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.

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.

Atypical Proliferative (Borderline) Serous Tumor in the Brain: A Case Report.

A 59-year-old woman with a remote history of invasive ductal carcinoma of the breast was found on a follow-up computed tomography scan of her brain to have a 1-cm lesion in the right frontal lobe in 2008. In the ensuing years, before her current admission, multiple imaging studies of the brain revealed that the lesion was stable and it was, therefore, interpreted as a small area of encephalomalacia related to a thrombosed cortical vein, a cavernoma, or treated metastatic breast cancer. In 2013, the patient underwent a bilateral salpingo-oophorectomy for ovarian tumors that were diagnosed as bilateral serous cystadenofibromas. A partial omentectomy showed no evidence of implants. In June 2016, the brain lesion was completely excised and diagnosed as an atypical proliferative (borderline) serous tumor. Immunohistochemical staining demonstrated that the tumor cells were immunoreactive for Pax8, WT-1, ER, and CK-7 and negative for Gata-3, PR, TTF-1, CDX-2, Napsin A, and CK-20, which was consistent with that diagnosis. We present a brief review of possible mechanisms to account for this unusual presentation and speculate that the most likely one is exfoliation of fallopian tube epithelial cells into the peritoneal cavity, which then gain access to lymphatics resulting in cells implanting in the brain and subsequently progressing to an atypical proliferative (borderline) serous tumor.

Diabetes Mellitus With Concurrent Cerebellar Degeneration and Necrosis in a Domestic Goose ( Anser anser domesticus).

A 5-year-old sexually intact male Toulouse goose ( Anser anser domesticus) was presented for ataxia, polyuria, and polydipsia. The goose was cachectic and exhibited head tremors. Results of plasma biochemical analysis and point-of-care glucometry revealed persistent hyperglycemia. Despite supportive care and oral glipizide, the goose died within 48 hours of presentation. Necropsy revealed severe pancreatic atrophy and fibrosis with regionally extensive cerebellar encephalomalacia and generalized Purkinje cell degeneration and necrosis. On a wet basis, hepatic zinc concentration was determined to be twice the reference interval by atomic absorption spectroscopy. Based on these findings, the pancreatic insufficiency with secondary diabetes mellitus was attributed to chronic zinc toxicosis. Despite birds' relative resistance to high blood glucose concentrations, prolonged hyperglycemia is suspected to have caused selective Purkinje cell degeneration and necrosis by glial activation, mitochondrial dysfunction, and glutamate toxicity, which resulted in the clinically observed motor deficits. This is consistent with experimental diabetic rat models. This case highlights the need for further investigation of the complex pathophysiology of diabetes mellitus in birds.

Polioencephalomalacia and Heart Failure Secondary to Presumptive Thiamine Deficiency, Hepatic Lipidosis, and Starvation in 2 Abandoned Siamese Cats.

Two 4-year-old spayed female Siamese cats were seized by the British Columbia Society for the Prevention of Cruelty to Animals after confinement to an abandoned housing unit without food for 9 weeks. One cat was found dead, and the second was euthanized within 24 hours due to neurologic deterioration despite therapy. Polioencephalomalacia of the caudal colliculus, hepatic lipidosis, cachexia, and congestive heart failure with cardiomyocyte atrophy were identified in both cats through postmortem examination and attributed to a prolonged period of starvation. Brain lesions were likely the result of thiamine deficiency (Chastek paralysis), which can be associated with both malnutrition and liver disease. This case highlights the importance of thiamine supplementation during realimentation of cats with hepatic lipidosis. Heart failure resulting from cachexia may have contributed to the death of the first cat and the morbidity of the second cat.

Fetal brain injury in survivors of twin pregnancies complicated by demise of one twin as assessed by in utero MR imaging.

OBJECTIVE: The aim of this study was to quantify the risk of brain abnormalities in single-twin demise of monochorionic pregnancies and to describe the type of brain injuries using ultrasound and in utero magnetic resonance (iuMR) imaging. METHODS: Monochorionic twin pregnancies complicated by the demise of one twin referred between 2004 and 2013 were reviewed. Ultrasound was performed in a tertiary centre prior to iuMR. The cases were subdivided into those associated with co-twin loss following fetoscopic laser ablative treatment for twin-twin transfusion syndrome (TTTS) and those associated with spontaneous fetal demise. RESULTS: Sixty-eight cases were identified, 27/68 following treatment for TTTS and 41/68 with spontaneous fetal demise. Nine (13.2%) had brain abnormalities on iuMR, and the rate of brain abnormalities was similar in the two groups. Expert ultrasound and iuMR findings agreed in three out of nine of those cases, and in six out of nine cases, ultrasound underestimated or missed the pathology. CONCLUSION: Monochorionic twin pregnancies with single fetal demise are complex pregnancies with increased risk of acquired brain pathology, although the rate of brain abnormalities in our study is lower than that of other publications. iuMR in such complicated pregnancies is a useful adjuvant imaging technique that appears to detect brain pathologies better than prenatal ultrasonography.

