BACKGROUND: Cluster headache is a severe and debilitating neurological condition characterized by intense, excruciating pain with a significant impact on patients\' wellbeing. Although different treatment options are available, many patients continue to experience inadequate relief. Therefore, experimental strategies are increasingly studied. One of the more promising approaches is the use of ketamine. We present the currently available evidence and our own data.
METHODS: In this mixed-methods paper, we first summarize the available evidence of ketamine for treatment of cluster headache based on a systematic review of literature in MEDLINE, EMBASE and the Cochrane library of systematic reviews. As the level of evidence is quite limited, we report our own cohort study with ten patients treated with ketamine infusions for cluster headache. They were followed up to investigate the patients\' experience of treatment success and quality of life.
RESULTS: The search and review of literature identified four reports with a total of 68 patients. All were uncontrolled case series. The current literature suggests that ketamine might decrease cluster headache. However, as the applied regimes and reported outcomes are highly heterogeneous, further analysis was futile. Our own data show high patient satisfaction with ketamine treatment.
CONCLUSIONS: Despite the limited evidence, ketamine might be considered a potential therapeutic approach for cluster headache. Therefore, further research including randomized controlled trials should be encouraged.
This article discusses the potential use of ketamine for the treatment of cluster headache, a severe neurological condition that can have a significant impact on patients\' quality of life. The authors conducted a systematic review of the existing literature on ketamine for the treatment of cluster headache. Additionally, they also presented their own cohort study of ten patients receiving ketamine infusions. The review of the literature revealed four reports with a total of 68 patients, all of which were uncontrolled case series. While the current literature suggests that ketamine may be effective in relieving cluster headache symptoms, the heterogeneity of treatment regimens and reported outcomes makes it difficult to draw definitive conclusions. The authors\' own cohort study found that patients were very satisfied with ketamine treatment, indicating a potential benefit of this approach. However, due to the limited evidence available, further research, including randomized controlled trials, is needed to better understand the efficacy of ketamine in the treatment of cluster headaches.

OBJECTIVE: Androgens have been hypothesized to be involved in the pathophysiology of cluster headache due to the male predominance, but whether androgens are altered in patients with cluster headache remains unclear.
METHODS: We performed a prospective, case-controlled study in adult males with cluster headache. Sera were measured for hormones including testosterone, luteinizing hormone (LH), and sex hormone-binding globulin in 60 participants with episodic cluster headache (during a bout and in remission), 60 participants with chronic cluster headache, and 60 age- and sex-matched healthy controls. Free testosterone (fT) was calculated according to the Vermeulen equation. Shared genetic risk variants were assessed between cluster headache and testosterone concentrations.
RESULTS: The mean fT/LH ratio was reduced by 35% (95% confidence interval [CI]: 21%-47%, p < 0.0001) in patients with chronic cluster headache and by 24% (95% CI: 9%-37%, p = 0.004) in patients with episodic cluster headache compared to controls after adjusting for age, sleep duration, and use of acute medication. Androgen concentrations did not differ between bouts and remissions. Furthermore, a shared genetic risk allele, rs112572874 (located in the intron of the microtubule associated protein tau (MAPT) gene on chromosome 17), between fT and cluster headache was identified.
CONCLUSIONS: Our results demonstrate that the male endocrine system is altered in patients with cluster headache to a state of compensated hypogonadism, and this is not an epiphenomenon associated with sleep or the use of acute medication. Together with the identified shared genetic risk allele, this may suggest a pathophysiological link between cluster headache and fT. ANN NEUROL 2024;95:1149-1161.

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Cluster headache is a rare, severe headache associated with hypothalamic dysfunction or sleep cycles. It is classified in the primary headache group in The International Classification of Headache Disorders-3-2018 (ICHD-3-2018). In this case report, we present a 62-year-old male patient whose cluster headache showed a five times longer remission interval after dental implant treatment and ceased for more than two years following cardiac stent therapy.

BACKGROUND: Current criteria help differentiate cluster headache from migraine. However, children may have overlapping features making it difficult to distinguish the 2 conditions, which may delay diagnosis. Differentiating cluster headache from migraine is important regarding treatment as well as diagnostic workup of secondary headache etiologies.
METHODS: Cases at a single pediatric children\'s hospital from 2015 to 2023 diagnosed with cluster headache before the age of 18 years were reviewed.
RESULTS: Twenty-five cases were identified of which 22 cases met criteria for either chronic, episodic, or probable cluster headache. Three cases were diagnosed with cluster headache by their provider, but documentation was insufficient to meet criteria for cluster headache. There were 16 females and 9 males between ages 6 and 17 years. Five cases were identified as symptomatic, 2 cases as chronic, 7 cases as episodic, and 13 cases as probable cluster headache. Symptomatic etiologies include Graves disease, optic neuritis, prolactinoma, hypothalamic pilocytic astrocytoma with carotid stenosis, and congenital right eye blindness. Migrainous features were common, including 76% with nausea, 36% with vomiting, 68% with photophobia, and 56% with phonophobia. Patients with cluster headache also had an independent diagnosis of migraine in 64%.
CONCLUSIONS: Children with cluster headache have a high frequency of migrainous symptoms and co-occurrent diagnosis of migraine. A careful history may differentiate cluster headache from migraine and treated accordingly. Children with cluster headache features should undergo screening for secondary causes with appropriate imaging and other studies. Except for prolactinoma, the symptomatic associations noted in this case series have not been reported before.

