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Biomedical subjects

Z Katsarava

Publications and source records attributed to Z Katsarava.

At least 19 recordsLinked to original sources

Company reference estimates for productivity loss due to migraine and productivity gains using rizatriptan 10 mg in Germany.

The prevalence of migraine in Germany is up to 14% in the female and up to 8% in the male population and peaks between the age of 35 and 45. Few studies have investigated the productivity loss and resulting costs attributable to migraine in Germany or addressed the question whether these costs can be reduced by optimal treatment. In recent years, 5-HT(1B/D) agonists (so-called triptans), a generation of drugs highly specific for migraine treatment, have been introduced. Seven 5-HT(1B/D) agonists have been approved in Germany with more than 20 dosage forms. We present a model that enables employers to estimate the annual cost of migraine and the annual cost that could be saved by treatment of migraine with rizatriptan compared with the use of non-specific antimigraine medication. A representative German company with 10,000 employees is used for the reference case analysis. This company is predicted to have 580 female and 284 male employees with migraine. These employees are estimated to lose 6992 workdays or 31.8 person years of productive effort annually due to migraine, valued approximately 1,431,719 euros. The value of work loss that could be avoided by treating migraine with rizatriptan is estimated at 619,094 euros annually. These data indicate that costs arising from lost productivity can be reduced by treating migraine headaches with a triptan.

Absenteeism↗

Central sensitization of the trigeminal and somatic nociceptive systems in medication overuse headache mainly involves cerebral supraspinal structures.

Trigeminal and somatic nociceptive systems were studied in controls (n=15), episodic migraine (n=16), analgesics (n=14) and triptan-induced medication overuse headache (MOH) (n=15) before and after withdrawal. Patients with MOH and comorbid depressive symptoms and depression without headache were studied to investigate the influence of depression. Trigeminal nociception was studied by simultaneous registration of pain-related cortical potentials (PREP) and nociceptive blink reflex (nBR) following nociceptive-specific electrical stimulation of the forehead. Somatic nociception was evaluated using PREP of upper limbs. We found facilitation of both trigeminal and somatic PREP but not of nBR in MOH, which normalized after withdrawal. No differences were found comparing analgesics vs. triptan MOH. No differences were observed between controls and patients with episodic migraine and depression without headache. A transient facilitation was found of trigeminal and somatic nociceptive systems in MOH, which was more pronounced on a supraspinal level.

Adult↗

One-year prevalence and socio-cultural aspects of chronic headache in Turkish immigrants and German natives.

The aim of this research was to study the prevalence of chronic headache (CH) and associated socio-cultural factors in Turkish immigrants and native Germans. Five hundred and twenty-three Turkish and German company employees were screened using a standard questionnaire. Those who suffered from headaches were also examined by a neurologist. Complete data were available for 471 (90%) subjects. Thirty-four participants (7.2%) had CH. Two independent factors for association with CH could be identified: overuse of acute headache medication (OR = 72.5; 95% CI 25.9-202.9), and being a first-generation Turkish immigrant compared with native Germans (OR = 4.4; 95% CI 1.4-13.7). In contrast, the factor associated with chronic headache was not increased in second-generation Turkish immigrants. Medication overuse was significantly more frequent in first-generation Turkish immigrants (21.6%) compared with second-generation Turkish immigrants (3.3%) and native Germans (3.6%; chi(2) = 38.0, P < 0.001). First-generation Turkish immigrants did not contact headache specialists at all, compared with 2.8% of second-generation Turkish immigrants and 8.8% of native Germans (chi(2) = 118.4, P < 0.001). Likewise no first-generation Turkish immigrant suffering from CH received headache preventive treatment, compared with 6.6% of native Germans (chi(2) = 19.1, P = 0.014). The data from this cross-sectional study reveal a high prevalence of chronic headache as well as a very low utilization of adequate medical care in first-generation Turkish immigrants in Germany.

Adult↗

Medication overuse headache: rates and predictors for relapse in a 4-year prospective study.

We present a prospective 4-year follow-up study of 96 patients with medication overuse headache following withdrawal. Complete datasets were available from 85 patients (89%) 6 months, from 79 patients (82%) 1 year and from 75 patients (78%) 4 years after withdrawal. Twenty-six patients (31%) relapsed within the first 6 months after withdrawal. The number of relapses increased to 32 (41%) 1 year and to 34 (45%) 4 years after withdrawal. The 4-year relapse rate was lower in migraine than in tension-type headache (32% vs. 91%, P<or=0.001) and combination of migraine and tension-type headache (32% vs. 70%, P<or=0.027) and also lower in patients overusing triptans than analgesics (21% vs. 71%, P<or=0.001). The study suggests that the majority of relapses occur within the first year after withdrawal and that the long-term success of withdrawal depends on the type of primary headache and the type of overused medication.

