Age at onset and sex ratio in cluster headache: observations over three decades

Five hundred and fifty-four patients with episodic cluster headache (ECH) and chronic cluster headache (CCH) were examined between 1963 and 1997. Mean age at onset was significantly higher in women with CCH compared with women with ECH and in men with ECH or CCH. In women with CCH age at onset was evenly distributed from 10 to 69 years, whereas in men with CCH and in both sexes with ECH, there was a peak when they were in their 20s. In women with ECH a second peak of onset occurred in their 50s. Although not statistically significant, primary CCH started later in women (mean 50.8 years) than secondary CCH (mean 35.5 years). There was a significant variation in the male : female ratio with respect to age at onset, being largest between 30 and 49 years of age (ECH 7.2 : 1; CCH 11.0 : 1) and lowest after 50 (ECH 2.3 : 1; CCH 0.6 : 1). During the observation period of more than 30 years there was a trend towards a decreasing male preponderance; the male : female ratio was significantly higher among patients with onset before rather than after 1970. The proportion of episodic vs. chronic CH did not change during the study period. The nature of the sex- and age-related pattern of cluster headache onset remains to be elucidated but mechanisms associated with sex hormone regulation, perhaps of hypothalamic origin, may be involved, as well as environmental factors related to lifestyle.     

Ipsilateral cluster headache and chronic paroxysmal hemicrania: two case reports

We report two patients with ipsilateral attacks of cluster headache and chronic paroxysmal hemicrania. The first patient, a 33-year-old man, started having attacks of chronic cluster headache at the age of 27. At 33, they were replaced by typical attacks of ipsilateral chronic paroxysmal hemicrania which showed a dramatic improvement with indomethacin 150 mg daily. After two days of complete remission, cluster headache attacks reappeared and persisted until verapamil, 360 mg a day, was added to indomethacin. The second patient, a 45-year-old man, first developed attacks of episodic cluster headache at the age of 35. At 44, he experienced ipsilateral typical attacks of chronic paroxysmal hemicrania, and two months later attacks of cluster headache. Under verapamil 240 mg daily, attacks of cluster headache disappeared, but those of chronic paroxysmal hemicrania increased in frequency until indomethacin 150 mg daily was added. These observations suggest a close relationship but not a similarity between cluster headache and chronic paraoxysmal hemicrania, and show the practical therapeutic interest of maintaining this distinction.     

Cataract in chronic cluster headache: two case reports and review of the literature

Cluster headache (CH) consists of attacks of severe, unilateral orbital/supraorbital/temporal pain, lasting for 15–180 min, occurring once or more times a day, and associated with ipsilateral conjunctival injection, lacrimation and other symptoms. Cataract is clouding of the lens of the eye causing a progressive and painless loss of vision. We describe the cases of two men (not relative, but with the same last name, which originates from north-eastern Italy) that in young adult age, after years of suffering from chronic CH, developed cataract on the same side of the pain attacks. Patient 1 was diagnosed as having cataract 18 years after the onset of episodic (and subsequently chronic) CH. Patient 2 began suffering from chronic CH at the age of 44 years and after 8 years he developed cataract. This is the first report of cataract in patient suffering of CH and occurring in the eye affected by the pain attack. No financial support received.     

Rehabilitation of neuromyelitis optica (Devic syndrome): three case reports

We describe the inpatient clinical rehabilitation course of three patients with neuromyelitis optica (NMO; Devic syndrome). These patients had varying functional deficits. Each patient improved in several functional independence measures (FIM domains) but had minimal to no progress in other domains after acute rehabilitation stays between 1 and 1.5 mos. NMO is a severe central nervous system demyelinating syndrome distinct from MS, characterized by optic neuritis, myelitis, and at least two of three criteria: longitudinally extensive cord lesion, MRI nondiagnostic for multiple sclerosis, or NMO-IgG seropositivity. Persons with NMO may demonstrate improved function with rehabilitation efforts; though gains may be lost to relapse. Future immunomodulatory intervention may augment the benefits of rehabilitation.     

Parenteral indomethacin (the INDOTEST) in cluster headache

The interval between indomethacin administration and clinical response may be extremely relevant in the assessment of chronic paroxysmal hemicrania (CPH) and other unilateral headache disorders like cluster headache (CH), with which CPH can be confounded. Indomethacin is inactive in CH; however, in some anecdotal reports in recent years, doubt has been cast on the ineffectiveness of indomethacin in CH. In this study, we have re-assessed the effect of indomethacin treatment in a group of 18 patients with episodic CH (three females and 15 males). From the day 8 of the active period, indomethacin 100 mg i.m. was administered every 12 h, for 2 consecutive days, in an open fashion. The mean daily attack frequency before the test (1.6 +/- 0.6) was not statistically different from that on day 1 (2.1 +/- 0.9) and day 2 (1.9 +/- 0.8) after indomethacin administration. The mean interval between indomethacin injection and the following attack (day 1 and day 2) was 4.6 + 1.1 h. We did not observe any refractory period in any patient after indomethacin. Since the 'expected' attack occurred when there theoretically could have been a protective effect after indomethacin administration, it can be reasonably assumed that there is no such protective effect. The use of a test dose of 100 mg i.m. indomethacin (INDOTEST) appears to provide a clear-cut answer in this situation. It may be a useful tool for a proper clinical assessment of unilateral headache with relatively short-lasting attacks when problems of classification arise. A correct diagnosis of CPH or CH is important, since a CPH diagnosis may imply a lifelong treatment with a potentially noxious drug.     

