker, M. Friede, and H. H. HenneckervonZepelin. 2005. Cephalalgia 25:1031–1041.
111. Pittler, M. H., and E. Ernst. 2004. The Cochrane Library issue 1. Chichester,England: John Wiley & Sons, Ltd.
112. Kuritzky, A., Y. Elhacham, Z. Yerushalmi, and R. Hering. 1994. Neurology 44(suppl. 2): A201 (abstract 293 P).
113. de Weerdt, C. J., H. P. R. Bootsma, and H. Hendriks. 1996. Phytomedicine3:225–230.
114. Heptinstall, S., and D. V. C. Awang. 1998. In Phytomedicines of Europe:Chemistry and biological activity, ed. L. D. Lawson and R. Bauer, 158–175. ACSSymposium Series 691. Washington, D.C.: American Chemical Society.
115. Johnson, E. S. 1983. MIMS Magazine (May 15): 32–34.
116. Johnson, S. 1984. Feverfew—A traditional remedy for migraine and arthritis, 118.London: Sheldon Press.
117. Fenton, D. A., E. R. Young, and J. D. Wilkinson. British Medical Journal286:1062 (letter).
118. Gardiner, A. 1996. Medicinal herbs and essential oils, 24. London: PromotionalReprint Co. Ltd.
119. Hausen, B. M., E. Busker, and R. Carle. 1984. Planta Medica 34:229–235.
120. Anderson, D., P. C. Jenkinson, R. S. Dewdney, S. D. Blowers, E. S. Johnson,and N. P. Kadam. 1988. Human Toxicology 7:145–152.
121. Hausen, B. M., and P. E. Osmundesn. 1983. Acta Dermatoloica Venereologia63:308–314.
122. Brattström, A. 2004. Ze 339 Schwezerische Zeitschrift für Ganzheitsmedizin 16(4):158–160.
123. Schlenger, R. 2004. DeutscheA apotheker Zeitungg 144 (8): 64–66.
124. Grossmann, M., and H. Schmidramsl. 2000. International Journal of ClinicalPharmacology and Therapy 38 (9): 430–435; Alternative Medical Review 6 (3):303–310 (2001).
125. Diener, H. C., V. W. Rahlfs, and U. Danesch. 2004. European Neurology 51 (2):89–97.
126. Lipton, R. B., H. Göbel, K. M. Einhäupl, K. Wilks, and A. Muskop. 2004.
Neurology 63:2240–2244.127. Danesch, U., and R. Rittinghausen. 2003. Headache 43 (1): 76–68.
128. Kalin, P. 2003. Forschende Komplementarmedizin und Klassische Naturheilkunde10 (suppl. 1): 42–44.
129. Mustafa, T., and K. C. Srivastava. 1990. Journal of Ethnopharmacology29:267–273.
130. Cady, R. K., C. P. Schreiber, M. E. Beach, and C. C. Hart. 2005. Medical ScienceMonitor 11 (9): 165–169.
131. Russo, E. 1998. Pain 76:3–8.
132. Rog, D. J., T. J. Nurmikko, T. Friede, and C. A. Young. 2005. Neurology 65 (6):812–819.



Feverfew/Ginger Formulation Provides Migraine Relief
HerbalGram. 2012; American Botanical Council
Reviewed: Cady RK, Goldstein J, Nett R, Mitchell R, Beach ME, Browning R. A double-blind placebo-controlled pilot study of sublingual feverfew and ginger (LipiGesic™M) in the treatment of migraine. Headache. 2011;51(7):1078-1086.

Migraine is a complex neurobiological disease characterized not only by headache, but also by nausea, photophobia (intolerance of bright light), phonophobia (intolerance of noise and speech), autonomic nasal symptoms, muscle pain, and cognitive disruption. Some attacks require bed rest, while others produce only mild or limited disability. Common acute treatments include acetaminophen/aspirin/caffeine combinations and over-the-counter nonsteroidal anti-inflammatory medications, as well as prescription products such as triptans and nonsteroidal anti-inflammatories. Because oral medications do not work for all migraine sufferers and because prescription medications are associated with adverse events, high costs, and quantity limits, there is a need for affordable, effective, alternative treatments.

