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Pediatric Neurology May 2024Periventricular leukomalacia (PVL) is a common brain injury in premature infants, and epilepsy remains a significant complication. One concerning electroencephalographic...
BACKGROUND
Periventricular leukomalacia (PVL) is a common brain injury in premature infants, and epilepsy remains a significant complication. One concerning electroencephalographic (EEG) pattern found is developmental and/or epileptic encephalopathy with spike-and-wave activation in sleep (DEE-SWAS). This pattern is associated with persistent neuropsychological and motor deficits, even without a diagnosis of epilepsy. The purpose of this study is to identify the relationships between various PVL grades and EEG patterns in this population on follow-up visits, especially the occurrence of DEE-SWAS pattern on EEG.
METHODS
This is a retrospective study of <36 weeks gestational age newborns who were followed in the neurodevelopmental clinic at Corewell Health East/Corewell Health Children's Hospital in Royal Oak, Michigan, between 2020 and 2022. Patients' demographics along with prematurity complications, diagnostic head ultrasound (HUS), and EEG studies were reviewed and graded. EEG studies are usually ordered when seizures were suspected.
RESULTS
A total of 155 newborns met the inclusion criteria. Twenty-six patients had PVL. Nine patients had grade 2 to 3 PVL based on HUS review. EEG was performed on 15 patients with PVL at a mean age of 22 months. More severe PVL grades were significantly associated with worse EEG patterns (P = 0.005). Five patients had DEE-SWAS pattern on EEG, all of whom had grade 2 or 3 PVL. Epilepsy was eventually diagnosed in three infants with PVL.
CONCLUSIONS
EEG can help identify important abnormal electrographic patterns in premature infants with PVL early in life; this might give a window of opportunity to intervene early and improve long-term developmental outcomes in this population.
PubMed: 38917516
DOI: 10.1016/j.pediatrneurol.2024.05.014 -
Journal of Neural Transmission (Vienna,... Jun 2024Benign hereditary chorea (BHC) is an inherited neurological disorder consisting of childhood-onset, nonprogressive chorea, generally without any other manifestations. In... (Review)
Review
Benign hereditary chorea (BHC) is an inherited neurological disorder consisting of childhood-onset, nonprogressive chorea, generally without any other manifestations. In most reported cases, the inheritance of BHC is autosomal dominant but both incomplete penetrance and variable expressivity are observed and can be caused by NKX2-1 mutations. The spectrum contains choreoathetosis, congenital hypothyroidism, and neonatal respiratory distress syndrome. The neurological symptoms can be misdiagnosed as Huntington's disease (HD). The two Polish families were diagnosed with NKX2-1 gene mutations and a literature review concerning the NKX2-1-related disorders was conducted. All family members were examined by experienced movement disorders specialists. PubMed database was searched to obtain previously described NKX2-1 cases. Whole exome sequencing (WES) was performed in one proband (Family A) and direct NKX2-1 sequencing in the second (Family B). Two Polish families were diagnosed with NKX2-1 gene mutations (p.Trp208Leu and p.Cys117Alafs*8). In one family, the co-occurrence of HD was reported. Forty-nine publications were included in the literature review and symptoms of 195 patients with confirmed NKX2-1 mutation were analyzed. The most common symptoms were chorea and choreiform movements, and delayed motor milestones. The NKX2-1 mutation should always be considered as a potential diagnosis in families with chorea, even with a family history of HD. Lack of chorea does not exclude the NKX2-1-related disorders.
PubMed: 38916623
DOI: 10.1007/s00702-024-02800-3 -
Journal of Clinical Sleep Medicine :... Jun 2024We report a case of severe central sleep apnea incidentally diagnosed during polysomnography for suspected obstructive sleep apnea. Characteristic clinical features...
We report a case of severe central sleep apnea incidentally diagnosed during polysomnography for suspected obstructive sleep apnea. Characteristic clinical features included episodic hyperventilation followed by apnea from hypocapnia, which did not follow a Cheyne-Stokes pattern. Combined with the identification of cerebellar and brainstem malformations known as the "molar tooth sign" on a brain MRI, developmental delay, and motor coordination problems, Joubert syndrome (a congenital disease) was first diagnosed at the age of 50 years. Central apneas were also observed during wakefulness, although not continuously. During sleep, continuous positive airway pressure and adaptive servo-ventilation were ineffective at the referring clinic and at our hospital. Supplemental oxygen decreased the frequency of central apneas and significantly shortened the duration of each central sleep apnea compared with room air. In contrast, the opposite response was observed with acetazolamide administration.
