BACKGROUND: Neonatal Hypoxic-Ischaemic Encephalopathy (HIE) increases the risk for neurodevelopmental impairment. Information on school-age memory function is limited in children who received hypothermia treatment (TH) f...BACKGROUND: Neonatal Hypoxic-Ischaemic Encephalopathy (HIE) increases the risk for neurodevelopmental impairment. Information on school-age memory function is limited in children who received hypothermia treatment (TH) for neonatal HIE. OBJECTIVES: To evaluate memory function in school-aged children who had neonatal HIE and TH and survived without major neuromotor impairment. METHOD: Fifty-one children with neonatal HIE and 41 typically developing (TD) peers participated. At age 6-8 years general cognitive abilities (FSIQ) were assessed with Wechsler Intelligence Scale for Children (WISC-V), immediate and delayed visual and verbal memory with Children's Memory Scale (CMS), everyday memory with Rivermead Behavioural Memory Test for Children (RBMT-C), and working memory with WISC-V. Real-life implications were assessed with Behavior Rating Inventory for Executive Function (BRIEF; Parent and Teacher). Group differences were examined and correlations calculated to assess associations between memory measures. Relationship maps illustrate co-occurring impairments. RESULTS: FSIQ was in the normal range for both groups but significantly lower in the HIE group. Children with HIE had significantly more deficits in working memory (20.4 % vs 0 %), verbal immediate (20.0 % vs 2.5 %), verbal delayed (17.8 % vs 2.5 %), visual immediate (28.9 % vs 7.5 %), and everyday memory (38.8 % vs 5.6 %). Relationship maps identified more co-occurring clinical/borderline impairments in children with HIE (45.1 % vs 4.9 %) and more frequent clinical impairments in real-world memory measures. CONCLUSION: Despite hypothermia treatment, and with general cognitive abilities in the normal range, children with neonatal HIE are at risk of memory impairments in multiple domains, affecting everyday functioning at home and school. Timely identification is important for individually targeted support.
Kollia E, Kokkinou E, Outsika C
… +20 more, Koltsida G, Zouvelou V, Vontzalidis A, Dalivigka Z, Veltra D, Sofocleous C, Marinakis NM, Tilemis FN, Yapijakis C, Anagnostopoulou KK, Loukas YL, Spanou M, Dinopoulos A, Nikaina E, Skiathitou AV, Siahanidou T, Georgiadou E, Moudaki A, Lykopoulou E, Pons R
BACKGROUND: Developmental and epileptic encephalopathy (DEE) includes diseases where there is developmental impairment related to both the underlying etiology independent of epileptiform activity and the epileptic enceph...BACKGROUND: Developmental and epileptic encephalopathy (DEE) includes diseases where there is developmental impairment related to both the underlying etiology independent of epileptiform activity and the epileptic encephalopathy. Patients often present with movement disorders (MD). This study aims to delineate the motor phenotype in a cohort of patients with DEE. METHODS: Retrospective review of 82 patients with DEE. MD type and distribution were documented and when available, video recordings were reviewed. RESULTS: Patients were classified into five etiological groups: 30.5 % had a likely genetic diagnosis, 29.3 % a confirmed genetic diagnosis, 18.3 % an inborn error of metabolism (IEM), 14.6 % an acquired brain lesion, and 7.3 % a brain dysplasia. Hyperkinetic MDs were present in 85.4 % of patients, including dystonia (48.8 %), stereotypies (22.0 %), chorea (20.7 %), hyperekplexia (15.9 %), tremor (14.6 %), and myoclonus (6.1 %). Parkinsonism was observed in 11 % of patients, ataxia in 8.5 % and multiple MDs in 50 %. Paroxysmal episodes of MD exacerbation occurred in 6 patients, and transient MD in 8. Dystonia was most frequent in patients with acquired brain lesions (p = 0.003). Parkinsonism was more frequent in patients with brain dysplasias and IEM (p = 0.043). CONCLUSIONS: This study confirms the high frequency of hyperkinetic and combined MD in DEE, and identifies characteristic MDs in conditions such SCN8A, FOXG1 and ARX related DEE, as well as ataxia and tremor in STXBP1, SCN1A, MTRFR, KCTD7 and 15q111-13 deletion. Novel observations, include the occurrence of paroxysmal dyskinetic exacerbations in FOXG1, axial stereotypies in KCNQ2, hyperekplexia in cortical dysplasia and Parkinsonism in ECHS1 with DEE.
