Poststreptococcal acute disseminated encephalomyelitis with basal ganglia involvement and auto-reactive antibasal ganglia antibodies.

Antibasal ganglia antibodies (ABGA) are associated with Sydenham's chorea and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. We present 10 patients with acute disseminated encephalomyelitis (ADEM) associated with Group A beta hemolytic streptococcal infection. The clinical phenotype was novel, with 50% having a dystonic extrapyramidal movement disorder, and 70% a behavioral syndrome. None of the patients had rheumatic fever or Sydenham's chorea. Enzyme-linked immunosorbent assay, Western immunoblotting, and immunohistochemistry were used to detect ABGA. Neurological (n = 40) and streptococcal (n = 40) controls were used for comparison. Enzyme-linked immunosorbent assay results showed significantly elevated ABGA in the patients with poststreptococcal ADEM. Western immunoblotting demonstrated ABGA reactivity to three dominant protein bands of 60, 67, or 80 kDa; a finding not reproduced in controls. Fluorescent immunohistochemistry demonstrated specific binding to large striatal neurones, which was not seen in controls. Streptococcal serology was also significantly elevated in the poststreptococcal ADEM group compared with neurological controls. Magnetic resonance imaging studies showed hyperintense basal ganglia in 80% of patients with poststreptococcal ADEM, compared to 18% of patients with nonstreptococcal ADEM. These findings support a new subgroup of postinfectious autoimmune inflammatory disorders associated with Group A beta hemolytic streptococcus, abnormal basal ganglia imaging, and elevated ABGA.     

Acute fulminant demyelinating disease: a descriptive study of 60 patients

BACKGROUND: Acute demyelinating encephalomyelitis (ADEM) is characterized by a severe inflammatory attack, frequently secondary to infectious events or vaccinations. To date, no clear criteria exist for ADEM, and the risk of subsequent evolution to multiple sclerosis (MS) remains unknown. OBJECTIVE: To evaluate the risk of evolution to MS after a first episode of ADEM. DESIGN: Observational, retrospective case study. SETTING: Thirteen French MS centers. Patients We retrospectively studied 60 patients with ADEM who were older than 15 years with no history suggestive of an inflammatory event who presented to MS centers from January 1, 1995, through December 31, 2005. We excluded 6 patients with multiphasic ADEM because this is a rare condition and somewhat difficult to classify. After a mean follow-up of 3.1 years (range, 1-10 years), the remaining 54 patients were then classified into 2 groups: monophasic ADEM (ADEM group) (n = 35) and clinically definite MS (MS group) (n = 19). MAIN OUTCOME MEASURES: Clinical, laboratory, magnetic resonance imaging, and follow-up data were evaluated for each group. RESULTS: Patients in the ADEM group more frequently had atypical symptoms of MS (26 of 35 [74%]) than patients with MS (8 of 19 [42%]) (P = .02). Oligoclonal bands were more frequently observed in the MS group (16 of 19 [84%]) than in the ADEM group (7 of 35 [20%]) (P <.001). Patients in the ADEM group more frequently had gray matter involvement (21 of 35 [60%]) than those in the MS group (2 of 19 [11%]) (P <.001). On the basis of these results, we consider that the presence of any 2 of the following 3 criteria could be used to differentiate patients with ADEM from those with MS in our cohort: atypical clinical symptoms for MS, absence of oligoclonal bands, and gray matter involvement. On this basis, 29 of the 35 patients in the ADEM group (83%) and 18 of the 19 patients in the MS group (95%) were classified in the appropriate category. CONCLUSIONS: Our study found some differences concerning the risk of evolution to clinically definite MS after a first demyelinating episode suggestive of ADEM. These findings led us to propose criteria that should now be tested in a larger, prospective cohort study.     

Cerebral grey matter pathology and fatigue in patients with multiple sclerosis: a preliminary study.