PubMed: 38916285
DOI: 10.5664/jcsm.11224 -
BioRxiv : the Preprint Server For... Jun 2024ECHS1 Deficiency (ECHS1D) is a rare and devastating pediatric disease that currently has no defined treatments. This disorder results from missense loss-of-function...
ECHS1 Deficiency (ECHS1D) is a rare and devastating pediatric disease that currently has no defined treatments. This disorder results from missense loss-of-function mutations in the gene that result in severe developmental delays, encephalopathy, hypotonia, and early death. ECHS1 enzymatic activity is necessary for the beta-oxidation of fatty acids and the oxidation of branched-chain amino acids within the inner mitochondrial matrix. The pathogenesis of disease remains unknown, however it is hypothesized that disease is driven by an accumulation of toxic metabolites from impaired valine oxidation. To expand our knowledge on disease mechanisms, a novel mouse model of ECHS1D was generated that possesses a disease-associated knock-in (KI) allele and a knock-out (KO) allele. To investigate the behavioral phenotype, a battery of testing was performed at multiple time points, which included assessments of learning, motor function, endurance, sensory responses, and anxiety. Neurological abnormalities were assessed using wireless telemetry EEG recordings, pentylenetetrazol (PTZ) seizure induction, and immunohistochemistry. Metabolic perturbations were measured within the liver, serum, and brain using mass spectrometry and magnetic resonance spectroscopy. To test disease mechanisms, mice were subjected to disease pathway stressors and then survival, body weight gain, and epilepsy were assessed. Mice containing KI/KI or KI/KO alleles were viable with normal development and survival, and the presence of KI and KO alleles resulted in a significant reduction in ECHS1 protein. ECHS1D mice displayed reduced exercise capacity and pain sensation. EEG analysis revealed increased slow wave power that was associated with perturbations in sleep. ECHS1D mice had significantly increased epileptiform EEG discharges, and were sensitive to seizure induction, which resulted in death of 60% of ECHS1D mice. Under basal conditions, brain structure was grossly normal, although histological analysis revealed increased microglial activation in aged ECHS1D mice. Increased dietary valine only affected ECHS1D mice, which significantly exacerbated seizure susceptibility and resulted in death. Lastly, acute inflammatory challenge drove regression and early lethality in ECHS1D mice. In conclusion, we developed a novel model of ECHS1D that may be used to further knowledge on disease mechanisms and to develop therapeutics. Our data suggests altered metabolic signaling and inflammation may contribute to epilepsy in ECHS1D, and these alterations may be attributed to impaired valine metabolism.
PubMed: 38915588
DOI: 10.1101/2024.06.13.598697 -
Journal of Osteopathic Medicine Jun 2024Prenatal substance exposure (PSE) can lead to various harmful outcomes for the developing fetus and is linked to many emotional, behavioral, and cognitive difficulties...
CONTEXT
Prenatal substance exposure (PSE) can lead to various harmful outcomes for the developing fetus and is linked to many emotional, behavioral, and cognitive difficulties later in life. Therefore, examination of the relationship between the development of associated brain structures and PSE is important for the development of more specific or new preventative methods.
OBJECTIVES
Our study's primary objective was to examine the relationship between the physical development of the amygdala, hippocampus, and parahippocampus following prenatal alcohol, tobacco, and prescription opioid exposure.
METHODS
We conducted a cross-sectional analysis of the Adolescent Brain and Cognitive Development (ABCD) Study, a longitudinal neuroimaging study that measures brain morphometry from childhood throughout adolescence. Data were collected from approximately 12,000 children (ages 9 and 10) and parents across 22 sites within the United States. Prenatal opioid, tobacco, and alcohol use was determined through parent self-report of use during pregnancy. We extracted variables assessing the volumetric size (mm) of the amygdala, hippocampus, and parahippocampal gyrus as well as brain volume, poverty level, age, sex, and race/ethnicity for controls within our adjusted models. We reported sociodemographic characteristics of the sample overall and by children who had PSE. We calculated and reported the means of each of the specific brain regions by substance exposure. Finally, we constructed multivariable regression models to measure the associations between different PSE and the demographic characteristics, total brain volume, and volume of each brain structure.
RESULTS
Among the total sample, 24.6% had prenatal alcohol exposure, 13.6% had prenatal tobacco exposure, and 1.2% had prenatal opioid exposure. On average, those with prenatal tobacco exposure were found to have a statistically significant smaller parahippocampus.
CONCLUSIONS
We found a significant association between prenatal tobacco exposure and smaller parahippocampal volume, which may have profound impacts on the livelihood of individuals including motor delays, poor cognitive and behavioral outcomes, and long-term health consequences. Given the cumulative neurodevelopmental effects associated with PSE, we recommend that healthcare providers increase screening rates, detection, and referrals for cessation. Additionally, we recommend that medical associations lobby policymakers to address upstream barriers to the effective identification of at-risk pregnant individuals, specifically, eliminating or significantly reducing punitive legal consequences stemming from state laws concerning prenatal substance use.
