Christian L Seifert, Andreas Woeller, Michael Valet, Claus Zimmer, Achim Berthele, Thomas Tölle, Till Sprenger
Background.- Pineal cysts have been suggested to be linked to headache pathogenesis. However, no systematic studies on this topic have been performed so far. Objective.- The aim of this study was to investigate the relationship between pineal cysts and headache and to determine the relevance of the cyst size in this context. Methods.- We conducted a case-control study of patients who consulted the neurological department between 1999 and 2006 to investigate the relationship between pineal cysts and headache and to determine the relevance of the cyst size. Results.- A total of 51 patients with pineal cyst were identified, thereby 51% were suffering from headache (half of them had migraine), whereas in the control group, only 25% had headache (thereof 31% suffered from migraine). There was a significant relationship between headache (as well as migraine) and pineal cysts (chi-square test), but no significant difference in pineal cyst diameter between the patient group with headache versus without headache (t-test). Conclusions.- Our data provide evidence for a causal relationship between pineal cysts and headache, respectively, migraine in this patient cohort.
Headache. 2010 Apr ;50 (4):666-8 20456152
Instituto Israelita de Ensino e Pesquisa Hospital Albert Einstein, Al Joaquim Eugenio de Lima, 881 cj 708, 01403-001, Sao Paulo, Brazil.
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Brain. 2012 Jun 19;: 22719000
Till Sprenger, Christian L Seifert, Michael Valet, Anna P Andreou, Annette Foerschler, Claus Zimmer, D Louis Collins, Peter J Goadsby, Thomas R Tölle, M Mallar Chakravarty
1 Department of Neurology, University of California, San Francisco, CA 94115-1080, USA.
Central post-stroke pain of thalamic origin is an extremely distressing and often refractory disorder. There are no well-established predictors for pain development after thalamic stroke, and the role of different thalamic nuclei is unclear. Here, we used structural magnetic resonance imaging to identify the thalamic nuclei, specifically implicated in the generation of central post-stroke pain of thalamic origin. Lesions of 10 patients with central post-stroke pain of thalamic origin and 10 control patients with thalamic strokes without pain were identified as volumes of interest on magnetic resonance imaging data. Non-linear deformations were estimated to match each image with a high-resolution template and were applied to each volume of interest. By using a digital atlas of the thalamus, we elucidated the involvement of different nuclei with respect to each lesion. Patient and control volumes of interest were summed separately to identify unique areas of involvement. Voxelwise odds ratio maps were calculated to localize the anatomical site where lesions put patients at risk of developing central post-stroke pain of thalamic origin. In the patients with pain, mainly lateral and posterior thalamic nuclei were affected, whereas a more anterior-medial lesion pattern was evident in the controls. The lesions of 9 of 10 pain patients overlapped at the border of the ventral posterior nucleus and the pulvinar, coinciding with the ventrocaudalis portae nucleus. The lesions of this area showed an odds ratio of 81 in favour of developing thalamic pain. The high odds ratio at the ventral posterior nucleus-pulvinar border zone indicates that this area is crucial in the pathogenesis of thalamic pain and demonstrates the feasibility of identifying patients at risk of developing central post-stroke pain of thalamic origin early after thalamic insults. This provides a basis for pre-emptive treatment studies.
Headache. 2012 Jul 23;: 22823926
Christian L Seifert, Stefano Magon, Kathrin Staehle, Claus Zimmer, Annette Foerschler, Ernst-Wilhelm Radue, Volker Pfaffenrath, Thomas R Tölle, Till Sprenger
From the Department of Neurology, Technische Universität München, Germany (C.L. Seifert, K. Staehle, T.R. Tölle, T. Sprenger); Department of Neuroradiology, Technische Universität München, Germany (C. Zimmer, A. Foerschler); Department of Neurology, Universitätsspital Basel, Switzerland (S. Magon, T. Sprenger); Division of Neuroradiology, Department of Radiology, Universitätsspital Basel, Switzerland (S. Magon, T. Sprenger); Headache Center Münchner Freiheit, Munich, Germany (V. Pfaffenrath); Medical Image Analysis Center, Basel, Switzerland (E.-W. Radue).
