Surgical Treatment of a Seven-Year-Old Boy with Refractory Epilepsy Due to Focal Cortical Dysplasia, Case Report

The most common developmental malformation encountered in patients with refractory epilepsy is Focal Cortical Dysplasia (FCD). Malformations of cortical development, in particular FCDs are identified in 20–25% of patients with focal epilepsy, and approximately 76% of these patients are supposed to suffer from drug-resistant epilepsy. A promising therapy option for these patients could be surgical treatment. We present a seven-year-old child with drug-resistant epilepsy, who underwent surgical treatment that had an excellent outcome. Throughout the period of five years, the index patient was admitted several times to the Department of Neurology at the University Pediatrics Clinic-Skopje. He was initially admitted at the age of two years, because of his first episode of febrile seizures accompanied by diarrhea. In the following period, during the hospitalization, febrile seizures also developed. CT findings showed a slight degree of front parietal cortical reduction, while the first MRI showed a slight dysmorphia at the frontal gyri, yet no focal abnormalities. The initial EEG revealed a bihemispheric epileptogenic focus. The reason for constant treatment alterations was drug-resistance. Although some encephalographic stabilization had been achieved, a full clinical response had never been obtained for a prolonged period. At the age of seven years, a pediatric epilepsy surgical team at the University School of Medicine–ACIBADEM, Turkey, evaluated the patient. The conclusion of the team was that the child is a candidate for surgical treatment of epilepsy. The child underwent surgery at the age of eight years and has been seizure free since.Keywords: Focal Cortical Dysplasia, Epilepsy, Surgery

LAMA2–ASSOCIATED CONGENITAL MUSCULAR DYSTROPHY: CASE REPORT

Introduction: LAMA2 Associated Muscular Dystrophy (LAMA2-RD) is one of the most common forms of congenital muscular dystrophy worldwide. Mutations in the LAMA2 gene affect the production of the α2 subunit of lamin-211 (merosine) and result in partial or complete deficiency of lamin-211. Inheritance is usually autosomal recessive.Case report: We present a patient who is dual heterozygous for two pathogenic variants in the LAMA2 gene, as demonstrated by targeted resection of 4800 clinically significant genes. c.4474dupT, p. (Tyr1492LeufsTer11), inherited from the mother and c.7732C> T, p. (Arg2578Ter), inherited from the father. With this genotype the patient is confirmed autosomal recessive disease, LAMA2-RD. Variant c.4474dupT, p. (Tyr1492LeufsTer11), in exon 31 of the LAMA2 gene, is a change that has not been reported in the literature.Conclusion: Genetic confirmation of the diagnosis is important for genetic counseling, prenatal diagnosis for each subsequent pregnancy in the family because the risk of an affected child is 25%.Keywords: LAMA2 associated muscular dystrophy, genetic testing of clinically relevant genes, genetic counseling

Need for Developmental Assessment

Introduction: When we start our work as medical professionals the most important was improving and understanding physical growth and nutrition. Today we know that as much important as good knowledge in physical examination is adequate assessment of personality and social development which is crucial for appropriate developmental assessment. In this context early identification of developmental delay is not just responsibility but either obligation of all health care professionals, especially pediatricians. Aim of the Study: The aim of this study is to analyze developmental monitoring based on parents informations in our hospital in order to find out which percentage of referred children has to be followed further and has to start with early intervention. Our ap�proach to developmental monitoring is: we start the pediatric assessment by taking very careful history of child. Second step is very careful examination in order to find if the child has same kind of organ dysfunction. In second step crucial is neurological examination especially if we know that children with developmental disabilities have very high rate of seizure disorder, structural MRI abnormali�ties - especially frontal atrophy… Pediatrician has to be aware that observation of the parent-child interaction also, may be an aid in identifying children with delayed development. Methodology and Sample: The developmental monitoring in 465 children at the age of 12 - 60 months, referred as children with developmental delay according to primary care pediatricians, special educators or family members in the period of 4 years (from January 2016 until the end of 2019) was implemented. The assessment of the evaluated sample is done using CDC developmental milestone checklist (Centers for Disease Control and Prevention) for specific ages -12 and 18 months and 2,3,4 and 5 years. To assess behavioral and emotional problems, physicians need information from family and people who see children in their everyday contexts. Results: The results were presented for each group separately. Conclusion: Research indicates that the first five years of a child’s life are critical to brain development, academic achievement and later life outcomes. The right developmental and behavioral assessment can change the trajectory of a child’s life forever

Phenylketonuria screening and management in southeastern Europe - survey results from 11 countries

