Reduction In Frequency Of Attacks Research Articles

Modified-release sildenafil reduces Raynaud's phenomenon attack frequency in limited cutaneous systemic sclerosis

To examine the effect of sildenafil in patients with Raynaud's phenomenon (RP) secondary to limited cutaneous systemic sclerosis (lcSSc). In this double-blind, placebo-controlled study, 57 patients with RP secondary to lcSSc were randomized to receive modified-release sildenafil 100 mg once daily for 3 days followed by modified-release sildenafil 200 mg once daily for 25 days or placebo. The primary assessment was the percentage change in the number of RP attacks per week in the per-protocol population. Secondary end points included Raynaud's Condition Score, duration of attacks, RP pain score, endothelial dysfunction assessed by a peripheral arterial tonometric (PAT) device, and serum biomarker levels. The mean percentage reduction from baseline to day 28 in attacks per week was greater for modified-release sildenafil than for placebo (-44.0% versus -18.1%, P = 0.034); the mean number of attacks per week improved from 25.0 at baseline to 19.3 after placebo treatment and from 30.5 to 18.7 after modified-release sildenafil treatment (P = 0.244). Decreases from baseline in Raynaud's Condition Score, duration of attacks, and RP pain score were not significantly different between groups. Mean values and changes from baseline in PAT responses and serum biomarker levels were similar between groups. The most frequent adverse events were headache and dyspepsia; the majority of adverse events were mild or moderate. Our findings indicate that modified-release sildenafil reduced attack frequency in patients with RP secondary to lcSSc and was well tolerated. Modified-release sildenafil may be a treatment option in this patient population.

Central modulation in cluster headache patients treated with occipital nerve stimulation: an FDG-PET study

BackgroundOccipital nerve stimulation (ONS) has raised new hope for drug-resistant chronic cluster headache (drCCH), a devastating condition. However its mode of action remains elusive. Since the long delay to meaningful effect suggests that ONS induces slow neuromodulation, we have searched for changes in central pain-control areas using metabolic neuroimaging.MethodsTen drCCH patients underwent an 18FDG-PET scan after ONS, at delays varying between 0 and 30 months. All were scanned with ongoing ONS (ON) and with the stimulator switched OFF.ResultsAfter 6-30 months of ONS, 3 patients were pain free and 4 had a ≥ 90% reduction of attack frequency (responders). In all patients compared to controls, several areas of the pain matrix showed hypermetabolism: ipsilateral hypothalamus, midbrain and ipsilateral lower pons. All normalized after ONS, except for the hypothalamus. Switching the stimulator ON or OFF had little influence on brain glucose metabolism. The perigenual anterior cingulate cortex (PACC) was hyperactive in ONS responders compared to non-responders.ConclusionsMetabolic normalization in the pain neuromatrix and lack of short-term changes induced by the stimulation might support the hypothesis that ONS acts in drCCH through slow neuromodulatory processes. Selective activation in responders of PACC, a pivotal structure in the endogenous opioid system, suggests that ONS could restore balance within dysfunctioning pain control centres. That ONS is nothing but a symptomatic treatment might be illustrated by the persistent hypothalamic hypermetabolism, which could explain why autonomic attacks may persist despite pain relief and why cluster attacks recur shortly after stimulator arrest. PET studies on larger samples are warranted to confirm these first results.

Auricular electroacupuncture reduces frequency and severity of Raynaud attacks

Acupuncture has been shown to influence skin perfusion and the subjective cold perception threshold. Therefore, we hypothesized that auricular electroacupuncture (EA) might reduce symptoms in primary Raynaud's phenomenon (PRP). Twenty-six patients with PRP received 6 cycles of auricular EA. After 3, 6 and 24 weeks attack frequency and severity were reevaluated using standardized questionnaires and a visual analogue scale (VAS). Skin temperature was assessed by infrared thermography and laser Doppler perfusion imaging was used to determine skin perfusion. Compared to baseline we found a significant reduction of attack frequency after 3 (p = 0.001) and 6 weeks (p < 0.001) of auricular EA. This improvement sustained following cessation of EA, after 24 weeks (p < 0.001). Furthermore, attack associated pain was reduced after 3 (p = 0.003), 6 (p = 0.003) and 24 weeks (p = 0.001) of treatment, while skin temperature and skin perfusion did not change significantly throughout the study period. Auricular EA reduces symptoms by means of frequency and severity of attacks in PRP but has no influence on skin perfusion and skin temperature.

