Translating the Cluster Headache Quality of Life Questionnaire (CHQ) from English to Dutch with the TRAPD method.

OBJECTIVE: Cluster headache is associated with a decreased quality of life (QoL). The increased focus on patient-reported outcome measures (PROMS) has led to the creation of a tailored Cluster Headache Quality of Life scale (CHQ). Our objective was to create and authenticate a Dutch version of the CHQ (CHQ-D). METHODS: The TRAPD model (Translation, Review, Adjudication, Pretesting, Documentation) was used to translate the CHQ from English to Dutch and ensure cross-cultural adaption. Pre-testing was performed in n = 31 participants, and validity was in a new sample of n = 40 participants who completed the CHQ twice at a 2-day interval. Intraclass correlation coefficient (ICC) and Cronbach's alpha were used to assess the validity and reproducibility of the CHQ-D. RESULTS: To produce the CHQ-D, we made five modifications based on pretesting. Participants finished the questionnaire in a median time of 10 min (IQR:10.0, 17.5) and 90% within 20 min. The majority of participants (74.2%) did not find it burdensome at all. The reliability of the CHQ-D was excellent (Cronbach's alpha: 0.94; ICC: 0.94). CONCLUSION: The CHQ-D is a valid and practical instrument for QoL in individuals with cluster headache. We aim to use CHQ-D as PROM in clinical research in the Netherlands to enforce international collaborations and comparisons of studies.

Intra- and interindividual attack frequency variability of chronic cluster headache.

BACKGROUND: The lack of knowledge about the intra- and interindividual attack frequency variability in chronic cluster headache complicates power and sample size calculations for baseline periods of trials, and consensus on their most optimal duration. METHODS: We analyzed the 12-week baseline of the ICON trial (occipital nerve stimulation in medically intractable chronic cluster headache) for: (i) weekly vs. instantaneous recording of attack frequency; (ii) intra-individual and seasonal variability of attack frequency; and (iii) the smallest number of weeks to obtain a reliable estimate of baseline attack frequency. RESULTS: Weekly median (14.4 [8.2-24.0]) and instantaneous (14.2 [8.0-24.5]) attack frequency recordings were similar (p = 0.20; Bland-Altman plot). Median weekly attack frequency was 15.3 (range 4.2-140) and highest during spring (p = 0.001) compared to the other seasons. Relative attack frequency variability decreased with increasing attack frequency (p = 0.010). We tabulated the weekly attack frequency estimation accuracies compared to, and the associated deviations from, the 12-week gold standard for different lengths of the observation period. CONCLUSION: Weekly retrospective attack frequency recording is as good as instantaneous recording and more convenient. Attack frequency is highest in spring. Participants with ≥3 daily attacks show less attack frequency variability than those with <3 daily attacks. An optimal balance between 90% accuracy and feasibility is achieved at a baseline period of seven weeks.The ICON trial is registered in ClinicalTrials.gov under number NCT01151631.

Transient side shift of cluster headache attacks after unilateral greater occipital nerve injection.

Attacks of cluster headache (CH) are usually side-locked in most, but not all, patients. In a few patients, the side may alternate between or, rarely, within cluster episodes. We observed seven cases in whom the side of CH attacks temporarily shifted immediately or shortly after unilateral injection of the greater occipital nerve (GON) with corticosteroids. In five patients with previously side-locked CH attacks and in two patients with previously side-alternating CH attacks, a side shift for several weeks occurred immediately (N = 6) or shortly (N = 1) after GON injection. We concluded that unilateral GON injections might cause a transient side shift of CH attacks through inhibition of the ipsilateral hypothalamic attack generator causing relative overactivity of the contralateral side. The potential benefit of bilateral GON injection in patients who experienced a side shift after unilateral injection should be formally investigated.

COVID-19 vaccination-triggered cluster headache episodes with frequent attacks.

