Cranial ultrasound in neonatal herpes simplex encephalitis.

Neonatal infection with herpes simplex virus (HSV) is associated with significant morbidity, high mortality, and long-term neurological sequelae. We report the clinical case of an infant with HSV encephalitis, where the initial diagnosis was established based on cranial ultrasound (CUS) findings. These findings revealed localized, asymmetrically distributed hyperechoic areas in the parenchyma and signs of brain swelling. CUS dynamics on days 7 and 14 after the onset of clinical symptoms demonstrated multiple subcortical and perivascular zones of encephalomalacia in the right hemisphere, accompanied by ex vacuo ventricular dilatation. The cerebellum, left basal ganglia, and left hemisphere appeared to be less affected by the pathological process.

Clinical characteristics of cystic encephalomalacia in children.

Purpose: To investigate the primary causes and clinical characteristics of cystic encephalomalacia (CE) in children. Methods: The clinical data of 50 children who were admitted to our hospital due to CE between January 2008 and December 2020 were retrospectively reviewed. Their primary causes, clinical manifestations and cranial magnetic resonance imaging features were analyzed. Results: Among all patients, 5 had prematurity, 19 had hypoxic-ischemic encephalopathy (HIE), 13 had intracranial infection, 14 had traumatic brain injury and hemorrhage, 4 had cerebral infarction, 2 had congenital genetic diseases, and 1 had hypoglycemia. The average time from primary disease onset to CE diagnosis was 70.1 ± 61.0 days. The clinical manifestations included speech or motor developmental delay (n = 33), epilepsy (n = 31), dystonia (n = 27), limb paralysis (n = 16), and visual or auditory impairment (n = 5). Patients with HIE as the primary cause of CE had a significantly higher occurrence of dystonia, while a significantly higher incidence of paralysis was observed in those with cerebral infarction as the primary cause. Conclusion: CE in children is mainly caused by HIE, intracranial infection, and cerebral hemorrhage. The major clinical manifestations included speech or motor developmental delay, epilepsy, and dystonia. Magnetic resonance imaging is an important tool for the diagnosis of CE.

MRCT and CT in the diagnosis of pediatric disease imaging: assessing imaging performance and clinical effects.

OBJECTIVE: This study focused on analyzing the clinical value and effect of magnetic resonance imaging plus computed tomography (MRCT) and CT in the clinical diagnosis of cerebral palsy in children. METHODS: From February 2021 to April 2023, 94 children diagnosed with cerebral palsy were selected from our hospital for study subjects. These patients were divided into CT and MRI groups, with CT examination given to the CT group and MRI examination given to the MRI group. The positive rate of the two examination methods in the diagnosis of cerebral palsy was compared, different imaging signs in two groups of children with cerebral palsy were compared, and the diagnostic test typing results between two groups were further analyzed. RESULTS: The diagnostic positivity rate of the children in the MRI group was 91.49%, which was significantly higher than that of the children in the CT group (70.21%) (P < 0.05). In both groups, encephalomalacia, bilateral frontal subdural effusions, and gray-white matter atrophy of the brain were the main signs, and the difference in the proportion of these three imaging signs between the two groups was not significant (P > 0.05). Differences between the two groups examined for cerebral palsy subtypes were not significant (P > 0.05). CONCLUSION: The positive rate of pediatric cerebral palsy examined by MRI is higher than that of CT diagnosis, but the clinic should organically combine the two to further improve the detection validity and accuracy.

Human chorionic gonadotropin decreases cerebral cystic encephalomalacia and parvalbumin interneuron degeneration in a pro-inflammatory model of mouse neonatal hypoxia-ischemia.