Adult↗

Lamotrigine reduces migraine aura and migraine attacks in patients with migraine with aura.

This study examined the efficacy of lamotrigine in the prevention of migraine aura. Fifty nine patients suffering from migraine with aura received lamotrigine in a controlled three year prospective open study. Treatment response was defined as a reduction of aura frequency each month by at least 50%. Primary endpoint was reached by three quarters of the patients. Lamotrigine significantly reduced both frequency of migraine aura (mean, 1.5 (SD, 0.6) each month before v 0.4 (0.7) after treatment; p < 0.001) and aura duration (mean, 27 (SD, 11) minutes before v 8 (14) after treatment; p < 0.001). Furthermore, more than three quarters of those patients with a reduction of aura symptoms experienced a significant reduction of frequency of migraine attacks (mean, 2.1 (SD, 1.0) each month before v 1.2 (1.1) after treatment; p < 0.001). Lamotrigine was highly effective in reducing migraine aura and migraine attacks. The strong correlation between reduction of aura symptoms and migraine attacks stresses the potential role of aura-like events and possibly cortical spreading depression as a trigger for trigeminal vascular activation, and subsequently the development of migraine headaches.

Adult↗

Clinical features and therapy of medication overuse headache.

Inappropriate use of headache medication (>15 times/month) for the treatment of headache episodes may contribute to the development of chronic headache which is refractory to most treatments. Physicians experienced in the treatment of migraine and other headaches are well aware that the daily intake of antipyretic or antiinflammatory analgesics, opioids, ergot alkaloids and "triptans" may result in chronic daily headache. Conversely, if a patient complains of chronic headache and takes pain medication every day, this headache is most likely to be caused and sustained by the medication and will vanish or improve with abstinence. Treatment includes drug withdrawal followed by structured acute therapy and initiation of migraine prophylactic treatment.

Headache Disorders↗

Incidence and predictors for chronicity of headache in patients with episodic migraine.

The authors followed 532 consecutive patients with episodic migraine (<15 days/month) for 1 year. Sixty-four patients (14%) developed chronic headache (>/=15 days/month). The odds ratios for developing CH were 20.1 (95% CI 5.7 to 71.5) comparing patients with a "critical" (10 to 14 days/month) vs "low" (0 to 4 days/month) and 6.2 (95% CI 1.7 to 26.6) in patients with an "intermediate" (6 to 9 days/month) vs "low" headache frequency and 19.4 (95% CI 8.7 to 43.2) comparing patients with and without medication overuse.

Adult↗

[Gordian knot: medication overuse headache].

Overuse of any kind of headache drugs may lead to the development of the medication overuse headache (MOH). Clinical features of MOH depend on the substance class that has been overused. Overuse of analgesics leads to a chronic tension-type like headache, the overuse of triptans to daily migraine-like headache or to the increase of migraine frequency. The delay between the drug overuse and onset of daily headache is shortest for triptans (1.7 years), longer for ergots (2.7 years) and longest for analgesics (4.8 years). Treatment includes withdrawal followed by structured acute therapy and initiation of specific prophylactic treatment for the underlying primary headache. The relapse rate after a successful withdrawal is about 30%. Predictors for relapse are tension-type headache and the overuse of analgesics in combination with codeine, caffeine or opioids.

Analgesics↗

The effect of multiple stimuli on the modulation of the 'nociceptive' blink reflex.

The 'nociceptive' blink reflex is a method of examining human trigeminal pain pathways. We explored temporal summation of this reflex by using a train of pulses, rather than a single pulse, and remote activation of diffuse noxious inhibitory control (DNIC), to improve reliability, flexibility and nociceptive specificity of this technique. The R2 component of the nociceptive blink reflex response (nR2) was assessed in 28 healthy volunteers using between 1 and 7 pulses per stimulus train (inter-pulse interval 5 ms). The effect of DNIC on single-, double-, and triple-pulse nR2 was investigated. Compared to single pulses, double and triple pulses increased the sensation of pain, reduced the tactile and pain thresholds, and facilitated the blink reflex responses (reduced onset latency, increased magnitude and persistence of nR2). The maximal reflex facilitation was achieved using a triple pulse. Higher pulse numbers had no additional facilitatory effect. Activation of the DNIC system using heterotopic pain suppressed the nR2 evoked by double and triple stimulation by 16 and 42%, respectively, but not the nR2 from a single pulse. Stimulation with double and triple pulses may be more suitable to study influences on nociceptive pathways than single pulses and may widen the methodological flexibility of the nociceptive blink reflex technique. This technique may be useful in studying the trigeminal nociceptive system with particular reference to primary headache disorders and their neuropharmacology.

