T2-hyperintense White Matter Lesions Research Articles

An automated tool for detection of FLAIR-hyperintense white-matter lesions in Multiple Sclerosis

In Multiple Sclerosis (MS), detection of T2-hyperintense white matter (WM) lesions on magnetic resonance imaging (MRI) has become a crucial criterion for diagnosis and predicting prognosis in early disease. Automated lesion detection is not only desirable with regard to time and cost effectiveness but also constitutes a prerequisite to minimize user bias. Here, we developed and evaluated an algorithm for automated lesion detection requiring a three-dimensional (3D) gradient echo (GRE) T1-weighted and a FLAIR image at 3 Tesla (T). Our tool determines the three tissue classes of gray matter (GM) and WM as well as cerebrospinal fluid (CSF) from the T1-weighted image, and, then, the FLAIR intensity distribution of each tissue class in order to detect outliers, which are interpreted as lesion beliefs. Next, a conservative lesion belief is expanded toward a liberal lesion belief. To this end, neighboring voxels are analyzed and assigned to lesions under certain conditions. This is done iteratively until no further voxels are assigned to lesions. Herein, the likelihood of belonging to WM or GM is weighed against the likelihood of belonging to lesions. We evaluated our algorithm in 53 MS patients with different lesion volumes, in 10 patients with posterior fossa lesions, and 18 control subjects that were all scanned at the same 3T scanner (Achieva, Philips, Netherlands). We found good agreement with lesions determined by manual tracing (R2 values of over 0.93 independent of FLAIR slice thickness up to 6mm). These results require validation with data from other protocols based on a conventional FLAIR sequence and a 3D GRE T1-weighted sequence. Yet, we believe that our tool allows fast and reliable segmentation of FLAIR-hyperintense lesions, which might simplify the quantification of lesions in basic research and even clinical trials.

Adult onset Pompe disease associated with multiple sclerosis

Dear Sirs,A 27-year-old woman was referred to our center regardingprogressive lower extremity weakness. Her symptomsbegan 3 years ago with fatigue related to the exertion andmild proximal lower extremity weakness. She had nomotor development issues and she denied family history ofneurological disease. There were non ocular or sensorycomplaints. At the age of 20, a routine analysis demon-strated an increase of liver enzymes with a normalabdominal echography. She refused hepatic biopsy andhepatology follow-up visits.The force was reduced to grade 4/5 symmetrically in thehip flexion. The right knee reflex was absent and presentedleft ankle clonus. Plantar responses were extensor. Theexam of the sensory was normal except for a diminishedvibratory sensory in right leg. She was unable to walk ontip-toes and heels. Laboratory investigations showed ALT119 UI/I (7-31), AST 98 UI/I (10-38), and CK 728 UI/I(20-170). Thyroid function, vitamin B12, folate, and acomplete autoimmune profile were normal. Blood exami-nation showed no evidence of herpes virus, CMV, EBV,syphilis, borrelia, HIV-1/2, HTLV-1, or hepatotropic viru-ses. Brain MRI T2-weighted images and FLAIR revealed 8hyperintense lesions involving periventricular white matter,juxtacortical areas, and one left mesencephalic lesion,suggestive of demyelination. None of them demonstratedgadolinium enhancement. MRI of the whole spinal cord wasnormal (Fig. 1). Intrathecal IgG-oligoclonal bands werepresent in the cerebrospinal fluid examination and no ple-ocytosis. Visual-evoked potentials showed delayedresponses on both eyes. Nerve conduction studies werenormal but the results of the electromyography were con-sistent with a myopathic pattern; thus, a deltoid musclebiopsy was performed. Histopathology demonstrated thepresence of vacuoles with abnormal accumulation on peri-odic acid-Schiff (PAS) stain (Fig. 2). The enzyme activityin lymphocytes was 19.00 nmol 9 min 9 g (patient) ver-sus 614.00 nmol 9 min 9 g (controls), and was similarlylow in skin biopsy as well as in the muscle biopsy reliable toglycogen storage disease type 2. The analysis of the GAAgene found heterozygosity for IVS1-13T[G (also called c.-32-13T[G), a frequent pathogenic mutation among adultpatients with Pompe disease, as well as heterozygosity forthe unknown change M1L(1A[T), an unclassified variant.A liver biopsy confirmed the diagnosis of mild chronichepatitis. In the subsequent 2 years, the patient has suffereda progression in her symptoms. Although enzyme replace-ment therapy was started, her limb weakness has worsenedand she is able to walk with the assistance of a cane. NewsMRIs showed the presence of new T2-hyperintense whitematter lesions. According to McDonald’s criteria, a diag-nosis of primary progressive multiple sclerosis (PPMS) wasmade [1].MS and combined muscle disease has only beendescribed in a few case reports: a boy affected with cen-tronuclear myopathy who developed RRMS [2], a case ofcombined facio-scapulo-humeral muscular dystrophy [3],a case with combined myotonic dystrophy [4], and twocases of MS and mitochondrial myopathy [5]. This is thefirst report of a patient with both Pompe myopathy andmultiple sclerosis. Given the high prevalence of multiplesclerosis in our population, we consider that the associationbetween these two entities in our patient is casual. Pompe

CYSTEINE-SPARING NOTCH3 MUTATIONS: CADASIL OR CADASIL VARIANTS?

