Late effects of medulloblastoma treatment: multidisciplinary approach of survivors.

PURPOSE: Medulloblastoma is one of the brain tumors with increased life expectancy due to improvements in treatment approaches. Besides the promising results, various undesirable effects can be encountered. This study's aim is to review long-term follow-up outcomes of our cases with medulloblastoma. METHODS: Age at diagnosis, histological type of medulloblastoma, resection extension, chemotherapy and radiotherapy schemes, follow-up duration, and endocrinological, neuropsychiatric, cardiological, auditory, and visual examination results were evaluated in 20 patients diagnosed between 2007 and 2018 and followed 5 years and more. RESULTS: Twenty of 53 patients were included to the study. Eleven (55%) were male. Mean age at diagnosis was 6.95 years; mean age at the time of the study was 14 years. Mean follow-up time was 8.95 years. In terms of surgery, 14 (70%) were gross total, 1 (5%) was near total, and 2 (10%) were subtotal resection. In histopathological examination, 14 (70%) were classical medulloblastoma, 4 (20%) were desmoplastic medulloblastoma, and 1 (5%) was anaplastic medulloblastoma. With regard to endocrinological evaluation, 15 (75%) patients had hypothyroidism, 5 (25%) had growth hormone deficiency, 7 (35%) had clinical growth hormone deficiency, and 5 (25%) had sex hormone disorders. In neuropsychiatric examination, 11 (55%) patients had neurological sequelae, 18 (90%) patients had psychiatric issues, and 14 (70%) patients had two or more neuropsychiatric problems simultaneously. One (5%) patient had mitral valve insufficiency. Twelve patients (60%) had hearing loss. According to visual examination, 6 (30%) patients had refraction problem, 4 (20%) had cataract, and 1 (5%) had dry eye. CONCLUSION: Careful monitoring of long-term side effects is important for improving the quality of life of medulloblastoma patients. Besides endocrinological and other somatic sequelae of the disease and treatment, increased neuropsychiatric problems showed us that only cure is not the issue while treating childhood medulloblastoma.

Five Years Follow-up of Opsoclonus-Myoclonus-Ataxia Syndrome-Associated Neurogenic Tumors in Children.

AIM: Opsoclonus-myoclonus-ataxia syndrome (OMAS) is a rare autoimmune disorder. Approximately half of the cases are associated with neuroblastoma in children. This study's aim is to review management of our cases with OMAS-associated neuroblastoma for treatment approach as well as long-term follow-up. METHODS: Age at onset of symptoms and tumor diagnosis, tumor location, histopathology, stage, chemotherapy, OMAS protocol, surgery, and follow-up period were evaluated retrospectively in six patients between 2007 and 2022. RESULTS: Mean age of onset of OMAS findings was 13.5 months and mean age at tumor diagnosis was 15.1 months. Tumor was located at thorax in three patients and surrenal in others. Four patients underwent primary surgery. Histopathological diagnosis was ganglioneuroblastoma in three, neuroblastoma in two, and undifferentiated neuroblastoma in one. One patient was considered as stage 1 and rest of them as stage 2. Chemotherapy was provided in five cases. The OMAS protocol was applied to five patients. Our protocol is intravenous immunoglobulin (IVIG) 1 g/kg/d for 2 consecutive days once a month and dexamethasone for 5 days (20 mg/m2/d for 1-2 days, 10 mg/m2/d for 3-4 days, and 5 mg/m2/d for the fifth day) once a month, alternatively by 2-week intervals. Patients were followed up for a mean of 8.1 years. Neuropsychiatric sequelae were detected in two patients. CONCLUSION: In tumor-related cases, alternating use of corticosteroid and IVIG for suppression of autoimmunity as the OMAS protocol, total excision of the tumor as soon as possible, and chemotherapeutics in selected patients seem to be related to resolution of acute problems, long-term sequelae, and severity.

