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1.
Clin Neurol Neurosurg ; 236: 108112, 2024 01.
Article in English | MEDLINE | ID: mdl-38232607

ABSTRACT

OBJECTIVE: Other primary headache disorders (OPHD) are under-investigated compared to frequent primary headache types like migraine, tension-type headache, and trigeminal autonomic cephalalgias. Knowledge of the distribution and characteristics of OPHD subtypes is crucial for their recognition. We aimed to determine the prevalence at the hospital and headache clinics and clinical characteristics of OPHDs in patients from 13 countries. METHODS: We analyzed a large dataset from the cross-sectional study Head-MENA-A (Middle East, North Africa, Asia). Consecutive patients over 10 years of age presenting with headaches were included from outpatient, inpatient, and emergency settings. A structured questionnaire addressing demographics, headache characteristics, accompanying symptoms, and triggers was administered. Headache subtypes were diagnosed according to the ICHD-3 criteria. RESULTS: Among patients complaining of headaches (n = 3722), 106 (2.9%) were diagnosed with OPHD. Fifty-two patients (1.4% of all headache patients) had only OPHD, while 54 (1.5%) had both OPHD and a co-existing primary headache (mostly migraine). All OPHDs were more common in females. The most frequent subtypes were new daily persistent headache and primary stabbing headache (0.2% each among all admitted patients). Photophobia and phonophobia were the most frequent accompanying symptoms, while physical activity (28.8%), stress (15.4%), and the Valsalva maneuver (15.4%) were the most common triggering factors. The majority of triggering factors were more pronounced in patients with both migraine and OPHD. CONCLUSIONS: Other primary headaches are rare and heterogeneous. Their high co-existence with migraine suggests shared predisposing factors, hinting at a "headache continuum" concept for primary headaches.


Subject(s)
Headache Disorders, Primary , Headache Disorders , Migraine Disorders , Female , Humans , Cross-Sectional Studies , Headache/epidemiology , Headache/diagnosis , Migraine Disorders/epidemiology , Migraine Disorders/diagnosis , Asia/epidemiology , Africa/epidemiology , Middle East/epidemiology , Headache Disorders, Primary/epidemiology
2.
J Headache Pain ; 24(1): 24, 2023 Mar 13.
Article in English | MEDLINE | ID: mdl-36915115

ABSTRACT

BACKGROUND: Headaches are frequent neurological disorders that are yet to be unveiled and treated comprehensively worldwide. Bearing in mind that the distribution of headache subtypes in neurology clinics (NC) is essential for planning appropriate diagnostic and therapeutic approaches, the primary goals of this multi-centric study are to carry out inter-regional comparisons by using current diagnostic criteria with evaluations of neurologists to delineate headache burden. METHODS: A cross-sectional study between April 1 and May 16, 2022 was conducted with the participation of 13 countries from the Middle East, Asia, and Africa. Patients were included in the study on a specific day each week during five consecutive weeks. All volunteers over the age of 18 and whose primary cause for admission was headache were examined. The patients admitted to NC or referred from emergency services/other services were evaluated by neurologists by means of the International Classification of Headache Disorders (ICHD-3) criteria. RESULTS: Among the 13,794 patients encountered in NC, headache was the primary complaint in 30.04%. The headache patients' mean age was 42.85 ± 14.89 (18-95 years), and 74.3% were female. According to the ICHD-3 criteria, 86.7% of the main group had primary headache disorders, 33.5% had secondary headaches, 4% had painful cranial neuropathies along with other facial and headaches, and 5.2% had headaches included in the appendix part showing some overlapping conditions. While the most common primary headache was migraine without aura (36.8%), the most common secondary headache was medication-overuse headache (MOH) (9.8%). Headaches attributed to COVID-19, its secondary complications, or vaccines continue to occur at rates of 1.2%-3.5% in current neurology practice. Pain severity was significantly lower in Ivory Coast and Sudan than in Türkiye, Turkish Republic of Northern Cyprus, Iran, Egypt, Senegal, Tatarstan, and Azerbaijan (p < 0.001). CONCLUSIONS: The study showed that migraine is still the most common motive for admissions to NC in different regions. Furthermore, MOH, an avoidable disorder, is the most common secondary headache type and appears to be a significant problem in all regions. Remarkably, pain perception differs between regions, and pain intensity is lower in Africa than in other regions.