In 1981, Devoghel achieved an 85.6% success rate in treating patients with treatment-refractory cluster headaches with alcoholization of the pterygopalatine ganglion (PPG) via the percutaneous suprazygomatic approach. Devoghel\'s study led to the theory that interrupting the parasympathetic pathway by blocking its transduction at the PPG could prevent or treat symptoms related to primary headache disorders (PHDs). Furthermore, non-invasive vagus nerve stimulation (nVNS) has proven to treat PHDs and has been approved by national regulatory bodies to treat, among others, cluster headaches and migraines.In this case series, nine desperate patients who presented with 11 longstanding treatment-refractory primary headache disorders and epidural blood patch-resistant postdural puncture headache (PDPH) received ultrasound-guided percutaneous suprazygomatic pterygopalatine ganglion blocks (PPGB), and seven also received nVNS. The patients were randomly selected and were not part of a research study. They experienced dramatic, immediate, satisfactory, and apparently lasting symptom resolution (at the time of the writing of this report). The report provides the case descriptions, briefly reviews the trigeminovascular and neurogenic inflammatory theories of the pathophysiology, outlines aspects of these PPGB and nVNS interventions, and argues for adopting this treatment regime as a first-line or second-line treatment rather than desperate last-line treatment of PDPH and PHDs.

Chronic cluster headache (CCH) is a rare but severely debilitating primary headache condition. A growing amount of evidence suggests that occipital nerve stimulation (ONS) can offer effective treatment in patients with severe CCH for whom conventional medical therapy does not have a sufficient effect. The paresthesia evoked by conventional (tonic) stimulation can be bothersome and may thus limit therapy. Burst ONS produces paresthesia-free stimulation, but the amount of evidence on the efficacy of burst ONS as a treatment for intractable CCH is scarce.
In this case series, we report 15 patients with CCH treated with ONS at Aarhus University Hospital, Denmark, from 2013 to 2020. Nine of these received burst stimulation either as primary treatment or as a supplement to tonic stimulation. The results were assessed in terms of the frequency of headache attacks per week and their intensity on the Numeric Rating Scale, as well as the Patient Global Impression of Change (PGIC) with ONS treatment.
At a median (range) follow-up of 38 (16-96) months, 12 of the 15 patients (80%) reported a reduction in attack frequency of ≥50% (a reduction from a median of 35 to 1 attack/week, p < 0.001). Seven of these patients were treated with burst ONS. A significant reduction was also seen in maximum pain intensity. Overall, 10 patients stated a clinically important improvement in their headache condition following ONS treatment, rated on the PGIC scale. A total of 16 adverse events (nine of which were in the same patient) were registered.
Occipital nerve stimulation significantly reduced the number of weekly headache attacks and their intensity. Burst ONS seems to function well alone or as a supplement to conventional tonic ONS as a preventive treatment for CCH; however, larger prospective studies are needed to determine whether the effect can be confirmed and whether the efficacy of the two stimulation paradigms is even.

UNASSIGNED: Cluster headache (CH) is a trigeminal autonomic cephalalgia characterized by attacks of severe unilateral pain associated with ipsilateral autonomic symptoms. Cluster headache attacks exhibit nocturnal predilection, and sleep disorders could be the first manifestation of an incipient cluster period. Sleep alterations in cluster headache patients may reflect the pivotal role of the hypothalamus, which is crucially involved in the pathophysiology of this primary headache. We describe the case of a patient affected by episodic cluster headache who experienced a sleep disorder after starting therapy with verapamil.
UNASSIGNED: A 47-year-old man was affected by episodic cluster headache, characterized by attacks of excruciating pain in the left orbital and temporal regions, associated with prominent ipsilateral vegetative symptoms. Headaches occurred during the night, with one or two nocturnal attacks appearing at 11.30-12 p.m. and 4-4.30 a.m. Preventive treatment with verapamil was started, with immediate pain relief. Later, he experienced consecutive nocturnal awakenings for a couple of weeks, always at the same time, without any pain or autonomic symptoms. He was not agitated and did not need to get out of bed; after the awakenings, he reported sleep disturbances with vivid dreams.
UNASSIGNED: This case represents the first description of recurrent cyclic nocturnal awakenings, without pain and autonomic symptoms, in a patient with episodic cluster headache during the active phase of a cluster bout. Nocturnal awakenings, started after the introduction of effective preventive therapy, might be an unusual form of \"ghost attacks.\" After the beginning of prophylactic therapy, patients often describe mild pain or localized pressure in the same localization of CH attack. Similarly, the appearance of sleep disturbances, without any pain or vegetative symptoms, should be regarded as a warning sign of a still active cluster bout. Since these manifestations may influence therapeutic management, they should be carefully investigated.

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Although coronavirus disease 2019 (COVID-19) mainly exhibits respiratory symptoms, neurological symptoms are also reported, with headache being the most common neurological symptom. Headache associated with COVID-19 is widely reported. However, there are few precise case reports concerning headaches in patients with a history of migraine, tension headaches, or cluster headaches associated with COVID-19. Herein, we report a case of a woman with a history of cluster headaches who showed an unusually severe bout 10 days before typical COVID-19 symptoms. Such a case has not been reported until now.