CT and MRI findings of human herpesvirus 6-associated encephalopathy: comparison with findings of herpes simplex virus encephalitis.

OBJECTIVE: It is important to differentiate human herpesvirus 6 (HHV-6)-associated encephalopathy from herpes simplex encephalitis (HSE). Although these conditions are similar with regard to involvement of the mesial temporal lobe, HSE is sensitive to acyclovir but HHV-6 encephalopathy is not. We compared the imaging findings of the two conditions. MATERIALS AND METHODS: We encountered eight cases of HHV-6 encephalopathy and nine cases of HSE. We divided an observation time into early, middle, and late periods defined as 0-2, 3-30, and more than 30 days from the onset of neurologic symptoms. Differences between HHV-6 encephalopathy and HSE on CT scans in the early period and in distribution and temporal changes in the affected regions on MR images in the three periods were analyzed. RESULTS: At MRI in the early and middle periods, all eight patients with HHV-6 encephalopathy had exclusive involvement of the mesial temporal lobes, and all nine patients with HSE had involvement of both the mesial temporal lobes and the extratemporal regions (p < 0.01). Among patients who underwent head MRI, six of six with HHV-6 encephalopathy but none of six with HSE had resolution of high signal intensity on T2-weighted and FLAIR images (p < 0.01). Among patients who underwent head CT in the early period, none of the four with HHV-6 encephalopathy and six of the seven with HSE had abnormal findings, including parenchymal swelling, decreased attenuation of affected regions, and abnormal gyral enhancement (p < 0.05). CONCLUSION: Serial MRI showed transient abnormal signal intensity in the mesial temporal lobes in patients with HHV-6 encephalopathy but persistent abnormal signal intensity in both the mesial temporal lobes and the extratemporal regions in patients with HSE. CT in the early period showed no abnormality in patients with HHV-6 encephalopathy but definite abnormal findings in patients with HSE. These differences may be useful in the differential diagnosis of the two conditions.

Heterogeneity and continuum of multiple sclerosis in Japanese according to magnetic resonance imaging findings.

There are two distinct subtypes of multiple sclerosis (MS) in Asians: optic-spinal (OSMS) and conventional (CMS). Longitudinally extensive spinal cord lesions (LESCLs) extending over three or more vertebral segments are characteristic of patients with OSMS, yet in Asians, one-fourth of CMS patients also have LESCLs. To clarify the distinction between LESCLs in OSMS and CMS, and to characterize the relationship between the presence of LESCLs and brain magnetic resonance imaging (MRI) findings, we studied 142 patients with clinically definite MS of relapsing-remitting onset and 12 patients with primary progressive MS (PPMS) by MRI of the whole spinal cord and brain. The former was diagnosed by Poser criteria, including 57 with OSMS, 67 with CMS and 18 with brainstem-spinal form of MS, while the latter by McDonald criteria. The presence of LESCLs throughout the entire clinical course was significantly more common in OSMS patients than in CMS patients, while brain lesions fulfilling the Barkhof criteria (Barkhof brain lesions) were significantly more common in CMS patients than OSMS patients. LESCLs in OSMS patients most frequently affected the upper to middle thoracic cord, with either holocord or central gray matter involvement. By contrast, 70% of LESCLs in CMS patients predominantly affected the peripheral white matter of the mid-cervical cord. LESCLs in patients with PPMS also showed preferential involvement of the peripheral white matter of the mid-cervical cord. One-third of OSMS patients had neither LESCLs nor Barkhof brain lesions more than 10 years after disease onset, and showed significantly milder disability than OSMS patients with LESCLs. These findings suggest that LESCLs are heterogeneous between OSMS and CMS patients, and that there are distinct subtypes of MS in Japanese, according to clinical and MRI findings.

Atopic myelitis with focal amyotrophy: a possible link to Hopkins syndrome.

