Long-Term Epidural Patching Outcomes and Predictors of Benefit in Patients With Suspected CSF Leak Nonconforming to ICHD-3 Criteria.

BACKGROUND AND OBJECTIVES: Spinal CSF leaks lead to spontaneous intracranial hypotension (SIH). While International Classification of Headache Disorders, Third Edition (ICHD-3) criteria necessitate imaging confirmation or low opening pressure (OP) for SIH diagnosis, their sensitivity may be limited. We offered epidural blood patches (EBPs) to patients with symptoms suggestive of SIH, with and without a documented low OP or confirmed leak on imaging. This study evaluates the efficacy of this strategy. METHODS: We conducted a prospective cohort study with a nested case-control design including all patients who presented to a tertiary headache clinic with clinical symptoms of SIH who completed study measures both before and after receiving an EBP between August 2016 and November 2018. RESULTS: The mean duration of symptoms was 8.7 ± 8.1 years. Of 85 patients assessed, 69 did not meet ICHD-3 criteria for SIH. At an average of 521 days after the initial EBP, this ICHD-3-negative subgroup experienced significant improvements in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Physical Health score of +3.3 (95% CI 1.5-5.1), PROMIS Global Mental Health score of +1.8 (95% CI 0.0-3.5), Headache Impact Test (HIT)-6 head pain score of -3.8 (95% CI -5.7 to -1.8), Neck Disability Index of -4.8 (95% CI -9.0 to -0.6) and PROMIS Fatigue of -2.3 (95% CI -4.1 to -0.6). Fifty-four percent of ICHD-3-negative patients achieved clinically meaningful improvements in PROMIS Global Physical Health and 45% in HIT-6 scores. Pain relief following lying flat prior to treatment was strongly associated with sustained clinically meaningful improvement in global physical health at an average of 521 days (odds ratio 1.39, 95% CI 1.1-1.79; p < 0.003). ICHD-3-positive patients showed high rates of response and previously unreported, treatable levels of fatigue and cognitive deficits. DISCUSSION: Patients who did not conform to the ICHD-3 criteria for SIH showed moderate rates of sustained, clinically meaningful improvements in global physical health, global mental health, neck pain, fatigue, and head pain after EBP therapy. Pre-treatment improvement in head pain when flat was associated with later, sustained improvement after EBP therapy among patients who did not meet the ICHD-3 criteria. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that epidural blood patch is an effective treatment of suspected CSF leak not conforming to ICHD-3 criteria for SIH.

Headache: Treatment update.

Primary headache disorders in particular migraine are one of the most common causes of disability worldwide. Given the high burden of migraine in terms of disability, there has been an effort to develop migraine specific therapies that has led to the availability of new drugs including 5HT1F receptor agonists-ditans (lasmiditan), small molecule calcitonin gene-related peptide (CGRP) receptor antagonists-gepants: (ubrogepant, rimegepant, atogepant) and anti-CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab and eptinezumab). However, some of these treatments incur a high cost and may not be a feasible option for most patients in resource limited settings. Lasmiditan and the gepants are a good option for patients with moderate-severe migraine attacks who cannot use triptans due variously to poor tolerability, or cardio- or cerebrovascular disease. For practical purposes, the new anti-CGRP monoclonal antibodies are best reserved for patients who have failed to have efficacy or had intolerable side effects from multiple traditional oral preventives.

Emerging drugs for the prevention of migraine.

INTRODUCTION: Migraine is a common and disabling neurological disorder. A greater understanding of the pathophysiological mechanisms underlying migraine has led to the availability of specific new drugs targeting calcitonin gene-related peptide (CGRP). The success of the CGRP inhibitors validates research efforts into migraine-specific therapies. AREAS COVERED: There are additional promising therapeutic targets that will be covered in this paper, focusing on the pain phase. They include pituitary adenylate cyclase-activating polypeptide (PACAP), the orexinergic system, the nitric oxide signaling pathway specifically neuronal nitric oxide synthase inhibitors (nNOSi), and metabotropic glutamate receptor 5 (mGluR5). EXPERT OPINION: Based on currently available research; the targets discussed in this paper are all on equal footing with each other in terms of their potential as effective novel migraine therapies. There is a need for more clinical trials to pinpoint which of these potential drug targets will be effective for migraine preventio.