Objective.- This study aims at investigating cortical thickness in cluster headache patients as compared with a healthy control group. Background.- The pathobiology of cluster headache is not yet fully understood, although a dysfunction of the hypothalamus has been suggested to be causal. Previous studies in migraine and trigeminal neuropathic pain have demonstrated changes in cortical thickness using cortex segmentation techniques, but no data have been published on cluster headache. Methods.- We investigated 12 men with episodic cluster headache during a phase without acute headache as well as age and sex-matched healthy controls using high resolution T1-weighted magnetic resonance imaging acquired at 3T and performed a categorical whole-brain surface-based comparison of cortical thickness between groups. Furthermore, a correlation analysis of disease duration and cortical thickness was conducted. Results.- In comparison with control subjects, we found a reduction of cortical thickness in the angular gyrus and the precentral gyrus in cluster headache patients contralaterally to the headache side. These reductions did not correlate with disease duration. The cortical thickness of an area within the primary sensory cortex correlated with disease duration. Conclusions.- This study demonstrates alterations in cortical thickness in cluster headache patients suggesting a potential role of cortical structures in cluster headache pathogenesis. However, it cannot be determined from this study whether the changes are cause or consequence of the disorder. The correlation of cortical thickness with disease duration in the somatosensory cortex may suggest disease-related plasticity in the somatosensory system.
Christian L Seifert, Michael Valet, Volker Pfaffenrath, Henning Boecker, Katharina V Rüther, Thomas R Tölle, Till Sprenger
Neurologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, München, Germany. firstname.lastname@example.org
A close association between pain, depression and disability has been shown. However, the neurometabolic correlates of this association have been barely investigated in disease states. Episodic cluster headache is a severe headache syndrome and represents a suitable disease model for the investigation of episodic pain. The aim of this study was to explore the relationship between depression and disability as well as pain scores and brain metabolism in patients with cluster headache during the disease period with repetitive pain attacks, but outside an acute attack. Thirteen patients with cluster headache underwent 2-[fluorine-18]-fluoro-2-deoxy-D-glucose positron emission (FDG-PET) and completed questionnaires on depression and disability as well as a pain visual analogue rating scale (VAS). A positive correlation between the depression scores and glucose metabolism was observed in the insular cortex. A positive correlation between the pain disability scores and brain metabolism was detected in the amygdala. The same applied to the pain visual analogue rating scores. Our data underline the association between severe episodic pain, depression and disability. In addition to this clinical observation, our results stress the importance of the insula and amygdala in pain processing and suffering.
Patients With Pain Disorder Show Gray-Matter Loss in Pain-Processing Structures: A Voxel-Based Morphometric Study.
Michael Valet, Harald Gündel, Till Sprenger, Christian Sorg, Mark Mühlau, Claus Zimmer, Peter Henningsen, Thomas R Tölle
Neurologische Klinik und Poliklinik (M.V., M.M., T.S., T.R.T.), Klinikum rechts der Isar, Technische Universität München, Germany; Abteilung Psychosomatik und Psychotherapie (H.G.), Medizinische Hochschule Hannover, Germany; Klinik und Poliklinik für Psychiatrie und Psychotherapie (C.S.), Klinikum rechts der Isar, Technische Universität München, Germany; Klinik und Poliklinik für Psychosomatische Medizin (H.G., P.H.), Psychotherapie und Med. Psychologie, Klinikum rechts der Isar, Technische Universität München, Germany; Abteilung für Neuroradiologie (C.Z.), Institut für Röntgendiagnostik, Klinikum rechts der Isar, Technische Universität München, Germany.
Objective: To investigate whether the functional changes in pain disorder might be reflected by structural brain changes. Pain disorder assessed with the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria is characterized by persistent and distressing chronic pain at one or more body sites which cannot be fully explained by a physiological process or somatic disorder. Psychological factors are thought to play a major role. Recent neuroimaging studies evidenced altered pain processing in patients suffering from this disorder. Methods: Fourteen right-handed women fulfilling the DSM-IV criteria for pain disorder and 25 healthy age-matched women were investigated with magnetic resonance imaging. In the voxel-based morphometry analysis, we compared both groups for changes of gray-matter density. We included age and Beck Depression Inventory scores as nuisance variables to minimize possible confounding effects of age or depressive comorbidity. Results: In the patient group, we found significant gray-matter decreases in the prefrontal, cingulate, and insular cortex. These regions are known to be critically involved in the modulation of subjective pain experiences. Conclusions: In the context of similar results in patients with other functional pain syndromes, such as fibromyalgia and chronic back pain, we suggest that structural changes in fronto-limbic brain circuits represent not only an objective marker of these pain syndromes but also constitute a critical pathophysiological element. These findings represent a further proof of the important role of central changes in pain disorder.