The pregnancy hormone, human chorionic gonadotropin (hCG) is an immunoregulatory and neurotrophic glycoprotein of potential clinical utility in the neonate at risk for cerebral injury. Despite its well-known role in its ability to modulate the innate immune response during pregnancy, hCG has not been demonstrated to affect the pro-degenerative actions of inflammation in neonatal hypoxia-ischemia (HI). Here we utilize a neonatal mouse model of mild HI combined with intraperitoneal administration of lipopolysaccharide (LPS) to evaluate the neuroprotective actions of hCG in the setting of endotoxin-mediated systemic inflammation. Intraperitoneal treatment of hCG shortly prior to LPS injection significantly decreased tissue loss and cystic degeneration in the hippocampal and cerebral cortex in the term-equivalent neonatal mouse exposed to mild HI. Noting that parvalbumin immunoreactive interneurons have been broadly implicated in neurodevelopmental disorders, it is notable that hCG significantly improved the injury-mediated reduction of these neurons in the cerebral cortex, striatum and hippocampus. The above findings were associated with a decrease in the amount of Iba1 immunoreactive microglia in most of these brain regions. These observations implicate hCG as an agent capable of improving the neurological morbidity associated with peripheral inflammation in the neonate affected by HI. Future preclinical studies should aim at demonstrating added neuroprotective benefit by hCG in the context of therapeutic hypothermia and further exploring the mechanisms responsible for this effect. This research is likely to advance the therapeutic role of gonadotropins as a treatment for neonates with neonatal brain injury.

Functional Recovery in a Patient of Abnormal Left Parieto-Occipital Encephalomalacia With Gliosis-Associated Genu Varum Deformity: A Case Report.

Parieto-occipital encephalomalacia is a macroscopic appearance of the brain with loss of cerebral parenchyma associated with gliosis in the brain's anatomical structures. It occurs because of the liquefaction of brain parenchymal necrosis after cerebral ischemia, infection, and haemorrhages. It is often surrounded by glial cell proliferation in response to damage. Rehabilitation after the manifestation of neurological function must be tailored, and well-coordinated intervention must be formulated. We present a case study of a 77-year-old male with parieto-occipital encephalomalacia associated with genu varum deformity with a complaint of generalized weakness, vertigo, giddiness, and fall with one episode of a seizure attack. Further, bilateral genu varum deformity was noted on the knees. Encephalomalcia is associated with vitamin D deficiency. The physiotherapy rehabilitation consisted of resolving the symptoms of the patient, along with working on strengthening weak muscles of the genu varum deformity of the patient. The proprioceptive neuromuscular facilitation (PNF) method is a popular rehabilitation strategy for regaining motor function. Numerous outcome measures were used to monitor the patient's progress. Outcome measures such as the tone grading scale (TGS), motor assessment scale (MAS), dynamic gait index (DGI), Barthel index (BI), and world health-related quality-of-life (WHORQOL) scales were used. The rehabilitation lasted for six weeks. Tele-rehabilitation also plays a crucial impact in the recovery of patients. By the end of our rehabilitation, the patient significantly improved in performing activities of daily living and improved his quality of life. Tele-rehabilitation helped us stay connected with the patient.

A ventriculomegaly feature computational pipeline to improve the screening of normal pressure hydrocephalus on CT.

OBJECTIVE: The objective of this study was to develop a computational pipeline that extracts objective features of ventriculomegaly from non-contrast CT (NCCT) for the accurate classification of idiopathic normal pressure hydrocephalus (NPH) from headache controls (HCs), Alzheimer's dementia (AD), and posttraumatic encephalomalacia (PTE). METHODS: Patients with possible NPH (n = 79) and a subset with definite NPH (DefNPH; n = 29) were retrospectively identified in the Veterans Affairs Informatics and Computing Infrastructure system, along with the AD (n = 62), PTE (n = 53), and HC (n = 59) cohorts. Image-processing pipelines were developed to extract a novel feature capturing the maximum eccentricity of the lateral ventricles (MaxEccLV), a proxy splenial angle (p-SA), the Evans indices (EI-x, -y, and -z), callosal angle, normalized maximum third-ventricle width, and CSF to brain volume ratio from their NCCT scans. The authors used t-tests to examine group differences in the features and multivariate logistic regression models for classification. Additionally, the NPH versus HC classifier was validated on external data. RESULTS: When NPH and DefNPH were compared with HC, AD, and PTE, significant differences were found in all features except the p-SA, which only significantly differed between NPH and PTE. The test-set area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were 0.98, 100%, and 98.3% for NPH versus HC classification; 0.94, 87.3%, and 85.5% for NPH versus AD; 0.96, 92.4%, and 90.6% for NPH versus PTE; and 0.96, 94%, and 88% for NPH versus the other groups using logistic regression under five-fold cross-validation. Consistently high performance was noted for DefNPH. The NPH versus HC classifier provided an AUC of 0.84, sensitivity of 76.9%, and specificity of 90% when assessed on external data. CONCLUSIONS: Including the novel MaxEccLV, this framework computes useful features of ventriculomegaly, which had not previously been algorithmically assessed on NCCT. This framework successfully classified possible and definite NPH from HC, AD, and PTE. Following validation on larger representative cohorts, this objective and accessible tool may aid in screening for NPH and differentiating it from symptomatic mimics such as AD and PTE.

