Introduction: Acute non-traumatic tetraplegia is an infrequent presentation in the pediatric emergency department, with thiamine metabolism dysfunction syndrome (TMDS) representing an even rarer cause. This article aims to report a case of acute and transient non-traumatic tetraplegia secondary to TMDS. Case Report: A previously healthy 1-year-and-3-month-old girl, with expected neurodevelopment was admitted with an acute onset of flaccid paraplegia, progressing to spastic tetraplegia. Initial laboratory tests were unremarkable. Cranial magnetic resonance imaging revealed changes in the basal ganglia, manifested as bilateral and symmetrical oval hypodensities with increased areas of permeation cavitation. Proton spectroscopy showed no clear lactate peak, indicative of an indeterminate nature. Whole exome sequencing identified heterozygosity of the SLC19A3 gene, compatible with TMDS. High-dose biotin and thiamine replacement therapy led to progressive symptom improvement and complete recovery. Discussion and Conclusion: TMDS-2 is an autosomal recessive neurometabolic condition caused by dysfunction of the SLC19A3 gene, often triggered by febrile illness. Thiamine, an essential vitamin crucial for cellular metabolism, is disrupted in this syndrome due to defects in genes encoding proteins involved in thiamine transport and metabolism. The clinical phenotype varies and can include encephalopathy, seizures, dysarthria, ophthalmoplegia, abnormal gait, areflexia, dystonia, and even death. Brain MRI typically reveals symmetrical changes in the basal ganglia. Treatment involves immediate thiamine and biotin supplementation, usually administered intravenously for acute cases and orally for chronic cases.
Background: Elimination disorders, such as urinary (enuresis) and fecal incontinence (encopresis), involve inappropriate voiding beyond the expected age due to developmental, psychological, or physiological factors. These conditions impact children's emotional well-being, self-esteem, social functioning, and family relationships. However, few studies have compared psychological functioning and family communication in affected children. This study examines general health, behavioral problems, and mother-child relationships in children with elimination disorders versus healthy peers. Methods: Seventy-two children participated: 25 with urinary incontinence, 24 with fecal incontinence, and 23 healthy controls. Participants were recruited from hospitals in Isfahan. Data were collected using standardized questionnaires: the General Health Questionnaire, Dyadic Adjustment Scale, Eyberg Child Behavior Inventory, and Mother-Child Relationship Evaluation. Statistical analyses included descriptive statistics, Shapiro-Wilk and Levene's tests for assumptions, and group comparisons using univariate and multivariate analysis of variance (ANOVA and MANOVA). Results: No significant differences were found between groups in maternal general health or marital satisfaction. However, children with elimination disorders displayed more severe behavioral problems and faced greater challenges in their mother-child relationships, including lower maternal acceptance and higher levels of overprotection and rejection. Conclusion and Recommendations: Elimination disorders are associated with behavioral difficulties and strained family interactions. Early psychological screening, family counseling, and public education are recommended to improve outcomes for affected children and their families.
Objective: Leigh syndrome, formerly known as infantile subacute necrotizing encephalomyelopathy, is a progressive neurometabolic disorder characterized by midbrain and brainstem lesions leading to rapid neurodegeneration. Pathological variants in over 80 nuclear encoded genes, predominantly affecting respiratory chain and energy metabolism proteins, have been implicated in Leigh syndrome. This paper aims to provide an overview of current understanding of Leigh syndrome, emphasizing clinical, pathological, and molecular genetic aspects, with a specific focus on anovel finding of adolescent onset Leigh syndrome associated with variant c.640G>A identified among Low German-speaking Mennonite families in Southwestern Ontario. Methods: We present a case series detailing the clinical manifestations of five patients homozygous for the c.640G>A (p.E214K) variant in the nuclear DNA encoded NDUFV1 gene, which affects mitochondrial respiratory chain complex 1. Additionally, in silico tools are used to evaluate the structural and functional role of this variant on complex 1 activity. Results: The five patients exhibited diverse clinical presentations associated with Leigh syndrome. Biochemical evaluation demonstrated mildly elevated cerebrospinal-fluid lactate in two patients and isolated complex I deficiency in skin fibroblasts. Brain MRI, when available, consistently showed symmetric T2-hyperintensities of the putamina and dorsal brainstem, characteristic of Leigh syndrome, with all patients developing rapid onset in adolescence. This variant represents a novel finding of adolescent onset Leigh syndrome in the Low German-speaking Mennonite population, contributing to our understanding of Leigh syndrome's genetic heterogeneity. Conclusion: This study underscores the clinical and genetic diversity of Leigh syndrome and highlights the importance of identifying novel mutations within specific populations for accurate diagnosis and targeted treatment strategies. Though no cure exists, thiamine therapy has been shown to provide clinical improvement.