Positron emission tomography ligand activation studies in the sports sciences: Measuring neurochemistry in vivo.
Henning Boecker, Gjermund Henriksen, Till Sprenger, Isabelle Miederer, Frode Willoch, Michael Valet, Achim Berthele, Thomas R Tölle
Nuklearmedizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Germany; Radiologische Universitätsklinik, FE Klinische Funktionelle Neurobildgebung, Rheinische Friedrich-Wilhelms-Universität Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany.
Functional neuroimaging with magnetic resonance imaging (fMRI) or positron emission tomography (PET) provides the methodology to unravel some of the fascinating, but hitherto largely unresolved interactions between physical exercise and brain function. Phenomena such as raised mood, pain modulation, and sport addiction associated with physical exercise are highly interesting psychophysical models that require further in depth understanding at the neurotransmitter level. PET ligand displacement studies allow in vivo monitoring of endogenous transmitter trafficking in the entire brain and, thereby, to identify the link between exercise-induced behavioral measures and the endogenous neurotransmitter release. This review focuses on the methodology of ligand displacement in the opioidergic system, which together with the dopaminergic system has been considered as a central neurotransmitter system underlying diverse sport-induced psychophysical effects. Understanding the basic principles of exercise-induced transmitter release in the brain will potentially aid clinical applications of endurance training, both as a preventative or therapeutic intervention.
Henning Boecker, Till Sprenger, Mary E Spilker, Gjermund Henriksen, Marcus Koppenhoefer, Klaus J Wagner, Michael Valet, Achim Berthele, Thomas R Tolle
Nuklearmedizinische Klinik, Klinikum rechts der Isar, Technische Universität München, 81675 München, Germany.
The runner's high describes a euphoric state resulting from long-distance running. The cerebral neurochemical correlates of exercise-induced mood changes have been barely investigated so far. We aimed to unravel the opioidergic mechanisms of the runner's high in the human brain and to identify the relationship to perceived euphoria. We performed a positron emission tomography "ligand activation" study with the nonselective opioidergic ligand 6-O-(2-[(18)F]fluoroethyl)-6-O-desmethyldiprenorphine ([(18)F]FDPN). Ten athletes were scanned at 2 separate occasions in random order, at rest and after 2 h of endurance running (21.5 +/- 4.7 km). Binding kinetics of [(18)F]FDPN were quantified by basis pursuit denoising (DEPICT software). Statistical parametric mapping (SPM2) was used for voxelwise analyses to determine relative changes in ligand binding after running and correlations of opioid binding with euphoria ratings. Reductions in opioid receptor availability were identified preferentially in prefrontal and limbic/paralimbic brain structures. The level of euphoria was significantly increased after running and was inversely correlated with opioid binding in prefrontal/orbitofrontal cortices, the anterior cingulate cortex, bilateral insula, parainsular cortex, and temporoparietal regions. These findings support the "opioid theory" of the runner's high and suggest region-specific effects in frontolimbic brain areas that are involved in the processing of affective states and mood.
Cerebral Processing of Histamine-Induced Itch Using Short-Term Alternating Temperature Modulation - An fMRI Study.
Michael Valet, Florian Pfab, Till Sprenger, Andreas Wöller, Claus Zimmer, Heidrun Behrendt, Johannes Ring, Ulf Darsow, Thomas R Tölle
Human neuroimaging studies on the physiology of itch have been hampered by the lack of reproducible "on-off" stimuli. Using a previously established biphasic temperature stimulus model, we investigated the cerebral activation pattern of itch processing in 12 healthy volunteers with functional magnetic resonance imaging. Itch was provoked on the right forearm with skin prick application of 1% histamine-dihydrochloride. Local temperature modulation allowed reproducible itch provocation above scratch threshold (defined as 33/100 on a visual analogue scale) during 25 degrees C, whereas itch declined below scratch threshold during the 32 degrees C stimulation period. No itch sensation was reported using 0.9% saline with temperature modulation. Itch sensation above scratch threshold was associated with increased activation of the thalamus, presupplementary motor area, anterior insular, inferior parietal, and dorsolateral prefrontal cortex, and decreased activation of the orbitofrontal, medial frontal, mid-cingulate, and primary motor cortex in comparison to saline. The biphasic temperature model allows rapid modulation of histamine-induced itch. The evoked itch sensation above scratch threshold is processed by a network of brain regions contributing to the encoding of sensory, emotional, attention-dependent, cognitive-evaluative and motivational aspects of itch.Journal of Investigative Dermatology advance online publication, 26 July 2007; doi:10.1038/sj.jid.5701002.