BACKGROUND: Sturge-Weber Syndrome (SWS) is a capillary-venous malformation which includes the brain (leptomeningeal venous capillary malformation), the eye (choroidal angioma) and the skin (facial portwine birthmark, FPB...BACKGROUND: Sturge-Weber Syndrome (SWS) is a capillary-venous malformation which includes the brain (leptomeningeal venous capillary malformation), the eye (choroidal angioma) and the skin (facial portwine birthmark, FPB). Structural epilepsy, glaucoma and FPBs pose therapeutic challenges. Considerable advances include improved neuroimaging, new antiseizure medication (ASM) and progress in epilepsy surgery. Yet, comprehensive data on epidemiology, clinical features, diagnostics, and treatment in contemporary pediatric SWS cohorts is scarce. METHODS: We conducted a multinational cross-sectional observational study in Germany, Switzerland and Austria to identify potential patients and build up a comprehensive database containing anonymized patient data. The patients' guardians and child neurologists filled in detailed questionnaires on histories, clinical features, diagnostic and therapeutic measures. RESULTS: Forty-seven SWS patients from Germany, Switzerland or Austria participated in our survey (111 notifications, i.e. the participation rate was 43 %). Prevalence was 7.37/million in Germany, 4.60/million in Switzerland, 2.61/million in Austria. Severity of skin, eye and brain involvement varied highly. Forty-three patients (91 %) were diagnosed with epilepsy. Median age at first seizure was 6.5 months. Thirty-two percent of the cohort received ASM in monotherapy, fifty-three percent received combination therapy and thirteen percent received no ASM. Eight percent underwent epilepsy surgery. CONCLUSIONS: In this European pediatric SWS cohort from a well-established tertiary child neurologist network, the condition was commonly diagnosed within the first year of life. 40 % of the cohort were seizure-free at inclusion; only 8.5 % of the cohort underwent epilepsy surgery. Our findings are concordant with published data from U.S. registries and case series. While our results indicate diagnostic improvement as compared to published studies, epilepsy management in SWS remains a challenge.
Cognitive deficits after childhood arterial ischemic stroke (AIS) can be observed in more than half the affected children, especially in executive functions. Previous research revealed some main factors that influence co...Cognitive deficits after childhood arterial ischemic stroke (AIS) can be observed in more than half the affected children, especially in executive functions. Previous research revealed some main factors that influence cognitive outcome after childhood AIS, including lesion location, lesion size, and age at stroke. However, the importance of lesion size particularly has been discussed controversially. Thus, the present study takes a closer look at the impact of lesion size on executive performance in children who suffered an AIS using both direct cognitive testing and parental ratings. The study sample comprised 14 patients after childhood AIS (mean age 12.71, 5 female) and 14 age- and sex-matched healthy controls (mean age 11.00, 6 female). Results of cognitive testing revealed that the patient group performed poorer in executive functioning compared to controls, but mostly within the normal range. Lesion size correlated with sustained attention performance and some of the parental rating scales. However, if these correlations were controlled for sustained attention, lesion size was no longer correlated with any parental rating scale. The results of the present study suggest that sustained attention performance mediates the correlation between parental ratings of executive functions and lesion size. This confounding factor may explain inconsistent results of the relationship between lesion size and cognitive outcome in previous research.
