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Increasingly effective targeted precision medicine is either already available or in development for a number of genetic childhood movement disorders. Patient‐centred, personalized approaches include the repurposing of existing treatments for specific conditions and the development of novel therapies that target the underlying genetic defect or dis...
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The term “epileptic encephalopathy” is used to describe a possible relationship between epilepsy and developmental delay. The pathogenesis of developmental encephalopathies, independent of epilepsy, can be defined by genetic control mechanisms. The aim of this study was to investigate the use of miRNAs as serum biomarkers for the determination and...
Citations
... Personalized medicine approaches are also being increasingly utilized to treat movement disorders [171]. By identifying genetic markers, biomarkers, and other factors that influence disease progression and treatment response, healthcare providers can tailor treatments to individual patients for better outcomes. ...
Movement disorders encompass a diverse group of neurological conditions characterized by abnormal voluntary or involuntary movements. These disorders can be classified broadly into hyperkinetic and hypokinetic disorders. Excessive, involuntary movements, including tremors, dystonia, chorea, and myoclonus characterize hyperkinetic disorders. Tremors are rhythmic, involuntary movements occurring at rest or during movement. Dystonia involves sustained muscle contractions, leading to twisting and repetitive movements or abnormal postures. Chorea manifests as brief, irregular, involuntary movements that flow from one body part to another. Myoclonus consists of sudden, brief muscle contractions, either spontaneous or in response to a stimulus. Hypokinetic disorders are characterized by a lack of movement or difficulty initiating movement, as seen in Parkinson's disease and Parkinsonism. Parkinson's disease is a progressive neurological disorder that primarily affects movement, causing tremors, stiffness, and difficulty with balance and coordination. Parkinsonism refers to a group of disorders with similar symptoms to Parkinson's disease but with different underlying causes. Diagnosing movement disorders involves a thorough clinical evaluation, including a detailed medical history and physical examination. Neuroimaging studies such as MRI, CT scans, and functional imaging techniques may be used to assess brain structure and function. Additionally, laboratory tests, including genetic testing and biochemical markers, can help diagnose certain movement disorders.
... Therefore, LEV may be an unsuitable medication for patients with SeLIE caused by PRRT2 mutations. For focal or focal origin seizures, OXC is a worthy priority for PRRT2-mutated patients, which is also effective for possible PKD in teen years [28]. It has recently been reported that VPA showed poor results on PRRT2-related epilepsy [29], and only three patients were treated with VPA. ...
Introduction
Self-limited infantile epilepsy (SeLIE) is a benign epilepsy. Previous studies have shown that monotherapy with most antiseizure medications can effectively relieve seizures in patients with SeLIE, but the efficacy of levetiracetam has not been investigated.
Objective
This study aimed to investigate the efficacy of levetiracetam in the treatment of SeLIE patients with PRRT2 mutations.
Methods
The clinical data of 39 SeLIE patients (21 males and 18 females, aged 4.79 ± 1.60 months) with pathogenic variants in PRRT2 or 16p11.2 microdeletion were retrospectively analyzed. Based on the use of initial antiseizure medication (ASM), the patients were classified into two groups: Levetiracetam group (LEG) and Other ASMs group (OAG). The difference of efficacy between the two groups was compared.
Results
Among the 39 SeLIE patients, 16 were LEG (10 males and 6 females, aged 5.25 ± 2.07 months), with whom two obtained a seizure-free status (12.50%) and 14 ineffective or even deteriorated (87.50%). Among the 14 ineffective or deteriorated cases, 13 were seizure-controlled after replacing levetiracetam with other ASMs including topiramate, oxcarbazepine, lamotrigine, and valproate, and the remaining one finally achieved remission at age 3. Of the 39 patients, 23 were OAG (11 males and 12 females; aged 4.48 ± 1.12 months), of whom 22 achieved seizure remission, except for one patient who was ineffective with topiramate initially and relieved by oxcarbazepine instead. Although there were no significant differences in gender and age of onset between the two groups, the effective rate was significantly different (12.50% in LEG vs. 95.65% in OAG) ( P < 0.01).
Conclusion
The findings showed that patients with SeLIE caused by the PRRT2 mutations did not benefit from the use of levetiracetam, but could benefit from other ASMs.