In patients with multiple sclerosis (MS), we investigated whether the extent of cerebral grey matter (GM) pathology is associated with the presence and severity of fatigue. We quantified cerebral GM pathology in 28 MS patients (14 with fatigue and 14 without fatigue) using magnetization transfer (MT) and diffusion tensor (DT) magnetic resonance imaging (MRI). The average MT ratio and mean diffusivity from cerebral GM did not differ between fatigued and non-fatigued patients. Fatigued and non-fatigued patients also did not differ in terms of GM pathology of the cerebral cortex of the frontal lobe and basal ganglia. No correlations were found between the fatigue severity scale scores and any of the MT- and DT-MRI quantities. These preliminary results suggest that structural GM pathology is not a major contributing factor to the development of fatigue in patients with MS.     

急性播散性脑脊髓炎与经典多发性硬化的临床对比分析

目的 寻找临床上鉴别急性播散性脑脊髓炎(acute disseminated encephalumyelitis,ADEM)与经典多发性硬化(classical multiple sclerosis,CMS)的方法.方法 回顾性分析20例ADEM和24例CMS患者的流行病学特点、临床症状、实验室检查和MRI,对各定性资料进行卡方检验,定量资料进行两独立样本的Wilcoxon秩和检验.结果 ADEM患者起病年龄[(27±15)岁]较CMS患者[(37±13)岁,Z=-2.218,P=0.027]小.ADEM患者通常有前驱感染史(75%),发热(65%)、脑膜刺激征(40%)、癫痫(25%),较CMS者常见(x2=23.652、18.609、9.189、4.514,均P＜0 05),脑病更多见于ADEM患者.ADEM患者血白细胞[(11 9±5.8)×109/L,Z=-2.030,P=0.042]、C反应蛋白(2.74 mg/L,Z=-3.028,P=0.002)、红细胞沉降率(11.00 mm/h,Z=-2 406,P=0.016)、脑脊液白细胞(9×106/L,Z=-2.781,P=0.005)较CMS患者[上述指标分别为(8.0±3.2)×109/L、0.49 mg/L、7.00 mm/h、2 ×106/L]高,脑脊液蛋白(ADEM组0.19 g/L,CMS组0.17 g/L)及寡克隆带(OCB)阳性率(ADEM组4/20,CMS组11/24)在两者间差异无统计学意义.在MRI上,ADEM患者更多见皮质灰质病灶(14/20,x2=15.213,P=0.000)、基底节区灰质病灶(14/20,x2=8.910,P=0.003)和脑干病灶(14/20,x2=5.867,P=0.015),脊髓病灶多近中央分布(83%,x2=11.542,P=0 001),病灶边界模糊(95%,x2=21.787,P=0.000);CMS患者更多见近皮质白质病灶(21/24,x2=17.628,P=0.000)、侧脑室旁病灶(21/24,x2=15.213,P=0.000)和胼胝体病灶(14/24,x2=8.640,P=0.003),脊髓病灶多呈偏心分布(85%),病灶边界清楚(75%).结论 ADEM与CMS无论在流行病学特点、临床症状,还是在脑脊液和MRI检查方面都有一定差异.

