Cystic Encephalomalacia in a Neonate With a Rash.

To investigate the primary causes and clinical characteristics of cystic encephalomalacia (CE) in children. 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. 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. 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.

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.

To compare the neurodevelopmental outcomes between preterm infants with diffuse excessive high signal intensity (DEHSI) and those without DEHSI on magnetic resonance (MR) images, in association with other white matter lesions. This retrospective study was approved by the institutional review board, and requirement to obtain informed consent was waived. High-risk preterm infants (n = 126) who underwent screening brain MR imaging at near-term-equivalent age were classified into two groups according to the presence of DEHSI. Bayley Scales of Infant Development-II, presence of cerebral palsy, and neurosensory impairment between 18 and 24 months of age were compared between the two groups. The associations of MR findings of other white matter lesions (cystic encephalomalacia, punctate lesions, loss of volume, ventricular dilatation, and delayed myelination) and subsequent outcomes were also analyzed. Outcome data were evaluated by using exact logistic regression analyses and Fisher exact test. DEHSI was present in 75% (95 of 126) of infants. Subsequent neurodevelopmental outcomes did not differ significantly between the two groups. Severe motor delay and cerebral palsy were more common in infants with both DEHSI and other white matter lesions as compared with infants with normal white matter (P = .001 and P < .001, respectively). Among other white matter lesions, cystic encephalomalacia (odds ratio, 19.6; 95% confidence interval: 1.3, 333.3) and punctate lesions (odds ratio, 90.9; 95% confidence interval: 6.4, 1000) were significant predictors of cerebral palsy. Although the incidence of DEHSI was high (75%) in preterm infants at near-term-equivalent age MR imaging, DEHSI was not predictive of following adverse outcomes. Cystic encephalomalacia and punctate lesions were more significant predictors of cerebral palsy.

To the Editors: A 5-week-old female born by C-section at 34 weeks of gestational age due to preeclampsia, with uncomplicated prenatal care, presented to an outside hospital with a 4-day-history of fever and seizure. The infant had a normal newborn screen and had been exclusively fed with formula since birth. On examination, she was febrile with a poor suck and hypertonia. Cerebrospinal fluid (CSF) analysis showed WBC of 134/mm3 (57% monocytes) with 5 red blood cells (RBC) 5/mm3, protein of 1044 mg/dL and glucose <20 mg/dL. Ampicillin, ceftazidime and vancomycin were initiated. CSF culture yielded Paenibacillus species by matrix-assisted laser desorption/ionization-time of flight. An MRI of the brain with and without contrast revealed extensive cerebritis with areas of tissue necrosis and central liquification with abscesses and cystic encephalomalacia (Fig. 1). Antibiotics were stopped and the patient was discharged to receive home hospice care on day 6 of hospitalization.FIGURE 1.: A: Brain MRI with and without contrast. B: sample obtained from the fontanelle.Two days following discharge, her parents presented to our institution to resume full medical care. CSF analysis from a transfontanelle bedside aspiration showed: glucose 32 mg/dL, protein 1869 mg/dL, RBC 1900/mm3, WBC cells 46/mm3, (57% neutrophils, 27% lymphocytes and 16% monocytes). CSF cultures remained negative but 16S rRNA sequencing (University of Washington Medical Center Laboratories) was positive for Paenibacillus spp. Antimicrobials were narrowed and the patient completed a 6-week course of IV ampicillin therapy. She later developed significant hydrocephalus requiring an endoscopic third ventriculostomy at 5 months. We obtained a complete sequence of the organism that initially grew outside the facility using a hybrid assembly approach of short- and long-read sequencing. Phylogenetic analyses indicated that when compared to 244 16SrRNA Paenibacillus species available, all 8 copies found in our genome clustered most closely with Paenibacillus dendritiformis (Table 1, Supplemental Digital Content 1, https://links.lww.com/INF/E805). Paenibacillus spp. was originally classified under the genus Bacillus until 1993, when they were segregated based on phylogenetic analysis of 16S rRNA.1 A few cases of Paenibacillus spp. infections have been described in pediatrics. DeLeon et al.2 reported a case of bacteremia and meningitis due to Paenibacillus alvei in a premature neonate resulting in cerebritis and cystic encephalomalacia and death. Hunt et al.3 reported a case of premature infant death due to probable Paenibacillus thiaminolyticus sepsis and meningitis. A recent case4 of P. dendritiformis meningitis in a 31-day-old premature infant who subsequently developed hemorrhagic meningoencephalitis, brain abscesses and encephalomalacia. A possible association of Paenibacillus spp. with postinfectious hydrocephalus in infants in sub-Saharan Africa has been reported.5 Most Paenibacillus spp. isolates are resistant to penicillin,6,7 susceptible to cefotaxime, gentamicin, rifampicin and vancomycin with the variability of sensitivity against erythromycin.7 However, in our case, an antibiogram using E-testing showed a low minimal inhibitory concentration (MIC) to penicillin and high MIC to vancomycin (Material 1, Supplemental Digital Content 1, https://links.lww.com/INF/E805). Several virulence markers have recently been described in some species of Paenibacillus.6 The reported pediatric cases of Paenibacillus spp. infections to date including our case were in infants born prematurely who developed severe CNS infections leading to poor outcomes. Consistent with a prior report,4P. dendritiformis in our case was found to be susceptible to penicillin.FIGURE 2.: A: A full phylogenetic tree of 244 Paenibacillus species. B: A subtree of (A) shows that the unknown sample most resembles P. dendritiformis. Only branches with a phylogenetic score greater than 70% are shown.

