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CLINICAL CASE

Woman with long-lasting migraines and high rates of relapse. CLINICAL CASE. Presented by: Carlo Lisotto Headache Centre Department of Neurosciences University of Padua , Italy. IDENTIFICATION. 39-year old woman with episodic migraine without aura and infrequent migraine with aura

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CLINICAL CASE

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  1. Woman with long-lasting migraines and high rates of relapse CLINICAL CASE Presented by: Carlo Lisotto Headache Centre Department of Neurosciences UniversityofPadua, Italy

  2. IDENTIFICATION • 39-year old woman with episodic migraine without aura and infrequent migraine with aura • She took several NSAIDs, without any benefit

  3. PAST CLINICAL HISTORY AND FAMILY HISTORY • She suffered from headaches since her late teens • The headaches gradually increased in duration and intensity and currently occur 2-3 times a month, last 3 to 4 days, and are extremely severe • The headaches reach peak intensity on average within 2-3 hours • Premonitory symptoms consist in fatigue, yawning, stiff neck, concentration problems and irritability • The headaches are frequently associated with pallor, nausea, phonophobia, photophobia, osmophobia and, sporadically, with vomiting • Mental strain, anxiety, lack of sleep, missing meals, exertion and changes in weather make the headaches worse • She reports 5 episodes of visual aura • Her grandmother had migraine, which resolved a few years after her menopause

  4. DIAGNOSTIC PROCEDURES • Physical and neurological examinations with fundoscopy showed no abnormalities • BP 120/80 mmHg • Pericranial muscles were slightly stiff and tender, and their tenderness was increased by digital pressure • No sign of temporomandibular dysfunction (TMD) • MRI with angiography of the brain showed small foci of hyperintensity in the deep white matter of both hemispheres; these abnormalities were considered non-specific and clinically unremarkable (Fig.1) • Tests for disorders of coagulation were normal • MIDAS score of 22 indicates severe disability

  5. Figure 1: THE PATIENT’S BRAIN MRI

  6. DIAGNOSIS • Migraine without aura + migraine with aura

  7. PAST TREATMENT • The patient had been treated unsuccessfully with NSAIDs and then given oral rizatriptan 10 mg with remarkable benefit • Rizatriptan was selected because of its rapid onset of action, taking into consideration that the patient’s attacks reach peak intensity within 2-3 hours on average • Rizatriptan 10 mg acted quickly in relieving the head pain and associated symptoms, thus rapidly restoring the patient’s functions • She was almost constantly pain-free within 2 hours, but unfortunately the pain tended to recur, usually 6 hours after taking the first dose

  8. TREATMENT • In the light of the relapses, the patient was recommended treatment with frovatriptan 2.5 mg once per day. If migraine recurs after initial relief it may be taken a second dose at a 2-h interval and not within the same attack. The total daily dose should not exceed 5 mg per day

  9. FOLLOW-UP VISIT • Assessment after 6 months: • rizatriptan and frovatriptan were equally effective (pain free 2 hrs after the first dose) • headache recurrence was much less frequent after taking frovatriptan than after rizatriptan use • fewer frovatriptan doses were required to treat her prolonged attacks • Consequently, the patient preferred frovatriptan: • favourable sustained effect with a lower rate of relapse • prevents the worsening of migraine attacks and reduces their severity

  10. COMMENTS (I) • White matter hyperintensities(brain MRI): • more prevalent in migraineurs than in the general population (12-47% of all patients) • more frequent in female patients and in migraineurs with aura • pathogenesis and clinical significance are still unclear • Long-lasting untreated severe migraine attacks result in significant disability and compromised function in a substantial proportion of patients (Fig. 2)1 1. Lipton RB, et al. Neurology 2007;68:343-349.

  11. Figure 2: MIGRAINE-ASSOCIATED DISABILITY Patients (%) Function normally Some impairment Severe impairment or bed rest Lipton RB, et al. Neurology 2007;68:343-349.

  12. COMMENTS (II) Migraine attacks • Almost three quarters of women have headaches that last over 24 hours, whereas only 50% of men have such long-lasting attacks 1 • The mean duration of women’s headaches was found to be 31 hours, while in men the mean duration was shorter, being 19 hours 2 • In clinical practice there is a huge inter-individual variability of migraine attacks in terms of severity, duration, associated symptoms and time to peak intensity • Usually attacks with a gradual-onset are long-lasting and are frequently associated with headache relapse 3 1. KelmanL. Headache 2006;46:942-953; 2. Pryse-Phillips W, et al. Headache 2006;46:1480-1486; 3. Lipton RB, et al. J Headache Pain 2004;5:123-130.

  13. COMMENTS (III) Triptans • Triptans with the shortest Tmax are believed to provide the fastest speed of action 1 • Triptans with longer half-lives seem to provide the lowest rates of headache relapse, with there being a significant inverse correlation between half-life and recurrence rate (Fig. 3) 2 • In clinical trials, responses to frovatriptan and rizatriptan were consistently similar in terms of pain-free at 2 hours rates, but frovatriptan was associated with a significantly lower incidence of recurrence (Fig. 4) 3,4 1 Johnston MM, Rapoport AM. Drugs 2010;70:1505-1518; 2.Géraud G, et al. Headache 2003; 43:376-388; 3. Tfelt-Hansen P, et al. Cephalalgia 2012;32:6-38; 4. Savi L, et al. J Headache Pain 2011;12: 219-226.

  14. Figure 3: INVERSE CORRELATION BETWEEN TRIPTANS HALF-LIVES AND RECURRENCE RATE Frovatriptan 17 26 23 Naratriptan 6 5 23 Eletriptan Half-life (hours) Incidence of relapse (%) 3.5 25 Almotriptan 3 30 Zolmitriptan 2.5 35 Sumatriptan 2 Rizatriptan 40 Geraud G, Keywood C, Senard JM. Headache 2003; 43:376-388.

  15. Figure 4: PERCENTAGE OF RELAPSES (IHS) IN THE ITT POPULATION (N=125) Episodes (%) Savi L, et al. J Headache Pain 2011;12: 219-226.

  16. COMMENTS (IV) Recurrence and frovatriptan • Relapse is one of the two main reasons for patients’ dissatisfaction with migraine treatment, together with incomplete pain relief 1 • The pivotal importance of this attribute was clearly pointed out by 86% of patients in a survey by Lipton et al.2 • Frovatriptan provided in this patient rapid efficacy comparable to that of rizatriptan • Conversely, the relapse rate was significantly lower after taking frovatriptan and the patient expressed a clear preference for this triptan, based on this crucial effect 1. Malik SN, et al. Headache 2006;46:773-780.; 2. Lipton RB, et al. Headache 2002;42(Suppl 1):S3-S9.

  17. COMMENTS (V) In conclusion • Frovatriptan seems to be unique in the triptan class, having the longest duration of action and the lowest recurrence rate • Compared to the other triptans, frovatriptan offers the advantage of a lower risk of relapse and therefore a more sustained effect • Frovatriptan represents a particularly favorable option for treating migraine attacks with a high rate of relapse

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