Background: We aimed to assess the current state of PKU screening and management in the region of southeastern Europe. Methods: A survey was performed involving all identified professionals responsible for the PKU management in the 11 countries from South-Eastern region of Europe (Albania, Bulgaria, Bosnia and Herzegovina, Croatia, Kosovo, Macedonia, Moldova, Montenegro, Romania, Serbia, Slovenia). The questionnaire was designed to assess the characteristics regarding PKU management in three main areas: nation-wide characteristics, PKU screening, and characteristics of the PKU management in the responding centre. It consisted of 56 questions. The distribution and collection of the questionnaires (via e-mail) was taking place from December 2013 to March 2014. Results: Responses from participants from 11 countries were included; the countries cumulative population is approx. 52.5 mio. PKU screening was not yet introduced in 4 of 11 countries. Reported PKU incidences ranged from 1/7325 to 1/39338 (and were not known for 5 countries). National PKU guidelines existed in 5 of 11 countries and 7 of 11 countries had PKU registry (registries included 40 to 194 patients). The number of PKU centers in each country varied from1 to 6. Routine genetic diagnostics was reported in 4 of 11 countries. Most commonly used laboratory method to assess phenylalanine levels was fluorometric. Tetrahydrobiopterine was used in only 2 of 11 countries. Most frequently, pediatricians were caring for the patients. Dietitian was a member of PKU team in only 4 of 11 countries, while regular psychological assessments were performed in 6 of 11 countries. Patient's PKU society existed in 7 of 11 countries. Conclusions: The region of southeastern Europe was facing certain important challenges of PKU screening and management. Neonatal PKU screening should be introduced throughout the region. Furthermore, PKU management was falling behind internationally established standards-of-care in many aspects

Phenylketonuria screening and management in southeastern Europe - survey results from 11 countries

Background: We aimed to assess the current state of PKU screening and management in the region of southeastern Europe. Methods: A survey was performed involving all identified professionals responsible for the PKU management in the 11 countries from South-Eastern region of Europe (Albania, Bulgaria, Bosnia and Herzegovina, Croatia, Kosovo, Macedonia, Moldova, Montenegro, Romania, Serbia, Slovenia). The questionnaire was designed to assess the characteristics regarding PKU management in three main areas: nation-wide characteristics, PKU screening, and characteristics of the PKU management in the responding centre. It consisted of 56 questions. The distribution and collection of the questionnaires (via e-mail) was taking place from December 2013 to March 2014. Results: Responses from participants from 11 countries were included; the countries cumulative population is approx. 52.5 mio. PKU screening was not yet introduced in 4 of 11 countries. Reported PKU incidences ranged from 1/7325 to 1/39338 (and were not known for 5 countries). National PKU guidelines existed in 5 of 11 countries and 7 of 11 countries had PKU registry (registries included 40 to 194 patients). The number of PKU centers in each country varied from1 to 6. Routine genetic diagnostics was reported in 4 of 11 countries. Most commonly used laboratory method to assess phenylalanine levels was fluorometric. Tetrahydrobiopterine was used in only 2 of 11 countries. Most frequently, pediatricians were caring for the patients. Dietitian was a member of PKU team in only 4 of 11 countries, while regular psychological assessments were performed in 6 of 11 countries. Patient's PKU society existed in 7 of 11 countries. Conclusions: The region of southeastern Europe was facing certain important challenges of PKU screening and management. Neonatal PKU screening should be introduced throughout the region. Furthermore, PKU management was falling behind internationally established standards-of-care in many aspects

ВажноÑÑ‚ на 6 минутниот теÑÑ‚ на одење во дијагноÑтика на ретка метаболна миопатија – приказ на Ñлучај на карнитин палмитоил транÑфераза 2 дефицит

