Extensive White Matter Lesions Research Articles

Deep coma and diffuse white matter abnormalities caused by sepsis-associated encephalopathy

In January, 2012, a 53-year-old woman with a history of progressive polyposis coli and hypertension was admitted to the intensive care unit (ICU) of our hospital because of septic shock 4 days after laparoscopic subtotal colectomy. She was intubated and mechanically ventilated, underwent emergent re-laparotomy for anastomotic leakage, and was treated with antibiotics. Blood cultures were positive for multiresistant Enterococcus faecium. After re-laparotomy the patient was sedated with midazolam for 2 days. The neurologist was consulted on the fourth postoperative day because of the patient’s persistent low level of consciousness. On neurological examination, we found no eye opening or motor response to a painful stimulus, intact brainstem refl exes, and generalised arefl exia of arms and legs with indiff erent plantar refl exes. We observed no signs indicative of minimally convulsive status epilepticus. During the period of septic shock and surgery, blood pressure had not been lower than 100/50 mm Hg and laboratory tests did not show abnormalities that could explain the patient’s coma. Non-contrast CT (NCCT) of the brain showed abnormal hypodensity of the complete white matter with swelling of the entire brain (fi gure); CT angiography was normal. Electromyography showed absence of motor unit potentials in arm and leg muscles without evidence for accompanying neuropathy. We made a diagnosis of sepsis-associated encephalopathy and critical illness myopathy. Because of the deep coma and the diff use and severely abnormal aspect of the white matter—both associated with poor outcome—dis continuation of treatment was discussed, but we recommended to continue treatment. On the ninth postoperative day the patient opened her eyes in response to painful stimuli, but there was still no motor response. Follow-up NCCT showed no improvement of the white matter abnormalities. In the following weeks the condition of the patient gradually improved and 4 weeks after the re-laparotomy she had regained full consciousness. When the patient was discharged from the ICU her muscle strength had gradually improved with movements against gravity now possible. At that time brain MRI was normal except for a small number of white matter lesions (fi gure). The patient was transferred to a rehabilitation centre 6 weeks after the initial onset of septic shock. At that point she was able to walk short distances. At last follow-up on Aug 19, 2012, she had regained independence in activities of daily living and was living at home. Sepsis-associated encephalopathy is a severe complication of sepsis and is associated with poor outcome. The reported incidence ranges from 9% to 71% because of variations in the defi nition. A recent study in an ICU showed that patients with sepsis secondary to intestinal infections are prone to develop septic encephalopathy, with Escherichia coli and Enterococcus faecium among the most frequently cultured bacteria. The exact pathogenesis of sepsis-associated encephalopathy remains unclear; disruption of the blood-brain barrier and mitochondrial dysfunction are probably involved. Imaging of the brain can show atrophy and periventricular white matter lesions. The diff use and severe white matter abnormalities like those we observed in our patient are rare and have been associated with poor outcome. This case shows that severe encephalopathy with extensive white matter lesions can be a reversible condition. Clinicians should realise that the fi rst signs of improvement of the clinical condition could still be observed beyond 7 days after onset.

Diffusion tensor magnetic resonance imaging for single subject diagnosis in neurodegenerative diseases

