Clinical findings of equine leukoencephalomalacia / Achados clínicos de leucoencefalomalácia equina

Equine leukoencephalomalacia (LEM) is a disease caused by the ingestion of food, especially corn, contaminated by fumonisin, a Fusarium verticillioides (synonymous with F. moniliforme) metabolite. The clinical signs of brain injuries have an acute onset and rapid evolution. This study aimed to describe the clinical findings in 11 animals diagnosed with LEM, including cerebrospinal fluid (CSF) analysis. Of these animals, 91% (10/11) were horses, and only 9% (1/11) were asinine. The clinical localization of the lesions was 64% (7/10) cerebral, manifested mainly by altered mental state and behavioral disturbance, and 36% (4/11) were brainstem lesions, manifested by incoordination, head tilt, nystagmus, facial hypoalgesia, difficulty in apprehension, chewing, and swallowing food. Postmortem findings revealed that 82% (9/11) of the lesions were in the cerebrum and 18% (2/11) in the brainstem. CSF findings, such as xanthochromia (43%, 3/7), hyperproteinorrachia (50%, 3/6), and pleocytosis (43%, 3/7) were observed. The affected animals showed neurological signs that were compatible with cerebral and/or brainstem injuries. The CSF from animals with LEM may present with xanthochromia, hyperproteinorrachia, and pleocytosis, reinforcing the fact that this disease should be included in the differential diagnosis of encephalomyelopathies.(AU)

A leucoencefalomalácia (LEM) é uma enfermidade que acomete equídeos causada pela ingestão de milho e seus derivados e feno contaminados pela micotoxina fumonisina, um metabólito do fungo Fusarium verticillioides (sinônimo para F. moniliforme). Os sinais clínicos apresentam início agudo e evolução rápida e são decorrentes de lesões encefálicas. O objetivo deste estudo é descrever os achados clínicos de 11 equídeos diagnosticados com LEM, incluindo a análise do líquido cefalorraquidiano (LCR). 91% dos animais afetados eram equinos e somente 9% (1/11) era asinino. A localização clínica das lesões era 64% (7/10) cerebrais, manifestadas por alterações no estado mental e comportamento e 36% (4/10) no tronco encefálico, manifestadas por incoordenação, desvio lateral de cabeça, nistagmo, hipoalgesia da face e dificuldade de apreensão, mastigação e deglutição de alimentos. Comparativamente, os achados post mortem revelaram que 82% (9/11) das lesões eram no cérebro e 18% (2/11) no tronco encefálico. Alterações no LCR, tais como xantocromia (43%, 3/7), hiperproteinorraquia (50%, 3/6) e pleocitose (43%, 3/7), foram observadas. Os animais afetados apresentaram sinais clínicos compatíveis com lesões encefálicas e/ou de tronco cerebral. O LCR de animais com LEM pode apresentar xantocromia, hiperproteinorraquia, e pleocitose, reforçando que esta doença deve ser incluída como diagnóstico diferencial de encefalomielites.(AU)

Clinical findings of equine leukoencephalomalacia / Achados clínicos de leucoencefalomalácia equina

Equine leukoencephalomalacia (LEM) is a disease caused by the ingestion of food, especially corn, contaminated by fumonisin, a Fusarium verticillioides (synonymous with F. moniliforme) metabolite. The clinical signs of brain injuries have an acute onset and rapid evolution. This study aimed to describe the clinical findings in 11 animals diagnosed with LEM, including cerebrospinal fluid (CSF) analysis. Of these animals, 91% (10/11) were horses, and only 9% (1/11) were asinine. The clinical localization of the lesions was 64% (7/10) cerebral, manifested mainly by altered mental state and behavioral disturbance, and 36% (4/11) were brainstem lesions, manifested by incoordination, head tilt, nystagmus, facial hypoalgesia, difficulty in apprehension, chewing, and swallowing food. Postmortem findings revealed that 82% (9/11) of the lesions were in the cerebrum and 18% (2/11) in the brainstem. CSF findings, such as xanthochromia (43%, 3/7), hyperproteinorrachia (50%, 3/6), and pleocytosis (43%, 3/7) were observed. The affected animals showed neurological signs that were compatible with cerebral and/or brainstem injuries. The CSF from animals with LEM may present with xanthochromia, hyperproteinorrachia, and pleocytosis, reinforcing the fact that this disease should be included in the differential diagnosis of encephalomyelopathies.(AU)

