T2-weighted Hyperintense Lesions Research Articles

Dimethyl fumarate preserves brainstem and cervical spinal cord integrity in radiologically isolated syndrome.

The first randomized placebo-controlled therapeutic trial in radiologically isolated syndrome (RIS), ARISE, demonstrated that treatment with dimethyl fumarate (DMF) delayed the onset of a first clinical event related to CNS demyelination and was associated with a significant reduction in new and/or newly enlarging T2-weighted hyperintense lesions. The purpose of this study was to explore the effect of DMF on volumetric measures, including whole brain, thalamic, and subcortical gray matter volumes, brainstem and upper cervical spine three-dimensional (3D) volumes, and brainstem and upper cervical spine surface characteristics. Standardized 3T MRIs including 3D isotropicT1-weighted gradient echo images were acquired at baseline and end-of-study according to the ARISE study protocol. The acquired datawere analyzed using Structural Image Evaluation Using Normalization of Atrophy (SIENA), FreeSurfer v7.3, and an in-house pipeline for 3D conformational metrics. Multivariate mixed models for repeated measures were used to analyze rates of change in whole brain, thalamic, subcortical gray matter, as well as change in the 3D surface curvature of the dorsal pons and dorsal medulla and 3D volume change at the medulla-upper cervical spinal cord. The study population consisted of 64 RIS subjects (DMF:30, placebo:34). No significant difference was seen in whole brain, thalamic, or subcortical gray matter volumes in treated vs. untreated RIS patients. A significant difference was observed in dorsal pons curvature with the DMF group having a lower least squares mean change of -4.46 (standard estimate (SE): 3.77) when compared to placebo [6.94 (3.71)] (p = 0.036). In individuals that experienced a first clinical event,a greater reduction in medulla-upper cervical spinal cord volume (p = 0.044) and a decrease in surface curvature was observed at the dorsal medulla (p = 0.009) but not at the dorsal pons (p = 0.443). The benefit of disease-modifying therapy in RIS may extend to CNS structures impacted by neurodegeneration that is below the resolution of conventional volumetric measures.

Potential thresholds of critically increased cardiac-related spinal cord motion in degenerative cervical myelopathy.

New diagnostic techniques are a substantial research focus in degenerative cervical myelopathy (DCM). This cross-sectional study determined the significance of cardiac-related spinal cord motion and the extent of spinal stenosis as indicators of mechanical strain on the cord. Eighty-four DCM patients underwent MRI/clinical assessments and were classified as MRI+ [T2-weighted (T2w) hyperintense lesion in MRI] or MRI- (no T2w-hyperintense lesion). Cord motion (displacement assessed by phase-contrast MRI) and spinal stenosis [adapted spinal canal occupation ratio (aSCOR)] were related to neurological (sensory/motor) and neurophysiological readouts [contact heat evoked potentials (CHEPs)] by receiver operating characteristic (ROC) analysis. MRI+ patients (N = 31; 36.9%) were more impaired compared to MRI- patients (N = 53; 63.1%) based on the modified Japanese Orthopedic Association (mJOA) subscores for upper {MRI+ [median (Interquartile range)]: 4 (4-5); MRI-: 5 (5-5); p < 0.01} and lower extremity [MRI+: 6 (6-7); MRI-: 7 (6-7); p = 0.03] motor dysfunction and the monofilament score [MRI+: 21 (18-23); MRI-: 24 (22-24); p < 0.01]. Both patient groups showed similar extent of cord motion and stenosis. Only in the MRI- group displacement identified patients with pathologic assessments [trunk/lower extremity pin prick score (T/LEPP): AUC = 0.67, p = 0.03; CHEPs: AUC = 0.73, p = 0.01]. Cord motion thresholds: T/LEPP: 1.67 mm (sensitivity 84.6%, specificity 52.5%); CHEPs: 1.96 mm (sensitivity 83.3%, specificity 65.6%). The aSCOR failed to show any relation to the clinical assessments. These findings affirm cord motion measurements as a promising additional biomarker to improve the clinical workup and to enable timely surgical treatment particularly in MRI- DCM patients. www.clinicaltrials.gov, NCT02170155.

Central intra-lesional iron deposits as a possible novel imaging marker at 7 Tesla MRI in Susac Syndrome - an exploratory study.