Migraine Chronification

Migraine is a disorder with variable natural history. In some sufferers, migraine evolves over time into a state of headaches on more days than not. This process of migraine chronification is poorly understood, but risk factors have been clearly identified. Herein, we first discuss the role of heritability and of genetic risk factors on migraine chronification. We follow with a discussion of the role of comorbid conditions and environmental exposures. We suggest that clinicians consider risk factor modification as part of migraine management, aspiring to not just relieve current pain and disability, but to avoid migraine progression. Reducing attack frequency, avoiding medication overuse, appropriately using preventive drugs and behavioral therapies, and encouraging weight loss should be part of migraine therapy to improve current pain and disability and also to avoid future pain and disability by preventing chronification.

Comparison of the effects of dietary factors in the management and prophylaxis of migraine.

Migraine is defined as a disorder characterized by intermittent headache episodes, accompanied with nausea, photophobia and/or phonophobia. Pharmacological therapy is in accordance with the severity of pain and may include acute, prophylactic and most commonly both approaches. The aim of the acute therapy is stopping or alleviating the attack or progression of the pain and, in case of a migraine attack that has started, lessening the pain. Preventive therapy aims to reduce attack frequency and severity. This study was designed to evaluate the effect of dietary factors in the management and prophylaxis of migraine in cases diagnosed as having migraine disorder according to the 2003-IHS criteria. Fifty consecutive Turkish patients (13 men, 37 women) with diagnosis of migraine were randomly divided into two groups for treatment protocols with the written approval of the ethics committee. The cases in the first group (K) were treated with metoprolol, vitamin B(2) (riboflavin), and naproxen sodium just at the aura or at the beginning of the attacks. The cases in the second group (D) were also supplied with a comprehensive dietary list arranged by our algology clinic in addition to the same medication protocol. There were no demographic differences between the cases (P > 0.05). VAS scores were lower in group D than group K (P < 0.01), and also the migraine attack frequencies and monthly amounts of analgesic consumed amounts were also statistically significantly less. It was concluded that beta-blocker and riboflavin therapy supplemented with a convenient diet with appropriate alternatives in patients with migraine disorder was associated with statistically significant decreases in headache frequency, intensity, duration and medication intake.

Long-term course and relapses of vestibular and balance disorders

The long-term course and the frequency of relapses for various peripheral vestibular disorders and somatoform phobic postural vertigo are discussed with respect to the clinically most important questions for thus afflicted patients. This review is mainly based on our own long-term follow-up studies and takes into consideration the most relevant literature. The following syndromes are discussed in detail. Vestibular neuritis: the recovery rate of peripheral vestibular function lies between 40-63% depending on early-onset treatment with corticosteroids; the recurrence rate within 10 years is 2%. Menière's disease} loss of auditory and vestibular function occurs mainly in the first 5 to 10 years; frequency of vertigo attacks may decline after 5 to 10 years; bilateral involvement increases with increasing duration of the condition in up to 30-50%; vestibular drop attacks may occur early or late within the course, mostly with spontaneous remission; high-dose and long-term treatment with betahistine significantly reduces attack frequency in Menière's disease, Benign paroxysmal positioning vertigo: the recurrence rate is 50% within 10 years (in females 58%, in males 39%), most recurrences (80%) being observed within the first year after initial relief; recurrence rate in the seventh decade is half of that in the sixth decade. Vestibular paroxysmia: medical treatment with carbamazepine or oxcarbazepine leads to a continuous significant reduction in attack frequency, intensity, and duration of 10-15% of baseline. Bilateral vestibulopathy: recovery of vestibular function is limited to single cases depending on their etiology. Phobic postural vertigo: within 5 to 16 years 27% of the patients are symptom-free, 48% improve, 22% remain unchanged, and 3% worsen; a detailed explanation of the mechanisms that cause and the factors that provoke attacks is imperative, as well as instructions for self-controlled desensitization within the context of behavioral therapy.