Radiation therapy for nasopharyngeal carcinoma affects the temporal lobes. This paper characterizes proton MR spectroscopic findings of the temporal lobes and correlates them with imaging changes. Single-voxel proton MR spectroscopic examinations were acquired from 13 healthy adult volunteers (25 spectra) and 18 patients (28 spectra). All patients had biopsy-confirmed nasopharyngeal carcinoma and were previously treated with radiation therapy. Six patients (33%) had a single treatment and 12 (67%) patients had two treatments. Point resolved spectroscopy (PRESS) method was used (TR = 3,000 ms, TE = 135 ms) and data processed automatically using the LCModel software package for metabolite quantification. Voxel size and geometry were adapted to the lesion to reduce skull-base lipid contamination. The metabolites were quantitated relative to water signal. For each location, an additional non-water-suppressed reference scan in fully relaxed conditions was performed. The imaging findings were divided into four categories: I, normal; II, edema only; III, contrast-enhancing lesions; and IV, cystic encephalomalacia. The N-acetyl-aspartate levels were reduced in 27 (96%) spectra. Choline was increased in 3 (11%), normal in 4 (14%), and reduced in 21 (75%) spectra. The creatine level was normal in 8 (29%) spectra and reduced in 20 (71%) spectra. Imaging showed 4 (14%) spectra with category-I imaging findings; 5 (18%) spectra with category-II findings; 15 (54%) spectra with category-III findings; and 4 (14%) spectra with category-IV findings. Magnetic resonance spectroscopy showed reduced N-acetyl-aspartate in radiation-induced temporal lobe changes. Creatine levels were relatively more stable. Choline levels may be increased, normal, or reduced. Imaging findings ranged from normal to contrast-enhancing lesions and cystic encephalomalacia.

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. 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. 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. 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.

A term male newborn is transferred to a tertiary care center 8 days after birth for evaluation of seizures. The neonate is born to a 35-year-old gravida 1 para 0 woman after a spontaneous pregnancy complicated by diet-controlled gestational diabetes and fetal pyelectasis, which resolved at 32 weeks. Prenatal maternal laboratory studies were unremarkable, and the only maternal medication used during pregnancy was a multivitamin. Both parents are known biotinidase deficiency carriers. Labor is spontaneous but complicated by 4 hours of failure to progress in an asynclitic presentation, which is converted to emergent cesarean section because of late decelerations without recovery. Estimated gestational age is 39 1/7 weeks based on estimated date of conception, but postdelivery examination reveals dry and peeling skin consistent with a gestational age of 41 weeks. Apgar scores are 3, 7, and 9 at 1, 5, and 10 minutes, respectively, and continuous positive airway pressure is required after delivery for respiratory distress. The neonate’s birthweight is 3.180 kg (32nd percentile), length is 50.4 cm (52nd percentile), and head circumference is 35.3 cm (63rd percentile). The neonate is initially transferred from the birth hospital to an outside NICU for monitoring of respiratory status with reportedly unremarkable physical examination findings. On admission to the outside NICU, blood cultures are sent and capillary blood gas measurements are unremarkable. Empiric antibiotics are deferred. Abnormal movements observed on day 2 after birth are described as rhythmic, involving more than 1 extremity, and sometimes resolving with holding. At the time, the infant’s condition is stable with 2 L nasal cannula at a fraction of inspired oxygen of 21% and he is breastfeeding on demand. The neonate is also noted to have significant right-sided torticollis. ### Progression Because of concern for seizures, electroencephalography (EEG) is performed, which reveals status epilepticus and numerous focal seizures over …