Abstract：

Objective To improve differential diagnosis between acute disseminated encephalomyelitis ( ADEM) and classical multiple sclerosis ( CMS).Methods All 20 cases of ADEM and 24 cases of CMS were examined.Their epidemiological and clinical findings,laboratory features and magnetic resonance imaging ( MRI) data were analyzed using x2 test for categorical variables,Wilcoxon Rank-Sum tests for continuous variables.Results ADEM and CMS showed no sex predominance.Patients with ADEM ((27 ±15) years) were younger than CMS ((37 ±13) years,Z= -2.218,P =0.027).The following findings were more commonly seen in ADEM compared with CMS:predemyelinating infectious disease (75% vs 4%,x2 =23.652,P = 0.000),fever (65% vs 4%,x2 =18.609,P = 0.000),meningeal irritation sign (40% vs 0,x2 = 9.189,P =0.002),seizure (25% vs 0,x2 =4.514,P = 0.034),and encephalopathy.ADEM patients were more likely to present with blood leucocytosis ( (11.9 ± 5.8) ×109/L vs (8.0±3.2) ×109/L,Z= -2.030,P=0.042),high C-reactive protein (2.74 mg/L vs 0.49 mg/L,Z = - 3.028,P = 0.002),increased erythrocyte sedimentation rate (11.00 mm/h vs 7.00 mm/h,Z= -2.406,P =0.016),and cerebrospinal fluid leucocytosis (9 × 106/L vs 2×106/L,Z =- 2.781,P = 0.005).There were no differences in cerebrospinal fluid protein and oligoclonal band between the two groups.The following MRI lesions were more commonly seen in ADEM patients:cortical gray matter lesions (14/20,x2=15.213,P=0.000),basal ganglia gray matter lesions (14/20,x2 =8.910,P = 0.003),and brainstem lesions ( 14/20,x2 = 5.867,P = 0.015).In contrast,lesions in subcortical white matter (21/24,x2 = 17.628,P =0.000),periventricular area (21/24,x2 =15.213,P=0.000) and corpus callosum ( 14/24,x2 = 8.640,P = 0.003 ) were more common in the MRI image of CMS patients.The lesions in spinal cord were usually centrally distributed in ADEM (83% ),while peripherally in CMS (85%,x2 = 11.542,P = 0.001).The lesions had poorly defined margins in ADEM (95%),but well defined margins in CMS (75%,x2 =21.787,P = 0.000).Conclusion There are differences in epidemiological and clinical findings,laboratory features and MRI appearances between ADEM and CMS.     

Anatomical MRI study of basal ganglia in bipolar disorder patients

This study examined possible anatomical abnormalities in basal ganglia structures in bipolar disorder patients. Caudate and putamen gray matter volumes, and globus pallidus total volume were measured with magnetic resonance imaging (MRI) in 22 DSM-IV bipolar patients (age+/-S.D.=36+/-10 years; eight drug-free and 14 lithium monotherapy patients) and 22 matched healthy control subjects (age+/-S.D.=38+/-10 years). No significant differences were found between bipolar patients and healthy control subjects for any of the basal ganglia measures (t-tests, P>0.05). Age was inversely correlated with left putamen volumes in patients (R=-0.44, P=0.04), but not in healthy control subjects (R=-0.33, P=0.14). Older patients (>36 years old) had a significantly larger left globus pallidus than younger ones (< or =36 years old) (ANOVA, P=0.01). In a multiple regression analysis, after entering age as independent variable, the length of illness predicted smaller left putamen volumes, explaining 10.4% of the variance (F=4.07, d.f.=2, P=0.03). No significant effects of episode type, number of prior episodes, or gender were found in any basal ganglia measurements (ANOVA, P>0.05). In conclusion, our findings indicate that the basal ganglia may be anatomically preserved in bipolar patients. This is in contrast to available findings for unipolar disorder. However, our findings also suggest that age and length of illness may have significant effects on basal ganglia structures in bipolar patients, which may be more pronounced among bipolar I patients, and of relevance for the pathophysiology of the disorder.     

Oligoclonal IgG band patterns in inflammatory demyelinating human and mouse diseases

We evaluated oligoclonal IgG band (OCB) patterns obtained by analyzing paired cerebrospinal fluid (CSF) and serum samples of 77 patients with acute demyelinating encephalomyelitis (ADEM) and 411 patients with multiple sclerosis (MS). OCBs were searched with isoelectric focusing and capillary immunoblotting. CSF-restricted OCBs were found in 89% of MS patients and 10% of ADEM patients (p<0.0001). Identical serum and CSF OCBs ('mirror pattern'), or no OCBs, were detected in 10% of MS patients and 84% of ADEM patients (p<0.0001). OCBs were also analyzed in 27 mice with proteolipid protein-induced experimental autoimmune encephalomyelitis (EAE). In this animal model, the 'mirror pattern' was the most frequently detected pattern (74%), with the immunizing antigen being the main OCB target. These results indicate that CSF analysis can help differentiate between MS and ADEM and that, similarly to EAE, the 'mirror pattern' observed in ADEM accounts for a predominantly systemic immune activation.     

