Recurrence of Cluster Headache After Carotid Thrombendarterectomy

SYNOPSIS
The pathophysiology of cluster headache is largely unknown. One important contributing factor may be an abnormal intracranial-extracranial hemodynamic state. A male patient suffered from chronic left-sided cluster headache for about 15 years. After the institution of lithium therapy the symptoms abated. He was completely free from cluster headache for more than 20 years, until the first postoperative day after a thrombo-endarterectomy for symptomatic 70% carotid stenosis.
This case report indicates the importance of abrupt carotid hemodynamic changes along with dysfunction of the cephalic sympathetic nervous system in the initiation of cluster headache.     

Ciliospinal Reflex Response in Cluster Headache

The ciliospinal reflex response is mainly mediated by second- and third-order sympathetic nerves to the dilatator muscle of the iris. As the pupillary response to various pharmacological agents indicates a sympathetic dysfunction in patients with cluster headache, the ciliospinal reflex was studied in 25 patients. Five of these patients with cluster headache exhibited a Horner-like syndrome (miosis, ptosis) on the symptomatic side. The pupillary responses to phenylephrine and tyramine showed that the Horner-like syndrome was due to postganglionic sympathetic nerve dysfunction. Their ciliospinal reflex response on the symptomatic side was significantly less than in controls and in other patients with cluster headache, lacking a Horner-like syndrome. This also applied to the nonsymptomatic side compared to the majority of cluster headache patients without any clinical evidence of sympathetic nerve dysfunction.
These findings seem to delineate those patients with a Horner-like syndrome as a subgroup, distinctly separated from the majority of cluster headache patients. Furthermore, the findings indicate that the Horner-like syndrome is not a consequence of repeated attacks of headache over many years, but is a manifestation of bilateral cephalic sympathetic dysfunction being more marked on the symptomatic side.
In 18 (72%) of our 25 patients, an asymmetric and lower ciliospinal reflex response on the symptomatic side was seen. In 3 (12%) patients, there was no difference in the response. In 4 patients (16%), the incorrect side was indicated by an asymmetric reflex response. Two of these patients (8%) had suffered from cluster headache on alternating sides.
In summary, the findings support the concept that dysfunction of the sympathetic nervous system, whether peripheral or central, is involved in the pathophysiology of cluster headache.     

The Enhanced Ciliospinal Reflex in Asymptomatic Patients With Cluster Headache is Due to Preganglionic Sympathetic Mechanisms

An amplified ciliospinal reflex response has been documented in patients with cluster headache, lacking a Horner like syndrome. The mechanism is unknown, Tentatively, it may be due to an increased release of monoamines from post-ganglionic sympathetic nerve endings or an increased density of postsynaptic adrenergic receptors in the dilatator muscle of the iris.
The instillation of a 1% phenylephrine solution into the conjunctival sac induces mydriasis by stimulating postsynaptic adrenergic receptors in the dilatator muscle of the iris, while the instillation of a 2% tyramine solution causes mydriasis by releasing noradrenaline from the presynaptic sympathetic nerve terminals in the iris.
According to these premises, a positive correlation shouId be expected between the ciliospinal reflex response and the pupillary response to tyramine, if the enhanced ciliospinal so-flex response was due to an increased presynaptic release of monoamines. No such correlation was found. Nor was there any positive correlation between the ciliospinal reflex response and the pupillary response to phenylephrine, contradicting an increased density of postsynaptic monoaminergic receptors in the dilatator muscle of the iris as the explanation. However, there was a significant positive correlation between the pupillary responses to phenylephrine and tyramine, ruling out any functionally caused "denervation" hypersensitivity in the dilatator muscle of the iris.
It is concluded that the amplified ciliospinal reflex response in cluster headache patients (lacking a Horner-like syndrome) reflects compensatory pathophysiological mechanisms proximal to the third-order sympathetic neuron.     