Although magnetic resonance imaging is a standard investigation in neurodegenerative disease, sensitive and specific markers for the underlying histopathological diagnosis are largely lacking. This report presents evidence to indicate that corticobasal degeneration and progressive supranuclear palsy, in particular, might be identifiable at a single subject level with diffusion tensor imaging. Patients with clinical diagnoses of Alzheimer's disease, semantic dementia and non-fluent primary progressive aphasia (n = 9 each) were contrasted with control subjects (n = 26) with the diffusion tensor imaging measures: fractional anisotropy, axial and radial diffusivity. At 1 year follow-up, all participants with non-fluent primary progressive aphasia had evolved either corticobasal degeneration (n = 5) or progressive supranuclear palsy (n = 4). The corticobasal degeneration/progressive supranuclear palsy set showed white matter abnormalities involving the entire cerebrum. Individual maps were similar to the group level results, even in the most minimally impaired patients. Fractional anisotropy was consistently the most sensitive metric. In Alzheimer's disease and semantic dementia, by contrast, group level and individual analyses revealed limited areas of abnormality centred on the posterior cingulate and rostral temporal lobes, respectively. In both groups radial diffusivity was the most sensitive metric. Scrutiny of the standard scores for each group's most sensitive metric revealed that, although the values for every patient with corticobasal degeneration or progressive supranuclear palsy fell outside 95% of the normal mean, none of the other two groups' members had values outside this range. Further underscoring the hypothesis that this finding relates specifically to a diffuse pathological process in the white matter of the tauopathies, and is not merely a function of disease severity, a grey matter analysis consisting of group level voxel-based morphometry revealed only focal areas of atrophy in all three groups. Consistent with past reports for the respective clinical syndromes, these were centred on the left frontal operculum and caudate nucleus in non-fluent primary progressive aphasia (the corticobasal degeneration/progressive supranuclear palsy set), anterior temporal lobes in semantic dementia, and hippocampus and posterior cingulate gyrus in Alzheimer's disease. Detection of this extensive white matter lesion in corticobasal degeneration and progressive supranuclear palsy-a pathologically proven feature of these conditions--in single subjects with diffusion tensor imaging appears to have strong diagnostic marker potential for these diseases.

Extents of White Matter Lesions and Increased Intraventricular Extension of Intracerebral Hemorrhage

To determine whether the extent of white matter lesions on a CT scan of acute intracerebral hemorrhage patients is associated with the prevalence and severity of intraventricular extension of hemorrhage. A post hoc analysis of Acute Brain Bleeding Analysis-IntraCerebral Hemorrhage cohort, a nationwide prospective cohort of acute intracerebral hemorrhage patients (total number of cohort subjects, 1,604). Spontaneous intracerebral hemorrhage patients (n = 1,262). None. The authors analyzed CT scan images taken within 48 hours after stroke onset. Extent of white matter lesions, volume of intracerebral hemorrhage, presence of intraventricular extension of hemorrhage, and intraventricular extension of hemorrhage score (approximation of intraventricular extension of hemorrhage volume) were measured using CT scans, and demographic, laboratory, clinical, and mortality data were also gathered through review of medical records and retrieval from the governmental statistical archive. The frequency of intraventricular extension of hemorrhage in our population was 27.2% (343 subjects). The proportion of extensive white matter lesions in intraventricular extension of hemorrhage subjects (33.8%) was higher than that of non-intraventricular extension of hemorrhage cases (16.3%; p < 0.01). Multivariable analysis showed that mild (odds ratio, 1.48; 95% confidence interval 1.05- 0.09; p < 0.01) and extensive (odds ratio, 2.73; 95% confidence interval 1.88-3.98; p < 0.01) white matter lesions were significantly associated with the presence of intraventricular extension of hemorrhage in spontaneous intracerebral hemorrhage patients. The estimated mean of the intraventricular extension of hemorrhage score from the extensive white matter lesions group (9.09 ± 0.76) was significantly higher than that of the no white matter lesions group (6.72 ± 0.78; p < 0.01 from analyses of covariances) after adjustment for relevant covariates. We documented that the severity of white matter lesions is related to the occurrence and amount of intraventricular extension of hemorrhage in spontaneous intracerebral hemorrhage cases.

