Epidemiology and clinical features of paroxysmal hemicrania: A systematic review and meta-analysis.

OBJECTIVE: To assess the prevalence or relative frequency of paroxysmal hemicrania and its clinical features in the adult general population and among adult patients evaluated for headache in tertiary care. BACKGROUND: Paroxysmal hemicrania is a rare trigeminal autonomic cephalalgia with characteristic attacks of headache, associated cranial autonomic symptoms and signs, and an absolute response to indomethacin. Its epidemiological burden remains unknown in both the adult general population and among adult patients evaluated for headache in a tertiary care setting. Moreover, the frequencies of the clinical features associated with paroxysmal hemicrania have not been well established. METHODS: A literature search of PubMed and Embase was conducted from January 1, 1988, to January 20, 2023. Eligible for inclusion were observational studies reporting the point prevalence or relative frequency of paroxysmal hemicrania or its clinical features in the adult general population or among adult patients evaluated for headache in tertiary care. Two independent investigators (M.J.H. and J.G.L.) performed the title, abstract, and full-text article screening. Each included study's risk of bias was critically appraised using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data. Estimates of prevalence or relative frequency were calculated using a random-effects meta-analysis. The between-study heterogeneity was assessed using the I2 statistic and further explored with meta-regression. This study was pre-registered on PROSPERO (identifier: CRD42023391127). RESULTS: A total of 17 clinic-based studies and one population-based study met the eligibility criteria. Importantly, an overall high risk of bias was observed across the eligible studies. The relative frequency of paroxysmal hemicrania was estimated to be 0.3% (95% CI, 0.2%-0.5%) among adult patients evaluated for headache in tertiary care with considerable heterogeneity (I2 = 76.4%). No cases with paroxysmal hemicrania were identified among 1,838 participants in a population-based sample. Moreover, the most prevalent cranial autonomic symptoms were lacrimation (77.3% [95% Cl, 62.7%-87.3%]), conjunctival injection (75.0% [95% Cl, 60.3%-85.6%]), and nasal congestion (47.7% [95% Cl, 33.6%-62.3%]). CONCLUSIONS: Our findings suggest that paroxysmal hemicrania is a rare disorder among adults evaluated for headache in tertiary care, while its prevalence in the general population remains unknown. Further studies focusing on the clinical features of paroxysmal hemicrania are warranted.

Interventions for altering blood pressure in people with acute subarachnoid haemorrhage.