Role of serostatus in pediatric neuromyelitis optica spectrum disorders: A nationwide multicentric study.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) are immune-mediated inflammatory disorders of the central nervous system (CNS) mostly presenting as optic neuritis and acute myelitis. NMOSD can be associated with seropositivity for aquaporin 4 antibody (AQP4 IgG), myelin oligodendrocyte glycoprotein antibody (MOG IgG), or can be seronegative for both. In this study, we retrospectively examined our seropositive and seronegative pediatric NMOSD patients. METHOD: Data were collected from all participating centres nationwide. Patients diagnosed with NMOSD were divided into three subgroups according to serology: AQP4 IgG NMOSD, MOG IgG NMOSD, and double seronegative (DN) NMOSD. Patients with at least six months of follow-up were compared statistically. RESULTS: The study included 45 patients, 29 female and 16 male (ratio:1.8), mean age 15.16 ± 4.93 (range 5.5-27) years. Age at onset, clinical manifestations, and cerebrospinal fluid findings were similar between AQP4 IgG NMOSD (n = 17), MOG IgG NMOSD (n = 10), and DN NMOSD (n = 18) groups. A polyphasic course was more frequent in the AQP4 IgG and MOG IgG NMOSD groups than DN NMOSD (p = 0.007). The annualized relapse rate and rate of disability were similar between groups. Most common types of disability were related to optic pathway and spinal cord involvement. Rituximab in AQP4 IgG NMOSD, intravenous immunoglobulin in MOG IgG NMOSD, and azathioprine in DN NMOSD were usually preferred for maintenance treatment. CONCLUSION: In our series with a considerable number of double seronegatives, the three major serological groups of NMOSD were indistinguishable based on clinical and laboratory findings at initial presentation. Their outcome is similar in terms of disability, but seropositive patients should be more closely followed-up for relapses.

Shared Biological Pathways and Processes in Patients with Intellectual Disability: A Multicenter Study.

BACKGROUND: Although the underlying genetic causes of intellectual disability (ID) continue to be rapidly identified, the biological pathways and processes that could be targets for a potential molecular therapy are not yet known. This study aimed to identify ID-related shared pathways and processes utilizing enrichment analyses. METHODS: In this multicenter study, causative genes of patients with ID were used as input for Disease Ontology (DO), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. RESULTS: Genetic test results of 720 patients from 27 centers were obtained. Patients with chromosomal deletion/duplication, non-ID genes, novel genes, and results with changes in more than one gene were excluded. A total of 558 patients with 341 different causative genes were included in the study. Pathway-based enrichment analysis of the ID-related genes via ClusterProfiler revealed 18 shared pathways, with lysine degradation and nicotine addiction being the most common. The most common of the 25 overrepresented DO terms was ID. The most frequently overrepresented GO biological process, cellular component, and molecular function terms were regulation of membrane potential, ion channel complex, and voltage-gated ion channel activity/voltage-gated channel activity, respectively. CONCLUSION: Lysine degradation, nicotine addiction, and thyroid hormone signaling pathways are well-suited to be research areas for the discovery of new targeted therapies in ID patients.

First pediatric case with primary familial brain calcification due to a novel variant on the MYORG gene and review of the literature.

Variants in the myogenesis-regulating glycosidase (MYORG) gene which is known as the first autosomal recessive gene that has been associated with primary familial brain calcification (AR-PFBC). Although adult patients have been reported, no pediatric case has been reported until now. Herein, we review the clinical and radiological features of all AR- PFBC patients with biallelic variants in the MYORG gene who were reported until now, and we report the youngest patient who has a novel homozygous variant. Since the first identification of the MYORG gene in 2018, 74cases of MYORG variants related to AR-PFBC were evaluated. The ages of symptom onset of the patients ranged between 7.5 and 87 years. The most frequent clinical courses were speech impairment, movement disorder and cerebellar signs. All patients showed basal ganglia calcification usually bilaterally with different severities. Conclusion; herein, we reported the first pediatric patient in the literature who had a novel homozygous variant in the MYORG gene with mild clinic findings.

Overview of therapeutic plasma exchange in pediatric neurology: a single-center experience.

Therapeutic plasma exchange (TPE) is used in the treatment of neurological, hematological, renal and autoimmune diseases with known or suspected immune pathogenesis. In comparison with neurological diseases of adults, knowledge about the use of TPE in children is incomplete. We report our experience on TPE in children with neurological diseases in a single institution and describe the underlying etiology, clinical course, treatment and outcome. We retrospectively evaluated 22 consecutive children (12 girls, 10 boys, aged 2-16 years) who underwent TPE in the pediatric intensive care unit between January 2010 and January 2017. There were 135 TPE procedures with median 6 TPE sessions per patient. Fresh frozen plasma was used as a replacement fluid in all cases. Most common indications were inflammatory polyneuropathy followed by acquired demyelinating diseases of the central nervous system. Other indications were autoimmune encephalitis and paraneoplastic limbic encephalitis. No mortality was recorded during TPE. The complication rate was 2.2% and consisted of transient events like hypotension and allergic reactions. Therapetic plasma exchange is one of the safe methods of treatment for neuroimmunological disorders in children, with Guillain-Barré syndrome as the most common indication.

