5 - Demyelinating Disorders

Objective To investigate the differences in the clinical symptoms and magnetic resonance imaging (MPd) findings of the spinal cord lesions between patients with neuromyelitis optica (NMO) and multiple sclerosis (MS) and explore the mechanisms that result in these differences. Methods The clinical symptoms and MRI findings of the spinal cord were retrospectively analyzed in 21 MS patients and 23 NMO patients admitted in the Third Affiliated Hospital of Sun Yat-Sen University from January, 2004 to January, 2007. Results Female patients were more frequently affected by NMO, and the NMO patients had a older mean age at onset with higher Expanded Disability Status Scale (EDSS) score than the MS patients. Chi-square test showed significant differences in the rotes of bilateral deep sensory dysfunction, zonesthesia, and sphincter disturbance between the NMO and MS patients (P<0.05). The majority of these clinical symptoms were found to result form corresponding spinal cord lesions defined by MRI. Conclusion NMO is a demyelinating disease that represents an independent clinical entity from MS, and has special mechanisms responsible for its characteristic clinical symptoms and MRI findings of the spinal cord. Key words: Neuromyelitis optica; Multiple sclerosis; Clinical symptoms; Magnetic resonance imaging

Should Spinal MRI Be Routinely Performed in Patients With Clinically Isolated Optic Neuritis?

Clinical and laboratory features distinguishing MOG antibody disease from multiple sclerosis and AQP4 antibody-positive neuromyelitis optica

Devic’s neuromyelitis optica (NMO) is an inflammatory demyelinating disease with a preferential lesion of optic nerves and spinal cord. The onset of the disease is mostly between 30 and 40 years, but NMO may occur at any age. We present a case report of unilateral vision disorder in a fifteen years old adolescent. In 1,5 months the patient felt spasticity and numbness in legs. On MRI with gadolinium enhancement there were demyelinating lesions in the left optic nerve and in spinal cord at the level of Th1 vertebra with breakdown of blood-brain barrier (BBB) and at level of ThIV–V and ThXI–XII vertebras without BBB breakdown. Brain MRI was intact. Test for anti-aquaporin antibodies was negative. Optical coherence tomography (OCT) revealed the macula volume decrease and reduction of peripapillary nerve fibers thickness of the left eye. After methylprednisolone pulse therapy spasticity and numbness regressed. Multiple sclerosis was diagnosed and beta-interferon was prescribed. MRI over time did not reveal changes. But OCT showed progression of optic nerve disc atrophy of the left eye. Besides the symptoms of right eye lesion were revealed too. The article presents the detailed analysis of concordance of the case to the criteria of Devic’s neuromyelitis optica and multiple sclerosis. The arguments “pro” and “contra” are provided.

Multiple sclerosis (MS) is the most frequent idiopathic inflammatory demyelinating disease of the central nervous system. Magnetic resonance imaging is the most important paraclinical parameter in the diagnosis of MS. If the MR criteria for dissemination in time and space are positive, the early diagnosis of MS may be established already after one clinical event; thus, MRI has an important impact on the initiation of early therapy in MS. Moreover, MRI is essential in monitoring disease activity and therapy effects. Atypical inflammatory demyelinating diseases include ADEM, neuromyelitis optica (Devic disease), Baló’s concentric sclerosis, Schilder’s disease, Marburg’s disease, tumefactive demyelinating lesions, and acute transverse myelitis. These entities may be separated from MS by a different clinical course and a particular appearance on MRI. Occasionally, these variants merge with MS.In addition to MS there are several other idiopathic inflammatory demyelinating diseases (IIDDs) which differ in clinical course, severity, and lesion distribution as well as in imaging, laboratory, and pathological findings. Some IIDDs have a restricted topographical distribution such as optic neuritis, transverse myelitis, and neuromyelitis optica. (Devic) Acute disseminated encephalomyelitis (ADEM) is a clinical monophasic inflammatory disease with a broad spectrum of clinical and radiologic features. The differentiation of tumor-like lesions sometimes may be challenging. Fulminant variants of IIDDs are Marburg’s disease, Baló’s concentric sclerosis, and Schilder’s disease characterized by acute and severe attacks, and lesions seen as typical on MRI.KeywordsMultiple SclerosisMultiple Sclerosis PatientExpand Disability Status ScaleOptic NeuritisDemyelinating DiseaseThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

