[Analysis of clinical and imaging features of 6 cases of linear scleroderma en coup de sabre with central nervous system involvement in children].

Objective: To summarize the clinical and imaging features of linear scleroderma en coup de saber (LSCS) with central nervous system involvement in children. Methods: The clinical data(clinical manifestations and imaging features) of 6 children diagnosed with LSCS with central nervous system involvement who were admitted to Beijing Children's Hospital Affiliated to Capital Medical University from May 2019 to November 2021 were retrospectively analyzed. Results: The 6 patients were all female, aged 6.8 (3.3, 11.0) years at the time of diagnosis, and aged 3.0 (1.7, 4.1) years at the time of discovery of facial skin lesions. Facial skin lesions appeared before neurological symptoms in 5 cases, and neurological symptoms appeared 2 months before skin lesions in 1 case. All the patients had "sword wound" skin lesions on the forehead with alopecia. Neurological manifestations included epileptic seizures in 6 cases, focal neurological defects in 5 cases, and headaches in 2 cases. The intracranial lesions were all ipsilateral to the skin lesions. The magnetic resonance imaging (MRI) of 6 cases showed abnormal signals mainly involving white matter in 1 hemisphere, and 3 cases showed local encephalomalacia. The scattered low signal was observed in 5 cases on susceptibility weighted imaging. Localized brain parenchyma or leptomeninges enhancement was seen on Gadolinium-enhanced sequences in 5 cases. Scattered foci of calcification on the affected side were seen on cranial CT in 4 cases. Skin biopsy was performed in 2 cases. Part of the lesion of the brain was removed in 1 case, and the pathological findings suggested small vasculitis, which was consistent with skin pathological changes. All patients received symptomatic treatment with antiepileptic drugs. Oral prednisone combined with methotrexate was given in 4 cases, and 1 case was given oral prednisone only. One case was presumed to be in the resting stage of the disease due to significant cerebral atrophy in half of the brain, and only antiepileptic drugs were added. The patients were followed up for 6-36 months. The skin lesions of scleroderma and alopecia did not progress in 5 cases, and hemifacial atrophy was developed in 1 case, which was considered to be combined with Parry-Romberg syndrome. The seizures were controlled in 4 cases. One case had reduced seizure frequency but left hemiplegia. One patient still had intractable epilepsy and paroxysmal headache. Conclusions: LSCS with central nervous system involvement is more common in girls, with seizures and neurological defects as the main manifestations. Intracranial lesions are mostly ipsilateral to the skin lesions. Cerebral microbleeds, calcification, and encephalomalacia foci are common, and the pathological changes in skin and intracranial lesions are consistent with small-vessel vasculitis. Prednisone combined with methotrexate treatment has shown some efficacy, but some children remain with refractory epilepsy and neurological deficit symptoms.

Screening of Risk Factors for Poor Prognosis in Patients with Refractory Epilepsy Secondary to Encephalomalacia.