An Open Pilot Study Assessing the Benefits of Quetiapine for the Prevention of Migraine Refractory to the Combination of Atenolol, Nortriptyline, and Flunarizine: Table 1

Migraine is a prevalent neurological disorder. Although prevention is the core of treatment for most, some patients are refractory to standard therapies. Accordingly, the aim of this study was to evaluate the use of Quetiapine (QTP) in the preventive treatment of refractory migraine, defined as previous unresponsiveness to the combination of atenolol, nortriptyline, and flunarizine. Thirty-four consecutive patients (30 women and 4 men) with migraine (ICHD-II), fewer than 15 days of headache per month, and not overusing symptomatic medications were studied. All participants had failed to the combination of atenolol (60 mg/day), nortriptyline (25 mg/day), and flunarizine (3 mg/day). Failure was defined as <50% reduction in attack frequency after 10 weeks of treatment. After other medications were discontinued, QTP was initiated at a single daily dose of 25 mg, and then titrated to 75 mg. After 10 weeks, headache frequency, consumption of rescue medications, and adverse events were analyzed. Twenty-nine patients completed the study. Three patients withdrew and two were lost to follow-up. Among those who completed, 22 (75.9%; 64.7% of the intention-to-treat population) had greater than 50% headache reduction. The mean frequency of migraine days decreased from 10.2 to 6.2 per month. Use of rescue medications decreased from 2.3 to 1.2 days/week. Adverse events were reported by nine (31%) patients. Although limited by the open design, this study provides pilot data to support the use of QTP in the preventive treatment of refractory migraine. Controlled studies are necessary to confirm these observations.

Zonisamida en el tratamiento preventivo de la migraña refractaria

Chronic migraine refractory to preventive treatment is a common clinical situation in general neurology clinics. The aim is to analyse our experience with zonisamide in the preventive treatment of patients with frequent refractory migraine. Those patients with no response or intolerance to topiramate and at least one more preventative received zonisamide. This drug was increased 25 mg per week up to 200 mg/day. The efficacy of zonisamide was evaluated in terms of 'response' (reduction in attack frequency below 50%) at the third month of treatment. Our series comprises a total of 172 patients, with ages ranging from 22 to 69 years. 85% were women. The final dosage of zonisamide was 50-200 mg/day, with the 100 mg/day being the most frequently administered dose. Zonisamide was efficacious (response) in 76 (44%) patients; response being excellent in 22 (13%). MIDAS score was reduced by 43.2%. Zonisamide was not tolerated by 27% of the patients, mainly due to subjective mental slowness or digestive symptoms. These results, obtained in a big sample of patients refractory or intolerant to topiramate and other preventatives, indicate that, at least in conditions of daily clinical practice, zonisamide, at relatively low dosages, is an option to be considered for the preventive treatment of patients with frequent migraine.

Riboflavin prophylaxis in pediatric and adolescent migraine

Migraine is a common disorder in childhood and adolescence. Studies on adults show the effectiveness and tolerability of riboflavin in migraine prevention, while data on children are scarce. This retrospective study reports on our experience of using riboflavin for migraine prophylaxis in 41 pediatric and adolescent patients, who received 200 or 400 mg/day single oral dose of riboflavin for 3, 4 or 6 months. Attack frequency and intensity decreased (P < 0.01) during treatment, and these results were confirmed during the follow-up. A large number of patients (77.1%) reported that abortive drugs were effective for controlling ictal events. During the follow-up, 68.4% of cases had a 50% or greater reduction in frequency of attacks and 21.0% in intensity. Two patients had vomiting and increased appetite, respectively, most likely for causes unrelated to the use of riboflavin. In conclusion, riboflavin seems to be a well-tolerated, effective, and low-cost prophylactic treatment in children and adolescents suffering from migraine.