ACTA2 mutation with childhood cardiovascular, autonomic and brain anomalies and severe outcome

Thoracic aortic aneurysm and dissection (TAAD) are associated with connective tissue disorders like Marfan syndrome and Loeys-Dietz syndrome, caused by mutations in the fibrillin-1, the TGFβ-receptor 1- and -2 genes, the SMAD3 and TGFβ2 genes, but have also been ascribed to ACTA2 gene mutations in adults, spread throughout the gene. We report on a novel de novo c.535C>T in exon 6 leading to p.R179C aminoacid substitution in ACTA2 in a toddler girl with primary pulmonary hypertension, persistent ductus arteriosus, extensive cerebral white matter lesions, fixed dilated pupils, intestinal malrotation, and hypotonic bladder. Recently, de novo ACTA2 R179H substitutions have been associated with a similar phenotype and additional cerebral developmental defects including underdeveloped corpus callosum and vermis hypoplasia in a single patient. The patient here shows previously undescribed abnormal lobulation of the frontal lobes and position of the gyrus cinguli and rostral dysplasis of the corpus callosum; she died at the age of 3 years during surgery due to vascular fragility and rupture of the ductus arteriosus. Altogether these observations support a role of ACTA2 in brain development, especially related to the arginine at position 179. Although all previously reported patients with R179H substitution successfully underwent the same surgery at younger ages, the severe outcome of our patient warns against the devastating effects of the R179C substitution on vasculature.

Accumulation of MRI Markers of Cerebral Small Vessel Disease is Associated with Decreased Cognitive Function. A Study in First-Ever Lacunar Stroke and Hypertensive Patients

Background: White matter lesions (WMLs), asymptomatic lacunar infarcts, brain microbleeds (BMBs), and enlarged perivascular spaces (EPVS) have been identified as silent lesions due to cerebral small vessel disease (cSVD). All these markers have been individually linked to cognitive functioning, but are also strongly correlated with each other. The combined effect of these markers on cognitive function has never been studied and would possibly provide more useful information on the effect on cognitive function.Methods: Brain MRI and extensive neuropsychological assessment were performed in 189 patients at risk for cSVD (112 hypertensive patients and 77 first-ever lacunar stroke patients). We rated the presence of any asymptomatic lacunar infarct, extensive WMLs, any deep BMB, and moderate to extensive EPVS in the basal ganglia. The presence of each marker was summed to an ordinal score between 0 and 4. Associations with domains of cognitive function (memory, executive function, information processing speed, and overall cognition) were analyzed with correlation analyses.Results: Correlation analyses revealed significant associations between accumulating cSVD burden and decreased performance on all cognitive domains (all p ≤ 0.001). Results remained significant for information processing speed (r = −0.181, p = 0.013) and overall cognition (r = −0.178, p = 0.017), after correction for age and sex. Testing of trend using linear regression analyses revealed the same results.Discussion: We tested a new approach to capture total brain damage resulting from cSVD and found that accumulation of MRI burden of cSVD is associated with decreased performance on tests of information processing speed and overall cognition, implying that accumulating brain damage is accompanied by worse cognitive functioning.

A Case of Amyloid-β-Related Angiitis: Histology, CSF-Findings and Treatment

Amyloid- β -related angiitis (ABRA) is characterized by vasculitis and accumulation of amyloid- β in vessel walls. In this case report we describe findings of cranial MRI, brain biopsy and cerebrospinal fluid in a patient with Amyloid- β -related angiitis. The cranial MRI displayed extensive multifocal white matter lesion and brain biopsy revealed amyloid angiopathy as well as granulomatous angiitis. In the cerebrospinal fluid our patient showed normal cell count, slightly elevated protein and intrathecal immunoglobulin synthesis which recovered during steroid therapy. We illustrate that detailed CSF analysis including tests for intrathecal immunoglobulin synthesis is very useful in monitoring the efficacy of therapy and disease activity in ABRA since cranial MRI and histology are not suitable for this purpose. In addition we propose that CSF findings may be very helpful in diagnosing ABRA and starting early immunosuppressive therapy. doi: http://dx.doi.org/10.4021/jnr123w

Higher ambulatory blood pressure relates to enlarged Virchow-Robin spaces in first-ever lacunar stroke patients

