Primary headaches.

Headache disorders, characterized by recurrent headache, are among the most common disorders of the nervous system. Primary headache disorders are by definition not the result of any other underlying disease or process. In this chapter the current status of cerebrospinal fluid (CSF) research and applications for clinical practice for the three main primary headaches - migraine, cluster headache, and tension-type headache - will be described. Primary headaches are clinically diagnosed disorders, with typically normal routine CSF measurements. Research in these headaches has been focused on identifying pathophysiologic pathways with a wide array of measured molecules. CSF research in the headache field is still in the discovery phase, with most studies performed in migraine and with unreplicated findings for most of the identified molecules. From a clinical standpoint it would be of great value if CSF biomarkers could be used as disorder-specific biomarkers for difficult primary headache cases, or to predict treatment responsiveness or risk for headache chronification. These applications are currently not yet feasible. For future research into CSF biomarkers for primary headache disorders, two different strategies should be employed: hypothesis-driven and nonhypothesis-driven biochemical research, to show new avenues for treatment strategies and develop prediction models for clinical use.

Blood-brain barrier breakdown in reversible cerebral vasoconstriction syndrome: Implications for pathophysiology and diagnosis.

OBJECTIVE: Diagnosis of reversible cerebral vasoconstriction syndrome (RCVS) is currently based on luminographic findings of vasoconstriction. In addition to vasoconstriction, the blood-brain barrier (BBB) breakdown has been postulated as a central mechanism of RCVS. Our aim was to document BBB breakdown in patients with RCVS and its role for the pathophysiology-based diagnosis of RCVS. METHODS: We prospectively recruited 72 consecutive patients with thunderclap headache who did not have aneurysmal subarachnoid hemorrhage from April 2015 to July 2016 at the Samsung Medical Center. Based on the International Classification of Headache Disorders-3 beta criteria and neuroimaging, patients were classified as having RCVS (n = 41; "definite" in 29 imaging-proven patients and "probable" in 12 imaging-negative patients), other secondary causes (n = 7), and thunderclap headache of undetermined cause (n = 24). BBB breakdown was evaluated using contrast-enhanced fluid-attenuated inversion recovery magnetic resonance imaging. RESULTS: BBB breakdown was documented in 20 (69.0%) patients with definite RCVS, 3 (25.0%) patients with probable RCVS, and none with other secondary causes. BBB breakdown was present in RCVS patients with (n = 4) and without (n = 19) concomitant posterior reversible encephalopathy syndrome. In patients with RCVS, the extent of BBB breakdown was independently associated with neurological complications (multivariate odds ratio = 1.48 per 1 territorial increase, 95% confidence interval = 1.04-2.12, adjusted p = 0.032). Three (12.5%) patients with thunderclap headache of undetermined cause were newly classified as having RCVS by the presence of BBB breakdown. INTERPRETATION: This is the first study to show BBB breakdown in patients with RCVS. This finding might broaden our understanding of the pathophysiology and clinical spectrum of RCVS. Ann Neurol 2017;81:454-466.

Clinical and diagnostic findings in patients with elevated cerebrospinal bilirubin.

INTRODUCTION: Cerebrospinal fluid (CSF) spectroscopy can identify subarachnoid haemorrhage (SAH) when CT is negative in patients presenting with acute severe headache. The primary objective of this study was to evaluate the clinical use and usefulness of CSF spectrophotometry. Secondary objectives were to identify other causes of elevated CSF bilirubin, to analyse headache descriptions and to compare clinical features in patients with an elevated CSF bilirubin among those with and without an intracranial vascular cause of SAH (avSAH). METHODS: Consecutive patients admitted to two hospitals in Enniskillen and Londonderry between 1 January 2004 and 30 September 2014 with CSF spectroscopy bilirubin results were identified from a clinical chemistry laboratory dataset. Patients with elevated CSF bilirubin were studied. Clinical demographics, delays to investigation and final diagnoses were recorded. Patients with avSAH were compared with patients without avSAH. RESULTS: Among 1813 patients with CSF spectrophotometry results, requests increased more than threefold during the study (p<0.001). Fifty-six patients had elevated CSF bilirubin. Ten (17.9%) had avSAH, of which 8 (14.3%) had aneurysmal SAH. Non-vascular causes of elevated CSF bilirubin included meningitis, spontaneous intracranial hypotension and carcinomatous meningitis. Headache descriptions varied. Time from headache onset to admission, CT scan and lumbar puncture did not differ significantly for patients with avSAH and non-avSAH. CSF red cell counts were higher among patients with avSAH than patients with non-avSAH (p=0.005). CONCLUSIONS: CSF bilirubin measurement has an important role in identifying avSAH in CT-negative patients presenting with a thunderclap headache. Better clinical selection of patients is required as CSF spectrophotometry, although sensitive, is not specific for SAH.