Medical treatment of vestibular disorders

Background: The lifelong prevalence of rotatory vertigo is 30%. Despite this high figure, patients with vertigo generally receive either inappropriate or inadequate treatment. However, the majority of vestibular disorders have a benign cause, take a favorable natural course, and respond positively to therapy. Objective: This review puts special emphasis on the medical rather than the physical, operative, or psychotherapeutic treatments available. Methods: A selected review of recent reports and studies on the medical treatment of peripheral and central vestibular disorders. Results/conclusions: In vestibular neuritis, recovery of the peripheral vestibular function can be improved by oral corticosteroids; in Menière's disease, there is first evidence that high-dose, long-term administration of betahistine reduces attack frequency; carbamazepine or oxcarbamazepine is the treatment of first choice in vestibular paroxysmia, a disorder mainly caused by neurovascular cross-compression; the potassium channel blocker aminopyridine provides a new therapeutic principle for treatment of downbeat nystagmus, upbeat nystagmus, and episodic ataxia type 2.

Spectrum of Pediatric Neuromyelitis Optica

Our goal was to describe the spectrum of clinical phenotypes, laboratory and imaging features, and treatment in pediatric patients with neuromyelitis optica. The study consisted of a retrospective chart review of patients followed in a pediatric multiple sclerosis center with a diagnosis of neuromyelitis optica spectrum disorder. Nine patients with neuromyelitis optica spectrum disorders were included, all of whom were female. There were 4 black children, 2 Latin American children, 2 white children, and 1 child of mixed Latin American/white heritage. Median age at initial attack was 14 years (range: 1.9-16 years). Median disease duration was 4 years (range: 0.6-9 years). Tests for neuromyelitis optica immunoglobulin G were positive for 7 patients. Eight patients had transverse myelitis and optic neuritis, and 1 patient had longitudinally extensive transverse myelitis without optic neuritis but had a positive neuromyelitis optica immunoglobulin G antibody titer. Cerebral involvement on MRI was found in all subjects, 5 of whom were symptomatic with encephalopathy, seizures, hemiparesis, aphasia, vomiting, or hiccups. Immunosuppressive therapy reduced attack frequency and progression of disability. Pediatric neuromyelitis optica has a diverse clinical presentation and may be difficult to distinguish from multiple sclerosis in the early stages of the disease. The recognition of the broad spectrum of this disease to include signs and symptoms of brain involvement is aided by the availability of a serum biomarker: neuromyelitis optica immunoglobulin G. Early diagnosis and immunosuppresive treatment may help to slow the accumulation of severe disability.

Treatment recommendations for migraine

The pharmacological treatment of migraine can be acute or preventive. Acute treatment attempts to stop the progression of an attack or relieve pain and functional impairment once an attack has begun, whereas preventive therapy is given to reduce attack frequency and severity. Additional benefits of preventive therapy include improving responsiveness to acute attack treatment, and reducing disability. Treatment protocols should also include education and reassurance, avoidance of triggers, nonpharmacological treatments, and physical and/or complementary medicine when appropriate. The treatment plan should be reassessed at regular intervals. Acute attack medication can be specific or nonspecific, and needs to be tailored to the individual patient. Backup and rescue medication should be available in case the initial treatment fails. The route of drug administration depends on attack severity, how rapidly the attack escalates, the patient's preference, the presence or absence of severe nausea or vomiting, and the need for rapid relief. Preventive migraine treatments include beta-blockers, antidepressants, calcium channel antagonists, 5-hydroxytryptamine antagonists, anticonvulsants, and NSAIDs. Preventive treatments are selected on the basis of the drugs' side-effect profiles and the patient's coexistent and comorbid conditions.

Success and failure of preventative migraine treatment with botulinum toxin type A: Association with a novel classification of migraine headache

Quite a few migraine patients have noticed a considerable decrease in attack frequency following BTX-A injections. Many migraineurs, however, do not experience such improvement. Is there a marker that would tease out prospective responders from non-responders? Patients experiencing a >75% reduction in attack frequency within 3 months of treatment were selected as responders. Patients who showed no change in attack frequency were selected as non-responders. The interviewer had no knowledge of the patient's response to BTX-A treatment before the interview was completed. Responders experienced significant drops in the number of attacks/month, attack duration, and headache intensity. Non-responders yielded identical values before and after treatment. There was one clear difference between the two groups: 92% of non-responders described their headache as exploding (extreme pressure inside the head), whereas 89% of the responders described their headache as imploding (extreme pressure outside the head) or ocular (extreme pressure behind the eyeball). Migraine with imploding or ocular headache is highly associated with successful prevention of attacks using BTX-A. However, migraine with exploding headache is highly associated with failure to block attacks using BTX-A.