Adult↗

[Recent new information on epidemiology of headache].

We reviewed the epidemiology of headache disorders for the most frequent primary headache-syndromes: migraine, tension-type headache and trigemino-autonomic headache syndromes. In the last years scientific data about headache disorders have increased. New studies investigated not only the prevalence of headaches, but also economic costs of this disorder. Epidemiologic headache research also investigates the quality of life.

Autonomic Nervous System Diseases↗

Differences of anti-nociceptive mechanisms of migraine drugs on the trigeminal pain processing during and outside acute migraine attacks.

The aim of this study was to investigate central anti-nociceptive mechanisms of i.v. acetylsalicylic acid (ASA) and oral zolmitriptan (ZOL) in migraine patients and healthy subjects using the 'nociceptive' blink reflex (nBR). Twenty-eight migraine patients received ASA (n = 14, 1000 mg i.v) or ZOL (n = 14, 5 mg p.o) during the acute migraine attack and interictally. Thirty healthy subjects received either ASA or ZOL vs. placebo using a double blind cross over design. nBR was recorded in all patients and subjects before, 60 and 90 min after treatment. ASA and ZOL did not inhibit nBR responses in healthy subjects. Both ASA and ZOL suppressed nBR responses (ASA by 68%, ZOL by 78%) only during the acute attack but not interictally. The data suggest, that the anti-nociceptive effects of migraine drugs on the trigeminal nociceptive processing are different during and outside an acute migraine attack.

Adult↗

Rates and predictors for relapse in medication overuse headache: a 1-year prospective study.

The authors prospectively studied 98 patients with medication overuse headache. The 1-year relapse rate was 38% but was lower for patients with migraine compared with tension-type headache (22% vs 73%, p < or = 0.002) and combination of migraine and tension-type headache (22% vs 77%, p < or = 0.0001). The rate was also lower for patients overusing triptans than ergots (19% vs 20%, NS) and analgesics (19% vs 58%, p < or = 0.001). The long-term success of withdrawal depends on the type of primary headache and the type of overused medication.

Adult↗

Abnormal habituation of 'nociceptive' blink reflex in migraine--evidence for increased excitability of trigeminal nociception.

We studied the habituation of the 'nociceptive' blink reflex (nBR) in 15 healthy subjects and 17 migraine patients interictally as well as during unilateral migraine headache within six hours of onset and after treatment. In healthy volunteers the mean regression coefficient (MRC) was - 3.9 following right sided and - 4.9 left sided stimulation. This equals an amplitude loss of 19.5% (5 x -3.9) and 24.5% (5 x -4.9), respectively, across five consecutive sweeps. An augmentation of nBR responses was found in migraine patients interictally: MRC = 3.3 following stimulation of the headache side (HA) and MRC = 4.0 of the non-headache side (non-HA). The differences were statistically significant (anova: d.f. = 1, F = 25.8, P < 0.001). During the migraine attack MRCs were negative both before (-5.0, HA and - 4.0, non-HA) and after treatment (-2.6, HA and - 1.9 non-HA) and significantly differed from those outside the migraine attack (anova: d.f. = 2, F = 12.4, P < 0.001). The demonstrated lack of habituation of the nBR responses indicates an abnormal trigeminal nociceptive processing in migraine patients outside the migraine attack.

Adult↗

Sensitization of trigeminal nociception specific for migraine but not pain of sinusitis.

Trigeminal pain processing was studied in 14 patients with unilateral migraine attacks and 14 age- and sex-matched patients with comparable unilateral headache from frontal sinusitis. Using a nociception-specific blink reflex method (nBR), a facilitation of nBR responses predominantly on the headache side was observed in migraine, but not in sinusitis. The facilitation of trigeminal nociception may be specific for migraine rather than a consequence of peripheral pain such as frontal sinusitis.

Acute Disease↗

Features of medication overuse headache following overuse of different acute headache drugs.