Susac syndrome (SuS) is a rare autoimmune disease that leads to hearing impairment, visual field deficits, and encephalopathy due to an occlusion of precapillary arterioles in the brain, retina, and inner ear. Given the potentially disastrous outcome and difficulties in distinguishing SuS from its differential diagnoses, such as multiple sclerosis (MS), our exploratory study aimed at identifying potential new SuS-specific neuroimaging markers. Seven patients with a definite diagnosis of SuS underwent magnetic resonance imaging (MRI) at 7 Tesla (7T), including T2* weighted and quantitative susceptibility mapping (QSM) sequences. T2 weighted hyperintense lesions were analyzed with regard to number, volume, localization, central vein sign, T1 hypointensity, and focal iron deposits in the center of SuS lesions ("iron dots"). Seven T MRI datasets from the same institute, comprising 75 patients with, among others, MS, served as controls. The "iron dot" sign was present in 71.4% (5/7) of the SuS patients, compared to 0% in our control cohort. Thus, sensitivity was 71.4% and specificity 100%. A central vein sign was only incidentally detected. We are the first to demonstrate this type of "iron dot" lesions on highly resolving 7T T2*w and QSM images in vivo as a promising neuroimaging marker of SuS, corroborating previous histopathological ex vivo findings.

Abstract #1405095: PCOS Diagnosis Leading to a Delayed Diagnosis of Cushing's Disease

Polycystic ovarian syndrome (PCOS) is a common disorder affecting pre-menopausal women. Diagnostic criteria for PCOS include menstrual irregularities, biochemical or clinical hyperandrogenism and/or evidence of polycystic ovaries on ultrasound. Any 2 of the above is sufficient for a diagnosis of PCOS. However, PCOS is a diagnosis of exclusion so other pathologies should be investigated including hypercortisolemia. We present a case of Cushing's Disease in which the patient’s clinical features were previously attributed to a diagnosis of PCOS delaying appropriate intervention. A 22-year-old nulligravida woman with no significant past medical history presented to the Ob/Gyn clinic with complaints of amenorrhea and infertility. Patient noted irregular menstrual cycles since attaining menarche, she denies any headaches, galactorrhea but reported facial hirsutism and weight gain. She was initially diagnosed with PCOS but had continued amenorrhea despite treatment with medroxyprogesterone acetate. Additional work up was ordered by Gyn which noted mildly elevated Prolactin at 30.84 ng/ml. MRI head/brain subsequently ordered noted a large T2 weighted hyperintense lesion measuring 2.2 x 1.65 x 2.0 cm involving the sella with extension suggesting a pituitary macro-adenoma. Patient was referred to endocrinology for additional work up. Further evaluation showed normal repeat prolactin level with dilution study normal at 11.9 ng/ml. She was found to have secondary hypogonadism with FSH - 5.32 mIU/ml, LH- 2.1IU/L and estradiol level at < 20 pg/ml. She also had secondary hypothyroidism with TSH 0.88 mIU/ml and free T4 at 0.64 ng/dl. Morning Cortisol was at 19.13 ug/uL with baseline ACTH elevated at 127 pg/ml. This showed adequate adrenal function but concern for ACTH dependent hypercortisolemia. She had 2 failed 1 mg dexamethasone suppression test with cortisol level at 10.92 ug/uL and 20.91 ug/uL with adequate dexamethasone levels. She had 2 elevated 24-hour urine cortisol at 72ug/24hr and 81ug/24hr. She also had 2 elevated midnight salivary cortisol level at 0.338ug/dl and 0.349ug/dl. Other labs showed normal IGF-1 and normal DHEA-S. Patient was diagnosed with Cushing Disease and underwent successful transsphenoidal resection of the pituitary macroadenoma. Post operative cortisol was <2 ug/ul, she was initiated on hydrocortisone 20mg am and 10mg pm. Patient had continued monitoring for recovery of hypothalamic-pituitary-axis. A month after the surgery, patient got pregnant and was continued on her hydrocortisone and levothyroxine replacement. In our case the diagnosis and treatment of Cushing's disease was delayed due to clinical features mimicking PCOS. PCOS is a diagnosis of exclusion, and our case illustrates the importance of excluding the other endocrine pathologies, such as Cushing's disease, to prevent delaying the appropriate treatment and to mitigate the risk of increased morbidity and mortality that may be associated with them.

