Cerebrovascular reactivity to hypercapnia in patients with migraine: A dual-echo arterial spin labeling MRI study.

OBJECTIVE: This study aimed to compare cerebrovascular reactivity between patients with migraine and controls using state-of-the-art magnetic resonance imaging (MRI) techniques. BACKGROUND: Migraine is associated with an increased risk of cerebrovascular disease, but the underlying mechanisms are still not fully understood. Impaired cerebrovascular reactivity has been proposed as a link. Previous studies have evaluated cerebrovascular reactivity with different methodologies and results are conflicting. METHODS: In this single-center, observational, case-control study, we included 31 interictal patients with migraine without aura (aged 19-66 years, 17 females) and 31 controls (aged 22-64 years, 18 females) with no history of vascular disease. Global and regional cerebrovascular reactivities were assessed with a dual-echo arterial spin labeling (ASL) 3.0 T MRI scan of the brain which measured the change in cerebral blood flow (CBF) and BOLD (blood oxygen level dependent) signal to inhalation of 5% carbon dioxide. RESULTS: When comparing patients with migraine to controls, cerebrovascular reactivity values were similar between the groups, including mean gray matter CBF-based cerebrovascular reactivity (3.2 ± 0.9 vs 3.4 ± 1% ΔCBF/mmHg CO2 ; p = 0.527), mean gray matter BOLD-based cerebrovascular reactivity (0.18 ± 0.04 vs 0.18 ± 0.04% ΔBOLD/mmHg CO2 ; p = 0.587), and mean white matter BOLD-based cerebrovascular reactivity (0.08 ± 0.03 vs 0.08 ± 0.02% ΔBOLD/mmHg CO2 ; p = 0.621).There was no association of cerebrovascular reactivity with monthly migraine days or migraine disease duration (all analyses p > 0.05). CONCLUSION: Cerebrovascular reactivity to carbon dioxide seems to be preserved in patients with migraine without aura.

Neuroimaging Findings in Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic Manifestations.

Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations is caused by TREX1 mutations. High-quality systematic follow-up neuroimaging findings have not been described in presymptomatic and symptomatic mutation carriers. We present MR imaging findings of 29 TREX1 mutation carriers (20-65 years of age) and follow-up of 17 mutation carriers (30-65 years of age). Mutation carriers younger than 40 years of age showed a notable number of punctate white matter lesions, but scan findings were generally unremarkable. From 40 years of age onward, supratentorial lesions developed with long-term contrast enhancement (median, 24 months) and diffusion restriction (median, 8 months). In these lesions, central susceptibility artifacts developed, at least partly corresponding to calcifications on available CT scans. Some lesions (n = 2) additionally showed surrounding edema and mass effect (pseudotumors). Cerebellar punctate enhancing lesions developed mainly in individuals older than 50 years of age. These typical neuroimaging findings should aid neuroradiologic recognition of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations, which may enable early treatment of manifestations of the disease.

Cranial Ultrasound Is an Important Tool in the Recognition of Life-Threatening Infratentorial Hemorrhage in Newborns.

Timely detection of severe infratentorial hemorrhage in neonates is crucial, especially in case of life-threatening brain stem compression and/or acute obstructive hydrocephalus, which need lifesaving neurosurgical intervention. Although the detection of infratentorial hemorrhage by ultrasound scanning is often considered as difficult, the use of additional acoustic windows and recognition of characteristic ultrasound features facilitate early diagnosis. In this case series, we report on newborns with severe, symptomatic infratentorial hemorrhage detected primarily by cranial ultrasound. We demonstrate the characteristic ultrasound features present in all cases and discuss how ultrasound diagnosis contributed to early diagnosis and treatment.

Systemic features of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations: a monogenic small vessel disease.

BACKGROUND: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a small vessel disease caused by C-terminal truncating TREX1 mutations. The disease is typically characterized by vascular retinopathy and focal and global brain dysfunction. Systemic manifestations have also been reported but not yet systematically investigated. METHODS: In a cross-sectional study, we compared the clinical characteristics of 33 TREX1 mutation carriers (MC+) from three Dutch RVCL-S families with those of 37 family members without TREX1 mutation (MC-). All participants were investigated using personal interviews, questionnaires, physical, neurological and neuropsychological examinations, blood and urine tests, and brain MRI. RESULTS: In MC+, vascular retinopathy and Raynaud's phenomenon were the earliest symptoms presenting from age 20 onwards. Kidney disease became manifest from around age 35, followed by liver disease, anaemia, markers of inflammation and, in some MC+, migraine and subclinical hypothyroidism, all from age 40. Cerebral deficits usually started mildly around age 50, associated with white matter and intracerebral mass lesions, and becoming severe around age 60-65. CONCLUSIONS: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations is a rare, but likely underdiagnosed, systemic small vessel disease typically starting with vascular retinopathy, followed by multiple internal organ disease, progressive brain dysfunction, and ultimately premature death.

