Nejvíce citovaný článek - PubMed ID 18513354
Different presurgical characteristics and seizure outcomes in children with focal cortical dysplasia type I or II
OBJECTIVE: We comprehensively characterized a large pediatric cohort with focal cortical dysplasia (FCD) type 1 to expand the phenotypic spectrum and to identify predictors of postsurgical outcomes. METHODS: We included pediatric patients with histopathological diagnosis of isolated FCD type 1 and at least 1 year of postsurgical follow-up. We systematically reanalyzed clinical, electrophysiological, and radiological features. The results of this reanalysis served as independent variables for subsequent statistical analyses of outcome predictors. RESULTS: All children (N = 31) had drug-resistant epilepsy with varying impacts on neurodevelopment and cognition (presurgical intelligence quotient [IQ]/developmental quotient scores = 32-106). Low presurgical IQ was associated with abnormal slow background electroencephalographic (EEG) activity and disrupted sleep architecture. Scalp EEG showed predominantly multiregional and often bilateral epileptiform activity. Advanced epilepsy magnetic resonance imaging (MRI) protocols identified FCD-specific features in 74.2% of patients (23/31), 17 of whom were initially evaluated as MRI-negative. In six of eight MRI-negative cases, fluorodeoxyglucose-positron emission tomography (PET) and subtraction ictal single photon emission computed tomography coregistered to MRI helped localize the dysplastic cortex. Sixteen patients (51.6%) underwent invasive EEG. By the last follow-up (median = 5 years, interquartile range = 3.3-9 years), seizure freedom was achieved in 71% of patients (22/31), including seven of eight MRI-negative patients. Antiseizure medications were reduced in 21 patients, with complete withdrawal in six. Seizure outcome was predicted by a combination of the following descriptors: age at epilepsy onset, epilepsy duration, long-term invasive EEG, and specific MRI and PET findings. SIGNIFICANCE: This study highlights the broad phenotypic spectrum of FCD type 1, which spans far beyond the narrow descriptions of previous studies. The applied multilayered presurgical approach helped localize the epileptogenic zone in many previously nonlesional cases, resulting in improved postsurgical seizure outcomes, which are more favorable than previously reported for FCD type 1 patients.
- Klíčová slova
- drug‐resistant epilepsy, epilepsy surgery, focal cortical dysplasia type 1, multilayered diagnostic protocol, pediatric patients,
- MeSH
- dítě MeSH
- elektroencefalografie MeSH
- epilepsie MeSH
- fokální kortikální dysplazie MeSH
- kohortové studie MeSH
- kojenec MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- malformace mozkové kůry, skupina I * komplikace chirurgie patofyziologie diagnostické zobrazování MeSH
- mladiství MeSH
- následné studie MeSH
- pozitronová emisní tomografie MeSH
- předškolní dítě MeSH
- refrakterní epilepsie * chirurgie diagnostické zobrazování patofyziologie etiologie MeSH
- výsledek terapie MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Focal cortical dysplasia (FCD) represents the most common cause of drug-resistant epilepsy in adult and pediatric surgical series. However, genetic factors contributing to severe phenotypes of FCD remain unknown. We present a patient with an exceptionally rapid development of drug-resistant epilepsy evolving in super-refractory status epilepticus. We performed multiple clinical (serial EEG, MRI), biochemical (metabolic and immunological screening), genetic (WES from blood- and brain-derived DNA), and histopathological investigations. The patient presented 1 month after an uncomplicated varicella infection. MRI was negative, as well as other biochemical and immunological examinations. Whole-exome sequencing of blood-derived DNA detected a heterozygous paternally inherited variant NM_006267.4(RANBP2):c.5233A>G p.(Ile1745Val) (Chr2[GRCh37]:g.109382228A>G), a gene associated with a susceptibility to infection-induced acute necrotizing encephalopathy. No combination of anti-seizure medication led to a sustained seizure freedom and the patient warranted induction of propofol anesthesia with high-dose intravenous midazolam and continuous respiratory support that however failed to abort seizure activity. Brain biopsy revealed FCD type IIa; this finding led to the indication of an emergency right-sided hemispherotomy that rendered the patient temporarily seizure-free. Postsurgically, he remains on antiseizure medication and experiences rare nondisabling seizures. This report highlights a uniquely severe clinical course of FCD putatively modified by the RANBP2 variant. PLAIN LANGUAGE SUMMARY: We report a case summary of a patient who came to our attention for epilepsy that could not be controlled with medication. His clinical course progressed rapidly to life-threatening status epilepticus with other unusual neurological findings. Therefore, we decided to surgically remove a piece of brain tissue in order to clarify the diagnosis that showed features of a structural brain abnormality associated with severe epilepsy, the focal cortical dysplasia. Later, a genetic variant in a gene associated with another condition, was found, and we hypothesize that this genetic variant could have contributed to this severe clinical course of our patient.