Response of Cluster Headache to Kudzu

Objective.— To describe the self-treatment of cluster headache with kudzu.
Background.— 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.
Methods.— 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.
Results.— In total, 11 (69%) experienced decreased intensity of attacks, 9 (56%) decreased frequency, and 5 (31%) decreased duration, with minimal side effects.
Conclusion.— 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.     

Latent dysautonomic pupillary lateralization in cluster headache. A pupillometric study

Forty-five patients with cluster headache in the asymptomatic phase were studied by electronic pupillography, testing autonomic function of both pupils pharmacologically. Topical sympathetically-acting mydriatics, tyramine and cocaine and the cholinoceptor blocker, homatropine, induced defective mydriatic responses on the symptomatic side, indicating latent impairment of sympathetic function. The abnormality was found in interattack intervals of the cluster period or during intercluster phases. The tyramine test can be proposed for objective diagnosis of cluster headache. We postulate that cluster attacks are triggered and lateralized by a permanent latent unilateral sympathetic dysfunction. Lithium reduced the mydriatic response to tyramine of the pupil contralateral to the pain, thus restoring the equilibrium between both pupils; this therapy may correct the asymmetric sympathetic function by attenuating the activity in the asymptomatic side.     

The Site of Sympathetic Deficit in Cluster Headache

The pattern of autonomic deficit in the face of cluster headache patients resembles the deficit in patients with a postganglionic sympathetic lesion from some other cause; however the presence of abnormal cardiac rhythms and bilateral pupillary reflex deficit in some patients with cluster headache suggests that the lesion might compromise central sympathetic drive. To investigate this possibility, the vasomotor and sudomotor startle reflex was investigated in the hands of sic cluster headache patients with ocular and thermoregulator signs of postganglionic sympathetic deficit in the face; for comparison, responses were also investigated in 15 patients with a lesion in the cervical sympathetic pathway from some other cause. The startle reflex was intact in the hands of the six cluster headache patients, but was diminished ipsilaterally in patients with a central or preganglionic sympathetic lesion and also, surprisingly, in patients with a postganglionic lesion caused by an aneurysm of the internal carotid artery. Ocular sympathetic deficit was greater in patients with an aneurysm of the internal carotid artery than in cluster headache patients or in patients with a postganglionic sympathetic lesion from some other cause; the aneurysm may have compromised neurons with projections to the face and hand, or could have induced transsynaptic degeneration of preganglionic fibers supplying both regions. The findings indicate that central sympathetic drive is not impaired in cluster headache patients; thus, a peripheral lesion probably induces sympathetic deficit on the symptomatic side of the face.     

2. Cluster Headache

Cluster headache is a strictly unilateral headache that is associated with ipsilateral cranial autonomic symptoms and usually has a circadian and circannual pattern. Prevalence is estimated at 0.5 to 1.0/1,000. The diagnosis of cluster headache is made based on the patient's case history. There are two main clinical patterns of cluster headache: the episodic and the chronic. Episodic is the most common pattern of cluster headache. It occurs in periods lasting 7 days to 1 year and is separated by at least a 1-month pain-free interval. The attacks in the chronic form occur for more than 1 year without remission periods or with remission periods lasting less than 1 month.
Conservative therapy consists of abortive and preventative remedies. Ergotamines and sumatriptan injections, sublingual ergotamine tartrate administration, and oxygen inhalation are effective abortive therapies. Verapamil is an effective and the safest prophylactic remedy. When pharmacological and oxygen therapies fail, interventional pain treatment may be considered. The effectiveness of radiofrequency treatment of the ganglion pterygopalatinum and of occipital nerve stimulation is only evaluated in observational studies, resulting in a 2 C+ recommendation.
In conclusion, the primary treatment is medication. Radiofrequency treatment of the ganglion pterygopalatinum should be considered in patients who are resistant to conservative pain therapy. In patients with cluster headache refractory to all other treatments, occipital nerve stimulation may be considered, preferably within the context of a clinical study.     