Acute Disseminated Encephalomyelitis with Prefrontal Cortex Involvement in a 9-Year-Old Child after COVID-19 Infection: A Case Report

AbstractThe aim of the study was to present the rare co-occurring radiological findings of a child presenting with acute disseminated encephalomyelitis (ADEM) with a spinal cord and prefrontal cortex involvement after coronavirus disease 2019 (COVID-19) illness. The patient, who had COVID-19 a few weeks earlier, presented with progressive weakness in the right upper and lower extremities. Neurological examination of the patient was performed, and cranial magnetic resonance imaging (MRI) was taken on the same day. Serum severe acute respiratory syndrome coronavirus immunoglobulin M antibody testing was positive. MRI of the brain parenchyma and thoracic spine revealed fluid-attenuated inversion recovery and T2-weighted hyperintense lesions. Additionally, mild contrast enhancement was observed in both the prefrontal cortexes. The patient was discharged 10 days later with complete clinical recovery. Unlike other post-COVID-19 ADEM cases presenting in the literature, prefrontal cortex involvement makes our case rare.

A rare case of intraosseous lipoma of distal tibia – A case report and review of literature

Introduction: Intraosseous lipoma is a very rare neoplasm accounting for &lt; 0.1 % of primary bone tumors. Pain is the leading symptom in majority of the reported cases but it can be asymptomatic. There is slight male predominance in occurrence of this lesion. The plain radiological findings are not specific and requires differential diagnosis. The lesion is mostly diagnosed by histopathological examination. Case report: A 31-year-old male presented with localized pain around the medial aspect of right ankle joint for one week. Examination revealed mild tenderness over the distal part of the right tibia over the medial aspect. Plain radiograph of the right leg showed well-defined expansile osteolytic lesion with sclerotic rim and calcified matrix at metaphysis of distal tibia. MRI showed enhancing T1-weighted hypo intense and T2-weighted hyperintense lesion. For this case, radiological impression was giant cell tumor with differential diagnosis of aneurysmal bone cyst and fibrous dysplasia. However, the histopathological examination showed intraosseous lipoma, consistent with stage II of Milgram’s classification. Conclusions: Although the diagnosis of intraosseous lipoma can be very challenging due to its rarity and indistinct plain radiograph findings, combination of computed tomography or magnetic resonance imaging may be useful by being able to show the presence of fat within the lesion. However, the clinicians, surgeons and radiologist should be familiar and be aware of these findings to be able to come to a correct diagnosis since not all cases need surgery and can be managed conservatively.

Diagnosis of meningeal melanomatosis in a dog using magnetic resonance imaging and cerebrospinal fluid findings.

A 13-year-old spayed female Labrador Retriever was presented with severe progressive tetraparesis. The neuroanatomic localization was the C1–C5 spinal cord segments with brainstem or cranial nerve involvement. Magnetic resonance imaging revealed diffuse T1-weighted and T2-weighted hyperintense lesions with strong contrast enhancement spreading through meninges of the cervical spinal cord and the brain. Few small round areas showing T1-weighted hyperintensity and T2-weighted hypointensity were scattered within the lesions. Cerebrospinal fluid analysis revealed neoplastic round cells and possible melanocytes. Malignant melanoma was suspected. At necropsy, the brain and the entire spinal cord were covered with thick, dark membranous tissue. Based on histopathologic findings, a positive response against Melan-A, and no melanoma identified outside the central nervous system, primary meningeal melanomatosis was diagnosed.

Brain MRI findings in a dog with late onset epileptic seizure after portosystemic shunt attenuation

A female Tibetan terrier aged five years and six months presented 23 months after portosystemic shunt attenuation due to generalised tonic–clonic epileptic seizure activity. Repeat MRI of the brain showed...

Chronic encephalopathy and locked-in state due to scrub typhus related CNS vasculitis

BackgroundScrub Typhus, prevalent in Asia-Pacific region, often has neurological manifestations in the setting of acute febrile illness, as acute encephalitis syndrome. Case reportA 20-year-old female, from western Rajasthan, India presented with calf pain followed by nausea, vomiting, dizziness, and sequentially progressive weakness of limbs, anarthria and loss of bladder control over 10 days. MRI Brain showed T2-weighted and FLAIR hyperintense lesions in corpus callosum, subcortical and periventricular white matter, basal ganglia, thalamus, brainstem and cerebellum producing starry sky appearance with diffusion restriction. Serum IgM for Scrub typhus was positive and patient progressively improved over 3 weeks with doxycycline. ConclusionsThis report highlights an unusual presentation of scrub typhus with subacute onset and static course, quadriparesis and locked-in state for 2 months, suspected based on red flags on neuroimaging and reversal of deficits with appropriate treatment.