Objective: The study was aimed at screening the independent prognostic risk factors for refractory epilepsy associated with encephalomalacia (REAE). Methods: Patients with REAE treated in the First People's Hospital of Linping District from January 2018 to December 2019 were selected. The prognosis was represented by Engel grading. Clinical data of the patients were collected, including age, sex, BMI, lesion sites, number of lesion sites, lesion size, seizure frequency, epilepsy type, and treatment methods. Independent risk factors for poor prognosis were screened by logistic regression analysis. The receiver operating characteristic curve (ROC) was used to evaluate the prognostic efficacy of independent risk factors. Results: A total of 48 patients were included in this study, including 31 patients (64.58%) in the good prognosis group and 17 patients (35.42%) in the poor prognosis group. The mean age of the poor prognosis group was higher than that of the good prognosis group (P = 0.002). The proportion of patients with multisite lesions in the poor prognosis group was higher than that in the good prognosis group (P = 0.016). The proportion of patients with cerebral malacia lesion diameter ≥ 3 cm in the poor prognosis group was higher than that in the good prognosis group (P = 0.002). The proportion of patients with attack frequency ≥ 2 times/month in the poor prognosis group was higher than in the good prognosis group (P = 0.002). The proportion of patients receiving surgical treatment in the poor prognosis group was lower than that in the good prognosis group (P < 0.001). Age, number of lesion sites, size of encephalomalacia, and seizure frequency were independent risk factors for the prognosis of patients with REAE (OR > 1, P < 0.05). Surgical treatment was an independent protective factor associated with the prognosis of patients with REAE (OR < 1, P < 0.05). The area under the ROC curve of surgical treatment was 0.83 (P = 0.004). The area under the ROC curve of the size of encephalomalacia was 0.72 (P = 0.008). There was a positive correlation between age and size of encephalomalacia and Engel grade (r > 0, P < 0.05). Surgical treatment was negatively correlated with Engel grade (r < 0, P < 0.05). The number of lesion sites and seizure frequency had no significant correlation with Engel (P > 0.05). The proportion of Engel I patients treated with surgery was higher than that treated with drugs (P = 0.001). The ratio of Engel III and IV patients treated with surgery was lower than that treated with medications (P < 0.05). Conclusion: Age, number of lesion sites, size of encephalomalacia, and seizure frequency are independent risk factors for the prognosis of patients with REAE. Surgical treatment is an independent prognostic factor for patients with REAE. Surgical treatment can significantly improve patient outcomes.

Red neurons in ovine polioencephalomalacia (cerebrocortical necrosis) are strongly amyloid precursor protein immunopositive.

The signature pathological feature of the pseudolaminar cerebrocortical necrosis found in polioencephalomalacia (PEM) of ruminants is the development of red (eosinophilic) neurons. These neurons are generally considered to be irredeemably injured but we have shown, for the first time, in ovine PEM cases, that most strongly express amyloid precursor protein (APP), which has a neuroprotective role in the brain. By contrast, neurons in unaffected cerebral cortices from control sheep were APP immunonegative. This finding suggests that, rather than being inevitably destined to die, some of these APP immunoreactive cortical neurons may survive and regain structural and functional integrity.

Heterogeneous immunoreactivity of axonal spheroids in focal symmetrical encephalomalacia produced by Clostridium perfringens type D epsilon toxin in sheep.

Since axonal injury (AI) is an important component of many veterinary neurologic disorders, we assessed the relative ability of a panel of antibodies (amyloid precursor protein, 3 subunits of neurofilament protein, protein gene product 9.5, ubiquitin, and synaptophysin) to detect axonal swellings or spheroids. Abundant axonal spheroids found in necrotic internal capsule foci produced in 4 sheep by chronic Clostridium perfringens type D epsilon neurotoxicity provided a model system in which to evaluate this important diagnostic tool. There was heterogeneous labeling of subsets of spheroids by the respective antibodies, suggesting that, in order to detect the complete spectrum of AI in diagnostic cases, a range of antibodies should be used, not only when spheroids are plentiful but also when they are few in number or incompletely developed. The application of insufficient markers in the latter cases can potentially lead to the contribution of AI to lesion pathogenesis being underappreciated.

Impact of Encephalomalacia and White Matter Hyperintensities on ASPECTS in Patients With Acute Ischemic Stroke: Comparison of Automated and Radiologist-Derived Scores.