Failure of Deep Brain Stimulation of the Posterior Inferior Hypothalamus in Chronic Cluster Headache - Report of Two Cases and Review of the Literature

Deep brain stimulation (DBS) has become a standard procedure for movement disorders such as Parkinson's disease, essential tremor or dystonia. Recently, deep brain stimulation of the posterior hypothalamus has been shown to be effective in the treatment of drug-resistant chronic cluster headache. DBS of the posterior inferior hypothalamus was performed on two patients with chronic cluster headaches, one 55-year-old man with medically intractable chronic cluster headache since 1996, and one 31-year-old woman with a chronic form since 2002. Both patients showed continuous worsening headaches in the last years despite high dose medical treatment. The patients fulfilled the published criteria for DBS in chronic cluster headaches. Electrodes were implanted stereotactically in the ipsilateral posterior hypothalamus according to the published coordinates (2 mm lateral, 3 mm posterior, 5 mm inferior) referenced to the mid-AC-PC line. The intra- and postoperative course was uneventful and postoperative MRI control documented regular position of the DBS electrodes. The current stimulation parameters were at 12 months postoperatively 0 neg., G pos.; 5.5 V; 60 micros; 180 Hz (Case 1) and 0 neg., G pos.; 3.0 V; 60 micros; 185 Hz, at 3 months postoperatively (Case 2). Surgery- or stimulation-related side effects were not observed. Both patients showed initial pain reduction in the first days whereas 12 respectively 3 month follow-up did not show a significant reduction in attack frequency or intensity. Deep brain stimulation of the posterior inferior hypothalamus is an experimental procedure and should be restricted to selected therapy-refractory patients and should be performed in centers experienced in patient selection and performance of DBS as well as postoperative pain treatment. A prospective multi-centre study is necessary to evaluate its effectiveness.

Migraine Patients as Trainers of Their Fellow Patients in Non-Pharmacological Preventive Attack Management: Short-Term Effects of a Randomized Controlled Trial

In conformity with current views on patient empowerment, we designed and evaluated the effects of home-based behavioural training (BT) provided by lay trainers with migraine to small groups of fellow patients. The primary aims of BT were to reduce attack frequency and increase perceived control over and self-confidence in attack prevention. In a randomized controlled trial the BT group (n = 51) was compared with a waitlist-control group (WLC), receiving usual care (n = 57). BT produced a minor (-21%) short-term effect on attack frequency and clinically significant improvement in 35% of the participants. Covariance analysis showed a non-significant trend (P = 0.07) compared with WLC. However, patients' perceived control over migraine attacks and self-confidence in attack prevention increased significantly with large effect sizes. Patients with high baseline attack frequency might benefit more from BT than those with low attack frequency. In conclusion, lay trainers with migraine strengthened fellow patients' perceived control, but did not induce a significant immediate improvement in attack frequency.

Quetiapine for the prevention of migraine refractory to the combination of atenolol + nortriptyline + flunarizine: an open pilot study

Migraine is a prevalent neurological disorder. Although prevention is the mainstream treatment, some patients are refractory to standard therapies. To evaluate the use of quetiapine (QTP) in the preventive treatment of refractory migraine, defined as previous unresponsiveness to the combination atenolol + nortriptyline + flunarizine. Thirty-four consecutive patients (30 women and 4 men) with migraine (ICHD-II) and headache attacks on less than 15 days per month not overusing symptomatic medications were studied. The main inclusion criterion was the lack of response (<50% reduction in attack frequency) after ten weeks to the combination of atenolol (60 mg/day) + nortriptyline (25 mg/day) + flunarizine (3 mg/day). The patients started on QTP as the sole treatment in a single daily dose of 25 mg, titrated to 75 mg. After ten weeks, headache frequency, consumption of rescue medications and adverse events were analyzed. Twenty nine patients completed the study. Among completers, 22 (75.9%; 64.7% of the intention-to-treat population) presented >50% headache reduction. The mean frequency of migraine days decreased from 10.2 to 6.2 and the average consumption of rescue medications decreased from 2.3 to 1.2 days/week. Adverse events were reported by 9 (31%) patients. Although limited by the open design, this study provides a pilot data to support the use of quetiapine in preventive treatment of refractory migraine.