Structural Nerve Remodeling at 3-T MR Neurography Differs between Painful and Painless Diabetic Polyneuropathy in Type 1 or 2 Diabetes.

Background The pathophysiologic mechanisms underlying painful symptoms in diabetic polyneuropathy (DPN) are poorly understood. They may be associated with MRI characteristics, which have not yet been investigated. Purpose To investigate correlations between nerve structure, load and spatial distribution of nerve lesions, and pain in patients with DPN. Materials and Methods In this prospective single-center cross-sectional study, participants with type 1 or 2 diabetes volunteered between June 2015 and March 2018. Participants underwent 3-T MR neurography of the sciatic nerve with a T2-weighed fat-suppressed sequence, which was preceded by clinical and electrophysiologic tests. For group comparisons, analysis of variance or the Kruskal-Wallis test was performed depending on Gaussian or non-Gaussian distribution of data. Spearman correlation coefficients were calculated for correlation analysis. Results A total of 131 participants (mean age, 62 years ± 11 [standard deviation]; 82 men) with either type 1 (n = 45) or type 2 (n = 86) diabetes were evaluated with painful (n = 64), painless (n = 37), or no (n = 30) DPN. Participants who had painful diabetic neuropathy had a higher percentage of nerve lesions in the full nerve volume (15.2% ± 1.6) than did participants with nonpainful DPN (10.4% ± 1.7, P = .03) or no DPN (8.3% ± 1.7; P < .001). The amount and extension of T2-weighted hyperintense nerve lesions correlated positively with the neuropathy disability score (r = 0.37; 95% confidence interval [CI]: 0.21, 0.52; r = 0.37; 95% CI: 0.20, 0.52, respectively) and the neuropathy symptom score (r = 0.41; 95% CI: 0.25, 0.55; r = 0.34; 95% CI: 0.17, 0.49, respectively). Negative correlations were found for the tibial nerve conduction velocity (r = -0.23; 95% CI: -0.44, -0.01; r = -0.37; 95% CI: -0.55, -0.15, respectively). The cross-sectional area of the nerve was positively correlated with the neuropathy disability score (r = 0.23; 95% CI: 0.03, 0.36). Negative correlations were found for the tibial nerve conduction velocity (r = -0.24; 95% CI: -0.45, -0.01). Conclusion The amount and extension of T2-weighted hyperintense fascicular nerve lesions were greater in patients with painful diabetic neuropathy than in those with painless diabetic neuropathy. These results suggest that proximal fascicular damage is associated with the evolution of painful sensory symptoms in diabetic polyneuropathy. © RSNA, 2019 Online supplemental material is available for this article.

Mild encephalitis/encephalopathy with a reversible splenial lesion in children.

We aimed to present clinical and radiologic characteristics of mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) in children. Eight children (5 boys and 3 girls; median age, 5.9 years; age range, 8 months to 14.1 years) diagnosed with MERS between September 2015 and June 2017 were included in the study. We reviewed the patient's data, including demographic characteristics, prodromal and neurologic symptoms, neurologic examination, magnetic resonance imaging and electroencephalography findings, laboratory findings, treatment, and prognosis. Prodromal symptoms were nausea and vomiting (n=6), diarrhea (n=6), and fever (n=3). Initial neurologic symptoms were seizures (n=4), delirious behavior (n=1), drowsiness (n=1), ataxia (n=1), transient blindness (n=2), abnormal speech (n=2), and headache (n=1). Two patients had a suspected infective agent: urinary tract infection caused by Escherichia coli and gastroenteritis caused by rotavirus. Seven patients had type I lesions, comprising characteristic symmetric ovoid (n=6) and band-shaped (n=1) T2-weighted hyperintense lesions at the spenium of corpus callosum, and one patient had type II lesion with additional symmetric posterior periventricular lesions. The lesions were isointense to mildly hypointense on T1-weighted imaging and did not show enhancement. All lesions displayed restricted diffusion. In all patients, neurologic symptoms completely normalized < 48 hours from the onset of symptoms without any sequelae. MERS has characteristic imaging features and favorable outcome.