Biochemical changes in the brain of hemiplegic migraine patients measured with 7 tesla 1H-MRS.

AIM: The aim of this study was to assess biochemical changes in the brain of patients with hemiplegic migraine in between attacks. METHODS: Eighteen patients with hemiplegic migraine (M:F, 7:11; age 38 ± 14 years) of whom eight had a known familial hemiplegic migraine (FHM) mutation (five in the CACNA1A gene (FHM1), three in the ATP1A2 gene (FHM2)) and 19 age- and sex-matched healthy controls (M:F, 7:12; mean age 38 ± 12 years) were studied. We used single-voxel 7 tesla (1)H-MRS (STEAM, TR/TM/TE = 2000/19/21 ms) to investigate four brain regions in between attacks: cerebellum, hypothalamus, occipital lobe, and pons. RESULTS: Patients with hemiplegic migraine showed a significantly lower total N-acetylaspartate/total creatine ratio (tNAA/tCre) in the cerebellum (median 0.73, range 0.59-1.03) than healthy controls (median 0.79, range (0.67-0.95); p = 0.02). In FHM1 patients with a CACNA1A mutation, the tNAA/tCre was lowest. DISCUSSION: We found a decreased cerebellar tNAA/tCre ratio that might serve as an early biomarker for neuronal dysfunction and/or loss. This is the first high-spectral resolution 7 tesla (1)H-MRS study of interictal biochemical brain changes in hemiplegic migraine patients.

Neurophysiological tests and neuroimaging procedures in non-acute headache (2nd edition).

BACKGROUND AND PURPOSE: A large number of instrumental investigations are used in patients with non-acute headache in both research and clinical fields. Although the literature has shown that most of these tools contributed greatly to increasing understanding of the pathogenesis of primary headache, they are of little or no value in the clinical setting. METHODS: This paper provides an update of the 2004 EFNS guidelines and recommendations for the use of neurophysiological tools and neuroimaging procedures in non-acute headache (first edition). Even though the period since the publication of the first edition has seen an increase in the number of published papers dealing with this topic, the updated guidelines contain only minimal changes in the levels of evidence and grades of recommendation. RESULTS: (i) Interictal EEG is not routinely indicated in the diagnostic evaluation of patients with headache. Interictal EEG is, however, indicated if the clinical history suggests a possible diagnosis of epilepsy (differential diagnosis). Ictal EEG could be useful in certain patients suffering from hemiplegic or basilar migraine. (ii) Recording evoked potentials is not recommended for the diagnosis of headache disorders. (iii) There is no evidence warranting recommendation of reflex responses or autonomic tests for the routine clinical examination of patients with headache. (iv) Manual palpation of pericranial muscles, with standardized palpation pressure, can be recommended for subdividing patient groups but not for diagnosis. Pain threshold measurements and EMG are not recommended as clinical diagnostic tests. (v) In adult and pediatric patients with migraine, with no recent change in attack pattern, no history of seizures, and no other focal neurological symptoms or signs, the routine use of neuroimaging is not warranted. In patients with trigeminal autonomic cephalalgia, neuroimaging should be carefully considered and may necessitate additional scanning of intracranial/cervical vasculature and/or the sellar/orbital/(para)nasal region. In patients with atypical headache patterns, a history of seizures and/or focal neurological symptoms or signs, MRI may be indicated. (vi) If attacks can be fully accounted for by the standard headache classification (IHS), a PET or SPECT scan will normally be of no further diagnostic value. Nuclear medical examinations of the cerebral circulation and metabolism can be carried out in subgroups of patients with headache for the diagnosis and evaluation of complications, when patients experience unusually severe attacks or when the quality or severity of attacks has changed. (vii) Transcranial Doppler examination is not helpful in headache diagnosis. CONCLUSION: Although many of the examinations described in the present guidelines are of little or no value in the clinical setting, most of the tools, including thermal pain thresholds and transcranial magnetic stimulation, have considerable potential for differential diagnostic evaluation as well as for the further exploration of headache pathophysiology and the effects of pharmacological treatment.

An early 18th-century case description of cluster headache.

We present a previously unreported early 18th-century description of cluster headache by the English antiquary Abraham de la Pryme (1671-1704) initially attributed to hydrophobia (rabies). We will also give a short overview of other descriptions of cluster and cluster-like headache in historical literature.