Tratamiento preventivo de la migraña crónica con zonisamida: un estudio en pacientes refractarios o intolerantes a topiramato

About half of the patients with chronic migraine do not respond or do not tolerate the different migraine preventatives.To analyse the efficacy and tolerability of zonisamide in the treatment of migraine in patients who had not responded or tolerated topiramate, the current drug of choice for the treatment of this condition.Those patients with no response or intolerance to topiramate received zonisamide. This drug was increased 25 mg per week up to a maximum of 200 mg/day. The efficacy of this drug was evaluated in terms of 'response' (reduction in attack frequency below 50%) at the third month of treatment.Our series comprises a total of 34 patients, most of them middle-aged women. All met chronic migraine criteria. Zonisamide showed efficacy (response) in 19 patients (56%), response being excellent in 6 (18%). Nine patients (26%) did not show response, whereas 6 (18%) did not tolerate the drug.The results, obtained in patients refractory to other preventatives and particularly to topiramate, suggest that zonisamide can be useful in the prevention of chronic migraine. Of course, controlled clinical trials are necessary to confirm these preliminary results.

Butterbur root extract and music therapy in the prevention of childhood migraine: An explorative study

Background Migraine is very common in school-aged children, but despite a number of pharmacological and non-pharmacological options for prophylaxis, randomized controlled evidence in children is small. Evidence-based prophylactic drugs may have considerable side effects. Objective This study was to assess efficacy of a butterbur root extract (Petadolex ®) and music therapy in primary school children with migraine. Design Prospective, randomized, partly double-blind, placebo-controlled, parallel-group trial. Methods Following a 8-week baseline patients were randomized and received either butterbur root extract ( n = 19), music therapy ( n = 20) or placebo ( n = 19) over 12 weeks. All participants received additionally headache education (“treatment as usual”) from the baseline onwards. Reduction of headache frequency after treatment (8-week post-treatment) as well as 6 months later (8-week follow-up) was the efficacy variable. Results Data analysis of subjects completing the respective study phase showed that during post-treatment, only music therapy was superior to placebo ( p = 0.005), whereas in the follow-up period both music therapy and butterbur root extract were superior to placebo ( p = 0.018 and p = 0.044, respectively). All groups showed a substantial reduction of attack frequency already during baseline. Conclusion Butterbur root extract and music therapy might be superior to placebo and may represent promising treatment approaches in the prophylaxis of paediatric migraine.

Occipital nerve stimulation for drug-resistant chronic cluster headache: a prospective pilot study

Drug-resistant chronic cluster headache (drCCH) is a devastating disorder for which various destructive procedures have been tried unsuccessfully. Occipital nerve stimulation (ONS) is a new, safe strategy for intractable headaches. We undertook a prospective pilot trial of ONS in drCCH to assess clinical efficacy and pain perception. Eight patients with drCCH had a suboccipital neurostimulator implanted on the side of the headache and were asked to record details of frequency, intensity, and symptomatic treatment for their attacks in a diary before and after continuous ONS. To detect changes in cephalic and extracephalic pain processing we measured electrical and pressure pain thresholds and the nociceptive blink reflex. Two patients were pain free after a follow-up of 16 and 22 months; one of them still had occasional autonomic attacks. Three patients had around a 90% reduction in attack frequency. Two patients, one of whom had had the implant for only 3 months, had improvement of around 40%. Mean follow-up was 15.1 months (SD 9.5, range 3-22). Intensity of attacks tends to decrease earlier than frequency during ONS and, on average, is improved by 50% in remaining attacks. All but one patient were able to substantially reduce their preventive drug treatment. Interruption of ONS by switching off the stimulator or because of an empty battery was followed within days by recurrence and increase of attacks in all improved patients. ONS did not significantly modify pain thresholds. The amplitude of the nociceptive blink reflex increased with longer durations of ONS. There were no serious adverse events. ONS could be an efficient treatment for drCCH and could be safer than deep hypothalamic stimulation. The delay of 2 months or more between implantation and significant clinical improvement suggests that the procedure acts via slow neuromodulatory processes at the level of upper brain stem or diencephalic centres.

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