45 research outputs found
Diagnosis and treatment evaluation in patients with spontaneous intracranial hypotension
Spontaneous intracranial hypotension is characterized by an orthostatic headache and audiovestibular symptoms alongside a myriad of other non-specific symptoms. It is caused by an unregulated loss of cerebrospinal fluid at the spinal level. Indirect features of CSF leaks are seen on brain imaging as signs of intracranial hypotension and/or CSF hypovolaemia as well as a low opening pressure on lumbar puncture. Direct evidence of CSF leaks can frequently, but not invariably, be observed on spinal imaging. The condition is frequently misdiagnosed due to its vague symptoms and a lack of awareness of the condition amongst the non-neurological specialities. There is also a distinct lack of consensus on which of the many investigative and treatment options available to use when managing suspected CSF leaks. The aim of this article is to review the current literature on spontaneous intracranial hypotension and its clinical presentation, preferred investigation modalities, and most efficacious treatment options. By doing so, we hope to provide a framework on how to approach a patient with suspected spontaneous intracranial hypotension and help minimize diagnostic and treatment delays in order to improve clinical outcomes
Phenotype of new daily persistent headache: subtypes and comparison to transformed chronic daily headache
BACKGROUND: It is unknown whether new daily persistent headache (NDPH) is a single disorder or heterogenous group of disorders, and whether it is a unique disorder from chronic migraine and chronic tension-type headache. We describe a large group of patients with primary NDPH, compare its phenotype to transformed chronic daily headache (T-CDH), and use cluster analysis to reveal potential sub-phenotypes in the NDPH group. METHODS: We performed a case-control study using prospectively collected clinical data in patients with primary NDPH and T-CDH (encompassing chronic migraine and chronic tension-type headache). We used logistic regression with propensity score matching to compare demographics, phenotype, comorbidities, and treatment responses between NDPH and T-CDH. We used K-means cluster analysis with Gower distance to identify sub-clusters in the NDPH group based on a combination of demographics, phenotype, and comorbidities. RESULTS: We identified 366 patients with NDPH and 696 with T-CDH who met inclusion criteria. Patients with NDPH were less likely to be female (62.6% vs. 73.3%, p < 0.001). Nausea, vomiting, photophobia, phonophobia, motion sensitivity, vertigo, and cranial autonomic symptoms were all significantly less frequent in NDPH than T-CDH (p value for all < 0.001). Acute treatments appeared less effective in NDPH than T-CDH, and medication overuse was less common (16% vs. 42%, p < 0.001). Response to most classes of oral preventive treatments was poor in both groups. The most effective treatment in NDPH was doselupin in 45.7% patients (95% CI 34.8-56.5%). Cluster analysis identified three subgroups of NDPH. Cluster 1 was older, had a high proportion of male patients, and less severe headaches. Cluster 2 was predominantly female, had severe headaches, and few associated symptoms. Cluster 3 was predominantly female with a high prevalence of migrainous symptoms and headache triggers. CONCLUSIONS: Whilst there is overlap in the phenotype of NDPH and T-CDH, the differences in migrainous, cranial autonomic symptoms, and vulnerability to medication overuse suggest that they are not the same disorder. NDPH may be fractionated into three sub-phenotypes, which require further investigation
New daily persistent headache: A systematic review and meta-analysis
OBJECTIVE: To perform a systematic review and meta-analysis of the epidemiology, precipitants, phenotype, comorbidities, pathophysiology, treatment, and prognosis of primary new daily persistent headache. METHODS: We searched PubMed/Medline, EMBASE, Cochrane, and clinicaltrials.gov until 31 December 2022. We included original research studies with any design with at least five participants with new daily persistent headache. We assessed risk of bias using National Institutes of Health Quality Assessment Tools. We used random-effects meta-analysis where suitable to calculate pooled estimates of proportions. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis compliant study is registered with PROSPERO (registration number CRD42022383561). RESULTS: Forty-six studies met inclusion criteria, predominantly case series, including 2155 patients. In 67% (95% CI 57-77) of cases new daily persistent headache has a chronic migraine phenotype, however new daily persistent headache has been found to be less likely than chronic migraine to be associated with a family history of headache, have fewer associated migrainous symptoms, be less vulnerable to medication overuse, and respond less well to injectable and neuromodulatory treatments. CONCLUSIONS: New daily persistent headache is a well described, recognisable disorder, which requires further research into its pathophysiology and treatment. There is a lack of high-quality evidence and, until this exists, we recommend continuing to consider new daily persistent headache a distinct disorder
Cytokines in primary headache disorders: a systematic review and meta-analysis