Distinguishing multicystic from focal encephalomalacia on delayed MRI in children with term hypoxic ischemic injury.

BACKGROUND AND PURPOSE: To define cystic patterns resulting from term hypoxic ischemic injury (HII) on delayed Magnetic Resonance Imaging (MRI) and determine associated HII patterns and lesions that reflect the severity of injury, from a database of African children with cerebral palsy. METHODS: Retrospective review of 1175 children with cerebral palsy due to term HII diagnosed on late MRI, identifying those with cystic changes. These were classified as multicystic or (multi-) focal-cystic, and were evaluated for associated injuries-thalami, basal ganglia, hippocampi, cerebellum, and presence of ulegyria. RESULTS: Three hundred and eighty-eight of 1175 (33%) children had cystic encephalomalacia. Two hundred and seven of 388 (53.3%) had focal-cystic and 181/388 (46.6%) had multicystic injury. The focal-cystic group comprised 87.9% (182/207) with thalamic injury, 25.6% (53/207) with basal ganglia injury, and 15% (31/207) with cerebellar involvement. Basal-ganglia-thalamus (BGT) pattern was present in 43.9% (91/207) and ulegyria in 69.6% (144/207). In the multicystic group, 88.9% (161/181) had thalamic injury, 30.9% (56/181) had basal ganglia injury, and 21% (38/181) had cerebellar involvement. BGT pattern was observed in 29.8% (54/181) and ulegyria in 28.7%. (52/181). Significant associations (p<.05) were found between multicystic injury and caudate/globus pallidus involvement, and between focal-cystic pattern of injury and ulegyria. CONCLUSIONS: Cystic encephalomalacia was seen in almost one-third of patients with term HII imaged with delayed MRI, with a similar prevalence of focal-cystic and multicystic injury. Multicystic injury was associated with caudate and globus pallidi involvement, typical of the BGT pattern of HII, whereas the focal-cystic pattern was associated with ulegyria, typical of watershed injury.

Delineating the phenotype of PNPLA8-related mitochondriopathies.

Pathogenic variants in PNPLA8 have been described either with congenital onset displaying congenital microcephaly, early onset epileptic encephalopathy and early lethality or childhood neurodegeneration with progressive microcephaly. Moreover, a phenotype comprising adulthood onset cerebellar ataxia and peripheral neuropathy was also reported. To our knowledge, only six patients with biallelic variants in PNPLA8 have been reported so far. Here, we report the clinical and molecular characterizations of three additional patients in whom exome sequencing identified a loss of function variant (c.1231C>T, p.Arg411Ter) in Family I and a missense variant (c.1559T>A, p.Val520Asp) in Family II in PNPLA8. Patient 1 presented with the congenital form of the disease while Patients 2 and 3 showed progressive microcephaly, infantile onset seizures, progressive cortical atrophy, white matter loss, bilateral degeneration of basal ganglia, and cystic encephalomalacia. Therefore, our results add the infantile onset as a new distinct phenotype of the disease and suggest that the site of the variant rather than its type is strongly correlated with the disease onset. In addition, these conditions demonstrate some overlapping features representing a spectrum with clinical features always aligning with different age of onset.

Presentation of Dyke-Davidoff-Masson Syndrome in a 32-Year-Old Female: Report of a Rare Case With a Literature Review.

