Cluster Attacks Research Articles

Beidseitige Nervus-occipitalis-Stimulation zur Behandlung des therapierefraktären chronischen Cluster-Kopfschmerzes: eigene Fallserie und Initiierung einer prospektiven Studie

The chronic cluster headache (CCH) is a disabling disorder for every patient. Treatment is a challenging situation for the physician. Some patients will not experience adequate resolution of their cluster attacks by medication and the prophylaxis does not reduce the attacks sufficiently. Therefore, other treatment options have to be found. Since December 2008 seven patients with CCH have been treated by bilateral occipital nerve stimulation (ONS) at the University Hospital Essen. Implantation of the electrodes and stimulation paradigms were standardised. The maximum follow-up to date is 12 months. ONS was successfully employed in all patients. The intensity of the attacks decreased by 50 %. The consumption of attack medication was reduced by 77 % on average. Some patients could reduce their medication prophylaxis. A tendency towards improved quality of life was seen in all patients by means of a standardised questionnaire (SF-36). One generator had to be exchanged due to infection. Scar formations required reoperation and adhesiolysis of the thoracic connector in another patient. 6 out of 7 patients would fully recommend the operation. Bilateral ONS is a promising treatment for CCH, with a low risk profile in our experience. Further studies have to be conducted to clarify the mechanism of the stimulation and optimal parameters of ONS. For this particular reason, patients with CCH have been included in a prospective study since October 2009.

Treatment of cluster headache: clinical trials, design and results.

The spontaneous capricious course of cluster headache may give rise to some problems when treatment is being evaluated. This is one of several explanations for there being so few well-designed, randomized, double-blind clinical trials in cluster headache. The standard treatment of acute attacks of cluster headache is inhalation of 100% oxygen. In the prophylaxis of episodic cluster headache, ergotamine, verapamil, lithium, serotonin, inhibitors and steroids are used. In chronic cluster, lithium is the drug of choice, but verapamil may also be tried. Recently, hyperbaric oxygen has been shown to immediately abort acute attacks, and it seems that it may also be useful in the prophylactic treatment. The introduction of the novel 5HT1 agonist sumatriptan as a symptomatic relief of cluster attacks represents further significant progress. Two randomized, double-blind, placebo-controlled, cross-over trials have shown sumatriptan 6 mg sc to be a rapid, effective and well-tolerated acute treatment for cluster headache attacks. Within 15 min of treatment, 74% of attacks on sumatriptan responded compared to 26% of placebo-treated attacks. Functional disability was also significantly improved. Increasing the dose to 12 mg did not offer significantly greater relief compared to sumatriptan 6 mg, but was associated with an increased incidence of adverse events. Interim analysis of 3 months of data from a recent multinational open trial comprising, 138 patients having treated 6353 attacks with subcutaneous sumatriptan 6 mg revealed a headache relief in 96% of attacks treated. There was no evidence of an increased incidence of adverse events with frequent use of sumatriptan. No tachyphylaxis was seen over the 3 months, suggesting that sumatriptan is effective and well tolerated also in long-term acute treatment for cluster headache.

Mere surgery will not cure cluster headache – implications for neurostimulation

This case study concerns a patient with primary chronic cluster headache, who was unresponsive to all treatments and consecutively underwent hypothalamic deep brain stimulation (DBS). DBS had no effect on the cluster attacks, but cured an existing polydipsia as well as restlessness. However, hypothalamic DBS produced a constant, dull headache without concomitant symptoms and a high-frequent tremor. All of these effects were repeated when the stimulation was stopped and than started again. DBS had no effect on a pathological weight gain from 70 kg to 150 kg due to bulimia at night, usually during headache attacks. This case illustrates that cluster headache is, in some patients, only one symptom of a complex hypothalamic syndrome. This case also underlines that the stimulation parameters and anatomical target area for hypothalamic DBS may be too unspecific to do justice to the clinical variety of patients and concomitant symptoms. Hypothalamic DBS is an exquisite and potentially life-saving treatment method in otherwise intractable patients, but needs to be better characterised and should only be considered when other stimulation methods, such as stimulation of the greater occipital nerve, are unsuccessful.