Enlarged Virchow-Robin spaces (EVRS) are considered to be a sign of cerebral small vessel disease. Hypertension is an important risk factor for cerebral small vessel disease, whereas ambulatory blood pressure (BP) is the strongest predictor of hypertension-related brain damage. However, the association between ambulatory BP levels and EVRS has never been investigated. The aim of this study was to determine the association between ambulatory BP levels and EVRS. In 143 first-ever lacunar stroke patients, we performed 24-h ambulatory BP monitoring after the acute stroke phase. On brain MRI we counted EVRS in the basal ganglia and the centrum semiovale. We graded the number of EVRS at each level into a three-category severity scale. We assessed the association between BP levels and EVRS by ordinal regression analysis. After adjusting for age, sex, extensive white matter lesions, and asymptomatic lacunar infarcts, higher day systolic (OR 1.21; 95 % CI 1.00–1.46 per 10 mmHg), day diastolic (1.18; 95 % CI 1.02–1.37 per 5 mmHg) and 24-h diastolic (OR 1.18; 95 % CI 1.01–1.37 per 5 mmHg) ambulatory BP levels were associated with EVRS at the basal ganglia level. No relation was found between ambulatory BP levels and EVRS in the centrum semiovale. Higher day ambulatory BP levels are associated with EVRS in the basal ganglia. This association was independent of the presence of extensive white matter lesions and asymptomatic lacunar infarcts. Our results imply that basal ganglia EVRS should be regarded as a separate manifestation of BP-related brain damage.

Rapid resolution of akinetic mutism in delayed post-hypoxic leukoencephalopathy with intravenous magnesium sulfate

Delayed post-hypoxic leukoencephalopathy is a rare condition marked by the development of neuropsychiatric symptoms, parkinsonism and akinetic mutism days to weeks after an individual has recovered from a prolonged cerebral hypoxic event. This syndrome can cause significant long-term neurologic dysfunction. At present there are no acute treatment strategies that have been identified that have been shown to alter the natural course of this disorder. In most instances all that can be offered to patients is early supportive care and then subsequent rehabilitation services. Case Report. A patient is presented who developed new onset encephalopathy, extrapyramidal symptoms and akinetic mutism three weeks after being discharged for a respiratory arrest from a drug overdose. MRI showed the development of extensive white matter and bilateral globus pallidus lesions. She had rapid resolution of akinetic mutism with intravenous magnesium sulfate as well as improvement in her other associated neurologic symptoms. The case report suggests the use of intravenous magnesium sulfate as an acute treatment for the akinetic mutism associated with delayed post-hypoxic leukoencephalopathy. In addition it also may improve the extrapyramidal and neuropsychiatric symptoms associated with this syndrome. This may be the first potential acute treatment for this rare neurologic condition.

Abstract 3212: Aggravated Intraventricular Hemorrhage and White Matter Lesions: A Nationwide Cohort of Intracerebral Hemorrhage Patients

Background. Intraventricular hemorrhage (IVH) secondary to intracerebral hemorrhage (ICH) is an important indicator of poor outcome. Location and size of hematoma have been known to associate with IVH, but other clinical and neuroimaging predictors are yet to be discovered. Among them, white matter lesion (WML), which reflects accumulation of chronic sublethal ischemic injuries and periventricular edema, may signify vulnerability of individual brain, hence being associated with development and aggravation of IVH. Methods. A total of 1,604 ICH patients were collected through 33 stroke centers in South Korea with nationwide coverage. We excluded 199 subjects whose computed tomography (CT) scans were taken more than 48 hours after symptom onset, 89 subjects whose images were of poor quality, 42 subjects who had primary IVH without ICH and 12 subjects who were misclassified. Finally, 1,262 acute ICH patients were included in our analysis dataset. Clinical, laboratory, and imaging information was collected during admission. Experienced stroke neurologists independently reviewed CT scans of included patients for rating WML (van Swieten method) and IVH scores, with good inter-rater agreements. IVH score is a recently proposed semi-quantitative and validated method for estimating volume of IVH. Functional outcomes included Glasgow coma scale score and mortality status at the end of 2006. Results. Among the 1,262 ICH patients, 343 subjects (27.2%) were found to have IVH. Patients with IVH are older and had higher level of blood glucose and ICH volume. The proportion of subjects with extensive WML was significantly higher in patients with IVH then those without IVH (33.8% vs. 16.3%; P &lt;0.01). The association between WML and IVH remained significant after controlling for relevant covariates (OR 1.43 and 95% CI 1.02 - 2.02 for mild WML; OR 2.66 and 95% CI 1.83 - 3.87 for extensive WML; compared to no WML). Estimated mean of IVH score of extensive WML group was also significantly higher than that of no WML group (estimated mean ± standard error; 11.5 ± 0.5 vs 9.4 ± 0.5; P =0.01 from analysis of covariance with Tukey’s post-hoc multiple comparison). For outcomes after ICH, presence of IVH was associated with increased odds of having surgical management (OR 3.48 and 95% CI 2.54 - 4.76), lower Glasgow coma scale score (OR 1.90 and 95% CI 1.46 - 2.48), and higher risk of long-term mortality (HR 1.30 and 95% CI 1.03 - 1.64). Conclusion. From this study, we documented that WML was associated with development and increased volume IVH in acute ICH patients. WML would be considered in diagnosis and management of ICH patients with IVH.