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.

Neuromyelitis optica mimics the morphology of spinal cord tumors.

Neuromyelitis optica (NMO) is an autoimmune disorder of the central nervous system, that predominantly affects the spinal cord and the optic nerve. Its key features include transverse myelitis, commonly associated with extensive inflammation spanning three or more consecutive vertebral segments. Longitudinal extensive spinal cord lesions can also occur in systemic autoimmune diseases, infections, vascular and metabolic disorders, subsequent to irradiation, intramedullary tumors and paraneoplastic myelopathies. We present a case study of an 8-year-old girl seropositive for antibodies against the aquaporin 4 who displayed longitudinal extensive spinal cord lesions, that was initially misdiagnosed as an intramedullary tumor.

Overview of pediatric peripheral facial nerve paralysis: analysis of 40 patients.

Peripheral facial nerve paralysis in children might be an alarming sign of serious disease such as malignancy, systemic disease, congenital anomalies, trauma, infection, middle ear surgery, and hypertension. The cases of 40 consecutive children and adolescents who were diagnosed with peripheral facial nerve paralysis at Baskent University Adana Hospital Pediatrics and Pediatric Neurology Unit between January 2010 and January 2013 were retrospectively evaluated. We determined that the most common cause was Bell palsy, followed by infection, tumor lesion, and suspected chemotherapy toxicity. We noted that younger patients had generally poorer outcome than older patients regardless of disease etiology. Peripheral facial nerve paralysis has been reported in many countries in America and Europe; however, knowledge about its clinical features, microbiology, neuroimaging, and treatment in Turkey is incomplete. The present study demonstrated that Bell palsy and infection were the most common etiologies of peripheral facial nerve paralysis.

Acute transverse myelitis in a child with Lyme disease and a review of literature.

Acute transverse myelitis is a rare Borellia burgdorferi-related neurologic complication in childhood. We present a 12-year-old girl who was diagnosed with acute transverse myelitis associated with a borreliosis infection. We also review clinical features in all five cases of Borellia burgdorferi-related transverse myelitis in children. We describe here the sixth child with borreliosis-related transverse myelitis.

Vici syndrome associated with sensorineural hearing loss and laryngomalacia.

The phenotypically heterogeneous, autosomal recessive Vici syndrome was first described in 1988 in a sister and brother with oculocutaneous albinism, agenesis of the corpus callosum, cataract, cardiomyopathy, cleft lip, and immunodeficiency. Only 14 cases of Vici syndrome have yet been reported, several involving morphologic and functional defects in addition to those described in the initial case. We report on a 3-month-old Turkish girl with Vici syndrome associated with laryngomalacia, further expanding the clinical spectrum. We also review clinical features in all 15 Vici syndrome patients, to distinguish general from less common signs. To the best of our knowledge, this report is the first of a Turkish patient with Vici syndrome.

Glutaric aciduria type II [corrected] and brain tumors: a case report and review of the literature.

Heritable diseases associated with childhood tumors are sometimes defined as a probable etiologic factor or a coincidence. First of all, we must know the actual number of patients. Herein a case with medulloblastoma associated with glutaric aciduria type II [corrected] is reported for this purpose. A 5-year-old boy was admitted with nausea, vomiting, and lethargy. In medical history, consanguinity and siblings with mental-motor retardation and epilepsy are remarkable. Growth retardation, macrocephaly, lethargy, tremor, bilateral nistagmus, and papilledema were prominent features in physical examination. Noncontrast computed tomography of the brain showed a hyper dense mass in the cerebellar vermis. Gross total resection was made and the histopathology of the tumor was medulloblastoma. Besides medical history and physical findings, radiologic white matter changes in the subcortical, periventricular regions, bilateral basal ganglia, and caudate nuclei in magnetic resonance images other than tumor led us to investigate the child for glutaric aciduria type II [corrected]. The level of the 2-OH glutaric acid was determined as being 12-fold high in the urine. Chemo-radiotherapy was performed after surgery. Our case was the third patient with medulloblastoma in the literature and is still alive with no evidence of the disease 19 months after the initial diagnosis.