To analyze the clinical, neuroimaging characteristics and positivity of the acquaporin water channel (NMO-IgG) in pediatric patients with neuromyelitis optica (NMO). This disorder could have a variable clinical expression. To address such variability, the term NMO spectrum has been suggested. We evaluated six pediatric patients, with a median age of 11 years at the time of the study, with the diagnosis of NMO by the Wingerchuck criteria. All the cases exhibited bilateral optic neuritis (ON). Four patients had abnormalities on brain MRI from the onset,although only three of them developed symptoms correlated to those lesions during the course of their disorder. NMO-IgG was positive in 80%. Optic neuropathy is the most impaired feature in NMO patients. Brain MRI lesions are not compatible with multiple sclerosis and positivity of the NMO-IgG are also present in NMO pediatric patients, confirming the heterogeneity in the expression of this disorder.

ImportanceMelanoma in children is rare, accounting for approximately 2% of all pediatric malignant neoplasms. However, for the past 30 years, the incidence of melanoma in those younger than 20 years has been increasing. Location of the primary tumor has been shown to be an important prognostic factor, with melanomas of the scalp and neck conferring a worse prognosis than those originating at other sites.ObjectiveTo examine the survival, demographic, tumor, and treatment characteristics of pediatric head and neck melanoma.Design, Setting, and ParticipantsWe performed a retrospective cohort study using information from the National Cancer Data Base from January 1, 1998, to December 31, 2012, on pediatric (≤18 years) and adult (>18 years) patients with head and neck melanoma. Data analysis was conducted from August 1, 2015, to June 30, 2016.ExposurePediatric age (≤18 years) at diagnosis of head and neck melanoma.Main Outcomes and MeasuresSurvival differences were estimated using a Cox proportional hazards regression model. Surgical outcomes, including nodal sampling and margin status, were estimated with generalized linear models comparing pediatric and adult patients. Patient demographic, tumor, and treatment characteristics were estimated using t tests and χ2 tests between pediatric and adult patients with head and neck melanoma for continuous and categorical data, respectively. ResultsOf the 84 744 patients with head and neck melanoma, 657 (0.8%) were 18 years or younger (mean [SD] age, 13.5 [4.7] years; 285 female and 372 male; 610 white). Pediatric and adult patients had similar demographics but different histologic subtypes (risk difference of pediatric vs adult patients: melanoma, not otherwise specified, 8.5% [95% CI, 4.7%-12.3%]; superficial spreading, 4.2% [95% CI, 0.89%-7.4%]; and lentigo maligna, –13.4% [95% CI, –14.1% to 12.6%]). Pediatric patients had tumors of similar mean depth to those in adult patients (pediatric, 1.54 mm; adult; 1.39 mm; absolute difference, 0.15 mm; [95% CI, –0.32 to 0.008]) and more frequent nodal metastases than did adult patients (risk difference of pediatric vs adult patients for stage T2, 23.9% [95% CI, 14.1%-33.6%]). Five-year survival among pediatric patients was higher for those with stage 1, 2, or 3 disease (absolute difference of pediatric vs adult patients: stage 1, 18% [95% CI, 9.7%-26.3%]; stage 2, 36% [95% CI, 25.3%-46.7%]; stage 3, 39% [95% CI, 26.8%-51.2%]; and stage 4, 2% [95% CI, –8.2% to 12.2%]).Conclusions and RelevanceAlthough pediatric patients with head and neck melanoma present with similar tumor depth and more frequent nodal metastases than do adult patients, younger patients have higher overall survival.