Angioglioma misdiagnosed as encephalomalacia on magnetic resonance imaging for over a decade.

We report a case of intractable seizures secondary to an angioglioma that was misdiagnosed as post-traumatic encephalomalacia for over a decade, with a discussion of the radiological findings and a review of the literature.

Cerebellar allocentric and action-intentional spatial neglect.

Contralesional hemispatial neglect most often results from lesions in the right posterior temporoparietal cortex. Less commonly, contralesional and ipsilesional neglect are caused by lesions in the frontal lobe. Although unilateral left cerebellar lesions have been reported to cause body-centered (egocentric) ipsilesional neglect, they have not been reported to cause left-side object-centered (allocentric) neglect together with a leftward action-intentional bias. We describe a patient who had these signs of neglect 7 months after a left cerebellar hemorrhage. This 61-year-old right-handed woman reported emotional lability and difficulty walking, frequently bumping into things on her left side. Neurologic examination revealed ocular dysmetria and left-side limb ataxia. Neuropsychological tests showed evidence of neglect. On a clock-drawing test, the patient accurately drew a circle but her number placement deviated to the left side. She showed the same leftward deviation when she tried to draw a circle composed of small triangles. Although her line bisection was normal, on an allocentric task of open-triangle cancellation she was most likely to neglect triangles with a left-side opening. Her performance on this task indicated left allocentric neglect. Her leftward deviation on the clock and figure drawing tasks seems to be a form of an action-intentional grasp, which may have been induced by right frontal dysfunction superimposed on a deficit of global attention.

Bovine diseases causing neurological signs and death in Mexican feedlots.

The number of large feedlot operations, similar to that of USA and Canada, has notably increased in Mexico in the last three decades. Clinical and laboratory diagnoses of neurological diseases in feedlot cattle are crucial in Mexico and Central America because of the high incidence of bovine paralytic rabies (BPR). Because of its zoonotic potential, BPR must be promptly diagnosed and differentiated from other bovine neurological diseases such as thrombotic meningoencephalitis (TME), polioencephalomalacia (PEM) and botulism. More recently, BPR and botulism have been diagnosed with increasing frequency in Mexican feedlots. Neither BPR nor botulism has relevant gross lesions, thus post-mortem diagnosis without laboratory support is impossible. Herein, we describe five outbreaks of neurological diseases in Mexican feedlots in which BPR, botulism and PEM were diagnosed either independently or in combination. A diagram illustrating the most conspicuous pathologic findings and ancillary laboratory test required to confirm the diagnoses of these neurological diseases in feedlot cattle is proposed.

Intracerebral lipopolysaccharide induces neuroinflammatory change and augmented brain injury in growth-restricted neonatal rats.

INTRODUCTION: Intrauterine growth restriction (IUGR) alters fetal development and is associated with neurodevelopmental abnormalities. We hypothesized that growth restriction from reduced intrauterine perfusion would predispose neonatal rats to subsequent inflammatory brain injury. METHODS: In this study, IUGR was achieved by induced placental insufficiency in pregnant rats at 14 days of gestation. IUGR offspring and sham-operated control pups were subsequently injected with intracerebral lipopolysaccharide (LPS) as a model of periventricular leukomalacia (PVL). RESULTS: LPS similarly elevates proinflammatory cytokines in the brains of both IUGR and control rat pups. However, the chemokines cytokine-induced neutrophil chemoattractant-1 (CINC-1) and macrophage chemoattractant protein-1 (MCP-1), as well as microglia activation, were significantly higher in LPS-treated IUGR rat pups as compared with LPS-treated controls. In addition to the unique brain inflammatory response, IUGR rat pups demonstrated increased brain damage with an increased number of apoptotic cells, larger lateral ventricular size, and more severe impairment of myelination. DISCUSSION: This study provides evidence that placental insufficiency may sensitize the innate immune system in the immature brain and reveals a possible link between brain inflammation and injury.

Toxic equine parkinsonism: an immunohistochemical study of 10 horses with nigropallidal encephalomalacia.