BACKGROUND: Chronic pharmaco-resistant pain syndrome (CPS) requires different therapeutic approaches based on the underlying pathology. Spinal cord stimulation (SCS) in children with chronic neuropathic pain syndrome (CN...BACKGROUND: Chronic pharmaco-resistant pain syndrome (CPS) requires different therapeutic approaches based on the underlying pathology. Spinal cord stimulation (SCS) in children with chronic neuropathic pain syndrome (CNPS) has been scarcely reported in the literature. OBJECTIVES: To present SCS as the rational treatment approach in children with chronic regional and generalized chronic neuropathic pain syndrome, its efficiency, complications and the role in neuromodulation. We present two children with chronic pain syndrome treated with SCS. A 14-year-old girl at the age of 8 manifested with signs of chronic regional pain syndrome (CRPS) type 1 in wrist and afterwards in knee, associated with allodynia, signs of local autonomic dysfunction, trophic changes of the skin, and loss of ambulation. Nerve biopsy showed inflammatory infiltrates and loss of small unmyelinated C in skin biopsy. A 17-year-old boy manifested at the age of 9 with clinical signs of acute central (CNS) and peripheral nervous system (PNS) involvement associated with headache, photophobia, ataxia, paraparesis, autonomic dysfunction and intensive generalized global neuropathic pain, especially in the lower extremities. Electromyoneurography (EMNG) at the first exam was compatible with Guillain Barre syndrome and subsequently several times during follow up EMNG and nerve biopsy were compatible with chronic inflammatory demyelinating polyneuropathy (CIDP). Treatment was maintained with i.v. immunoglobulins (IVIG) and steroids without functional improvement. In both children functional psychosomatic, orthopedic and rheumatologic causes were excluded including painful genetic neuropathies. Seven and eight years after the onset of symptoms and signs of CPS in both children, epidural SCS was implanted, followed by pain relief up to 100 % with complete recovery of motor function, local skin changes and of intraepidermal nerve fiber density in a girl. A boy became ambulant, 50 % up to 75 % pain control was attained, and only partial recovery of sphincter control. CONCLUSION: SCS as minimally invasive neurosurgical method may be efficient in resolving chronic pain and in restoring functional abilities of affected extremities. SCS should be considered as a treatment approach in children with chronic regional and generalized (pharmacoresistant) neuropathic pain syndrome resistant to all established treatment modalities.
BACKGROUND: Corpus callosum (CC) measurements are used as a biomarker of white matter volume in infants born very preterm (VPT; gestational age≤32 weeks). Although smaller CC measurements are found in both children born...BACKGROUND: Corpus callosum (CC) measurements are used as a biomarker of white matter volume in infants born very preterm (VPT; gestational age≤32 weeks). Although smaller CC measurements are found in both children born VPT and those with cerebral palsy (CP) compared to neurotypical children born at term, there is a lack of research specifically comparing CC measurements in VPT children with and without CP at different ages. PARTICIPANTS AND METHODS: We compared five CC measurements (total length, and thickness of genu, body, isthmus, and splenium) calculated on the midsagittal plane of T1 magnetic resonance imaging (MRI) in a retrospective case-control study between VPT children with (case) and without CP (control) matched 1:1 by age at MRI at different ages (<12 months age; 5-11 years-old). RESULTS: Seventy-four VPT children were included (median age 5.8 months [2.1-89.3], 34 females). Children with CP showed shorter length (45.3 mm [40.9-66.2] vs 50.9 mm [44.5-69]; p = 0.01), smaller isthmus thickness (1.8 mm [1.2-2.2] vs 2.2 mm [1.8-4.1]; p = 0.03), and smaller splenium thickness (3.5 [2.7-7.9] vs 5 mm [3.7-9.8]; p = 0.04) compared to children without CP. Comparison of the two groups by age at MRI, showed significantly smaller splenium thickness in both infants (<12 months age) and children (5-11 years-old) with CP than in controls. CONCLUSION: Infants and children born VPT with CP had smaller CC measurements than those without CP, with the posterior region being the most affected. Splenium thickness in VPT infants could serve as a biomarker for white matter damage, potentially leading to CP.