Spectrum of epilepsy in Wilson's disease with electroencephalographic, MR imaging and pathological correlates

Background Seizures are uncommon in Wilson's disease. Objective To analyze profile of seizures in WD and to correlate with EEG and MR imaging observations. Subjects and methods 41/490 patients (8.3%) of WD were documented to have seizures. Autopsy observations were available in 3 cases. Results The age at onset of seizures was 12.8 ± 5.7 years. Seizure — preceded the onset of characteristic features of WD (19.5%); occurred concurrently (46.3%); or, followed de-coppering therapy (29.2%) and occurred as terminal event (4.8%). The types of seizures were: generalized tonic–clonic — 29, simple partial — 8, complex partial — 6, partial seizures with secondary generalization — 2 and periodic myoclonus — 1. Six patients had multiple seizure types and 4 had status epilepticus. EEG abnormalities were frequent (19/24) consisting of background slowing and epileptiform discharges. MRI ( n = 20) revealed varying degree of atrophy and signal changes involving basal ganglia, brainstem and white matter. The duration of follow-up was 8.1 ± 9.2 years. The outcome of seizure was: no recurrence — 68.3%, breakthrough seizures — 17.1%, poor control — 9.7% and no follow-up — 4.9%. Two of them succumbed following cluster attacks. Autopsy revealed cavitatory lesions in white matter in frontal, temporal and parietal areas with varying involvement of cortical ribbon. Patients with seizures had more often white matter changes than those without. It was also noted that patients whose seizures were not controlled had MRI suggestive of cavitation of white matter, though the reverse was not true. Conclusions This is the largest series regarding epilepsy in WD. Seizures are not uncommon and could occur at any stage. Deafferentation of white matter tracts from cortex may contribute for seizure in WD.

Cluster Attacks Responsive to Recreational Cannabis and Dronabinol

Pharmacological preparations of cannabinoid compounds have a variety of therapeutic uses in medicine, including different pain syndromes, but have not been previously reported as beneficial for cluster headache. We present a patient with cluster headache who was refractory to multiple acute and preventive medications but successfully aborted his attacks with recreational marijuana use; subsequent use of dronabinol provided equally effective pain relief. The beneficial effect may be related to the high concentration of cannabinoid receptors in the hypothalamus, which has been implicated as a site of dysfunction in neuroimaging studies of patients with cluster headache.

Response of Cluster Headache to Kudzu

To describe the self-treatment of cluster headache with kudzu. Many cluster headache patients take over-the-counter (OTC) kudzu extract in the belief that it helps their cluster attacks. Kudzu's actual efficacy has not been studied. A database of cluster headache patients was questioned about their use of various alternative remedies to treat their cluster headache. Of 235 patients identified, 16 had used kudzu, consented to interviews, and provided medical records. In total, 11 (69%) experienced decreased intensity of attacks, 9 (56%) decreased frequency, and 5 (31%) decreased duration, with minimal side effects. Anecdotal evidence suggests that a component in OTC products labeled as kudzu may prove useful in managing cluster headache. This hypothesis should be tested with a randomized clinical trial.

Cluster headache and related disorders

Cluster headache is a well-known primary headache syndrome occurring much less frequently than migraine, with a prevalence of approximately 5/10,000 of the adult population and a strongly male predilection. Cluster headache is the most prevalent of a group of unilateral headache syndromes known as trigeminal autonomic cephalalgias and can be differentiated from migraine by clinical and pathophysiological features. Cluster headache also exhibits a differing therapeutic response to medications when compared with migraine. Cluster attacks are known for their brief intense unilateral excruciating pain with unilateral autonomic features often associated with restlessness in contrast to migraine. The great majority of patients are successfully managed with medical therapy. Treatment is pharmacologic, both as abortive treatments for an ongoing attack and daily prophylactic treatment. Prophylaxis aims to induce and maintain a remission. Health care professionals familiar with the features of cluster headache should have no trouble making the diagnosis and creating a treatment plan.