Among 22 consecutive patients with myelitis, of unknown etiology, and atopic diathesis (atopic myelitis) who from April 2002 to March 2006 had been studied in our clinic, 5 (23%) showed focal amyotrophy in one or two limbs. These 5 patients were subjected to combined clinical, electrophysiological, neuroimaging and immunological studies. Ages were 18 to 58-years-old (average 39). Four showed amyotrophy of unilateral or bilateral upper limbs while one showed amyotrophy in both thighs. All patients showed on-going denervation potentials in the affected muscles, while motor conduction study including F wave was normal except for in one patient who showed prolonged F wave latency in one nerve. Two had localized high signal intensity lesions involving anterior horns on spinal cord MRI and three showed abnormalities suggesting pyramidal tract involvement on motor evoked potentials. All had a present and/or past history of atopic disorders and specific IgE against common environmental allergens, such as mite antigens and cedar pollens, and four showed mild eosinophilia, all of which were compatible with atopic myelitis. When clinical and laboratory findings were compared between atopic myelitis with (n=5) or without focal amyotrophy (n=17), the former showed a significantly higher frequency of present and past history of asthma (80% vs. 24%, p=0.0393) and tended to have higher EDSS scores (3.8+/-1.6 vs. 3.1+/-1.4). Two patients showed mild to moderate improvements after immunotherapies such as methylprednisolone pulse therapy or plasma exchange, while two recovered with low dose corticosteroids and one without treatment had a gradually progressive course. Although atopic myelitis preferentially involves the posterior column of the cervical spinal cord, it is possible that anterior horn cells are affected in some cases of atopic myelitis, especially in patients with asthma. This suggests a possible link between atopic myelitis and Hopkins syndrome (asthmatic amyotrophy).

Heterogeneity of aquaporin-4 autoimmunity and spinal cord lesions in multiple sclerosis in Japanese.

Opticospinal multiple sclerosis (OSMS) in Asians has similar features to the relapsing-remitting form of neuromyelitis optica (NMO) seen in Westerners. OSMS is suggested to be NMO based on the frequent detection of specific IgG targeting aquaporin-4 (AQP4), designated NMO-IgG. The present study sought to clarify the significance of anti-AQP4 autoimmunity in the whole spectrum of MS. Sera from 113 consecutive Japanese patients with clinically definite MS, based on the Poser criteria, were assayed for anti-AQP4 antibodies by immunofluorescence using GFP-AQP4 fusion protein-transfected HEK-293T cells. Sensitivity and specificity of the anti-AQP4 antibody assay, 83.3 and 100%, respectively, were calculated using serum samples with NMO-IgG status predetermined at the Mayo Clinic. The anti-AQP4 antibody positivity rate was significantly higher in OSMS patients (13/48, 27.1%) than those with CMS (3/54, 5.6%), other neurological diseases (0/52) or healthy controls (0/35). None of the 11 patients tested with a brainstem-spinal form of MS were positive. Among OSMS patients, the antibody positivity rate was highest in OSMS patients with longitudinally extensive spinal cord lesions (LESCLs) extending over three vertebral segments and brain lesions that fulfilled the Barkhof criteria (5/9, 55.6%). Multiple logistic analyses revealed that emergence of the anti-AQP4 antibody was positively associated only with a higher relapse rate, but not with optic-spinal presentation or LESCLs. Compared with anti-AQP4 antibody-negative CMS patients, anti-AQP4 antibody-positive MS patients showed significantly higher frequencies of severe optic neuritis, acute transverse myelitis and LESCLs while most conditions were also common to anti-AQP4 antibody-negative OSMS patients. The LESCLs in anti-AQP4 antibody-positive patients were located at the upper-to-middle thoracic cord, while those in anti-AQP4 antibody-negative OSMS patients appeared throughout the cervical-to-thoracic cord. On axial planes, the former most frequently showed central grey matter involvement, while holocord involvement was predominant in the latter. In contrast, LESCLs in anti-AQP4 antibody-negative CMS patients preferentially involved the mid-cervical cord presenting a peripheral white matter-predominant pattern, as seen in the short lesions. Anti-AQP4 antibody-positive MS patients fulfilling definite NMO criteria showed female preponderance, higher relapse rate, greater frequency of brain lesions and less frequent responses to interferon beta-1b than anti-AQP4 antibody-negative OSMS patients with LESCLs. These findings suggested that LESCLs are distinct in anti-AQP4 antibody positivity and clinical phenotypes. There were cases of anti-AQP4 antibody-positive MS/NMO distinct from CMS, and anti-AQP4 antibody-negative OSMS with LESCLs in Japanese. This indicated that the mechanisms producing LESCLs are also heterogeneous in cases with optic-spinal presentation, namely AQP4 autoimmunity-related and -unrelated.