Chronic ingestion of yellow star thistle (Centaurea solstitialis) or Russian knapweed (Acroptilon repens) causes nigropallidal encephalomalacia (NPE) in horses with an abrupt onset of neurologic signs characterized by dystonia of lips and tongue, inability to prehend food, depression, and locomotor deficits. The objectives of this study were to reexamine the pathologic alterations of NPE and to conduct an immunohistochemistry study using antibodies to tyrosine hydroxylase and α-synuclein, to determine whether NPE brains show histopathologic features resembling those in human Parkinson disease. Results confirm that the NPE lesions are located within the substantia nigra pars reticulata, sparing the cell bodies of the dopaminergic neurons in the substantia nigra pars compacta, and in the rostral portion of the globus pallidus, with partial disruption of dopaminergic (tyrosine hydroxylase-positive) fibers passing through the globus pallidus. No abnormal cytoplasmic inclusions like the Lewy bodies of human Parkinson disease were seen in these NPE brains. These findings indicate that equine NPE may serve as a large animal model of environmentally acquired toxic parkinsonism, with clinical phenotype directly attributable to lesions in globus pallidus and substantia nigra pars reticulata rather than to the destruction of dopaminergic neurons.

Structural lesion in the brain is a risk factor of childhood intractable epilepsy.

Most of the intractable epilepsy cases are of paediatric age group. Eighty per cent of intractable epilepsy is symptomatic and have got structural lesion. These lesions are easily detectable by doing neuro-imaging. One hundred and four children with epilepsy were enrolled in two groups; in group A 52 intractable epilepsy patients and in group B 52 well controlled epilepsy patients from the child neurology unit of Bangabandhu Sheikh Mujib Medical University. Mean age of intractable group and well-controlled group was 4.45±3.66 years and 6.45±5.24 years respectively. Male were more in both groups. Abnormal neuro-imaging was significantly higher in intractable group; 78.8% children of the intractable epilepsy group had one or more structural lesions. Cortical atrophy, ventricular dilatation and encephalomalacia were the most frequent detectable lesions. Bilateral lesions and presence of multiple abnormalities were more in association with intractability. Structural lesions were detected more in cases with focal neurological deficit and structural abnormality having statistically significant difference.

St Theresa's dart and a case of religious ecstatic epilepsy.

OBJECTIVE: : We report a case of ecstatic seizures with religious overtones in a patient whose semiology resembles that of Saint Theresa of Avila (1515 to 1582), and review the anatomical basis of this phenomenon. BACKGROUND: : Seizures with an emotional component are typically associated with negative sensations. Ecstatic seizures, particularly those with a religious character, are rarely reported, although they hold an important place in history, as a number of religious figures have been posited to be epileptic. Here, we present a patient with ecstatic seizures whose semiology and religious overtones resemble those of Saint Theresa of Avila (1515 to 1582), and discuss the anatomical basis of this phenomenon. METHOD: : Case report. RESULTS: : Evaluation of the patient demonstrated right temporal encephalomalacia on magnetic resonance imaging of the brain. Electroencephalogram showed focal slowing and poorly defined sharp waves in the right frontotemporal region. This area of pathology concurs with prior studies that localize ecstatic seizures to the anterior insula or temporal lobes. CONCLUSIONS: : Ecstatic seizures may involve the right temporal region. Although interpretation of ecstatic seizures is subject to individual variation, a similar localization and our patient's religious background may explain the resemblance between the semiology of his seizures, and that of Saint Theresa's visions as described almost 5 centuries ago.

Leukoencephalomalacia and laminar neuronal necrosis following smoke inhalation in a dog.

Acute respiratory and neurologic disease after smoke inhalation are well documented, but human patients may also develop delayed-onset neurologic symptoms associated with leukoencephalomalacia after exposure to smoke or carbon monoxide. In this case, a dog developed progressive neurologic signs 6 days after rescue from an apartment fire. At necropsy 9 days after smoke inhalation, leukoencephalomalacia of the central cerebral white matter was accompanied by laminar necrosis of cerebrocortical neurons. This is the first report of delayed posthypoxic leukoencephalopathy in a nonhuman animal.

Multicystic encephalomalacia as an end-stage finding in abusive head trauma.

Abusive head trauma (AHT) is one of the most severe forms of physical child abuse. If a child initially survives severe AHT the neurological outcome can be poor. In recent years several children were seen who developed multicystic encephalomalacia (MCE) after documented severe AHT. A search of the Netherlands Forensic Institute database in The Hague was performed. Inclusion criteria were cases of AHT between 1999 and 2010 where the child was under the age of 1 year old at the time of trauma. Trauma mechanism and radiological information were collected. Five children, three boys and two girls (mean age 57 days, range 8-142 days) who developed cystic encephalomalacia after inflicted traumatic brain injury were included. Survival ranged from 27 to 993 days. In all cases judicial autopsy was performed. All cases came before court and in each case child abuse was considered to be proven. In two cases the perpetrator confessed, during police interrogation, to shaking of the child only. Although a known serious outcome, this is one of the few reports on MCE as a result of AHT. In all cases the diagnosis was confirmed at autopsy.