- Klíčová slova
- RANBP2, epilepsy surgery, focal cortical dysplasia, hemispherotomy, refractory status epilepticus,
- MeSH
- dítě MeSH
- DNA MeSH
- epilepsie * komplikace MeSH
- fokální kortikální dysplazie * MeSH
- komplex proteinů jaderného póru * MeSH
- lidé MeSH
- midazolam MeSH
- molekulární chaperony * MeSH
- nemoci mozku * MeSH
- předškolní dítě MeSH
- progrese nemoci MeSH
- refrakterní epilepsie * genetika chirurgie MeSH
- status epilepticus * genetika chirurgie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- DNA MeSH
- komplex proteinů jaderného póru * MeSH
- midazolam MeSH
- molekulární chaperony * MeSH
- ran-binding protein 2 MeSH Prohlížeč
Magnetic Resonance Imaging (MRI) has revolutionized our ability to non-invasively study the brain's structural and functional properties. However, detecting myelin, a crucial component of white matter, remains challenging due to its indirect visibility on conventional MRI scans. Myelin plays a vital role in neural signal transmission and is associated with various neurological conditions. Understanding myelin distribution and content is crucial for insights into brain development, aging, and neurological disorders. Although specialized MRI sequences can estimate myelin content, these are time-consuming. Also, many patients sent to specialized neurological centers have an MRI of the brain already scanned. In this study, we focused on techniques utilizing standard MRI T1-weighted (T1w) and T2 weighted (T2w) sequences commonly used in brain imaging protocols. We evaluated the applicability of the T1w/T2w ratio in assessing myelin content by comparing it to quantitative T1 mapping (qT1). Our study included 1 healthy adult control and 7 neurologic patients (comprising both pediatric and adult populations) with epilepsy originating from focal epileptogenic lesions visible on MRI structural scans. Following image acquisition on a 3T Siemens Vida scanner, datasets were co registered, and segmented into anatomical regions using the Fastsurfer toolbox, and T1w/T2w ratio maps were calculated in Matlab software. We further assessed interhemispheric differences in volumes of individual structures, their signal intensity, and the correlation of the T1w/T2w ratio to qT1. Our data demonstrate that in situations where a dedicated myelin-sensing sequence such as qT1 is not available, the T1w/T2w ratio provides significantly better information than T1w alone. By providing indirect information about myelin content, this technique offers a valuable tool for understanding the neurobiology of myelin-related conditions using basic brain scans.