Cluster headache associated with moyamoya

A 34-year-old man with right-sided cluster headache presented with a stroke from right-sided moyamoya. Following surgery on the right, both moyamoya and cluster headache remitted, but eighteen months later a cluster attack and symptoms of cerebral ischemia from moyamoya recurred on the left. Again, following surgery on the left, both moyamoya symptoms and cluster attacks disappeared. Cluster headache secondary to moyamoya has not previously been described.Electronic supplementary materialThe online version of this article (doi:10.1007/s10194-008-0081-3) contains supplementary material, which is available to authorized users.

The Second Lebanon War: The Question of Proportionality and the Prospect of Non-Lethal Warfare

Following the Second Lebanon War (2006), the United Nations condemned Israel's use of cluster bombs and attacks on convoys as disproportionate. But the term ‘proportionality’ is ill defined, and disproportionate harm is often confused with unnecessary and intentional harm. Cluster bombs, for example, highlight unnecessary and intentional harm, not disproportionality. Attacks on convoys, however, may be disproportionate if harm to noncombatants is unintentional and necessary but excessive. ‘Excessive’ can be defined with an algorithm that compares enemy civilian deaths with the compatriot lives saved, or by a ‘gut feeling’ that an ordinary and sensible person has when the limits of proportionality are breached. Regardless of definition, disproportionate harm always poses a danger in asymmetrical conflicts where it is often difficult to distinguish combatants from noncombatants. In this environment, non-lethal weapons may offer parties to the conflict the capacity to gain their military objectives without causing disproportionate harm.

Clinical pharmacology of the serotonin receptor agonist, zolmitriptan

Migraine is a common, often disabling, neurovascular disease that has been shown to be associated with abnormal serotonergic activity. Drugs that modulate serotonin receptors are commonly used in the acute treatment of a migraine attack. Zolmitriptan, a 5-hydroxytryptophan1B/1D receptor agonist, is once such drug that is used in acute migraine therapy. Zolmitriptan is FDA approved for the treatment of acute migraine attacks and there is recent literature demonstrating its efficacy in the acute treatment of cluster attacks. It is rapidly absorbed and is detectable in the plasma within 2 – 5 min for the nasal spray formulation and within 15 min for the oral formulations. Zolmitriptan reaches peak plasma levels in 2 – 4 h and significant plasma levels are maintained for up to 6 h and lower levels for over 15 h. As zolmitriptan's metabolism is predominantly hepatic, patients with severe hepatic impairment should not receive zolmitriptan. However, only 25% of zolmitriptan is bound to plasma proteins and thus it is unlikely for drug interactions involving the displacement of highly protein-bound drugs. Zolmitriptan is generally very well tolerated and less than half of patients in clinical trials have reported adverse events, most of which are mild and transient, although rare serious cardiovascular events have been reported with all triptans. When patients are appropriately selected, zolmitriptan is both a safe and effective acute care migraine treatment. In this review the biological role of serotonin and its receptors is covered, followed by an in-depth review of the pharmacodynamics, pharmacokinetics and efficacy of zolmitriptan. Finally, the clinical application of zolmitriptan's use in patients is dicussed.

Valsalva-induced cluster headache

A case valsalva-induced cluster headache is presented. Cluster attacks induced by valsalva manoeuvres alone were only recently described, and such patients have features of cough headache and cluster headache. Attacks occurred a couple of times a week in the patient presented, solely triggered by valsalva manoeuvres including coughing, sneezing or straining and not by exercising.

