Effectiveness and Safety of Epilepsy Surgery for Pediatric Patients with Intractable Epilepsy: A Clinical Retrospective Study from a Single-Center Experience.

INTRODUCTION: Pediatric epilepsy surgery is an effective treatment modality for patients with drug-resistant epilepsy (DRE). Early pediatric surgery yields favorable results for DRE in terms of seizure control and neurophysiological outcome. In this study, pediatric patients were categorized based on their age (above 3 years old and below 3 years old) to demonstrate the effectiveness and safety of surgical procedures. METHODS: In this retrospective, single-center study, 60 pediatric patients who underwent epilepsy surgery at Istanbul Faculty of Medicine between 2002 and 2018 were evaluated. Overall morbidity and mortality rates, as well as seizure outcomes of the patients, were assessed and compared based on two age groups: those aged 3 years old or younger and those older than 3 years old. The effectiveness of invasive monitoring was also evaluated in relation to pathological results. The postoperative seizure outcome rates were evaluated using Engel's classification, with an average follow-up period of 8.7 years. RESULTS: Out of the total number of patients, 47 (78.4%) underwent resective surgery, while 13 (21.6%) had palliative surgery. Ten patients (16.6%) had invasive monitoring. Among all patients, 34 were classified as Engel I and II (56.6%), while 26 were classified as Engel III and IV (43.4%) postoperatively. 47% of patients who were under 3 years old, 60.4% of patients who were over 3 years old, and 50% of patients who underwent invasive monitoring had a favorable seizure outcome (Engel I-II). Postoperative morbidity and mortality rates were 35% (n = 21) and 1.6% (n = 1), respectively. CONCLUSION: Pediatric epilepsy surgery is an important treatment modality for preserving cognitive abilities and providing effective treatment for pediatric DRE. In our study, we claim that both invasive monitoring and epilepsy surgery lead to favorable seizure outcomes for all age groups. Further clinical studies should be conducted to provide more reliable data on the safety and effectiveness of the surgery, particularly in patients under the age of three.

Splenic Artery Embolization in a Patient With Intracranial Hemorrhage Due to Refractory Persistent Immune Thrombocytopenia.

BACKGROUND: Managing intracranial bleeding in patients with refractory immune thrombocytopenia is difficult. OBSERVATION: A 16-year-old female refractory to prednisolone, intravenous immunoglobulin, eltrombopag, and cyclosporin exhibited heavy menstrual bleeding requiring packed red blood cell transfusions. Autoimmune antibodies were detected, indicating of lupus, and hydroxychloroquine sulfate was administered. In month 6 following the diagnosis, the patient presented with intracranial hemorrhage. Splenic artery embolization promptly increased platelets, and the patient was discharged without any neurological sequela. In month 5 of embolization, the patient's platelet count continued to exceed 300,000/µL without any medical treatment. CONCLUSIONS: Splenic artery embolization is a life-saving procedure in refractory immune thrombocytopenia.

Recurrent Blistering Skin Lesions and Reversible Monocular Abducens Paralysis in a Patient with CD59 Deficiency.

Congenital CD59 deficiency is an autosomal recessive disease characterized by mild-to-moderate chronic intravascular hemolysis, relapsing demyelinating peripheral neuropathies, and recurrent ischemic central nervous system strokes. We report a 2-year-old Turkish girl with a history of two episodes of Guillain-Barré syndrome-like acute weakness, reversible monocular abducens paralysis, and recurrent blistering skin lesions during periods of upper respiratory tract infections. Reversible monocular abducens palsy and recurrent blistering skin lesions have not been reported previously in cases of congenital CD59 deficiency.

Monogenic lupus due to spondyloenchondrodysplasia with spastic paraparesis and intracranial calcification: case-based review.