Subject(s)
COVID-19 , Headache Disorders, Secondary , Headache Disorders , Migraine Disorders , Humans , Female , Adult , Middle Aged , Male , Cross-Sectional Studies , COVID-19/complications , Headache/diagnosis , Headache/epidemiology , Headache/therapy , Headache Disorders/diagnosis , Headache Disorders/epidemiology , Headache Disorders/therapy , Migraine Disorders/diagnosis , Asia , Headache Disorders, Secondary/diagnosis , Middle East/epidemiology , Africa/epidemiology , Hospitals
3.
HNO ; 58(11): 1085-93, 2010 Nov.
Article in German | MEDLINE | ID: mdl-20809193

ABSTRACT

BACKGROUND: Music therapy in chronic tonal tinnitus according to the "Heidelberger model" presents an effective treatment, which is substantiated by neuroscientific and psychological evaluation. METHOD: The music therapy approach was specifically extended to include noisiform tinnitus, taking sound quality and cardiovascular influences into consideration. Outcome criteria were psychological tinnitus load, psychophysiologic parameters and brain imaging procedures. RESULTS: Psychological outcomes of the pilot study indicate that 21 of the 23 patients (i.e. more than 90%) achieved a reliable reduction of symptoms (TQ scores: pre: 40.1 ± 11.4; post: 27.9 ± 12.8; at 3-month-follow-up: 24.0 ± 12.2). Results of the imaging examinations demonstrated neuroplastic changes in the putamen and insula. Psychophysiological measurements indicate cardiovascular influences on noisiform tinnitus. DISCUSSION: Therapy success depends on the sound quality of the tinnitus; therefore, any treatment should take this into consideration. Cardiovascular influences were important insofar as active control of the heart rate was an important predictor of long-term therapy outcome. Overall, brain imaging data confirm the top-down-model of tinnitus generation.


Subject(s)
Music Therapy/methods , Tinnitus/diagnosis , Tinnitus/rehabilitation , Female , Humans , Male , Middle Aged , Treatment Outcome
4.
Cephalalgia ; 30(4): 457-66, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19673896

ABSTRACT

An altered neurovascular coupling has been proposed in migraine. We aimed to investigate neurovascular coupling during a mental task interictally in patients with migraine without aura (MO) by near-infrared spectroscopy (NIRS). Twelve migraineurs and 12 healthy controls were included. Using NIRS, we recorded the magnitude and latency of cortical changes in oxyhaemoglobin (HbO(2)) and deoxyhaemoglobin (Hb) during the colour-word matching Stroop test via 16 channels covering the forehead. We found no differences in the magnitude of responses between migraineurs and healthy subjects in the incongruent Stroop task subtracted by the neutral Stroop task on either side of the frontal cortex for HbO(2) (left, P = 0.984; right, P = 0.406) or Hb (left, P = 0.689; right, P = 0.406) values. No differences in error rate (P = 0.611) or reaction time (P = 0.936) were found between healthy subjects and MO patients for incongruent tasks. The present study suggests that vascular reactivity and oxygen supply during a mental task in patients with MO are intact interictally.


Subject(s)
Cerebral Cortex/physiology , Executive Function/physiology , Migraine without Aura/physiopathology , Spectroscopy, Near-Infrared , Adolescent , Adult , Cerebral Cortex/blood supply , Female , Forehead , Hemoglobins/metabolism , Humans , Middle Aged , Migraine without Aura/metabolism , Oxyhemoglobins/metabolism , Reaction Time/physiology , Stroop Test , Young Adult
5.
Cephalalgia ; 29(10): 1059-68, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19735534