Cerebromalacia with epilepsy and cortical blindness in a laboratory Japanese macaque (Macaca fuscata).

The authors performed a pathological examination of a 5-year-old female laboratory Japanese monkey who developed cortical blindness and epileptic seizures. Generalized, tonic-clonic seizures started to occur during behavioral training to get the animal to enter a carrying cage for future psychological experiments. Blindness was suspected because of a lack of approaching behavior toward foods such as fruits. Although the monkey was extensively treated with anticonvulsants, the clinical signs did not improve. An increased serum creatine phosphokinase (CPK) level and bilateral occipital brain atrophy were detected. Histopathologically, a severe degree of cerebromalacia was detected bilaterally in the occipital lobe, and necrosis and gliosis were seen mainly in the temporal lobe. Focal inflammation was found in the meninges. No other changes were observed in other nervous tissues or organs, and no signs of a parasitic or viral infection were found in the systemic organs. Spontaneously occurring lesions in the central nervous system have been rarely reported in laboratory monkeys. In the present case, the cause of cerebromalacia could not be confirmed, but the relationship between symptoms such as abnormal vision and the presence of brain lesions was distinct. The authors believe that this case is a valuable historical control case for the laboratory Japanese macaque.

Focal symmetrical encephalomalacia in a goat.

Focal symmetrical encephalomalacia (FSE) is the most prominent lesion seen in the chronic form of enterotoxemia caused by Clostridium perfringens type D in sheep. However, this lesion has not been reported in goats. The current paper reports a case of FSE in a goat from the state of Paraíba in the Brazilian semiarid region. As reported by the farmer, 30, 4-48-month-old animals from a flock of 150 goats died after showing nervous signs, including blindness and recumbence, for periods varying between 1 and 14 days. The flock was grazing native pasture supplemented with wheat and corn bran. Additionally, lactating goats were supplemented with soybeans. A 4-month-old goat with nervous signs was examined clinically and then necropsied 3 days after the onset of clinical signs. Bilateral, focal, and symmetrical areas of brown discoloration were observed in the internal capsule and thalamus. Histologic lesions in these areas consisted of multifocal, bilateral malacia with a few neutrophils; endothelial cell swelling; perivascular edema; and hemorrhages. The etiology of these lesions was not determined. However, FSE is considered pathognomonic for C. perfringens type D enterotoxemia in sheep, and it is speculated that this microorganism was the etiologic agent in the present case. The flock had been vaccinated against type D enterotoxemia only once, approximately 3 months before the beginning of the outbreak. Insufficient immunity due to the incorrect vaccination protocol, low efficacy of the vaccine used, and a diet including large amounts of highly fermentable carbohydrates were suspected to be predisposing factors for this outbreak.

Dextromethorphan is protective against sensitized N-methyl-D-aspartate receptor-mediated excitotoxic brain damage in the developing mouse brain.

Enhanced glutamate release and inflammation play an important role in the pathogenesis of developmental brain injury. Although N-methyl-d-aspartate receptor (NMDAR) antagonists potently attenuate neonatal brain damage in several animal models, they can also impact trophic functions in the developing brain. As a consequence, high-affinity NMDAR antagonists have been shown to trigger widespread apoptotic neurodegeneration in the newborn brain. Dextromethorphan (DM), a low-affinity NMDAR antagonist with anti-inflammatory properties, may be neuroprotective against excitotoxic and inflammation-enhanced excitotoxic brain injury, without the associated stimulation of apoptotic degeneration. Using an established newborn mouse model of excitotoxic brain damage, we determined whether systemic injection of DM significantly attenuates excitotoxic lesion size. We investigated several doses and time regimens; a dose of 5 microg/g DM given in a combination of both pre-injury and repetitive post-injury treatment proved most effective. DM treatment significantly reduced lesion size in gray and white matter by reducing cell death as shown by a decreased Fluoro-Jade B staining and caspase-3 activation. Pre-treatment with interleukin-1beta and lipopolysaccharide enhanced NMDAR-mediated excitotoxic brain injury and microglial cell activation. This sensitizing effect was abolished by DM treatment, as the effectiveness of DM in reducing lesion size and microglial cell activation was similar to phosphate-buffered saline-pre-treated controls. In all cases, no gender-specific differences were detected. DM treatment did not trigger any apoptotic neurodegeneration (caspase-3 cleavage, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, Fluoro-Jade B staining). Although functional parameters were not measured, our data corroborate reports that DM is neuroprotective and that it may therefore improve functional outcome following perinatal brain injury.