Carnitine palmityltransferase II (CPT2) deficiency and migraine headache: two case reports

BACKGROUND: Migraine headache is common and has multiple etiologies. A number of mitochondrial anomalies have been described for migraine, and mitochondrial dysfunction has been implicated as one potential pathophysiological mechanism. Carnitine is used by mitochondria for fatty acid transportation; its deficiency, however, has not been implicated in migraine pathophysiology. METHODS AND RESULTS: Two adolescent girls presented to the Headache Center at Cincinnati Children's Hospital Medical Center with frequent headaches and were diagnosed with migraine by the International Headache Society (IHS) criteria. Both girls had a history of recurrent fatigue, muscle cramps, and multiple side effects from their prophylactic treatment. Carnitine levels were measured and found to be low. Carnitine supplementation was initiated. Both patients had a reduction in headache frequency, as well as an improvement in their associated symptoms and other complaints. A skin and muscle biopsy obtained from one patient revealed a partial carnitine palmityltransferase II deficiency in the muscle only. CONCLUSIONS: Carnitine palmityltransferase II deficiency may represent another etiology for migraine headache, and may be useful in further defining the pathophysiology of migraine. When properly recognized, supplementation with carnitine may improve the outcome of the migraine as well as the carnitine-associated symptoms.     

Dynamic mechanical (brush) allodynia in cluster headache

OBJECTIVE: To examine the occurrence of dynamic mechanical (brush) allodynia (BA) in patients with cluster headache (CH). BACKGROUND: Cutaneous allodynia was described in migraine. It was related to sensitization of neurons in the trigeminal nucleus caudalis (TNC). This phenomenon has not been previously described in cluster headache. METHODS: We examined adult patients with episodic or chronic CH for the presence of BA. Demographic data and the characteristics of CH were obtained through a questionnaire. Allodynia testing was performed by repetitively applying a 4x4-inch gauze pad to skin areas in the trigeminal and cervical dermatomes. Degree of allodynia was measured on a 100-mm visual analog scale (VAS). The relations between the location and severity of headache and allodynia were assessed. RESULTS: Ten patients (all male, mean age 39.3) were included in the study. Seven had episodic CH (ECH) and 3 had chronic CH (CCH). Two patients were in acute attack when tested for BA. In total, 4 (40%) of the 10 patients had BA (2 [28.6%] of the 7 with ECH and 2 [66.7%] of the 3 with CCH). Median disease duration was 22 years for patients with BA and 12 years for patients without BA. Of the two patients in acute attack, one had BA, ipsilateral to the headache, which was reduced 20 minutes after treatment, along with reduced headache severity. CONCLUSIONS: This is the first report on the occurrence of cutaneous allodynia in CH. The presence of BA in CH may be related to CH type (episodic vs. chronic) and to the duration of disease. These results support the concept that allodynia in CH may result from a time-dependent process of neuronal sensitization.     

Schistosomiasis (Bilharzia) of the spinal cord: case reports and clinical profile

Eight cases of schistosomiasis of the spinal cord are described. These fall into two groups. Four patients had clinical and myelographic evidence of lesions in the conus medullaris and were found to have bilharzial granulomas at operation. Four patients had normal or equivocal myelographic appearances, but the coincidence of unexplained lower cord or cauda equina lesions with evidence of bilharzia led to the presumed diagnosis of spinal cord bilharzia. These patients, together with data from 39 cases reported in the world literature since 1969, have been used to compile a clinical profile of this condition. The clinical picture is the product of two types of reaction to bilharzial infestation, granuloma and necrotic myelitis, affecting the lower cord and cauda equina in varying proportions. Granuloma is the better defined entity because it is diagnosed following operation and biopsy. Myelitis is seldom proved and its diagnosis depends on circumstantial evidence. Both S. mansoni and S. haematobium may be responsible for either type.     

Episodic cluster headache and narcolepsy: a case report

A patient who first presented with episodic cluster headache later developed narcolepsy. In spite of REM sleep alterations associated with narcolepsy, the frequency and distribution of pain attacks did not change when narcolepsy occurred and were similar to those seen in cases of episodic cluster without narcolepsy. The lack of influence of narcolepsy on the pattern of cluster pains questions the role of REM sleep states in triggering pain in episodic cluster.     

Alpha-2-delta ligands for singultus (hiccup) treatment: three case reports

Chronic idiopathic singultus (hiccup) is a debilitating condition affecting mostly elderly males. While in the past, pharmacologic singultus treatment was mostly “trial and error,” more recently, treatment has become both more evidence based and pathophysiology guided. A combination of an acidity-reducing drug (H₂-receptor blocker or proton pump inhibitor) with baclofen (gamma-amino-butyric-acid receptor type B agonist) has become the most widely used regimen. Some clinicians replace or supplement baclofen with gabapentin. We present three cases of chronic idiopathic hiccup managed with gabapentin or another alpha-2-delta ligand, pregabalin. This is the first reported use of pregabalin for this indication.     