ABSTRACT

It has been recently noticed that dust originating from deserts can be transported to other continents by the atmosphere and has an adverse effect on public health, such as increased asthma attacks. Dust originating from the Saharan Desert could initiate a series of reactions upon contact with cloud water and results in the formation of reduced iron (Fe(2+)), oxalate and various basic amino acids. We aimed to evaluate whether the simulation of Saharan dust-containing atmospheric conditions could trigger the trigeminovascular system. Freely moving rats incubated within simulated atmospheric conditions containing (i) Saharan dust, (ii) Co(60) gamma ray-treated Saharan dust (sterilized) and (iii) dust-free air, were investigated for the presence of c-fos expression in trigeminal nucleus caudalis (TNC) and for NOx (nitrate+nitrite) levels in blood samples. Atmospheric samples were analysed for microorganisms. Saharan dust-containing atmospheric conditions induced c-fos expression in nociceptive neurons within TNC. The number of c-fos+ neurons in superficial lamina of TNC was significantly higher in the Saharan dust group (32.9 +/- 5.3, P = 0.0001) compared with dust-free air (11.02 +/- 2.7) or Co(60)-treated Saharan dust groups (15.01 +/- 2.4). An increase in NOx levels was detected in blood samples of rats exposed to Saharan dust-containing atmosphere. This study has revealed an unknown environmental factor as a possible trigger for headache. It is the first time that transport of Saharan dust with the atmospheric air stream has been documented to be able to trigger the trigeminovascular system in animals. Further studies are needed to explore the mechanisms and molecules that mediate the nociceptive effect and to guide new treatment strategies.


Subject(s)
Desert Climate , Dust/immunology , Environmental Exposure , Neurons/immunology , Particulate Matter/toxicity , Trigeminal Nuclei/blood supply , Trigeminal Nuclei/immunology , Africa, Northern , Animals , Male , Neurons/drug effects , Rats , Rats, Wistar , Trigeminal Nuclei/drug effects
6.
Cephalalgia ; 29(10): 1125-8, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19735538
7.
HNO ; 56(7): 678-85, 2008 Jul.
Article in German | MEDLINE | ID: mdl-18566786

ABSTRACT

Tinnitus has a very high prevalence, with more than one million patients in the German population needing treatment for it. About 50% of them suffer from so-called tonal tinnitus, i.e., tinnitus with a well-defined frequency. Although tinnitus is one of the most common symptoms in ENT medicine, the existing treatments are polypragmatic and often lack a scientific foundation. Based on this fact, a novel music therapy concept was developed, evaluated, and scientifically substantiated (with psychological, audiological, and functional imaging procedures in the diagnosis and treatment). The advantages of the described therapy are the integration of known and well-proven acoustic and psychotherapeutic techniques. They were converted to specific music therapy interventions (resonance training, neuroauditive cortex reprogramming, and tinnitus desensitization). More than 190 patients suffering from chronic tonal tinnitus were effectively treated. The results indicate that the therapy is highly advantageous in terms of treatment duration, effectiveness, and follow-up stability compared with customary interventions. Furthermore, the results of brain imaging strongly suggest the usefulness of further investigation and discussion in the realm of neuronal tinnitus modeling.


Subject(s)
Clinical Trials as Topic/statistics & numerical data , Evidence-Based Medicine/statistics & numerical data , Music Therapy/methods , Music Therapy/statistics & numerical data , Tinnitus/epidemiology , Tinnitus/rehabilitation , Germany/epidemiology , Prevalence , Treatment Outcome
8.
Cephalalgia ; 28(4): 309-17, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18279433

ABSTRACT

Otoacoustic emission (OAE) testing enables us to identify the cochlear component of a hearing disorder and to monitor objectively minute changes in cochlear status undetectable by other audiological methods. Contralateral sound-induced suppression is mediated by medial superior olivary complex efferents which induce hyperpolarization counteracting the amplifying effects of outer hair cell (OHC) activity. The aim of this study was to assess functions of cochlea and its efferents in migraine using OAE testing and contralateral suppression of transiently evoked OAEs (TEOAE). Fifty-three migraineurs (106 ears) and 41 healthy subjects (82 ears) were included and pure tone audiometry (PTA), speech discrimination scores (SDS), distortion product OAE (DPOAE), TEOAE and contralateral suppression of TEOAEs were tested. PTA and SDS of migraineurs and controls were not different (P > 0.05). DPOAEs were tested between 1 and 6 kHz and a significant difference was detected only at 5 kHz frequency, where DPOAE amplitudes in migraine with aura (MA) were lower than in controls (P < 0.03). The mean amplitudes of TEOAEs were statistically insignificant between controls and migraine groups. Contralateral sound stimulus induced significant decrease in amplitudes of TEOAE (P = 0.005) in controls. In patients with migraine without aura and MA, mean amplitudes of TEOAEs were not suppressed by contralateral sound stimulus (P > 0.05). As PTA, SDS and DPOAE tests demonstrate normal functioning of inner ear between 1 and 4 kHz, absence of suppression of the TEOAEs by contralateral sound stimulation indicates the presence of dysfunction either in the medial olivocochlear complex in the brainstem or at the synaptic transmission between olivocochlear efferents and OHCs in the cochlea. Disruption in the contralateral suppression may be one of the mechanisms predisposing to the phonophobia symptom associated with migraine headache.