OBJECTIVE: Little clinical data is available for advanced cases of spinal muscular atrophy (SMA) type 1, particularly those requiring ventilation support. Therefore, this study aimed to evaluate the effectiveness of nusi...OBJECTIVE: Little clinical data is available for advanced cases of spinal muscular atrophy (SMA) type 1, particularly those requiring ventilation support. Therefore, this study aimed to evaluate the effectiveness of nusinersen treatment on motor and respiratory function in advanced cases of SMA type 1. METHODS: This observational cohort study included seven patients with advanced SMA type 1, requiring permanent ventilator support and tracheostomy, at Hyogo Medical University School of Medicine Hospital between July 2017 and July 2019. The primary outcome was change in motor function, assessed using the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) score. Subjective changes, which could not be measured with CHOP-INTEND, were also evaluated. The secondary outcomes included changes in respiratory function, measured by tidal volume (TV) and transcutaneous carbon dioxide (TcCO) levels. RESULTS: Two patients showed a meaningful improvement in CHOP-INTEND scores (an increase of 4 points) after 2-3 years of nusinersen treatment. The remaining five showed changes ranging from 0 to 2 points. Subjective changes were observed in all patients. Patient respiratory function outcomes varied; TV increased in two patients and decreased in five, and TcCO levels decreased in three patients and increased in four. CONCLUSIONS: Nusinersen may provide meaningful improvement in motor function in some patients with advanced SMA type 1; however, treatment response may take a while and varies between individuals. Further research is needed to substantiate these findings and identify potential prognostic factors for nusinersen treatment.
BACKGROUND: Mild traumatic brain injuries (mTBIs) are common in childhood and adolescence, but their long-term effects remain poorly understood. OBJECTIVE: Examine cognitive performances and perceived injury symptoms, on...BACKGROUND: Mild traumatic brain injuries (mTBIs) are common in childhood and adolescence, but their long-term effects remain poorly understood. OBJECTIVE: Examine cognitive performances and perceived injury symptoms, on average, six years after an mTBI in school-aged children and adolescents, and to evaluate longitudinal changes in performance and symptoms during the follow-up period. MATERIALS AND METHOD: Finnish children aged 7-15 years who were cared for mTBI at Turku University Hospital during 2010-2016, with brain imaging and neuropsychological assessment linked to the event available, were identified and targeted for follow-up assessment. We gathered cognitive performance and injury symptom data, as recorded at 1-3 months post-injury, retrospectively from the hospital patient records. Age-appropriate versions of Wechsler Intelligence Scale, Conners Continuous Performance Test II, PedsQL™ Multidimensional Fatigue Scale and semi-structured interview of symptoms were used as outcome measures at follow-up. RESULTS: Age-adjusted verbal performance scores of the participants deteriorated during follow-up, and were predicted by younger age at injury, male sex, and lower verbal performance scores at the original assessment. At follow-up 64.9 % reported one or more injury symptoms, with 48.6 % of those displaying symptoms at the original assessment continuing to report symptoms at follow-up. The most persistent injury symptoms were verbal difficulties, headache and fatigue. CONCLUSIONS: The results stress the importance of identifying and monitoring children recovering slowly after a hospital-treated mTBI, as they might be at increased risk for long-lasting problems.