MR tractography based on directional diffusion function validation in somatotopic organization of the pyramidal tract.

RATIONALE AND OBJECTIVES: Conventional tractography based on the "streamline" method only partially visualizes the pyramidal tract because of fiber crossing with other white matter tracts. Recently a new tractography method based on directional diffusion function (DDF) has been proposed. This method was reported to visualize the pyramidal tract to a larger extent than conventional techniques do. To validate the DDF-based tractography method, we studied the somatotopic organization of the pyramidal tract in the posterior limb of the internal capsule (PLIC). MATERIALS AND METHODS: Pyramidal tracts in the intact hemispheres of 14 brain tumor patients were drawn using the directional diffusion function-based tractography method. Each pyramidal tract was divided into four fiber bundles according to the cephalocaudal positions of their termination in the precentral gyrus. The cephalocaudal positions in the precentral gyrus of the four fiber bundles were correlated with their positional relationships in the PLIC along the mediolateral and anteroposterior axes. RESULTS: Fiber bundles terminating more caudally in the precentral gyrus were located significantly more anteriorly in the PLIC (r = 0.59, Spearman's correlation coefficient, P < .0001). On the other hand, no significant correlation was shown between the cephalocaudal positions in the precentral gyrus of the four fiber bundles and their relative positions in the PLIC along the mediolateral axis. CONCLUSIONS: Estimated organization of the fiber bundles of the pyramidal tract in the PLIC was consistent with anatomically known somatotopic organization, which supported the validity of the DDF-based tractography method.

Cortical damage in Alzheimer's disease estimation in medial and lateral aspects of the cerebrum using an improved mapping method based on diffusion-weighted magnetic resonance imaging.

RATIONALE AND OBJECTIVES: A method of estimating and mapping the cortical damage resulting from neurodegenerative diseases based on diffusion-weighted imaging was recently proposed. We improved on this method to visualize the cortical damage in Alzheimer's disease (AD) in the lateral and medial aspects of the cerebral hemispheres and to provide anatomic references. MATERIALS AND METHODS: Damage in the cerebral cortex was estimated based on diffusivity in the subcortical white matter according to a previously published method. A map of subcortical mean diffusivity (MD) was superimposed on the corresponding anatomic image so that the spatial extent of the abnormality could be anatomically localized. The right and left hemispheres were separated to evaluate the medial and lateral aspects of each hemisphere. This method was applied to 10 healthy subjects and 11 AD patients. MDs within 20 cortical regions were visually evaluated and statistically compared between AD and healthy subjects at a significance level of P < .01. RESULTS: In addition to the involvement of the lateral aspects of the bilateral parietal and temporal lobes and clear sparing of the bilateral pericentral regions that were previously reported, significant MD elevation was observed in the medial aspects of the right frontal, bilateral parietal, and right temporal lobes. The extent of MD abnormalities was easily identified by the background anatomic image. CONCLUSIONS: Results suggested that AD damage in the lateral and medial cerebral cortex can be visualized with an anatomic reference using our method.

Automated method for identification of patients with Alzheimer's disease based on three-dimensional MR images.