Subject(s)
Cochlea/physiopathology , Cochlear Nerve/physiopathology , Migraine Disorders/physiopathology , Olivary Nucleus/physiopathology , Otoacoustic Emissions, Spontaneous , Acoustic Stimulation , Adolescent , Adult , Audiometry, Pure-Tone , Audiometry, Speech , Auditory Pathways , Cochlear Nerve/cytology , Evoked Potentials, Auditory , Female , Humans , Male , Middle Aged , Neural Inhibition/physiology , Neurons, Efferent/physiology , Olivary Nucleus/cytology
9.
Acta Neurochir (Wien) ; 149(10): 1041-7; discussion 1047-8, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17876498

ABSTRACT

BACKGROUND: Though cerebral vasospasm is one of the most serious complications of subarachnoid haemorrhage (SAH), its complex pathogenesis is poorly understood and available clinical treatment options are unsatisfactory. This study was designed to examine the efficacy of leflunomide, an immunomodulatory agent with inhibitory properties, on vascular smooth muscle cell proliferation and inflammation in a rabbit cerebral vasospasm model. METHODS: Twenty-two adult New-Zealand rabbits were assigned to 4 groups: control, SAH, SAH plus vehicle, SAH plus leflunomide. Subarachnoid haemorrhage was induced by administration of 1 ml of fresh unheparinised autologous arterial blood into the cisterna magna. Oral leflunomide (2 mg/kg) or vehicle treatment was started 12 h after the induction of subarachnoid haemorrhage and administered once a day. Three days later, the animals were sacrificed and the basilar artery was examined histologically for the lumen area and the thickness of the vessel wall. Inflammatory reaction was also examined by counting white blood cells within the vessel wall by means of light microscopic examination using haematoxylin and eosin staining. FINDINGS: Severe and moderate vasospasms were detected in the basilar artery of the SAH and SAH plus vehicle treated groups, respectively. Leflunomide effectively reduced the vasospasm of the basilar artery. Compared to the vehicle treated group, leflunomide significantly reduced the lumen area (p < 0.01) and hyperplasia of the vessel wall (p < 0.01). Although inflammatory response within the vessel wall was reduced in the leflunomide treated group, no statistical significance was found between groups (p = 0.07). CONCLUSION: This study demonstrates for the first time that leflunomide treatment attenuates cerebral vasospasm in a rabbit SAH model while inflammatory reaction in the vessel wall is not affected. Although further studies are needed to reveal its molecular mechanisms in relieving vasospasm, leflunomide may provide a therapeutic potential for human cerebral vasospasm induced by SAH.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Basilar Artery/drug effects , Isoxazoles/pharmacology , Subarachnoid Hemorrhage/pathology , Vasospasm, Intracranial/prevention & control , Animals , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Basilar Artery/pathology , Disease Models, Animal , Fibromuscular Dysplasia/pathology , Isoxazoles/adverse effects , Leflunomide , Leukocyte Count , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/pathology , Rabbits , Vasoconstriction/drug effects , Vasospasm, Intracranial/pathology
10.
Neurorehabil Neural Repair ; 21(5): 455-9, 2007.
Article in English | MEDLINE | ID: mdl-17426347

ABSTRACT

OBJECTIVES: The effectiveness of 2 different types of gait training in stroke rehabilitation, rhythmic auditory stimulation (RAS) versus neurodevelopmental therapy (NDT)/Bobath- based training, was compared in 2 groups of hemiparetic stroke patients over a 3-week period of daily training (RAS group, n = 43; NDT/Bobath group =35). METHODS: Mean entry date into the study was 21.3 days poststroke for the RAS group and 22.3 days for the control group. Patients entered the study as soon as they were able to complete 5 stride cycles with handheld assistance. Patients were closely equated by age, gender, and lesion site. Motor function in both groups was pre-assessed by the Barthel Index and the Fugl-Meyer Scales. RESULTS: Pre- to posttest measures showed a significant improvement in the RAS group for velocity (P = .006), stride length (P = .0001), cadence (P = .0001) and symmetry (P = .0049) over the NDT/Bobath group. Effect sizes for RAS over NDT/Bobath training were 13.1 m/min for velocity, 0.18 m for stride length, and 19 steps/min for cadence. CONCLUSIONS: The data show that after 3 weeks of gait training, RAS is an effective therapeutic method to enhance gait training in hemiparetic stroke rehabilitation. Gains were significantly higher for RAS compared to NDT/Bobath training.