P834: Nocebo effect dissociates the laser-pain rating from the N2/P2 laser evoked potential amplitude

Interim Analysis of a Phase 1 Study of the Antibody-Drug Conjugate SGN-CD19A in Relapsed or Refractory B-Lineage Acute Leukemia and Highly Aggressive Lymphoma

Multiple sclerosis (MS)is a long lasting, chronic and auto-immune disease which affects central nervous system. In this auto-immune disease, our own immune system damages the body.It is a disabling disease of spinal cord and brain, specially deteriorates optic nerve of eyes. The disease is caused when immune system of the body attacks on myelin sheath which is a protective layer of neurons; the structural and functional unit of nervous system. This sheath protects the nerve fibers. Damage to myelin sheath exposes the nerve fibers, which slows down or blocks the nerve impulse passing through the nerve. This disease appears between the ageof 20 to 50 years in most cases. Statistics reveal that it is more common in women than men. The causes of this disease are unknown but scientists believe that the risk factor of this disease is the combination of genetics and environment. Its symptoms include effects on body movements involving loss of balance, weakness or numbness in limbs, dizziness, body pains, electric shock sensations specially in neck region,fatigue,difficulty swallowing, slurred speechand vertigo.It also involves problems relating sexual, bowel and bladder functions. It may also cause depression and anxiety.The symptoms are different in children than adults. It starts with acute encephalomyelitis, including fever, stiff neck, seizures, coma and confusion. It these symptoms persist, doctor should be consulted immediately.&#x0D; Research has shown that there are some factors whichcan increase the chances of its development. These factors include;age,climate, Vitamin D and other auto-immune diseases. MS can occur at any age in one’s life but its onset is common between 20 to 50 years. The risk of developing of MS in twin babies is 1 in 4 cases. However, younger and older people can be affected too.Considering the factor of climate, MS is found to be more common in countries found in temperate regions of the world. Statistics have shown that MS was common in people living in New Zealand, Canada, USA and many other European countries. All of us know what is the importance of vitamins. It has been observed that lower levels of Vitamin D and decreased sunlight exposure are related with greater risk of this disease. Many people suffer from auto-immune diseases for example pernicious anemia, Inflammatory bowel disease, Type I Diabetes Mellitus and thyroid problems. Recent studies show that person already facing the trouble of auto-immune disease is at higher risk of getting MS. Multiple sclerosis (MS) has been divided into four basic types: Primary progressive MS (PPMS), Secondary Progressive MS (SPMS), Progressive Relapsing MS (PRMS) and Relapsing Remitting MS (RRMS).&#x0D; Recent findings from a National MS Society estimated that nearly 1 million people in the United States are affected with MS. This is more than double the last reported number, and the first national research on MS prevalence since 1975. The society also estimated that 2.3 million people live with MS globally.&#x0D; There is no specific laboratory or diagnostic test to check for MS. For detection of MS, differential diagnosis is used in which signs, symptoms and patients condition is used to rule out the overall scenario. Some blood tests are recommended by doctors which check specific biomarkers associated with MS. MRIis helpfuland it can reveal some areas of spinal cord and brain to see lesions.Spinal tap in which a small sample of cerebrospinal fluid is removed from the spinal canal for laboratory analysis. This sample can show abnormalities in antibodies that are associated with MS.Electric signals produced by nervous system in response to specific stimuli are recorded in a test called Evoked potential test. It’s unfortunate that there is no complete cure of this disease up-till now. Treatment helps tospeed up the, slowing the progression of the disease and managing MS symptoms to help patient live a better life. Treatment for attacks includes the useof corticosteroids and plasma exchange.&#x0D; Previously, it was thought that this disease is uncommon in Pakistan. But new data shows its prevalence to be 10 in 10,0000 of population. It is affecting the Pakistani population on same patterns as found in West. It is found to be more common in women than men. It has been affecting more people who are passing third decade of life. Among its types, Relapsing-Remitting MS (RRMS) is more common in Pakistan. It’s unfortunate that the reports about this disease are few in numbers and there is a need to conduct a thorough research in hope of finding a complete cure of this disease and making the life of patients affected by it much more comfortable.