A Case of Amyloid-β-Related Angiitis: Histology, CSF-Findings and Treatment

Amyloid- β -related angiitis (ABRA) is characterized by vasculitis and accumulation of amyloid- β in vessel walls. In this case report we describe findings of cranial MRI, brain biopsy and cerebrospinal fluid in a patient with Amyloid- β -related angiitis. The cranial MRI displayed extensive multifocal white matter lesion and brain biopsy revealed amyloid angiopathy as well as granulomatous angiitis. In the cerebrospinal fluid our patient showed normal cell count, slightly elevated protein and intrathecal immunoglobulin synthesis which recovered during steroid therapy. We illustrate that detailed CSF analysis including tests for intrathecal immunoglobulin synthesis is very useful in monitoring the efficacy of therapy and disease activity in ABRA since cranial MRI and histology are not suitable for this purpose. In addition we propose that CSF findings may be very helpful in diagnosing ABRA and starting early immunosuppressive therapy. J Neurol Res. 2012;2(4):168-171 doi: https://doi.org/10.4021/jnr123w

CARASIL新規変異例の病態と画像所見

A 44-year-old female was referred to our department for the evaluation of diffuse leukoencephalopathy. She had exhibited lumbago and gait disturbance due to lumbar spondylosis in the third decade of her life. She had become bed-ridden at 42 of age. Besides, she had developed with cognitive decline and decreased speech in her early forties. Consanguinity was recognized in her family pedigree, such that her father and her maternal grandmother were cousins. One of her elder brothers was found to have developed similar neurological abnormalities. She had never been hypertensive. Blood and cerebrospinal fluid examinations were negative. Cranial MRI revealed extensive white matter lesions, but there were no abnormal findings in her MRA. Locally decreased cerebral blood flow was revealed by cranial SPECT. Despite the lack of alopecia, we considered the diagnosis of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). Her DNA analysis disclosed a novel mutation (c.G821A, p.R274Q) with homozygosity, also identified in the affected elder brother. The in vitro assay for TGFβ repressor activity of HTRA1 implied that the appearance of CARASIL-associated alopecia was independent of TGFβ repressor activity. Longitudinally performed MR spectroscopy showed that her leukoenceplopathy was characterized by early demyelination and intact axonal integrity.

