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.

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.

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.

Distinctive Neuroimaging Pattern in Term Newborns With Neonatal Placental Encephalopathy: A Case Series.

BACKGROUND: Identifying antepartum versus intrapartum timing and the cause of neonatal encephalopathy (NE) often remains elusive owing to our limited understanding of the underlying pathophysiological processes and lack of appropriate biomarkers. OBJECTIVES: This retrospective observational study describes a case series of term newborns with NE who displayed a recognizable magnetic resonance imaging pattern of immediately postnatal brain abnormalities that rapidly evolved toward cavitation. Our aim is to (1) report this neuroimaging pattern, (2) look for placental determinants, and (3) depict the outcome. DESIGN/METHODS: This is a unicentric retrospective case series reporting the clinical, radiological, and laboratory findings of NE associated with a distinctive neuroimaging pattern, that is, immediately postnatal extensive corticosubcortical T2 hyperintensities, followed by rapid corticosubcortical cavitation that does not match the neuroimaging picture of intrapartum hypoxic-ischemic encephalopathy (HIE). RESULTS: Seven term newborns presented bilateral corticosubcortical hyperintensities that were detected on T2 between day of life (DOL) 1-4, which rapidly evolved toward cystic encephalomalacia, that is, between DOL9 and DOL12. All these newborns presented with moderate/severe NE. The outcome was either neonatal death or quadriplegic cerebral palsy and epilepsy. None of the reported patients fulfilled the criteria of a high likelihood of acute intrapartum hypoxic-ischemic or quadriplegic cerebral palsy. All these newborns were exposed to chronic and/or acute placental inflammation and/or hypoxic-ischemic. CONCLUSIONS: To further define the antepartum causes of NE, early neuroimaging and a placental examination are recommended. Brain T2 hyperintense injuries before DOL4 followed by rapid cavitation before DOL12 might be biomarkers of NE from an antepartum/placental origin.

Multicystic Encephalomalacia: The Neuropathology of Systemic Neonatal Parechovirus Infection.

The Neuropathology of Human Parechovirus (HPeV) is not widely described due to the relatively recent discovery of the virus combined with a limited number of autopsy case reports. We report the case of an infant boy born at 38 weeks who, six days after birth, presented with fever and severe neurological dysfunction. Human Parechovirus Type 3 (HPeV3) RNA was detected in his cerebrospinal fluid (CSF) and blood. He died five days after his initial presentation. Neuropathologic examination demonstrated multicystic encephalomalacia (ME). This case report confirms that white matter pathology is dominant in HPeV3 infection. A unique feature, of HPeV encephalomalacia is absence of CSF pleocytosis and minimal inflammation in the meninges. The findings permit comment on the pathogenesis of brain injury by this virus.

Clinical and Genetic Characteristics of Mitochondrial Encephalopathy Due to FOXRED1 Mutations: Two Chinese Case Reports and a Review of the Literature.

Background: As one of the assembly factors of complex I in the mitochondrial respiratory chain, FOXRED1 plays an important role in mitochondrial function. However, only a few patients with mitochondrial encephalopathy due to FOXRED1 defects have been reported. Methods: Two Chinese patients with mitochondrial encephalopathy due to mutations in FOXRED1 were identified through trio whole-exome sequencing. The clinical presentation, laboratory data, brain imaging findings, and genetic results were collected and reviewed. All previously reported cases with FOXRED1-related mitochondrial encephalopathy were collected using a PubMed search, and their data were reviewed. Results: Two patients presented with severe neurodevelopmental delay, epilepsy, high lactic acid levels, and remarkable diffuse brain atrophy and polycystic encephalomalacia during early infancy. Trio whole-exome sequencing revealed compound heterozygous variants in both patients: one case harbored a c.606_607delAG frameshift variant and a c.1054C>T (p.R352W) variant. At the same time, the other carried a novel c.352C>T (p.Q118X) variant and a reported c.1054C>T (p.R352W) variant. To date, nine patients have been reported with FOXRED1 defects, including our two cases. The most common presentations were neurodevelopment delay (100%), epilepsy (80%), poor feeding (30%), and vision loss (20%). Multisystem involvement comprised cardiovascular dysfunction (30%), abnormal liver function (20%), and hypoglycemia (10%). The neuroimaging results ranged from normal to severe cerebral atrophy and polycystic encephalomalacia in early infancy. Eleven pathogenic variants in FOXRED1 have been reported, comprising six missense variants, two non-sense variants, two frameshift variants, and one splice variant; among these the c.1054C>T (p.R352W) and c.612_615dupAGTG (p.A206SfsX15) variants are more common. Conclusion: FOXRED1-related mitochondrial disorders have high clinical and genetic heterogeneity. Our study expanded the clinical and genetic spectrum of FOXRED1 defects. Early infantile onset and progressive encephalopathy are the most common clinical presentations, while the variants c.1054C>T (p.R352W) and c.612_615dupAGTG (p.A206SfsX15) may be critical founder mutations.

Progressive multifocal leukoencephalopathy in a patient with systemic lupus erythematosus: Clues to early diagnosis.

A case of progressive multifocal leukoencephalopathy (PML) occurring on low dose immunosuppression for systemic lupus erythematosus (SLE) and Sjogren's syndrome (SS) is presented. Neurologic changes in patients with SLE or SS should not be assumed to be a disease manifestation. Importantly, serious opportunistic infections such as PML can occur in minimally immunosuppressed rheumatic patients. Early diagnosis, facilitated by scrutiny of MRI findings, should trigger measures to reconstitute immunity in an otherwise fatal disease.

MR Imaging of hypoxic ischemic encephalopathy - Distribution Patterns and ADC value correlations.

BACKGROUND AND PURPOSE: Neonatal hypoxic-ischemic encephalopathy causes hypoxic brain injury. Due to differences in brain maturity at time of insult, severity of hypotension and duration of insult, there are four distinct patterns of brain injury. Magnetic resonance imaging is the most sensitive modality for evaluating these patterns of brain injury. Additional role of Diffusion weighted imaging and ADC values can be useful in the evaluation of such cases. We conducted this study to analyse the usefulness of ADC values in the brain tissue affected by hypoxic-ischemic injury. MATERIALS AND METHODS: We conducted a prospective study of all the patients referred to our department for magnetic resonance scanning of brain with history of hypoxic ischemic encephalopathy and clinical features cerebral palsy. 23 Cases with imaging manifestations of hypoxic ischemic encephalopathy were included in the study. We studied distribution patterns of HIE in our cases and calculated the ADC values of involved as well as normal grey and white matter. Further, sensitivity, specificity, predictive values, and likelihood ratios for each dichotomized diffusion and ADC values were obtained Wilson Score method. RESULTS: The most common distribution pattern in our study was involvement of peri-rolandic area (15 cases, 65%). ADC values were significantly (p < 0.005) increased in abnormal white matter. No significant changes (p = 0.8) were seen in ADC values of normal and abnormal grey matter. CONCLUSIONS: Due to significant increase in ADC values of affected white matter, ADC value can be used as a marker to detect chronic sequel of hypoxic ischaemic brain injury. Another observation was the perirolandic brain tissue being most common area of involvement in the cases with cerebral palsy.