Subject(s)
Acoustic Stimulation , Gait Disorders, Neurologic/physiopathology , Gait Disorders, Neurologic/rehabilitation , Stroke/complications , Aged , Aged, 80 and over , Female , Gait Disorders, Neurologic/etiology , Humans , Male , Middle Aged , Recovery of Function/physiology , Rehabilitation/methods , Single-Blind Method , Stroke/physiopathology , Stroke Rehabilitation , Time Factors , Treatment Outcome
12.
HNO ; 55(5): 375-83, 2007 May.
Article in German | MEDLINE | ID: mdl-17082957

ABSTRACT

BACKGROUND: Chronic tinnitus, one of the most common disorders in ENT medicine, requires comprehensive and interdisciplinary treatment. OBJECTIVE: An innovative music therapy approach, developed at the German Center for Music Therapy Research in cooperation with the ENT clinic of the University of Heidelberg ("Heidelberg Model"), strives to integrate the tinnitus sound into a musically controllable acoustic process. The aim of the present study is to evaluate the effectiveness of this current treatment. METHODS: We carried out a prospective, two-armed (music therapy group vs control group) study with 20 patients (10 males, 10 females; mean age 51+/-7 years), suffering from decompensated chronic tinnitus (mean score in the Tinnitus Questionnaire TQ=46.8+/-9.6). The target variables involved TQ values, pre- and post-measurements, and follow-up after 3 and 6 months. RESULTS: Group comparison yields a highly statistically and clinically significant decrease in mean TQ-scores pre- and post in the music therapy group by 25 points or 52% on average as compared to 2 points (4%) in the control group [univariate ANOVA: (F(1,31)=14.19, P=0.001), effect size d=1.73]. Logarithmic regression analysis reveals a fast onset and long lasting effect of music therapy (B=-8.9; F(1,125)=32.11, P=0.000). DISCUSSION: The effectiveness of this highly economic approach was proven as the innovative music therapy concept yields statistically and clinically significant results which remain stable throughout follow-up. Further investigations with larger sample sizes and using brain imaging should strengthen these findings.


Subject(s)
Music Therapy/methods , Patient Care Team , Tinnitus/diagnosis , Tinnitus/rehabilitation , Adult , Chronic Disease , Female , Germany , Humans , Male , Middle Aged , Outcome Assessment, Health Care , Pilot Projects , Treatment Outcome
13.
Rev Neurol (Paris) ; 161(6-7): 655-7, 2005 Jul.
Article in English | MEDLINE | ID: mdl-16141950

ABSTRACT

Migraine is a disabling neurovascular disorder with a complex pathophysiology. Functional imaging and magneto encephalographic studies strongly suggest that Cortical Spreading Depression (CSD) constitutes the biological basis for the neurologic aura that precedes headache in one fourth of migrainers. It is likely that the aura is the generator of the headache since experimentally, CSD triggers the activation of the trigeminovascular system, possibly through matrix metalloproteases activation which is associated with an increase in vascular permeability. These data may have therapeutic implications: strategies to block trigeminal activation or its downstream consequences are central to treat the acute headache whereas strategies to block events lying upstream of trigeminal activation would be crucial in prophylaxis.


Subject(s)
Cortical Spreading Depression/physiology , Migraine Disorders/physiopathology , Brain Chemistry/physiology , Cerebrovascular Circulation/physiology , Humans , Migraine Disorders/etiology , Migraine Disorders/metabolism , Migraine with Aura/etiology , Migraine with Aura/metabolism , Migraine with Aura/physiopathology
14.
Brain ; 124(Pt 12): 2490-502, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11701602