INTRODUCTION: Patients with developmental and epileptic encephalopathies (DEEs) have multiple comorbidities and high healthcare needs. Whether health services meet the needs of this patient population and their families...INTRODUCTION: Patients with developmental and epileptic encephalopathies (DEEs) have multiple comorbidities and high healthcare needs. Whether health services meet the needs of this patient population and their families is not well understood. We explored caregiver perspectives on their child's health service use, satisfaction with health services, and priorities for improvement. METHODS: Caregivers of patients with DEEs completed online questionnaires containing specifically designed quantitative and qualitative questions to assess their perceptions of their child's health service use over a 12-month period. We analysed the quantitative data using descriptive and non-parametric statistics and the qualitative data using content analysis. RESULTS: Seventy-five caregivers participated. Over 12-months, 52 (69.3 %) patients presented to the emergency department, 70 (93.3 %) saw ≥3 medical professionals, and 45 (60 %) saw ≥3 allied health professionals (n = 45, 60.0 %). Caregivers were satisfied with their child's healthcare when they perceived healthcare professionals to be compassionate and knowledgeable. Caregivers were dissatisfied when they perceived that healthcare professionals were not knowledgeable about DEEs, or they felt unheard, unsupported, needed to advocate for their child's healthcare and disability funding, and perceived care coordination to be lacking. Hospital care and parent psychological support were caregivers' top priorities for improvement to the healthcare system. DISCUSSION: Care coordination and access to knowledgeable healthcare professionals and psychological supports should be prioritised to achieve more appropriate models of care for patients with DEEs. Further research should evaluate models of care which incorporate these features to determine if they provide high value healthcare and improve the patient and family journey.
OBJECTIVE: Management of ketogenic diet (KD) in case of prolonged anesthesia in children. METHODS: We conducted a retrospective study in the pediatric neurosurgery department of Rothschild Hospital Foundation in France....OBJECTIVE: Management of ketogenic diet (KD) in case of prolonged anesthesia in children. METHODS: We conducted a retrospective study in the pediatric neurosurgery department of Rothschild Hospital Foundation in France. All the children who underwent long term anesthesia (>4h) in case of neurosurgery for drug resistant pediatric epilepsy surgery between September 2020 and January 2024 were included, excluding patients with suspected metabolic disorder or without blood sample. Children were analyzed in three subgroups: Children under regular diet before surgery constituted the Non-KD group; strict maintenance of KD with no carbohydrate intake during surgery constituted the KD-S group (stringent); carbohydrate intravenous intake during surgery in a patient treated by KD represented the KD-B group (broken). RESULTS: 22 patients were included, among whom 6 under ketogenic diet (KD). After 4 h of anesthesia, children maintained in strict ketogenic diet (KD-S, n = 3) exhibited non-lactic metabolic acidosis (pH 7.13 vs 7.34, p = 1.38x10) associated with an increased anionic gap (17.1 mM vs 9.6 mM, p = 1.58 x10). SIGNIFICANCE: Current recommendations for anesthesia during long term anesthesia (>4h) with strict no-carbohydrate intake during anesthesia in case ok KD may be at risk of life-threatening metabolic acidosis, in a context of absence of protocolized monitoring of variations in hyperketosis throughout a prolonged fast. A KD-management protocol, including routine monitoring of ketosis in addition to usual monitoring (lactacidemia, kaliemia and glycemia), and low carbohydrates intravenous perfusion throughout prolonged general anesthesia, should be implemented throughout prolonged general anesthesia, especially for infants younger than 2 years.