Survivability Analysis of A Cluster System with 4th Generation Security Mechanism: Regeneration

Cluster systems have been gradually more popular and are being broadly used in a variety of applications. On the other hand, many of those systems are not tolerant to system failures and moreover we cannot prevent all faults and attacks. In this paper, we analyze a cluster system's ability to maintain the critical services even in face of faulty and intrusions with 4th Generation Security Mechanism: Regeneration. The experiments have been demonstrated that the proposed mechanism can be used to analyze and proactively manage the effects of cluster network faults and attacks, and restore accordingly. The survivability level is greatly enhanced by the addition of functionality to targeted systems while maintaining the critical service and avoiding large incremental costs.

Behandlung eines atypischen und therapierefraktären Clusterkopfschmerzes mit Topiramat

Cluster headache is the third most frequent type of primary cephalgia only exceeded in frequency by tension-type headache and migraine. Cluster headache is characterized by periodic attacks of unilateral excruciating pain and accompanying autonomic features. It is arguably the most disabling form of primary headache. Therefore, prompt recognition of this disorder is necessary to provide an opportunity for effective treatment. We report on a patient with cluster headache, who complained about an atypical interval of dull headache between the cluster attacks, thus excluding the differential diagnosis of hemicrania continua. The common drugs for acute cluster attacks proved to be ineffective as well as prophylactic treatment with steroids and verapamil. Only administration of topiramate led to relief of pain.

The impact of SARS on epilepsy: The experience of drug withdrawal in epileptic patients

SummaryBackgroundDuring the 2003 severe acute respiratory syndrome (SARS) outbreak, many patients avoided hospital visit because of fear of infection. Antiepileptic drug (AED) withdrawal is a risk factor for seizure recurrence. Therefore, seizure control during the SARS outbreak is a good model for examining the impact of drug withdrawal in seizure control.MethodsAll seizures experienced by each patient before, during, and after the SARS outbreak periods were registered in each patient's seizure diary. The patients were divided into four groups according to the presence of drug withdrawal as well as seizure attack. In each group, seizures occurring during three different periods were compared. Risk factors for seizure recurrence were also examined.ResultsOf 227 cases, 49 stopped taking medication during the outbreak. Among them, 28 suffered seizure attacks during AED withdrawal. Four cases developed cluster attacks and two cases had status epilepticus after AED withdrawal. AED withdrawal produced a significant increase in seizure frequency. The major risk factors for withdrawal seizures were symptomatic etiologies, polytherapy and non-seizure free before AED withdrawal.ConclusionsThe SARS outbreak adversely affected seizure control because of AED withdrawal. Patients with polytherapy, non-seizure free and symptomatic etiologies were more susceptible to recurrence of seizures after AED withdrawal.

Cluster Headache Pharmacotherapy

Cluster headache is a well-known primary headache syndrome with a prevalence of about 5/10,000 of the adult population, making it much less common than migraine. Diagnostic terms such as histaminic cephalalgia, Horton's headache and ciliary neuralgia have been used for what is now known as cluster headache. This disorder can be differentiated from migraine by clinical and pathophysiologic features. Cluster headache also exhibits a differing therapeutic response to medications when compared with migraine. The pharmacologic treatment of cluster is reviewed in this article. In contrast to migraine, men are 3-4 times more likely to be diagnosed with cluster headache than women, and the cluster headache population is older. Cluster attacks are known for their brief intense unilateral excruciating pain during susceptible periods known as cluster periods, which typically last weeks. Attack-free months generally follow. Pain is experienced in the distribution of the trigeminal nerve, with unilateral autonomic features. Most patients are successfully managed with medical therapy. Medication management can be divided into abortive treatments for an ongoing attack and prophylactic treatment. Prophylaxis aims to induce and maintain a remission. There are a variety of different medications for abortive and prophylactic therapy, accompanied by a variable amount of evidence-based medicine. For patients refractory to medical management, interventional procedures are available as a last resort. Most procedures are directed against the sensory trigeminal nerve and associated ganglia, eg, anesthetizing the sphenopalatine ganglion.