Aquaporin 4 antibody (AQP4-Ab)-negative patients with longitudinally extensive transverse myelitis (LETM) behave differently from those with AQP4-Ab. Aquaporin 4 antibody-negative neuromyelitis optica (NMO) is rare when good assays are used. To assess if AQP4-Ab-negative patients with LETM share similar disease characteristics with AQP4-Ab-positive patients or whether they have distinct features and alternative diagnoses. DESIGN We collated clinical and paraclinical data on patients with LETM identified through the Oxford NMO clinical database. Aquaporin 4 antibodies were tested using 2 sensitive assays. We describe the features of patients with LETM, compare findings between patients with and without AQP4-Ab, and describe alternative diagnoses in AQP4-Ab-negative patients. Single specialist UK center for NMO. Seventy-six adult patients with LETM. Comparison of clinical and paraclinical data. Fifty-eight percent of patients were AQP4-Ab positive. Alternative diagnoses could usually be identified in AQP4-Ab-negative patients, including those fulfilling NMO diagnostic criteria. Only 6.5% of patients had "true" seronegative NMO and 6.5% had idiopathic LETM. There were some important differences between AQP4-Ab-positive and -negative cases, including older onset age, higher proportion of females, lower incidence of simultaneous optic neuritis, lower frequency of conus involvement, and higher prevalence of coexisting autoimmune disorders in AQP4-Ab-positive cases. Attack severity and degree of recovery were similar in the 2 groups. Patients with LETM without AQP4-Ab include a number of different diagnostic categories and it is not surprising therefore that they show important differences compared with AQP4-Ab-positive patients, even when considering only those fulfilling current NMO diagnostic criteria. Thus, we suggest that diagnoses such as myelin-oligodendrocyte glycoprotein antibody disease, multiple sclerosis, acute disseminated encephalomyelitis, and postinfectious disorders should be exclusions in the NMO diagnostic criteria and AQP4-Ab-positive and antibody-negative NMO/NMO spectrum disorder cohorts should be analyzed separately.

To investigate spinal cord and brain atrophy in neuromyelitis optica (NMO), and its relationship with other MRI measurements and clinical disability, compared with patients with multiple sclerosis (MS) and healthy controls (HC). We recruited 35 patients with NMO, 35 patients with MS, and 35 HC, who underwent both spinal cord and brain MRI. Mean upper cervical cord area (MUCCA), brain parenchymal fraction (BPF), gray matter fraction (GMF), white matter fraction (WMF), and spinal cord and brain lesion loads were measured and compared among groups. Multivariate associations between MUCCA and brain volume measurement and clinical variables were assessed by partial correlations and multiple linear regression. Patients with NMO showed smaller MUCCA than HC (p = 0.004), and patients with MS had a trend of smaller MUCCA compared to HC (p = 0.07), with no significant difference between the patient groups. Patients with NMO showed lower BPF than HC, and patients with MS had lower BPF and GMF than patients with NMO. In NMO, MUCCA was correlated with Expanded Disability Status Scale score (EDSS), number of relapses, and total spinal cord lesion length, while in MS, MUCCA was correlated with WMF and EDSS. MUCCA was the only independent variable for predicting clinical disability measured by EDSS in NMO (R(2) = 0.55, p < 0.001) and MS (R(2) = 0.17, p = 0.013). NMO showed predominately spinal cord atrophy with mild brain atrophy, while MS demonstrated more brain atrophy, especially in the gray matter. MUCCA is the main MRI-derived parameter for explaining clinical disability in NMO and MS, and may serve as a potential biomarker for further clinical trials, especially in NMO.