Brain Involvement in Neuromyelitis Optica Spectrum Disorders

Neuromyelitis optica spectrum disorders (NMOSDs) are severe inflammatory demyelinating disorders of the central nervous system. Brain involvement is increasingly recognized. To study brain involvement in NMOSDs among Hong Kong Chinese patients. Retrospective study of patients with NMOSDs. Tertiary medical center in Hong Kong. Patients Thirty-four Hong Kong Chinese patients with NMOSDs of 2 years or longer were recruited. Brain and spinal cord magnetic resonance imaging was performed during NMOSD attacks and was repeated yearly for the first 3 years. We evaluated clinical features of NMOSDs associated with brain involvement and brain lesions on magnetic resonance imaging. Among 34 patients with NMOSDs of 2 years or longer, 20 (59%) had brain involvement. The mean age at onset among these 20 patients was 45.6 years (age range, 19-67 years); 18 were women. Eleven patients (32% of all the patients with NMOSDs) had clinical manifestation of brain involvement, 19 patients (56%) had brain abnormalities on magnetic resonance imaging consistent with inflammatory demyelination, and 2 patients (6%) fulfilled criteria for multiple sclerosis. Clinical manifestation of brain involvement included the following: trigeminal neuralgia; vomiting, vertigo, ataxia, dysphagia, and tetraparesis from lesions around the third and fourth ventricles and aqueduct; homonymous hemianopia, aphasia, hemiparesis, and cognitive impairment from extensive hemispheric white matter lesions; and ataxia, diplopia, hiccups, facial sensory loss, internuclear ophthalmoplegia, hemisensory loss, and hemiparesis from other lesions in the midbrain, pons, cerebellar peduncles, and medulla. Eight patients (24%) developed brainstem encephalitis clinically, and brainstem encephalitis was the initial clinical manifestation in 6 patients (18%). Brain abnormalities on magnetic resonance imaging were detected in brainstem in 15 patients (44%), hemispheric periventricular white matter in 7 patients (21%), deep white matter in 7 patients (21%), corpus callosum in 4 patients (12%), subcortical white matter in 3 patients (9%), thalamus in 2 patients (6%), hypothalamus in 1 patient (3%), basal ganglia in 1 patient (3%), internal capsule in 1 patient (3%), periaqueductal gray matter in 1 patient (3%), and around the third and fourth ventricles in 1 patient (3%); large confluent lesions were detected in 2 patients (6%). Brain involvement manifesting clinically as brainstem encephalitis is common among Hong Kong Chinese patients with NMOSDs.

CADASIL

See related article, page 137. In 1977, Sourander and Walinder1 described a family with neuropsychiatric disease, a relapsing course, and cognitive impairment. The disorder began in early adulthood, affected women and men, and lasted for 10 to 15 years. At brain necropsy, there were multiple small infarcts, particularly of the basal ganglia, thalamus, periventricular white matter, and pons. Vascular changes were prominent in small muscular arteries and in arterioles of the pia-arachnoid, basal ganglia, thalamus, mesencephalon, pons, and cerebellum and in small vessels of the cerebral and cerebellar white matter. The disorder was thought to be genetically transmitted by an autosomal-dominant mechanism and was called hereditary multi-infarct dementia. In 1993, the monogenic disorder, cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), was mapped to chromosome 19q12 by Tournier-Lasserve et al.2 Now, CADASIL is recognized as the most common hereditary cause of vascular cognitive impairment and may present clinically as migraine with aura, mood disturbance, recurrent strokes, cognitive impairment, and MRI-based extensive white matter lesions, lacunar infarcts, cerebral microbleeds, and brain atrophy.3–5 Most cases are caused by missense mutations of the Notch3 gene that create or eliminate cysteine residues.6 Characteristic ultrastructural changes in skin and muscle vessels include granular osmophilic material in the arteriolar media. During the past several decades, our understanding of CADASIL has advanced. In relation to clinical manifestations, it has been suggested that: cardiovascular risk factors (eg, hypertension, smoking) may modulate clinical expression of CADASIL7; migraine with atypical aura may be a distinguishing feature of the disorder8; and overall burden of lacunar infarcts may importantly impact on the occurrence of cognitive impairment and disability, whereas white matter lesions may not be predictive of these domains.9,10 In relation to structural brain changes elucidated by …

Lymphomatosis cerebri: clinical characteristics, neuroimaging, and pathological findings

Lymphomatosis cerebri is a rare variant of primary central nervous system lymphoma. We present a case involving a 56-year-old immunocompetent woman who complained of rapid deterioration of her higher brain function over a 4-month period. Magnetic resonance imaging showed extensive white-matter lesions. During brain biopsy, a diffusely infiltrating lymphoma with distinctive immunohistochemical features was detected. Awareness of this unique presentation and early tissue diagnosis provide the best hope for instituting appropriate treatments.