BACKGROUND. Automated software-based Alberta Stroke Program Early CT Score (ASPECTS) on unenhanced CT is associated with clinical outcomes after acute stroke. However, encephalomalacia or white matter hyperintensities (WMH) may result in a falsely low automated ASPECTS if such findings are interpreted as early ischemia. OBJECTIVE. The purpose of this study was to assess the impact of encephalomalacia and WMH on the automated ASPECTS in patients with acute stroke, in comparison with the radiologist-derived ASPECTS and clinical outcomes. METHODS. This retrospective three-center study included 459 patients (322 men, 137 women; median age, 65 years) with acute ischemic stroke treated by IV thrombolysis who underwent baseline unenhanced CT within 6 hours after symptom onset and MRI within 24 hours after treatment. ASPECTS was determined by automated software and by three radiologists in consensus. Presence of encephalomalacia and extent of WMH (categorized using the modified Scheltens score [mSS]) were also determined using MRI. Kappa coefficients were used to compare the ASPECTS between automated- and radiologist-derived methods. Multivariable logistic regression analyses and ROC analyses were performed to explore the predictive utility of the baseline ASPECTS for unfavorable clinical outcomes (90-day modified Rankin score of 3-6) after thrombolysis. RESULTS. The median automated software-derived ASPECTS was 9, and the median radiologist consensus-derived ASPECTS was 10. Agreement between automated and radiologist-consensus ASPECTS, expressed as kappa, was 0.68, though agreement was 0.76 in patients without encephalomalacia and 0.08 in patients with encephalomalacia. In patients without encephalomalacia, agreement decreased as the mSS increased (e.g., 0.78 in subgroup with mSS < 10 vs 0.19 in subgroup with mSS > 20). By anatomic region, agreement was highest for the lateral middle cerebral artery (κ, 0.52) and lowest for the internal capsule (κ, 0.18). In multivariable analyses, both the automated (odds ratio, 0.69) and the radiologist-consensus (odds ratio, 0.57) ASPECTS independently predicted an unfavorable clinical outcome. For unfavorable outcome, the automated ASPECTS had an AUC of 0.70, sensitivity of 60.4%, and specificity of 70.7%, whereas the radiologist-consensus ASPECTS had an AUC of 0.72, sensitivity of 60.4%, and specificity of 80.5%. CONCLUSION. Presence of encephalomalacia or extensive WMH results in a lower automated than radiologist-consensus ASPECTS, which may impact predictive utility of automated ASPECTS. CLINICAL IMPACT. When using an automated software-derived ASPECTS, radiologists should manually confirm the score in patients with encephalomalacia or extensive leukoencephalopathy.

Experimental Imaging Study of Encephalomalacia Fluid-Attenuated Inversion Recovery (FLAIR) Hyperintense Lesions in Posttraumatic Epilepsy.

This study introduced new MRI techniques such as neurite orientation dispersion and density imaging (NODDI); NODDI applies a three-compartment tissue model to multishell DWI data that allows the examination of both the intra- and extracellular properties of white matter tissue. This, in turn, enables us to distinguish the two key aspects of axonal pathology-the packing density of axons in the white matter and the spatial organization of axons (orientation dispersion (OD)). NODDI is used to detect possible abnormalities of posttraumatic encephalomalacia fluid-attenuated inversion recovery (FLAIR) hyperintense lesions in neurite density and dispersion. Methods. 26 epilepsy patients associated with FLAIR hyperintensity around the trauma encephalomalacia region were in the epilepsy group. 18 posttraumatic patients with a FLAIR hyperintense encephalomalacia region were in the nonepilepsy group. Neurite density and dispersion affection in FLAIR hyperintense lesions around encephalomalacia were measured by NODDI using intracellular volume fraction (ICVF), and we compare these findings with conventional diffusion MRI parameters, namely, fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Differences were compared between the epilepsy and nonepilepsy groups, as well as in the FLAIR hyperintense part and in the FLAIR hypointense part to try to find neurite density and dispersion differences in these parts. Results. ICVF of FLAIR hyperintense lesions in the epilepsy group was significantly higher than that in the nonepilepsy group (P < 0.001). ICVF reveals more information of FLAIR(+) and FLAIR(-) parts of encephalomalacia than OD and FA and ADC. Conclusion. The FLAIR hyperintense part around encephalomalacia in the epilepsy group showed higher ICVF, indicating that this part may have more neurite density and dispersion and may be contributing to epilepsy. NODDI indicated high neurite density with the intensity of myelin in the FLAIR hyperintense lesion. Therefore, NODDI likely shows that neurite density may be a more sensitive marker of pathology than FA.

Striatal necrosis caused by Lichtheimia ramosa in a neonatal calf.