Castro D, Sejersen T, Bello L
… +16 more, Buccella F, Cairns A, Carranza-Del Río J, de Groot IJM, Elman L, Inzani I, Klein A, Mayer OH, Miller H, Onofri A, Araújo APQC, Schara-Schmidt U, Vanden Wyngaert K, Ward LM, Wilmshurst JM, Quinlivan R
BACKGROUND: Duchenne muscular dystrophy (DMD) is a rare neuromuscular disorder characterized by a progressive decline in muscle function, leading to loss of ambulation, respiratory and cardiac failure, and ultimately dea...BACKGROUND: Duchenne muscular dystrophy (DMD) is a rare neuromuscular disorder characterized by a progressive decline in muscle function, leading to loss of ambulation, respiratory and cardiac failure, and ultimately death. Improvements in DMD management have increased patient life expectancy; therefore, there is a growing requirement for patients to transfer from paediatric to adult care services. There is also a need for clear recommendations to guide this process. AIM: To establish international consensus guidelines regarding best practices for transitioning patients with DMD from paediatric to adult care and ensuring continuity of treatment. METHODS: Consensus statements were developed using the Delphi process and scored using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The initiative was led by a steering committee (one non-voting chair and two voting members) who recruited 15 expert panellists to form the consensus group. Following an initial systematic literature search, the consensus group voted in three voting rounds. Round 1 (free-text responses to questions) and Round 2 (importance ranking of statements) were completed using an online survey. Round 3 (voting on final consensus statements) took place during a virtual consensus meeting. CONSENSUS STATEMENTS: Consensus was reached on 48 statements covering the topics of transition planning, the transition process, post-transfer management, communicating with young people with DMD and supporting them with the transition to adult life. CONCLUSION: These consensus statements provide guidelines for improving transition practices for young people with DMD and promoting continued care at a comparable standard in adulthood.
Baer S, Rebert M, Burger P
… +14 more, Mandel JL, Villeneuve N, Gibaud M, Altuzarra C, Villega F, Cances C, Lacan L, Nguyen S, Lesca G, Isnard H, Allani-Essid N, Laugel V, Coutelle R, de Saint Martin A
SLC6A1 (Solute Carrier Family 6 Member 1) variants are associated with SLC6A1-neurodevelopmental disorders (SLC6A1-NDD), which manifest as early-onset epilepsy, intellectual developmental disorder, and autism spectrum di...SLC6A1 (Solute Carrier Family 6 Member 1) variants are associated with SLC6A1-neurodevelopmental disorders (SLC6A1-NDD), which manifest as early-onset epilepsy, intellectual developmental disorder, and autism spectrum disorder. There have been over 300 reported cases so far. A retrospective analysis of 14 patients with de novo SLC6A1 variants was conducted to assess their developmental milestones, epilepsy progression, antiseizure medication, and, for some, a comprehensive neurodevelopmental evaluation. Data from 14 additional families were also collected using the GenIDA participatory database, aiming to better characterize the natural history of genetic forms of NDDs. Most patients exhibited normal early motor development, but delays in communication and language skills were observed. Their intellectual functioning varied, mostly falling within the low average to moderate intellectual developmental disorder range, with a predominant expressive and receptive language disorder. More than half of the group displayed autistic features, particularly stereotypic behavior. Behavioral disorders such as hyperactivity, anxiety, impulsivity, or inhibition were common concerns for parents. The first seizures occurred between 14 months and 5 years, mainly presenting as generalized seizures (atonic falls, absences, atypical absences, myoclonic-atonic seizures). EEG results frequently showed bursts of rhythmic delta activity, persisting from childhood to adulthood, with epilepsy primarily responding well to antiseizure medication in most of the reported cases. This study exhibited a distinct electroclinical and neurodevelopmental phenotype in young children, suggesting the importance of early genetic testing for SLC6A1-NDD diagnosis.