Benzodiazepine and hiccup: three case reports

Hiccup is a sudden contraction of the inspiratory muscles, followed by an abrupt closure of the glottis, thus producing a characteristic sound. In the literature, some drugs have been reported to induce hiccup. We discuss three case reports after administration of benzodiazepine to healthy young subjects during two clinical trials. In the first study (a bioequivalence trial of two forms of lormetazepam, tablets and oral solution), 12 subjects were included in an open controlled crossover study with two periods separated by a washout of 7 days. Two subjects presented with hiccup after administration of lormetazepam (2mg oral solution). The symptom resolved in 10 and 40 minutes, respectively. In one subject, rechallenge with a tablet of lormetazepam was positive. The aim of the second study was to assess the effect of sleep deprivation and lorazepam-induced sedation on saccadic eye movements in 12 healthy subjects. Hiccup occurred in one subject 3h 15 after administration of a single oral dose of lorazepam (2mg) and resolved in 45 minutes. All cases were evaluated according to the French imputation method. These observations are discussed with regard to the drug classes mentioned most frequently in the literature.     

Sodium valproate in the treatment of cluster headache: an open clinical trial

The effect of prophylactic treatment with sodium valproate in cluster headache was investigated in an open pilot study. Fifteen cluster headache patients were studied of whom two suffered from chronic cluster headache and thirteen from the episodic type. The dose used was between 600 and 2000 mg per day in two divided doses. Eleven out of the fifteen patients (73.3%) reacted favorably to the treatment. Nine reported a complete disappearance of pain and two, a marked improvement. Sodium valproate appears to be an effective drug in the treatment of cluster headache. A double-blind controlled study is needed for further evaluation.     

A case of parasellar meningioma mimicking cluster headache

A medical history of a 46-year-old male is reported. At 23 years of age, he started having diffuse pain in the left side of his head for up to 30 min once or twice a month. At 28, the pain changed into left-sided cluster headache-like attacks with 2-3 h duration and with ipsilateral conjunctival injection, lacrimation, and rhinnorhea, but with short-lasting free intervals of about two to three weeks. At 36, the pattern of the attacks corresponded to chronic migrainous neuralgia. At 40, the symptoms changed to painful ophthalmoplegia-picture. A left-sided parasellar meningioma was then diagnosed. Removal of the tumor caused complete amelioration. The case history is suggested to support the hypothesis that the cavernous sinus region is involved in cluster headache.     

Dynamic mechanical (brush) allodynia in cluster headache: a prevalence study in a tertiary headache clinic

Cutaneous allodynia (CA) has been described in migraine and has been related to treatment failure. There are little data about the incidence of CA in other primary headache syndromes such as cluster headache (CH). The objectives of this study are to evaluate the prevalence of dynamic mechanical (brush) allodynia (BA) in CH patients attending a tertiary headache clinic, and to assess its relation to disease characteristics. Adult patients with episodic or chronic CH were recruited. We obtained demographic data and data on disease characteristics through a structured questionnaire, and tested the patients for brush allodynia BA by applying a 4 × 4 gauze pad over the V₁, C₂/C₃ and C₈ skin areas bilaterally. The prevalence of allodynia in the entire study population and in the different sub-groups was calculated. We also examined the association between CA and demographic parameters, and its association with disease characteristics. Forty-one patients were recruited (22 men, 19 women; mean age 44.9 years). Twenty-two had chronic CH (CCH) and 19 had episodic CH (ECH). Mean disease duration was 14.1 years (12.3 the CCH group and 15.7 in the ECH group). Overall, 20 (49%) patients were allodynic. There was no statistically significant association between the presence of allodynia and age, gender, diagnosis (episodic vs. chronic CH), disease duration or disease severity. In conclusion, BA was common in this CH patient sample. The therapeutic implications of the presence of BA in CH need to be further studied.     

Case reports: sudden worsening of cluster headache: A signal of aneurysmal thrombosis and enlargement

We report a 55-year-old man presenting with symptoms of cluster headache, including throbbing pain behind the left eye, tearing, and rhinorrhea. Magnetic resonance imaging and magnetic resonance angiography revealed no abnormalities. Two days of intravenous dihydroergotamine resolved his pain. His headaches were somewhat relieved with a treatment regimen of 100 mg of imipramine each night, 40 mg of propranolol twice a day, 250 mg of divalproex three times a day, and dihydroergotamine nasal spray for breakthrough headaches. Two months later, the severity of his pain increased dramatically. Repeat imaging revealed a large thrombosed left posterior communicating artery aneurysm. Following obliterative surgery, his headaches are infrequent and mild and resemble tension headaches. Dramatic changes in headache characteristics can be an indicator of aneurysmal enlargement and thrombosis. This case illustrates the importance of repeat imaging when a patient's headache significantly worsens.