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PubMed2004

Age-dependent MRI-detected lesions at early stages of transient global ischemia in rat brain.

Although ischemic stroke has higher incidence and severity in aged than in young humans, the age factor is generally neglected in ischemia animal models. This study was aimed at comparing age-dependent effects at early stages of transient global cerebral ischemia (TGCI) in rats. TGCI was induced in two groups of rats (3-6 and 20-24 months old, respectively) by exposure to 15% oxygen and 15 min occlusion of the two common carotid arteries. Brains were analysed in vivo by MRI-apparent diffusion coefficient (ADC) and T2 maps--at 1-3 h post-TGCI and in vitro by histochemical examination of triphenyltetrazolium chloride (TTC)-stained slices. At 1-3 h post-TGCI, a higher incidence of lesions was found in aged than in young rats especially in the hippocampus and cortex (occipital plus parietal) but not in the thalamus. The lesioned regions showed lower ADC values in aged than in younger rats. The most substantial ADC decreases were associated with enhanced spin-spin relaxation and lower TTC staining. The different responses of the two age groups support the use of aged animals for investigations on different ischemia models. Our model of brain ischemia appears appropriate for further studies including drug effects.

Aging↗
PubMed2006

Neuroprotective effect of hyperbaric oxygen therapy monitored by MR-imaging after embolic stroke in rats.

The potential neuroprotective effects of hyperbaric oxygen (HBO) were tested in an embolic model of focal cerebral ischemia with partially spontaneous reperfusion. Rats (n = 10) were subjected to embolic middle cerebral artery occlusion (MCAO) and diffusion weighted MRI (DWI) was performed at baseline, 1, 3, and 6 h after MCAO to determine the ADC viability threshold yielding the lesion volumes that best approximated the 2,3,5-triphenyltetrazolium chloride (TTC) infarct volumes at 24 h (experiment 1). For assessment of neuroprotective effects, rats were treated with 100% oxygen at 2.5 atmospheres absolute (ATA, n = 15) or normobaric room air (n = 15) for 60 min beginning 180 min after MCAO (experiment 2). DWI-, perfusion (PWI)- and T2-weighted MRI (T2WI) started within 0.5 h after MCAO and was continued 5 h, 24 h (PWI and T2WI only), and 168 h (T2WI only). Infarct volume was calculated based on TTC-staining at 24 h (experiment 1) or 168 h (experiment 2) post-MCAO. ADC-lesion evolution was maximal between 3 and 6 h. In experiment 2, the relative regional cerebral blood volume (rCBV) of both groups showed similar incomplete spontaneous reperfusion in the ischemic core. HBO reduced infarct volume to 145.3 +/- 39.6 mm3 vs. 202.5 +/- 58.3 mm3 (control, P = 0.029). As shown by MRI and TTC, HBO treatment demonstrated significant neuroprotection at 5 h after embolic focal cerebral ischemia that lasted for 168 h.

Animals↗
PubMed2005

Multiple-quantum vector field imaging by magnetic resonance.

We introduce a method for non-invasively mapping fiber orientation in materials and biological tissues using intermolecular multiple-quantum coherences. The nuclear magnetic dipole field of water molecules is configured by a CRAZED sequence to encode spatial distributions of material heterogeneities. At any given point r in space, we obtain the spherical coordinates of fiber orientation (theta,phi) with respect to the external field by comparing three signals ||G(X)||, ||(Y)||, and ||G(Z)|| (modulus), acquired with linear gradients applied along the X, Y, and Z axes, respectively. For homogeneous isotropic materials, a subtraction ||G(Z)|| - ||G(X)|| - ||G(Y)|| gives zero. With anisotropic materials, we find an empirical relationship relating ||G(Z)|| - ||G(X)|| - ||G(Y)||/(||G(X)|| + ||G(Y)|| + ||G(Z)||) to the polar angle theta, while ||G(X|| - ||G(Y)||/(||G(X)|| + ||G(Y)|| + ||G(Z)||) is related to the azimuthal angle phi. Experiments in structured media confirm the structural sensitivity. This technique can probe length scales not accessible by conventional MRI and diffusion tensor imaging.

Animals↗
PubMed2004

Sudden deafness with vertigo as a sole manifestation of anterior inferior cerebellar artery infarction.