Imaging Human Cerebral Pain Modulation by Dose-dependent Opioid Analgesia: A Positron Emission Tomography Activation Study Using Remifentanil.
* Assistant Professor, ‡ Professor and Chairman, Klinik für Anaesthesiologie, † Assistant Professor, § Associate Professor, Neurologische Klinik und Poliklinik, Technische Universität München, Klinikum rechts der Isar. ∥ Assistant Professor, Department of Radiology, Aker University Hospital, Oslo, Norway; Nuklearmedizinische Klinik und Poliklinik, Technische Universität München, Klinikum rechts der Isar.
BACKGROUND:: Previous imaging studies have demonstrated a number of cortical and subcortical brain structures to be activated during noxious stimulation and infusion of narcotic analgesics. This study used O-water and positron emission tomography to investigate dose-dependent effects of the short-acting mu-selective opioid agonist remifentanil on regional cerebral blood flow during experimentally induced painful heat stimulation in healthy male volunteers. METHODS:: Positron emission tomography measurements were performed with injection of 7 mCi O-water during nonpainful heat and painful heat stimulation of the volar forearm. Three experimental conditions were used during both sensory stimuli: saline, 0.05 mug . kg . min remifentanil, and 0.15 mug . kg . min remifentanil. Cardiovascular and respiratory parameters were monitored noninvasively. Across the three conditions, dose-dependent effects of remifentanil on regional cerebral blood flow were analyzed on a pixel-wise basis using a statistical parametric mapping approach. RESULTS:: During saline infusion, regional cerebral blood flow increased in response to noxious thermal stimulation in a number of brain regions as previously reported. There was a reduction in pain-related activations with increasing doses of remifentanil in the thalamus, insula, and anterior and posterior cingulate cortex. Increasing activation occurred in the cingulofrontal cortex (including the perigenual anterior cingulate cortex) and the periaqueductal gray. CONCLUSIONS:: Remifentanil induced regional cerebral blood flow increases in the cingulofrontal cortex and periaqueductal gray during pain stimulation, indicating that mu-opioidergic activation modulates activity in pain inhibitory circuitries. This provides direct evidence that opioidergic analgesia is mediated by activation of established descending antinociceptive pathways.
Till Sprenger, Michael Valet, Ralph Woltmann, Claus Zimmer, Rainer Freynhagen, Eberhard F Kochs, Thomas R Tölle, Klaus J Wagner
Neurologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Moehlstr. 28, D-81675 Muenchen, Germany. email@example.com.
Little is known about the effects of low-dose S-(+)-ketamine on the cerebral processing of pain. We investigated the effects of subanesthetic IV S-(+)-ketamine doses on the perception of experimental painful heat stimuli. Healthy volunteers were evaluated with functional magnetic resonance imaging (fMRI) while receiving the painful stimuli in conjunction with placebo and increasing doses (0.05, 0.1, 0.15 mg . kg(-1). h(-1)) of ketamine infusion. Vital variables were monitored and all subjects rated pain intensity and unpleasantness on a numerical rating scale. Alterations in consciousness were measured using a psycho-behavioral questionnaire. Pain unpleasantness declined as ketamine dosage was increased (55.1% decrease, placebo versus 0.15 mg . kg(-1). h(-1) ketamine). Pain intensity ratings also decreased with increasing ketamine dosage but to a lesser extent (23.1% decrease). During placebo administration, a typical pain activation network (thalamus, insula, cingulate, and prefrontal cortex) was found, whereas decreased pain perception with ketamine was associated with a dose-dependent reduction of pain-induced cerebral activations. Analysis of the dose-dependent ketamine effects on pain processing showed a decreasing activation of the secondary somatosensory cortex (S2), insula and anterior cingulate cortex. This part of the anterior cingulate cortex (midcingulate cortex) has been linked with the affective pain component that underlines the potency of ketamine in modulating affective pain processing.