Cluster headache management with methylphenidate (Ritalin)

The authors report rapid cluster headache relief in a 43-year-old man with a 5-year history of refractory cluster headache. The patient described complete headache relief within 10 minutes of taking 10 mg of methylphenidate (Ritalin) when used to abort the onset of his headaches. Subsequently, a scheduled Ritalin dose taken each morning was sufficient to prevent his nightly headaches. In addition, 1 week of prophylactic methylphenidate therapy halted the series of cluster headaches. This is the first reported case of relief of cluster headaches with methylphenidate.     

Pupillary functional asymmetry in patients with muscle contraction headache

Twenty-five patients with 'muscle contraction headache' (MCH) underwent tyramine pupillary tests, and 15 of them also underwent physiologic pupillary tests and cold pressor tests. Twenty healthy controls underwent tyramine pupillary tests, physiologic pupillary tests, and cold pressor tests. In the tyramine pupillary tests and the physiologic pupillary tests, the controls showed a symmetric mydriasis. In contrast, MCH patients showed asymmetric mydriasis after tyramine instillation and in the physiologic pupillary tests. In the cold pressor tests MCH patients reacted in the same manner as the controls. It is suggested that MCH patients have pupillary sympathetic imbalance. The role of this imbalance in the pathogenesis of MCH remains uncertain.     

Clusterlike Headache in a Patient With a Pituitary Adenoma. With a Review of Literature

A man had left-sided atypical clusterlike headache for II years before he developed symptoms and signs consistent with acromegaly. Preoperative evaluation revealed raised levels of somatomedin C and growth hormone. An MR indicated a left-sided intrasellar mass measuring 8 x 7.5 x 10 mm. He underwent surgery and microscopy confirmed the diagnosis of a benign hypophyseal adenoma. Postoperatively, the acromegalic features regressed, and for the last 4 years the patient has been completely free from headache attacks. On pharmacological testing of the pupillary response to 19 and 5% phenylephrine and 2% tyramine solutions, there was no convincing evidence of persistent sympathetic dysfunction on the earlier symptomatic side.     

Orbital Phlebography: A Comparison Between Cluster Headache and Other Headaches

Orbital phlebography has previously been found to be pathologic in 8 of 13 patients with episodic cluster headache. To compare the frequency and pattern of the pathologic findings in cluster headache with those in other headache categories, orbital phlebographies were carried out in patients with cluster headache, cervicogenic headache, migraine and tension-type headache (tension headache). The investigations were evaluated independently by two radiologists, one of whom had no knowledge of the diagnoses. The frequencies of pathologic findings were at maximal 2/12 in the cluster headache group, 2/11 in the cervicogenic headache group, 5/12 in the migraine group and 5/15 in the tension-type headache group. The investigators agreed completely in the evaluation of 39/50 phlebograms, with lesser disagreements in 7. In conclusion, the frequency of pathologic findings at orbital phlebography in cluster headache was not higher than in the other diagnostic categories investigated, and the pattern of the pathology was generally the same.     

MRI of Intracranial Arteries in Nitroglycerin Induced Cluster Headache Attacks

Eight patients with episodic cluster headache, five in active episode, three out of episode, were investigated as to diameters of intracranial arteries before and after nitroglycerin (NG) administration. The diameter of all intracranial carotids were increased about 10 minutes after NG, although more in the patients in episode than in patients out of episode. The dilatation remained for the next 60 minutes in the patients who did not get a cluster headache attack. There was a normalization of the diameters of the internal carotid arteries compared to the initial values, at maximum pain in all patients who got a cluster headache attack. Similar changes were also found in the basilar arteries. The findings support the hypothesis of a constriction of intracranial arteries at maximum pain in cluster headache attacks to stop the pain.     

Post‐Traumatic Cluster Headache: From the Periphery to the Central Nervous System?