Migraine is associated with an increased risk of deep white matter lesions, subclinical posterior circulation infarcts and brain iron accumulation: the population-based MRI CAMERA study.

Previous studies have suggested that migraine is a risk factor for brain lesions, but methodological issues hampered drawing definite conclusions. Therefore, we initiated the magnetic resonance imaging (MRI) 'CAMERA' (Cerebral Abnormalities in Migraine, an Epidemiological Risk Analysis) study. We summarize our previously published results. A total of 295 migraineurs and 140 controls were randomly selected from a previously diagnosed population-based sample (n = 6039), who underwent an interview, physical examination and a brain MRI scan. Migraineurs, notably those with aura, had higher prevalence of subclinical infarcts in the posterior circulation [odds ratio (OR) 13.7; 95% confidence interval (CI) 1.7, 112]. Female migraineurs were at independent increased risk of white matter lesions (WMLs; OR 2.1; 95% CI 1.0, 4.1), and migraineurs had a higher prevalence of brainstem hyperintense lesions (4.4% vs. 0.7%, P = 0.04). We observed a higher lifetime prevalence of (frequent) syncope and orthostatic insufficiency in migraineurs; future research needs to clarify whether autonomic nervous system dysfunction could explain (part of) the increased risk of WMLs in female migraineurs. Finally, in migraineurs aged < 50 years, compared with controls, we found evidence of increased iron concentrations in putamen (P = 0.02), globus pallidus (P = 0.03) and red nucleus (P = 0.03). Higher risks in those with higher attack frequency or longer disease duration were found consistent with a causal relationship between migraine and lesions. This summary of our population-based data illustrates that migraine is associated with a significantly increased risk of brain lesions. Longitudinal studies are needed to assess whether these lesions are progressive and have relevant (long-term) functional correlates.

Iron accumulation in deep brain nuclei in migraine: a population-based magnetic resonance imaging study.

A small magnetic resonance imaging (MRI) study showed increased iron depositions in the periaqueductal grey matter in migraineurs, suggestive of a disturbed central antinociceptive neuronal network. With 1.5-T MRI, we assessed iron concentrations in seven deep brain nuclei in a large population-based cohort. We compared T2 values between migraineurs (n = 138) and controls (n = 75), with multivariate regression analysis. Analyses were conducted in age strata (< 50, n = 112; > or = 50) because iron measures are increasingly influenced by non-iron-related factors in the older group. Overall, migraineurs and controls did not differ, nor did migraineurs with vs. without aura. In the younger migraineurs compared with controls, T2 values were lower in the putamen (P = 0.02), globus pallidus (P = 0.03) and red nucleus (P = 0.03). Similarly, in these younger migraineurs, controlling for age, those with longer migraine history had lower T2 values in the putamen (P = 0.01), caudate (P = 0.04) and red nucleus (P = 0.001). Repeated migraine attacks are associated with increased iron concentration/accumulation in multiple deep nuclei that are involved in central pain processing and migraine pathophysiology. It remains unclear whether iron accumulation in the antinociceptive network has a causative role in the development of (chronic) migraine headache.

Syncope in migraine: the population-based CAMERA study.

OBJECTIVE: To examine the association between migraine and syncope-related autonomic nervous system (ANS) symptoms. METHODS: A population-based study among migraineurs with and without aura (n = 323) and control subjects (n = 153) was conducted. A systematic questionnaire and cardiovascular measurements during rest, while standing, and after venipuncture addressed the prevalence of syncope, orthostatic intolerance, orthostatic hypotension (OH), and the postural tachycardia syndrome (POTS) in migraineurs and control subjects. RESULTS: The lifetime prevalence of syncope in all participants was 41%, more often in women (45 vs 32%; p = 0.02). Compared with control subjects, migraineurs had a higher lifetime prevalence of syncope (46 vs 31%; p = 0.001), frequent syncope (five or more attacks) (13 vs 5%; p = 0.02), and orthostatic intolerance (32 vs 12%; p < 0.001). There was no association between ANS symptoms and the severity of migraine or migraine subtype. Cardiovascular measurements and the prevalence of POTS and OH did not differ significantly between migraineurs and control subjects. CONCLUSION: This population-based study demonstrated an elevated prevalence of syncope and orthostatic intolerance in migraineurs without clear interictal signs of autonomic nervous system dysfunction.

MRI findings in migraine.