Kauth F, Bertolini A, Wendel EM
… +27 more, Koukou G, Naggar IE, Chung J, Baumann M, Schödl C, Lechner C, Bigi S, Blaschek A, Hengstler JG, Schimmel M, Nosadini M, Sartori S, Puthenparampil M, Van's Gravesande KS, Drenckhahn A, Nikolaus M, Kauffmann B, Thiels C, Häusler MG, Eckenweiler M, Karenfort M, Marina AD, Selek A, Öncel I, Kornek B, Reindl M, Rostásy K
BACKGROUND: Early onset pediatric multiple sclerosis (EOPMS) provides an early window of opportunity to understand the mechanisms leading to MS. OBJECTIVE: To investigate clinical, laboratory and imaging differences betw...BACKGROUND: Early onset pediatric multiple sclerosis (EOPMS) provides an early window of opportunity to understand the mechanisms leading to MS. OBJECTIVE: To investigate clinical, laboratory and imaging differences between children with early onset pediatric MS (<11 years, EOPMS) and late onset pediatric MS (≥11 years, LOPMS). METHODS: Mostly prospectively collected data of children with MS including clinical presentation, MRI at onset, time to second relapse, relapse rate, treatment history, and CSF markers were eligible. RESULTS: In total 274 children were included, n = 53 children with EOPMS and n = 221 children with LOPMS. In children with EOPMS both sexes were equally affected, while in LOPMS the female sex was more prevalent (p < 0.001). Presence of additional oligoclonal bands (OCBs) in the cerebrospinal fluid (CSF) was comparable in both age groups (92.3 % vs 89.5 %). Children with EOPMS had more relapses in the first 2 years (p = 0.004). Children with LOPMS had significantly more spinal lesions (p = 0.001). Presence of a prior EBV infection tested in a subset of children with EOPMS (n = 34) was only detected in 27/34 (79 %). CONCLUSION: Our findings suggest that both groups share important similarities but also important differences such as an increased relapse rate and a higher amount of infratentorial lesions in EOPMS. Furthermore, our results allude to a prior EBV-infection possibly not being an indispensable requirement for the development of MS in children with EOPMS.
BACKGROUND: The study aimed to describe a new Ommaya reservoir implantation method in late-onset SMA patients, assessing its safety and effectiveness under standard clinical conditions. METHODS: Prospective observational...BACKGROUND: The study aimed to describe a new Ommaya reservoir implantation method in late-onset SMA patients, assessing its safety and effectiveness under standard clinical conditions. METHODS: Prospective observational study. Lumbar intrathecal access was unfeasible due to significant scoliosis and prior spinal surgeries with instrumentation. Patients were infused with Nusinersen through the Ommaya reservoir at Hospital Universitario La Paz (Spain) following the standard dosing protocol. RESULTS: The cohort was composed of 6 patients, 5 individuals with type 2 SMA (83.3 %), and 1 patient presenting with type 3 SMA. 4 of the patients were functionally sitters (66.7 %) and 2 had lost this ability prior to initiating treatment (non-sitters). Mean treatment was 34.7 months. Patient discharge was done in all the cases within 48 h post-admission; no significant postoperative complications or during administration of nusinersen were reported. Functional progress was observed in all patients. Hammersmith Functional Motor Scale Expanded (HFMSE) showed a low average increase (1.0), attributed to the severity of baseline functional impairments. Improvements in upper extremity motor function, measured by the Revised Upper Limb Module (RULM), were more pronounced, with an average improvement of 3.3. Disability levels as measured by the Egen Klassifikation 2 (EK2) scale, declined by 4.4. CONCLUSION: the current study broadens knowledge regarding the efficacy and safety of using an Ommaya reservoir to administer nusinersen in patients with SMA Types 2 and 3. The technique demonstrated rapid, straightforward drug delivery through a subcutaneous needle, maintaining optimal sterility without radiation or the need for a multidisciplinary team.
OBJECTIVES: Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy that requires significant caregiver input across the lifespan. This predominantly falls on parents, who are faced with considerable...OBJECTIVES: Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy that requires significant caregiver input across the lifespan. This predominantly falls on parents, who are faced with considerable challenges including physical demands, financial burdens, and sustained pressure on mental wellbeing leading to mental health difficulties. We aimed to develop a grounded theory model for the process of coping and adjustment that occurs when caring for a child who has a diagnosis of DS. METHODS: Using a Constructivist Grounded Theory methodology, we conducted five focus groups, each with 4-6 participants, and 24 in total. They were recruited via convenience sampling through a national Dravet syndrome patient advocacy group. Focus group dialogue was recorded, transcribed, and coded into themes to generate a theory of coping and adjustment that is grounded in the data. RESULTS: We developed a model of coping and adjustment for parents caring for a child with Dravet syndrome. The model includes contextual factors that impact on parents (loss and insufficient resource). We found a prominent theme of trauma and explored how parents responded to this trauma over time. All parents described a primary coping response reflecting the high levels of stress they had to contend with. Some parents were able to describe a secondary coping style that appeared to support healthier long-term coping and adjustment. SIGNIFICANCE: The study provides novel insight into the ways in which parents cope and adjust to caring for a child with DS, with a focus on adapting to trauma. These insights provide the foundation for the creation of targeted therapeutic interventions for parents of children with developmental and epileptic encephalopathies (DEEs), which we outline and discuss.