Dyke-Davidoff-Masson syndrome (DDMS) is a rare congenital or acquired neurological disorder that most commonly affects the pediatric population but is also rarely reported in adults. DDMS results from brain injury in the intrauterine or early years of life. It is characterized by prominent cortical sulci, hyperpneumatization of the frontal sinus, unilateral cerebral hemiatrophy with ventricular dilation, and associated bony thickness of the cranial vault. Seizures and asymmetric hemiparesis are the most consistent findings in DDMS with facial asymmetry and mental retardation widely reported. Herein, we report a case of a 32-year-old female patient with DDMS presenting with a history of seizure and right-sided hemiparesis. Neuroimaging findings showed asymmetric cerebral encephalomalacia and gliosis with ex vacuo ventricular dilatation and calvarial diploic space widening. Our case report is unique in the sense that our patient presented with DDMS in adulthood with no signs of mental retardation or history of seizures during childhood and well-controlled seizures on monotherapy. Given the adult presentation of DDMS is unusual and rarely reported in the medical literature, our case report will help physicians to keep DDMS high on differential diagnoses in such cases. Awareness of the clinical features of DDMS on imaging can facilitate a timely and accurate diagnosis, thereby enabling appropriate and prompt management.

Case report: Neonatal diabetes mellitus caused by KCNJ11 mutation presenting with intracranial hemorrhage.

Neonatal diabetes mellitus (NDM) is a rare type of monogenic diabetes. At present, most published studies have focused on the types of gene mutations associated with NDM and the therapeutic effect of sulfonylureas (SUs) on the disease; few studies on NDM-associated intracranial hemorrhage (ICH) exist. In addition, p.V59M mutations generally lead to intermediate DEND (iDEND: intermediate developmental delay and neonatal diabetes) syndrome without epilepsy. Here, we present a case of a 1-month-old male infant who was diagnosed with NDM caused by a KCNJ11 missense mutation (p.V59M), presenting with cerebral injury. In the early stage of the disease, continuous insulin dose adjustment did not achieve an ideal level of blood glucose. Although blood glucose was subsequently controlled by oral SUs, which were administered after the genetic test result, the patient still displayed epilepsy and developmental delay. In this case report, we present our experience in the treatment of the infant, switching from insulin to oral SUs and we thought that SUs have limited effects on improving the prognosis of neurodevelopmental disturbances in NDM with foci of encephalomalacia. In addition, there may be a relationship between KCNJ11 missense mutations and cerebral injury, and further research must be carried out to confirm these points.

Erratum: Pseudo-feeders as a red flag of impending or ongoing severe brain damage in Vein of Galen Aneurysmal Malformation.

[This corrects the article DOI: 10.3389/fped.2022.1066114.].

Encephalomalacia/gliosis, deep venous thrombosis, and cancer in Arg393His antithrombin Hanoi and the potential impact of the ß-amyloid precursor protein (APP) on thrombosis and cancer.