A leucoencefalomalácia (LEM) é uma enfermidade que acomete equídeos causada pela ingestão de milho e seus derivados e feno contaminados pela micotoxina fumonisina, um metabólito do fungo Fusarium verticillioides (sinônimo para F. moniliforme). Os sinais clínicos apresentam início agudo e evolução rápida e são decorrentes de lesões encefálicas. O objetivo deste estudo é descrever os achados clínicos de 11 equídeos diagnosticados com LEM, incluindo a análise do líquido cefalorraquidiano (LCR). 91% dos animais afetados eram equinos e somente 9% (1/11) era asinino. A localização clínica das lesões era 64% (7/10) cerebrais, manifestadas por alterações no estado mental e comportamento e 36% (4/10) no tronco encefálico, manifestadas por incoordenação, desvio lateral de cabeça, nistagmo, hipoalgesia da face e dificuldade de apreensão, mastigação e deglutição de alimentos. Comparativamente, os achados post mortem revelaram que 82% (9/11) das lesões eram no cérebro e 18% (2/11) no tronco encefálico. Alterações no LCR, tais como xantocromia (43%, 3/7), hiperproteinorraquia (50%, 3/6) e pleocitose (43%, 3/7), foram observadas. Os animais afetados apresentaram sinais clínicos compatíveis com lesões encefálicas e/ou de tronco cerebral. O LCR de animais com LEM pode apresentar xantocromia, hiperproteinorraquia, e pleocitose, reforçando que esta doença deve ser incluída como diagnóstico diferencial de encefalomielites.(AU)

Leukoencephalomalacia in horses associated with immature corn consumption / Surto de leucoencefalomalacia em equinos associado ao consumo de milho verde

Horse leukoencephalomalacia (ELEM) is a disease caused by the ingestion of mycotoxins (fumonisins) produced by fungi of the genus Fusarium that infect corn and/or its byproducts. This disease has been described by ingestion of mature corn with humidity above 15% at temperatures below 20°C. The aim of this paper was to report an outbreak of leukoencephalomalacia in horses fed with immature corn. Two horses out of three showed neurological signs approximately seven days after eating immature corn in its reproductive phase (R2, milky grains). Corn was harvested and administered directly to the animals, with no storage. Deaths occurred approximately 24 hours after the onset of clinical signs. Grossly, there were multifocal dark red to brown areas in the white matter of the telencephalon and hyppocampus and thalamus. Histologically, there was edema and hemorrhage in several areas of the telencephalon white matter, which corresponded to dark red to brown areas observed in the macroscopy. There was also foci of malacia with presence of reactive astrocytes with abundant eosinophilic cytoplasm and inflammatory cells. Diffuse capillary wall degeneration and endothelial cell swelling were also observed. Two ppm of fumonisin were detected by immunoaffinity column method (VICAM) in the immature corn sample. The water activity in this cereal, when the grain is still milky, is 0.98 and can predispose it to growth of mycotoxin-producing fungi. In the present case, fumonisin was found in milky grains in the beginning of the reproductive phase (R2), which suggested that even immature corn may be infected by Fusarium spp. and should not be administered to horses.(AU)