BACKGROUND: The pathophysiology of cluster headache and how cluster episodes are triggered, are still poorly understood. Recurrent inflammation of the trigeminovascular system has been hypothesized. It was noted that some long-term attack-free cluster headache patients suddenly developed a new cluster episode shortly after COVID-19 vaccination. METHODS: Cases are described from patients with cluster headache who reported a new cluster episode within days after COVID-19 vaccination. All cases were seen in a tertiary university referral center and a general hospital in the Netherlands between March 2021 and December 2021, when the first COVID-19 vaccinations were carried out in The Netherlands. Clinical characteristics of the previous and new cluster episodes, and time between the onset of a new cluster episode and a previous COVID-19 vaccination were reported. RESULTS: We report seven patients with cluster headache, who had been attack-free for a long time, in whom a new cluster episode occurred within a few days after a COVID-19 vaccination. INTERPRETATION: COVID-19 vaccinations may trigger new cluster episodes in patients with cluster headache, possibly by activating a pro-inflammatory state of the trigeminocervical complex. COVID-19 vaccinations may also exacerbate other neuroinflammatory conditions. .

Unilateral increased visual sensitivity in cluster headache: a cross-sectional study.

BACKGROUND AND OBJECTIVES: Increased sensitivity to light and patterns is typically associated with migraine, but has also been anecdotally reported in cluster headache, leading to diagnostic confusion. We wanted to assess whether visual sensitivity is increased ictally and interictally in cluster headache. METHODS: We used the validated Leiden Visual Sensitivity Scale (L-VISS) questionnaire (range 0-36 points) to measure visual sensitivity in people with episodic or chronic cluster headache: (i) during attacks; (ii) in-between attacks; and in episodic cluster headache (iii) in-between bouts. The L-VISS scores were compared with the L-VISS scores obtained in a previous study in healthy controls and participants with migraine. RESULTS: Mean L-VISS scores were higher for: (i) ictal vs interictal cluster headache (episodic cluster headache: 11.9 ± 8.0 vs. 5.2 ± 5.5, chronic cluster headache: 13.7 ± 8.4 vs 5.6 ± 4.8; p < 0.001); (ii) interictal cluster headache vs controls (5.3 ± 5.2 vs 3.6 ± 2.8, p < 0.001); (iii) interictal chronic cluster headache vs interictal ECH in bout (5.9 ± 0.5 vs 3.8 ± 0.5, p = 0.009), and (iv) interictal episodic cluster headache in bout vs episodic cluster headache out-of-bout (5.2 ± 5.5 vs. 3.7 ± 4.3, p < 0.001). Subjective visual hypersensitivity was reported by 110/121 (91%; 9 missing) participants with cluster headache and was mostly unilateral in 70/110 (64%) and ipsilateral to the ictal pain in 69/70 (99%) participants. CONCLUSION: Cluster headache is associated with increased ictal and interictal visual sensitivity. In contrast to migraine, this is mostly unilateral and ipsilateral on the side of the ictal pain.

Guidelines of the International Headache Society for Controlled Clinical Trials in Cluster Headache.

In 1995, a committee of the International Headache Society developed and published the first edition of the Guidelines for Controlled Trials of Drugs in Cluster Headache. These have not been revised. With the emergence of new medications, neuromodulation devices and trial designs, an updated version of the International Headache Society Guidelines for Controlled Clinical Trials in Cluster Headache is warranted. Given the scarcity of evidence-based data for cluster headache therapies, the update is largely consensus-based, but takes into account lessons learned from recent trials and demands by patients. It is intended to apply to both drug and neuromodulation treatments, with specific proposals for the latter when needed. The primary objective is to propose a template for designing high quality, state-of-the-art, controlled clinical trials of acute and preventive treatments in episodic and chronic cluster headache. The recommendations should not be regarded as dogma and alternative solutions to particular methodological problems should be explored in the future and scientifically validated.

Repeated greater occipital nerve injections with corticosteroids in medically intractable chronic cluster headache: a retrospective study.