Paul Schmidt, Christian Gaser, Milan Arsic, Dorothea Buck, Annette Förschler, Achim Berthele, Muna Hoshi, Rüdiger Ilg, Volker J Schmid, Claus Zimmer, Bernhard Hemmer, Mark Mühlau
Department of Neurology, Technische Universität München, Munich, Germany.
In Multiple Sclerosis (MS), detection of T2-hyperintense white matter (WM) lesions on magnetic resonance imaging (MRI) has become a crucial criterion for diagnosis and predicting prognosis in early disease. Automated lesion detection is not only desirable with regard to time and cost effectiveness but also constitutes a prerequisite to minimize user bias. Here, we developed and evaluated an algorithm for automated lesion detection requiring a three-dimensional (3D) gradient echo (GRE) T1-weighted and a FLAIR image at 3 Tesla (T). Our tool determines the three tissue classes of gray matter (GM) and WM as well as cerebrospinal fluid (CSF) from the T1-weighted image, and, then, the FLAIR intensity distribution of each tissue class in order to detect outliers, which are interpreted as lesion beliefs. Next, a conservative lesion belief is expanded toward a liberal lesion belief. To this end, neighboring voxels are analyzed and assigned to lesions under certain conditions. This is done iteratively until no further voxels are assigned to lesions. Herein, the likelihood of belonging to WM or GM is weighed against the likelihood of belonging to lesions. We evaluated our algorithm in 53 MS patients with different lesion volumes, in 10 patients with posterior fossa lesions, and 18 control subjects that were all scanned at the same 3T scanner (Achieva, Philips, Netherlands). We found good agreement with lesions determined by manual tracing (R2 values of over 0.93 independent of FLAIR slice thickness up to 6mm). These results require validation with data from other protocols based on a conventional FLAIR sequence and a 3D GRE T1-weighted sequence. Yet, we believe that our tool allows fast and reliable segmentation of FLAIR-hyperintense lesions, which might simplify the quantification of lesions in basic research and even clinical trials.
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University Department of Neurology, Reference Center for Neurovascular Disorders, Ministry of Health and Social Welfare of the Republic of Croatia, Sestre milosrdnice University Hospital, Zagreb, Croatia. firstname.lastname@example.org
Pineal cysts occur in all ages, predominantly in adults in the fourth decade of life. In series of magnetic resonance imaging (MRI) studies, the prevalence of pineal cysts ranged between 1.3% and 4.3% of patients examined for various neurologic reasons and up to 10.8% of asymptomatic healthy volunteers. The diagnosis of pineal cyst is usually established by MRI with defined radiological criteria to distinguish benign pineal cyst from tumors of this area. A recent study demonstrated the findings obtained by transcranial sonography to correspond to those obtained by MRI in the detection of both pineal gland cyst and pineal gland itself, and could be used in the future mainly as follow up examination. Pineal cysts usually have no clinical implications and remain asymptomatic for years. The most common symptoms include headache, vertigo, visual and oculomotor disturbances, and obstructive hydrocephalus. Less frequently, patients present with ataxia, motor and sensory impairment, mental and emotional disturbances, epilepsy, circadian rhythm disturbances, hypothalamic dysfunction of precocious puberty, and recently described occurrence of secondary parkinsonism. Symptomatic cysts vary in size from 7 mm to 45 mm, whereas asymptomatic cysts are usually less than 10 mm in diameter, although a relationship between the cyst size and the onset of symptoms has been proved to be irrelevant in many cases. There is agreement that surgical intervention should be undertaken in patients presenting with hydrocephalus, progression of neurologic symptoms, or cyst enlargement. Tissue sample of the pineal lesion can be obtained by open surgery, stereotaxy and neuroendoscopy.
Sevgi Sarikaya-Seiwert, Bernd Turowski, Daniel Hänggi, Giesela Janssen, Hans-Jakob Steiger, Walter Stummer
Departments of Neurosurgery.