Assessment of Early Evidence of Multiple Sclerosis in a Prospective Study of Asymptomatic High-Risk Family Members

Subclinical inflammatory demyelination and neurodegeneration often precede symptom onset in multiple sclerosis (MS). To investigate the prevalence of brain magnetic resonance imaging (MRI) and subclinical abnormalities among asymptomatic individuals at risk for MS. The Genes and Environment in Multiple Sclerosis (GEMS) project is a prospective cohort study of first-degree relatives of people with MS. Each participant's risk for MS was assessed using a weighted score (Genetic and Environmental Risk Score for Multiple Sclerosis Susceptibility [GERSMS]) comprising an individual's genetic burden and environmental exposures. The study dates were August 2012 to July 2015. Participants in the top and bottom 10% of the risk distribution underwent standard and quantitative neurological examination, including disability status, visual, cognitive, motor, and sensory testing, as well as qualitative and quantitative neuroimaging with 3-T brain MRI and optical coherence tomography. This study included 100 participants at risk for MS, with 41 at higher risk (40 women [98%]) and 59 at lower risk (25 women [42%]), at a mean (SD) age of 35.1 (8.7) years. Given the unequal sex distribution between the 2 groups, the analyses were restricted to women (n = 65). When considering all measured outcomes, higher-risk women differed from lower-risk women (P = .01 by omnibus test). Detailed testing with a vibration sensitivity testing device in a subgroup of 47 women showed that higher-risk women exhibited significantly poorer vibration perception in the distal lower extremities (P = .008, adjusting for age, height, and testing date). Furthermore, 5 of 65 women (8%) (4 at higher risk and 1 at lower risk) met the primary neuroimaging outcome of having T2-weighted hyperintense brain lesions consistent with the 2010 McDonald MRI criteria for dissemination in space. A subset of participants harbor many different neuroimaging features associated with MS, including perivenous T2-weighted hyperintense lesions and focal leptomeningeal enhancement, consistent with the hypothesis that these individuals are at higher risk of developing clinical symptoms of MS than the general population. Higher-risk asymptomatic family members of patients with MS are more likely to have early subclinical manifestations of MS. These findings underscore the importance of early detection in high-risk individuals. clinicaltrials.gov Identifier: NCT01353547.

Canine spinal cord glioma

Spinal cord glioma is uncommonly reported in dogs. We describe the clinicopathologic and diagnostic features of 7 cases of canine spinal cord glioma and briefly review the veterinary literature on this topic. The median age at presentation was 7.2 y. Six females and 1 male were affected and 4 dogs were brachycephalic. The clinical course lasted from 3 d to 12 wk, and clinical signs were progressive and associated with multiple suspected neuroanatomic locations in the spinal cord. Magnetic resonance imaging of 6 cases revealed T2-weighted hyperintense lesions with variable contrast enhancement in the spinal cord. All dogs had a presumptive clinical diagnosis of intraparenchymal neoplasia or myelitis based on history, advanced imaging, and cerebrospinal fluid analysis. Euthanasia was elected in all cases because of poor outcome despite anti-inflammatory or immunosuppressive treatment or because of poor prognosis at the time of diagnosis. Tumor location during autopsy ranged from C1 to L6, with no clear predilection for a specific spinal cord segment. The diagnosis was based on histopathology and the immunohistochemistry expression of glial fibrillary acidic protein, oligodendrocyte lineage transcription factor 2, 2',3'-cyclic-nucleotide 3'-phosphodiesterase, neuron-specific enolase, synaptophysin, and Ki-67. Diagnoses consisted of 4 cases of oligodendroglioma, 2 cases of gliomatosis cerebri, and 1 astrocytoma. This case series further defines the clinicopathologic features of canine spinal glioma and highlights the need for comprehensive immunohistochemistry in addition to routine histopathology to confirm the diagnosis of these tumors.

Peginterferon beta-1a: a review of its use in patients with relapsing-remitting multiple sclerosis.

Peginterferon beta-1a (Plegridy™), an interferon beta-1a conjugated to a methoxy polyethylene glycol (PEG) molecule, is available in the EU and the USA for the treatment of adults with relapsing-remitting multiple sclerosis (RRMS). In a 96-week multinational, phase III study in this patient population (ADVANCE), subcutaneous peginterferon beta-1a 125 µg every 2 weeks significantly reduced the adjusted annualized relapse rate over 48 weeks, compared with placebo, corresponding to 36% fewer relapses per patient-year. Significant reductions versus placebo were also observed in the risk of relapse and disability progression, the number of new or newly enlarging T2-weighted hyperintense lesions, and various other magnetic resonance imaging endpoints. The efficacy of peginterferon beta-1a was sustained over 96 weeks, with preliminary data from the first year of an ongoing 2-year extension of ADVANCE indicating continued benefit longer-term. In ADVANCE, peginterferon beta-1a had an acceptable tolerability profile that was consistent with that of established interferon beta treatments. Adverse events were generally mild or moderate in severity, with injection-site erythema and influenza-like illness reported most commonly. Amongst other adverse events of special interest, peginterferon beta-1a was not associated with an increased risk of autoimmune disorders, depression/suicidal ideation, infections or seizures. In the absence of head-to-head studies, definitive conclusions on the comparative efficacy and tolerability of peginterferon beta-1a versus existing therapies are not yet possible. Although final data from the extension of ADVANCE are awaited, current evidence suggests subcutaneous peginterferon beta-1a every 2 weeks extends the treatment options currently available for adults with RRMS, with the dosing regimen imparting potential compliance advantages over non-PEGylated interferon beta formulations that require more frequent administration.