A three-year, multi-parametric MRI study in patients at presentation with CIS

OBJECTIVES: To define the extent of overall brain damage in patients with clinically isolated syndromes (CIS) suggestive of multiple sclerosis (MS) and to identify non-conventional magnetic resonance (MR) metrics predictive of evolution to definite MS. METHODS: Brain conventional and magnetization transfer (MT) MRI scans were obtained from 208 CIS patients and 55 matched healthy controls, recruited in four centres. Patients were assessed clinically at the time of MRI acquisition and after a median period of 3.1 years from disease onset. The following measures were derived: T2, T1 and gadolinium (Gd)- enhancing lesion volumes (LV), normalized brain volume (NBV), MTR histogram-derived quantities of the normal-appearing white matter (NAWM) and grey matter (GM). RESULTS: During the follow-up, 43 % of the patients converted to definite MS. At baseline, a significant inter-centre heterogeneity was detected for T2 LV (p = 0.003), T1 LV (p = 0.006), NBV (p < 0.001) and MTR histogram-derived metrics (p < 0.001). Pooled average MTR values differed between CIS patients and controls for NAWM (p = 0.003) and GM (p = 0.01). Gdactivity and positivity of International Panel (IP) criteria for disease dissemination in space (DIS), but not NAWM and GM MTR and NBV, were associated with evolution to definite MS. The final multivariable model retained only MRI IP criteria for DIS (p = 0.05; HR = 1.66, 95 % CI = 1.00-2.77) as an independent predictor of evolution to definite MS. CONCLUSIONS: Although irreversible tissue injury is present from the earliest clinical stages of MS, macroscopic focal lesions but not "diffuse" brain damage measured by MTR are associated to an increased risk of subsequent development of definite MS in CIS patients.     

CSF beta-1 Globulin--a potential marker in differentiating multiple sclerosis and acute disseminated encephalomyelitis: a preliminary study

The exact diagnosis of demyelinating diseases is an enigma even in the best neurological centres. In the present study, the potential role of differential CSF proteins has been critically evaluated in differentiating multiple sclerosis (MS) and acute disseminated encephalomyelitis (ADEM). Cellulose acetate electrophoresis was carried out on CSF and serum samples of 14 MS patients, 23 ADEM patients and 30 controls. There was no statistically significant difference between serum electrophoresis of controls and MS patients. However, in case of CSF electrophoresis there was a statistically significant decrease in beta-1 fraction in 92.2% of MS patients (p=0.01). A comparison between serum electrophoresis of controls and ADEM patients indicated a statistically significant decrease in serum albumin in 87% patients and an increase of alpha-2 globulin in 73.9%. There was no statistically significant difference between CSF electrophoresis of controls and ADEM patients except for the prealbumin fraction which was raised in 60.9% of patients. No statistically significant difference was seen between the serum electrophoresis of ADEM and MS patients. However, on comparing CSF electrophoresis, it was seen that beta-1 fraction was significantly higher in ADEM patients (p<0.05). The predictive value of beta-1 fraction in differentiating MS and ADEM was then evaluated. The negative predictive value was 100% indicating that all samples with a beta-1 fraction of>6.5% cannot be diagnosed as MS. The significant decrease in beta-1 fraction in MS patients may prove to be an early indicator in differentiating between MS and ADEM patients.     

Relationship between clinical course and Diffusion-weighted MRI findings in sporadic Creutzfeldt-Jakob Disease

The aim of this study was to investigate the relationship between clinical course and diffusion-weighted MRI (DWI) findings in sporadic Creutzfeldt-Jakob Disease (sCJD). We reviewed clinical records and MRI examination in nine probable sCJD. According to hyperintense signal distribution on DWI, the patients were classified into two groups with cortical ribbon plus basal ganglia hyperintensity (6/9) and with only increased cortical signals (3/9). Clinical features including quadriparesis (3/6), akinetic mutism (2/6), and dysphasia (2/6), which were usually observed in the more advanced stage of CJD, were noted only in patients with cortical ribbon plus basal ganglia hyperintensity at the time of initial DWI examination. The patients with the cortical plus basal ganglia hyperintensity (6.4+/-1.7 weeks) had a shorter interval from symptom onset to akinetic mutism than those with only cortical ribbon hyperintensity (26.0+/-22.5 weeks) (p=0.02). These findings suggest that DWI may predict the clinical course of CJD.     