A 12-day-old male calf that did not want breast milk from birth died following neurological signs such as staggering. Postmortem examination revealed bleeding and encephalomalacia in the left striatum and frontal lobe. Histopathologically, necrotic granulomatous encephalitis with numerous fungi was detected. The fungi were positively stained with anti-Rhizomucor mouse monoclonal antibodies. Lichtheimia ramosa was detected in formalin-fixed paraffin-embedded samples of the affected tissue by molecular methods. To the best of our knowledge, striatal necrosis caused by L. ramosa in a neonatal calf has not been reported. This study provides the first evidence of striatal necrosis caused by L. ramosa in a neonatal calf.

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.

Huge chronic subdural haematoma formation in an encephalomalacia stroke cavity.

A patient suffering from a cerebrovascular ischaemic stroke may present similar symptoms to a patient with a chronic subdural haematoma (CSDH). Head CT imaging of an old extensive hemispheric infarction may appear hypodense in a similar fashion as CSDH. We described a 46-year-old man with a 2-week history of mild headache and worsening right lower extremity hemiparesis. Eight years prior, he suffered a left middle cerebral artery territory infarct. The head CT scan showed a huge, slightly hypodense area on the left brain, causing a significant mass effect. A new stroke was of concern versus a chronic subdural haematoma inside the old encephalomalacia stroke cavity. Only three previously reported cases of CSDH occupying an encephalomalacic cavity had been reported. This rare presentation should be considered in the differential diagnosis in patients with a history of cerebrovascular stroke. MRI is useful in making a correct diagnosis.

First case report of cerebral folate deficiency caused by a novel mutation of FOLR1 gene in a Chinese patient.

BACKGROUND: Cerebral folate deficiency (CFD) is a neurological disease, hallmarked by remarkable low concentrations of 5-methyltetrahydrofolic acid (5-MTHF) in cerebrospinal fluid (CSF). The primary causes of CFD include the presence of folate receptor (FR) autoantibodies, defects of FR encoding gene FOLR1, mitochondrial diseases and congenital abnormalities in folate metabolism. CASE PRESENTATION: Here we first present a Chinese male CFD patient whose seizure onset at 2 years old with convulsive status epilepticus. Magnetic Resonance Imaging (MRI) revealed the development of encephalomalacia, laminar necrosis in multiple lobes of the brain and cerebellar atrophy. Whole Exome Sequencing (WES) uncovered a homozygous missense variant of c.524G > T (p.C175F) in FOLR1 gene. Further laboratory tests demonstrated the extremely low level of 5-MTHF in the CSF from this patient, which was attributed to cerebral folate transport deficiency. Following the intravenous and oral treatment of calcium folinate, the concentrations of 5-MTHF in CSF were recovered to the normal range and seizure symptoms were relieved as well. CONCLUSIONS: One novel variation of FOLR1 was firstly identified from a Chinese male patient with tonic-clonic seizures, developmental delay, and ataxia. The WES and laboratory results elucidated the etiology of the symptoms. Clinical outcomes were improved by early diagnosis and proper treatment.

Biofuels Co-Products Tolerance and Toxicology for Ruminants: An Update.

Corn co-products are a co-product of the dry and wet corn-milling ethanol manufacturing industry. The dry mill corn co-product is distiller's grains. Distillers grain can be further categorized into dry distillers grains (DDG), DDG with solubles, wet distillers grains with solubles (WDGS), modified WDGS, and corn syrup (solubles). Wet mill ethanol production produces 2 main feed stuffs: corn gluten (wet and dry) and heavy steep water.

Prevalence of MRI abnormalities in people with epilepsy in rural China.