Mutations in the Notch3 gene in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) usually involve cysteine residues.1 We report a cysteine-sparing mutation (A1020P) in association with a CADASIL-compatible phenotype in two German families. ### Case histories. The index patient 1 is a 49-year-old woman with a medical history of sensorineural hearing loss of adolescent onset. At the age of 34, arterial hypertension was diagnosed. Since her 40s she reported episodes of unilateral headache, vertigo, and nausea. In addition, the patient had intermittent paresthesias and weakness of the left extremities, reduced fine motor skills, cognitive slowing, and impaired memory. MRI in 2003 revealed widespread T2-hyperintense white matter lesions (WMLs) (figure, A). Electron microscopic examination of a skin biopsy showed deposits of osmiophilic material between the smooth-muscle cells of small arteries (figure e-1 on the Neurology ® Web site at www.neurology.org), and immunostaining with a Notch3 monoclonal antibody showed granular labeling of vascular smooth-muscle cells (figure e-2). Figure Axial T2-weighted (A, C, E) and fluid-attenuated inversion recovery MRIs (B, D) of the index patient (A), the index patient’s mother (B), and patient 2 (D), compatible with widespread ischemic leukoaraiosis Note especially the absence of white matter lesions (WMLs) in the anterior temporal lobes in all three individuals. The MRI of the index patient’s uncle (C), although characterized as a mutation carrier, only showed a slight pallor of the white matter and dilated Virchow Robin spaces. (E) MRI of the father of the …

Colitis ulcerosa asociada a enfermedad de Vogt-Koyanagi-Harada

We report the case of a female patient who was diagnosed with Vogt-Koyanagi-Harada disease at the age of 14 years and who developed myelopathy, resulting in paraparesis. A cerebral magnetic resonance imaging scan revealed the presence of T2-hyperintense lesions in the periventricular white matter, suggesting demyelinization. Twelve years later, ulcerative colitis was diagnosed during workup for abdominal pain associated with bloody diarrhea. The association of these two diseases has previously been reported anecdotically. The management of the ulcerative colitis was complicated by the patient's neurological manifestations. Even though recent reports support the use of anti-TNF drugs in the management of Vogt-Koyanagi-Harada-associated uveitis, because of the lack of experience in patients with neurological symptoms, and the presence of apparently demyelinating lesions in our patient, we did not use these drugs in this case.

Silent ischemic infarcts are associated with hemorrhage burden in cerebral amyloid angiopathy

Neuropathologic studies suggest an association between cerebral amyloid angiopathy (CAA) and small ischemic infarctions as well as hemorrhages. We examined the prevalence and associated risk factors for infarcts detected by diffusion-weighted imaging (DWI). We performed retrospective analysis of MR images from 78 subjects with a diagnosis of probable CAA and a similar aged group of 55 subjects with Alzheimer disease or mild cognitive impairment (AD/MCI) for comparison. DWI and apparent diffusion coefficient (ADC) maps were inspected for acute or subacute infarcts. We also examined the association between DWI lesions and demographic variables, conventional vascular risk factors, and radiographic markers of CAA severity such as number of hemorrhages on gradient-echo MRI and volume of T2-hyperintense white matter lesions. Twelve of 78 subjects with CAA (15%) had a total of 17 DWI-hyperintense lesions consistent with subacute cerebral infarctions vs 0 of 55 subjects with AD/MCI (p = 0.001). The DWI lesions were located primarily in cortex and subcortical white matter. CAA subjects with DWI lesions had a higher median number of total hemorrhages (22 vs 4, p = 0.025) and no difference in white matter hyperintensity volume or conventional vascular risk factors compared to subjects with CAA without lesions. MRI evidence of small subacute infarcts is present in a substantial proportion of living patients with advanced cerebral amyloid angiopathy (CAA). The presence of these lesions is associated with a higher burden of hemorrhages, but not with conventional vascular risk factors. This suggests that advanced CAA predisposes to ischemic infarction as well as intracerebral hemorrhage.

„Numb chin Syndrom” als Erstsymptom einer Multiplen Sklerose?