RATIONALE AND OBJECTIVES: An automated method for identification of patients with cerebral atrophy due to Alzheimer's disease (AD) was developed based on three-dimensional (3D) T1-weighted magnetic resonance (MR) images. MATERIALS AND METHODS: Our proposed method consisted of determination of atrophic image features and identification of AD patients. The atrophic image features included white matter and gray matter volumes, cerebrospinal fluid (CSF) volume, and cerebral cortical thickness determined based on a level set method. The cortical thickness was measured with normal vectors on a voxel-by-voxel basis, which were determined by differentiating a level set function. The CSF spaces within cerebral sulci and lateral ventricles (LVs) were extracted by wrapping the brain tightly in a propagating surface determined with a level set method. Identification of AD cases was performed using a support vector machine (SVM) classifier, which was trained by the atrophic image features of AD and non-AD cases, and then an unknown case was classified into either AD or non-AD group based on an SVM model. We applied our proposed method to MR images of the whole brains obtained from 54 cases, including 29 clinically diagnosed AD cases (age range, 52-82 years; mean age, 70 years) and 25 non-AD cases (age range, 49-78 years; mean age, 62 years). RESULTS: As a result, the area under a receiver operating characteristic (ROC) curve (Az value) obtained by our computerized method was 0.909 based on a leave-one-out test in identification of AD cases among 54 cases. CONCLUSION: This preliminary result showed that our method may be promising for detecting AD patients.

Cortical thickness difference across the central sulcus visualized in the presence of vasogenic edema.

PURPOSE: To confirm the cortical thickness difference across the central sulcus (CS) visualized in the presence of vasogenic edema on MRI. MATERIALS AND METHODS: T2-weighted images of 70 cerebral hemispheres showing vasogenic edema infiltrating into subcortical white matter around the CS were studied retrospectively. Two neuroradiologists measured the cortical thickness of the anterior and posterior banks of the CS, precentral sulci (PrCS), and postcentral sulci (PoCS). Additionally, we compared the cortical thickness of the anterior and posterior banks of each sulcus visually using a grading scale. RESULTS: On T2-weighted images, the cerebral cortex was highlighted by a high signal-intensity vasogenic edema in the adjacent white matter, and its thickness was readily measurable. The unique cortical thickness difference between the anterior and posterior banks of the CS were confirmed with measurements of 2.67 and 1.48 mm (p<0.0001). The cortical measurements across other cerebral sulci were 2.04 and 1.95 mm (NS) for the PrCS, and 1.67 and 1.77 mm (NS) for the PoCS. The cortical thickness ratios were 1.86 for the CS, 1.05 for the PrCS, and 0.96 for the PoCS. On visual evaluation, the anterior bank of the CS was thicker than the posterior bank in 93% (65/70). For the PrCS and PoCS, the thickness of the anterior and posterior banks appeared to be equal in over 70% of the patients. CONCLUSION: A prominent cortical thickness difference across the CS in the presence of vasogenic edema was confirmed. This finding is considered to facilitate the identification of the CS in patients with brain tumors.

Intraorbital lobular capillary hemangioma (pyogenic granuloma).

A 44-year-old man with a history of a foreign body in his right eye visited our hospital. On computed tomography a well-enhanced mass with low attenuation septal walls and a capsule was detected in the right orbit. On magnetic resonance imaging the mass showed inhomogenous high intensity on T2-weighted images and low intensity on diffusion-weighted images. The mass was histopathologically diagnosed as a lobular capillary hemangioma. This is the first report about image findings of lobular capillary hemangioma in the orbit.

Infantile hypophosphatasia combined with vitamin B6-responsive seizures and reticular formation lesions on magnetic resonance imaging: A case report.

BACKGROUND: Hypophosphatasia (HPP) is a rare genetic disorder characterized by rachitic bone manifestations and a low serum alkaline phosphatase (ALP) level. It is caused by mutations in the tissue non-specific alkaline phosphatase (TNSALP) gene, which encodes the tissue non-specific isozyme of ALP. HPP patients exhibit various presentations depending on their age at onset, such as infantile HPP combined with vitamin B6-responsive seizures. CASE PRESENTATION: A newborn with infantile HPP presented with tonic convulsions from day 5 after birth and received intravenous vitamin B6 (10mg/kg/day pyridoxal phosphate). Eleven days later, frequent apneic episodes occurred, and head magnetic resonance imaging (MRI) showed bilateral reticular formation lesions in the brain stem, including the medulla oblongata. After the pyridoxal phosphate dose was increased (to 40mg/kg/day), the patient's seizures and apnea resolved, and her MRI findings also improved. Genetic testing revealed that she was homozygous for the 1559delT mutation of TNSALP. CONCLUSIONS: High-dose pyridoxal phosphate is a useful treatment for HPP-induced seizures and might improve reticular formation lesions.

