Neonatal Hyperekplexia: Is It Still a Diagnostic Challenge? Evidence From a Systematic Review.

Hyperekplexia is a neurologic disorder characterized by an exaggerated startle reflex in response to different types of stimuli. Hyperekplexia is defined by the triad of neonatal hypertonia, excessive startle reflexes, and generalized stiffness following the startle. Although uncommon, hyperekplexia can lead to serious consequences such as falls, brain injury, or sudden infant death syndrome.Aim of this study was to identify cases of neonatal hyperekplexia with a confirmed genetic diagnosis and to establish the genotype-phenotype correlation at onset. Articles were selected from 1993 to 2024 and PRISMA Statement was applied including newborns within 28 days of life. So, we retrieved from literature 14 cases of genetically confirmed neonatal hyperekplexia. The onset of clinical manifestations occurred in the first day of life in 8 of 14 patients (57.14%). Clinical findings were muscle stiffness (100%), startle reflex (66.66%), apnea/cyanosis (41.66%), positive nose-tapping test (33.33%), jerks (33.33%), jitteriness (25%), and ictal blinking (25%). Genes involved were GLRA1 in 9 of 14 (64.28%), SLC6A5 in 2 of 14 (14.28%), GPHN in 1 of 14 (7.14%), and GLRB in 2 of 14 (14.28%). Patients showed heterozygous (66.66%) or homozygous (33.33%) status. In 7 of 14 cases (50%), the condition occurred in other family members. A genotype-phenotype correlation was not achievable.Timely diagnosis is crucial to improve the natural history of hyperekplexia avoiding/reducing possible major complications such as sudden infant death syndrome, brain injury, and serious falls. Early differentiation from epilepsy minimizes treatment cost and improves the quality of life of patients.

PYRIDOXINE-dependent epilepsy (PDE): An observational study of neonatal cases on the role of pyridoxine in patients treated with standard anti-seizure medications.

BACKGROUND: The main objective of this study was to evaluate the neurological consequences of delayed pyridoxine administration in patients diagnosed with Pyridoxin Dependent Epilepsies (PDE). MATERIALS AND METHODS: We reviewed 29 articles, comprising 52 genetically diagnosed PDE cases, ensuring data homogeneity. Three additional cases were included from the General Pediatric Operative Unit of San Marco Hospital. Data collection considered factors like age at the first seizure's onset, EEG reports, genetic analyses, and more. Based on the response to first-line antiseizure medications, patients were categorized into four distinct groups. Follow-up evaluations employed various scales to ascertain neurological, cognitive, and psychomotor developments. RESULTS: Our study includes 55 patients (28 males and 27 females), among whom 15 were excluded for the lack of follow-up data. 21 patients were categorized as "Responder with Relapse", 11 as "Resistant", 6 as "Pyridoxine First Approach", and 2 as "Responders". The neurological outcome revealed 37,5 % with no neurological effects, 37,5 % showed complications in two developmental areas, 15 % in one, and 10 % in all areas. The statistical analysis highlighted a positive correlation between the time elapsed from the administration of pyridoxine after the first seizure and worse neurological outcomes. On the other hand, a significant association was found between an extended latency period (that is, the time that elapsed between the onset of the first seizure and its recurrence) and worse neurological outcomes in patients who received an unfavorable score on the neurological evaluation noted in a subsequent follow-up. CONCLUSIONS: The study highlights the importance of early recognition and intervention in PDE. Existing medical protocols frequently overlook the timely diagnosis of PDE. Immediate administration of pyridoxine, guided by a swift diagnosis in the presence of typical symptoms, might improve long-term neurological outcomes, and further studies should evaluate the outcome of PDE neonates promptly treated with Pyridoxine.

Epileptic spasms in infants: can video-EEG reveal the disease's etiology? A retrospective study and literature review.