ABSTRACT

Nitric oxide (NO) has been implicated in migraine pathogenesis based on the delayed development of typical migraine headache 4-6 h after infusing the NO donor nitroglycerin [glyceryl trinitrate (GTN)] to migraineurs. Furthermore, inhibiting the synthesis of NO by treatment with a NO synthase (NOS) inhibitor attenuates spontaneous migraine headaches in 67% of subjects. Because NO has been linked to inflammation and cytokine expression, we investigated the delayed consequences of brief GTN infusion (30 min) on the development of meningeal inflammation in a rat model using doses relevant to the human model. We found dose-dependent Type II NOS [inducible NOS (iNOS)] mRNA upregulation in dura mater beginning at 2 h and an increase in the corresponding protein expression at 4, 6 and 10 h after infusion. Type II NOS immunoreactivity was expressed chiefly within resident meningeal macrophages. Consistent with development of a delayed inflammatory response, we detected induction of interleukin 1beta in dura mater at 2 and 6 h and increased interleukin 6 in dural macrophages and in rat cerebrospinal fluid at 6 h after GTN infusion. Myeloperoxidase-positive cells were rarely found. Leakage of plasma proteins from dural blood vessels was first detected 4 h after GTN infusion, and this was suppressed by administering a specific Type II NOS inhibitor [L-N(6)-(1-iminoethyl)-lysine (L-NIL)]. In addition to cytokine induction, macrophage iNOS upregulation and oedema formation after GTN infusion, dural mast cells exhibited granular changes consistent with secretion at 4 and 6 h. Because iNOS was expressed in dural macrophages following topical GTN, and in the spleen after intravenous injection, the data suggest that the inflammatory response is mediated by direct actions on the dura and does not develop secondary to events within the brain. Our findings point to the importance of new gene expression and cytokine expression as fundamental to the delayed response following GTN infusion, and support the hypothesis that a similar response develops in human meninges after GTN challenge.


Subject(s)
Meningitis/immunology , Meningitis/physiopathology , Migraine Disorders/immunology , Migraine Disorders/physiopathology , Animals , Blood Proteins/metabolism , Dura Mater/immunology , Dura Mater/metabolism , Gene Expression/immunology , Interleukin-1/analysis , Interleukin-1/biosynthesis , Interleukin-6/analysis , Interleukin-6/biosynthesis , Macrophages/chemistry , Macrophages/immunology , Macrophages/metabolism , Male , Mast Cells/chemistry , Mast Cells/drug effects , Mast Cells/immunology , Nitric Oxide/immunology , Nitric Oxide Synthase/genetics , Nitric Oxide Synthase Type II , Nitroglycerin/pharmacology , RNA, Messenger/analysis , Rats , Rats, Sprague-Dawley , Vasodilator Agents/pharmacology
15.
Brain Res ; 917(2): 174-81, 2001 Nov 02.
Article in English | MEDLINE | ID: mdl-11640903

ABSTRACT

Brief cerebral ischemia is reported to cause selective neuronal necrosis, apoptotic cell death, silent infarcts and, when recurrent, cognitive decline. Acute administration of selegiline and EGb 761 have been shown to have anti-apoptotic and neuroprotective effects in experimental ischemia. Their daily use is currently advised to slow down cognitive decline in patients with vascular dementia. Hence, unlike previous studies, we studied the neuroprotective action of chronic daily administration of these drugs in Swiss mice subjected to 30-min middle cerebral artery occlusion and 72 h of reperfusion since this model was reported to induce a slowly evolving infarct with profuse apoptotic cell death. Infarct area was evaluated by H&E staining on coronal brain sections and, apoptotic cells were identified by histological criteria, terminal transferase-mediated d-UTP nick-end labeling (TUNEL) and by immunohistochemical detection of caspase-cleaved actin fragments (fractin). Fifty-one mice received daily intraperitoneal injections of 10 mg/kg selegiline (n=18) or 50 mg/kg EGb 761 (n=17) or equal volume of saline (n=16) for 10-14 days before but not on the day of insult. The infarct volume, number of TUNEL- and fractin-positive cells were significantly reduced in treatment groups by 30, 42 and 51% (selegiline) and, 27, 27 and 29% (EGb 761), respectively. These data suggest that prophylactic use of selegiline and EGb 761 could increase the brain's resistance to mild ischemic injury.