Long-term neurodevelopmental sequelae are a potential concern in neonates following in utero exposure to severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2). We report 2 neonates born to SARS-CoV-2 positive mothers, who displayed early-onset (day 1) seizures, acquired microcephaly, and significant developmental delay over time. Sequential MRI showed severe parenchymal atrophy and cystic encephalomalacia. At birth, neither infant was SARS-CoV-2 positive (nasopharyngeal swab, reverse transcription polymerase chain reaction), but both had detectable SARS-CoV-2 antibodies and increased blood inflammatory markers. Placentas from both mothers showed SARS-CoV-2-nucleocapsid protein and spike glycoprotein 1 in the syncytiotrophoblast, fetal vascular malperfusion, and significantly increased inflammatory and oxidative stress markers pyrin domain containing 1 protein, macrophage inflammatory protein 1 βη, stromal cell-derived factor 1, interleukin 13, and interleukin 10, whereas human chorionic gonadotropin was markedly decreased. One infant (case 1) experienced sudden unexpected infant death at 13 months of age. The deceased infant's brain showed evidence of SARS-CoV-2 by immunofluorescence, with colocalization of the nucleocapsid protein and spike glycoprotein around the nucleus as well as within the cytoplasm. The constellation of clinical findings, placental pathology, and immunohistochemical changes strongly suggests that second-trimester maternal SARS-CoV-2 infection with placentitis triggered an inflammatory response and oxidative stress injury to the fetoplacental unit that affected the fetal brain. The demonstration of SARS-CoV-2 in the deceased infant's brain also raises the possibility that SARS-CoV-2 infection of the fetal brain directly contributed to ongoing brain injury. In both infants, the neurologic findings at birth mimicked the presentation of hypoxic-ischemic encephalopathy of newborn and neurologic sequelae progressed well beyond the neonatal period.

Linear skull fractures in young children occasionally result in growing skull fractures. Neurosurgical correction of growing skull fractures (GSFs) by dural repair with cranioplasty is considered a safe and effective treatment with good prognosis. A 3-month-old boy fell from the stairs head first on to the floor. Initially he did not show any neurological symptoms. Craniography revealed a linear fracture of the right occipito-parietal skull bone. Cranial computer tomography showed a right-sided subdural haemorrhage, expanding beneath the fracture site, as well as contusion and swelling of the right hemisphere, leading to a modest midline shift. He was transferred to the paediatric intensive care unit for further evaluation and observation. After admission, he gradually lost consciousness and developed right-sided fixated eyes. Lowest EMV-scores were 1–4-T. Intracranial pressure, measured by an intraventricular probe, remained normal. Conservative treatment was chosen for the intracranial haemorrhage, and artificial ventilation and sedation was needed for 3 days. He developed a paresis and temporary focal epileptic activity of the left arm. This resolved over the months after discharge. Physical examination at 10 months of age (7 months after discharge) however revealed a soft pulsatile mass on the right occipito-parietal scalp. Bone ridges were felt around a discontinuum of the skull bone. Plain craniography showed a large occipito-parietal skull defect. Cerebral cranial magnetic resonance imaging revealed a cystic encephalomalacia, dilatation of the right ventricle and modest herniation of brain tissue into the skull defect (Fig. 1). Operative correction with both dural repair to resolve the herniation and cranioplasty to cover the dura and skull defect was performed. During surgery, the bone defect appeared to be covered with tissue which was later microscopically determined as granulation tissue. A dural cranioplasty with pericranium and alloplastic bone reconstruction with methacrylic resin (Palacos) was used. Four days post-surgery the patient was discharged in good general condition. GSFs are rare complications of linear skull fractures. Estimated incidence is 0.05%–1% of all skull fractures [2,3,4]. Most GSFs occur in the first 3 years of life, but are documented from perinatal period up to adulthood [1,3,4,5]. Interval time between head injury and diagnosis of GSF varies from 1 day to more than 1 year [4,6]. Clinical presentation includes seizures, focal neurological deficit and loss of consciousness [3,4,5]. Characteristic pathophysiological features of GSFs are defined as (1) linear skull fracture, gaping more than 4 mm, (2) Fig. 1 Cerebral MRI scan at the age of 10 months (7 months after initial right-sided linear skull fracture) showing cystic encephalomalacia with leptomeningeal cyst and herniation of brain tissue into the fracture site with occipital ventricular dilatation Eur J Pediatr (2003) 162: 556–557 DOI 10.1007/s00431-003-1256-1

Background: Molybdenum cofactor deficiency (MoCD) is a rare autosomal recessive inborn error of metabolism causing deficiency in molybdenum-dependent enzymes, leading to accumulation of toxic metabolites such as sulfite, resulting in severe neurological damage. We describe a neonate with MoCD type B. Clinical Description: A term neonate, the third child of third-degree consanguineous parents, presented with seizures and encephalopathy shortly after birth. There were two prior sibling deaths due to neonatal seizures. The neonate had hypotonia and exaggerated startle response (hyperekplexia) but no facial dysmorphism. Management and Outcome: Biochemical testing showed undetectable serum uric acid. Brain magnetic resonance imaging revealed findings classical of MoCD with cystic encephalomalacia and lactate peaks on magnetic resonance spectroscopy. Whole-exome sequencing confirmed a homozygous pathogenic variant in the MOCS2 gene. Conclusion: In neonates presenting with refractory seizures and encephalopathy soon after birth, without perinatal asphyxia, MoCD should be suspected, especially in the context of consanguinity or sibling deaths. Low uric acid and suggestive neuroimaging, guide the diagnosis, confirmed by genetic testing. Treatment remains supportive.