Surgical strategy for multiple huge spinal extradural meningeal cysts. Case report.

The authors describe the case of an 8-year-old boy who developed spastic paraparesis and hypalgesia below the middle thoracic level. Magnetic resonance (MR) imaging showed huge and multiple extradural cystic lesions posterior to the spinal cord from T-5 to S-1, which were associated with severe spinal cord compression, especially at the T5-8 level. Using constructive interference in steady state (CISS) MR imaging, many septa were visible that were dividing the cysts in a tandem arrangement, and the multiple cysts were distributed far laterally, extending to the root sleeves. Three transdural communications of cerebrospinal fluid into the cysts, including one that was located ventrally, were revealed by multiangled observation using CISS MR imaging and intraoperative inspection. The huge and multiple appearances of the extradural meningeal cysts on MR images suggested various stages of growth of these cysts. As this case demonstrates, cysts of this type (huge, multiple, extradural meningeal [arachnoid] cysts) need to be completely removed during one-stage surgery.

Additional hippocampectomy in the surgical management of intractable temporal lobe epilepsy associated with glioneuronal tumor.

In surgery for epileptogenic glioneuronal tumor in the temporal lobe, whether additional hippocampectomy is needed remains in dispute. We retrospectively analysed clinical profile and seizure outcome in a consecutive series of six patients, paying special attention to pathophysiologic conditions in the ipsilateral hippocampus. Long-term video electroencephalography (EEG) monitoring showed attenuation of background activity, followed by ictal discharges in the ipsilateral temporal region in five cases. (18)Fluorodeoxyglucose-positron emission tomography (FDG-PET) in five cases showed hypometabolism in the ipsilateral medial temporal lobe. Intraoperative electrocorticography (ECoG) after removal of the tumor revealed frequent paroxysmal activity or electrographic seizure activity on the hippocampus in five cases. A high incidence of hippocampal pathology, such as hippocampal sclerosis in four cases and dysgenesis in one case, was demonstrated. Five patients who underwent additional hippocampectomy along with resection of the tumor became completely seizure-free. Our findings indicated a proclivity for the epileptogenic zone to encompass the medial structures and for hippocampal pathology to be present even when no direct medial tumor involvement was identified. Thus, it is conceivable that removal of the hippocampus with the guidance of pre- and intraoperative multimodal examinations, in addition to resection of the tumor, may be recommended to achieve 'complete' freedom from seizures.

Quantitative perfusion imaging with pulsed arterial spin labeling: a phantom study.

PURPOSE: Pulsed arterial spin labeling (PASL) is a magnetic resonance (MR) method for measuring cerebral blood flow. Although several validation studies for PASL in animals and humans have been reported, no reports have detailed the fundamental study of PASL using a flow phantom. We compared the true and theoretical flow rates in a flow phantom to confirm the analytical validity of quantitative perfusion imaging with Q2TIPS sequence. METHODS: We built a flow phantom consisting of a 40-mm diameter plastic syringe filled with plastic beads and small plastic tubes 4 mm in diameter. Gd-DTPA-doped 8L water solution (0.1 mM) was circulated between the syringe and a tank through a plastic tube by a constant flow pump while the flow rate was adjusted between 0 and 2.61 cm/s. Q2TIPS sequence parameters were TI(1)=50 ms and TI(2)=1400 ms. Five imaging slices of 50 subtraction images were acquired sequentially in a distal-to-proximal direction using a single-shot echo planar imaging (EPI) technique. The theoretical flow rate calculated based upon the previously reported kinetic model for Q2TIPS was compared with the true flow rate. RESULTS: A good linear relationship was observed between the theoretical, F', and true flow rates, F, in a flow rate range of 1.43 to 1.95 cm/s (F'=1.024*F-1.915, R(2)=0.902). The ratio of theoretical to true flow rate was 92 (+/-) 4%. CONCLUSION: Flow rate was quantified with reasonable accuracy when the entire amount of labeled bolus within the phantom could be recovered. Our experiment confirmed the analytical validity of Q2TIPS and suggested that blood flow measurement may be feasible using the Q2TIPS pulse sequence and kinetic model of the PASL equation.