INTRODUCTION: For long time, migraine has been considered to be an episodic, multifactorial, neurovascular disorder, without long-term consequences to the brain, although an association between migraine and clinical stroke and white matter hyperintense lesions has been suggested in numerous studies. Due to various methodological problems no definite conclusion could be drawn from these studies. STATE OF THE ART: Recently, data from a population-based cross-sectional MRI study were published, establishing migraine to be a true and independent risk factor for white matter lesions (in female migraine patients) and subclinical posterior circulation territory infarcts. PERSPECTIVES: The methodology and results of previous investigations of a relationship between migraine and clinical ischemic stroke, silent infarction and white matter lesions are reviewed, and integrated in the results from the new population-based MRI study. CONCLUSION: Brain infarction occurs far more frequently than expected in migraine patients, most pronounced in migraine with aura (8 percent have subclinical cerebellar infarcts), although most infarcts remain clinically silent. Female migraine patients are at increased risk of deep white matter lesions, independent of the effects of cardiovascular risk factors. The influence of migraine severity (attack frequency) on the risk of both types of lesions suggests a causal relationship between migraine severity and lesion load. Future studies are needed to assess whether these (probably) ischemic lesions have relevant (long-term) functional correlates.

Routine cervical spine radiography for trauma victims: Does everybody need it?

OBJECTIVE: The purpose of this study was to evaluate the indication for routine cervical spine radiography in trauma patients. METHODS: Prospective analysis of radiologic and clinical findings was performed during a 5-year period. Patients suitable for a clinical decision rule were reviewed separately. RESULTS: Of the 1,757 consecutive patients included in the study, 38 were diagnosed with a cervical spine injury. Of the 599 patients suitable for the clinical decision rule, 62 had midline cervical tenderness, including 2 with cervical spine injury. No additional cervical spine injuries were found during follow-up. CONCLUSION: It is within good practice, and it is also cost-effective, to obtain a cervical spine radiograph only on clinical parameters in trauma patients with no apparent bodily trauma and optimal parameters. With this clinical decision rule, 30.6% of all cervical spine series were redundant, and no (occult) spinal fractures would have been undetected.

Sonography in a clinical algorithm for early evaluation of 1671 patients with blunt abdominal trauma.

OBJECTIVE: The purpose of this study was to evaluate the efficacy of sonography in our algorithm when differentiating patients with blunt abdominal trauma who need immediate surgery from patients who would benefit from further diagnostic workup or who need no treatment. SUBJECTS AND METHODS: We performed abdominal sonography as the primary screening tool in 1671 consecutive patients in our prospective study. Radiologists performed sonography in the trauma room within minutes of the arrival of each patient. Hemodynamic instability in conjunction with positive sonographic findings led to emergency laparotomy. Otherwise, positive sonographic findings warranted additional diagnostic tests. Observing free fluid or organ injury caused us to categorize sonographic findings as positive. RESULTS: Sonography correctly identified all patients requiring emergency laparotomy. No inconclusive laparotomies were performed in this group. The sensitivity of sonography for revealing intraabdominal injury was 88%, the specificity was 100%, and the accuracy was 99%. In 132 patients (8%), abdominal CT was performed. CT revealed relevant posttraumatic abnormalities in 61% of all patients. Four hundred seventy patients with negative sonographic findings were discharged approximately 12 hr after admission; two of these patients (0.4%) were mistakenly discharged. Trauma scores did not influence the efficacy of sonography. CONCLUSION: Our algorithm that uses sonography as the primary diagnostic tool provides accurate, fast, cost-effective, and noninvasive initial management of patients with blunt abdominal trauma. Our test characteristics were excellent indicators of the need for emergency laparotomy. Sonography also achieves high values in revealing relevant injury. Our algorithm produced medically satisfactory and economically prudent management of patients with blunt abdominal trauma.

Echo planar MRI of the heart on a standard system: validation of measurements of left ventricular function and mass.

OBJECTIVE: Our goal was to validate cardiac measurements derived from multishot echo planar MRI (EPI) as compared with the well validated conventional GRE technique. METHOD: Ten healthy subjects underwent breath-hold EPI and non-breath-hold GRE imaging in the short axis orientation of the left ventricle (LV) on a standard 1.5 T MR system. Ten section levels were obtained to encompass the entire LV. Measurements were obtained of end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF), LV mass, time to end-systole (TES), and peak filling rate (PFR). Analysis of variance was performed to determine agreement between GRE- and EPI-derived measurements. RESULTS: The acquisition time for EPI was much shorter than that for GRE (2.5 vs. 15 min). Both imaging techniques yielded good quality images allowing LV volumetrics. Agreement between GRE and EPI was best for measurements of EDV, SV, and LV mass; somewhat less agreement was found for ESV, EF, TES, and PFR. The intraobserver variability for measuring TES and PFR was higher for GRE than EPI (one sided F test; critical values at p = 0.05 were > 3.18). CONCLUSION: Multishot EPI of the heart provides accurate measurements of LV function and mass in a time-efficient manner.