Dyskinetic crisis in GNAO1-related disorders: clinical perspectives and management strategies.

Background: GNAO1-related disorders (GNAO1-RD) encompass a diverse spectrum of neurodevelopmental and movement disorders arising from variants in the GNAO1 gene. Dyskinetic crises, marked by sudden and intense exacerbations of abnormal involuntary movements, present a significant challenge in GNAO1-RD. Objectives: This study aimed to establish a standardized framework for understanding dyskinetic crises, addressing crucial aspects such as definition, triggers, diagnostic criteria, complications, and management strategies. Methods: A Delphi consensus process was conducted involving international experts in GNAO1-RD. The panel of thirteen experts participated in three voting rounds, discussing 90 statements generated through a literature review and clinical expertise. Results: Consensus was achieved on 31 statements, defining dyskinetic crises as abrupt, paroxysmal episodes involving distinct abnormal movements in multiple body regions, triggered by emotional stress or infections. Dyskinetic crises may lead to functional impairment and complications, emphasizing the need for prompt recognition. While individualized pharmacological recommendations were not provided, benzodiazepines and clonidine were suggested for acute crisis management. Chronic treatment options included tetrabenazine, benzodiazepines, gabapentin, and clonidine. Deep brain stimulation should be considered early in the treatment of refractory or prolonged dyskinetic crisis. Conclusion: This consensus provides a foundation for understanding and managing dyskinetic crises in GNAO1-RD for clinicians, caregivers, and researchers. The study emphasizes the importance of targeted parental and caregiver education, which enables early recognition and intervention, thereby potentially minimizing both short- and long-term complications. Future research should concentrate on differentiating dyskinetic crises from other neurological events and investigating potential risk factors that influence their occurrence and nature. The proposed standardized framework improves clinical management, stakeholder communication, and future GNAO1-RD research.

Genetics of Pediatric Epilepsy: Next-Generation Sequencing in Clinical Practice.

Epilepsy is one of the most common neurological disorders with diverse phenotypic characteristics and high genetic heterogeneity. Epilepsy often occurs in childhood, so timely diagnosis and adequate therapy are crucial for preserving quality of life and unhindered development of a child. Next-generation-sequencing (NGS)-based tools have shown potential in increasing diagnostic yield. The primary objective of this study was to evaluate the impact of genetic testing and to investigate the diagnostic utility of targeted gene panel sequencing. This retrospective cohort study included 277 patients aged 6 months to 17 years undergoing NGS with an epilepsy panel covering 142 genes. Of 118 variants detected, 38 (32.2%) were not described in the literature. We identified 64 pathogenic or likely pathogenic variants with an overall diagnostic yield of 23.1%. We showed a significantly higher diagnostic yield in patients with developmental delay (28.9%). Furthermore, we showed that patients with variants reported as pathogenic presented with seizures at a younger age, which led to the conclusion that such children should be included in genomic diagnostic procedures as soon as possible to achieve a correct diagnosis in a timely manner, potentially leading to better treatment and avoidance of unnecessary procedures. Describing and discovering the genetic background of the disease not only leads to a better understanding of the mechanisms of the disorder but also opens the possibility of more precise and individualized treatment based on stratified medicine.

Needs and Experiences of Children and Adolescents with Pediatric Multiple Sclerosis and Their Caregivers: A Systematic Review.

In the present study we conduct a systematic review to evaluate the needs and experience of people with pediatric multiple sclerosis (MS) and their caregivers. The literature search was conducted across 10 academic databases, adhering to PRISMA-P guidelines. Quality appraisal was conducted using the mixed method appraisal test for individual studies, and GRADE-CERQual to establish overall confidence of findings. Results were analyzed using a process of narrative synthesis. We identified 26 studies which included 2253 children/adolescents with MS (CAMS) and 1608 caregivers. MS was reported to negatively impact experiences for CAMS in domains such as of school performance, social relationships, mental health, and overall physical functioning. Specifically, fatigue and social support were reported as the most important barriers and facilitators for CAMS, respectively. In terms of caregiver experience, negative impacts were reported on social functioning, mental health, and quality of life. Additionally, lack of awareness concerning MS was one of the biggest challenges reported. Caregivers expressed needs for psychological and social support. This study provides the first evidence regarding the needs and experiences of CAMS and their caregivers. Findings can be used to address policy gaps for supporting families affected by pediatric MS.

ASSOCIATION BETWEEN APOLIPOPROTEIN E POLYMORPHISMS AND EPILEPSY IN CHILDREN.

