Bahadir Konuskan

Disease Course and Treatment Responses in Children With Relapsing Myelin Oligodendrocyte Glycoprotein Antibody–Associated Disease

Importance Myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) are consistently identified in a range of demyelinating disorders in adults and children. Current therapeutic strategies are largely center specific, and no treatments have been formally evaluated. Objective To examine the clinical phenotypes, treatment responses, and outcomes of children with relapsing MOG-Ab–associated disease. Design, Setting, and Participants This study prospectively collected demographic, clinical, and radiologic data from 102 patients from 8 countries of the EU Paediatric Demyelinating Disease Consortium from January 1, 2014, through December 31, 2016. Patients were treated according to local protocols. Main Outcomes and Measures Annualized relapse rates (ARRs) and Expanded Disability Status Scale (EDSS) scores before and during treatment with disease-modifying drugs (DMDs). Results A total of 102 children were identified (median [range] age, 7.0 [1.5-7.9] years; male to female ratio, 1.0:1.8; white to other race/ethnicity ratio, 3.6:1.0). Original diagnoses were neuromyelitis optica spectrum disorder (44 patients [43.1%]), acute disseminated encephalomyelitis followed by optic neuritis (20 [19.6%]), multiphasic disseminated encephalomyelitis (20 [19.6%]), and relapsing optic neuritis (18 [17.6%]). In all, 464 demyelinating events were reported. Treated patients had more relapses (median, 3.0; range, 1.0-17.0) than untreated patients (median, 1.0; range 1.0-7.0) (P = .009) and higher EDSS scores (median, 1.5; interquartile range, 0-2.5) than untreated patients (median, 1.0; interquartile range, 0-1.5) (P < .001). Fifty-two children (51.0%) received DMDs: 28 (53.8%) were treated with 1 DMD, 17 (32.7%) with 2, and 7 (13.5%) with 3 or more sequential DMDs. Patients relapsed during all treatments, with a total of 127 relapses on treatment reported. No changes in median ARR and EDSS score were observed between the preinitiation and postinitiation phases of interferon beta and glatiramer acetate treatment (n = 11). The median ARR was reduced from 1.84 to 1.0 with azathioprine (n = 20, P < .001), 1.79 to 0.52 with mycophenolate mofetil (n = 15, P = .003), and 2.12 to 0.67 with rituximab (n = 9, P < .001), although the median EDSS score remained unchanged. An improvement in ARR (from 2.16 to 0.51, P < .001) and EDSS score (from 2.2 to 1.2, P = .01) was observed in the 12 patients treated with regular intravenous immunoglobulins. Conclusions and Relevance Although commonly used to treat patients with multiple sclerosis, DMDs were not associated with clinical improvement in children with MOG-Ab–associated disease, whereas azathioprine, mycophenolate mofetil, rituximab, and particularly intravenous immunoglobulins were associated with a reduction in relapse frequency. A correct diagnosis of relapsing MOG-Ab–associated disorders is therefore important to optimize immune treatment.

Unfavorable outcome of pediatric onset multiple sclerosis: Follow-up in the pediatric and adult neurology departments of one referral center, in Turkey

BACKGROUND The prevalence of MS starting under 18 years of age ranges between 2-10% of the total MS population. OBJECTIVE We aimed to examine the clinical and long term follow-up data of pediatric-onset cases in our institutional MS database. METHOD We evaluated the clinical data from the MS database of the Departments of Neurology and Pediatric Neurology of Hacettepe University Hospital. RESULTS The clinical features of 74 patients who had experienced the first attack before age 18 years comprised 3.9% of our MS population. Median age at onset was 15 (3, 5-17, IQR=3.63) years, and female: male ratio was 2.4. The most frequent symptom at onset was brainstem/cerebellar dysfunction (32.4%). Seventy two patients (97.3%) initially had relapsing remitting course and in the follow-up, 17 (23%) of them developed secondary progressive (SP) course. The median interval to develop SPMS course was 10 (5-21, IQR=8) years. At the last visit, median disease duration was 6.67 (0.83-25, IQR=9.06) years, 41 (55.4%) of them had EDSS of ≥4. CONCLUSION These findings illustrate the profile of our pediatric MS patients: almost all are relapsing-remitting initially; about one fourth become secondarily progressive in 10 years, and about half acquire disability EDSS ≥4 in mean 8 years.

Acute Abducens Nerve Paralysis in the Pediatric Emergency Department: Analysis of 14 Patients.