BACKGROUND: Subarachnoid haemorrhage has an incidence of up to nine per 100,000 person-years. It carries a mortality of 30% to 45% and leaves 20% dependent in activities of daily living. The major causes of death or disability after the haemorrhage are delayed cerebral ischaemia and rebleeding. Interventions aimed at lowering blood pressure may reduce the risk of rebleeding, while the induction of hypertension may reduce the risk of delayed cerebral ischaemia. Despite the fact that medical alteration of blood pressure has been clinical practice for more than three decades, no previous systematic reviews have assessed the beneficial and harmful effects of altering blood pressure (induced hypertension or lowered blood pressure) in people with acute subarachnoid haemorrhage. OBJECTIVES: To assess the beneficial and harmful effects of altering arterial blood pressure (induced hypertension or lowered blood pressure) in people with acute subarachnoid haemorrhage. SEARCH METHODS: We searched the following from inception to 8 September 2020 (Chinese databases to 27 January 2019): Cochrane Stroke Group Trials register; CENTRAL; MEDLINE; Embase; five other databases, and five trial registries. We screened reference lists of review articles and relevant randomised clinical trials. SELECTION CRITERIA: Randomised clinical trials assessing the effects of inducing hypertension or lowering blood pressure in people with acute subarachnoid haemorrhage. We included trials irrespective of publication type, status, date, and language. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data. We assessed the risk of bias of all included trials to control for the risk of systematic errors. We performed trial sequential analysis to control for the risks of random errors. We also applied GRADE. Our primary outcomes were death from all causes and death or dependency. Our secondary outcomes were serious adverse events, quality of life, rebleeding, delayed cerebral ischaemia, and hydrocephalus. We assessed all outcomes closest to three months' follow-up (primary point of interest) and maximum follow-up. MAIN RESULTS: We included three trials: two trials randomising 61 participants to induced hypertension versus no intervention, and one trial randomising 224 participants to lowered blood pressure versus placebo. All trials were at high risk of bias. The certainty of the evidence was very low for all outcomes. Induced hypertension versus control Two trials randomised participants to induced hypertension versus no intervention. Meta-analysis showed no evidence of a difference between induced hypertension versus no intervention on death from all causes (risk ratio (RR) 1.60, 95% confidence interval (CI) 0.57 to 4.42; P = 0.38; I2 = 0%; 2 trials, 61 participants; very low-certainty evidence). Trial sequential analyses showed that we had insufficient information to confirm or reject our predefined relative risk reduction of 20% or more. Meta-analysis showed no evidence of a difference between induced hypertension versus no intervention on death or dependency (RR 1.29, 95% CI 0.78 to 2.13; P = 0.33; I2 = 0%; 2 trials, 61 participants; very low-certainty evidence). Trial sequential analyses showed that we had insufficient information to confirm or reject our predefined relative risk reduction of 20% or more. Meta-analysis showed no evidence of a difference between induced hypertension and control on serious adverse events (RR 2.24, 95% CI 1.01 to 4.99; P = 0.05; I2 = 0%; 2 trials, 61 participants; very low-certainty evidence). Trial sequential analysis showed that we had insufficient information to confirm or reject our predefined relative risk reduction of 20% or more. One trial (41 participants) reported quality of life using the Stroke Specific Quality of Life Scale. The induced hypertension group had a median of 47 points (interquartile range 35 to 55) and the no-intervention group had a median of 49 points (interquartile range 35 to 55). The certainty of evidence was very low. One trial (41 participants) reported rebleeding. Fisher's exact test (P = 1.0) showed no evidence of a difference between induced hypertension and no intervention on rebleeding. The certainty of evidence was very low. Trial sequential analysis showed that we had insufficient information to confirm or reject our predefined relative risk reduction of 20% or more. One trial (20 participants) reported delayed cerebral ischaemia. Fisher's exact test (P = 1.0) showed no evidence of a difference between induced hypertension and no intervention on delayed cerebral ischaemia. The certainty of the evidence was very low. Trial sequential analysis showed that we had insufficient information to confirm or reject our predefined relative risk reduction of 20% or more. None of the trials randomising participants to induced hypertension versus no intervention reported on hydrocephalus. No subgroup analyses could be conducted for trials randomising participants to induced hypertension versus no intervention. Lowered blood pressure versus control One trial randomised 224 participants to lowered blood pressure versus placebo. The trial only reported on death from all causes. Fisher's exact test (P = 0.058) showed no evidence of a difference between lowered blood pressure versus placebo on death from all causes. The certainty of evidence was very low. AUTHORS' CONCLUSIONS: Based on the current evidence, there is a lack of information needed to confirm or reject minimally important intervention effects on patient-important outcomes for both induced hypertension and lowered blood pressure. There is an urgent need for trials assessing the effects of altering blood pressure in people with acute subarachnoid haemorrhage. Such trials should use the SPIRIT statement for their design and the CONSORT statement for their reporting. Moreover, such trials should use methods allowing for blinded altering of blood pressure and report on patient-important outcomes such as mortality, rebleeding, delayed cerebral ischaemia, quality of life, hydrocephalus, and serious adverse events.

Early trigeminal nerve involvement in Listeria monocytogenes rhombencephalitis: case series and systematic review.