Subarachnoid Hemorrhage and Headache.

PURPOSE FOR REVIEW: Subarachnoid hemorrhage is a serious and life-threatening medical condition which commonly presents with an acute headache. Unfortunately, it remains frequently misdiagnosed at initial presentation with dire consequences in terms of patient morbidity and mortality. The goal of this paper is to review salient features in the clinical history, as well as recently developed clinical decision rules, which can help determine which patients warrant further investigation for subarachnoid hemorrhage when the initial presentation is that of an acute headache. RECENT FINDINGS: A recent prospective observational study showed that occipital location, stabbing quality, presence of meningism, and onset of headache during exertion were characteristics in the clinical history that can distinguish the headache of SAH from other causes. The Ottawa headache rule is a clinical decision tool which was developed to help identify patients presenting to the ED with acute non-traumatic headache who require investigation to rule out subarachnoid hemorrhage. Using this tool, it is recommended that patients who meet any one of the following 6 criteria are investigated further: Onset greater than or equal to 40 years, presence of neck pain or stiffness, witnessed loss of consciousness, onset during exertion, thunder clap headache (pain peaking within 1 s), or limited neck flexion on exam. An informed and thoughtful approach that takes into account the timing, presentation, risk factors, and resources, as discussed here, should help distinguish between the patient that warrants further evaluation and intervention for SAH and one who does not. The Ottawa SAH rule is a useful clinical decision tool for young inexperienced clinicians in order to avoid missed diagnoses. However, its clinical value is limited by its low specificity. Clinical decision tools with higher specificity are needed.

Risk of individual malignant neoplasms in patients with sickle cell disease: English national record linkage study.

OBJECTIVE: Case reports suggest that there may be an increased risk of some cancers associated with sickle cell disease. However, population-based studies are scarce and there is no comprehensive enumeration of the risks across the whole range of site-specific cancers. Our aim was to provide this. DESIGN: We used an English national dataset of linked statistical records of hospital admissions and deaths from 1999 to 2011 to undertake a retrospective cohort study. SETTING: England. PARTICIPANTS: Records of all hospital admissions in England with SCD or with conditions included in the control cohort. MAIN OUTCOME MEASURES: Rate ratios were calculated comparing rates of cancer in a sickle cell disease cohort and a control cohort, confining the analyses to people whose ethnicity was recorded as Black. RESULTS: Comparing the sickle cell disease cohort with the cohort without sickle cell disease, the rate ratio for all cancers combined was 2.1 (95% confidence interval 1.7-2.5). There were significantly high rate ratios for haematological malignancies, including Hodgkin's lymphoma (rate ratio 3.7, 1.5-8.4), non-Hodgkin's lymphoma (2.6, 1.3-4.8), multiple myeloma (5.5, 2.8-10.1), lymphoid leukaemia (3.3, 1.3-8.0) and myeloid leukaemia (10.0, 4.6-21.5). Four solid tumours showed elevated rate ratios: colon cancer (2.8, 1.2-5.5), non-melanoma skin cancer (4.4, 1.3-12.2), kidney cancer (5.4, 2.3-11.5) and thyroid cancer (5.1, 1.3-15.4). CONCLUSIONS: The risk of some malignancies may be raised in patients with sickle cell disease. However, this study was based on administrative data without the scope to validate these against patients' full clinical records. Our findings need confirmation or refutation. If confirmed, work to elucidate, at the genetic and molecular level, why people with sickle cell disease have elevated risks of individual cancers might make contributions to the fundamental understanding of carcinogenesis.