A heterozygous Arg393His point mutation at the reactive site of antithrombin (AT) gene causing thrombosis in a Vietnamese patient is reported and named as Arg393His in AT-Hanoi. The present variant is characterized by a severe reduction of functionally active AT plasma concentration to 42% of normal resulting in multiple severe thrombotic events such as cerebral venous thrombosis (CVT) (encephalomalacia/gliosis), recurrent deep venous thrombosis (DVT) and the development of kidney cancer. Today the complexity of thrombophilia has grown with appreciation that multiple inherited and acquired risk factors may interact to result in a clinically thrombotic phenotype. This article focuses on the following issues: (1) pathophysiology and clinical conditions of Arg393His in AT-Hanoi; (2) "two way association" between cancer and thrombosis in which venous thromboembolism (VTE) can be both a presenting sign and a complication of cancer; (3) efficacy of anticoagulants used for the prevention of cancer-related thrombosis; (4) conditions of acquired risk factors such as cancer or genetic disorders via epigenetic modifications in gene-gene (epistasis) and/or gene-environment interactions such as in Lesch-Nyhan disease (LND), in which the ß-amyloid precursor protein (APP) that may interact to predispose a patient to thrombosis and cancer. It is also necessary to study the hypoxanthine-guanine phosphoribosyltransferase (HGprt) enzyme, AT, and APP using expression vectors for exploring their impact on LND, thrombosis as well as other human diseases, especially the ones related to APP such as Alzheimer's disease (AD) and cancer. For such a purpose, the construction of expression vectors for HGprt and APP, with or without the glycosyl-phosphatidylinositol (GPI) anchor, was performed as described in Ref. #148 (Nguyen, K. V., Naviaux, R. K., Nyhan, W. L. Lesch-Nyhan disease: I. Construction of expression vectors for hypoxanthine-guanine phosphoribosyltransferase (HGprt) enzyme and amyloid precursor protein (APP). Nucleosides Nucleotides Nucleic Acids 2020, 39: 905-922). In the same manner, the construction of expression vectors for AT and APP can be performed as shown in Figure 6. These expressions vectors, with or without GPI anchor, could be used as tools for (a) studying the effects of Arg393His mutation in AT; (b) studying the emerging role of Arg393His mutation in AT and cancer; (c) studying intermolecular interactions between APP and AT. Furthermore, the construction of expression vectors as described in Ref. #148, especially the one with GPI, can be used as a model for the construction of expression vectors for any protein targeting to the cell plasma membrane for studying intermolecular interactions and could be therefore useful in the vaccines as well as antiviral drugs development (studying intermolecular interactions between the spike glycoprotein of the severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, as well as its variants and the angiotensin-converting enzyme 2, ACE2, in coronavirus disease 2019 (COVID-19) [155],[156], for example).

Severe encephalopathy associated with SARS-CoV-2 Omicron BA.1 variant infection in a neonate.

INTRODUCTION: The coronavirus disease 2019 (COVID-19), including the Omicron variant, is less severe in children than in adults. To date, there has been no detailed description of COVID-19-associated severe encephalopathy due to the Omicron variant during the neonatal and early infantile periods. CASE PRESENTATION: During the outbreak of the Omicron variant, a 29-day-old male presented with a pale and ill appearance. The patient was intubated for mechanical ventilation owing to recurrent apnea, which subsequently turned out to be a breath-holding that may have been caused by seizure. In addition, nonconvulsive status epilepticus was observed. Total duration of repetitive seizure activities was approximately 30 min per hour when seizures were most severe. Brain magnetic resonance imaging (MRI) on day 14 revealed extensive hyperintensity in the T2 sequence, hypointensity in the fluid-attenuated inversion recovery (FLAIR) sequence in the deep and subcortical white matter, and diffusion restriction in the corpus callosum. The Omicron BA.1 variant of the severe acute respiratory syndrome coronavirus 2 was detected in his respiratory sample. Follow-up MRI on day 45 revealed multiple cystic cavitations. CONCLUSION: Although COVID-19 is not severe in most children, life-threatening conditions such as COVID-19-associated severe encephalopathy can occur during the neonatal and early infantile periods.

Cystic Encephalomalacia in a Young Woman After Cardiac Arrest Due to Diabetic Ketoacidosis and Thyroid Storm.

Cystic encephalomalacia is commonly reported in neonates with prenatal or perinatal hypoxic events. It is rarely observed in adults. A 25-year-old woman with a history of type 1 diabetes mellitus and hyperthyroidism presented to the emergency department with diabetic ketoacidosis (DKA) and a thyroid storm. She sustained cardiac arrest due to ventricular fibrillation and subsequently developed hypoxic encephalopathy. Initial brain computed tomography showed no significant findings; however, follow-up magnetic resonance imaging three months later revealed cystic encephalomalacia in the bilateral parieto-occipital lobes. A Tc-99m ethyl cysteinate dimer (ECD) brain perfusion scan revealed extensive hypoperfusion in the bilateral frontal and parieto-occipital lobes. She showed severe cognitive impairment and marked spasticity in all her limbs. Although cystic encephalomalacia is mostly reported in neonates with hypoxic injury, it can be seen in adults with hypoxic encephalopathy, leading to a significant neurological deficit.