Objectives Sixth cranial nerve (SCN) palsy is an uncommon but important neurological problem in patients admitted to pediatric emergency department. The underlying etiology of SCN palsy has a wide range from viral infections to intracranial tumors; therefore, a careful and systematic approach is necessary while examining these patients. Methods Fourteen patients who presented with acute SCN paralysis to pediatric emergency department during the last 10 years were examined. Results The age at the time of admission ranged between 14 months and 16 years (median, 9.5 years). Of the 14 patients, 5 were girls and 9 were boys. A total of 3 of the 14 patients had bilateral cranial nerve VI paralysis, and 9 patients had additional abnormal findings on neurological examination. Neuroimaging studies included cranial tomography (n = 3) and brain magnetic resonance imaging in all patients. The underlying etiology was malignancy (n = 3); glioma, medulloblastoma, acute lymphoblastic leukemia, and dural sinus thrombosis (n = 2); as well as Guillain-Barre syndrome (n = 2), multiple sclerosis (n = 1), pseudotumor cerebri (n = 1), and meningitis (n = 1). The remaining 4 patients had miscellaneous benign etiologies. Conclusions Other lesions of primary brain tumors causing increased intracranial pressure constitute 50% of the underlying etiology, followed by Guillain-Barre syndrome (14.2%). However, these patients had neurological symptoms signs, in addition to diplopia or SCN paralysis. Patients admitted to pediatric emergency department with acute SCN paralysis should be examined in detail to disclose the underlying etiology especially if they present with additional clinical signs or symptoms.

Mesenchymal stem cell application in children with subacute sclerosing panencephalitis

Subacute sclerosing panencephalitis (SSPE) is a serious, often fatal disease that responds poorly to current treatment modalities. Recently, the ability of mesenchymal stem cells (MSCs) to produce neurotrophic factors and inflammatory molecules has placed them among potential treatment agents for neurological conditions. We report the results of four patients treated with MSC for SSPE. The patients were followed up clinically, and by periodical laboratory evaluations, magnetic resonance imaging (MRI), and electroencephalography. One patient deteriorated to stage III of the disease, two patients remained in the same stage, and one died from disease progression and respiratory problems. Neurological findings and electroencephalography scores were consistent with the clinical course of the patient whereas MRI showed new inflammatory lesions in two patients. This is the first report of the application of MSC in SSPE. No benefit is demonstrated.

Congenital Tuberculosis after in-vitro Fertilization in a Woman Previously Undiagnosed with Tuberculosis Salpingitis

Congenital tuberculosis (TB) is rarely seen with only several hundred cases reported in the literature. Because genitourinary TB causes infertility, rates of congenital TB have been low. However, the increased availability of assisted reproductive technology allows emergence of congenital TB if mothers are not properly evaluated and treated before implantation of the embryos. Diagnosis of congenital TB is difficult due to nonspecific symptoms, and a high index of suspicion is required for early diagnosis in infants. Here we present a 3-month-old infant with congenital tuberculosis after in vitro fertilization (IVF).

Clinical presentation of anti-N-methyl- d -aspartate receptor and anti-voltage-gated potassium channel complex antibodies in children: A series of 24 cases

OBJECTIVE The symptomatology and paraclinical findings of antibody-mediated encephalitis, a relatively novel disorder, are still being characterized in adults and children. A high index of suspicion is needed in order to identify these cases among children presenting with various neurological symptoms. The aim of this study is to examine the clinical, demographic and laboratory findings and outcome of children with anti-NMDAR and anti-VGKC encephalitis for any typical or distinctive features. METHODS Cases diagnosed with anti-N-Methyl d-aspartate receptor (NMDAR) and anti-voltage gated potassium channel (VGKC) antibody-mediated encephalopathy in four major child neurology centers are described. RESULTS In four years, 16 children with NMDAR and 8 children with VGKC antibody-associated disease were identified in the participating centers. The most frequent initial manifestation consisted of generalized seizures and cognitive symptoms in both groups. Movement abnormalities were frequent in anti-NMDAR patients and autonomic symptoms, in anti-VGKC patients. Cerebrospinal fluid (CSF) protein, cell count and IgG index were normal in 9/15 anti-NMDAR and 5/8 anti-VGKC patients tested. EEG and MRI findings were usually nonspecific and non-contributory. The rate and time of recovery was not related to age, sex, acute or subacute onset, antibody type, MRI, EEG or CSF results. Treatment within 3 months of onset was associated with normal neurological outcome. CONCLUSIONS Our results suggest anti-NMDAR and VGKC encephalopathies mostly present with non-focal neurological symptoms longer than 3 weeks. In contrast with adult cases, routine CSF testing, MRI and EEG did not contribute to the diagnosis in this series.