Diagnosis of rare inherited neuromuscular disorders is sometimes delayed due to variations in time of onset, different clinical appearance and limited diagnostic possibilities. The management of patients  starts  with neurological examination, followed by  specific laboratory tests  and neurophysiologic assessment. In the  era of molecular medicine, molecular biology tools are useful in avoiding some of the invasive investigations such as muscle biopsy. We present a boy with a mild form of metabolic myopathy due to carnitine  palmitoyltransferase  2 deficiency diagnosed upon timed functional assessment. A child had delayed developmental milestones, associated with fatigue and muscle pain during exercising and longer walks. There were no episodes of myoglobinuiria during exercise or during febrile illnesses. Neurological examination reveled proximal muscle weakness. Serum creatine kinase (CK) and serum lactate were above normal limits. Serum acylcarnitine profile was normal. Short timed functional tests such as 10 meters  walk/run test  showed normal results. Nord Star Ambulatory Assessment showed difficulties in balance and jumping. Diagnosis of myopathy was suspected after performance of 6-minute walk test, when the passed distance was 327 meters with slowing and fatigue. EMG and echocardiography were within normal range. Diagnosis was established by sequencing  of the CPT II gene which revealed   c.338C>T (p.Ser113Leu) mutation in homozygous form as characteristic CPT II deficiency profile.Дијагнозата на ретките невромуÑкулни заболувања е понекогаш пролонгирана заради различното вре- ме на почеток на Ñимптомите, различната клиничка Ñлика и ограничените дијагноÑтички можноÑти. Обработката на пациентот започнува Ñо невролошки преглед, по што Ñледат Ñпецифични лаборато- риÑки теÑтови и неврофизиолошки иÑпитувања. Во ера на молекуларната медицина, генетÑката анали- за овозможува да Ñе избегнат некои од инвазивните иÑпитувања, како на пример муÑкулната биопÑија. Прикажуваме момче Ñо блага форма на метаболичка миопатија Ñо карнитин палмитоил транÑфераза 2 (CPT II) дефицит, која е дијагноÑтицирана врз оÑнова на временÑка функционална проценка. Детето имало забавен моторен развој, Ñо замор и муÑкулна болка во тек на вежбање или подолго одење. Ðема- ло епизоди на миоглобинурија во тек на вежбање или во тек на фебрилни болеÑти. Ðевролошкиот пре- глед покажа прокÑимална муÑкулна ÑлабоÑÑ‚. СерумÑката креатин киназа и ÑерумÑкото ниво на лакта- ти беа над нормалните граници. СерумÑкиот профил на ацил карнитини беше нормален. Кратките функционални теÑтови како 10 метри одење/трчање покажаа уредни резултати. Nord Star Ambulatory Assessment  – теÑтирањето покажа потешкотии во рамнотежата и при Ñкокање. Сомнение за вродена миопатија Ñе поÑтави по изведување на подолготраен функционален теÑÑ‚ – 6-минутниот теÑÑ‚ на одење кога поминатата  Ð´Ð¸Ñтанца беше 327 метри Ñо уÑпорување и замор. Електроневромиографијата и ехо- кардиографијата кај детето покажаа нормални наоди. Дијагнозата беше потврдена Ñо Ñеквенциони- рање на CPT II генот Ñо региÑтрирање на c.338C>T (p.Ser113Leu) мутација  Ð²Ð¾ хомозиготна форма која е карактериÑтична за CPT II дефицит

Компарација на шеÑÑ‚ минутниот теÑÑ‚ на одење кај деца Ñо различни невромуÑкулни болеÑти и здрави деца на возраÑÑ‚ од 5 до 14 години