Sudden deafness without associated neurological symptoms and signs is typically attributed to a viral inflammation of the labyrinth. Although sudden deafness occurs with anterior inferior cerebellar artery (AICA) infarction, the deafness is usually associated with other brainstem or cerebellum signs such as crossed sensory loss, lateral gaze palsy, facial palsy, Horner syndrome or cerebellar dysmetria. An 84-year-old woman suddenly developed right-sided tinnitus, hearing loss, vertigo and vomiting. Audiometry and electronystagmography documented absent auditory and vestibular function on the right side. T2-weighted and diffusion-weighted MRI showed a tiny infarct in the right lateral inferior pontine tegmentum. AICA occlusion can cause sudden deafness and vertigo without brainstem or cerebellar signs.

Acute Disease↗
PubMed2006

Periventricular nodular heterotopia: A challenge for epilepsy surgery.

Pharmacoresistant focal epilepsies due to periventricular nodular heterotopia are a diagnostic and therapeutic challenge because of the need of invasive presurgical diagnostics and the selection of an optimal surgical approach. Invasive investigations in previous studies showed that focal epileptic activity can be correlated predominantly either with one of the nodular heterotopia or with neocortical epileptogenic zones distant to the periventricular nodules. Up to now, invasive recordings were required for localization of epileptic activity and its correlation to heterotopia. The following case presentation reports on a non-invasive approach using magnetic source imaging (MSI) combined with intraoperative ECoG. MSI combines preoperative data from magnetic resonance imaging (MRI) with magnetoencephalography (MEG). The MSI data for definition of the localization of the epileptic activity and functional important areas were coregistered with the intraoperative high-field-MRI and diffusion tensor imaging-based fiber tracking (DTI) of the visual pathway using a neuronavigational system. A neuronavigation-guided surgical resection of the epileptogenic area was performed leaving the heterotopia and the visual tract fibers intact. Postoperatively preservation of the visual fields was documented and the frequency of seizures was markedly reduced.

Brain Diseases↗
PubMed2005

Clinical features and pathomechanisms of syringomyelia associated with spinal arachnoiditis.

BACKGROUND: Syringomyelia is a common intramedullary lesion associated with spinal arachnoiditis and obstruction of the foramen magnum such as in Chiari's malformation. Disturbance of cerebrospinal fluid flow around the spinal cord has an important role in the development of syringomyelia due to spinal arachnoiditis; however, the exact mechanisms have not been clarified. The purpose of this retrospective study is to understand the clinical features and pathomechanisms of syringomyelia secondary to spinal arachnoiditis and to provide the current choice of surgical treatment in this difficult clinical entity. METHODS: Clinical and radiological findings in 15 patients with syringomyelia associated with spinal arachnoiditis who underwent surgical treatment in our institutes between 1982 and 2000 were reviewed. All patients presented with paraparesis or tetraparesis on admission. RESULTS: Magnetic resonance imaging (MRI) or computed tomography-myelography revealed that the syrinx predominantly existed at the thoracic levels. Five patients showed complete block of the thoracic subarachnoid space by conventional myelography. T2-weighted MRI showed diffuse intramedullary hyperintensity at the level of arachnoiditis. As the first surgical treatment, 10 patients underwent syringo-peritoneal shunt placement. Three patients were treated with a syringo-subarachnoid shunt, and 2 patients were treated with a ventriculoperitoneal shunt. Eight patients required further shunting operations for syringomyelia 2 months to 12 years after the first surgery. Neurologic improvement was obtained in 9 patients (60%) with decreased size of the syrinx. One patient remained stable; 5 patients showed gradual deterioration. CONCLUSIONS: The syrinx originated from the thoracic levels where severe adhesion of the subarachnoid space was present. The mechanisms of syrinx formation may be based on the increased interstitial fluid in the spinal cord. Shunting procedures were effective in some population of the patients. Decompression procedures of the spinal subarachnoid space may be an alternative primary surgical treatment except for patients with longitudinally extensive arachnoiditis.

Adult↗
PubMed1999

Fulminant form of acute disseminated encephalomyelitis: successful treatment with hypothermia.

We described herein a case of the fulminant form of acute disseminated encephalomyelitis (ADEM) that developed after mycoplasma pneumonia. A 28-year-old man who presented with fever, headache, and writing difficulty was admitted to our hospital in August 1997. He developed hernia on the 3rd hospital day. Surgical decompression and intravenous prednisolone failed to halt his progressive deterioration. We introduced systemic hypothermia and he has shown marked recovery; despite having Broca's type aphasia, he could comprehend spoken language and communicate with others by gesture. Head MRI demonstrated diffuse high signals over the white matter on fluid attenuated inversion recovery (FLAIR) images, which suggested extensive demyelination. The clinical course, imaging studies and presence of polymorphonuclear dominant leucocytosis in the blood and CSF in the patient are somewhat similar to findings in acute hemorrhagic leukoencephalitis, however, the result of a brain biopsy was inconclusive. The fulminant form of ADEM is usually fatal. Treatments such as corticosteroids, intravenous immunoglobulin, and surgical decompression have been performed to improve the prognosis. Our case results indicate that hypothermia, which suppresses both brain edema and immune response, may be included in the repertoire of treatment for the fulminant form of ADEM.