Aquaporin-4 antibody neuromyelitis optica following anti-NMDA receptor encephalitis

Encephalitis associated with anti-N-Methyl-D-Aspartate Receptor (NMDAR) antibodies is an autoimmune encephalopathy often associated with teratoma [1]. Neuromyelitis optica (NMO) is an inflammatory demyelinating disorder of the central nervous system (CNS) associated with antibodies against aquaporin 4 (AQP4) [2]. Here, we report the case of a patient who developed limbic encephalitis (LE) followed by NMO, whose serum harbored anti-NMDAR and anti-AQP4 IgG antibodies. A 50-year-old woman presented with subacute, shortterm memory loss, confusion, and behavioral changes. Routine blood tests, an infectious disease screening, an electroencephalogram (EEG) and cerebral spinal fluid (CSF) tests were all negative, whereas a brain MRI showed a T2-weighted, hyperintense medial temporal cortex. A pelvic mass was detected by computed tomography (CT) scan. Two months later, she underwent a hystero-adnexectomy with the removal of an ovarian teratoma. A diagnosis of paraneoplastic LE was made. Tests for classical onconeural antibodies (Hu, Ri, Ma2, CV2/CMRP5, amphiphysin, Yo) proved negative. Her memory deficit started to improve 4 months after surgery, when she received repeated courses of low-dose oral steroids. One month later, she had only residual retrograde amnesia (Fig. 1e). Five months later, she developed drowsiness, cervical itching, and impaired gait. Within 2 weeks, she had developed paraplegia and MRI showed multiple T2weighted hyperintense lesions in the pons, hypothalamus, medulla oblongata, and cervical spine (Fig. 1a–c). A CSF analysis proved negative (normal white cell count and proteins, and absence of IgG intrathecal synthesis). Plasmaexchange and high-dose intravenous steroids were initiated, resulting in a slow improvement of strength. Nine months later, she presented with left-eye optic neuritis. High-dose intravenous steroids were partially effective. Three months later, a relapse occurred with weakness of the right limbs. An MRI disclosed new lesions in the pons and dorsal spine (Fig. 1d). Her serum and CSF were tested for AQP4-IgG-Ab by indirect immunofluorescence on a commercial assay (Euroimmun, Lubeck, Germany) [3], proving positive on serum (titer 1:100). The test was extended to NMDAR-IgG-Ab, also proving positive on serum (1:32) and on CSF. The patient was treated with plasma-exchange and oral steroids, with benefit. Three months later, her CSF analysis revealed a normal white cell count and increased protein content (84 mg/dl); matching oligoclonal bands were detected in the CSF and serum. Human leukocyte typing disclosed the presence of the class I allele B8 and class II DR3-DQ2 (DRB1*03-DQB1*02). AQP4-IgG-Aband NMDAR-IgG-Ab-positivity were both confirmed, but a decrease in serum Ab titer was shown (both Abs serum titer 1:10; NMDAR-Ab CSF titer 1:3, 2); VGCC-, AMPAR-, GABAbR-, LGI1and CASPR2-Abs tested negative. Treatment with azathioprine was started. Eight months later, her conditions were stable. This patient presented with LE followed by NMO 1 year later, and tested positive for AQP4and NMDAR-Abs. To M. Zoccarato M. F. Pelizza B. Giometto L. Zuliani (&) Department of Neurology, Ospedale Ca’Foncello, Azienda Unita Locale Socio-Sanitaria 9 Treviso, Piazza Ospedale 1, 31100 Treviso, Italy e-mail: luigizuliani77@gmail.com

Transient interhemispheric disconnection in a case of insulinoma-induced hypoglycemic encephalopathy