Psychosis Associated with Acquired Porencephaly-Cause or Incidental Finding? Case Report and Review of Literature.

Porencephaly, a rare disease affecting the central nervous system, is represented by a cerebrospinal fluid-filled cavity in the brain. There are two types of porencephalic cavities: congenital and acquired. Porencephaly is mainly associated with neurological and developmental consequences. Associated psychotic symptoms were reported in a few cases, and due to this fact, there is a knowledge gap regarding the diagnostic and therapeutic approach to such cases. We present the case of a 32-year-old male diagnosed with a psychotic disorder associated with acquired porencephaly. The porencephalic cystic lesions were most probably due to a traumatic brain injury at the age of 6 years old. The psychotic symptomatology consisted of interoceptive/visceral hallucinations, delusions with persecutory and religious/magic content and disorganised behaviour. The porencephalic cavity was confirmed by a computed tomography scan. The patient was treated over the course of time with risperidone, olanzapine and zuclopenthixol. The existing literature regarding other cases of psychosis associated with porencephaly is discussed. In conclusion, even though porencephaly was asymptomatic for a long period of time, we argue that there is a causal relationship between the chronic psychotic symptoms and the porencephalic cyst in our case.

Pre-Existing Non-Disabling Encephalomalacia Confers Risk to Stroke Outcomes After Endovascular Treatment.

BACKGROUND: Patients with previous stroke episodes tend to have poor outcomes after an endovascular treatment (EVT). Encephalomalacia (EM) is an objective indicator of previous strokes but has not been systematically investigated. The fundamental aim of this exploration is to investigate the effects of a pre-existing non-disabling EM on clinical outcomes after EVT. METHODS: Consecutive patients undergoing an EVT due to the anterior circulation large vessel occlusion (LVO) strokes were enrolled in the study. The pre-existing EM was defined as the focal hypodense lesions (≥ 3 mm in maximum diameter) on a non-contrast cranial CT using axial images before EVT. The primary outcome was the 90-day functional assessment using the modified Rankin Scale (mRS) score. The safety outcome was the incidence of symptomatic intracranial hemorrhage (sICH) defined as any hemorrhage within 24 h after an EVT, which is responsible for an increase of ≥ 4 points in the score of National Institutes of Health Stroke Scale (NIHSS). RESULTS: Of the 433 patients analyzed in this investigation, a pre-existing non-disabling EM was observed in 106 (24.5%) patients. After adjusting for potential confounding factors, patients with contralateral EM (OR = 2.68, 95% CI = 1.13-6.31; P = 0.025) and with an EM+ > 20 mm in maximum diameter (OR = 2.21, 95% CI = 1.01-4.85; P =0.048) were substantially associated with unfavorable outcomes (mRS > 2). For the sICH, we did not observe any association with the pre-existing EM (P > 0.05). CONCLUSIONS: A pre-existing non-disabling EM is common and safe in patients undergoing EVT. However, a contralateral EM and the large size of EM may predict an unfavorable outcome at 90 days, which should receive more attention before EVT.

Fetal Brain Injury in Rhesus Isoimmunization Fetus.

This report presents a rare fetal and neonatal complication brain injury (encephalomalacia and ventriculomegaly) as a consequence of severe fetal anemia resulting from Rhesus (Rh) isoimmunization. A 28-year-old gravida 4 para 3 woman was referred at 21+4 weeks of gestation to the fetal medicine clinic as a case of Rh isoimmunization. Fetal ultrasound showed a normal anatomy scan with normal brain structure, but with severe fetal anemia. The patient was treated with multiple intrauterine transfusions, but still developed complications post-transfusions. This case shows that severe cerebral developmental anomalies can occur because of severe fetal anemia secondary to Rh isoimmunization, such as in this case - ventriculomegaly and encephalomalacia. It has been concluded that proper antenatal counseling and early intervention for severe fetal anemia are beneficial to prevent such complications from occurring. It is crucial to consider appropriate antenatal and postnatal radiological imaging for such cases.