Multiple focal cortical dysplasias presenting with intractable epilepsy: case report]

A 14-year-old female, who had intractable epilepsy associated with multiple focal cortical dysplasias (FCD), was reported. She developed intractable epilepsy at the age of 7 and was diagnosed as having frontal lobe epilepsy based on the seizure semiology and interictal EEG. MRI revealed multiple lesions in the right frontal, bilateral occipital and left parietal lobes. EEG demonstrated that ictal discharge was preceded by spike on the right frontal region and FDG-PET showed hypometabolic area in the right frontal lobe. Chronic subdural electrode recordings from the right frontal lobe indicated that ictal onset zone was located around the right frontal lesion, especially frontal tip and base, and these areas including the lesion were resected. Postoperatively, residual seizure was noted although seizure frequency was decreased. It is well known that, postoperatively, satisfactory seizure outcome can be obtained in patients with FCD. However, further investigation in terms of surgical indication and strategies for multiple FCD should be needed.     

Atypical case of hemiconvulsions-hemiplegia-epilepsy syndrome revealing contralateral focal cortical dysplasia

Hemiconvulsions-hemiplegia-epilepsy syndrome (HH/HHE) is a rare epileptic syndrome consisting of a prolonged unilateral convulsion producing a persisting hemiplegia, sometimes followed by epilepsy. We report on a 13-month-old male who presented with febrile left-sided HH syndrome with right hemispheric unilateral cytotoxic oedema followed by hemispheric atrophy on magnetic resonance imaging (MRI). Six months later the child progressively developed refractory focal epilepsy, including right hemiclonic seizures, and nearly continuous left frontal rhythmic spikes, suggesting the presence of a focal cortical dysplasia (FCD). A repeat MRI at 2 years of age showed left frontal FCD. This unusual case of dual pathology--right HH syndrome and left FCD--suggests that some other factor than the malformation determined the prolonged status and brain atrophy. The kinetics of regional cortical maturation could explain this unusual condition.     

Epilepsy surgery in the first months of life: a large type IIb focal cortical dysplasia causing neonatal drug‐resistant epilepsy

Focal cortical dysplasia is a common cause of medically refractory epilepsy in infancy and childhood. We report a neonate with seizures occurring within the first day of life. Continuous video‐EEG monitoring led to detection of left motor seizures and a right frontal EEG seizure pattern. Brain MRI revealed a lesion within the right frontal lobe without contrast enhancement. The patient was referred for epilepsy surgery due to drug resistance to vitamin B6 and four antiepileptic drugs. Lesionectomy was performed at the age of two and a half months, and histopathological evaluation confirmed the diagnosis of focal cortical dysplasia type IIb (FCD IIb). The patient is free of unprovoked seizures without medication (Engel Class I) and is normally developed at 36 months after surgery. The case study demonstrates that FCD IIb may cause seizures within the first day of life and that epilepsy surgery can be successfully performed in medically intractable patients with a clearly identifiable seizure onset zone within the first three months of life. Although radical surgery such as hemispherectomy and multi‐lobar resections are over‐represented in early infancy, this case also illustrates a favourable outcome with a more limited resection in this age group.     

Ictal haemodynamic changes in a patient affected by “subtle” Epilepsia Partialis Continua

We report on a 64 year-old woman presenting with Epilepsia Partialis Continua (EPC) affecting the left hand since the age of 24 without neurological deficit. Structural MRI showed a region of focal cortical dysplasia (FCD) over the right central gyrus and lesions in the mesial frontal and occipital cortex secondary to perinatal hypoxic injury. Ictal spike haemodynamic mapping using simultaneous EEG-fMRI revealed significant BOLD signal changes prominent in the region of FCD (larger cluster), occipital cortex (global statistical maximum), prefrontal cortex and cerebellum. The cluster over FCD was in good agreement with the result of EEG source analysis.Our findings provide an interesting illustration of the ability of EEG-fMRI to reveal epileptogenic networks confirming the intrinsic epileptogenic properties of dysplastic neurons.     

Widespread frontal lobe cortical dysplasia or partial hemimegalencephaly: a continuum of the spectrum

Focal cortical dysplasia (FCD) type II and hemimegalencephaly (HME) are currently considered as a continuum of pathology, the most important distinction being the extent or the size/volume of the lesion. While partial HME involving the posterior cortex has been well described, we present an unusual case with a dysplastic lesion of the whole frontal lobe. A 17‐year‐old boy had focal seizures from the age of nine years. Apart from diminished right‐hand dexterity, his neurological and cognitive status were unremarkable. The course of his epilepsy exhibited a relapsing‐remitting pattern, with prolonged periods of remission. Imaging showed dysplastic left frontal lobe (including paracentral lobule) thickened cortex with an abnormal gyration pattern resembling polymicrogyria, as well as dystrophic calcifications and hypodensity scattered throughout the white matter. This patient represents an intermediate case within the FCD type II/HME spectrum. Localization of the lesion in the frontal lobe as well as clinical characteristics (childhood onset, relapsing‐remitting epilepsy, without hemiparesis and overt cognitive impairment) are more consistent with FCD type II, while a range of MRI features is shared between HME and FCD type II.     