A leucoencefalomalácia dos equinos (ELEM) é uma doença causada pela ingestão de micotoxinas (fumonisinas) produzidas por fungos do gênero Fusarium que infectam o milho e/ou seus subprodutos. A doença tem sido descrita pela ingestão de milho maduro com umidade acima de 15% em temperatura ambiente abaixo de 20°C. O objetivo deste trabalho foi relatar um surto de leucoencefalomacia em equinos alimentados com milho verde. Dois equinos de três animais apresentaram sinais clínicos neurológicos aproximadamente sete dias após iniciarem a ingestão de milho verde na fase reprodutiva (R2, grãos leitosos) com palha e talos, colhido no máximo 24 horas antes de ser administrado. A morte ocorreu aproximadamente 24 horas após o início dos sinais clínicos. Macroscopicamente havia no sistema nervoso central áreas multifocais acinzentadas e amareladas na substância branca do telencéfalo, no hipocampo e no tálamo. Histologicamente observou-se edema e hemorragia em diversas áreas da substância branca do telencéfalo, que correspondiam às áreas acinzentadas observadas na macroscopia. Havia, também, próximo as áreas hemorrágicas, focos de malacia com presença de astrócitos reativos com abundante citoplasma eosinophilico e algumas células inflamatórias. Degeneração das paredes dos capilares e tumefação das células endoteliais também foram observadas. Na análise da amostra de milho pelo método de colunas de imunoafinidade (VICAM) foram detectados 2ppm de fumonisina. A atividade de água neste cereal, quando o grão ainda está leitoso, é de 0,98, o que predispõe ao crescimento de fungos produtores de micotoxinas. No presente caso fumonisina foi encontrada nos grãos leitosos no início da fase reprodutiva (R2), o que sugere que mesmo o milho ainda imaturo pode estar infectado por Fusarium spp. e não deve, também, ser administrado aos equinos.(AU)

Leucoencefalomalácia em equídeos da região Leste de Mato Grosso / Leukoencephalomacia in Equidae of the Eastern Region of Mato Grosso, Brazil

Background: Fumonisins produced by Fusarium verticillioides are among the most important medical mycotoxins known. The intake of concentrate based on corn and corn by-products contaminated with fumonisins can cause severe poisoning in horses. The injuries are observed mainly in the white matter of the brain, and the disease is known as Equine Leukoencephalomalacia (ELEM). This study aims to describe and discuss the epidemiological, clinical and diagnostic aspects of an outbreak of ELEM occurred in three farms in the municipalities of Canarana and Água Boa, in the eastern region of Mato Grosso, Brazil. Materials, Methods & Results: The outbreak occurred between May and August 2010. The disease affected six horses and four mules of different ages and sex. Clinical examination was only possible in animals with chronic evolution of the disease. All the affected animals showed neurological clinical signs such as ataxia and recumbency, which progressed to death or sudden death. Histopathological analysis showed foci of necrosis that predominantly affected the white matter, and the presence of gitter cells. Degenerative lesions were observed in the liver of the animals. Mortality rate ranged from 12.5 to 71%, and lethality reached 100%. The cases were preceded by sudden drops in the weather temperature. Fumonisins levels of 6.6 ppm were detected in the feed of the animals. Discussion: The presumptive diagnosis of leukoencephalomalacia was consistent and based on clinical and epidemiological studies. However, the definitive diagnosis was based upon the histological features of the brain including the presence of extensive areas of malacia. Moreover, the animals were being fed with corn or corn by-products contaminated with fumonisins levels considered to be toxic to equids. The mortality and lethality rates are in agreement with outbreaks described in previous studies. The animals showed neurological signs as the predominant clinical manifestation, with gait ataxia followed by recumbency, prostration and death between 24 h and 29 days. Similarly to other reports, the disease was more frequent in adult animals, which succumbed in 24-48 h. Conversely, the evolution of the disease in young animals was of 10 to 29 days. Sudden death was more prevalent in the mules. Previous studies have shown a predominance of cerebral and brainstem lesions in horses, whereas in mules the clinical signs are related to brainstem lesions. Corn and corn byproducts are commonly used as energy supplementation to horses in the southern of Mato Grosso state, but outbreaks of the disease are uncommon. This may be influenced by the prevalence of hot climate conditions, which does not favor the production of toxin by the fungus. The atypical low weather temperatures (9-11ºC) observed prior to the outbreak could have contributed to the mycotoxin production by F. verticillioides, which requires temperatures between 8-12°C to produce toxins. However, the disease in the region may be underestimated, considering that the practice of necropsies is not common among field technicians, mainly in the occurrence of sporadic deaths among horses intended for work. Preventive measures include avoiding the use of corn and corn by-products for horses after periods of sudden drops in temperature in the region. Furthermore, clinical and epidemiological surveys and post-mortem and histopathological analyses are undoubtedly important for appropriate differential diagnosis, especially in equids with neurological signs.