Progressive gray matter damage in patients with relapsing-remitting multiple sclerosis: a longitudinal diffusion tensor magnetic resonance imaging study

BACKGROUND: Diffusion tensor magnetic resonance imaging (DT MRI) has the potential to provide in vivo information about tissue microstructure. In multiple sclerosis (MS), DT MRI has disclosed the presence of occult structural damage in the normal-appearing brain tissues. OBJECTIVE: To investigate whether DT MRI is sensitive to longitudinal changes of brain damage that may occur beyond the resolution of T2-weighted images in patients with relapsing-remitting MS. DESIGN: Twenty-six untreated patients with relapsing-remitting MS were followed up for 18 months. Dual-echo, DT and postcontrast T1-weighted MRIs of the brain were obtained at baseline and then every 3 months. Mean diffusivity (D) histograms of normal-appearing gray (GM) and white matter were produced. Total T2-hyperintense and T1-hypointense lesion volumes; normalized whole brain tissue, GM, and white matter volumes; percentage brain volume change between the study entry and exit images; average lesion D; and fractional anisotropy were also calculated. RESULTS: During the study period, a significant decrease of normalized whole brain tissue, average lesion fractional anisotropy and normal-appearing GM D histogram peak height, and a significant increase of average normal-appearing GM D and T2-hyperintense lesion volumes were observed. Changes of normal-appearing GM diffusivity were independent of the concomitant changes of normalized whole brain tissue and GM volumes. CONCLUSIONS: The DT MRI findings show progressive microstructural changes in the normal-appearing GM of patients with untreated relapsing-remitting MS. Such changes do not reflect a concomitant development of brain atrophy and confirm the importance of GM pathology in MS.     

Three-dimensional proton spectroscopy of deep gray matter nuclei in relapsing-remitting MS

The metabolic changes in the deep gray matter (GM) nuclei, thalamus, and basal ganglia of patients with relapsing-remitting multiple sclerosis were investigated with quantitative, multivoxel, three-dimensional proton MR spectroscopy. This technique facilitated the study of several bilateral structures in a single session at sub-cubic centimeter spatial resolution. Compared with 9 matched control subjects, the deep GM nuclei of 11 patients showed 7% lower N-acetylaspartate and 14% higher choline levels (p = 0.02 for both).     

Acute disseminated encephalomyelitis

Acute disseminated encephalomyelitis (ADEM) is an uncommon inflammatory demyelinating disease of the central nervous system. The true incidence of the disease in India is undetermined and is likely to be more frequent than reported, as the common antecedent events, exanthematous fevers and Semple antirabies vaccination, which predispose to ADEM, are still prevalent. The existing evidence suggests that ADEM results from a transient autoimmune response towards myelin or other self-antigens, possibly via molecular mimicry, or by non-specific activation of auto-reactive T cell clones. ADEM is a monophasic illness with favourable long-term outcome. Involvement of neuroaxis is variable and can be diffuse or multifocal and site restricted. Magnetic resonance imaging (MRI) is highly sensitive in detecting white matter lesions and the lesions described are rather extensive and subcortical in location. Involvement of the deep gray matter, particularly basal ganglia, is more frequent. Oligoclonal bands in CSF are usually absent. No therapy has been established by controlled trials in ADEM. Use of high-dose methylprednisolone, plasma exchange, and IVIG are based on the analogy of the pathogenesis of ADEM with that of multiple sclerosis (MS). Differentiation of ADEM from the first attack of MS is important from prognostic as well as therapeutic point of view. However, in the absence of biological marker, at times differentiation of ADEM from the initial presentation of MS may not be possible even by combination of clinical, CSF analysis, and MRI. This differentiation is more relevant to India where the incidence of MS is low.     