Electroencephalographic findings in anti- N -methyl-d-aspartate receptor encephalitis in children: A series of 12 patients

OBJECTIVE Anti-N-methyl-d-aspartate receptor encephalitis (a-NMDARe) is an acute or subacute encephalopathy where electroencephalogram (EEG) is frequently obtained as part of the workup. Although no diagnostic EEG finding has been described so far, the definition of specific or typical patterns might help to distinguish this group among various encephalopathies of childhood. We examined EEG recordings of our patients with a-NMDARe in order to describe the most frequent findings. METHODS Clinical and laboratory data and digital EEG recordings of 12 pediatric patients diagnosed with a-NMDARe in two major child neurology centers are evaluated. RESULTS We reviewed 43 EEG recordings from 12 children with a-NMDARe and followed their evolution for a median of 6 (range: 1-60) months. Initial EEG was abnormal in 11/12 patients. The most frequent finding was focal or diffuse slowing of the background rhythm. Generalized rhythmic delta activity, brief rhythmic discharges (BRDs), and occipital intermittent rhythmic delta activity (OIRDA) were seen in two patients each. Diffuse excess beta frequency activity was seen in three patients. Extreme delta brushes were observed in 5/12 (41.7%) patients, disappeared in 4-6months (two patients), or persisted at 10-17months (two patients). Epileptic activity was seen in seven patients (58%) and lateralized periodic discharges in one. On follow-up EEGs, most epileptic activity disappeared in a median of 8months. CONCLUSIONS A normal EEG is rare in a-NMDARe. Focal or diffuse slowing, epileptic activity, and extreme delta brush are common findings. Epileptic activity in early EEGs do not persists in most patients. Severe diffuse slowing may predict neurological impairment if confirmed in larger series.

Multiple Sclerosis with Onset Younger Than 10 Years in Turkey

Abstract Objective To identify the demographics, clinical characteristics, disease course, treatment patterns, and disability levels of multiple sclerosis (MS) patients with onset under the age of 10 years (early onset multiple sclerosis, EOMS). Methods EOMS patients were reviewed retrospectively in detailed records from 27 child neurology centers. Patients with preschool (≤7 years) and school age (>7 years) onset were compared. Results There were 30 children (16 girls, 14 boys) who have disease onset between 4 and 10 (mean8.1 ± 1.8) years. MS was relapsing‐remitting in 29 (96.7%) and primary progressive in one (3.3%) of the patients. In patients with onset ≤7 years, motor symptoms (54.5%) and encephalopathy (45.5%) predominated, while in those with onset >7 years brainstem (42.1%), sensory (26.3%), and optic nerve (26.3%) involvement were the most frequent presentations. Conclusions MS starting ≤7 years differs from the 7‐10‐year‐old group by the higher rate of motor symptoms and more attacks in the first year: the latter suggests a more inflammatory character for EOMS.

Retrospective analysis of children with myelin oligodendrocyte glycoprotein antibody-related disorders

BACKGROUND Knowledge has been expanding on myelin oligodendrocyte glycoprotein (MOG) antibody-associated central nervous system disorders. We delineate the clinical and paraclinical findings and outcome of our pediatric patients with MOG antibody seropositive disease. METHODS We retrospectively analyzed the clinical presentation, cerebrospinal fluid findings, magnetic resonance imaging (MRI) studies, course and outcome of children seropositive for anti-MOG IgG. RESULTS Total 20 children with neurological symptoms and serum anti-MOG IgG were identified from six centers in Turkey. Median age at onset was 9 years (mean 8.8 ± 5.0 years, range: 1.5-16.5 years). Final diagnoses were acute disseminated encephalomyelitis (ADEM) (n = 5), ADEM + optic neuritis (n = 4), neuromyelitis optica spectrum disorder (NMOSD) (n = 3), myelitis (n = 2), relapsing optic neuritis (n = 2), multiphasic DEM (n = 3), and unclassified relapsing demyelinating disease (n = 1). Seven/20 (35%) children experienced a single episode while 13/20 (65%) had a least one relapse during follow-up. On MRI, subcortical white matter, brainstem, and corpus callosum were preferentially involved regions. Full recovery was observed in 15/20 (75%) children. CONCLUSION MOG autoimmunity in children has a wide clinical spectrum, tendency to relapse, and a favourable outcome compared with other relapsing demyelinating diseases.

Assessment of Peripheral Neuropathy in Patients with β-Thalassemia via Electrophysiological Study: Reevaluation in the Era of Iron Chelators

Abstract Peripheral neuropathy is one of the complications of β-thalassemia (β-thal) that has been investigated in limited reports. We aimed to detect the rate of peripheral neuropathy and risk factors for neuropathy development in patients with β-thal. The study was performed in patients with β-thal intermedia (β-TI) or β-thal major (β-TM). Prospective electrophysiological studies were achieved via standard procedures. A total of 27 patients were enrolled in the study. Electrophysiological studies for both motor and sensory nerves were within normal range. In motor nerve studies, delayed peroneal nerve latency was found in patients with high ferritin levels, increased ulnar nerve amplitude was detected in patients ≥20 years old, and increased tibial nerve amplitude was seen in patients with low copper levels. We could not show peripheral neuropathy in our patients. Increased ferritin level, older age, and copper deficiency may cause mild changes in electrophysiological studies of motor nerves.