Modelos animais das leucodistrofias hereditárias humanas / Animal models of human hereditary leukodistrophies

As leucoencefalopatias representam um grupo amplo e bastante heterogêneo de doenças que acometem a substância branca do sistema nervoso central. As etiologias adquiridas são mais prevalentes, contudo um amplo número de doenças genéticas hereditárias que cursam com alterações na mielina (leucodistrofias) tem sido descritas nas últimas duas décadas. Ainda bastante desconhecidas da classe médica geral, as leucodistrofias representam condições clínicas monogênicas resultantes de diferentes mecanismos fisiopatológicos na produção de componentes da mielina normal, incluindo defeitos metabólicos hereditários em enzimas lisossomais e peroxissomais e defeitos de fatores de transcrição nucleares e de proteínas de superfície neuronal. Apesar de parte dos princípios fisiopatogênicos e achados neuropatológicos serem bastante semelhantes em amplo aspecto de todas as condições, muitos dos mecanismos envolvidos nos sinais clínicos neurológicos e na origem das disfunções mielínicas são ainda desconhecidos. Muitos dos conhecimentos adquiridos acerca das mutações e disfunções observadas tiveram sua origem a partir de estudos experimentais em modelos animais. Esta revisão objetiva rever os principais modelos animais desenvolvidos para estudo das leucodistrofias humanas.

The leukoencephalopathies represent a wide and heterogeneous group of diseases that affect the central nervous system white matter. The acquired etiologies are more prevalent, however a large number of hereditary genetic disorders that occur with changes in myelin (leukodystrophies) has been described in the last two decades. Still quite unknown to the medical profession, the leukodystrophies represent monogenic clinical conditions resulting from different pathophysiological mechanisms in the production of normal myelin content, including hereditary metabolic defects in lysosomal and peroxisomal enzymes and in nuclear transcription factors and neuronal surface proteins. Although part of the pathophysiological principles and neuropathological findings are very similar in all the broad spectrum of conditions, many of the mechanisms involved in neurological clinical signs and the origin of myelin disorders are still unknown. Many of the acquired knowledge about the genetic mutations and dysfunctions observed had their origin from experimental studies in animal models. This review aims to review the main animal models developed to study the human leukodystrophies.

Modelos animais das leucodistrofias hereditárias humanas / Animal models of human hereditary leukodistrophies

As leucoencefalopatias representam um grupo amplo e bastante heterogêneo de doenças que acometem a substância branca do sistema nervoso central. As etiologias adquiridas são mais prevalentes, contudo um amplo número de doenças genéticas hereditárias que cursam com alterações na mielina (leucodistrofias) tem sido descritas nas últimas duas décadas. Ainda bastante desconhecidas da classe médica geral, as leucodistrofias representam condições clínicas monogênicas resultantes de diferentes mecanismos fisiopatológicos na produção de componentes da mielina normal, incluindo defeitos metabólicos hereditários em enzimas lisossomais e peroxissomais e defeitos de fatores de transcrição nucleares e de proteínas de superfície neuronal. Apesar de parte dos princípios fisiopatogênicos e achados neuropatológicos serem bastante semelhantes em amplo aspecto de todas as condições, muitos dos mecanismos envolvidos nos sinais clínicos neurológicos e na origem das disfunções mielínicas são ainda desconhecidos. Muitos dos conhecimentos adquiridos acerca das mutações e disfunções observadas tiveram sua origem a partir de estudos experimentais em modelos animais. Esta revisão objetiva rever os principais modelos animais desenvolvidos para estudo das leucodistrofias humanas. (AU)

The leukoencephalopathies represent a wide and heterogeneous group of diseases that affect the central nervous system white matter. The acquired etiologies are more prevalent, however a large number of hereditary genetic disorders that occur with changes in myelin (leukodystrophies) has been described in the last two decades. Still quite unknown to the medical profession, the leukodystrophies represent monogenic clinical conditions resulting from different pathophysiological mechanisms in the production of normal myelin content, including hereditary metabolic defects in lysosomal and peroxisomal enzymes and in nuclear transcription factors and neuronal surface proteins. Although part of the pathophysiological principles and neuropathological findings are very similar in all the broad spectrum of conditions, many of the mechanisms involved in neurological clinical signs and the origin of myelin disorders are still unknown. Many of the acquired knowledge about the genetic mutations and dysfunctions observed had their origin from experimental studies in animal models. This review aims to review the main animal models developed to study the human leukodystrophies. (AU)