Background Opsoclonus is often associated with serious neurological and paraneoplastic pathology. Pediatric ophthalmologists play an important role in its diagnosis. Methods This study was a retrospective chart review of patients seen for suspicion of opsoclonus. Results A total of 259 patients were identified for whom opsoclonus was suspected, of which 83 (32%) were found to be true opsoclonus. The ophthalmology consultation changed the course of evaluation in 44 of the 117 patients who received ophthalmologic evaluation (38%). Sixteen (9%) were found to have primary ophthalmic diagnoses. Of the 83 children with opsoclonus, 36 (43%) had paraneoplastic opsoclonus-myoclonus-ataxia syndrome (OMAS), 32 (39%) had nonparaneoplastic OMAS, one (1.2%) had optic pathway glioma, 5 (6.0%) had other neurological diseases, 2 (2.4%) had hydrocephalus, 6 (7.2%) had benign neonatal opsoclonus, and one (1.2%) had opsoclonus of unknown etiology. Most patients (78 patients; 94%) received brain magnetic resonance imaging (MRI), followed by MRI of the chest/abdomen/pelvis and urine catecholamines in 57 patients each (69%). Conclusions Extensive evaluation is usually performed to rule out underlying neoplastic pathology and includes MRI of the brain, neck, chest, and abdomen and urine catecholamine studies. Pediatric ophthalmologists can help to make critical ophthalmic diagnoses in a minority of cases. If involved early in the diagnostic course, this may spare children unnecessary testing.
Trisomy of the short arm of chromosome 12 (trisomy 12p) is a rare chromosomal abnormality causing dysmorphic features, congenital anomalies, intellectual disabilities, developmental delays, and seizures. Detailed information regarding the types of seizures is scarce owing to the low incidence of seizures. In contrast, 18p deletions and seizures are rare. Previous reports on trisomy 12p or monosomy 18p are limited, and little is known about epilepsy in children with trisomy 12p or monosomy 18p. Here, we report a case of 46,XX,der(18)t(12;18)(p11.2;p11.2) with repeatedly disturbed consciousness accompanied with alternating hemiplegia, corresponding to the electroencephalogram findings. G-banding of the parents showed balanced translocation of the mother. The last hospitalization occurred when our patient was 12 years old. She presented with disturbed consciousness and left-sided hemiplegia. Electroencephalography showed continuous 1-2 Hz slow waves in the right hemisphere and a theta burst in the left hemisphere. Based on the genes on chromosomes 12 and 18, the symptoms seemed to be related to partial trisomy 12p. Our case suggests the possibility of a novel seizure phenotype associated with trisomy 12p.
22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal microdeletion disorder, presenting with a broad spectrum of congenital abnormalities and neuropsychiatric symptoms. Movement disorder is one of the most common neurological manifestation of the syndrome. The literature reports that early Parkinson's disease and dystonia in particular are associated with the syndrome. We here describe the first known case of choreiform movement disorder in a girl suffering from 22q11.2DS, responsive to tetrabenazine after a relapsing-remitting course.