BACKGROUND: The role of inflammation and cytokines in the pathophysiology of primary headache disorders is uncertain. We performed a systematic review and meta-analysis to synthesise the results of studies comparing peripheral blood cytokine levels between patients with migraine, tension-type headache, cluster headache, or new daily persistent headache (NDPH), and healthy controls; and in migraine between the ictal and interictal stages. METHODS: We searched PubMed/Medline and Embase from inception until July 2022. We included original research studies which measured unstimulated levels of any cytokines in peripheral blood using enzyme-linked immunosorbent assay or similar assay. We assessed risk of bias using the Newcastle-Ottawa Quality Assessment Scale. We used random effects meta-analysis with inverse variance weighted average to calculate standardised mean difference (SMD), 95% confidence intervals, and heterogeneity for each comparison. This study is registered with PROSPERO (registration number CRD42023393363). No funding was received for this study. RESULTS: Thirty-eight studies, including 1335 patients with migraine (32 studies), 302 with tension-type headache (nine studies), 42 with cluster headache (two studies), and 1225 healthy controls met inclusion criteria. Meta-analysis showed significantly higher interleukin (IL)-6 (SMD 1.07, 95% CI 0.40-1.73, p = 0.002), tumour necrosis factor (TNF)-α (SMD 0.61, 95% CI 0.14-1.09, p = 0.01), and IL-8 (SMD 1.56, 95% CI 0.03-3.09, p = 0.04), in patients with migraine compared to healthy controls, and significantly higher interleukin-1β (IL-1β) (SMD 0.34, 95% CI 0.06-0.62, p = 0.02) during the ictal phase of migraine compared to the interictal phase. Transforming growth factor (TGF)-β (SMD 0.52, 95% CI 0.18-0.86, p = 0.003) and TNF-α (SMD 0.64, 95% CI 0.33-0.96, p = 0.0001) were both higher in patients with tension-type headache than controls. CONCLUSIONS: The higher levels of the proinflammatory cytokines IL-6, IL-8 and TNF-α in migraine compared to controls, and IL-1β during the ictal stage, suggest a role for inflammation in the pathophysiology of migraine, however prospective studies are required to confirm causality and investigate the mechanisms for the increase in cytokine levels identified. Cytokines may also have a role in tension-type headache. Due a lack of data, no conclusions can be made regarding cluster headache or NDPH
Patient experience of diagnosis and management of spontaneous intracranial hypotension: a cross-sectional online survey
OBJECTIVES: To present the results of a survey of patients with spontaneous intracranial hypotension (SIH) secondary to spinal cerebrospinal fluid (CSF) leak, documenting the patient experience of its diagnosis and management as well as quantifying its impact on quality of life. DESIGN: A cross-sectional anonymous online survey was designed in conjunction with the CSF Leak Association patient charity. The survey included questions on diagnosis, investigations and treatments received, as well as validated disability and quality of life questionnaires. PARTICIPANTS: Sixty-four patients with a confirmed diagnosis of SIH who were receiving treatment within the UK were included in the analysis. The mean age was 42.8 years, 94% were female and 43 had ongoing symptoms of SIH. RESULTS: Patients who presented to their general practitioner with symptoms of SIH were seen an average three times before being referred to a specialist, and in just under half of patients, the diagnosis was not made by the first specialist they saw. There was variability in which investigations were performed and how urgently they were organised. The mean EuroQol (EQ-5D-5L) Visual Analogue Scale score was 36.4/100 and median Headache Impact Test-6 score was 68/78 (very severe impact). More than half of the respondents reported that they had to amend work duties due to SIH, more than a quarter reported that they had lost their job and two-thirds reported that their condition had affected their financial health. Only 23.4% of patients felt that they had received enough help and advice to manage their pain due to SIH. CONCLUSIONS: SIH is a highly disabling disorder, affecting multiple domains, including pain, mobility, activities of daily living, financial circumstances and employment. Diagnostic delay and misdiagnosis are common, and currently there is a lack of consistency in the investigation and management of SIH in the UK
An open-label observational study and meta-analysis of non-invasive vagus nerve stimulation in medically refractory chronic cluster headache
BACKGROUND: Many patients with cluster headache (CH) are inadequately controlled by current treatment options. Non-invasive vagus nerve stimulation (nVNS) is reported to be effective in the management of CH though some studies suggest that it is ineffective. OBJECTIVE: To assess the safety and efficacy of nVNS in chronic cluster headache (CCH) patients. METHOD: We prospectively analysed data from 40 patients with refractory CCH in this open-label, observational study. Patients were seen in tertiary headache clinics at the National Hospital for Neurology and Neurosurgery and trained to use nVNS as preventative therapy. Patients were reivewed at one month and then three-monthly from onset. The primary endpoint was number of patients achieving ≥50% reduction in attack frequency at 3  months. A meta-analysis of all published studies evaluating the efficacy of nVNS in CCH was also conducted. We searched MEDLINE and EMBASE for all studies investigating the use of nVNS as a preventive or adjunctive treatment for CCH with five or more participants. Combined mean difference and responder proportions with 95% confidence intervals (CI) were calculated from the included studies. RESULTS: 17/40 patients (43%) achieved ≥50% reduction in attack frequency at 3  months. There was a significant reduction in monthly attack frequency from a baseline of 124 (±67) attacks to 79 (±63) attacks in month 3 (mean difference 44.7; 95% CI 25.1 to 64.3; p < 0.001). In month 3, there was also a 1.2-point reduction in average severity from a baseline Verbal Rating Scale of 8/10 (95% CI 0.5 to 1.9; p = 0.001). Four studies, along with the present study, were deemed eligible for meta-analysis, which showed a responder proportion of 0.35 (95% CI 0.07 to 0.69, n = 137) and a mean reduction in headache frequency of 35.3 attacks per month (95% CI 11.0 to 59.6, n = 108), from a baseline of 105 (±22.7) attacks per month. CONCLUSION: This study highlights the potential benefit of nVNS in CCH, with significant reductions in headache frequency and severity. To better characterise the effect, randomised sham-controlled trials are needed to confirm the beneficial response of VNS reported in some, but not all, open-label studies