等电聚焦电泳联合免疫印迹法检测寡克隆区带诊断神经系统炎性脱髓鞘疾病

目的 探讨等电聚焦电泳(IEF)联合免疫印迹法检测寡克隆区带(OB)在神经系统炎性脱髓鞘疾病(IDD)中的应用.方法 IEF联合免疫印迹法检测112例IDD及24例神经系统非炎性疾病(NIND)患者血清和脑脊液中OB,并进行对比分析.结果 与视神经脊髓炎(5/21,23.8%,x2=32.679)、急性播散性脑脊髓炎(1/4,Fisher精确检验)、系统性自身免疫病继发中枢神经系统IDD(3/19,15.8%,x2=37.425)、周围神经系统IDD(0,x2=51.944)和NIND(0,x2=51.944)患者比较,多发性硬化(MS)患者脑脊液OB阳性率(44/46,91.7%)显著升高(P＜0.01).IEF联合免疫印迹法检测OB诊断MS的敏感度为91.7%,特异度为89.8%,高于其他检测方法.2例急性播散性脑脊髓炎患者和1例MS患者血清和脑脊液OB有相同条带,呈"镜像分布".结论 IEF联合免疫印迹法检测OB在MS诊断中具有一定的临床价值.

Abstract：

Objective To explore the diagnostic value of oligoclonal band (OB) detected by isoelectric focusing (IEF) with immunoblotting in inflammatory demyelinating diseases (IDD) in nervous system.Methods Serum and cerebrospinal fluid (CSF) OB was detected by IEF with immunoblotting in 112 patients with IDD ( multiple sclerosis ( MS):n = 48;neuromyelitis optica ( NMO):n = 21:acute disseminated encephalomyelitis ( ADEM):n = 4;secondary IDD from systemic autoimmune diseases:n = 19;peripheral nervous system IDD:n =20) and 24 patients with non-inflammatory neurological disease (NIND).Results CSF-restricted OB was detected in 91.7% (44/48) of MS patients,23.8% (5/21) of NMO patients(x2nmO vs MS= 32.679),1/4 of ADEM patients (Fisher' s excact test),15.8% (3/19) of secondary IDD patients (x2secondary IDD vs MS = 37.425 ),0 of peripheral nervous system IDD patients (x2peripheral nervous system IDD vs MS =37.425) and 0 of NIND patients (x2NIND vs MS =37.425).MS patients had significantly higher percentage of patients with CSF-restricted OB ( all P ＜0.01),compared with NIND and other IDD patients.The sensitivity and specificity of OB detected by IEF with immunoblotting for MS were 91.7% and 89.8%,which were higher than that of OB detected by other methods.Identical serum and CSF OB ( "mirror pattern" ) was detected in 2 of 4 ADEM patients and 1 of 48 MS patients.Conclusion IEF with immunoblotting to detect OB is a reliable method of diagnosis for MS.     

Cytokines and chemokines in cerebrospinal fluid and serum of adult patients with acute disseminated encephalomyelitis

Cytokines and chemokines contribute to the pathogenesis of acute disseminated encephalomyelitis (ADEM). Using a multiplex immunochemiluminescence ELISA, we measured 8 Th1/Th2 cytokines and 18 chemokines in the cerebrospinal fluid (CSF) and serum of 17 ADEM patients, 14 multiple sclerosis (MS) patients, and 7 healthy controls (HCs). Relative to HCs, ADEM patients had significantly high mean CSF concentrations of chemokines with attractant/activating properties towards neutrophils (CXCL1 and CXCL7), monocytes/T cells (CCL3 and CCL5), Th1 cells (CXCL10), and Th2 cells (CCL1, CCL22, and CCL17). Mean CSF concentrations of CXCL7, CCL1, CCL22, and CCL17 were higher in ADEM than in MS, whereas those of CCL11 were lower in MS than in ADEM and HCs. CSF pleocytosis correlated with CSF concentrations of CXCL1, CXCL10, CCL1, CCL17, and CCL22. Most of the functionally homologous chemokines correlated with each other. CSF Th1/Th2 cytokines were not detectable in most samples. Their mean concentrations did not differ in the three groups, and the same held for serum cytokines and chemokines. Our data suggest that the upregulation of chemokines active on neutrophils and Th2 cells differentiates ADEM from MS inflammation, and that both Th1 and Th2 chemokines might be produced in ADEM. Chemokines upregulated in ADEM could become CSF biomarkers after a posteriori evaluations in unselected case series.     