A correlation between head trauma and cluster headache is believed to exist. We report a case of post-traumatic episodic cluster headache that fulfills the criteria of the International Classification of Headache Disorders, 2nd edition. The distinctive features of this case are: a close temporal relation between head trauma and headache onset; pain ipsilateral to the side of trauma; mild severity of trauma; episodic course well-responsive to low doses of verapamil. Given the close temporal relation between the 2 events, multiple hypotheses can be advanced about a possible role of head trauma in the pathogenesis of cluster headache.     

Cluster Headache: The Ventilatory Response to Transient Hypoxia with Pure Nitrogen

SYNOPSIS
To determine whether the carotid body plays a pathogenetic role in cluster headache, 20 cluster headache patients have been studied. Of these, 11 patients were in the interparoxysmal cluster phase, and 9 were in remission. Comparison was made with healthy subjects matched for sex, age, and smoking habits. Transient hypoxia was induced by inhalation of 1–8 breaths of 100% nitrogen (N₂), until the arterial oxygen saturation (SaO₂) decreased to around 80%. Changes in ventilation (tidal volume, inspiratory minute ventilation (V_I ), and end-tidal PCO₂ (P_ETCO₂)), were analyzed breath-by-breath.
Under basal conditions, cluster headache patients had a slightly higher SaO₂ and V_I when compared to controls. P_ETCO ₂ was significantly lower (P < 0.05) during the cluster period as measured by Wilcoxon signed rank test for paired data, and during remission, according to the Student's paired t-test, in comparison with controls. After exposure to N₂, no significant difference was found in the rate of reduction of SaO₂ between any of the groups. A higher absolute increase in V_I , but a relative (%) decrease in V_I at moderate hypoxia were measured, the differences between patients and controls being on the border of the level of significance. Chemoreceptor sensitivity of the carotid body, expressed as the slope of a regression curve obtained by plotting the increase in V_I against the reduction in SaO 2 , showed no statistical difference between the groups. The results do not support the hypothesis of a pathogenetic role for the carotid body in cluster headache.     

Zolmitriptan Nasal Spray in the Acute Treatment of Cluster Headache: A Meta-Analysis of Two Studies

Objective.— To conduct an individual subject meta‐analysis of available controlled studies of zolmitriptan nasal spray in the acute treatment of cluster headache. Background.— Two double‐blind, placebo‐controlled, randomized, crossover studies of zolmitriptan nasal spray in the acute treatment of cluster headache, with similar patient populations, protocol designs, doses, and clinical endpoints have been published. Methods.— In both double‐blind studies, each patient was to treat 3 attacks, 1 with placebo, 1 with zolmitriptan 5 mg, and 1 with zolmitriptan 10 mg in a randomized, crossover manner. Headache intensity was rated on a 5‐point scale (none to very severe). The primary endpoint was headache relief at 30 minutes post dose: reduction from moderate, severe, or very severe pain to mild or none. A multilevel, random‐effects, logistic regression model was used to analyze the data. Results.— A total of 121 patients (100 male; 64.5% with episodic cluster headache) provided efficacy data for at least 1 attack. Zolmitriptan 5 mg and 10 mg were significantly more effective at providing headache relief at 30 minutes post treatment than placebo (odds ratio 3.48; 95% confidence interval 1.49‐8.10 and odds ratio 8.68; 95% confidence interval: 3.35‐22.5, respectively). For episodic cluster headache, response rates were 35.6%, 51.7%, and 73.7% for placebo, zolmitriptan 5 mg (odds ratio 2.5; P = .06 vs placebo), and 10 mg (odds ratio 9.9; P < .001 vs placebo), respectively. For chronic cluster headache, response rates were 17.2%, 41.9%, and 40.7% for placebo, zolmitriptan 5 mg (odds ratio 8.1; P = .035), and 10 mg (odds ratio 7.6; P = .046), respectively. Zolmitriptan was well tolerated in both studies with no serious adverse events reported. Conclusion.— Zolmitriptan nasal spray at a dose of 5 mg and 10 mg is efficacious in the acute treatment of episodic and chronic cluster headache.