Objective: Epileptic spasms are a type of seizure defined as a sudden flexion or extension predominantly of axial and/or truncal limb muscles that occur with a noticeable periodicity. Routine electroencephalogram supports the diagnosis of epileptic spasms, which can occur due to different causes. The present study aimed to evaluate a possible association between the electro-clinical pattern and the underlying etiology of epileptic spasms in infants. Materials and methods: We retrospectively reviewed the clinical and video-EEG data on 104 patients (aged from 1 to 22 months), admitted to our tertiary hospital in Catania and the tertiary hospital in Buenos Aires, from January 2013 to December 2020, with a confirmed diagnosis of epileptic spasms. We divided the patient sample into structural, genetic, infectious, metabolic, immune, and unknown, based on etiology. Fleiss' kappa (К) was used to assess agreement among raters in the electroencephalographic interpretation of hypsarrhythmia. A multivariate and bivariate analysis was conducted to understand the role of the different video-EEG variables on the etiology of epileptic spasms. Furthermore, decision trees were constructed for the classification of variables. Results: The results showed a statistically significant correlation between epileptic spasms semiology and etiology: flexor spasms were associated with spasms due to genetic cause (87.5%; OR < 1); whereas mixed spasms were associated with spasms from a structural cause (40%; OR < 1). The results showed a relationship between ictal and interictal EEG and epileptic spasms etiology: 73% of patients with slow waves and sharp waves or slow waves on the ictal EEG, and asymmetric hypsarrhythmia or hemi hypsarrhythmia on the interictal EEG, had spasms with structural etiology, whereas 69% of patients with genetic etiology presented typical interictal hypsarrhythmia with high-amplitude polymorphic delta with multifocal spike or modified hypsarrhythmia on interictal EEG and slow waves on the ictal EEG. Conclusion: This study confirms that video-EEG is a key element for the diagnosis of epileptic spasms, also playing an important role in the clinical practice to determine the etiology.

Need for palliative care from birth to infancy in pediatric patients with neurological diseases.

BACKGROUND: Palliative care is a comprehensive treatment approach that guarantees comfort for pediatric patients and their families from diagnosis to death. The techniques used for neurological patients in the field of palliative care can enhance the quality of care provided to patients with neurological disorders and support their families. PURPOSE: This study aimed to analyze the palliative care protocols in use in our department, describe the palliative course in the clinical setting, and propose the implementation of hospital palliative care for long-term prognosis of patients with neurological diseases. METHODS: This retrospective observational study examined the application of palliative care from birth to early infancy in neurological patients. We studied 34 newborns with diseases affecting the nervous system impairing prognosis. The study was conducted from 2016 to 2020 at the Neonatology Intensive Care Unit and the Pediatric Unit of the San Marco University Hospital in Catania, Sicily, Italy. RESULTS: Despite current legislation in Italy, no palliative care network has been activated to meet the needs of the population. In our center, given the vast number of patients with neurological conditions requiring palliative care, we should activate a straightforward departmental unit for neurologic pediatric palliative care. CONCLUSION: The establishment of specialized reference centers that manage significant neurological illnesses is due to neuroscience research progress in recent decades. Integration with specialized palliative care is sparse but now seems essential.

Impressive efficacy of the ketogenic diet in a KCNQ2 encephalopathy infant: a case report and exhaustive literature review.

Background: KCNQ2 encephalopathy is characterized by neonatal-onset epilepsy and developmental impairment, due to "de novo" KCNQ2 pathogenic variants. According to literature data, sodium channel blocking agents appear to be the best treatment options for the disease. Reports describing the use of ketogenic diet (KD) in the KCNQ2 pediatric population are limited. The non-conservative amino acid substitution p.Ser122Leu in KCNQ2 is associated with a broad spectrum of inheritance modalities, clinical phenotypes and outcomes; no previous reports of the same variant treated with KD are available in literature. Case Description: We described a 22-month-old female with seizure onset on day 2 of life. At three months of age, she presented refractory status epilepticus (SE) that did not respond to midazolam and carbamazepine, which was added once a "de novo" p.Ser122Leu KCNQ2 variant was demonstrated. KD was the only treatment that led to cessation of seizures. The baby maintained seizures remission and achieved neurodevelopmental milestones. Conclusions: To define an overt genotype-phenotype correlation for KCNQ2 pathogenic variants is a challenge; we propose the KD as a valuable treatment for refractory seizures and impaired neurodevelopment in infants harboring "de novo" mutations in the KCNQ2 gene.

Omalizumab treatment in a 12 year-old girl with chronic spontaneous urticaria.

Background: Omalizumab is a recombinant humanized IgG monoclonal antibody, which binds the Fc region of free IgE prevent its binding to its high-affinity receptor (FcεR1) on mast cells and basophils. Omalizumab was approved as add-on therapy for moderate-to-severe persistent allergic asthma and for patients with chronic spontaneous urticaria resistant to antihistamine treatment. Patient and results: This article reports effective and safe treatment of a 12 years old girl with add-on omalizumab. On an initial dose of omalizumab of 300 mg once every 4 weeks, the patient experienced resolution of symptoms to a degree that exceeded the effect of previous treatments. Conclusion: Convincing evidence in support of the efficacy and safety of Omalizumab in the treatment of CSU in adolescent has accumulated over the past few years.