Multidisciplinary consensus guideline for the diagnosis and management of spontaneous intracranial hypotension.

BACKGROUND: We aimed to create a multidisciplinary consensus clinical guideline for best practice in the diagnosis, investigation and management of spontaneous intracranial hypotension (SIH) due to cerebrospinal fluid leak based on current evidence and consensus from a multidisciplinary specialist interest group (SIG). METHODS: A 29-member SIG was established, with members from neurology, neuroradiology, anaesthetics, neurosurgery and patient representatives. The scope and purpose of the guideline were agreed by the SIG by consensus. The SIG then developed guideline statements for a series of question topics using a modified Delphi process. This process was supported by a systematic literature review, surveys of patients and healthcare professionals and review by several international experts on SIH. RESULTS: SIH and its differential diagnoses should be considered in any patient presenting with orthostatic headache. First-line imaging should be MRI of the brain with contrast and the whole spine. First-line treatment is non-targeted epidural blood patch (EBP), which should be performed as early as possible. We provide criteria for performing myelography depending on the spine MRI result and response to EBP, and we outline principles of treatments. Recommendations for conservative management, symptomatic treatment of headache and management of complications of SIH are also provided. CONCLUSIONS: This multidisciplinary consensus clinical guideline has the potential to increase awareness of SIH among healthcare professionals, produce greater consistency in care, improve diagnostic accuracy, promote effective investigations and treatments and reduce disability attributable to SIH.

Forecasting migraine with machine learning based on mobile phone diary and wearable data.

INTRODUCTION: Triggers, premonitory symptoms and physiological changes occur in the preictal migraine phase and may be used in models for forecasting attacks. Machine learning is a promising option for such predictive analytics. The objective of this study was to explore the utility of machine learning to forecast migraine attacks based on preictal headache diary entries and simple physiological measurements. METHODS: In a prospective development and usability study 18 patients with migraine completed 388 headache diary entries and self-administered app-based biofeedback sessions wirelessly measuring heart rate, peripheral skin temperature and muscle tension. Several standard machine learning architectures were constructed to forecast headache the subsequent day. Models were scored with area under the receiver operating characteristics curve. RESULTS: Two-hundred-and-ninety-five days were included in the predictive modelling. The top performing model, based on random forest classification, achieved an area under the receiver operating characteristics curve of 0.62 in a hold-out partition of the dataset. DISCUSSION: In this study we demonstrate the utility of using mobile health apps and wearables combined with machine learning to forecast headache. We argue that high-dimensional modelling may greatly improve forecasting and discuss important considerations for future design of forecasting models using machine learning and mobile health data.

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.

A case of recurrent flight-induced cerebrospinal fluid shunt overdrainage.

Shunted patients often complain of headaches after flights. The effect of air travel on shunt systems is unknown. We describe the case of a patient with longstanding hydrocephalus, who suffered flight-induced clinical deterioration and shunt overdrainage in two independent occasions. The patient, clinically stable for 1.5 and 5 years before each episode, reported severe headaches starting during the descent stages of the air travel. On both occasions, brain MRI imaging demonstrated pronounced ventricular size reduction. This case suggests that flight-induced shunt overdrainage can occur and should be suspected in patients with prolonged headaches and/or clinical deterioration triggered by air travel.

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.

Effect of position on intracranial pressure and compliance: a cross-sectional study including 101 patients.

OBJECTIVE: A better understanding of the effect of position on intracranial pressure (ICP) and compliance is important for the development of treatment strategies that can restore normal cerebrospinal fluid (CSF) dynamics. There is limited knowledge on the effect of position on intracranial compliance. In this cross-sectional study the authors tested the association of pulse amplitude (PA) with position and the day/night cycle. Additionally, they describe the postural ICP and PA changes of patients with "normal" ICP dynamics. METHODS: This single-center retrospective study included patients with suspected and/or confirmed CSF dynamics abnormalities who had been examined with elective 24-hour ICP monitoring between October 2017 and September 2019. Patients had been enrolled in a short exercise battery including four positions: supine, lumbar puncture position in the left lateral decubitus position, sitting, and standing. Each position was maintained for 2 minutes, and mean ICP and PA were calculated for each position. The 24-hour day and night median ICP and PA data were also collected. Linear regression models were used to test the correlation of PA with position and day/night cycle. All linear regressions were corrected for confounders. The postural ICP monitoring results of patients without obvious ICP dynamics abnormality were summarized. RESULTS: One hundred one patients (24 males and 77 females) with a mean age of 39 ± 13years (mean ± standard deviation) were included in the study. The adjusted linear regression models demonstrated a significant association of ICP with position and day/night cycle, with upright (sitting and standing) and day ICP values lower than supine and night ICP values. The adjusted linear regression model was also significant for the association of PA with position and day/night cycle, with upright and day PA values higher than supine and night PA results. These associations were confirmed for patients with and without shunts. Patients without clear ICP dynamics abnormality had tighter control of their postural ICP changes than the other patients; however, the difference among groups was not statistically significant. CONCLUSIONS: This is the largest study investigating the effect of postural changes on intracranial compliance. The results of this study suggest that PA, as well as ICP, is significantly associated with posture, increasing in upright positions compared to that while supine. Further studies will be needed to investigate the mechanism behind this association.