Pineal cysts are benign and often asymptomatic intracranial entities. Occasionally they can lead to neurological symptoms through growth or due to intracystic hemorrhage. The purpose of the current report is to describe their clinical characteristics and treatment options. In the current study, the authors illustrate the course of disease in 3 patients who developed neurological symptoms due to hemorrhage into a pineal cyst. Two of their patients had additional cerebral disease, and regular MR imaging examinations were conducted. This circumstance allowed documentation of growth and intracystic hemorrhage. After the occurrence of new neurological symptoms with severe headache, MR images showed a fluid-fluid interface due to intracystic hemorrhage. The third patient presented with acute triventricular hydrocephalus and papilledema due to aqueductal stenosis caused by intracystic hemorrhage. In all 3 cases, excision of the pineal cysts via an infratentorial/supracerebellar approach was performed. Histological examination revealed the characteristic structure of pineal cyst in all cases, with hemorrhagic residues in the form of hemosiderin deposits. All patients recovered fully after surgical removal of the cysts. Furthermore, resolution of occlusive hydrocephalus could be demonstrated in those cases with ventricular enlargement. Pineal cysts without neurological symptoms are often discovered as incidental findings on cranial MR images. In contrast, neurological symptoms such as severe headache, diplopia, or Parinaud syndrome, may occur as a result of pineal apoplexy due to intracystic hemorrhage. The authors' cases confirm that MR imaging can identify intracystic hemorrhage by a characteristic fluid-fluid interface. Their experience suggests that microsurgical resection of cysts may be an effective and curative treatment option.
Psychological assessment of malingering in psychogenic neurological disorders and non-psychogenic neurological disorders: relationship to psychopathology levels.
Department of Neurology, University Medical Center Groningen, University of Groningen, The Netherlands. email@example.com
BACKGROUND AND PURPOSE It remains unknown whether psychological distress causes malingering in patients with psychogenic symptoms. METHODS We studied 26 patients with psychogenic neurological disorders on psychopathology and malingering in comparison with 26 patients with various neurological conditions and 18 matched healthy controls (HC). RESULTS Psychogenic patients showed the highest levels of psychological complaints and malingering, but non-psychogenic neurological patients also showed significantly more psychological distress and malingering compared with HC. Psychological distress was related to the degree of malingering, in both patient groups. CONCLUSION This data does not formally support a causal relationship between psychological distress and psychogenic neurological disorders, but suggests that a part of the psychological complaints is a general result of having an illness. The clinical implication of this study is that psychological distress is not sufficient for diagnosing functional complaints. Also, if a patient scores normal on a test for malingering, this does not mean that he or she is not suffering from psychogenic symptoms.
Mikrobiol Z. ;70 (2-3):40-7 18663920
[Glycopolymers of microorganisms: molecular relationship between structure, function, and biological activity].
The results of the Department of Biochemistry investigations during the recent 5 years are presented. For the first time the structures of O-specific polysaccharides of lipopolysaccharides of representatives of Enterobacteriaceae new genus--Rahnella aquatilis have been established. The structures are represented by linear or branched mono-, tri- and hexasaccharides. As well as in other Enterobacteriaceae representatives only one hydrohylated acid--3-hydroxytetradecanoic has been established in lipids A of R. aquatilis. It was shown that toxicity and pyrogeneity of lipopolysaccharides R. aquatilis and Ralstonia solanacearum are due to the acyl-, phosphoryl- and free hydroxylic groups of lipids A. Physico-chemical properties and substrated specificity of enzymes-glycoproteins (alpha-L-rhmanosidase, a-N-acetylgalactosaminidase, collagenase and keratinase) have been studied. On the basis of the data concerning substrate specificity of the above enzymes the possible trends of their practical usage are considered.