Investigation Into Sleep Disturbance of Patients Suffering from Cluster Headache

The new discoveries relating to cluster headache (CH) encouraged the study of the relationship of the hypothalamus to respiratory physiology and its comorbidity with sleep apnoea. The question is whether the apnoeas are more frequent during REM sleep and the desaturations could be involved as triggers of the cluster attacks. Furthermore, could the connection with the hypothalamus, already proved, be responsible for an alteration in the structure of REM sleep and a chemoreceptor dysfunction. We set out to analyse when polysomnography investigation is necessary in patients with CH. We studied 37 patients suffering from episodic CH, 31 (83.8%) men and six (16.2%) women. For the control group, we selected 35 individuals, 31 (88.6%) men and four (11.4%) women. There was a greater percentage of obstructive sleep apnoea (OSA) in patients with CH (58.3%) compared with the control group (14.3%) and with the general population (2-4%). In cases of pain during sleep, the majority is deflagrated during the REM phase, following a desaturation episode. A stratified analysis of the apnoea/hypnoea index relating to body mass index (BMI) and age showed that patients with CH have 8.4 times more chance of exhibiting OSA than normal individuals (P < 0001). This risk increases to 24.38 in patients with a BMI > 25 kg/m(2) and increases to 13.5 in patients > 40 years old. Surprisingly, the risk decreases sharply in patients with a BMI < 25 kg/m(2) and who are < 40 years old. Due to the fact that polysomnography is a complex, costly and sometimes difficult examination, we suggest, in concordance with the results, that it should be carried out routinely in patients with CH that exhibit a BMI of > 25 kg/m(2) and/or in patients who are > 40 years of age.

Topiramate in the treatment of cluster headache.

Cluster headache is a well-characterized, strictly unilateral headache with cranial autonomic features and can be classified as episodic or chronic. Cluster attacks reliably are short-lived, often have a clockwise regularity, and can occur daily for weeks or months during an active cluster period. Pharmacologic treatment for this disorder can be divided into abortive and prophylactic agents. Prophylactic agents aim to quickly induce and maintain a remission. Short-term prophylaxis may be attained with the use of steroids, ergotamine, or methysergide, but these agents are not as suitable for continuous use. Verapamil and lithium commonly are used for longer periods and other agents, such as melatonin and baclofen, also are considered useful. There has been increased interest in the use of anticonvulsants for pain syndromes such as primary headache disorders. This includes topiramate use for cluster prophylaxis; a number of open-label studies have had encouraging results. This article provides an overview of topiramate and the open-label studies of this agent in the prevention of cluster headache.

Persistence of attacks of cluster headache after trigeminal nerve root section.