Spondyloenchondrodysplasia (SPENCD) is a rare skeletal dysplasia characterized with platyspondyly and metaphyseal lesions of the long bones mimicking enchondromatosis, resulting in short stature. SPENCD often coexists with neurologic disorders and immune dysregulation. Spasticity, developmental delay and intracranial calcification are main neurologic abnormalities. Large spectrum of immunologic abnormalities may be seen in SPENCD, including immune deficiencies and autoimmune disorders with autoimmune thrombocytopenia and systemic lupus erythematosus as the most common phenotypes. SPENCD is caused by loss of tartrate-resistant acid phosphatase (TRAP) activity, due to homozygous mutations in ACP5, playing a role in non-nucleic acid-related stimulation/regulation of the type I interferon pathway. We present two siblings, 13-year-old girl and 25-year-old boy with SPENCD, from consanguineous parents. Both patients had short stature, platyspondyly, metaphyseal changes, spastic paraparesis, mild intellectual disability, and juvenile-onset SLE. The age at disease-onset was 2 years for girl and 19 years for boy. Both had skin and mucosa involvement. The age at diagnosis of SLE was 4 years for girl, and 19 years for boy. The clinical diagnosis of SPENCD was confirmed by sequencing of ACP5 gene, which revealed a homozygous c.155A > C (p.K52T), a variant reported before as pathogenic. Juvenile-onset SLE accounts for about 15-20% of all SLE cases. But, the onset of SLE before 5-years of age and also monogenic SLE are rare. Our case report and the literature review show the importance of multisystemic evaluation in the diagnosis of SPENCD and to remind the necessity of investigating the monogenic etiology in early-onset and familial SLE cases.

Evaluation of mental performance and cognitive functions of children and adolescents diagnosed with radiologically isolated syndrome.

BACKGROUND: Radiologically isolated syndrome (RIS) is a condition characterized by asymptomatic, incidentally detected demyelinating plaques in the CNS in a patient without typical clinical findings of multiple sclerosis (MS). This study aimed to compare the mental status and cognitive functions of child and adolescent RIS cases with healthy controls and to investigate the relationship between psychometric test results and the demyelinating lesion characteristics. METHODS: The mental status and cognitive functions of 12 RIS cases and 12 healthy controls were compared. Semi-structured interviews, behavioral evaluations, depression and anxiety scales, neuropsychological test battery, and an intelligence test were applied for the evaluation of mental state and cognitive functions. These results were compared with the number and localization of demyelinating lesions. RESULTS: Sustained attention, visual-motor coordination, short-term memory skills, and ability to use visual-spatial information were found worse in the RIS group. There was no correlation between mental state and cognitive functions, and the number and localization of demyelinating lesions. CONCLUSION: Our study showed that pediatric RIS cases may have worse cognitive performance than healthy controls, but no correlation was found between the number and location of demyelinating lesions and psychiatric findings. Although it is controversial whether psychiatric disorders and cognitive disabilities have predictive value in terms of MS conversion in pediatric RIS cases, these subjects were not included in the scope of this study.

Angioedema-like presentation as the presenting finding of juvenile myositis and juvenile dermatomyositis in 2 patients.

BACKGROUND: Juvenile dermatomyositis (JDM) is the most common subtype of idiopathic inflammatory myopathies in childhood. Gottron's papules, shawl sign, periorbital heliotrope rash, and periungual telengiectasis are characteristic skin findings of the disease. Besides characteristic skin involvement, some other skin findings, such as angioedema, may be seen prior or in the course of the disease. The presence of angioedema in JDM is emphasized in this report. CASE PRESENTATIONS: We present 2 unrelated girls, aged 2 (case 1) and 12 years (case 2), who had developed symmetrical weakness in the proximal muscles, muscle pain, elevated muscle enzymes and angioedema. Both cases had abnormal muscle magnetic resonance imaging findings, suggestive of inflammatory myositis. Muscle biopsy was performed only in case 1, and major histocompatibility complex-1 expression on myofibers was shown consistent with JDM. Cases were diagnosed as probable and definite JDM, respectively. Angioedema was prominent, particularly in the lips and extremities of both cases, without laboratory evidence of C1 inhibitor deficiency or capillary leak syndrome, and absence of family history. Mast cell-mediated, acquired angioedema was the most likely diagnosis. In both cases, skin and muscle findings improved significantly with steroid treatment. CONCLUSION: We suggest that angioedema may be among the characteristic skin findings in JDM, and may be included in subsequent definitions.

Acute flaccid myelitis outbreak through 2016-2018: A multicenter experience from Turkey.