Brain MRI and Ophthalmic Biomarkers of Intracranial Pressure.

OBJECTIVE: To evaluate the utility of brain MRI and ophthalmic biomarkers for the prediction of intracranial hypertension, we have studied the association between six biomarkers and 24-hour intracranial pressure (ICP) monitoring results in 45 patients. METHODS: This single-centre observational study includes patients who underwent 24-hour ICP monitoring, brain MRI (within three months) and ophthalmic assessment (during ICP monitoring). Six biomarkers were investigated: pituitary gland shape, vertical tortuosity of the optic nerve, distension of the optic nerve sheath, optic disc protrusion (MRI), papilloedema (slit lamp biomicroscopy) and spontaneous venous pulsations (SVP, infrared video recordings). RESULTS: Forty-five patients (mean age 39±14SD, 38 females) met the inclusion criteria. All 6 biomarkers had a significant association with 24-hour ICP. Concave pituitary gland was observed with moderately elevated median ICP. Protrusion of the optic disc (MRI), papilloedema and absence of SVP were associated with the highest median ICP values. Twenty patients had raised ICP (median 24-hour ICP>5.96 mmHg, cut-off obtained through Youden index calculation). Patients with all normal biomarkers had normal median ICP in 94% (St.Err.=6%) of the cases. All the patients with 3 or more abnormal biomarkers had intracranial hypertension. The combination of at least one abnormal biomarker in MRI and ophthalmic assessments was highly suggestive of intracranial hypertension (AUC 0.94, 95% CI 0.93-0.94) CONCLUSIONS: Brain MRI and ophthalmic biomarkers can non-invasively guide the management of patients with suspected CSF dynamics abnormalities. Patients with multiple abnormal biomarkers (≥3) or a combination of abnormal MRI and ophthalmic biomarkers are likely to have intracranial hypertension and should be managed promptly.

Clinical Presentation, Investigation Findings, and Treatment Outcomes of Spontaneous Intracranial Hypotension Syndrome: A Systematic Review and Meta-analysis.

Importance: Spontaneous intracranial hypotension (SIH) is a highly disabling but often misdiagnosed disorder. The best management options for patients with SIH are still uncertain. Objective: To provide an objective summary of the available evidence on the clinical presentation, investigations findings, and treatment outcomes for SIH. Data Sources: Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline-compliant systematic review and meta-analysis of the literature on SIH. Three databases were searched from inception to April 30, 2020: PubMed/MEDLINE, Embase, and Cochrane. The following search terms were used in each database: spontaneous intracranial hypotension, low CSF syndrome, low CSF pressure syndrome, low CSF volume syndrome, intracranial hypotension, low CSF pressure, low CSF volume, CSF hypovolemia, CSF hypovolaemia, spontaneous spinal CSF leak, spinal CSF leak, and CSF leak syndrome. Study Selection: Original studies in English language reporting 10 or more patients with SIH were selected by consensus. Data Extraction and Synthesis: Data on clinical presentation, investigations findings, and treatment outcomes were collected and summarized by multiple observers. Random-effect meta-analyses were used to calculate pooled estimates of means and proportions. Main Outcomes and Measures: The predetermined main outcomes were the pooled estimate proportions of symptoms of SIH, imaging findings (brain and spinal imaging), and treatment outcomes (conservative, epidural blood patches, and surgical). Results: Of 6878 articles, 144 met the selection criteria and reported on average 53 patients with SIH each (range, 10-568 patients). The most common symptoms were orthostatic headache (92% [95% CI, 87%-96%]), nausea (54% [95% CI, 46%-62%]), and neck pain/stiffness (43% [95% CI, 32%-53%]). Brain magnetic resonance imaging was the most sensitive investigation, with diffuse pachymeningeal enhancement identified in 73% (95% CI, 67%-80%) of patients. Brain magnetic resonance imaging findings were normal in 19% (95% CI, 13%-24%) of patients. Spinal neuroimaging identified extradural cerebrospinal fluid in 48% to 76% of patients. Digital subtraction myelography and magnetic resonance myelography with intrathecal gadolinium had high sensitivity in identifying the exact leak site. Lumbar puncture opening pressures were low, normal (60-200 mm H2O), and high in 67% (95% CI, 54%-80%), 32% (95% CI, 20%-44%), and 3% (95% CI, 1%-6%), respectively. Conservative treatment was effective in 28% (95% CI, 18%-37%) of patients and a single epidural blood patch was successful in 64% (95% CI, 56%-72%). Large epidural blood patches (>20 mL) had better success rates than small epidural blood patches (77% [95% CI, 63%-91%] and 66% [95% CI, 55%-77%], respectively). Conclusions and Relevance: Spontaneous intracranial hypotension should not be excluded on the basis of a nonorthostatic headache, normal neuroimaging findings, or normal lumbar puncture opening pressure. Despite the heterogeneous nature of the studies available in the literature and the lack of controlled interventional studies, this systematic review offers a comprehensive and objective summary of the evidence on SIH that could be useful in guiding clinical practice and future research.