Subject(s)
Brain Ischemia/prevention & control , Brain/drug effects , Brain/physiology , Neuroprotective Agents/pharmacology , Plant Extracts/administration & dosage , Selegiline/administration & dosage , Selegiline/pharmacology , Actins/chemistry , Animals , Apoptosis , Caspases/physiology , Cerebral Infarction/pathology , Drug Administration Schedule , Ginkgo biloba , Immunity, Innate , In Situ Nick-End Labeling , Mice , Neurons/metabolism , Neurons/physiology , Plant Extracts/pharmacology
16.
J Cereb Blood Flow Metab ; 21(3): 195-201, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11295873

ABSTRACT

A method for dynamic, high-resolution cerebral blood flow (CBF) imaging is presented in this article. By illuminating the cortex with laser light and imaging the resulting speckle pattern, relative CBF images with tens of microns spatial and millisecond temporal resolution are obtained. The regional CBF changes measured with the speckle technique are validated through direct comparison with conventional laser-Doppler measurements. Using this method, dynamic images of the relative CBF changes during focal cerebral ischemia and cortical spreading depression were obtained along with electrophysiologic recordings. Upon middle cerebral artery (MCA) occlusion, the speckle technique yielded high-resolution images of the residual CBF gradient encompassing the ischemic core, penumbra, oligemic, and normally perfused tissues over a 6 x 4 mm cortical area. Successive speckle images demonstrated a further decrease in residual CBF indicating an expansion of the ischemic zone with finely delineated borders. Dynamic CBF images during cortical spreading depression revealed a 2 to 3 mm area of increased CBF (160% to 250%) that propagated with a velocity of 2 to 3 mm/min. This technique is easy to implement and can be used to monitor the spatial and temporal evolution of CBF changes with high resolution in studies of cerebral pathophysiology.


Subject(s)
Cerebrovascular Circulation/physiology , Cortical Spreading Depression/physiology , Image Processing, Computer-Assisted/methods , Infarction, Middle Cerebral Artery/physiopathology , Lasers , Animals , Brain Ischemia/diagnosis , Brain Ischemia/physiopathology , Disease Models, Animal , Infarction, Middle Cerebral Artery/diagnosis , Male , Rats , Rats, Wistar , Scattering, Radiation
17.
Stroke ; 31(8): 1974-80; discussion 1981, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10926966

ABSTRACT

BACKGROUND AND PURPOSE: Reperfusion injury is one of the factors that unfavorably affects stroke outcome and shortens the window of opportunity for thrombolysis. Surges of nitric oxide (NO) and superoxide generation on reperfusion have been demonstrated. Concomitant generation of these radicals can lead to formation of the strong oxidant peroxynitrite during reperfusion. METHODS: We have examined the role of NO generation and peroxynitrite formation on reperfusion injury in a mouse model of middle cerebral artery occlusion (2 hours) and reperfusion (22 hours). The infarct volume was assessed by 2,3,5-triphenyl tetrazolium chloride staining; blood-brain barrier permeability was evaluated by Evans blue extravasation. Nitrotyrosine formation and matrix metalloproteinase-9 expression were detected by immunohistochemistry. RESULTS: Infarct volume was significantly decreased (47%) in animals treated with the nonselective nitric oxide synthase (NOS) inhibitor N(omega)-nitro-L-arginine (L-NA) at reperfusion. The specific inhibitor of neuronal NOS, 7-nitroindazole (7-NI), given at reperfusion, showed no protection, although preischemic treatment with 7-NI decreased infarct volume by 40%. Interestingly, prereperfusion administration of both NOS inhibitors decreased tyrosine nitration (a marker of peroxynitrite toxicity) in the ischemic area. L-NA treatment also significantly reduced vascular damage, as indicated by decreased Evans blue extravasation and matrix metalloproteinase-9 expression. CONCLUSIONS: These data support the hypothesis that in addition to the detrimental action of NO formed by neuronal NOS during ischemia, NO generation at reperfusion plays a significant role in reperfusion injury, possibly through peroxynitrite formation. Contrary to L-NA, failure of 7-NI to protect against reperfusion injury suggests that the source of NO is the cerebrovascular compartment.