Listeria monocytogenes is associated with rhombencephalitis. However, the exact mechanisms of brainstem invasion remains poorly understood. Here, we demonstrate clinical and radiological data suggesting that Listeria may invade the brainstem via the trigeminal nerve. Three females (41, 64 and 70 years) with culture proven L. monocytogenes bacteremia and rhombencephalitis were investigated in the period of 2014-16. T2-weighted and contrast-enhanced T1-weighted MRI revealed a cerebellopontine abscess in all three patients, including the involvement of the trigeminal nerve root. In two patients, MRI also revealed selective contrast enhancement of the sensory trigeminal tract in the pons and medulla oblongata. Prior to any other neurological symptoms, two patients complained of hypoesthesia and a tingling sensation in the ipsilateral half of the face, consistent with sensory trigeminal nerve dysfunction on that side. In addition, we identified another 120 cases of Listeria rhombencephalitis following a systematic review. Cranial nerves VII, V, IX, and X, respectively, medulla oblongata, cerebellum and pons, were the most frequently involved brain structures. The present clinical and radiological findings corroborate earlier data from animal experiments, indicating that L. monocytogenes may be capable of retrograde intra-axonal migration along the cranial nerves. We suggest that in a subset of patients with rhombencephalitis L. monocytogenes enters the cerebellopontine angle through the trigeminal nerve, invading the brainstem via the sensory trigeminal nuclei.

l-arginine and l-NMMA for assessing cerebral endothelial dysfunction in ischaemic cerebrovascular disease: A systematic review.

Endothelial dysfunction (ED), in particular cerebral ED, may be an essential biomarker for ischaemic cerebrovascular disease. However, there is no consensus on methods to best estimate cerebral ED. In this systematic review, we evaluate the use of l-arginine and NG -monomethyl-l-arginine (l-NMMA) for assessment of cerebral ED. A systematic search of PubMed, EMBASE and the Cochrane Library was done. We included studies investigating cerebrovascular response to l-arginine or l-NMMA in human subjects with vascular risk factors or ischaemic cerebrovascular disease. Seven studies (315 subjects) were eligible according to inclusion and exclusion criteria. Studies investigated the effect of age (n=2), type 2 diabetes mellitus (DM) (n=1), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) (n=1), leukoaraiosis (n=1), and prior ischaemic stroke or transient ischaemic attack (TIA) (n=2) on cerebral ED. Most studies applied transcranial Doppler to quantify cerebral ED. Endothelium-dependent vasodilatation (EDV) induced by l-arginine was impaired in elderly and subjects with leukoaraiosis, but enhanced in CADASIL patients. Studies including subjects with prior ischaemic stroke or TIA reported both enhanced and impaired EDV to l-arginine. Responses to l-NMMA deviated between subjects with type 2 DM and the elderly. We found only few studies investigating cerebral endothelial responses to l-arginine and l-NMMA in subjects with vascular risk factors or ischaemic cerebrovascular disease. Inconsistencies in results were most likely due to variations in methods and included subject populations. In order to use cerebral ED as a prognostic marker, further studies are required to evaluate the association to cerebrovascular disease.

The diagnostic accuracy of carcinoembryonic antigen to detect colorectal cancer recurrence - A systematic review.

INTRODUCTION: Carcinoembryonic Antigen (CEA) has been used as a tumor marker in the follow-up of colorectal cancer for more than 40 years. Controversy exists regarding its diagnostic applicability due to a relatively low sensitivity and a questionable effect on mortality. The aim of this review was to assess the diagnostic accuracy of CEA in detecting recurrence after intended curative surgery for primary colorectal cancer. METHODS: Systematic literature searches were performed in PubMed, EMBASE and Cochrane databases, and articles were chosen based on predefined inclusion criteria. Reference lists from included articles were manually searched for additional publications of relevance. RESULTS: Forty-two original studies with generally representative populations and long follow-up were included. Data were reported on outcomes from 9,834 CEA tests during follow-up. Reporting on the reference standards used was not optimal. Sensitivity of CEA ranged from 17.4 % to 100 %, specificity ranged from 66.1 % to 98.4 %, positive predictive value ranged from 45.8 % to 95.2% and negative predictive value ranged from 74.5 % to 100 %. CONCLUSION: Results point toward a sensitivity of CEA ranging between 50 % and 80 %, and a specificity and negative predictive value above 80 %. Results on positive predictive value showed low reliability. Overall, CEA did not effectively detect treatable recurrences at an early stage, and a clinically relevant effect on patient mortality remains to be proven.