BACKGROUND: We aimed first to describe trends in cognitive performance over time in a large patient cohort (n = 203) from a single tertiary centre for paediatric epilepsy surgery over the period of 16 years divided in two (developing-pre-2011 vs. established-post-2011). Secondly, we tried to identify subgroups of epilepsy surgery candidates with distinctive epilepsy-related characteristics that associate with their pre- and post-surgical cognitive performance. Thirdly, we analysed variables affecting pre-surgical and post-surgical IQ/DQ and their change (post- vs. pre-surgical). METHODS: We analysed IQ/DQ data obtained using standardized neuropsychological tests before epilepsy surgery and one year post-surgically, along with details of patient's epilepsy, epilepsy surgery and outcomes in terms of freedom from seizures. Using regression analysis, we described the trend in post-operative IQ/DQ. Cognitive outcomes and the associated epilepsy- and epilepsy surgery-related variables were compared between periods before and after 2011. Using multivariate analysis we analysed the effect of individual variables on pre- and post-operative IQ/DQ and its change. RESULTS: Epilepsy surgery tends to improve post-surgical IQ/DQ, most significantly in patients with lower pre-surgical IQ/DQ, and post-surgical IQ/DQ strongly correlates with pre-surgical IQ/DQ (Rho = 0.888, p < 0.001). We found no significant difference in pre-, post-surgical IQ/DQ and IQ/DQ change between the periods of pre-2011 and post-2011 (p = 0.7, p = 0.469, p = 0.796, respectively). Patients with temporal or extratemporal epilepsy differed in their pre-surgical IQ/DQ (p = 0.001) and in IQ/DQ change (p = 0.002) from those with hemispheric epilepsy, with no significant difference in post-surgical IQ/DQ (p = 0.888). Groups of patients with different underlying histopathology showed significantly different pre- and post-surgical IQ/DQ (p < 0.001 and p < 0.001 respectively) but not IQ/DQ change (p = 0.345).Variables associated with severe epilepsy showed effect on cognitive performance in multivariate model. DISCUSSION: Post-surgical IQ/DQ strongly correlates with pre-surgical IQ/DQ and greatest IQ/DQ gain occurs in patients with lower pre-surgical IQ/DQ scores. Cognitive performance was not affected by changes in paediatric epilepsy surgery practice. Pre- and post-operative cognitive performances, as well as patients' potential for cognitive recovery, are highly dependent on the underlying aetiology and epileptic syndrome.
Malformations of cortical development (MCD) comprise a broad spectrum of developmental brain abnormalities. Patients presenting with MCDs often suffer from drug-resistant focal epilepsy, and some become candidates for epilepsy surgery. Their likelihood of achieving freedom from seizures, however, remains uncertain, and depends in a major part on the underlying pathology. Tissue samples obtained in epilepsy surgery form the basis of definite histopathological diagnosis; however, new molecular genetic methods have not yet been implemented in diagnostic processes for MCD cases. Furthermore, it has not been completely understood how the underlying pathology affects patients' outcomes after epilepsy surgery. We performed a systematic literature review of studies describing both histopathological and molecular genetic findings in MCD, along with studies on epilepsy surgery outcomes. We aimed to correlate the genetic causes with the underlying morphological abnormalities in focal cortical malformations and to stress the importance of the underlying biology for patient management and counseling. From the summarized findings of multiple authors, it is obvious that MCD may have a diverse genetic background despite a similar or even identical histopathological picture. Even though most of their molecular genetic findings converge on various levels of the PI3K/AKT/mTOR pathway, the exact mechanisms underlying MCD formation have not yet been completely described or indeed how this pathway generates a diverse range of histological abnormalities. Based on our findings, we therefore propose that all patients diagnosed and operated for drug-resistant epilepsy should have an integrated molecular and pathological diagnosis similar to the current practice in brain tumor diagnostic processes that might lead to more accurate diagnosis and effective stratification of patients undergoing epilepsy surgery.
- Klíčová slova
- mTOR, epilepsy surgery, malformations of cortical development, neuropathology, somatic variant,
- MeSH
- epilepsie genetika patologie MeSH
- fosfatidylinositol-3-kinasy MeSH
- genetické asociační studie MeSH
- lidé MeSH
- malformace mozkové kůry genetika patologie MeSH
- mozek abnormality patologie MeSH
- mozková kůra patologie MeSH
- nemoci mozku patologie MeSH
- refrakterní epilepsie genetika patologie MeSH
- signální transdukce MeSH
- TOR serin-threoninkinasy MeSH
- záchvaty patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- systematický přehled MeSH
- Názvy látek
- TOR serin-threoninkinasy MeSH