Transient asymptomatic white matter lesions following Epstein-Barr virus encephalitis

We present the case of a patient with Epstein-Barr virus (EBV) encephalitis who developed abnormal white matter lesions during the chronic phases of the infection. A 2-year-old-boy was admitted for a 2 day history of decreased activity with ataxic gait. The results of the physical examination were unremarkable except for generalized lethargy and enlarged tonsils with exudates. Brain magnetic resonance imaging (MRI) at admission showed multiple high signal intensities in both basal ganglia and thalami. The result of EBV polymerase chain reaction (PCR) of the cerebral spinal fluid was positive, and a serological test showed acute EBV infection. The patient was diagnosed with EBV encephalitis and recovered fully without any residual neurologic complications. Subsequently, follow-up MRI at 5 weeks revealed extensive periventricular white matter lesions. Since the patient remained clinically stable and asymptomatic during the follow-up period, no additional studies were performed and no additional treatments were provided. At the 1-year follow-up, cranial MRI showed complete disappearance of the abnormal high signal intensities previously seen in the white matter. The patient continued to remain healthy with no focal neurologic deficits on examination. This is the first case of asymptomatic self-limited white matter lesions seen in serial MRI studies in a Korean boy with EBV encephalitis.

Early ‘‘Relapse’’ After Herpetic Encephalitis: Extensive White Matter Lesions in an Infant With Interferon Production Deficit

Acute secondary neurological deterioration after herpes simplex encephalitis has been reported. An immune-mediated process is thought to be responsible for some cases. The authors report the case of an infant who presented with fever, irritability, and orofacial involuntary movements, 15 days after herpes encephalitis onset. Polymerase chain reaction for herpes simplex virus was negative, and the magnetic resonance imaging revealed extensive white matter lesions. Chorea appeared only 11 days later. Raised immunoglobulin G index with oligoclonal bands and spreading of white matter lesions corroborated an immune-mediated etiology. An interferon production deficit was also detected. This case alerts that this form of ''relapse'' appears earlier than previously reported. A high level of suspicion is needed in the presence of atypical neurological deterioration and early white matter lesions should be considered as a warning sign. This case is also relevant because it associates, for the first time, an immune-mediated ''relapse'' to an interferon production deficit.

Dominant perivenular enhancement of tumefactive demyelinating lesions in multiple sclerosis

A 51-year-old woman presented with aphasia and bifrontal MRI lesions with punctuate and vague linear enhancement (figure). She improved spontaneously but 4 months later deteriorated due to the large mass and required cranial decompression. Innumerable, perivenular enhancements perpendicular to the lateral ventricles were seen within extensive bihemispheric white matter lesions. Multiple sclerosis (MS) was …

Severe leukoencephalopathy with fulminant cerebral edema reflecting immune reconstitution inflammatory syndrome during HIV infection: a case report