Trigeminal microvascular decompression for short-lasting unilateral neuralgiform headache attacks
A significant proportion of patients with short-lasting unilateral neuralgiform headache attacks (SUNHA) are refractory to medical treatments. Neuroimaging studies have suggested a role for ipsilateral trigeminal neurovascular conflict with morphological changes in the pathophysiology of this disorder. We present the outcome of an uncontrolled open-label prospective single centre study conducted between 2012 and 2020, to evaluate the efficacy and safety of trigeminal microvascular decompression in refractory chronic SUNHA with magnetic resonance imaging evidence of trigeminal neurovascular conflict ipsilateral to the pain side. Primary endpoint was the proportion of patients who achieved an "excellent response", defined as 90-100% weekly reduction in attack frequency, or "good response", defined as a reduction in weekly headache attack frequency between 75% and 89% at final follow-up, compared to baseline. These patients were defined as responders. The study group consisted of 47 patients of whom 31 had SUNCT and 16 had SUNA (25 females, mean age ± SD 55.2 years ± 14.8). Participants failed to respond or tolerate a mean of 8.1 (±2.7) preventive treatments pre-surgery. Magnetic resonance imaging of the trigeminal nerves (n = 47 patients, n = 50 symptomatic trigeminal nerves) demonstrated ipsilateral neurovascular conflict with morphological changes in 39/50 (78.0%) symptomatic nerves and without morphological changes in 11/50 (22.0%) symptomatic nerves. Post-operatively, 37/47 (78.7%) patients obtained either an excellent or a good response. Ten patients (21.3%, SUNCT = 7 and SUNA = 3) reported no post-operative improvement. The mean post-surgery follow-up was 57.4 ± 24.3 months (range 11-96 months). At final follow-up, 31 patients (66.0%) were excellent/good responders. Six patients experienced a recurrence of headache symptoms. There was no statistically significant difference between SUNCT and SUNA in the response to surgery (p = 0.463). Responders at the last follow-up were however more likely not to have interictal pain (77.42% vs 22.58%, p = 0.021) and to show morphological changes on the magnetic resonance imaging (78.38% vs 21.62%, p = 0.001). The latter outcome was confirmed in the Kaplan Meyer analysis, where patients with no morphological changes were more likely to relapse overtime compared to those with morphological changes (p = 0.0001). All but one patient who obtained an excellent response without relapse, discontinued their preventive medications. Twenty-two post-surgery adverse events occurred in 18 patients (46.8%) but no mortality or severe neurological deficit was seen. Trigeminal microvascular decompression may be a safe and effective long-term treatment for short-lasting unilateral neuralgiform headache attacks patients with magnetic resonance evidence of neurovascular conflict with morphological changes
The prevalence of headache disorders in Postural Tachycardia Syndrome: A systematic review and meta-analysis of the literature
BACKGROUND: Headache is a common presentation of postural tachycardia syndrome, yet robust prevalence data is lacking. OBJECTIVES: To undertake a systematic review and meta-analysis to estimate the prevalence of headache disorders in postural tachycardia syndrome, and to explore the potential shared pathophysiological mechanisms that underpin these conditions as well as treatment options. METHODS: Three databases were searched for publications evaluating prevalence of migraine (primary outcome) and general and orthostatic headache (secondary outcomes) in patients with postural tachycardia syndrome. Two independent reviewers selected studies and extracted data. A random-effects meta-analysis calculated the pooled prevalence of migraine in postural tachycardia syndrome. A narrative literature review explored the pathophysiology and treatment options for concurrent headache disorders and postural tachycardia syndrome. RESULTS: Twenty-three articles met inclusion criteria. Estimated pooled prevalence of migraine in postural tachycardia syndrome was 36.8% (95% CI 2.9-70.7%). Various shared pathophysiological pathways for these conditions, as well as proposed treatment strategies, were identified.Limitations: Heterogeneity of study design, populations, and methodology for identifying headache disorders and postural tachycardia syndrome limited the generalisability of results. CONCLUSIONS: Migraine is a commonly reported comorbidity in POTS, however the true prevalence cannot be determined from the current literature. Further studies are required to assess this comorbidity and investigate the underlying mechanisms, as well as identify effective treatment strategies
Autonomic symptoms in migraine: Results of a prospective longitudinal study
OBJECTIVES:
To assess the prevalence and burden of autonomic symptoms in migraine, and determine the relationship with migraine frequency.
