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|Year : 2019 | Volume
| Issue : 2 | Page : 450-451
Malformations of cortical development and inverted hippocampal inversion: The questions raised
Manjari Tripathi, Divyani Garg
Department of Neurology, All India Institute of Medical Sciences, New Delhi, India
|Date of Web Publication||13-May-2019|
Dr. Manjari Tripathi
Department of Neurology, Room No 705, Neurosciences Centre, All India Institute of Medical Sciences, New Delhi - 110 029
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Tripathi M, Garg D. Malformations of cortical development and inverted hippocampal inversion: The questions raised. Neurol India 2019;67:450-1
Malformations of cortical development (MCD) include a group of central nervous system disorders in children with developmental delay and in young adults with epilepsy. Classification schemes were introduced based upon the earliest steps in neural development that get interrupted, that is, neuronal proliferation, migration and differentiation. These disorders may arise from genetic or environmental causes. The genetic causes include single gene defects, chromosomal abnormalities and also a multifactorial etiology. Environmental causes include drugs, toxins, and maternal conditions. Updates to the classification were introduced in 2001 and 2005 and relied more on genetics, and noted that MCDs of varying severity may arise from the same gene mutation. Hippocampal malrotation (HIMAL) or incomplete-hippocampal inversion (IHI) occur due to incomplete infolding of the mesial temporal lobe structures during embryological development. The condition leads to an atypical appearance of the hippocampus, that is either rounded or pyramidal shaped, or with a medial location along the choroid fissure, or with verticalization of the collateral sulcus.
A study published by Munirathinam et al., prospectively evaluates the prevalence and clinical characteristics of MCD and inverted hippocampal inversion (IHI) in patients with intractable epilepsy. The authors propose that IHI could be an epileptogenic abnormality and could give rise to drug-refractory epilepsy (DRE).
The authors evaluated 3200 patients with epilepsy of which 416 (13%) were deemed to have intractable epilepsy. 85 out of 416 patients were determined to have MCD and IHI. The presence of IHI was based on volumetric assessment of the hippocampus. MCDs were present in 46 (11%) and IHI in 39 (9%) patients with DRE. IHI was observed on the left side in 87% and the right side in 13% of the patients.
The prevalence of MCDs in patients with DRE in this study is lower than that reported in other studies. MCD is a common cause of childhood DRE. Around 15% of all childhood epilepsy is resistant to pharmacotherapy. Of these children, around 40% of cases are due to MCDs. In the present study, the patient population that was included in the study was between 10 and 65 years, and therefore, childhood cases were likely to have been missed, leading to an underestimation of the prevalence. In addition, structural imaging involved the use of 1.5 Tesla magnetic resonance imaging (MRI) of the brain, and hence, some lesions could have, on radiological assessment, gone undetected.
IHI has been reported to occur in healthy subjects in various studies but also in patients with epilepsy, particularly in association with MCD and temporal lobe epilepsy (TLE), with a prevalence ranging from 30 to 50%. In addition, IHI has also been noted to occur in midline cranial defects such as agenesis of the corpus callosum as well as other genetic abnormalities. In total, IHI was found in 17% of the normal subjects related to the left hippocampus and in 6% normal subjects related to the right hippocampus.
The occurrence of IHI more commonly on the left side in this study has been corroborated in earlier studies although there seems to be no correlation of laterality with TLE.
The prevalence of IHI in patients with epilepsy is a debatable issue. The prevalence has been found to be significantly higher in patients with several epilepsy syndromes such as Rolandic epilepsy but not in patients with TLE, compared to the control population. It has also been reported to be higher in patients with febrile status epilepticus in the FEBSTAT study. This study affords some insight into this dilemma, with the authors finding a significantly higher prevalence of IHI in patients with DRE. However, the use of control subjects in this study could have shed more light on this aspect. MCDs are important causes of refractory seizures needing surgery in our population too.
The most common seizure type observed with both MCD and IHI was a complex-partial seizure. It was observed as the dominant seizure type in 67% of MCD and 65% of IHI patients. A detailed description of the clinical features of these seizures and any differences from those described for TLE of other causes would have been additionally informative.
The authors have characterized a few clinical differences between the patients with DRE with MCD and IHI. For the MCD group, the age of onset of seizures was less than 5 years, whereas in the IHI group, it was between 5 and 20 years. A change in seizure semiology from generalized to partial seizures, favored the diagnosis of MCD over IHI. MCDs tended to range from focal findings to multiple structural malformations in the brain. There were no differences reported with respect to the type of seizure, presence of clustering of seizures or status epilepticus, electroencephalographic findings, febrile seizures, neurocutaneous markers or family history.
A comparison of cognitive dysfunction between the MCD and IHI groups was revealing. The intelligence quotient scores and the memory quotient scores were measured using the Wechsler's adult intelligence scale III and Wechsler's memory scale. These scored were significantly lower in the MCD group compared to the IHI group. This is likely to reflect the multifocal brain involvement in MCD, also reported in this study.
This study raises some important questions and urges the need for additional research work. Does IHI occur more commonly in patients with epilepsy compared to drug-refractory epilepsy? What is the incidence of various hippocampal abnormalities in Indian patients? How do they correlate with other demographic, clinical, and imaging features? What are the additional neuropsychological impacts of IHI, both in normal subjects, and in the context of epilepsy patients?
Overall, the study secures some important points in adding details to the description of DRE in the context of MCD and IHI. A case series with a larger number of subjects and a control arm along with an in-depth description of the subsets of cognitive impairment and features associated with drug refractoriness would be welcome.
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