IntroductionImmune reconstitution inflammatory syndrome is a well-known complication in HIV-infected patients after initiation of highly active antiretroviral therapy resulting in rapid CD4+ cell count recovery and suppression of viral load. Generally, immune reconstitution inflammatory syndrome is based on opportunistic infections, but rare cases of immune reconstitution inflammatory syndrome inducing demyelinization of the nervous system have also been observed.Case presentationA 37-year-old African woman with HIV infection diagnosed at 13 years of age was admitted to the emergency department after experiencing backache, severe headache, acute aphasia and psychomotor slowing for one week. Nine weeks earlier, highly active antiretroviral therapy in this patient had been changed because of loss of efficacy, and a rapid increase in CD4+ cell count and decrease of HIV viral load were observed. Magnetic resonance imaging of the brain showed extensive white matter lesions, and analysis of cerebrospinal fluid revealed an immunoreactive syndrome. Intensive investigations detected no opportunistic infections. A salvage therapy, including osmotherapy, corticosteroids and treatment of epileptic seizures, was performed, but the patient died from brainstem herniation 48 hours after admission. Neuropathologic examination of the brain revealed diffuse swelling, leptomeningeal infiltration by CD8 cells and enhancement of perivascular spaces by CD8+ cells.ConclusionImmune reconstitution inflammatory syndrome in this form seems to represent a severe autoimmunologic disease of the brain with specific histopathologic findings. This form of immune reconstitution inflammatory syndrome did not respond to therapy, and extremely rapid deterioration led to death within two days. Immune reconstitution inflammatory syndrome may also occur as severe leukoencephalopathy with fulminant cerebral edema during HIV infection with rapid immune reconstitution.

Endothelial Activation in Lacunar Stroke Subtypes

Lacunar stroke (LS) can be subtyped according to the absence (isolated lacunar infarct [ILA]) or presence of concomitant white matter lesions (WML) and/or asymptomatic lacunar infarcts. Endothelial activation is thought to play a pivotal role in the subtype with WML and/or asymptomatic lacunar infarcts. The aim of this study was to evaluate whether endothelial activation is associated with WML and/or asymptomatic lacunar infarcts in LS patients. Here, we determined levels of circulating blood markers of endothelial function in LS patients. In 149 patients, all of whom had brain-MRI, levels of tissue plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1), tPA-PAI-1 complex, von Willebrand factor, tissue factor, thrombomodulin, and coagulation factor VIII were determined. Levels of blood markers were related to subtypes of LS and adjusted for age, gender, and vascular risk factors. In subtypes of LS, tPA activity was increased in patients with WML (0.79 IU/mL vs 0.44 IU/mL for ILA; P=0.02) and PAI-1-antigen levels were lowest in patients with WML (27.5 ng/mL vs 44.0 ng/mL for ILA; P=0.02). The association between WML and PAI-1 remained significant after multivariable analysis (OR, 0.99; 95% CI, 0.98-1.00 per ng/mL change of PAI-1; P=0.04). We found further evidence for the hypothesis of endothelial activation in the subtype of LS caused by a diffuse small vessel vasculopathy, as we found higher levels of tPA in patients with concomitant extensive WML than in those with ILA. Second, low levels of PAI-1 were associated with WML. We postulate that differences in activity of components of the fibrinolytic system might contribute to WML development.

Incidental findings on MRI scans of patients presenting with audiovestibular symptoms

BackgroundThe evaluation of patients presenting with audiovestibular symptoms usually includes MRI of the internal auditory meatus, the cerebellopontine angle and the brain. A significant percentage of these scans will present unexpected, incidental findings, which could have important clinical significance.ObjectiveTo determine the frequency and clinical significance of incidental findings on MRI scans of patients with audiovestibular symptoms.Materials and methodsA retrospective analysis of 200 serial MRI scans.ResultsGender distribution: equal. Age range: 17-82 years. One-hundred and four scans (52%) were normal and 1 scan (0.5%) demonstrated a unilateral vestibular schwannoma. Ninety-five scans (47.5%) demonstrated incidental findings. Sixty-six of these (33%) were considered of ishaemic origin and did not require further action. Five (2.5%) scans demonstrated significant findings which warranted appropriate referral; Two Gliomas (1%), 2 cases of extensive White Matter Lesions (1%), 1 lipoma (0.5%). The remaining scans demonstrated various other findings.ConclusionInvestigation of patients with audiovestibular symptoms with MRI scans revealed incidental findings in a significant percentage (47.5%). The majority of these findings were benign warranting no further action and only 2.5% required further referral. It is the responsibility of the referring Otolaryngologist to be aware of these findings, to be able to assess their significance, to inform the patient and if needed to refer for further evaluation.