We report a case of a 22-year-old male who was transferred to our hospital in a comatose state following successive seizures. Low blood glucose had been detected upon his arrival at the previous hospital. He became responsive 12days after the onset of coma. Upon regaining consciousness he exhibited severe dysarthria and several interhemispheric disconnection signs such as intermanual conflict, left-hand dysgraphia, left hemispatial neglect confined to the right hand, impaired interhemispheric transfer, and unilateral constructional apraxia of the right hand. Brain MRI disclosed T2-weighted and diffusion-weighted hyperintense lesions with reduced apparent diffusion coefficients in the bilateral centrum semiovale, splenium of the corpus callosum, right posterior limb of the internal capsule, and bilateral middle cerebellar peduncles. As the MRI findings vanished, his interhemispheric disconnection signs gradually resolved. Abdominal imaging studies revealed a pancreatic tumor, which was later endocrinologically diagnosed as an insulinoma. This is an extremely rare report of interhemispheric disconnection signs due to hypoglycemic encephalopathy. The lesions in the bilateral centrum semiovale likely contributed to the interhemispheric disconnection signs.

Placebo-Controlled Phase 3 Study of Oral BG-12 or Glatiramer in Multiple Sclerosis

BackgroundBG-12 (dimethyl fumarate) is in development as an oral treatment for relapsing–remitting multiple sclerosis, which is commonly treated with parenteral agents (interferon or glatiramer acetate).MethodsIn this phase 3, randomized study, we investigated the efficacy and safety of oral BG-12, at a dose of 240 mg two or three times daily, as compared with placebo in patients with relapsing–remitting multiple sclerosis. An active agent, glatiramer acetate, was also included as a reference comparator. The primary end point was the annualized relapse rate over a period of 2 years. The study was not designed to test the superiority or noninferiority of BG-12 versus glatiramer acetate.ResultsAt 2 years, the annualized relapse rate was significantly lower with twice-daily BG-12 (0.22), thrice-daily BG-12 (0.20), and glatiramer acetate (0.29) than with placebo (0.40) (relative reductions: twice-daily BG-12, 44%, P<0.001; thrice-daily BG-12, 51%, P<0.001; glatiramer acetate, 29%, P=0.01). Reductions in disability progression with twice-daily BG-12, thrice-daily BG-12, and glatiramer acetate versus placebo (21%, 24%, and 7%, respectively) were not significant. As compared with placebo, twice-daily BG-12, thrice-daily BG-12, and glatiramer acetate significantly reduced the numbers of new or enlarging T2-weighted hyperintense lesions (all P<0.001) and new T1-weighted hypointense lesions (P<0.001, P<0.001, and P=0.002, respectively). In post hoc comparisons of BG-12 versus glatiramer acetate, differences were not significant except for the annualized relapse rate (thrice-daily BG-12), new or enlarging T2-weighted hyperintense lesions (both BG-12 doses), and new T1-weighted hypointense lesions (thrice-daily BG-12) (nominal P<0.05 for each comparison). Adverse events occurring at a higher incidence with an active treatment than with placebo included flushing and gastrointestinal events (with BG-12) and injection-related events (with glatiramer acetate). There were no malignant neoplasms or opportunistic infections reported with BG-12. Lymphocyte counts decreased with BG-12.ConclusionsIn patients with relapsing–remitting multiple sclerosis, BG-12 (at both doses) and glatiramer acetate significantly reduced relapse rates and improved neuroradiologic outcomes relative to placebo. (Funded by Biogen Idec; CONFIRM ClinicalTrials.gov number, NCT00451451.)