Spontaneous intracranial hypotension.

Since the introduction of magnetic resonance imaging (MRI), spontaneous intracranial hypotension has been diagnosed much more frequently. The aim of this review is to discuss the symptoms and signs of the condition, in particular the characteristics of the associated headache, with sudden onset after sitting or standing, so that it can be included under the rubric of 'thunderclap headache'. This type of headache, like post lumbar puncture headaches, may be caused by cerebral vasodilatation and exacerbated by lowered pressure of the cerebrospinal fluid (CSF). Other symptoms include neck stiffness, nausea, vomiting, vertigo, tinnitus, deafness, and cognitive abnormalities. The clinical picture can sometimes mimic frontotemporal dementia, and the behaviour of some patients can sometimes be described as hypoactive-hypoalert, with somnolence, impaired attention, and stereotyped motor activity. Sagging of the brain, caused by leakeage of the CSF, can cause lesions in the brainstem with stupor, gaze palsies, and cranial nerve palsies. The condition can be a risk factor for cerebral venous thrombosis because of slowing of the blood flow and distortion of the blood vessels. The clinical picture may well suggest the diagnosis, but the headache may possibly indicate a subarachnoid haemorrhage. However, MRI will help to confirm the diagnosis and to localize the site of the CSF leak. MRI myelograms are of particular value, but if they are equivocal a computed tomography myelogram should be performed. The leakage of CSF is due to a tear in the dura, most frequently where the spinal roots leave the subarachnoid space. If this does not heal with bedrest, an epidural blood patch or a percutaneous injection of fibrin glue may be needed. More information is required on long-term follow-up.

Thunderclap headache and normal computed tomographic results: value of cerebrospinal fluid analysis.

OBJECTIVE: To determine the sensitivity, specificity, and negative and positive predictive values of cerebrospinal fluid (CSF) xanthochromia for detection of ruptured cerebral aneurysms in patients with thunderclap headache (sudden and severe headache with maximal intensity at onset). PATIENTS AND METHODS: We identified patients who presented to our emergency department with symptoms of thunderclap headache between January 1, 1998, and January 1, 2008. Those with normal results on computed tomography (CT) of the head were selected for inclusion in the study. All consenting adult patients had undergone a lumbar puncture procedure for CSF analysis. Xanthochromia was assessed by visual inspection. All patients with a normal CT result were further evaluated by conventional 4-vessel catheter angiography. If no aneurysms were detected in the initial study, the procedure was performed again within 7 to 14 days. All patients were followed up clinically for a mean period of approximately 29 months. RESULTS: A total of 152 patients were identified (mean +/- SD age, 44.7+/-15.8 years; 53 men). Cerebrospinal fluid xanthochromia was present in 18 patients (12%), 13 (72%) of whom were ultimately diagnosed as having aneurysmal subarachnoid hemorrhage. A single patient who tested negative for xanthochromia and had a normal CT result was subsequently found to have a ruptured middle cerebral artery aneurysm. The sensitivity, specificity, positive predictive value, and negative predictive value of CSF xanthochromia for detection of cerebral aneurysms were 93%, 95%, 72%, and 99%, respectively. CONCLUSION: Although not perfect, visual inspection of CSF in patients with a history suggestive of subarachnoid hemorrhage remains a highly valuable and simple test to detect a recently ruptured aneurysm.