The double-blind, placebo-controlled pilot study reviewed herein compared the efficacy of a unique lipid-based formulation of the sublingual homeopathic product LipiGesic™ M (PuraMed BioScience; Schofield, Wisconsin), which contains what the manufacturer states is a “3x”* preparation of feverfew (Tanacetum parthenium, Asteraceae) herb and a “2x”* preparation of ginger (Zingiber officinale, Zingiberaceae) root, (in a base of “Colloidal Silicon Dioxide, Natural Peppermint Flavor, N.F. Grade Olive Oil.” A peppermint (Mentha x piperita, Lamiaceae)-flavored sublingual preparation was used as a placebo. The trial tested the herbal-homeopathic preparation as an abortive treatment for acute episodic migraine. Secondary objectives included evaluation of persistent or recurrent headache 2 to 24 hours following treatment, assessment of adverse events, and comparison of migraine questionnaire scores between the treatment and placebo.

Sixty subjects enrolled in the study; data for 59 were included in the analysis. The subjects (46 women and 14 men) were aged 13 to 60 years, met criteria for International Headache Society migraine with or without aura, and had a history of migraine for more than 1 year. They had experienced between 2 to 6 attacks per month during the previous 3 months; at least 75% of their attacks had begun with mild headache. The subjects were able to differentiate migraine from non-migraine headache.

Conducted at 3 investigational sites, the study included 2 visits: one at screening and 1 exit visit 1 month later. The subjects were randomized 3:1 to receive either sublingual feverfew/ginger (n=45) or a matching placebo (n=15). The subjects were asked to treat all migraine attacks over the 1-month period, regardless of the intensity. They were instructed to treat with sequential administrations of 2 unit dose applicators. The liquid from 1 applicator was applied sublingually, held under the tongue for 60 seconds, and then swallowed. After 5 minutes, the second dose was administered. If headache pain persisted 1 hour later, the subjects could take a further 2 unit dose.

At screening, all subjects provided a medical, medication, and migraine history. Vital signs were recorded, and the subjects completed the Revised Patient Perception of Migraine Questionnaire (PPMQ-R). At the second visit, the subjects returned their completed headache diaries documenting the onset of headache pain and presence of migraine-associated symptoms, time of treatment with study medication, symptoms at 1 and 2 hours following treatment, time of relief, recurrence of symptoms within 24 hours after treatment, and adverse events.

Of those subjects using sublingual feverfew/ginger, 32% reported being pain-free at 2 hours post-dose compared with 16% using placebo (P=0.02). At 2 hours post-dose, the percentage of attacks rated as no pain or mild pain was 64% for sublingual feverfew/ginger compared with 39% for placebo (P=0.003). Pain level differences on a 4-point scale were -0.24 for those receiving feverfew/ginger and -0.04 for those using placebo (P=0.006). At 2 hours post-treatment, a statistically significant difference was noted in migraine symptoms and headache characteristics between the 2 groups. This included superiority of the treatment over placebo in eliminating the pulsating character of the headache (P=0.007); the worsening of headache with activity (P=0.015); and the presence of light sensitivity (P=0.001), sound-sensitivity (P=0.003), and nausea (P=0.02). The treatment was well tolerated.

Recurrence of headache was not analyzable because there were only 9 attacks in the placebo group that were pain-free at 2 hours after treatment. Of the 47 attacks that became pain-free at 2 hours in the active group, the recurrent rate was 20.4%, meaning return of moderate to severe migraine pain or use of rescue medication (i.e., conventional treatment) within 22 hours of becoming pain-free. Evaluation of the subjects’ responses on the PPMQ-R revealed statistical superiority for the treatment over placebo in total score (P=0.30), efficacy (P=0.04), and functionality (P=0.02).

According to the authors, the complex layers involved in the treatment of acute migraine are not addressed in clinical guidelines. Often, adverse events are interpreted by patients differently than by their healthcare providers. Consequently, an “adherence gap” exists between what providers think patients need for treatment and what patients seek from treatment. This is apparent, say the authors, in the fact that the use of triptans, considered the “gold standard” of migraine treatment, is not increasing by those with migraine headaches. Patients are seeking more than what triptans can provide.  “Understanding this ‘adherence gap’ represents the distance between evidence-based medicine and patient-centered care,” write the authors, calling for future studies to understand more completely the treatment dynamics of the migraine population.

The authors conclude that this study supports the efficacy of lipid-based sublingual feverfew/ginger in the acute treatment of migraine when administered early in the migraine attack.
—Shari Henson

* 3x and 2x refer to the degree of dilution in the process of producing a homeopathic preparation from a “mother tincture,” an ethanolic and/or water extract at a ratio of 1:1.

