Qualitative and Quantitative Neuropathology Approaches Using Magnetic Resonance Microscopy (Diffusion Tensor Imaging) and Stereology in a Hexachlorophene Model of Myelinopathy in Sprague-Dawley Rats

It is well established that hexachlorophene, which is used as an antibacterial agent, causes intramyelinic edema in humans and animal models. The hexachlorophene myelinopathy model, in which male Sprague-Dawley rats received 25 to 30 mg/kg hexachlorophene by gavage for up to 5 days, provided an opportunity to compare traditional neuropathology evaluations with magnetic resonance microscopy (MRM) findings. In addition, stereology assessments of 3 neuroanatomical sites were compared to quantitative measurements of similar structures by MRM. There were positive correlations between hematoxylin and eosin and luxol fast blue stains and MRM for identifying intramyelinic edema in the cingulum of corpus callosum, optic chiasm, anterior commissure (aca), lateral olfactory tracts, pyramidal tracts (py), and white matter tracts in the cerebellum. Stereology assessments were focused on the aca, longitudinal fasciculus of the pons, and py and demonstrated differences between control and treated rats, as was observed using MRM. The added value of MRM assessments was the ability to acquire qualitative 3-dimensional (3-D) images and obtain quantitative measurements of intramyelinic edema in 26 neuroanatomical sites in the intact brain. Also, diffusion tensor imaging (fractional anisotropy [FA]) indicated that there were changes in the cytoarchitecture of the white matter as detected by decreases in the FA in the treated compared to the control rats. This study demonstrates creative strategies that are possible using qualitative and quantitative assessments of potential white matter neurotoxicants in nonclinical toxicity studies. Our results lead us to the conclusion that volumetric analysis by MRM and stereology adds significant value to the standard 2-D microscopic evaluations.

Correlation of MRI with the Neuropathologic Changes in Two Cats with Bromethalin Intoxication

ABSTRACT Two cats were presented with multifocal neurological signs. One cat’s signs progressed over 2 wk; the other cat progressed over 5 days. Examinations were consistent with a process involving the prosencephalon, vestibular system, and general proprioceptive/upper motor neuron systems. MRI of the brain and cervical spinal cord reveal widespread T2 hyperintensity of the white matter. Affected areas included the cerebrum, cerebral peduncles, corticospinal tracts of the pons and medulla, and the cerebellum. T2 hyperintensity was present in all funiculi of the spinal cord. Diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps were consistent with cytotoxic or intramyelinic edema. Differential diagnosis included toxic or metabolic/degenerative leukoencephalopathies. Necropsies revealed widespread spongy degeneration of the central nervous system white matter. Toxicologic assays of liver specimens revealed desmethylbromethalin, a metabolite of bromethalin. Bromethalin is a rodenticide that causes uncoupling of oxidative phosphorylation. Antemortem diagnosis is challenging. DWI and ADC maps were instrumental in narrowing the differential diagnosis and raised the index of suspicion for bromethalin. Bromethalin intoxication should be considered in all animals with a progressive course of multifocal neurologic deficits. MRI, specifically, DWI and ADC maps, may serve as a biomarker of cytotoxic or intramyelinic edema associated with spongiform leukoencephalomyelopathy.

Encephalitis with Prolonged but Reversible Splenial Lesion

Introduction: The splenium of the corpus callosum has a specific structure of blood supply with a tendency towards blood-brain barrier breakdown, intramyelinic edema, and damage due to hypoxia or toxins. Signs and symptoms of reversible syndrome of the splenium of the corpus callosum typically include disorientation, confusion, impaired consciousness, and epileptic seizures. Case report: A previously healthy 32-year-old man suffered from weakness, headache, and fever. Subsequently, he developed apathy, ataxia, and inability to walk, and therefore was admitted to the hospital. Cerebrospinal fluid showed protein elevation (0.9 g/l) and pleocytosis (232/1 ul). A brain MRI showed hyperintense lesions in the middle of the corpus callosum. The patient was treated with antibiotics, and subsequently, in combination with steroids. Two months later, the hyperintense lesions in the splenium and the basal ganglia had disappeared. Almost seven months since his hospitalization in the Department of Neurology, the patient has returned to his previous employment. He now does not exhibit any mental changes, an optic edema and urological problems have improved. In addition, he is now actively engaged in sports. Conclusion: We have described a case of a 32-year-old man with confusion, ataxia, and inability to stand and walk. The man developed a febrile meningeal syndrome and a hyperintense lesion of the splenium, which lasted for two months. Neurological changes, optic nerve edema, and urinary retention have resolved over the course of seven months. We think that the prolonged but transient lesion of the splenium may have been caused by encephalitis of viral origin.