... Precision medicine refers to treatments that are tailored or targeted to the needs of the individual based on their genetic, biomarker, phenotypic, and/or psychosocial characteristics. 1 While having an established history in fields such as paediatric oncology, with a focus on identifying specific biological mechanisms and molecular pathways to provide specific treatment recommendations and improve outcomes in childhood cancer, 2 precision medicine is increasingly being applied across other paediatric fields, including for children with neurodevelopmental disorders. Globally it has been estimated that there are 53 million children and young people who have a neurodevelopmental disorder. ...
... Recently, precision medicine for neurodevelopmental disorders has predominantly harnessed advances in genomic sequencing technologies to increase our ability to identify single gene mutations, diagnose a multitude of rare neurodevelopmental disorders, and gain insights into pathogenesis. 1 There have been clear successes in the application of such a precision medicine approach to monogenic neurodevelopmental disorders. Paediatric monogenic neurological disorders affect around 1% of children at birth, and neurological disorders in general are the primary cause of disability in global burden of disease analysis. ...
... A monogenic diagnosis does however enable prospective reproductive decision-making for parents, facilitated through genetic counselling. 1,12 While common genetic variants have been identified as important and cumulative contributors ...
Precision medicine refers to treatments that are targeted to an individual's unique characteristics. Precision medicine for neurodevelopmental disorders (such as cerebral palsy, attention‐deficit/hyperactivity disorder, obsessive–compulsive disorder, Tourette syndrome, and autism spectrum disorder) in children has predominantly focused on advances in genomic sequencing technologies to increase our ability to identify single gene mutations, diagnose a multitude of rare neurodevelopmental disorders, and gain insights into pathogenesis. Although targeting specific gene variants with high penetrance will help some children with rare disease, this approach will not help most children with neurodevelopmental disorders. A ‘pathway’ driven approach targeting the cumulative influence of psychosocial, epigenetic, or cellular factors is likely to be more effective. To optimize the therapeutic potential of precision medicine, we present a biopsychosocial integrated framework to examine the ‘gene–environment neuroscience interaction’. Such an approach would be supported through harnessing the power of big data, transdiagnostic assessment, impact and implementation evaluation, and a bench‐to‐bedside scientific discovery agenda with ongoing clinician and patient engagement.
What this paper adds
Precision medicine has predominantly focused on genetic risk factors.
The impact of environmental risk factors, particularly inflammatory, metabolic, and psychosocial risks, is understudied.
A holistic biopsychosocial model of neurodevelopmental disorder causal pathways is presented.
The model will provide precision medicine across the full spectrum of neurodevelopmental disorders.
Precision medicine aims to understand the mechanisms of diseases and to find treatments adapted to each individual or group of patients, on the basis of biological characteristics and environment. It uses new tools based on digital technologies. Narrative medicine was theorized, in the 2000s, as a reaction to the increasing technicality and the notion of a lack of human relations in care: It focuses on recognizing the essential place of the patient's experience of illness and life history in the diagnosis and management of diseases as well as in the training of caregivers. These two opposite currents are rarely considered together. In fact, they have in common the basic principle that each patient is unique, and both are often more closely intertwined than we think, especially in the field of child neurology. Five case histories and discussions presented here aim to demonstrate that combining the precision approach with the narrative approach can improve the diagnosis, treatment, classification, and understanding of neurological conditions, as well as enhance the dialog with families and make teaching more meaningful. Not only rare diseases but common problems, such as paroxysmal events, pain, epilepsy, intellectual disability, and autism spectrum disorder, are addressed from both perspectives.
Precision medicine is a patient-centered approach that aims to translate new knowledge to optimize the type and timing of interventions for the greatest benefit to individual patients. There is considerable interest in applying this approach to treatments designed to slow or halt the progression of neurodegenerative diseases. Indeed, effective disease-modifying treatment (DMT) remains the greatest unmet therapeutic need in this field. In contrast to the enormous progress in oncology, precision medicine in the field of neurodegeneration faces multiple challenges. These are related to major limitations in our understanding of many aspects of the diseases. A critical barrier to advances in this field is the question of whether the common sporadic neurodegenerative diseases (of the elderly) are single uniform disorders (particularly related to their pathogenesis) or whether they represent a collection of related but still very distinct disease states. In this chapter, we briefly touch on lessons from other fields of medicine that might be applied to the development of precision medicine for DMT in neurodegenerative diseases. We discuss why DMT trials may have failed to date, and particularly the importance of appreciating the multifaceted nature of disease heterogeneity and how this has and will impact on these efforts. We conclude with comments on how we can move from this complex disease heterogeneity to the successful application of precision medicine principles in DMT for neurodegenerative diseases.