PubMed: 38915228
DOI: 10.1515/jom-2023-0277 -
The Clinical Neuropsychologist Jun 2024Multiple sclerosis (MS) may include not only severe neurological signs and symptoms, but also cognitive and psychiatric disturbances. When psychiatric symptoms precede...
Multiple sclerosis (MS) may include not only severe neurological signs and symptoms, but also cognitive and psychiatric disturbances. When psychiatric symptoms precede or are comorbid with MS, it poses a clinical challenge, because it may lead to a mistaken diagnosis of MS as a psychiatric disorder, delaying proper treatment. We describe the neuropsychological profile of a female patient with MS whose diagnosis was delayed due to neuropsychiatric symptoms. : A comprehensive analysis of the medical history and the results of a teleneuropsychological assessment of a 36-year-old Mexican woman with a diagnosis of relapsing--remitting MS (RRMS) was performed. : The patient indicates a long history of psychotic, anxious, and depressive features years before the first neurological symptom that led to MS going unnoticed for several years. Language, attentional, perceptual, motor, and learning skills were found to be preserved. Short-term memory and spatial orientation problems were identified, with decreased processing speed and executive dysfunction, including working memory and planning deficits. : The patient has a non-typical presentation of neuropsychological alterations with cognitive and behavioral symptoms that resemble dorsolateral frontal lobe syndrome. This case study highlights the importance of considering MS in differential diagnosis of patients with psychiatric symptoms, even in the absence of obvious neurological signs.
PubMed: 38914594
DOI: 10.1080/13854046.2024.2370963 -
Child's Nervous System : ChNS :... Jun 2024Encephalocele represent a group of disorders which is characterised by extracranial herniation of the leptomeninges, brain, and CSF through a structural defect in the...
BACKGROUND
Encephalocele represent a group of disorders which is characterised by extracranial herniation of the leptomeninges, brain, and CSF through a structural defect in the cranium. They are usually associated with other intracranial anomalies which may impact the neurological development.
AIM
This study aimed to assess the predictors of neurological development of patients undergone surgical excision of occipital encephalocele.
METHODS
All patients with occipital encephaloceles operated over the last decade (2012-2022). The sac size, presence of hydrocephalous, and associated anomalies were noted. The biopsy of these patients were reviewed and categorised as those which contains mature neural tissue and those without. The neurological outcomes were assessed by social, language, cognitive, and motor milestone and has been stratified into no delay, mild (1 of 4), moderate (2 or 3 of 4), and severe development delay (4 of 4).
RESULTS
Total of 35 patients were included with median age of 10 months (IQR = 5-20 months). Fifteen (42.9%) patients had sac size of ≥ 5 cm, and 23 (65.7%) patients had mature neural tissues on biopsy. The median follow-up period was 6.4 years (IQR = 4.38-10.65) years. Seventeen (49.6%) patients had moderate to severe developmental delay. The sac size of ≥ 5 cm (AOR = 33.5; 95%CI = 3.35-334.8) (p = 0.003) and presence of mature neural content in the sac (AOR = 13.32; 95%CI = 1.1-160.36) (p = 0.041) were associated with significant neurodevelopmental delay.
CONCLUSION
The presence of a large sac of ≥ 5 cm and the presence of mature neural tissues on histopathological specimen of patients with encephalocele point towards the possibility of poor neurological development.
PubMed: 38913184
DOI: 10.1007/s00381-024-06506-5 -
Journal of Neurologic Physical Therapy... Jun 2024Visual biofeedback can be used to help people post-stroke reduce biomechanical gait impairments. Using visual biofeedback engages an explicit, cognitively demanding...
BACKGROUND AND PURPOSE
Visual biofeedback can be used to help people post-stroke reduce biomechanical gait impairments. Using visual biofeedback engages an explicit, cognitively demanding motor learning process. Participants with better overall cognitive function are better able to use visual biofeedback to promote locomotor learning; however, which specific cognitive domains are responsible for this effect are unknown. We aimed to understand which cognitive domains were associated with performance during acquisition and immediate retention when using visual biofeedback to increase paretic propulsion in individuals post-stroke.
METHODS
Participants post-stroke completed cognitive testing, which provided scores for different cognitive domains, including executive function, immediate memory, visuospatial/constructional skills, language, attention, and delayed memory. Next, participants completed a single session of paretic propulsion biofeedback training, where we collected treadmill-walking data for 20 min with biofeedback and 2 min without biofeedback. We fit separate regression models to determine if cognitive domain scores, motor impairment (measured with the lower-extremity Fugl-Meyer), and gait speed could explain propulsion error and variability during biofeedback use and recall error during immediate retention.