OBJECTIVE: Pregnancy-induced hypertension with proteinuria (preeclampsia-PE) is linked to increased vascular reactivity, increased vasoconstrictors, endothelial damage and platelet hyperaggregation, which are also typical features of migraine patients. Thus, we investigated the association between headache and PE. METHODS: In a case-control study, we evaluated the occurrence of primary headache forms in 75 women with a recent history of PE. Seventy-five controls were selected from women having uneventful pregnancy at term. Both groups were matched for age and parity. Subjects' headache history was evaluated by using an ad hoc structured questionnaire. The International Headache Society criteria for primary headaches were applied to diagnose the specific form of headache. RESULTS: In PE cases, gestational age at parturition was 34.2+/-3.8 weeks and birthweight was 1820+/-746 g, whereas in controls they were 39.3+/-1.5 weeks and 3365+/-437 g, respectively (P < 0.01). Sixty-six (44%) subjects suffered from headache. Headache was significantly more frequent in PE (47/75) than in controls (19/75), OR 4.95 (95% CI, 2.47-9.92). Migraine without aura was more frequently present in cases than in controls while episodic tension-type headache was equally distributed among groups. Fifty-two patients met the criteria of severe PE. The number of patients suffering from headache was significantly higher in severe patients (39 cases, 75%) than in those with moderate PE (8 cases, 34.8%), OR = 5.63 (95% CI, 1.97-16.03). With respect to controls, PE patients reported a more frequent onset at menarche, more menstrually related attacks and an increased rate of improvement during pregnancy. CONCLUSION: This study shows that there is a strong association between migraine history and PE development, namely with the severe form of PE.
Dose-related association of MTHFR 677T allele with risk of ischemic stroke: evidence from a cumulative meta-analysis.
Neurovascular Clinical Science Unit, Mater Misericordiae University Hospital, Eccles St, Dublin 7, Ireland.
BACKGROUND Data are conflicting concerning ischemic stroke risk associated with a common polymorphism in the gene encoding 5,10-methylenetetrahydrofolate reductase (MTHFR 677C-->T), which predisposes to hyperhomocystinemia in vivo. METHODS We performed a systematic review and meta-analysis of published relevant literature. We included cohort, case-control, or cross-sectional studies reporting the frequencies of heterozygous (CT) and homozygous (TT) genotypes in (a) all stroke/TIA (overall group) and (b) imaging-proven ischemic stroke (best-phenotyped group). RESULTS Among 14 870 subjects, the pooled estimated risk of stroke/TIA associated with the 677T allele increased in a dose-dependent manner (T allele pooled OR 1.17, 95%CI 1.09 to 1.26, TT genotype pooled OR 1.37, 95%CI 1.15 to 1.64). An almost-identical relationship was observed when the analysis was restricted to imaging-proven ischemic stroke (T allele pooled OR 1.18, 95%CI 1.09 to 1.29, TT genotype pooled OR 1.48, 95%CI 1.22 to 1.8). CONCLUSIONS A graded increase in ischemic stroke risk with increasing MTHFR 677T allele dose was observed, suggesting an influence of this polymorphism as a genetic stroke risk factor and supporting other evidence indicating a causal relationship between elevated homocysteine and stroke.
Pineal cysts are common findings in neuroimaging studies. The cysts are more frequent in women in their third decade of life. Pineal cysts can be symptomatic, headache is the most common symptom. The pineal gland has important physiological implications in humans, but little is known about the impact of pineal cysts in human physiology. We report 5 headache patients with pineal cyst, 4 women, 1 man, mean age 37.6, mean cyst diameter 10.1 mm. Two patients had migraine without aura, 1 migraine with aura, 1 chronic migraine, and 1 hemicrania continua. Three patients had strictly unilateral headaches. We hypothesize pineal cysts may be not incidental in headache patients, inducing an abnormal melatonin secretion.
Division of Pediatric Neurosurgery, Department of Pediatric Surgery, Silesian University School of Medicine, ul. Medyków 16, 40-752 Katowice, Poland. firstname.lastname@example.org
INTRODUCTION Little is known about the incidence and symptomatology of pineal cysts in children. Until now, the proper management of this group of patients has not been established. PURPOSE The purpose of this study was to evaluate the epidemiological and clinical features of pineal cysts in children and adolescents and to try to find guidelines for their management. METHODS AND RESULTS We analyzed 24 patients (17 girls, mean age 9, and 7 boys, mean age 14) with pineal cysts found as the only pathology on MRI. Six patients were treated surgically (excision of the cysts via a supracerebellar-infratentorial approach) because of the progression of neurological symptoms or the enlargement of the cyst at follow-up. In this group of patients, no surgery-related complications were noted, nor was residual cyst observed on postoperative MRI. In 4 cases, histological examination revealed simple cysts, but in 2 cases pineocytomas were diagnosed. Preoperative symptoms disappeared except light headache in 2 cases and in 1 case no improvement was obtained. The remaining 18 patients had a mean follow-up of 38 months (range 24-60 months). None of the cysts diminished or collapsed. We also measured the circadian pattern of melatonin secretion as well as beta-HCG and AFP levels in serum before surgery. We found very high night levels of melatonin in both of the patients with pineocytomas, while the patients with pineal cysts showed normal or depressed melatonin secretion profile. CONCLUSION We concluded that though most pineal cysts were clinically benign they should be followed up for many years. If the cyst grows larger in follow-up MRI study and neurological symptoms are progressive, surgical treatment should be performed. In the authors' opinion, one of the markers discriminating benign and neoplastic lesions may be melatonin.