The aim of this study was to determinate the importance of 6MWT in children diagnosed with neuromuscular diseases. We evaluated the distances walked and the level of fatigue manifested. The data were correlated with the distances walked by healthy children at the same age. Materials and methods: Eleven children diagnosed with neuromuscular diseases such as Duchenne muscular dystrophy   (6), congenital myopathy  (2), myasthenia gravis (2)  and SMA type 3 (1)  performed the6-minute walk test (6ÐœWT) according to ATS statement: guidelines for the six-minute walk test. Weakness and fatigue were registered in the examined group. Collected data were correlated with the results obtained from a group of healthy children at the same age and gender. Percent-predicted distance on the 6MWT was computed from normative values to determine weakness, excluding the influence of age and height of the children on 6MWT results. Fatigue was determined by the percentage of decrement in distance walked from the first to sixth minute. Results: Fatigue was registered in 52% of all children with neuromuscular diseases. Student's t-test showed a statistically significant difference between the average distance walked from 1-6  minute by children with neuromuscular diseases compared to average distance walked by healthy children at the same age and the result was t = 6.2381 P < 0.0001 with 95% CI and DF10. Pearson's correlation coefficients showed a strong negative linear correlation (r= -0.913897 p <0.01) between fatigue and percent- predicted 6MWT distance in children with neuromuscular diseases. Conclusion: The 6-minute walk test has proven diagnostic value in newly evaluated patients suspected of having a neuromuscular disease. It has a monitoring value for follow-up of disease progression and the effectiveness of treatment.Целта на трудот е да Ñе утврди значењето на 6-минутниот теÑÑ‚ на одење кај деца Ñо невромуÑкулни бо- леÑти. Во Ñтудијата беа евалуирани поминатите диÑтанци, како и Ñтепенот на замор кај иÑпитаниците. Резултатите од теÑтирањето Ñе корелирани Ñо диÑтанците поминати од групата здрави деца на иÑта возраÑÑ‚. Материјал и методи: ЕдинаеÑет деца Ñо дијагноÑтички потврдени невромуÑкулни болеÑти, муÑкулна диÑтрофија на Duchenne (6), конгенитална миопатија (2), мијаÑтенија Ð³Ñ€Ð°Ð²Ð¸Ñ (2) и Ñпинална муÑкулна атрофија (1), го изведоа 6-минутниот теÑÑ‚ на одење (6-minute walk test, 6ÐœWT), почитувајќи го протоколот Ñпоред ÐТС правилата (ATS statement: guidelines for the six-minute walk test). СлабоÑÑ‚ и замор беа забележани кај изведување на 6-минутниот теÑÑ‚ на одење од Ñтрана на иÑпитуваната група. Резултатите беа Ñпоредени Ñо поÑтигањата и резултатите од овој теÑÑ‚ кај 11 здрави деца на иÑта возраÑÑ‚ и пол Ñо иÑпитаниците. За да Ñе процени Ñтепенот на ÑлабоÑÑ‚ беше одредуван процент од предиктивната вредноÑÑ‚ на поминатата диÑтанца за 6 минути Ñпоред нормативни Ñкали, Ñо цел да биде иÑклучено влијанието на возраÑта и виÑината на децата врз вредноÑтите нa 6MWT. Заморот беше изразен како процент на намалување на поминатата диÑтанца за време од 1 минута мерено од првата кон шеÑтата минута. Резултати: Замор бешe региÑтриран кај 52% од Ñите теÑтирани деца Ñо не- вромуÑкулни болеÑти. Student-овиот t-теÑÑ‚ покажа поÑтоење на ÑтатиÑтички значајна разлика помеѓу Ñредната вредноÑÑ‚ од поминатите диÑтанци од првата до шеÑтата минута кај децата Ñо невромуÑкулни болеÑти Ñпоредено Ñо Ñредната вредноÑÑ‚ од поминатите диÑтанци кај здравите  Ð²Ñ€Ñници (t = 6,2381, P< 0,0001 Ñо интервал на доверба  95% и Ñтепен на Ñлобода  10). Pearson–овите теÑтови на корелација покажаа Ñилна негативна линеарна корелација (r= -0, 913897, p <0, 01) помеѓу заморот  Ð¸ процент од предвидената диÑтанца при 6-минутниот теÑÑ‚ на одење кај децата Ñо невромуÑкулни болеÑти. Заклу- чок: ШеÑÑ‚ минутниот теÑÑ‚ на одење има потврдена дијагноÑтичка важноÑÑ‚ кај новооткриени пациенти под Ñомнение за невромуÑкулна болеÑÑ‚. ИÑто така, тој е значаен метод за Ñледење на Ñтепенот на прогреÑија на болеÑта и ефективноÑта на Ñпроведената терапија

Newborn screening in southeastern Europe

The aim of our study was to assess the current state of newborn screening (NBS) in the region of southeastern Europe, as an example of a developing region, focusing also on future plans. Responses were obtained from 11 countries. Phenylketonuria screening was not introduced in four of 11 countries, while congenital hypothyroidism screening was not introduced in three of them; extended NBS programs were non-existent. The primary challenges were identified. Implementation of NBS to developing countries worldwide should be considered as a priority

Mapping the differences in care for 5,000 Spinal Muscular Atrophy patients, a survey of 24 national registries in North America, Australasia and Europe

Spinal muscular atrophy (SMA) is an autosomal recessive genetic disorder characterised by the degeneration of motor neurons and progressive muscle weakness. It is caused by homozygous deletions in the survival motor neuron gene on chromosome 5. SMA shows a wide range of clinical severity, with SMA type I patients often dying before 2\ua0years of age, whereas type III patients experience less severe clinical manifestations and can have a normal life span. Here, we describe the design, setup and utilisation of the TREAT-NMD national SMA patient registries characterised by a small, but fully standardised set of registry items and by genetic confirmation in all patients. We analyse a selection of clinical items from the SMA registries in order to provide a snapshot of the clinical data stratified by SMA subtype, and compare these results with published recommendations on standards of care. Our study included 5,068 SMA patients in 25 countries. A total of 615 patients were ventilated, either invasively (178) or non-invasively (437), 439 received tube feeding and 455 had had scoliosis surgery. Some of these interventions were not available to patients in all countries, but differences were also noted among high-income countries with comparable wealth and health care systems. This study provides the basis for further research, such as quality of life in ventilated SMA patients, and will inform clinical trial planning