Apolipoprotein E (APOE) plays an important role in lipid metabolism and is a proven risk factor for development of dementia and other neurodegenerative diseases. The aim of the study was to determine the possible connection between particular APOE alleles, blood lipid profile and different types of epilepsy in children. Alleles of the APOE gene, blood cholesterol (total, high-density lipoprotein and low-density lipoprotein (LDL) cholesterol, and triglyceride levels were analyzed in blood samples of 111 children with epilepsy and 118 age- and sex-matched children without epilepsy. Distribution of APOE genotypes was the same in children of both groups. Significantly increased levels of total cholesterol and LDL cholesterol were found in control group (Z=3.49 and 3.52 respectively, p<0.01). No statistically significant difference was found between the genotypes of children with idiopathic and symptomatic epilepsy (χ2=1.96; df=2; p>0.05). There were statistically significant differences in the levels of total cholesterol (Z=2.09; p<0.05) and LDL cholesterol (Z=2.05; p<0.05) according to the type of epilepsy in favor of symptomatic epilepsy. The study confirmed that there was no connection between APOE and type of epilepsy in children and showed the children with epilepsy to have lower total cholesterol and LDL cholesterol levels. Interestingly, this also held true for children with idiopathic epilepsy compared to those with symptomatic condition.

POSTERIOR CORTEX SEIZURES - PEDIATRIC CHALLENGES.

Posterior cortex seizures have a complex semiologic presentation that is especially challenging in the pediatric population. Therefore, using clinical presentation in localizing ictal involvement is not sufficient in children, thus making this type of epilepsy quite under-recognized. As most of the ictal symptoms are subjective and could well be overshadowed by symptoms arising from adjacent cortices, primarily temporal and central ones, it is necessary not to overlook this large source of pharmacoresistant epilepsies. The parietal lobe as part of an extensive synaptic network is a great imitator, thus quite often producing inaccurate localization readings on scalp electroencephalography (EEG) due to very scattered interictal discharges and uninformative ictal recordings. Using direct cortical recordings in delineating the epileptogenic zone is helpful in some cases but even highly experienced epileptologists may erroneously interpret some features as arising from other localizations, especially the frontal lobe. Epilepsy surgery from the posterior quadrant is still quite rare and relatively unsuccessful, especially in non-lesional epilepsies due to elaborate mechanisms of connectivity, misleading semiology, and non-localizing EEG recordings, possibly due to insufficiency of parietal cortex synchronicity. Applying the aforementioned to the pediatric age makes it perhaps the most difficult challenge for a pediatric epileptologist.

APPEARANCE OF NEURODEVELOPMENTAL DISORDERS IN CHILDREN DELIVERED POST-TERM: A CROSS-SECTION STUDY.

GOAL: To analyze the appearance of neurodevelopmental disorders in children delivered post-term and to find out whether prolonged pregnancy may be a cause of such disorders in a selected group participants. PATIENTS AND METHODS: This study included a cohort of 34 children born post-term suffering from neurodevelopmental disorders who were treated at the Service for psycho-physiological and speaking disorders in Mostar, Bosnia and Herzegovina during an 18-year period. RESULTS: There were 59.4% of male and 40.6% female patients (P=0.002). The most common neurodevelopmental disorder in the sample was intellectual disability (38.2%), followed by epilepsy (26.4%), delayed psychomotor development (14.7%), and cerebral palsy (11.7%) (P<0.001). The correlation between mothers' parity and post-term delivery was found (P=0.016). CONCLUSION: Post-term delivery may be the cause of neurodevelopmental disorders. The most common disorder among them were intellectual difficulties.

Sphenoid sinus aspergilloma in trans-sphenoidal surgery for pituitary adenomas.

BACKGROUND: Simultaneous appearance of sphenoid sinus aspergilloma and pituitary adenoma is a very rare finding. METHODS: Retrospective analysis of patients with sellar and sphenoid sinus mass lesions who underwent trans-sphenoidal surgery was performed. Demographic data, medical history, predisposing factors, clinical picture, neurological status and radiological findings were reviewed. All patients underwent a trans-sphenoidal microsurgical treatment, and acquired specimens underwent both histopathological and microbiological analysis. RESULTS: Sphenoid sinus aspergilloma was encountered in seven patients. Three patients had an isolated sphenoid sinus aspergilloma and four patients with pituitary macroadenoma had a sphenoid aspergilloma as an incidental finding. CONCLUSIONS: Sphenoid sinus aspergilloma can be found during trans-sphenoidal surgery for pituitary adenomas. Sphenoid sinus extirpation followed by adenomectomy is the treatment of choice unless invasive aspergilloma is encountered requiring additional antifungal therapy.

Surgical treatment of prolactinomas--our experience.

The dilemma of whether to apply surgical or drug treatment to prolactinomas has been ongoing for the past 30 years. The aim of this study is to compare the early postoperative values of prolactin (PRL) in two groups of patients with prolactinomas: those who underwent primary surgical-treatment, and those who underwent surgery after a dopamine agonist (DA) therapy. We present the results of surgical treatment on a series of 161 patients with prolactinomas. Surgery was the primary treatment in 65 patients, while 96 patients had surgery following a long-term treatment with a DA. All surgically treated prolactinomas were operated in the standard transsphenoidal, microsurgical approach. The criteria for hyperprolactinemia remission was a PRL level under 25 ng/ml. Early normalization of PRL was achieved in 92% of those patients who underwent primary surgical-treatment, yet it was achieved in only 42% of patients who were operated on after receiving a long-term drug treatment with a DA. The highest prevalence of postoperative normalization of PRL was achieved in a group of patients with microadenomas who were primarily operated on (98%). The worst results in postoperative normalization of PRL were found in the group of patients with macroadenomas who received a long-term drug treatment with a DA first. These results show our surgical experience in treating prolactinomas. Using surgical treatment, the best clinical outcome was achieved with microprolactinomas and intrasellar, well-confined macroprolactinomas. Nevertheless, we stress the need of an individualized approach and recommend treatment in multidisciplinary centres for pituitary diseases.