INTRODUCTION: Current prophylactic drugs for cluster headache are associated with limited efficacy, serious side effects and poor tolerability. Greater occipital nerve injection (GON-injection) has been proven effective and safe as a single, one-time injection in episodic (ECH), and to a lesser extent, chronic cluster headache (CCH). We aim to analyse the effectiveness and safety of repeated GON-injections in medically intractable chronic cluster headache (MICCH). METHODS: Clinical data of all cluster headache patients who had received at least one GON-injection between 2014 and 2018 in our tertiary headache centre were retrieved from patients' medical records. Clinical history was taken as part of routine care shortly before and 6 weeks after GON-injection. RESULTS: We identified 47 MICCH patients (79 injections), and compared results with 22 non-MI CCH patients (30 injections) and 50 ECH patients (63 injections). Nineteen MICCH patients received repeated injections (32 in total, range 2-8). Rates of clinical relevant improvement to a first injection were similar in all groups (MICCH: 60%, non-MICCH 73%, ECH 76%; attack freedom: MICCH: 30%, non-MICCH 32%, ECH 43%). Furthermore, no difference in response to the first and second injection was shown between groups (all p > 0.29). Median effect duration in MICCH was 6 weeks (IQR 2.8-12 weeks). Side effects were only mild and local. CONCLUSION: In this retrospective analysis, first and repeated GON-injections were well-tolerated and equally effective in MICCH as in non-MICCH, and ECH.

Clinical symptoms of androgen deficiency in men with migraine or cluster headache: a cross-sectional cohort study.

BACKGROUND: To compare symptoms of clinical androgen deficiency between men with migraine, men with cluster headache and non-headache male controls. METHODS: We performed a cross-sectional study using two validated questionnaires to assess symptoms of androgen deficiency in males with migraine, cluster headache, and non-headache controls. Primary outcome was the mean difference in androgen deficiency scores. Generalized linear models were used adjusting for age, BMI, smoking and lifetime depression. As secondary outcome we assessed the percentage of patients reporting to score below average on four sexual symptoms (beard growth, morning erections, libido and sexual potency) as these items were previously shown to more specifically differentiate androgen deficiency symptoms from (comorbid) anxiety and depression. RESULTS: The questionnaires were completed by n = 534/853 (63%) men with migraine, n = 437/694 (63%) men with cluster headache and n = 152/209 (73%) controls. Responders were older compared to non-responders and more likely to suffer from lifetime depression. Patients reported more severe symptoms of clinical androgen deficiency compared with controls, with higher AMS scores (Aging Males Symptoms; mean difference ± SE: migraine 5.44 ± 0.90, p <  0.001; cluster headache 5.62 ± 0.99, p <  0.001) and lower qADAM scores (quantitative Androgen Deficiency in the Aging Male; migraine: - 3.16 ± 0.50, p <  0.001; cluster headache: - 5.25 ± 0.56, p <  0.001). Additionally, both patient groups more often reported to suffer from any of the specific sexual symptoms compared to controls (18.4% migraine, 20.6% cluster headache, 7.2% controls, p = 0.001). CONCLUSION: Men with migraine and cluster headache more often suffer from symptoms consistent with clinical androgen deficiency than males without a primary headache disorder.

A prospective open label 2-8 year extension of the randomised controlled ICON trial on the long-term efficacy and safety of occipital nerve stimulation in medically intractable chronic cluster headache.

BACKGROUND: We demonstrated in the randomised controlled ICON study that 48-week treatment of medically intractable chronic cluster headache (MICCH) with occipital nerve stimulation (ONS) is safe and effective. In L-ICON we prospectively evaluate its long-term effectiveness and safety. METHODS: ICON participants were enrolled in L-ICON immediately after completing ICON. Therefore, earlier ICON participants could be followed longer than later ones. L-ICON inclusion was stopped after the last ICON participant was enrolled in L-ICON and followed for ≥2 years by completing six-monthly questionnaires on attack frequency, side effects, subjective improvement and whether they would recommend ONS to others. Primary outcome was the change in mean weekly attack frequency 2 years after completion of the ICON study compared to baseline. Missing values for log-transformed attack-frequency were imputed for up to 5 years of follow-up. Descriptive analyses are presented as (pooled) geometric or arithmetic means and 95% confidence intervals. FINDINGS: Of 103 eligible participants, 88 (85%) gave informed consent and 73 (83%) were followed for ≥2 year, 61 (69%) ≥ 3 year, 33 (38%) ≥ 5 years and 3 (3%) ≥ 8.5 years. Mean (±SD) follow-up was 4.2 ± 2.2 years for a total of 370 person years (84% of potentially 442 years). The pooled geometric mean (95% CI) weekly attack frequency remained considerably lower after one (4.2; 2.8-6.3), two (5.1; 3.5-7.6) and five years (4.1; 3.0-5.5) compared to baseline (16.2; 14.4-18.3). Of the 49/88 (56%) ICON ≥50% responders, 35/49 (71%) retained this response and 15/39 (38%) ICON non-responders still became a ≥50% responder for at least half the follow-up period. Most participants (69/88; 78% [0.68-0.86]) reported a subjective improvement from baseline at last follow-up and 70/88 (81% [0.70-0.87]) would recommend ONS to others. Hardware-related surgery was required in 44/88 (50%) participants in 112/122 (92%) events (0.35 person-year-1 [0.28-0.41]). We didn't find predictive factors for effectiveness. INTERPRETATION: ONS is a safe, well-tolerated and long-term effective treatment for MICCH. FUNDING: The Netherlands Organisation for Scientific Research, the Dutch Ministry of Health, the NutsOhra Foundation from the Dutch Health Insurance Companies, and Medtronic.