Adult↗
PubMed1998

Slowly progressive cystic leukoencephalopathy with megalencephaly in a Japanese boy.

A Japanese boy with megalencephaly and leukoencephalopathy was reported. The clinical characteristics were as follows; slowly progressive megalencephaly starting at 8 months, and motor impairment with ataxia and spasticity, with relatively preserved intelligence and well-controlled epilepsy, and the following MRI findings; diffuse leukoencephalopathy in the supratentorial white matter with cystic subcortical white matter in the temporal tips and the fronto-parietal lobes. This corresponds to vacuolating leukoencephalopathy with megalencephaly, which was recently reported in European countries. In Japan, there were similar case reports previously, however, the patients were diagnosed as having Alexander's disease. It seems that this new leukoencephalopathy must also be seen among Japanese.

Brain↗
PubMed2003

[Brain oedema following blood-brain barrier disruption: mechanisms and diagnosis].

Brain oedema following blood-brain barrier (BBB) disruption, or vasogenic oedema, is present in most cases of brain oedema. According to the Starling's law, water, ions and plasma proteins cross the BBB toward the interstitium if the driving forces for transmural bulk flow are excessive (mechanical origin) and/or if the BBB permeability is enhanced (chemical origin). Both mechanisms coexist in most cases. Excessive elevation of the gradient of hydrostatic pressure with lost of cerebral autoregulation has been proved in ischaemia/reperfusion and trauma, and suggested in acute mountain sickness and eclampsia. The BBB permeability can be enhanced by immediate (chemical mediators) or delayed (cellular infiltration) inflammatory response, or by alteration of the membrane integrity. This later can be transient (hyperosmolar BBB disruption), or permanent by activation of matrix metalloproteinase or by neovascularization with BBB breakdown. The reference method for the diagnosis of vasogenic oedema is the MRI diffusion-weighted imaging.

Blood-Brain Barrier↗
PubMed2006

Pitfalls in the diagnosis of brain tumours.

Establishing the diagnosis of a brain tumour is not always a straightforward process. Many non-neoplastic neurological diseases can mimic brain neoplasms on neuroimaging or on histological examination, including multiple sclerosis, stroke, pyogenic abscess, toxoplasmosis, tuberculosis, cysticercosis, fungal infections, syphilis, sarcoidosis, Behçet disease, radiation necrosis, venous thrombosis, and others. Conversely, several types of brain neoplasms, such as glioblastomas, low-grade gliomas, CNS lymphomas, and brain metastases, can present in the absence of typical tumefactive lesions, posing significant diagnostic challenges. In this Review, we discuss the process of accurately establishing the diagnosis of brain tumours, focusing on pitfalls commonly encountered in clinical practice. We also discuss the rational use and limitations of new diagnostic techniques, such as diffusion-weighted MRI, perfusion-weighted MRI, magnetic resonance spectroscopy, single-photon emission tomography, and positron emission tomography, as well as new tools for histological examination, such as immunohistochemistry and molecular genetics analysis.

Brain Diseases↗
PubMed2001

Listeria spinal cord abscess responsive to trimethoprim-sulfamethoxazole monotherapy.

OBJECTIVE: To describe an alternative antibiotic regimen for the treatment of central nervous system Listeria monocytogenes infection. BACKGROUND: Classical treatment of listeria infections of the brain and spinal cord has included ampicillin in combination with gentamicin and chloramphenicol. Antibiotic resistance to L. monocytogenes is extraordinarily low, and the combined risks of nephrotoxicity, ototoxicity, and agranulocytosis in an already critically ill patient make the potential use of trimethoprim-sulfamethoxazole monotherapy for coverage or treatment of listeria an important alternative. METHODS: Case report. RESULTS: A 58-year-old woman presented with a two-week history of progressive quadriplegia. Gadolinium enhanced MRI showed diffuse edema of the cervical and thoracic spine with ring-enhancing lesions. Cerebrospinal fluid and blood cultures both grew L. monocytogenes. Spinal cord biopsy of the lesion revealed inflammation with necrosis and also grew listeria. Intravenous trimethoprim-sulfamethoxazole (8 mg/kg in four divided doses) was administered for six weeks with resultant arrest of neurological symptoms and stabilization of the clinical course. Although the patient was quadraparetic she was able to be discharged to a rehabilitation facility. CONCLUSIONS: Trimethoprim-sulfamethoxazole monotherapy may be a potential alternative option for critically ill patients with central nervous system L. monocytogenes infection.