Although the brain is an important part of a person's sexual life, little is known about the correlations between sexual response and brain activation. This study examines brain response through clinical testing to reveal a number of brain structures whose activation are relevant to sexual arousal besides psychological testing according to the common traditional values and standards of Iranian society. Based on initial self-report, 25 homosexual and 25 heterosexual males participated in this test to elucidate the identity and sexual trends via Minnesota Multiphasic Personality Inventory (MMPI-2). Also, an fMRI technique - by presenting distinct homo-and heterosexual sex erotic pictures during the test - was employed in neural correlates of sexual arousal via BOLD signal measuring and Statistical Parametric Mapping (SPM) analysis. In five selected homosexuals by the most appropriate MMPI test score, brain activities were significantly detected in midbrain, amygdala, anterior cingulate gyrus, frontal cortex, orbitofrontal cortex, globus pallidus, thalamus and putamen when the participant saw the erotic pictures during the test, which were responsive to sexual arousal. Also, bilateral caudate nucleus, left angular gyrus and bilateral pallidum were activated, but five selected heterosexuals showed no activation in these areas (P<0.001). Likewise, the MMPI method confirmed that homosexuality was relevant to diverse life positions, biological and socioeconomic aspects. The maximum positive correlations were pairwise found in parietal lobule by r = 0.61 (P<0.05) and in frontal gyrus by r = 0.64 (p=0.10), and the minimum negative correlations were in globus palladus by r =-0.18 (p<0.10) and r =-0.16 (p<0.10) for homosexuals and heterosexuals, correspondingly. These results may be useful for understanding the different neural mechanisms of personality recognition and sexual orientation changes while incorporating the individual's history and experience simultaneously into the assessment.
Pediatric lower motor neuron disease is clinically and genetically heterogeneous. We characterized disease progression among children with the spinal muscular atrophy (SMA) phenotype having 2:0 (group A) and 2:1 (group B) of the survival motor neuron 1/2 ( SMN1 : SMN2 ) genotype over 1 year. We included children aged 0 to 12 with the SMA phenotype between January 2018 and December 2021. Their demographic, clinical (Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders [CHOP-INTEND] scores), electrophysiological, radiological, and genetic data were collected from past medical records. The sequential CHOP-INTEND scores and the compound muscle action potential (CMAP) amplitudes were compared using an analysis of covariance test, controlling for age and sex. A linear regression was run to determine the association between the ages of the patients and the CHOP-INTEND scores. Among nine children in group A and six in group B, the decline of the mean (standard deviation) CHOP-INTEND score from the initial value to the 12th-month follow-up value was significant only in group A. CHOP-INTEND scores did not significantly differ between the two groups at the first admission but were significantly lower in group A at the subsequent visits. Group A patients had significantly lower CMAP amplitudes than patients in group B. There was a moderate, negative association between the age of patients and the CHOP-INTEND scores in group A. Group A patients had a significantly higher age-dependent decline in CHOP-INTEND scores and CMAP values than group B, although their age and the severity of weakness did not significantly differ at presentation.
Idiopathic intracranial hypertension (IIH), a clinical disorder also known as pseudotumor cerebri, is characterized by increased intracranial pressure of unknown causes. Although it is most commonly observed in young obese women, IIH can also occur in the pediatric population; however, it is extremely rare in infants. Infants do not typically exhibit characteristic signs and symptoms of IIH, making it challenging to diagnose. Additionally, treatment modalities for this disease remain uncertain. We report an 8-month-old female child admitted to the pediatric emergency department with IIH. Our patient presented initially with fever, vomiting, and diarrhea, and then she developed inability to abduct the left eye. Papilledema was not detected in our patient. Magnetic resonance imaging and lumbar puncture contributed to diagnosis of the patient. Dexamethasone (0.5 mg/kg/d, twice a day) and acetazolamide (5 mg/kg/d) were administered; dexamethasone was stopped at the 48th hour after esotropia had resolved. The patient developed left ptosis in the first month after discharge. Acetazolamide was administered for a duration of 5 months and was discontinued once the patient's eye findings improved. With a sudden onset of neurological findings in a healthy infant with normal neuroimaging, IIH should be considered in the differential diagnosis and cerebrospinal fluid pressure should be measured. The principles of treatment for this disease are based on adult guidelines, but the efficacy of acetazolamide has also been reported in the pediatric population, like in our case.
A middle-aged male presented with subacute onset, progressive illness with diarrhea, persistent hiccups, bilateral hand tremors, gait imbalance, multifocal myoclonus, and weight loss. Clinically, the patient also had cachexia, pallor, oral thrush, and hepatosplenomegaly.. Investigation indicated chronic HIV infection, anemia of chronic disease, transaminitis, hyponatremia, CSF pleocytosis (lymphocyte predominant), elevated CSF protein, diffuse pachymeningeal enhancement on the brain MRI, mediastinal and abdominal necrotic lymphadenopathy, circumferential bowel wall thickening, and hepatosplenomegaly on CECT abdomen. CECT chest exhibited centrilobular nodular opacities. His sputum gene Xpert (R) MTB/RIF was positive for Mycobacterium tuberculosis. He had disseminated tuberculosis with tubercular meningitis, which caused persistent hiccups, gait abnormalities, and multifocal myoclonus. His symptoms resolved with antitubercular treatment. Myoclonus is a rare occurrence with tubercular meningitis.