Intraarterial therapy for acute ischemic stroke: investigation of prognostic factors.

BACKGROUND: Intraarterial therapy (IAT) for acute cerebral infarction has been proven to be profitable. However, the criteria for the indications, the choice of the thrombolytic agents, and the use of adjunctive agents are controversial. We retrospectively analyzed the prognostic factors of IAT. MATERIALS AND METHODS: From 1994 to 2003, 28 patients underwent IAT due to middle cerebral artery occlusion (17 women and 11 men; median age, 69 years old). We evaluated the following prognostic parameters: institution of treatment, degree of paralysis at visit, size of high-intensity area on diffusion-weighted images, dose of intraarterial urokinase administration, elapsed time from symptom onset to completion of IAT, presence of penetration of embolus by microcatheter and microguidewire, recanalization after IAT, intracranial hemorrhage (ICH) within 24 hours after IAT, and intravenous heparin administration after IAT. The outcome was evaluated at discharge and was classified into the following categories according to the modified Rankin Scale: independence (0 to 2), dependence (3 to 5), and death (6). RESULTS: Seven patients were judged to be independent, 16 patients were judged to be dependent, and five patients died. Patients with recanalization after IAT had a better outcome than those without (p < 0.05); patients with intracranial hemorrhage had a worse outcome than those without (p < 0.05); and patients with intravenous heparin administration after IAT had a better outcome in activities of daily living than those without (p < 0.05). CONCLUSION: In addition to ICH and recanalization, our results suggested that intravenous heparin administration after IAT had a favorable effect on patient outcome.

Upregulation of vascular growth factors in multiple sclerosis: correlation with MRI findings.

Vascular permeability changes precede the development of demyelinating lesions in multiple sclerosis (MS), and vessel wall thickening and capillary proliferation are frequently seen in autopsied MS lesions. Although vascular growth factors are critical for inducing such vascular changes, their involvement in MS has not been extensively studied. Thus, we examined the involvement of various vascular growth factors in MS according to their clinical phase and subtype. We measured serum levels of vascular endothelial growth factor (VEGF), acidic and basic fibroblast growth factors (FGF) and platelet-derived growth factors (PDGFs)-AA, -AB and -BB in 50 patients with MS (27 opticospinal MS and 23 conventional MS patients) and 33 healthy controls using sandwich enzyme immunoassays. Correlations between growth factor changes and brain and spinal cord MRI findings were then analyzed. Serum VEGF concentrations were significantly higher in MS patients in relapse than in controls (p = 0.0495) and in MS patients in remission (p = 0.0003), irrespective of clinical subtype. Basic FGF was significantly increased in conventional MS patients, but not opticospinal MS patients compared with controls (p = 0.0291), irrespective of clinical phase. VEGF at relapse showed a significant positive correlation with the length of spinal cord lesions on MRI (r = 0.506, p = 0.0319). The results suggest that an increase in serum VEGF concentration might be involved in MS relapse and the formation of longitudinally extensive spinal cord lesions.

Estimation of white matter connectivity based on a three-dimensional directional diffusion function in diffusion tensor MRI.