AIM: We aim to describe the demographic characteristics, etiology, neurophysiology, imaging findings, treatment, prognosis, and prognostic factors of acute flaccid myelitis. METHODS: The clinical data, laboratory test and, magnetic resonance imaging (MRI) results of pediatric patients diagnosed with acute flaccid myelitis according to the Centers for Disease Control criteria between August 1, 2016, and December 31, 2018, from 13 centers in Turkey were reviewed. RESULTS: Of the 34 cases identified, 31 were confirmed (91.2%). Eighteen patients (55.9%) were boys. The median patient age was 4 years (interquartile range 2.5-6.9 years). Most of the patients were admitted in 2018 (n = 27). A preceding history of a febrile illness was reported in all patients, with a median of 4 days (interquartile range 3-7 days) before symptom onset. Thirty-one patients had T2 hyperintensity on spinal MRI, and 18 patients had cerebrospinal fluid pleocytosis. The most common infectious agents were entero/rhinoviruses (n = 5) in respiratory specimens. All patients except one received immunotherapy either alone or in combination. Among 27 patients with follow-up data 24 had persistent weakness. Involvement of four limbs together with an abnormal brain MRI at onset were associated with a poor prognosis. CONCLUSION: The number of patients with acute flaccid myelitis increased since 2012, spiking with every 2-year interval, largely in the pediatric population. The median age decreases with every outbreak. Clinicians should be aware of the clinical picture for early collection of specimens and early start of rehabilitation programs. Further studies are needed to better characterize the etiology, pathogenesis, risk factors, and treatment of this rare condition.

Acute ophthalmoparesis and persistent mydriasis: expanding the clinical spectrum of anti-GQ1b positive cranial neuropathy in a 5.5-year-old girl.

Sakarya Günes A, Maras Genç H, Uyur Yalçin E, Yilmaz V, Saruhan Direskeneli G, Kara B. Acute ophthalmoparesis and persistent mydriasis: expanding the clinical spectrum of anti-GQ1b positive cranial neuropathy in a 5.5-year-old girl. Turk J Pediatr 2019; 61: 794-797. Acute ophthalmoparesis without ataxia (AO) is an atypical form of Miller- Fisher syndrome (MFS) and is rare in children. Anti-GQ1b antibodies can be detected in patients with AO, as in MFS. A 5.5-year-old girl had total ophthalmoparesis, blurred vision, ptosis, diplopia and mydriasis non-reactive to light or near stimuli with preserved consciousness and deep tendon reflexes. She had no ataxia. Cerebrospinal fluid (CSF) examination and cranial MRI were normal. Serum antiGQ1b antibodies were positive. She was diagnosed with AO and intravenous Immunoglobulin (IVIG) was ordered, 400 mg/ kg/day, for 5 days. Ophthalmoparesis and blurred vision improved in a few weeks. At the end of the first year, mydriasis still persisted, but improved and became responsive to near stimuli. Pupillary involvement may be seen in approximately 50% of MFS patients, and improvement in a few weeks or months has been reported in adults. Our case shows the expanding clinical spectrum of anti-GQ1b positive cranial neuropathy as early-onset AO and prolonged mydriasis more than one year.

Evaluation of the association between sexual dysfunction and demyelinating plaque location and number in female multiple sclerosis patients.

Purpose To investigate the frequency of sexual dysfunction (SD) in female multiple sclerosis (MS) patients and to explore its association with the location and number of demyelinating lesions. Material and Methods We evaluated 42 female patients and 41 healthy subjects. All patients underwent neurological examination and 1.5 T brain and full spinal MRI. All subjects completed the female sexual function index (FSFI), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and Short-Form 36 Quality of Life Scale (SF-36). All participants were also evaluated for serum thyroid stimulating hormone (TSH), T4, estradiol, and total testosterone. Results No statistically significant differences between the MS and control groups were found for age, body mass index (BMI), serum TSH, T4, E2, and total testosterone level. MS patients had a statistically significantly lower FSFI and SF-36 scores and higher BDI and BAI scores compared with healthy subjects. The location and number of demyelinating lesions were not associated with SD. Conclusion In our cohort, this difference in SD appears unrelated to the location and number of demyelinating lesions. These findings highlight the importance of the assessment and treatment of psychiatric comorbidities, such as depression and anxiety, in MS patients reporting SD.