BACKGROUND:
Autonomic symptoms in migraine have been theorized to occur in the setting of inter-ictal sympathetic hypoactivity and hyper-sensitivity. There is limited data prospectively assessing cranial and extra-cranial autonomic symptoms with a validated instrument, or longitudinal data on the relationship between migraine disease activity and autonomic symptoms.
METHODS:
Patients attending a single tertiary academic center were recruited into a prospective cohort study between September 2020 and June 2022. In addition to standard clinical care, they completed several surveys including the Composite Autonomic Symptom Scale (COMPASS-31) questionnaire, a validated survey of autonomic symptoms.
RESULTS:
A total of 43 patients (66.7% female, median age 42, IQR 17) were included in the final analysis. There was a baseline 20 monthly headache days (MHD) (IQR 21.7), and 65.1% of the population had chronic migraine by ICHD-3 criteria. A significantly elevated weighted COMPASS-31 score was reported in 60.5% of respondents (mean 30.3, SD 13.3) at baseline. After 12 months treatment, significant improvements were reported in migraine frequency (median MHD 20–8.7) and disability (median Migraine Disability Assessment Score 67–48), but not in autonomic symptoms (mean score 30.3, SD 11.2).
CONCLUSIONS:
Autonomic symptoms were frequently reported in patients with migraine. However, they did not correlate with headache frequency or reversion to episodic frequency. Further study is required to elucidate specific approaches and treatments for autonomic symptoms, and further evaluate the underlying pathophysiological mechanisms
An open-label observational study and meta-analysis of non-invasive vagus nerve stimulation in medically refractory chronic cluster headache
BackgroundMany patients with cluster headache (CH) are inadequately controlled by current treatment options. Non-invasive vagus nerve stimulation (nVNS) is reported to be effective in the management of CH though some studies suggest that it is ineffective.ObjectiveTo assess the safety and efficacy of nVNS in chronic cluster headache (CCH) patients.MethodWe prospectively analysed data from 40 patients with refractory CCH in this open-label, observational study. Patients were seen in tertiary headache clinics at the National Hospital for Neurology and Neurosurgery and trained to use nVNS as preventative therapy. Patients were reivewed at one month and then three-monthly from onset. The primary endpoint was number of patients achieving ≥50% reduction in attack frequency at 3  months. A meta-analysis of all published studies evaluating the efficacy of nVNS in CCH was also conducted. We searched MEDLINE and EMBASE for all studies investigating the use of nVNS as a preventive or adjunctive treatment for CCH with five or more participants. Combined mean difference and responder proportions with 95% confidence intervals (CI) were calculated from the included studies.Results17/40 patients (43%) achieved ≥50% reduction in attack frequency at 3  months. There was a significant reduction in monthly attack frequency from a baseline of 124 (±67) attacks to 79 (±63) attacks in month 3 (mean difference 44.7; 95% CI 25.1 to 64.3; p < 0.001). In month 3, there was also a 1.2-point reduction in average severity from a baseline Verbal Rating Scale of 8/10 (95% CI 0.5 to 1.9; p = 0.001). Four studies, along with the present study, were deemed eligible for meta-analysis, which showed a responder proportion of 0.35 (95% CI 0.07 to 0.69, n = 137) and a mean reduction in headache frequency of 35.3 attacks per month (95% CI 11.0 to 59.6, n = 108), from a baseline of 105 (±22.7) attacks per month.ConclusionThis study highlights the potential benefit of nVNS in CCH, with significant reductions in headache frequency and severity. To better characterise the effect, randomised sham-controlled trials are needed to confirm the beneficial response of VNS reported in some, but not all, open-label studies