Pharmacotherapy for Cluster Headache.

Cluster headache is characterised by attacks of excruciating unilateral headache or facial pain lasting 15 min to 3 h and is seen as one of the most intense forms of pain. Cluster headache attacks are accompanied by ipsilateral autonomic symptoms such as ptosis, miosis, redness or flushing of the face, nasal congestion, rhinorrhoea, peri-orbital swelling and/or restlessness or agitation. Cluster headache treatment entails fast-acting abortive treatment, transitional treatment and preventive treatment. The primary goal of prophylactic and transitional treatment is to achieve attack freedom, although this is not always possible. Subcutaneous sumatriptan and high-flow oxygen are the most proven abortive treatments for cluster headache attacks, but other treatment options such as intranasal triptans may be effective. Verapamil and lithium are the preventive drugs of first choice and the most widely used in first-line preventive treatment. Given its possible cardiac side effects, electrocardiogram (ECG) is recommended before treating with verapamil. Liver and kidney functioning should be evaluated before and during treatment with lithium. If verapamil and lithium are ineffective, contraindicated or discontinued because of side effects, the second choice is topiramate. If all these drugs fail, other options with lower levels of evidence are available (e.g. melatonin, clomiphene, dihydroergotamine, pizotifen). However, since the evidence level is low, we also recommend considering one of several neuromodulatory options in patients with refractory chronic cluster headache. A new addition to the preventive treatment options in episodic cluster headache is galcanezumab, although the long-term effects remain unknown. Since effective preventive treatment can take several weeks to titrate, transitional treatment can be of great importance in the treatment of cluster headache. At present, greater occipital nerve injection is the most proven transitional treatment. Other options are high-dose prednisone or frovatriptan.

Thalamus structure and function determine severity of cognitive impairment in multiple sclerosis.

OBJECTIVE: This study investigates whether changes in functional connectivity, diffusivity, and volume of the thalamus can explain different severities of cognitive impairment in multiple sclerosis (MS). METHODS: An inception cohort of 157 patients with MS (104 women, mean age 41 years), 6 years postdiagnosis, was divided into 3 groups: cognitively preserved (CP, n = 108), mildly cognitively impaired (MCI, n = 22), and more severely cognitively impaired (SCI, n = 27). These groups were matched to 47 healthy controls (HC, 28 women, mean age 41 years). Thalamic volume, thalamic skeleton diffusivity (fractional anisotropy [FA] and mean diffusivity [MD]), and thalamic resting-state functional connectivity (FC) were compared between groups. RESULTS: Thalamic volume was significantly lower in all patient groups compared to controls, with lowest volumes in patients with SCI, and no difference between CP and MCI. Thalamic skeleton FA was decreased in SCI compared to HC only; MD was increased in SCI compared to all other groups. Thalamic FC was increased in SCI with a total of 15 regions, mainly sensorimotor, frontal, and occipital parts of the brain. Thalamic volume, FC, and MD remained independent predictors in a linear regression model (R(2) = 0.46), together with male sex and a lower level of education. Lesion and whole-brain volumes were not significant predictors. CONCLUSIONS: These findings indicate that thalamic changes in structure and function are highly informative regarding overall cognitive performance in MS. Increased thalamic FC only became apparent in SCI, possibly as a sign of maladaption.