An Epileptic Seizure Disorder Characterized by Abnormal Cortical Development

Ehung Chin^*
*Correspondence: Ehung Chin, Department of Medical Research, Tungs Taichung Metrohabor Hospital, Taiwan, Email:

Keywords

Drug-resistant epilepsy • Feline lissencephaly • Canine cortical dysplasia

Introduction

In mortal neurology, the contortion of the cortical development (MCD) is a miscellaneous group of lesions, due to the neuronal migration and association diseases, which have been honored, decreasingly, in cases with medicineresistant epilepsy. A lack of a livery, well-defined clinico-pathological bracket of these diseases, is extensively conceded in the epilepsy literature and hence attempts to classify the MCD to address the specific features of these diseases, including embryological, histopathological, imaging, and inheritable aspects, have been proposed. “Cortical dysplasia” has been generically espoused to describe a variety of MCDs, including cerebral heterotopia and polymicrogyria. The term “focal cortical dysplasia” (FCD) indicates a type of MCD firstly described by Taylor and associates, as one point of which there's the presence of large dysplastic neurons and/ or “balloon cells”. Minimum, atomic abnormalities of the cortical armature in cases with generalized epilepsy, are generally encompassed under the term “microdysgenesis”. Other forms of abnormal cortical development, including type I and II lissencephaly, polymicrogyria, and hemimegalencephaly, can be regarded as complex blights in the cell migration, in some cases, with distinct inheritable etiologies [1,2].

Reports of epileptic seizure exertion, due to a MCD in creatures, as well as descriptions of such a neural contortion, are veritably rare. Epileptic seizures, in addition to other neurological signs, have been proved in creatures affected with severe natural anomalies, similar as hydrocephalus, lissencephaly, and porencephaly, and sometimes in tykes with cerebrocortical lesions. Reports of focal cortical dysplasia cases showing delicate to treat seizures, included a Pekingese canine with an associated necrotizing meningoenchephalitis, a Shi- Tzu with a concurrent porencephaly, a Golden Retriever with bilateral temporal cortical lesions and a mixed strain canine with an associated granulomatous meningoenchepalitis. Lissencephaly has been described as associated with epileptic seizure exertion in many cases, that included four Lasha Apsos(,8), a Pekingese, a mixed strain canine, an Australian Kelpie, a Shi-Tzu, a line haired Fox Terrier an Irish Setter, a domestic cat, and two litters of Korat pussycats. Then we describe the clinical and neuropathological features of three cases of youthful creatures with a MCD, affected with severe clusters of epileptic seizures, despite the starting of antiepileptic medicines (AEDs).

Literature Review

Case 1 was a 3 month old mixed strain manly canine, appertained because severe epileptic seizure exertion starting one month before, when the canine was set up homeless by the present proprietor. The epileptic seizures were characterized by the alcohol-clonic generalized exertion, including autonomic signs. The frequency of the seizure exertion was precipitously adding and, at donation, was represented by a diurnal cluster of six to 10 epileptic seizures. The blood parameters and the cerebrospinal fluidm (CSF) were normal, whilst the glamorous resonance imaging (MRI) was declined by the proprietor for fiscal issues. Phenobarbital remedy (3 mg/ kg every 12 h), introduced after the neurological examination, was ineffective, despite its blood position in the remedial range of 25 μg/ mL. The canine was euthanized upon the proprietor’s request a many days latterly [3].

Case 2 was a 21 day old manly Border Collie, presented light and underdeveloped with progressive neurological signs, including an altered mentation, circling, ataxia, and the unforeseen onset of epileptic cluster seizures m (five in 24 h), the day before the donation. The other littermates were normal, and no history of poison exposure was reported. The blood parameters were normal, and the proprietor declined farther disquisition, including a MRI checkup. The canine was treated with benzodiazepine (1 mg/ kg per rectum, doubly daily) and phenobarbital2.5 mg/ kg intramuscularly, every 8 h, without any enhancement. The canine was humanely euthanized upon the proprietor’s request, ten days latterly due to the presence of seizures every 2–3h. Case 3 was a 2.5 month old domestic shorthaired manly cat, presented with a fleetly progressive epileptic seizure exertion, which in a many days reached the frequence of one occasion every 15 min. The other littermates were normal, and no history of poison exposure was reported. The individual tools weren't performed because of the proprietor constraint. The administration of benzodiazepine (1 mg/ kg intravenously) and phenobarbital (up to 5 mg/ kg IM) were ineffective, and the cat was euthanized upon the proprietor’s request, a many days latterly [4].

The gross postmortem findings were normal in all the creatures, except for the smarts of cases 1 and 3, which showed anomalies of the telencephalic regions. The smarts and samples of the major organs were fixed in a phosphatesoftened 4 formalin result and also routinely reused for histology. In case 1, the transverse sections of the telencephalon showed a loss of the normal distinction between the argentine and white matter, shallow sulci, and a mild blowup of the ventricular depressions. The other encephalic areas were grossly normal. The cat brain (case 3) showed a bilateral and nearly symmetrical anomaly of the cortical components. The gyri and sulci appeared roughly developed, giving a bumpy appearance of the cortical face. The transverse sections of the fixed brain showed the absence of the nimbus radiata, an desultorily thickened cortex, a loss of sulci, and a broadening gyri. The argentine-white matter junction was saved but had an irregular appearance. The rudimentary capitals, thalamus, brain stem, and cerebellum were macroscopically normal Five micron-thick towel sections were stained with hematoxylin and eosin (HE), Luxol presto blue (LFB), and Bielchowsky tableware stain.