Background: Naegleria fowleri is a high-temperature freshwater-living amoeba causing PAM by invading nasal epithelium. N. fowleri lives ubiquitously in high-temperature freshwater, but only around 400 cases of PAM have been published worldwide. The mortality rate is 98%. No treatment is 100% effective. Case Presentation: A previously healthy 17-year-old female presented to an urgent care center with fever, headache, sore throat, ear pain, and dizziness. She had swum in freshwater 5 days prior. Her symptoms progressed to altered mental status, photo-and phonophobia, and neck stiffness. Within 4 days, she developed increased intracranial pressure (ICP) and eventually brain death. Two unsuccessful lumbar punctures (LPs) were attempted before the third provided cerebrospinal fluid (CSF) for polymerase chain reaction (PCR) analysis. Magnetic resonance imaging (MRI) showed diffuse cerebral edema, effacement of basal cisterns, tonsillar herniation with diffuse loss of gray-white matter differentiation, leptomeningitis, bifrontal encephalitis with evolving frontal lobe cortical infarcts, and ventriculitis. She was treated with metronidazole, vancomycin, ceftriaxone, acyclovir, and doxycycline. Her increased ICP progressed to brain death, and she died 11 days after lake exposure. CSF PCR was reported positive for N. fowleri the day after her death. Conclusions: Despite advances in diagnostic testing for N. fowleri with PCR, mortality rate is high and current treatments are highly ineffective. This case highlights the importance of epidemiological exposure and considering PAM on the differential diagnosis. Although headache and fever are benign symptoms, they could also represent the first stages of a deadly disease and their progression should be addressed promptly.
Cerebral palsy (CP) is a common condition in children that affects movement and posture due to nonprogressive disruptions during cerebral development. Patients with CP are at a higher risk of developing mental health disorders due to social and physical factors. In total, 28 to 57% of children diagnosed with CP exhibit psychiatric diagnoses or symptoms. The symptoms of intellectual disability and related behavioral disorders that are often associated with CP can be easily confused with the symptoms of a mood disorder. Therefore, there is a possibility of a delay in the diagnostic procedure and the commencement of treatment, which could potentially endanger the mental health of the adolescent and result in long-term complications. By shedding light on diagnosis, treatment, and the follow-up process, this case series, which includes two adolescents with bipolar disorder and CP comorbidity, aims to contribute to the limited literature.
AbstractSpinal cord malformations, known as “spinal dysraphisms” encompass a diverse range of spinal abnormalities characterized by incomplete median closure of mesenchymal, bone, and nervous tissues. They are classified as “open,” involving both the spinal cord and overlying tissues, or “occult,” affecting only nervous system structures. Neurulation abnormalities along the neural tube, from the rostral to the caudal portions, primarily cause these malformations. Clinical presentations vary, including cutaneous manifestations like hemangiomas, dimples, hair tufts, and scoliosis. “Tethered cord syndrome,” often associated with these malformations, manifests as a clinical syndrome rather than a primary anomaly. Newborns are typically asymptomatic, with malformations often identified by associated skin abnormalities. Older children may experience pain, sensory/motor disturbances, urinary/anal sphincter abnormalities, and muscle weakness affecting mobility. Neuroimaging, crucial for diagnosis and treatment planning, includes ultrasound, CT, and MRI. Surgical intervention, tailored to specific malformation subtypes, may involve the repair of myelomeningocele soon after birth or conservative management for asymptomatic occult dysraphism. Rehabilitation encompasses physical, occupational, recreational, and speech therapies. Prevention is paramount, emphasizing the role of health care professionals in prenatal care and education. This review aims to provide a systematic classification of spinal cord malformations to aid clinicians in diagnosis and management.