A 34-year-old previously healthy woman presented with a five-day history of subacute onset of a numb chin. Examination on admission revealed isolated hypesthesia on the left side of the chin and lower lip. Brain magnetic resonance imaging (MRI) demonstrated a lesion involving the pontine trigeminal fibers and multiple periventricular T2-hyperintense white matter lesions suggestive of inflammatory /demyelinating disease. Cerebrospinal fluid analysis revealed oligoclonal IgG bands (only in cerebrospinal fluid) and an increased IgG index. A follow-up MRI after four months demonstrated new supratentorial brain lesions, confirming a syndrome, highly suggestive of multiple sclerosis as the likely underlying diagnosis. TREATMENT AND FOLLOW-UP: The facial sensory disturbance resolved spontaneously. Prophylactic treatment with interferon-beta was started. The numb chin syndrome may be the initial presentation of a clinically isolated syndrome suggestive of multiple sclerosis. Prophylactic immunomodulatory treatment may be started after the suspicion of inflammatory/demyelinating activity is confirmed.

Relationship among neuroimaging indices of cerebral health during normal aging

Sensitive measures of brain aging show great promise for gauging factors that affect aging and degenerative processes, such as risk genes or therapy. Here we examined age-related trends for three indices of cerebral health: gyral gray matter (GM) thickness, dilation of sulcal spaces with CSF, and the volume of T2-hyperintense white matter (HWM) lesions. The study involved 31 healthy adults age 57-82 years old. Measurements of average GM thickness, average sulcal span and HWM volume were performed using high-resolution 3D T1- and T2-weighted brain MR images. Age-related trends for the three cerebral health indices were consistent with previously published work though the analysis of their covariance led to a previously unreported relationship. Simultaneous multiple regression found that dilation of cortical sulci were primarily (t = 2.59, P < 0.01) related to the increases in HWM volume and secondarily related (t = -2.51, P < 0.01) to the reductions of the cortical GM thickness. The are-corrected correlation between reduction in GM thickness and increases in HWM volume, was not significant (P = 0.34). These findings are of interest in designing quantitative measures of brain aging for monitoring individual patients and in large-scale clinical trials.

White matter lesions and cognition

Neurologists and neuroradiologists often see small T2-hyperintense lesions in the hemispheric white matter of patients who undergo MR imaging. Such findings often lead to neurologic consultation, particularly when the reason for MR imaging was not to study the white matter. While these “unidentified bright objects” have often been considered unimportant (usually when few in number), such lesions are a bad omen, predictive of stroke and dementia. Most commonly these lesions have a vascular etiology, and yet because we cannot image the small arteries directly we do not yet understand the nuances of leukoaraiosis.1,2 The study by Deary et al. in this issue of Neurology takes advantage of psychometric data from the Scottish Mental Survey of 1932.3 Forty nondemented patients underwent repeat cognitive testing 70 years later. As well, all had MRI, including diffusion tensor, magnetization transfer, and T2-weighted sequences. The principal result was that the fractional anisotropy (FA) measurements taken in the centrum semiovale were modestly but significantly correlated with current cognitive function (at a …

Multifocal leukoencephalopathy and polyneuropathy after 18 years on interferon a

Multifocal leukoencephalopathy and sensory-motor polyneuropathy have not been reported as side-effects of long-lasting interferon α therapy in a single patient. In a 77-year-old man interferon α2b and interferon α2a were administered subsequently but continuously since 1984 for hairy cell leukemia. Since early 2000, left-sided hemi-hypesthesia occurred and the patient developed gait disturbance, proximal weakness of the lower limbs, bilateral stocking-type sensory disturbances, and restless leg syndrome. Repeated cerebral magnetic resonance images showed multifocal T2-hyperintense white matter lesions supratentorially. The nerve conduction velocity of the peroneal and sural nerve was reduced. After exclusion of various differential diagnoses of leukoencephalopathy and application of a screening program for polyneuropathy, central and peripheral nervous system abnormalities were attributed to the long-lasting interferon α therapy. In single patients abnormally long-lasting interferon α therapy may cause multifocal white matter lesions supratentorially and sensory-motor polyneuropathy.

Neuropathy and cognitive impairment following vaccination with the OspA protein of Borrelia burgdorferi.

Neurological syndromes that follow vaccination or infection are often attributed to autoimmune mechanisms. We report six patients who developed neuropathy or cognitive impairment, within several days to 2 months, following vaccination with the OspA antigen of Borrelia burgdorferi. Two of the patients developed cognitive impairment, one chronic inflammatory demyelinating polyneuropathy (CIDP), one multifocal motor neuropathy, one both cognitive impairment and CIDP, and one cognitive impairment and sensory axonal neuropathy. The patients with cognitive impairment had T2 hyperintense white matter lesions on magnetic resonance imaging. The similarity between the neurological sequelae observed in the OspA-vaccinated patients and those with chronic Lyme disease suggests a possible role for immune mechanisms in some of the manifestations of chronic Lyme disease that are resistant to antibiotic treatment.