Diffusion tensor (DT) magnetic resonance imaging (MRI) provides the directional information of local neuronal fibers, and has been used to estimate the neuroanatomical connectivity in the cerebral white matter. Several methods for white matter tractography have been developed based on DT-MRI. However, it has been difficult to estimate the white matter tract pathways in the fiber crossing and branching region because of the ambiguity of the principal eigenvector and/or low anisotropy due to the partial volume effect. In this paper, we proposed a new method for white matter tractography, which permits fiber tract branching and passing through crossing regions. Our tractography method is based on a three-dimensional (3D) directional diffusion function (DDF), which was given by a 3D anisotropic Gaussian function defined by normalized three eigenvalues and their corresponding eigenvectors of DT. The DDF was used for generation of a 3D directional diffusion field and for determination of the connectivity between the voxels in fiber tracking. To extract the white matter tract region, DDF-based tractography (DDFT) method used the directional diffusion field instead of a threshold fractional anisotropy map, which has been used in the conventional methods, so that low anisotropy voxels in the branching and crossing regions may be included. We applied the DDFT method and two conventional tractography methods (a streamline technique and a tensorline algorithm) to DT-MRI data of five normal subjects for visualizing the pyramidal tract. Our method visualized the pathways connected to a large portion of the primary motor cortex, including foot, hand and face motor areas, passing through the crossing regions with other white matter tracts in all subjects, whereas the conventional methods showed only a small portion of the pyramidal tract. The pyramidal tract pathways estimated by our method were consistent with the neuroanatomical knowledge. In conclusion, the DDFT method may be useful in assisting neuroradiologists in estimating the white matter tracts.

Intrathecal activation of the IL-17/IL-8 axis in opticospinal multiple sclerosis.

There are two distinct subtypes of multiple sclerosis in Asians, opticospinal (OS-multiple sclerosis) and conventional (C-multiple sclerosis). In OS-multiple sclerosis, selective and severe involvement of the optic nerves and spinal cord is characteristic, though its mechanisms are unknown. The present study aimed to find out possible differences in the cytokine/chemokine profiles in CSF between OS-multiple sclerosis and C-multiple sclerosis and to delineate the relationships between these profiles and neuroimaging and pathological features. Sixteen cytokines/chemokines, namely interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17, interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, granulocyte colony-stimulating factor (G-CSF), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1beta (MIP-1beta), were measured simultaneously in CSF supernatants from 40 patients with relapsing-remitting multiple sclerosis (20 OS-multiple sclerosis and 20 C-multiple sclerosis) at relapse and 19 control patients with spinocerebellar degeneration (SCD), together with intracellular production of IFN-gamma and IL-4 in CSF CD4+ T cells. In CSF supernatants relative to controls, IL-17, MIP-1beta, IL-1beta and IL-13 were only significantly increased in OS-multiple sclerosis patients, while TNF-alpha was only significantly increased in C-multiple sclerosis patients, using a cut-off level of 1 pg/ml. IL-8 was significantly elevated in both OS-multiple sclerosis and C-multiple sclerosis patients. MCP-1 was significantly decreased in both OS-multiple sclerosis and C-multiple sclerosis patients, while IL-7 was only significantly decreased in C-multiple sclerosis patients. IL-17, IL-8 and IL-5 were significantly higher in OS-multiple sclerosis patients than in C-multiple sclerosis patients. The increases in IL-17 and IL-8 in OS-multiple sclerosis were still significant even after exclusion of the patients undergoing various immunomodulatory therapies. Assays of intracellular cytokine production revealed that both the IFN-gamma+IL-4- T-cell percentage and intracellular IFN-gamma/IL-4 ratio in CSF cells were significantly greater in C-multiple sclerosis patients than in controls. Contrarily, OS-multiple sclerosis patients showed not only a significantly greater percentage of IFN-gamma+IL-4- T cells than controls but also a significantly higher percentage of IFN-gamma-IL-4+ T cells than C-multiple sclerosis patients. Among the cytokines elevated in multiple sclerosis, only IL-8 showed a significant positive correlation with the Expanded Disability Status Scale of Kurtzke score. Both the length of the spinal cord lesions on MRI and the CSF/serum albumin ratio had a significant positive correlation with IL-8 and IL-17 in multiple sclerosis, in which the spinal cord lesions were significantly longer in OS-multiple sclerosis than in C-multiple sclerosis. Three of six spinal cord specimens from autopsied OS-multiple sclerosis cases demonstrated numerous myeloperoxidase-positive neutrophils infiltrating necrotic lesions. These findings strongly suggest that in OS-multiple sclerosis, in addition to the Th1 cell upregulation seen in C-multiple sclerosis, intrathecal activation of the IL-17/IL-8 axis inducing heavy neutrophil infiltration contributes to extensive spinal cord lesion formation.