The named sections were stained immunohistochemically (IHC) with antibodies against the glial fibrillary acidic protein (GFAP, 11000; DakoCytomation, Carpinteria, CA, USA), and phosphorylated neurofilaments (clone 2F11, 11500; DakoCytomation). The heat-convinced epitope reclamation was performed for both labels. The primary antibodies were incubated overnight at 4 C and the immunoreactivity was detected by the avidin biotin peroxidase complex system (Vectastain ® Elite ABC-Peroxidase tackle; Vector Laboratories,Inc., Burlingame, CA, USA), using, 3′-diaminobenzidine as chromogen. The negative controls were attained by forgetting the primary antibody [5].

Discussion

In all cases, the morphological features of the observed lesions were reflective of different forms of a MCD. The histopathological pattern of case 1 was harmonious with a form of cortical dysplasia of Taylor type IIb. This reality is characterized by a massive spillover of abnormal neurons of the corticalwhite matter junction, the laminar relief of megalic and dysmorphic neurons (“balloon cells”) and well- saved white matter. Taylor-type IIb focal cortical dysplasia (FCD) has not been reported in the veterinary literature up until now.

FCD is a honored condition in humans and, since its first description, it was considered a cause of medically intractable epilepsy. The factual prevalence is unknown, but among people with pharmacoresistant epileptic seizures, especially children, it accounts for utmost neocortical epilepsy cases. FCD is classified in type I, II, and III depending on the morphology, the expression of the proteins and the association with other brain lesions. Mortal MRI in FCD I generally shows no visible changes, while in FCD II, the focal cortical thickening, fuzziness between the argentine and white matter, the white matter hyperintensity on T2 weighted images (T2WI) and fluid downgraded inversion recovery (faculty), the widened gyri, and abnormal sulci can be observed. There are some available ways used for the precise discovery of the FCD lesions in mortal drug, which show a good performance, substantially grounded on automated styles. Reports of the MRI appearance of cortical dysplasia are lacking in veterinary drug and only one study reported the MRI of a Golden Retriever with a bilaterally symmetrical cortical dysplasia that revealed symmetrical hippocampal and periventricular hyperintensities on T2 weighted images.

In humans the standard treatment is the surgical resection of the lesion where, especially in type II, FCD has been associated with better seizure issues. The absence of a visible lesion on MRI is one of the topmost challenges in epilepsy surgery and has led to an increase in invasive electroencephalography (EEG) studies.

In recent times, single causative gene mutations have been set up for mortal FCD, presumably due to the involvement of genes garbling nonsupervisory proteins within the mechanistic target of the rapamycin (mTOR) pathway.

Conclusion

Since in pediatric neurology, these diseases are generally associated with epilepsy, we suggest that although there's no direct substantiation, the MCDs in our cases may be responsible for epileptogenesis. All cases described in this handwriting showed severe clusters of epileptic seizures that failed to ameliorate with combined antiepileptic remedy. Indeed if the antiepileptic treatment introduced in our cases could be bettered, the worsening of the seizure’s frequence, lead us to consider the possibility of medicine resistant epilepsy. Still, we cannot count a better treatment response using combined AED. In fact, although the presence of a high prevalence of medicine resistance in mortal cases with a MCD, a period of medicine responsiveness could be achieved in a small proportion of cases. Likewise, in pediatric cases, the AED pharmacokinetic may be different, compared to grown-ups and the adaptation of boluses or the frequence of administration may be useful. So, in the case of a suspected MCD, an attempt with an aggressive antiepileptic treatment is recommended.

We suggest that although rare a MCD may be responsible for the development of epileptic seizure exertion in youthful creatures and that, at least in some cases, the operation of MRI ways might grease the in vivo identification of some cortical deformations in creatures with epilepsy.

References

1. Saitsu, Hirotomo, Mitsuhiro Kato, Takeshi Mizuguchi, and Keisuke Hamada, et al. "De novo mutations in the gene encoding STXBP1 (MUNC18-1) cause early infantile epileptic encephalopathy." Nat Genet 40(2008):782-788.

Google Scholar, Crossref

2. Hamosh, Ada, Alan Scott F, Joanna Amberger, and David Valle, et al. "Online Mendelian inheritance in man (OMIM)." Human Mutat 15(2000):57-61.

Google Scholar, Crossref

3. DiMauro, Salvatore, Eric Schon A, Valerio Carelli, and Michio Hirano. "The clinical maze of mitochondrial neurology." Nat Rev Neurol 9(2013):429-444.

Google Scholar, Crossref

4. Yin, Xiaomeng, Beisha Tang, Xiao Mao, and Jinxin Peng, et al. "The genotypic and phenotypic spectrum of PARS2-related infantile-onset encephalopathy." J Human Gen 63(2018):971-980.

Google Scholar, Crossref

5. Darin, Niklas, Anders Oldfors, Ali‐Reza Moslemi, and Elisabeth Holme, et al. "The incidence of mitochondrial encephalomyopathies in childhood: clinical features and morphological, biochemical, and DNA abnormalities." Ann Neurol 49(2001):377-383.

Google Scholar, Crossref