Neonatal stroke outcome studies demonstrate variable findings of either relatively spared intellectual function or persistent impairments. Volumetric measurement of the brain can provide more precise data on lesion-cognition outcomes. We studied 7 children with unilateral focal lesions from prenatal stroke. Whole-brain magnetic resonance imaging scans were analyzed to produce volumes of cortical gray matter, total white matter, cerebrospinal fluid, lesion, and lesion constricted fluid, and we ascertained the relationship of morphometric variables to intellectual and clinical outcome. Children with cystic encephalomalacia plus atrophy had poorer outcomes than children with atrophy or gliosis alone. These children also demonstrated the largest lesion size, smallest gray matter volume, and greatest proportion of hyperintense white matter in the affected hemisphere. Findings suggest that the type and size of the lesion, in addition to the integrity of white matter and residual cortex, may be better predictors of intellectual functioning than either of these indices alone.

QUANTIFICATION OF CEREBRAL OXYGENATION AND HAEMODYNAMICS IN SICK NEWBORN INFANTS BY NEAR INFRARED SPECTROPHOTOMETRY

Dyke-Davidoff-Masson syndrome (DDMS) is a rare clinical entity caused by a neurological disorder that results from cerebral injury in -utero or in early infancy resulting in unilateral brain atrophy. The resulting clinical presentation is with hemiplegia, seizures, developmental delay and behavioural disorders. Our case is a 12-year-old boy who presented with hemiparesis, poor scholastic performance and seizures. The MRI brain revealed a decreased volume of the right cerebral hemisphere with gliotic change in the frontal region. The right cerebral peduncle appeared small in size with cystic encephalomalacia and thinning of the corpus callosum. MRI findings were suggestive of DDM syndrome. The electroencephalogram was abnormal. An early recognition will help reduce disability with physiotherapy and anticonvulsant therapy.

Ovarian cancer is the second most common cause of death among gynecologic malignancies. Ovarian cancer is generally diagnosed at an advanced stage due to nonspecific signs and symptoms. This case report presents a 50-yearold woman with an ovarian tumor suggestive of malignancy, diagnosed based on imaging findings and an elevated tumor marker CA 125. The gold standard examination, histopathological biopsy, could not be performed. The patient presented with abdominal distension, abdominal pain, and recurrent shortnessof breath. Chest X-ray revealed recurrent pleural effusion. Abdominal CT scan demonstrated ascites accompanied by a solid ovarian mass suggestive of malignancy and a significant elevation of CA 125 tumor marker with a CA 125/CEA ratio of 622/1.7. However, cytological examination of the ascitic fluiddid not indicate malignancy. The patient underwent repeated evacuation of pleural effusion and ascitic fluid. Biopsy or surgical intervention could not be performed; therefore, histopathological confirmation of the tumor was not possible. Recurrent seizures were observed in this patient, with brain MRI showing gliosis and cystic encephalomalacia. The patient received six cycles of neoadjuvant chemotherapy with carboplatin and paclitaxel, with the last dose administered on June 21, 2025. On June 29, 2025, however, the patient passed away after one day of hospitalization, the primary presenting complaint being decreased consciousness. The gold standard for diagnosing ovarian cancer is histopathological biopsy. If a histopathological biopsy cannot be performed,a combination of imaging examinations, cytology of ascitic fluid or pleural effusion, and an elevated CA 125:CEA ratio greater than 25 may be used. In this patient, ascitic fluid cytology yielded negative results, possibly due to inadequate sampling. Recurrent seizures and decreased consciousness in this patient may have been caused by gliosis, sequelae of stroke, or possible metastasis, thereby necessitating additional diagnostic modalities. Establishing a diagnosis of ovarian cancer poses unique challenges. A combination of imaging, tumor markers, and fluid cytology can serve as valuable modalities to guide the diagnosis of ovarian cancer when histopathological biopsy cannot be performed.

Chapter 26 - Brain-Specific Mitochondrial Aminoacyl-tRNA Synthetase Disorders: Mitochondrial Arginyl-Transfer RNA Synthetase Deficiency