Brain. 2002;125(pt 5):976‐984.Cluster headache is a strictly unilateral headache that occurs in association with cranial autonomic features. We report a patient with a trigeminal nerve section who continued to have attacks. A 59‐year‐old man described a 14‐year history of left‐sided episodes of excruciating pain centred on the retro‐orbital and orbital regions. These episodes lasted 1‐4 h, recurring 2‐3 times daily. The attacks were associated with ipsilateral ptosis, conjunctival injection, lacrimation, rhinorrhoea and facial flushing. From 1986 to 1988, he had trials of medications without any benefit. In February 1988, he had complete surgical section of the left trigeminal sensory root that shortened the attacks in length for 1 month without change in their frequency or character. In April 1988, he had further surgical exploration and the root was found to be completely excised; post‐operatively, there was no change in the symptoms. From 1988 to 1999, he had a number of medications, including verapamil and indomethacin, all of which were ineffective. Prednisolone 30 mg orally daily rendered the patient completely pain free. Sumatriptan 100 mg orally and 6 mg subcutaneously aborted the attack after approximately 45 and 15 min, respectively. He was completely anaesthetic over the entire left trigeminal distribution. Left corneal reflex was absent. Motor function of the left trigeminal nerve was preserved. Neurological and physical examination was otherwise normal. MRI scan showed a marked reduction in the calibre of the left trigeminal nerve from the nerve root exit zone in the pons to Meckel's cave. An ECG‐gated three‐dimensional multislab MRI inflow angiogram was performed. No dilatation was observed in the left internal carotid artery during the cluster attack. Blink reflexes were elicited with a standard electrode and stimulus. Stimulation of the left supraorbital nerve produced neither ipsilateral nor contralateral blink reflex response. Stimulation of the right supraorbital nerve produced an ipsilateral response with a mean R2 onset latency of 36 ms and a contralateral response with a mean R2 onset latency of 32 ms. Lack of ipsilateral vessel dilatation makes the role of vascular factors in the initiation of cluster attacks questionable. With complete section of the left trigeminal sensory root the brain would perceive neither vasodilatation nor a peripheral neural inflammatory process; however, the patient continued to have an excellent response to sumatriptan. The case illustrates that cluster headache may be generated primarily from within the brain, and that triptans may have anti‐headache effects through an entirely central mechanism. Comment: A truly remarkable case. It has been said that a single case can make one rethink everything about a disorder. Dr. Goadsby's group has demonstrated a potential “cluster generator” in the hypothalamus. Now, with this case, they provide evidence that in a patient with no peripheral afferent information and no internal carotid artery changes, sumatriptan still works—evidence of its central effects in cluster. SJT The efficacy of oral sumatriptan in this patient raises the possibility of loss of blood‐brain barrier integrity. Might the surgical interventions have breached the BBB? It would be interesting to know whether a gadolinium MRI showed any evidence for this. DSM

What predicts evolution from episodic to chronic cluster headache?

Curr Pain Headache. Rep 2002 Feb;6(1):65‐70Over the last few years, attention has increasingly been focused on the evolution of cluster headache over time. Predictive factors have been identified that are correlated with an increased risk of unfavorable evolution from the episodic form to the chronic form of cluster headache. Late onset, the presence of sporadic attacks, a high frequency of cluster periods, and short‐lived duration of remission periods when the headache is still in its episodic form all correlate with a possible worsening of the clinical picture over time. The reasons for evolution of episodic cluster headache to chronic are still unknown, but some factors, such as head trauma and other lifestyle factors—eg, cigarette smoking and alcohol intake—have been suggested as having a negative influence on the course of cluster headache over time.Comment: Further longitudinal epidemiological research is needed to assess the impact of smoking cessation in these patients and to confirm or refute the hypotheses suggested in this paper. DSM Lee Kudrow documented that smoking, like nitroglycerin, lowers oxygen tension, which in turn can precipitate cluster attacks. Another possibility is that smoking and nitroglycerine are nitric oxide (NO) delivery systems and that the NO both precipitates attacks and worsens long‐term cluster prognosis. SJT

Risk factors and outcome of mood disorders in epilepsy: a case-control study

Background: This case-control study investigated both the risk factors and outcome of mood disorders in epilepsy. Methods: For this study, 44 patients with both epilepsy and a mood disorder (study group) were compared with 44 randomly selected patients of epilepsy without a mood disorder (control group). Psychiatric diagnosis was made as per ICD-10 Diagnostic Criteria for Research (ICD-10 DCR). International classification for seizure types (1981) was used for classification of seizure types. Results: Of the patients in the study group, a majority were educated up to at least primary level, had later onset of seizures, longer duration of epilepsy and cluster attacks. The outcome of mood disorders in epilepsy was found good in most. Conclusions: Educated patients who develop epilepsy at a later age and patients with poorly controlled epilepsy are more likely to experience mood disorders. In most patients with epilepsy, mood disorders remit completely; notably, in some patients affective symptoms resolve spontaneously.