Subject(s)
Endothelium, Vascular/metabolism , Infarction, Middle Cerebral Artery/complications , Nitrates/metabolism , Nitric Oxide/biosynthesis , Oxidants/metabolism , Reperfusion Injury/metabolism , Animals , Biomarkers , Blood-Brain Barrier/drug effects , Blood-Brain Barrier/physiology , Coloring Agents , Enzyme Inhibitors/pharmacology , Evans Blue , Indazoles/pharmacology , Infarction, Middle Cerebral Artery/metabolism , Infarction, Middle Cerebral Artery/pathology , Infarction, Middle Cerebral Artery/prevention & control , Matrix Metalloproteinase 9/biosynthesis , Mice , Nitric Oxide Synthase/antagonists & inhibitors , Nitroarginine/pharmacology , Permeability/drug effects , Reperfusion Injury/drug therapy , Reperfusion Injury/etiology , Reperfusion Injury/pathology , Tyrosine/analogs & derivatives , Tyrosine/biosynthesis
18.
Brain Res ; 873(1): 26-33, 2000 Aug 04.
Article in English | MEDLINE | ID: mdl-10915807

ABSTRACT

We recently demonstrated that a long-lasting transmission defect in cortical synapses caused motor dysfunction after brief middle cerebral artery (MCA) occlusion in the rat despite rapid recovery of axons. In this experimental study, we have examined the impact of differential recovery of synapses and axons on generation of motor-evoked potentials (MEP) recorded from contralateral paralyzed and ipsilateral unaffected muscles, to gain insight into mechanisms of MEPs recorded from stroke patients by transcranial magnetic stimulation (TMS). MEPs generated by focal electrical stimulation of the forelimb area of motor cortex were simultaneously recorded from the brain stem, contra- and ipsilateral forelimb and contralateral hindlimb muscles in rats subjected to transient MCA occlusion. The effect of ischemia on cortical activity and axonal conduction was differentially studied by proximal or distal occlusion of the MCA. Regional cerebral blood flow changes in the forelimb area were monitored by laser-Doppler flowmetry during ischemia and reperfusion. In addition, synaptic transmission within the forelimb area of motor cortex was examined by intracellular and extracellular recording of potentials generated by stimulation of the premotor area. No MEP response was recorded during ischemia. Upon reperfusion: (i) motor axons readily regained their excitability and cortical stimulation caused successive pyramidal volleys (recorded as D waves from the brain stem) and a MEP from contralateral paralytic muscles although synaptic activation of motor pathways was not feasible; (ii) the amplitude of pyramidal volley was increased; (iii) MEPs with a longer latency were recorded from the ipsilateral forelimb. In conclusion, differential recovery of synapses and axons after ischemia may account for some previously unexplained findings (such as preserved MEPs in paralysed muscles) observed in cortical stimulation studies of stroke patients.


Subject(s)
Evoked Potentials, Motor , Ischemic Attack, Transient/physiopathology , Animals , Brain Stem/physiopathology , Motor Cortex/blood supply , Motor Cortex/physiopathology , Muscle, Skeletal/physiopathology , Physical Stimulation , Rats , Rats, Wistar , Synaptic Transmission , Transcranial Magnetic Stimulation
20.
Eur Spine J ; 9(1): 80-4, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10766083

ABSTRACT

A 17-year-old patient with pre-existing grade II spondylolisthesis of L5/S1 sustained a partial disruption of the left sacroiliac joint with haematoma of the iliac muscle after a fall. The haematoma probably led to occlusion of the left ureter, resulting in a urinary tract infection. After initial conservative treatment the patient developed fever and radicular pain of the left leg. Magnetic resonance imaging (MRI) revealed a left-sided epidural abscess at L5/S1, which had probably spread from the infected iliac haematoma along the injured sacroiliac joint. Prompt surgical drainage and antibiotic coverage with cefuroxime and flucloxacillin led to rapid clinical improvement. Staphylococcus aureus was identified as the pathogen. At follow-up 6 months postoperatively all symptoms had resolved, while MRI still revealed residual osseous oedema of the sacroiliac joint. The haematoma of the iliac muscle resolved without surgical intervention.


Subject(s)
Accidental Falls , Epidural Abscess/etiology , Lumbosacral Region , Pelvis/injuries , Staphylococcal Infections/etiology , Staphylococcus aureus/isolation & purification , Wounds, Nonpenetrating/complications , Adolescent , Diagnosis, Differential , Epidural Abscess/diagnosis , Epidural Abscess/microbiology , Epidural Abscess/surgery , Humans , Magnetic Resonance Imaging , Male , Staphylococcal Infections/diagnosis , Staphylococcal Infections/microbiology , Staphylococcal Infections/surgery , Suction , Tomography, X-Ray Computed , Wounds, Nonpenetrating/diagnosis
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