Magnetic resonance studies of brain lesions in patients with Kawasaki disease.

We evaluated brain lesions in patients with coronary arterial lesions (CAL) as a complication of Kawasaki disease (KD) by magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA). Among 47 patients who underwent coronary angiography for the evaluation of CAL due to KD at Kyushu University Hospital from April 1996 to September 2004, 24 patients were evaluated prospectively by brain MRI and MRA 0.1-21.2 years after the onset of KD. Although most patients had irritability or lethargy, none of them had significant neurological symptoms or signs during the acute phase, except one who showed neck stiffness. In one patient with no apparent neurological symptoms out of the 24 patients, brain MRI and MRA revealed right cerebellar infarction and obliteration of the right posterior inferior cerebellar artery, respectively. These results revealed the presence of cerebrovascular lesion in one of the 24 KD patients with CAL and suggested the need to consider the possibility of brain lesions in severe cases of KD with or without neurological symptoms.

Mapping of subcortical white matter abnormality in Alzheimer's disease using diffusion-weighted magnetic resonance imaging.

RATIONALE AND OBJECTIVES: White matter (WM) abnormality in Alzheimer's disease (AD) has been less well characterized than cortical damage. We studied the spatial distribution of the subcortical WM abnormality using diffusion-weighted magnetic resonance imaging (DWI). MATERIALS AND METHODS: Twenty-one AD patients and seven healthy, elderly subjects were included. DWIs were obtained using a cerebrospinal fluid (CSF)-nulled pulse sequence to reduce the partial volume contamination of CSF signal. Diffusivity in the subcortical WM voxels was mapped onto the cortical surface using original software so that the spatial distribution of subcortical WM damage, which was visualized as an area of increased diffusivity, could be viewed in a three-dimensional map. The damages in the lateral surface of the bilateral cerebral hemispheres were visually evaluated, and severities of the damages in five brain regions were compared with each other. In addition, the severity of the damage in each region was correlated with patient's mini-mental state examination (MMSE) score. RESULTS: In both hemispheres, clear sparing of the pericentral regions and predominant involvement of the parietal and temporal regions were revealed with statistical significance (P < .05, respectively). Marginal correlation (P < .05 uncorrected for multiple comparisons) was observed between the damage severity in the bilateral frontal and right temporal regions and patient's MMSE score. CONCLUSION: We demonstrated a subcortical WM abnormality over the parietal and temporal regions with clear sparing of the pericentral region using our mapping method, which supported the hypothesis that the subcortical WM abnormality in AD originates in Wallerian degeneration.

Cerebral white matter degeneration in frontotemporal dementia detected by diffusion-weighted magnetic resonance imaging.

RATIONALE AND OBJECTIVE: Brain tissue damage in frontotemporal dementia (FTD) has never been systematically studied using diffusion-weighted imaging (DWI). We studied FTD patients using DWI to determine whether microstructural changes in white matter can be detected in vivo. MATERIALS AND METHODS: Thirteen FTD patients and 15 aged healthy subjects were studied. Mean diffusivity (MD) abnormalities in 28 white matter regions were visually evaluated. In addition, MD values in 10 white matter regions relative to that in the ipsilateral postcentral gyrus were measured. The results were compared between healthy subjects and FTD patients. RESULTS: The visual rating resulted in a significant MD elevation in FTD patients in the bilateral high superior frontal gyri, right orbitofrontal gyrus, bilateral anterior temporal lobes, and left middle temporal lobe (P < .01, respectively). Relative MD comparison revealed a significant MD elevation in FTD patients in the bilateral high superior frontal gyri, bilateral orbitofrontal gyri, and bilateral anterior temporal lobes (P < .05 after Bonferroni correction, respectively). CONCLUSION: Our results demonstrated white matter MD abnormalities in FTD patients. It was suggested that the observed white matter MD abnormalities are secondary to damage in the overlying cortex.