Unusual cause of acute neurologic deficit in childhood: primary central nervous system vasculitis presenting with basilar arterial occlusion.

INTRODUCTION: Primary central nervous system (CNS) vasculitis of childhood is a rare disorder. The most common signs and symptoms are acute severe headache and focal neurologic deficit. It should be suspected in children who have an acquired neurologic deficit that remains unexplained after an initial basic evaluation. Diagnosis usually depends on brain magnetic resonance imaging and conventional angiography of cerebral vasculature. Stenosis is the most common angiographic finding and it usually affects the middle cerebral artery and its branches. Anterior and posterior circulation is rarely involved. CASE REPORT: In this report, we describe an 8-year-old boy who presented with vertebrobasilar insufficiency symptoms and primary CNS vasculitis diagnosis was made later.

Epidemiologic, clinical, and imaging findings in brucellosis patients with osteoarticular involvement.

OBJECTIVE: The aim of this study was to assess the epidemiologic and clinical features, complications, imaging findings, and outcomes for brucellosis patients with osteoarticular involvement. SUBJECTS AND METHODS: This prospective study was performed over 4 years (December 2000-December 2004). The subjects were 251 Turkish patients (age range, 2-77 years) who were diagnosed with brucellosis during that period. Joint sonography, radiography, radionuclide bone scintigraphy, and MRI were performed in all patients with osteoarticular and spinal manifestations. RESULTS: The disease was acute in 92 patients (36.7%), subacute in 48 patients (19.1%), and chronic in 111 patients (44.2%). Sonography of the joints showed bursitis in 13 patients (5.2%). Radiography, MRI, and scintigraphy revealed 71 patients (28.3%) with sacroiliitis, 26 (10.4%) with spondylodiskitis, three (1.2%) with acute osteomyelitis, and one (0.4%) with avascular necrosis of the femoral head. All patients received combinations of either two or three antibiotics. Surgery was performed in three patients with spinal instability or radiculopathy. CONCLUSION: Brucellosis is endemic to some regions. MRI is the method of choice for diagnosing osteoarticular and spinal complications of human brucellosis, especially during the early phase. It is important to differentiate tuberculous spondylodiskitis from brucellar spondylodiskitis because proper treatment for each of these diseases can prevent complications. The radiologic findings for these two forms of spondylodiskitis are similar, so serologic testing for brucellosis is necessary in such cases.

Clinical pattern and abdominal sonographic findings in 251 cases of brucellosis in southern Turkey.

OBJECTIVE: The aim of this study was to report the clinical features, complications, abdominal sonographic findings, and treatment outcomes for a series of brucellosis cases in southern Turkey. SUBJECTS AND METHODS: This prospective study involved 251 patients (age range, 2-77 years) who were hospitalized with brucellosis during a 4-year period. Patients were classified as having acute (< 3 months), subacute (3-12 months), or chronic (> 12 months) disease. Physical, laboratory, and abdominal sonographic findings were analyzed. RESULTS: The disease was acute in 92 cases (36.7%), subacute in 48 (19.1%), and chronic in 111 (44.2%). Sonographic examination of the abdomen showed enlarged periportal lymph nodes in 23 patients (9.2%), splenomegaly in 21 (8.4%), hepatomegaly in 15 (6%), pleural effusion in 7 (2.8%), splenic abscesses in 4 (1.6%), splenic cysts in 2 (0.8%), acute appendicitis in 2 (0.8%), and acute acalculous cholecystitis in 1 patient (0.4%). The main hematologic and biochemical manifestations were anemia, elevated erythrocyte sedimentation rate, elevated C-reactive protein, and elevated transaminase levels. All patients were treated with combinations of either two or three antibiotics. Surgery was performed in the patients with acute appendicitis, acute cholecystitis, and multiple splenic cysts. CONCLUSION: Brucellosis is endemic to Turkey. Sonographic examination is the method of choice for diagnosing abdominal complications of human brucellosis. This disease should be included in the differential diagnosis for any patient with enlarged periportal lymph nodes. The specific treatment regimen and duration of therapy should be based on sites of organ involvement and complications.