AIM: To evaluate the efficacy of initial pharmacotherapy for infantile epileptic spasm syndrome (IESS) with electro-clinical outcome characteristics. METHOD: A retrospective comparative cohort study with 280 IESS patient...AIM: To evaluate the efficacy of initial pharmacotherapy for infantile epileptic spasm syndrome (IESS) with electro-clinical outcome characteristics. METHOD: A retrospective comparative cohort study with 280 IESS patients was designed; I. vigabatrin monotherapy (n = 129, 46 %); II. hormonotherapy (ACTH/oral prednisolone) (n = 73, 26 %); and III. vigabatrin plus early initiation of hormonotherapy in the first 14 days (n = 78, 28 %). Two types of outcomes were defined: (1) short-term outcome with spasm cessation time ≤42 days and resolution of hypsarrhythmia on the EEG on ≤3 months and (2) long-term outcome with spasm relapse rate or evolution to a new epileptic syndrome. RESULTS: The etiology-specific diagnoses of the IESS cohort were defined according to the ILAE classification: structural (n = 131, 46.8 %), genetic (n = 28, 10 %), metabolic (n = 13, 4.6 %), immune-infectious (n = 10, 3.6 %), and unknown (n = 98, 35 %). Each treatment modalities had similar short- and long-term outcome characteristics. However, hormonotherapy with steroids (ACTH/oral prednisolone) provided "early IESS resolution" with spasm cessation and resolution of hypsarrhythmia (p = 0.042). The relapse rates of IESS were significantly higher in the etiology well-defined group compared to the unknown group (p = 0.005). The genetic-etiology specific group was more likely to have evolved to a new electro-clinical syndrome with a rate of 83.3 % than the others (p = 0.039). CONCLUSION: We observed that the early initiation of hormonotherapy with VGB (sequential therapy) should be investigated in etiology well-defined subgroup with short- and long-term outcome characteristics.
Childhood-onset mitochondrial disorders are rare genetic diseases that often manifest with neurological impairment due to altered mitochondrial structure or function. To date, pathogenic variants in 373 genes across the...Childhood-onset mitochondrial disorders are rare genetic diseases that often manifest with neurological impairment due to altered mitochondrial structure or function. To date, pathogenic variants in 373 genes across the nuclear and mitochondrial genomes have been linked to mitochondrial disease, but the ensuing genetic and clinical complexity of these disorders poses considerable challenges to their diagnosis and management. Nevertheless, despite the current lack of curative treatment, recent advances in next generation sequencing and -omics technologies have laid the foundation for precision mitochondrial medicine through enhanced diagnostic accuracy and greater insight into pathomechanisms. This holds promise for the development of targeted treatments in this group of patients. Against a backdrop of inherent challenges and recent technological advances in mitochondrial medicine, this review discusses the current diagnostic approach to a child with suspected mitochondrial disease and outlines management considerations of particular relevance to paediatric neurologists. We highlight the importance of mitochondrial expertise centres in providing the laboratory infrastructure needed to supplement uninformative first line genomic testing with focused and/or further unbiased investigations where needed, as well as coordinating an integrated multidisciplinary model of care that is paramount to the management of patients affected by these conditions.