OBJECTIVE: To assess the prevalence of brain MRI abnormalities in people with epilepsy in rural China and to compare it with that of individuals in the United Kingdom. METHODS: Brain MRI scans were obtained in people with epilepsy who participated in a rural community-based program in China between July 2010 and December 2012. Individual epileptogenic lesion types were reviewed and their associations with seizure control examined. The MRI findings were compared with 2 previous similar studies in the United Kingdom. RESULTS: Among the 597 individuals (58% male, median age 38 years) with MRI scans analyzed, 488 (82%) had active epilepsy. The MRI was abnormal in 389 individuals (65%), with potentially epileptogenic lesion in 224 (38%) and nonspecific abnormalities in 165 (28%), and 108 (18%) were potentially resectable. The potentially epileptogenic lesions were less frequently detected in children (<18 years old, 12 of 68, 18%) than in adults (212 of 529, 40%; p < 0.001). In people with potentially epileptogenic lesions, 67% (150 of 224) had failed ≥2 antiseizure medications. They had higher risk of uncontrolled epilepsy than those with normal MRI (risk ratio [RR] 1.25; p < 0.001) and those with nonspecific abnormality (RR 1.15; p = 0.002) after adjustment for age and sex. The diagnostic yield of MRI was similar to that reported in community- and hospital-based studies in the United Kingdom. CONCLUSIONS: More than one-third of people with chronic epilepsy in rural China have potentially epileptogenic lesions identifiable on brain MRI, with two-thirds fulfilling the definition of pharmacoresistance. These findings highlight the magnitude of the unmet needs for epilepsy surgery in China.

A Pacchionian Puzzle.

A 73-year-old male with a history of chronic ataxia presented with transient facial droop to the Emergency Department. A CT angiogram and MRI with diffusion weighted imaging (DWI) were negative for stroke. However, incidental note was made of numerous giant arachnoid granulation pits in the posterior fossa predominantly involving the left occipital bone (Figure 1). These arachnoid pits demonstrated multiple foci of herniation of the adjacent cerebellar parenchyma into the pits with gliosis of the herniated parenchyma and focal encephalomalacia of the subjacent cerebellar parenchyma. Review of bone windows on a remote CT brain performed almost 13 years earlier confirmed this to be a longstanding abnormality (Figure 2). The patient's physical exam was suggestive of cerebellar ataxia with left-sided dysmetria on finger to nose testing and a wide-based unsteady gait.

The impact of MEG results on surgical outcomes in patients with drug-resistant epilepsy associated with focal encephalomalacia: a single-center experience.

PURPOSE: To analyze the impact of magnetoencephalography (MEG) results on surgical outcomes in patients with drug-resistant epilepsy secondary to encephalomalacia. METHODS: We retrospectively reviewed 121 patients with drug-resistant epilepsy associated with encephalomalacia who underwent MEG followed by resection surgery. Patients were subdivided into concordant MEG group and dis-concordant MEG group for analysis based on whether the MEG results were in concordance with epileptogenic zones or not. RESULTS: 121 patients were included in the present study. The MEG spike sources of 73 (60.33%) patients were in concordance with epileptogenic zones while the MEG spike sources of the other 48 (39.67%) were in dis-concordance with epileptogenic zones. Favorable seizure outcomes were achieved in 79.45% (58 of 73) of patients with concordant MEG results while only 62.50% (30 of 48) of patients with dis-concordant MEG results were seizure free with a follow-up of 2-10 years. The differences of seizure-free rate between patients with concordant MEG results and dis-concordant MEG results were statistically significant. For patients with concordant MEG results, bilateral lesions on MRI are the only independent predictor of unfavorable seizure outcomes. For patients with discordant MEG results, duration of seizures is the only independent predictor of unfavorable seizure outcomes. CONCLUSIONS: Concordant MEG results are associated with favorable seizure outcomes. Bilateral lesions on MRI independently predict unfavorable seizure outcomes in patients with concordant MEG results while longer seizure durations independently predict unfavorable seizure outcomes in patients with dis-concordant MEG results.

Multicystic encephalomalacia: An autopsy report of 4 cases

Multicystic encephalomalacia is varying sized cystic lesions in the brain encountered in developing fetuses or infants. These cysts start at the periventricular area and may extend onto the cortex. The cause of the formation of these cystic lesions is secondary to an ischemic or hypoxic insult, which leads to liquefactive necrosis and subsequent formation of gliotic cyst walls having an admixture of microglia. We discuss four autopsy cases that had multicystic encephalomalacia to highlight the scenarios in which these lesions are encountered.