Background: Recently we showed that antibodies to myelin oligodendrocyte glycoprotein (MOG) can be found in aquaporin-4 (AQP4)-immunoglobulin (IgG) seronegative pediatric and adult patients with definite and high-risk neuromyelitis optica (NMO). Objective: The purpose of this study was to describe the clinical characteristics and temporal dynamics of MOG-IgG in AQP4-IgG seronegative pediatric patients presenting with definite NMO. Methods: Children with definite NMO who were referred for further testing of serum antibodies for AQP4 and MOG with a cell-based assay were included in this study. Clinical disease course, cerebrospinal fluid and magnetic resonance imaging (MRI) studies of these patients were reviewed. Results: Between 2008 and 2012 eight children who fulfilled the diagnostic criteria of definite NMO were recruited. Two children with definite NMO tested positive for AQP4-IgG but were negative for MOG-IgG antibodies. Three children had an absence of AQP4-IgG and MOG-IgG antibodies. Three children with definite NMO had high titers of serum MOG-IgG antibodies (≥1: 160), but no AQP4-directed humoral immune response. Longitudinal analysis of serum samples of the latter three children showed persisting high MOG-IgG titers over time. Conclusion: Pediatric patients presenting with clinical symptoms and MRI findings highly suggestive of NMO but with high and persisting MOG-IgG antibody titers are most likely to represent a distinct subgroup of acute demyelinating diseases with important clinical and therapeutic implications.

Anti-aquaporin 4 antibodies are specific markers for Devic's disease. This study aimed to test if this high specificity holds in the context of a large spectrum of systemic autoimmune and non-autoimmune diseases. Anti-aquaporin-4 antibodies (NMO-IgG) were determined by indirect immunofluorescence (IIF) on mouse cerebellum in 673 samples, as follows: group I (clinically defined Devic's disease, n=47); group II [inflammatory/demyelinating central nervous system (CNS) diseases, n=41]; group III (systemic and organ-specific autoimmune diseases, n=250); group IV (chronic or acute viral diseases, n=35); and group V (randomly selected samples from a general clinical laboratory, n=300). MNO-IgG was present in 40/47 patients with classic Devic's disease (85.1% sensitivity) and in 13/22 (59.1%) patients with disorders related to Devic's disease. The latter 13 positive samples had diagnosis of longitudinally extensive transverse myelitis (n=10) and isolated idiopathic optic neuritis (n=3). One patient with multiple sclerosis and none of the remaining 602 samples with autoimmune and miscellaneous diseases presented NMO-IgG (99.8% specificity). The autoimmune disease subset included five systemic lupus erythematosus individuals with isolated or combined optic neuritis and myelitis and four primary Sjögren's syndrome (SS) patients with cranial/peripheral neuropathy. The available data clearly point to the high specificity of anti-aquaporin-4 antibodies for Devic's disease and related syndromes also in the context of miscellaneous non-neurologic autoimmune and non-autoimmune disorders.

Background: Benign paroxysmal positional vertigo (BPPV) is characterized by brief, intense episodes of vertigo triggered by abrupt changes in head position. It is generally accepted as being most common in adults, while it is regarded as rare in children. It is necessary to compare the disease between pediatric and adult patients for a better understanding of the disease's characteristics and its natural history. This study aimed to identify the clinical characteristics of BPPV in children and compare them with those of adult BPPV patients. Methods: All children ≤ 18 years old who were diagnosed with BPPV were selected by searching the electronic database of our hospital. Clinical features were identified by medical record review. For adult patients, we collected data from patients > 19 years of age. Results: A total of 30 pediatric (13.65 ± 4.15 years old) and 264 adult patients (60.86 ± 13.74 years old) were included in the study. Among pediatric patients, the lateral canals were involved in 80% and the posterior canals in 16.67%. In adult patients, the lateral and posterior canals were involved similarly (p = 0.007). The degree of nystagmus in pediatric patients was 6.82 ± 12.09, while in adults it was 15.58 ± 20.90 (p < 0.001). The concurrent dizziness disorder was higher in the pediatric group and recurrence was higher in the adult group. In the regression analysis, it was found that adult patients had a stronger nystagmus with a value of 6.206 deg/sec, and the risk of concurrent dizziness disorder was found to be 5.413 times higher in the pediatric group (p < 0.05). Conclusions: BPPV occurs in pediatric patients with lower prevalence, but it cannot be overlooked. In the pediatric group, a relatively high proportion of patients demonstrated lateral canal involvement, weaker nystagmus, and additional dizziness disorder.