Anti-Infective Agents↗
PubMed1999

Fatal outcome due to cyclosporine neurotoxicity with associated pathological findings.

We present a case of death likely to be directly due to cyclosporine (CsA) neurotoxicity. To date, there have been no reports of deaths directly due to CsA neurotoxicity, nor has an associated histological lesion been described independent of confounding processes. A 54-year-old male received an HLA-matched-unrelated BMT for CML. He developed progressive encephalopathy and on day +79 had a generalized seizure. All CSF studies were negative for infectious causes. MRI revealed diffuse, symmetrical white matter abnormalities located in the occipital sub-cortex, thalamus, mid brain, pons, and cerebellum which were typical of CsA toxicity. The patient died of central respiratory failure within 72 h of discontinuing CsA. Autopsy revealed diffuse patchy white matter edema and astrocytic injury without evidence of axonopathy, demyelination, microvascular injury, or infectious/inflammatory process. This case demonstrates previously undescribed lethal CsA neurotoxicity and may reveal an associated primary pathological lesion.

Central Nervous System Diseases↗
PubMed2005

[Infectious diseases of brain parenchyma in adults: imaging and differential diagnosis aspects].

Infectious diseases of the central nervous system have often to be considered in differential diagnosis, particularly in immunocompromised persons. Neuroimaging, specifically advanced techniques such as diffusion-weighted MRI and perfusion MRI contribute much to the differentiation of various brain infections and to delineation of brain infections from other, for instance, neoplastic diseases. In this review we present the imaging criteria for the most important brain infections in adults and discuss in detail differential diagnostic aspects.

Adult↗
PubMed2002

Aphasia severity: Association with cerebral perfusion and diffusion.

BACKGROUND: Previous studies of the relationship between perfusion, diffusion, and stroke suggest that the extent of cerebral hypoperfusion may be a better indicator of neurological status than lesion size in the early phases of recovery. It is not clear how these factors are related to aphasia severity. AIMS: The purpose of this study was to investigate the relationship between cerebral perfusion, diffusion, and aphasia severity in stroke. METHODS #ENTITYSTARTX00026; PROCEDURE: Nine participants were examined within 24 hours of stroke onset and six were re-examined at 1 month post stroke. The examination included administration of an aphasia test, a face recognition task, and a neuroimaging session including T2-, perfusion-, and diffusion-weighted MRI. OUTCOMES #ENTITYSTARTX00026; RESULTS: Participants with a variety of aphasia types and severity were included in the study. Visual inspection suggested larger perfusion abnormality than the actual lesion in eight of nine subjects at day 1. The correlation between aphasia severity and hypoperfusion was significant at day 1 and at 1 month post stroke. However, this was not the case for the relationship between aphasia severity and lesion size where the correlation was not statistically significant at day 1 or at 1 month post stroke. CONCLUSIONS: These results suggest that cerebral hypoperfusion is a more accurate indicator of aphasia severity in early stroke than lesion volume.

Journal Article↗
PubMed2003

Magnetic resonance-based techniques for the study and management of multiple sclerosis.

Conventional magnetic resonance imaging (cMRI) is widely used for diagnosing multiple sclerosis (MS) and for monitoring its activity and evolution. However, the correlation between cMRI and clinical findings of MS is limited, possibly due to the low pathological specificity of the abnormalities seen on cMRI scans and to the inability of cMRI to quantify the extent of the damage of the normal-appearing tissues. Magnetization transfer and diffusion-weighted MRI can quantify the extent and pathological severity of structural changes occurring within and outside cMRI-visible MS lesions. Proton MR spectroscopy can add information on the biochemical nature of such changes. Finally, functional MRI can provide new insights into the role of cortical adaptive changes in limiting the clinical consequences of MS structural damage. The application of quantitative MR-based techniques is changing dramatically our understanding of how MS causes irreversible disability and there is increasing perception that these methodologies should be more extensively employed in clinical trials to derive innovative information.

Brain↗
PubMed1999

Voxel-based mapping of irreversible ischaemic damage with PET in acute stroke.