Long-term clinical and radiologic follow-up of Schilder's disease.

BACKGROUND: Schilder's disease is a rare, subacute, or chronic demyelinating disorder that mainly affects children and generally shows a monophasic course. CASE: Here, we present three boys diagnosed with Schilder's disease, age at onset 10-14 years, and followed up for 4-8 years. All of them presented with headache, two with encephalopathy and vomiting, and one with diplopia and vertigo. Cranial magnetic resonance imaging (MRI) showed two large demyelinating lesions, asymmetric in two patients and symmetric in the other. They were treated with steroid therapy. There were no radiologic relapses after discontinuation of corticosteroid therapy in all patients, but clinical attack without objective clinical findings was observed in one patient. Mild memory deficits and decline in school performance were the only neurologic sequelae in two patients. Cranial MRI findings showed significant shrinkage, but persistent T2-weighted hyperintensity of white matter lesions and loss of ring contrast enhancement at the end of the steroid therapy. There were no differences between the radiologic findings at the end of the steroid therapy and subsequent follow-ups. CONCLUSION: Although Schilder's disease is considered to be a variant of MS, it behaves more like ADEM with its monophasic course, and low recurrence rates. Radiologic features include shrinkage of mass lesions after steroid therapy, but sequel lesions remain same at the subacute and chronic stage.

Pyruvate dehydrogenase-E1α deficiency presenting as recurrent acute proximal muscle weakness of upper and lower extremities in an 8-year-old boy.

The mitochondrial pyruvate dehydrogenase enzyme complex (PDHC) plays an important role in aerobic energy metabolism and acid-base equilibrium. PDHC contains of 5 enzymes, 3 catalytic (E1, E2, E3) and 2 regulatory, as well as 3 cofactors and an additional protein (E3-binding protein) encoded by nuclear genes. The clinical presentation of PDHC deficiency ranges from fatal neonatal lactic acidosis to chronic neurologic dysfunction without lactic acidosis. Paroxysmal neurologic problems such as intermittent ataxia, episodic weakness, exercise-induced dystonia and recurrent demyelination may also be seen although they are rare. Here, we present an 8-year-old boy complaining of acute proximal muscle weakness of upper and lower extremities with normal mental status. He had a history of Guillain-Barré-like syndrome at the age of 2 years. Electrophysiologic studies showed sensorial polyneuropathy findings in the first attack and sensorimotor axonal polyneuropathy findings in the last attack. The genetic analysis revealed a previously reported hemizygote novel mutation of the PDHA1 gene (p.A353T/c.1057G > A), which encodes the E1α subunit of PDHC. Thiamine was ordered (15 mg/kg/day), dietary carbohydrates were restricted and clinical findings improved in a few weeks. This rare phenotype of PDHC deficiency is discussed.

The frequency of late-onset Pompe disease in pediatric patients with limb-girdle muscle weakness and nonspecific hyperCKemia: A multicenter study.

The aim of this multicenter study was to screen for late-onset Pompe disease in high-risk children with limb-girdle muscle weakness and nonspecific hyperCKemia using the dried blood spot (DBS) test. Seventy-two children from four pediatric neurology departments in Turkey were enrolled in the study: 37 with limb-girdle muscle weakness and 35 with nonspecific hyperCKemia. Acid α-glucosidase (GAA) activity was measured on DBS by tandem mass spectrometry. Six patients tested positively for Pompe disease. In three patients, one with the limb-girdle muscle weakness and two with nonspecific hyperCKemia, this was confirmed by genetic analysis. The overall frequency of late-onset Pompe disease in the study population was 4.2%. The c.1784C>T mutation found in one patient is a new mutation whereas the c.1655T>C mutation detected in the other two patients is not novel. In conclusion, Pompe disease should be suspected in patients with limb-girdle muscle weakness and nonspecific hyperCKemia. The DBS test is a safe and reliable method of diagnosis but must be confirmed by genetic analysis. In patients with a positive DBS test and negative genetic analysis, tissue assay of GAA should be considered.