The importance of ambulatory blood pressure monitoring in children and adolescents.

The objective of this study was to present our data on ambulatory blood pressure monitoring (ABPM) in children and adolescents referred to our Department because of casual BP elevation over the 95th percentile on at least 3 visits in primary care office. ABPM studies in 139 children, 94 boys and 45 girls, mean age 14.14 (range 4-19) years, were reviewed. A total of 107 (76.98%) children had hypertension according to the ABPM criteria. Primary hypertension (PH) was diagnosed in 89 (64.03%), secondary hypertension (SH) in 18 (12.95%) and white coat hypertension (WCH) in 32 (23.02%) children. In both PH and SH groups, hypertension was predominantly systolic (60.67% and 55.56%, respectively). There was no statistically significant difference in diurnal and nocturnal systolic and diastolic blood pressure (BP) loads between PH and SH groups. The non-dipping phenomenon was detected in 49.44%, 66.66% and 40.62% of children with PH, SH and WCH, respectively. The mean pulse pressure values were 60.41, 58.58 and 52.25 mm Hg in the PH, SH and WCH groups, respectively. A statistically significant difference was found in pulse pressure values between PH and WCH (df=55, t=6.15, P<0.01) groups and between SH and WCH groups (df=31, t=3.18, P=0.001). Target organ damage was diagnosed in 16 (17.98%) children with PH and in 5 (27.78%) children with SH. None of the children with WCH had target organ damage. ABPM is indispensable for establishing the diagnosis of hypertension in children. It is the only reliable method of WCH diagnosis.

Postnatal evaluation and outcome of infants with antenatal hydronephrosis.

This study was aimed at evaluating the clinical outcome of infants with antenatally diagnosed hydronephrosis. Our objective was also to determine whether there is a significant correlation between anterior posterior pelvic diameter (APPD) and urinary tract abnormalities detected. We retrospectively analyzed data of 145 infants collected between January 2000 and May 2010. Inclusion criteria were the presence of APPD > or = 5 mm on prenatal US scan after 20 weeks of gestation, at least 6-month follow-up and at least two postnatal US scans. Most patients underwent renal scintigraphy (n = 140, 96.6%) and micturating cystourethrography (n = 141, 97.2%). Of 145 infants, 77 (53.1%) had idiopathic or transient hydronephrosis. The second most common diagnosis was vesicoureteral reflux found in 21 (14.4%) infants, followed by ureteropelvic junction obstruction without significant kidney damage found in 18 (12.4%) infants. The relative risk of significant urologic abnormality according to the degree of antenatal hydronephrosis (ANH) was 21.25 (95% CI: 2.95-156.49) for severe ANH, 1.57 (95% CI: 0.94-2.62) for moderate ANH and 0.47 (95% CI: 0.33-0.66) for mild ANH. There was a significant increase in the riskper increasing degree of hydronephrosis. In 19 out of 145 (13.2%) infants, immediate surgery was required. These data support the need of antenatal detection and long-term postnatal follow-up of infants with ANH.

Oblique transsphenoethmoidal approach to the cavernous sinus.

Pituitary adenomas frequently invade the cavernous sinus. The standard transsphenoidal approach does not provide satisfactory visualization of the cavernous sinus structures. The transcranial approach has no advantages, and increases the operative trauma and complications. The oblique transsphenoethmoidal approach, a modified standard transsphenoidal approach, was used to treat 19 patients with pituitary adenomas invading the cavernous sinus. Complete tumor removal was achieved in 15 patients and subtotal removal in 4 patients. The patients tolerated this modified transsphenoethmoidal approach well and the postoperative results were satisfactory. Although the number of patients was too small to allow any statistical analysis, the results, compared with other series, are encouraging.

Reversible "brain atrophy" in patients with Cushing's disease.

During the past 25 years, we came across 60 patients with corticotroph pituitary adenomas and Cushing's disease. Neuroradiological examination showed prominent volume loss of the brain parenchyma, unexpected for the patient's age. This "brain atrophy" appeared to regress after surgical removal of pituitary adenoma and normalization of cortisol level. Observed difference between degree of "brain atrophy" in the Cushing's disease group and in the control group was statistically significant (p < 0.001). The degree of "brain atrophy" correlated well with the duration of Cushing's disease. Partial reversibility of "brain atrophy" was noticed during the 2nd, 3rd and 4th year after surgery and normalization of cortisol level. Increased cortisol level is one of the causative factors in pathogenesis of "brain atrophy". Loss of brain volume is at least partially reversible after normalization of cortisol levels.