Objective mapping of irreversible tissue damage in the acute stage of ischaemic stroke would be useful for prognosis and in assessing the efficacy of therapeutic manoeuvres in impeding extension of infarction. From our database of 30 patients studied with 15O-PET within 5-18 h after onset of first-ever middle cerebral artery territory stroke, we extracted a subgroup of 19 survivors (age 74.6 +/- 8.5 years) in whom late CT coregistered with PET was available to determine final infarct topography. By means of a voxel-based analysis of the PET data, we determined putative thresholds for irreversible tissue damage as the lower limit of the 95% confidence interval calculated from all voxels within the ultimately non-infarcted brain parenchyma ipsilateral to the insult. The following values were found: 8.43 ml/100 ml/min, 0.87 ml/100 ml/min, 1.64 ml/100 ml, 0.27 and 2.21/min, for cerebral blood flow (CBF), oxygen consumption (CMRO2), blood volume (CBV), oxygen extraction fraction and the ratio CBF : CBV, respectively. Voxels below these thresholds occurred significantly more frequently in the final infarct region than in the non-infarcted parenchyma for CBF and CMRO2 (P = 0.016 and P = 0.0045, respectively, Wilcoxon test), but not for the other PET variables. Furthermore, with both CBF and CMRO2, the percentage of irreversible tissue damage voxels in the affected hemisphere relative to the opposite hemisphere was significantly positively correlated to both the volume of final infarct and the neurological outcome at 2 months (all P < 0.005, Spearman ranked test). These findings validate our voxel-based CBF and CMRO2 thresholds for probabilistic mapping of irreversible tissue damage within the 5-18 h interval after stroke onset; however, whether they would be applicable to earlier intervals remains to be determined. Transfer of our procedure for determination of irreversible tissue damage thresholds to other imaging modalities such as single proton emission computed tomography and diffusion-weighted MRI should be straightforward.

Aged↗
PubMed2003

Occipito-temporal connections in the human brain.

Diffusion tensor MRI (DT-MRI) provides information about the structural organization and orientation of white matter fibres and, through the technique of 'tractography', reveals the trajectories of cerebral white matter tracts. We used tractography in the living human brain to address the disputed issue of the nature of occipital and temporal connections. Classical anatomical studies described direct fibre connections between occipital and anterior temporal cortex in a bundle labelled the inferior longitudinal fasciculus (ILF). However, their presence has been challenged by more recent evidence suggesting that connections between the two regions are entirely indirect, conveyed by the occipito-temporal projection system--a chain of U-shaped association fibres. DT-MRI data were collected from 11 right-handed healthy subjects (mean age 33.3 +/- 4.7 years). Each data set was co-registered with a standard MRI brain template, and a group-averaged DT-MRI data set was created. 'Virtual' in vivo dissection of occipito-temporal connections was performed in the group-averaged data. Further detailed virtual dissection was performed on the single brain data sets. Our results suggest that in addition to the indirect connections of the occipito-temporal projection system: (i) a major associative connection between the occipital and anterior temporal lobe is provided by a fibre bundle whose origin, course and termination are consistent with classical descriptions of the ILF in man and with monkey visual anatomy; (ii) the tractography-defined ILF is structurally distinct from fibres of the optic radiation and from U-shaped fibres connecting adjacent gyri; (iii) it arises in extrastriate visual 'association' areas; and (iv) it projects to lateral and medial anterior temporal regions. While the function of the direct ILF pathway is unclear, it appears to mediate the fast transfer of visual signals to anterior temporal regions and neuromodulatory back-projections from the amygdala to early visual areas. Future tractography studies of patients with occipito-temporal disconnection syndromes may help define the functional roles of the direct and indirect occipito-temporal pathways.

Adult↗
PubMed2004

Alpha-syntrophin deletion removes the perivascular but not endothelial pool of aquaporin-4 at the blood-brain barrier and delays the development of brain edema in an experimental model of acute hyponatremia.

The formation of brain edema, commonly occurring as a potentially lethal complication of acute hyponatremia, is delayed following knockout of the water channel aquaporin-4 (AQP4). Here we show by high-resolution immunogold analysis of the blood-brain-barrier that AQP4 is expressed in brain endothelial cells as well as in the perivascular membranes of astrocyte endfeet. A selective removal of perivascular AQP4 by alpha-syntrophin deletion delays the buildup of brain edema (assessed by Diffusion-weighted MRI) following water intoxication, despite the presence of a normal complement of endothelial AQP4. This indicates that the perivascular membrane domain, which is peripheral to the endothelial blood-brain barrier, may control the rate of osmotically driven water entry. This study is also the first to demonstrate that the time course of edema development differs among brain regions, probably reflecting differences in aquaporin-4 distribution. The resolution of the molecular basis and subcellular site of osmotically driven brain water uptake should help design new therapies for acute brain edema.

Animals↗