Highly active antiretroviral therapy reverses brain metabolite abnormalities in mild HIV dementia.

OBJECTIVE: To determine whether cerebral metabolite abnormalities normalize with highly active antiretroviral therapy (HAART). BACKGROUND: Patients with HIV-cognitive motor complex (HIV-CMC) show cerebral metabolite abnormalities in the early stages of dementia. METHODS: Sixteen patients with HIV-CMC were evaluated before and after HAART, and compared with 15 HIV-negative healthy volunteers. Cerebral metabolite ratios and concentrations in the frontal lobe and basal ganglia were measured using proton MRS (1H MRS). RESULTS: In 14 of 16 patients who tolerated HAART, CD4 count increased by 133+/-101 cells/mm3 (p = 0.0003), HIV Dementia Scale score increased by 1.8+/-2.4 points (p = 0.02), and AIDS dementia complex (ADC) stage decreased by 0.54+/-0.54 points (p = 0.003). The initially increased choline/creatine (CHO/CR) reversed in the midfrontal cortex (-8.0%; p = 0.02) and in the basal ganglia (-14.7%; p = 0.01). The initially elevated myoinositol (MI)/CR and myoinositol concentration [MI] in the basal ganglia also decreased (MI/CR: -14.1%; p = 0.005; [MI]: 11.8%; p = 0.02), along with normalization of [MI] in the frontal white matter (11.4%; p = 0.05). Furthermore, the change in [MI] in the frontal white matter correlated with the change in CD4 count (r = -0.67, p = 0.03) and with the change in ADC stage (p = 0.04). CONCLUSIONS: HAART improves HIV-CMC in addition to systemic measures of HIV infection. 1H MRS detects improvement of brain injury measured by cerebral metabolites, particularly the glial marker [MI], in patients with early HIV-CMC after HAART. In addition, the degree of improvement in clinical severity of HIV-CMC is related to the degree of recovery with [MI].     

Acute disseminated encephalomyelitis: study of factors involved in a possible development towards multiple sclerosis

Acute disseminated encephalomyelitis (ADEM) is an uncommon disease characterized by inflammation and demyelination of the central nervous system (CNS). It typically occurs after a viral infection or vaccination and is more frequent in children. Its immediate and longterm prognosis is expected to be good (20% of cases with sequelae). Although ADEM is typically monophasic, occasional relapses may occur. Differential diagnosis, mostly in the early phases, is established with multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the CNS that may have worse prognosis. Traditionally it has been believed that 10% of ADEM patients develop MS. However, this percentage could be higher according to several recently published clinical series. Some clinical and paraclinical patterns are considered to confer risk of developing MS when present in ADEM patients. Our study has aimed to: a) describe a series of 29 patients (22 children and 9 adults) admitted in our hospital and diagnosed of ADEM between 1990 and 2005; b) study those patients considered to have risk patterns of developing MS, and c) compare the child and adult populations of our series. After a median 55 month follow-up, 6 children (27%) and no adults developed MS. In our series, risk patterns for developing MS predicted conversion to MS more accurately in children than in adults. Eight patients (6 children and 2 adults) had sequelae, cognitive in 6 of them. Our work supports that also observed in recent publications: that both conversion to MS or presence of sequelae after an episode of ADEM are more frequent than traditionally considered.     