References
1. Ferrari MD, Roon KI, Lipton RB, Goadsby PJ. Oral triptans (serotonin 5-HT1B/1D agonists) in acute migraine treatment: A meta-analysis of 53 trials. Lancet. 2001;358(9294):1668-1675.
2. Cady RK, Schreiber CP, Beach ME, Hart CC. Gelstat Migraine® (sublingually administered feverfew and ginger compound) for acute treatment of migraine when administered during the mild pain phase. Med Sci Monit. September 2005;11(9):PI65-PI69.
3. Witt CM, Lüdtke R, Willich SN. Homeopathic treatment of patients with migraine: A prospective observational study with a 2-year follow-up period. J Altern Complement Med. 2010;16(4):347-355.



Petasites hybridus / Pestwurz

Die Kasuistik weist auf eine dosisabhängige Wirksamkeit einer Pestwurz-Prophylaxe bei Migräne hin. Dies zeigt sich auch anhand des sehr sorgfältig geführten Anfallstagebuchs. Unterstützt wird diese Annahme durch das Anfallsrezidiv nach völligem Absetzen und die erneute Remission bei Wiederaufnahme der Prophylaxemedikation.

Pestwurz-Extrakte weisen entzündungshemmende und spasmolytische Wirkungen auf, deretwegen sie seit geraumer Zeit genutzt und auch zunehmend wissenschaftlich beforscht werden [1]-[5]. Sie scheinen grundsätzlich als Migräne-­Prophylaktikum geeignet, wenngleich die lange verfolgte Theorie meningealer Ge­fäßspasmen als Ursache der Migräneattacken in letzter Zeit erheblich in Zweifel gezogen wurde.

Neben Behandlung und Prophylaxe von allergischen und bronchialobstruktiven Erkrankungen [6] werden Pestwurz-Ex­trakte seit geraumer Zeit ausschließlich für die Prophylaxe der Migräne empfohlen; eine therapeutische Wirkung im Anfall ist dagegen nicht beschrieben.

Es liegen mindestens 4 randomisiert placebokontrollierte Studien und mindestens 2 Reviews vor: Der erste [7] überblickt 2 als hochwertig eingestufte Studien mit 60 bzw. 233 Patienten [8], [9], wobei in der größeren Studie 2 Verumgruppen mit 100 und 150 mg / d gebildet worden waren. Der ­Review kommt zu dem Schluss, dass nach 3-4 Monaten in beiden Verumgruppen mit der Dosis von 150 mg / d die Anfallsfrequenz deutlicher sank und die Responderraten höher waren als mit 100 mg / d. Ein Poolen der Daten wurde aus verschiedenen Gründen nicht für sinnvoll erachtet, es müssten mehr und methodologisch bessere Studien vorliegen.

Obwohl nahezu zeitgleich publiziert, würdigt der andere Review [10] 2 weitere randomisiert placebokontrollierte Stu­dien [11], [12], insgesamt also 4, die sämtlich nach ca. 4 Monaten auf eine bessere Wirksamkeit des Verums gegenüber Placebo hinwiesen. Die gewählten Dosierungen variierten zwischen 2 × 25 mg / d und 3 × 50 mg / d; bessere Ergebnisse erzielten die höheren Dosierungen. Es wird insgesamt ein Evidenzgrad B verliehen (Good Scientific Evidence, Skala von A bis E).

Sicherheit
Pestwurz-Extrakte gelten als gut verträglich. Sie werden in Deutschland seit 1972, in Kanada seit 1996, in den USA spätestens seit 1998 und in Japan seit 2003 in größerem Umfang als Migräne-, in jüngerer Vergangenheit aber auch vermehrt als Allergieprophylaxe eingesetzt. Aus Deutschland wurden 9 Verdachtsfälle bezüglich Leberschäden gemeldet und sorgfältig analysiert. In einem Fall schien ein Zusammenhang möglich [13]. Bezüglich des grundsätzlich möglichen Gehaltes an als krebserregend und lebertoxisch ­eingestuften Pyrrolizidinalkaloiden ließ das National Center for Natural Products Research 21 in den USA erhältliche Pestwurz-Extrakte analysieren und befand sie für sicher. Andere ernsthafte unerwünschte Wirkungen wurden weder in den Studien noch aus der breiten Anwendung beschrieben.

Für das Produkt Petadolex® lässt sich in Deutschland der dauerhafte Gebrauch zwischen 1992 und 2010 während etwa 200 000 Patientenjahren überschauen, für die USA, Kanada und Japan zusammen zwischen 2010 und 2015 während etwa 56 000 Patientenjahren.

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