Placebo-Controlled Phase 3 Study of Oral BG-12 for Relapsing Multiple Sclerosis

BackgroundBG-12 (dimethyl fumarate) was shown to have antiinflammatory and cytoprotective properties in preclinical experiments and to result in significant reductions in disease activity on magnetic resonance imaging (MRI) in a phase 2, placebo-controlled study involving patients with relapsing–remitting multiple sclerosis.MethodsWe conducted a randomized, double-blind, placebo-controlled phase 3 study involving patients with relapsing–remitting multiple sclerosis. Patients were randomly assigned to receive oral BG-12 at a dose of 240 mg twice daily, BG-12 at a dose of 240 mg three times daily, or placebo. The primary end point was the proportion of patients who had a relapse by 2 years. Other end points included the annualized relapse rate, the time to confirmed progression of disability, and findings on MRI.ResultsThe estimated proportion of patients who had a relapse was significantly lower in the two BG-12 groups than in the placebo group (27% with BG-12 twice daily and 26% with BG-12 thrice daily vs. 46% with placebo, P<0.001 for both comparisons). The annualized relapse rate at 2 years was 0.17 in the twice-daily BG-12 group and 0.19 in the thrice-daily BG-12 group, as compared with 0.36 in the placebo group, representing relative reductions of 53% and 48% with the two BG-12 regimens, respectively (P<0.001 for the comparison of each BG-12 regimen with placebo). The estimated proportion of patients with confirmed progression of disability was 16% in the twice-daily BG-12 group, 18% in the thrice-daily BG-12 group, and 27% in the placebo group, with significant relative risk reductions of 38% with BG-12 twice daily (P=0.005) and 34% with BG-12 thrice daily (P=0.01). BG-12 also significantly reduced the number of gadolinium-enhancing lesions and of new or enlarging T2-weighted hyperintense lesions (P<0.001 for the comparison of each BG-12 regimen with placebo). Adverse events associated with BG-12 included flushing and gastrointestinal events, such as diarrhea, nausea, and upper abdominal pain, as well as decreased lymphocyte counts and elevated liver aminotransferase levels.ConclusionsIn patients with relapsing–remitting multiple sclerosis, both BG-12 regimens, as compared with placebo, significantly reduced the proportion of patients who had a relapse, the annualized relapse rate, the rate of disability progression, and the number of lesions on MRI. (Funded by Biogen Idec; DEFINE ClinicalTrials.gov number, NCT00420212.)

Bevacizumab as salvage therapy for progressive brain stem gliomas

ObjectiveThere is no standard of care for patients with progredient brain stem gliomas. Therefore, we report about clinical, radiological and metabolic response to anti-angiogenic treatment with bevacizumab in a series of 3 patients with gliomas involving the brain stem. Patients and methodsThree patients with histologically confirmed gliomas involving the brain stem were treated with bevacizumab for tumor progression. The clinical data, histopathological findings as well as MRI and PET follow up examinations during bevacizumab therapy were retrospectively analyzed. ResultsThe histopathological diagnosis revealed an anaplastic astrocytoma WHO grade III in two patients and an astrocytoma WHO grade II in 1 patients with clinical and neuroradiological signs of malignization. One patient is still progression-free 97weeks after initiation of bevacizumab therapy. Mean progression-free survival and overall survival for the other two patients after initiation of bevacizumab therapy was 34.5weeks and 43.5weeks. During bevacizumab therapy mean KPS improved from 60 to 80 and mean dosage of daily dexamathasone was reduced from 7.3mg to 1.3mg. MRI showed a decrease of T2 weighted hyperintense lesions in all patients and a decrease of contrast enhancement in two patients. 18F-FET-PET showed a decrease of tracer uptake in all cases (mean maximum decrease: 25%). ConclusionIn this series treatment of progressive gliomas involving the brain stem with bevacizumab resulted in an improved clinical condition of the patients as well as a reduction of the T2 weighted lesions and reduced amino acid uptake in the tumor area. It therefore may represent a therapeutic salvage option for this type of tumor.

Impact of Stress Hyperglycemia on Myocardial Salvage Following Successfully Recanalized Primary Acute Myocardial Infarction

Elevated blood glucose on admission may worsen outcome after acute myocardial infarction (AMI). No relationship has been identified between admission blood glucose level and myocardial salvage in patients with AMI. This study assessed 150 consecutive patients with a first AMI who underwent percutaneous coronary intervention within 24 h from onset of symptoms. Plasma blood glucose was measured on admission. Stress hyperglycemia was defined as blood glucose ≥10 mmol/L (180 mg/dl). The extent of myocardial salvage 7 days after AMI was evaluated on cardiovascular magnetic resonance imaging (CMRI) as the difference between areas of myocardium at risk (T2-weighted hyperintense lesion) and areas of late gadolinium enhancement. The association between stress hyperglycemia and myocardial salvage index (MSI) was investigated in patients with and without diabetes. Among non-diabetic patients, MSI was lower in those with stress hyperglycemia than in those without. No significant difference in MSI was noted between diabetes patients with or without stress hyperglycemia. On multivariate analysis, stress hyperglycemia in patients without diabetes was an independent predictor of MSI. Stress hyperglycemia affects MSI, indicating that the manipulation of glucose levels could be a potential therapeutic target for salvaging ischemic damage.