Serial magnetic resonance imaging in children with postinfectious encephalitis

We analyzed follow-up magnetic resonance images (MRI) in eight children with clinical postinfectious encephalitis (PIE), and discussed their pathogeneses. Three categories of MRI findings were apparent: (1) multifocal lesions in the white matter with/without basal ganglia involvement consistent with acute disseminated encephalomyelitis (ADEM) (three patients); (2) single or multifocal lesions localized only in the gray matter (two patients); and (3) localized lesions in the brain stem, basal ganglia or cerebellum. Some lesions in the patients in Categories 1 and 2 migrated or were resolved quickly, sometimes within 10 days. Gadolinium caused linear or spotty enhancement in the patients in Category 2. These findings suggest that Categories 1 and 2 are a self-limiting allergic angiopathy without demyelination. In contrast, the lesions in the patients in Category 3 were fixed, and not resolved within 6 months (three patients). The pathogenesis of Category 3 is not known. All except one patient had no prednisolone (PSL) therapy, however; all lesions were resolved completely or markedly reduced in size, which indicates PSL therapy is not always necessary in patients with PIE.     

MRI volumetry and proton MR spectroscopy of the brain in Lafora disease

PURPOSE: To determine brain involvement in Lafora disease by means of 3-T MRI volumetry and 1H magnetic resonance (MR) spectroscopy. METHODS: Ten patients with Lafora disease and 10 healthy controls were included in the study. The diagnosis of Lafora disease was proven genetically by the presence of mutations in the EPM2A gene in all patients, and their evolution was staged in three groups according to their functional state. MRI volumetry was performed by means of AX3DT1 images with assessment of the cerebellum and the brainstem, by using the program Stereonauta, and all the brain structures, by using voxel-based morphometry. [1H]MR spectroscopy was performed by using an Eclipse PRESS sequence probe system with 8-cc voxels positioned in the occipital and frontal cortexes, basal ganglia, pons, and cerebellar hemispheres. Spectral peak areas corresponding to NAA (N-acetylaspartate), creatine, and choline were obtained. RESULTS: MRI volumetry showed no statistically significant differences in patients compared with healthy controls in any of the analyzed structures. Analysis of [1H]MR spectroscopy data showed a statistically significant reduction in the NAA/creatine ratio in patients compared with controls in the frontal (p = 0.001) and occipital cortex (p = 0.043), basal ganglia (p = 0.002), and cerebellar hemispheres (p = 0.007). The NAA/choline and choline/creatine ratios were statistically significantly different in the frontal cortex (p = 0.005). No correlation was observed between the disease-evolution stage and MRI-measured volumes (range, -0.92 to 0.44) or [1H]MR spectroscopy values (range, -0.29 to 0.50). CONCLUSIONS: In our series of Lafora disease patients, [1H]MR spectroscopy was more sensitive than structural MRI to detect brain involvement. The brain cortex, especially frontal cortex, cerebellum, and basal ganglia, showed the greatest metabolic changes.     

MRI quantification of gray and white matter damage in patients with early–onset multiple sclerosis

Background and objective Contrary to what happens in adult–onset multiple sclerosis (MS), in a previous preliminary magnetic resonance imaging (MRI) study we showed only subtle normal–appearing brain tissue changes in patients with earlyonset MS. Our objective was to evaluate the presence and extent of tissue damage in the brain normalappearing white matter (NAWM) and gray matter (GM) from a larger population of patients with earlyonset MS. Methods Using diffusion tensor (DT) and magnetization transfer (MT) MRI, we obtained DT and MT ratio (MTR) maps of the NAWM and GM from 23 patients with early–onset MS and 16 sex– and age–matched healthy volunteers. Results Compared with healthy volunteers, patients with early–onset MS had significantly increased average MD (p = 0.02) and FA peak height (p = 0.007) and decreased average FA (p <0.0001) of the NAWM.Brain dual–echo lesion load was significantly correlated with average FA (r = –0.48, p = 0.02) and with FA peak height (r = 0.45, p = 0.03) of the NAWM. No MTR and diffusion changes were detected in the GM. Conclusions This study confirms the paucity of the ‘occult’ brain tissue damage in patients with earlyonset MS. It also suggests that in these patients GM is spared by the disease process and that NAWM changes are likely to be secondary to Wallerian degeneration of fibers passing through macroscopic lesions.