RESULTS
Visuospatial/constructional skills and motor impairment best-explained propulsion error during biofeedback use (adjusted R 2 = 0.56, P = 0.0008), and attention best-explained performance variability (adjusted R 2 = 0.17, P = 0.048). Language skills best-explained recall error during immediate retention (adjusted R 2 = 0.37, P = 0.02).
DISCUSSION AND CONCLUSIONS
These results demonstrate that specific cognitive domain impairments explain variability in locomotor learning outcomes in individuals with chronic stroke. This suggests that with further investigation, specific cognitive impairment information may be useful to predict responsiveness to interventions and personalize training parameters to facilitate locomotor learning.
PubMed: 38912856
DOI: 10.1097/NPT.0000000000000487 -
Cureus Jun 2024Malformations of cortical development (MCD) are a group of disorders affecting the normal development of the human cortex and are significant causes of delay in...
Malformations of cortical development (MCD) are a group of disorders affecting the normal development of the human cortex and are significant causes of delay in psychomotor development and epilepsy in children. Lissencephaly (smooth brain) forms a major group of brain malformations. Microtubules help in the migration of neuronal cells. Defect in tubulin gene alpha-tubulin (TUBA), beta-tubulin (TUBB), and gamma-tubulin (TUBG) leads to defective neuronal migration. This group of disorders is termed as "tubulinopathies." The important genes implicated in causing lissencephaly are LIS1, XLIS, and TUBA1A gene. Recently, a mutation in the TUBG1 gene is associated with it. Here, we report a one-and-a-half-year-old girl with global developmental delay, microcephaly, infantile-onset epilepsy, epileptic spasms, dysmorphism, and motor signs. There was no significant birth history. Neuroimaging (MRI) showed a broad thick gyri and a decreased number of sulci suggestive of lissencephaly/pachygyria spectrum. There was dilatation of the ventricles, and no grey matter heterotopia was noted. Sleep EEG showed multifocal epileptiform discharges. The child was treated with multiple anti-seizure medicines (ASMs). A genetic test, whole exome sequencing, was done to determine the etiology of MCD. A heterozygous missense variation in exon 6 of the TUBG1 gene was identified and reported as a "variant of unknown significance." Still, because the genotype matched with the clinical phenotype of the patient, it was considered clinically significant. Therefore, a complete diagnosis of TUBG1 mutation-associated cortical malformation (lissencephaly/pachygyria) with microcephaly and early-onset epilepsy was established. TUBG1 mutation is de novo in most cases, but parental testing is recommended. The parents of such patients need to be counseled about the need for prenatal testing and the risk of the disease to siblings. The overall prognosis in such cases is poor because of refractory seizures, physical limitations, and intellectual disability.
PubMed: 38912084
DOI: 10.7759/cureus.62749 -
Neurobiology of Language (Cambridge,... 2024Research points to neurofunctional differences underlying fluent speech between stutterers and non-stutterers. Considerably less work has focused on processes that...
Research points to neurofunctional differences underlying fluent speech between stutterers and non-stutterers. Considerably less work has focused on processes that underlie stuttered vs. fluent speech. Additionally, most of this research has focused on speech motor processes despite contributions from cognitive processes prior to the onset of stuttered speech. We used MEG to test the hypothesis that reactive inhibitory control is triggered prior to stuttered speech. Twenty-nine stutterers completed a delayed-response task that featured a cue (prior to a go cue) signaling the imminent requirement to produce a word that was either stuttered or fluent. Consistent with our hypothesis, we observed increased beta power likely emanating from the right pre-supplementary motor area (R-preSMA)-an area implicated in reactive inhibitory control-in response to the cue preceding stuttered vs. fluent productions. Beta power differences between stuttered and fluent trials correlated with stuttering severity and participants' percentage of trials stuttered increased exponentially with beta power in the R-preSMA. Trial-by-trial beta power modulations in the R-preSMA following the cue predicted whether a trial would be stuttered or fluent. Stuttered trials were also associated with delayed speech onset suggesting an overall slowing or freezing of the speech motor system that may be a consequence of inhibitory control. Post-hoc analyses revealed that independently generated anticipated words were associated with greater beta power and more stuttering than researcher-assisted anticipated words, pointing to a relationship between self-perceived likelihood of stuttering (i.e., anticipation) and inhibitory control. This work offers a neurocognitive account of stuttering by characterizing cognitive processes that precede overt stuttering events.
PubMed: 38911458
DOI: 10.1162/nol_a_00138