Medical treatment of SUNCT and SUNA: a prospective open-label study including single-arm meta-analysis.

INTRODUCTION: The management of short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA) remains challenging in view of the paucity of data and evidence-based treatment recommendations are missing. METHODS: In this single-centre, non-randomised, prospective open-label study, we evaluated and compared the efficacy of oral and parenteral treatments for SUNCT and SUNA in a real-world setting. Additionally, single-arm meta-analyses of the available reports of SUNCT and SUNA treatments were conducted. RESULTS: The study cohort comprised 161 patients. Most patients responded to lamotrigine (56%), followed by oxcarbazepine (46%), duloxetine (30%), carbamazepine (26%), topiramate (25%), pregabalin and gabapentin (10%). Mexiletine and lacosamide were effective in a meaningful proportion of patients but poorly tolerated. Intravenous lidocaine given for 7-10 days led to improvement in 90% of patients, whereas only 27% of patients responded to a greater occipital nerve block. No statistically significant differences in responders were observed between SUNCT and SUNA. In the meta-analysis of the pooled data, topiramate was found to be significantly more effective in SUNCT than SUNA patients. However, a higher proportion of SUNA than SUNCT was considered refractory to medications at the time of the topiramate trial, possibly explaining this isolated difference. CONCLUSIONS: We propose a treatment algorithm for SUNCT and SUNA for clinical practice. The response to sodium channel blockers indicates a therapeutic overlap with trigeminal neuralgia, suggesting that sodium channels dysfunction may be a key pathophysiological hallmark in these disorders. Furthermore, the therapeutic similarities between SUNCT and SUNA further support the hypothesis that these conditions are variants of the same disorder.

Paradoxical response of intracranial pressure to shunt valve setting adjustments.

BACKGROUND: The hydrodynamics of cerebrospinal fluid shunts have been described in vitro; however, knowledge on the response of intracranial pressure (ICP) to valve settings adjustments in vivo is limited. This study describes the effect of adjusting the shunt valve setting on ICP in a cohort of patients with complex symptom management. METHOD: Single-centre retrospective observational study. Patients who underwent ICP-guided valve setting adjustments during 24-h continuous ICP monitoring, between 2014 and 2019, were included. Patients with suspected shunt malfunction were excluded. Median night ICP before and after the valve adjustments were compared (Δ night ICP). The responses of ICP to valve adjustment were divided into 3 different groups as follows: expected, paradoxical and no response. The frequency of the paradoxical response and its potential predicting factors were investigated. RESULTS: Fifty-one patients (37 females, 14 males, mean age 38 years) receiving 94 valve setting adjustments met the study inclusion criteria. Patients' underlying conditions were most commonly hydrocephalus (47%) or idiopathic intracranial hypertension (43%). The response of ICP to valve setting adjustments was classified as 'expected' in 54 cases (57%), 'paradoxical' in 17 cases (18%) and 'no effect' (Δ night ICP < 1 mmHg) in 23 cases (24%). There was a significant correlation between the Δ night ICP and the magnitude of valve setting change in both the investigated valves (Miethke ProGAV, p = 0.01 and Medtronic Strata, p = 0.02). CONCLUSIONS: Paradoxical ICP changes can occur after shunt valve setting adjustments. This observation should be taken into account when performing ICP-guided valve adjustments and is highly relevant for the future development of "smart" shunt systems.