OBJECTIVE: To investigate pharmacologic features such as mean critical duration until onset of medication-overuse headache (MOH) (MCDO), mean critical monthly intake frequencies (MCMIF), and mean critical monthly dosages (MCMD) as well as specific clinical features of MOH after overuse of different acute headache drugs, with a focus on newly approved triptans. METHODS: In a prospective study 98 patients with MOH according to International Headache Society (IHS) criteria underwent standardized inpatient withdrawal from their medication. Patient diaries and structured interviews were used to calculate the MCDO, MCMIF, and MCMD for each substance group. RESULTS: The MCDO was shortest for triptans (1.7 years), longer for ergots (2.7 years), and longest for analgesics (4.8 years). The MCMIF was lowest for triptans (18 single doses per month), higher for ergots (37), and highest for analgesics (114). Although patients overusing ergots and analgesics typically had a daily tension-type headache, patients with triptan-induced MOH were more likely to describe a (daily) migraine-like headache or an increase in migraine frequency. CONCLUSION: Overuse of triptans leads to MOH faster and with lower dosages compared with ergots and analgesics. Clinical features of MOH depend on the type of overused headache medication. Pharmacologic and clinical characteristics of triptan-induced MOH call for the renewal of the current IHS classification.

Acute Disease↗

Acute migraine headache: possible sensitization of neurons in the spinal trigeminal nucleus?

OBJECTIVE: To investigate trigeminal sensory processing in patients with migraine using a novel "nociception-specific" blink reflex. METHODS: Seventeen patients with unilateral migraine headache were studied within 6 hours of onset. Blink reflexes were elicited with a standard stimulating electrode (standard blink reflex) and concentric stimulating electrode (nociception-specific blink reflex) during the acute migraine attack, after treatment with IV lysine acetylsalicylate (1,000 mg) or oral zolmitriptan (5 mg) and interictally. RESULTS: After standard stimulation, no differences were detected for the R1 and R2 onset latencies and areas under the curve (AUC) between the different time points and the headache and nonheadache side. Nociception-specific stimulation revealed a shortening of R2 onset latencies (44.3 +/- 5.4 ms for headache side vs 48.9 +/- 5.8 ms for nonheadache side) during the acute migraine attack compared with the headache-free interval (49.8 +/- 5.3 vs 49.8 +/- 4.5 ms). The AUC of the R2 increased on the headache side by 680% and on the nonheadache side by 230% compared with the headache-free interval. Drug treatment parallel to pain relief increased the onset latencies (zolmitriptan: 48.0 +/- 8.2 ms for headache side vs 52.3 +/- 7.6 ms for nonheadache side; lysine acetylsalicylate: 48.0 +/- 5.0 ms for headache side vs 51.2 +/- 5.6 ms for nonheadache side) and reduced the AUC of R2 (zolmitriptan by 45% and lysine acetylsalicylate by 48%). CONCLUSION: The data suggest temporary sensitization of central trigeminal neurons during acute migraine attacks.

Acute Disease↗

Optimized stimulation and recording parameters of human 'nociception specific' blink reflex recordings.

OBJECTIVE: Few non-invasive methods are available for studying trigeminal nociception in humans. The 'nociception specific' blink reflex (nBR) is elicited by a preferential stimulation of trigeminal nociceptive fibers and is highly sensitive to changes in trigeminal nociception. The aim of this study was to establish its optimal stimulation parameters. METHODS: The inter-individual variability of R2 responses (41 healthy subjects), symmetry of R2 responses after right vs. left sided stimulation (25 subjects), optimal stimulation parameters (3 groups, each 16 subjects) and re-test reliability over time (15 subjects) were studied. RESULTS: The nBR had a R2 response with a latency of 44.7+/-7.3ms, but no R1 response. The mean difference of R2 latencies (right vs. left sided stimulation) was 0.4+/-2.1(SD)ms, the mean ratio of the R2 response areas (RA) was 1.05+/-0.39 (SD). Thus, lateral differences of onset latencies greater than 4.6ms (0.4+4.2 (2SD)) or >1.83-fold (1.05+0.78 (2SD)) of RA can be assumed as outside of normal range. Long inter-block intervals of 7min minimized the cumulative habituation of R2 RAs to 23%, onset latencies remained constant. Re-test reliability over 4 weeks was high both for latencies (Crohnbach's alpha=0.85) and RAs (alpha=0.94). CONCLUSIONS: The nBR with the established stimulation parameters could be used for studying trigeminal nociception.

Adult↗