The aim of this study was to verify and confirm the close correlation between the absence of the medullary arcuate nucleus and sudden death in a 4-month-old infant. Careful neuropathological examination of the cerebral hemispheres, basal ganglia, and cerebellum demonstrated no relevance to the death. The brainstem region, normally occupied by the nuclei, was cut into several serial sections so as not to lose any details. The largest median part of the medullary arcuate nucleus was completely absent, and only very small groups of residual neurons in its most lateral part were still detectable; the rest of the brainstem showed no abnormalities. In the absence of other lesional, degenerative, or malformative causes, the sudden and unexpected death of this infant was likely due to severe hypoplasia/aplasia of the medullary arcuate nucleus. The anatomo-functional development of the nucleus and its crucial role in the control of respiratory and cardiac autonomic reactivity in sleep during the first year of life may provide an important contribution to the pathogenic interpretation.
Inborn Errors of Metabolism (IEM), though heterogenous, are not uncommon. Neurologic manifestations predominate. Without universal newborn screening, early diagnosis and treatment may lessen neuromorbidity. Hence, this study was done to understand small molecule neurometabolic disorders' presentation, diagnostic clues, and outcome. Small molecule neurometabolic disorder was diagnosed in 45 children (postneonatal onset) over 14 years (2008-2022) in a tertiary care hospital. Clinical and laboratory data were retrospectively analyzed. There were 26 boys and 19 girls. The median age at diagnosis was 19 months (interquartile range [IQR] 8-38 months). The median diagnostic delay was 12 months in chronic encephalopathy (IQR 1-24 months) and 1 month (IQR 0.2- 5.5 months) in the acute encephalopathy group (p <= 0.01). The presentation mode was chronic encephalopathy/myopathy in 29 (64.4%) and acute encephalopathy in 11 (24.4%). Diagnostic clues included unexplained developmental delay (n = 27, 60%), tone abnormalities (n = 26, 57.7%), movement disorder and ataxia (n = 16, 35.5%), acute encephalopathy (n = 11, 24.4%), neuroregression (n = 10, 22.2%), macrocephaly (n = 10, 22.2%), and alopecia (n = 4, 8.9%). Diagnostic/suggestive blood-spot tandem mass spectrometry (TMS) was seen in 34/38 (89.5%) children. Neuroimaging helped clinch the diagnosis in 17 (47%) children. Diagnostic categories were organic acidemias (n = 25, 55.6%), urea cycle disorders (n = 11, 24.4%), aminoacidopathies (n = 5, 11.1%), and fatty acid oxidation disorders (n = 4, 8.9%). The neurodevelopmental outcome was normal in 13 (28.8%), mild delay in 12 (26.6%), severe delay in 11 (24.4%), 3 deaths (6.6%), and 6 (13.3%) children being lost to follow-up. Overall, the outcome was favorable in 55% of cases. Unexplained developmental delay with tone abnormalities with or without movement disorders is a joint presentation of late-onset neurometabolic diseases. Neuroimaging studies and laboratory tests like blood-spot TMS help identify many small molecule disorders.
Seizures in infancy are one of the main manifestations of disorders in the central nervous system that can have important etiologies. The development of anticonvulsant drugs and the importance of drug selection in infants, due to more complex underlying etiologies, compared with older ages, explicate the essentiality of executing clinical investigations to appraise the optimal therapeutic approach. The objective of the current investigation is to juxtapose two therapeutic approaches involving intravenous levetiracetam and intravenous phenobarbital in the management of neonatal seizures. This is a randomized controlled clinical trial study on 100 infants who were referred to the Hazrat Masoumeh (S) Hospital in Qom owing to convulsions. Infants with seizure who fulfilled the inclusion criteria were arbitrarily allocated to one of the two intervention cohorts: intravenous levetiracetam or intravenous phenobarbital, and therapeutic responses were compared. There was a substantial relationship between seizure time, seizure etiology, anticonvulsant therapy type, and treatment responsiveness. As a result, the risks of not responding to therapy and increasing the dose were approximately 6 and 5 times higher, respectively, in the group that experienced seizures in the fourth week than in the other groups. Infants with cerebrovascular anomalies were more prone to not responding to treatment. Furthermore, children administered phenobarbital had a 2.5-fold higher chance of not responding to treatment than those given levetiracetam ( p = 0.043).