Double-blind, multicenter trial to compare the efficacy of intramuscular dihydroergotamine plus hydroxyzine versus intramuscular meperidine plus hydroxyzine for the emergency department treatment of acute migraine headache.
S C Carleton, R F Shesser, M P Pietrzak, C R Chudnofsky, S Starkman, D L Morris, G Johnson, K J Rhee, C W Barton, J E Chelly, J Rosenberg, M K Van Valen
Department of Emergency Medicine, University Hospital of Cincinnati, OH 45267-0769, USA. Steven.Carleton@uc.edu
STUDY OBJECTIVE To evaluate intramuscular dihydroergotamine in direct comparison with opioid analgesia in the treatment of acute migraine headache. METHODS This was a prospective, multicenter, double-blind trial performed in the emergency departments of 11 general hospitals in the United States. One hundred seventy-one patients between the ages of 18 and 60 years who presented to the ED with acute migraine headache were enrolled. Patients were randomly assigned to receive either 1 mg dihydroergotamine (DHE) or 1.5 mg/kg meperidine (MEP) by intramuscular injection. The anti-nauseant hydroxyzine (H) was coadministered in both treatment groups. RESULTS One hundred fifty-six patients were evaluable. Treatment groups were comparable in sample size, demographics, and baseline measurements of headache pain. Reduction of headache pain as measured on a 100-mm visual analog scale was 41+/-33 mm (53.5% reduction) for the DHE group, and 45+/-30 mm (55.7% reduction) for the MEP group at 60 minutes after treatment (difference=2.2%; 95% confidence interval [CI]-10%, 14.5%; P=.81). Reduction in the severity of nausea and improvement in functional ability were similar between treatment groups. Central nervous system adverse events were less common in the DHE group (DHE 23.5% versus MEP 37.6%, difference-14.1%: 95% CI -28%, 0%). In particular, dizziness was reported less commonly with DHE than MEP (2% versus 15%, difference=-13%: 95% CI -21%,-5%). CONCLUSION In this prospective, double-blind trial of a convenience sample of ED patients randomly assigned to one of two treatment regimens, DHE and MEP were comparable therapies for acute migraine. The use of DHE avoids several problems associated with opioid analgesia, including dizziness.
INSERM U 330 and Department of Neurology, Université de Bordeaux II, France.
The burden of migraine in terms of cost and impact on socioeconomic indicators is still controversial. In a recent comparative study between migraineurs and controls from the French general population, we show that only general practitioner (GP) consultations and complementary examinations are more frequent in migraineurs. In this paper, we compare the socioeconomic impact of migraine versus another common neurological disease, low back pain, which has similar consequences in term of deficiencies, disabilities, and handicaps. Our study is a subproject of the Gazel cohort study, conducted on 20,000 volunteers working in the "Electricité et Gaz de France" company. The socioeconomic impact was evaluated prospectively by the number of workdays missed between 1989 and 1992 in 436 subjects with migraine but without low back pain (M group), 590 subjects with low back pain but without migraine (L group), 555 subjects with migraine and low back pain (ML group), and in 1005 subjects without headache or low back pain (C group). Moreover, in 1993 all subjects completed a mailed questionnaire on their 6-months' history of use of medical services. The number of workdays missed during this 4-year period was statistically greater in the ML group (58.1 days), followed by the L group (38.4 days), the C group (35.1 days), and the M group (31.8 days)(p = 0.0001). For the use of medical services, the results were different according to the different indicators: GP consultations were more frequent in the ML and M groups, specialist consultations and complementary examinations in the L and C groups. In conclusion, migraine and low back pain seem to have a similar socioeconomic impact. Absenteeism is particularly high when both neurological disorders are present.