Combined imaging of epileptic foci and brain metabolism using MEG and FDG-PET]

A 17-year-old woman developed left hemiparesis at the age 6 months. She had suffered from focal motor seizures associated with tonic extension of her left extremities since the age of 10 years. The interictal scalp EEG demonstrated frequent spike-and-slow-wave complexes dominantly in the right frontal area. MRI showed an old cerebral infarction in the right frontal lobe. Simultaneous recordings of magnetoencephalography (MEG) and EEG were obtained by using a 204-channel whole-head MEG system. Equivalent current dipoles (ECDs) calculated from epileptic spikes on MEG were scattered in the cortex adjacent to the lesion in the right frontal lobe. Positron emission tomography with 18-fluoro-2-deoxyglucose (FDG-PET) in the interictal state showed hypometabolism in the lesion and its adjacent area. The super-imposed images of the dipole and PET showed that epileptic foci surrounded the lesion. The multimodality imaging is useful for evaluation of patients with epilepsy for possible indication of surgery.     

Longitudinal study of cognitive function in two patients with focal cortical dysplasia

To clarify the relationship between epileptic attacks and cognitive dysfunction, we examined the serial findings of 123I-IMP single photon emission computed tomography (SPECT) in relation to the intelligence quotient (IQ), assessed by Wechsler Intelligence Scale of Children-Revised, in two female patients with focal cortical dysplasia (FCD) over a 10-year period. The age of patient 1 at the initial assessment was 2 years, and the age of patient 2 was 9 months. They developed complex partial epilepsy in infancy, and were treated with antiepileptic drugs, which remained effective until 11 years of age, when their epileptic attacks recurred. Patient 1, a 14-year-old girl with FCD of the left parietal lobe suffered from dyscalculia, right-left disorientation, and finger agnosia even when she was free of epileptic attacks. Following the recurrence of seizures which occurred every night, she became unable to understand what was said to her. A hypoperfusion area detected by 123I-IMP SPECT was restricted to the left parietal lobe during the seizure-free period, but spread to the temporo-parietal lobes following the recurrence. Her verbal IQ declined from 94 (at 9 years of age) to 63 (at 11 years and 8 months). After her seizures were controlled again (at 14 years and 4 months), the 123I-IMP SPECT findings improved. Patient 2, a 12-year-old girl with FCD of the left frontal lobe, showed cognitive dysfunction. Her verbal IQ declined from 91 (at 7 years and 5 months) to 76 (at 11 years and 8 months) following a recurrence of epileptic attacks. 123I-IMP SPECT showed hypoperfusion in the left frontal lobe, where the accumulation count ratio (left/right ratio) declined from 0.86 (at 3 years) to 0.64 (at 11 years). These findings suggest that epileptic attacks are related to cognitive dysfunction in FCD patients. This cognitive dysfunction appears to correlate with the appearance of hypoperfusion areas, as detected by 123I-IMP SPECT.     

Myelination and organization of the frontal white matter in children: a diffusion tensor MRI study.

Myelination is critical for the functional development of the brain, but the time course of myelination during childhood is not well known. Diffusion tensor MR imaging (DTI) provides a new method for estimating myelination in vivo. Myelin restricts diffusion of water transverse to the axons, causing diffusion to be anisotropic. By quantifying the anisotropy, the progressive myelination of axons can be studied. Central white matter of the frontal lobe was studied in seven children (mean age 10 years) and five adults (mean age 27 years). Anisotropy in the frontal white matter was significantly lower in children than in adults, suggesting less myelination in children. Measurement of the coherence of white matter revealed that the right frontal lobe had a more regular organization of axons than the left frontal lobe, in both children and adults. The results demonstrate that maturation of the frontal white matter continues into the second decade of life. The time course of prefrontal maturation makes it possible that myelination is a basis for the gradual development of prefrontal functions, such as increased working memory capacity.     

术中1.5T核磁共振外科治疗难治性癫癎

目的探讨应用术中1.5T核磁共振(MRI)治疗难治性癫癎的手术效果。方法手术治疗难治性癫癎15例,利用术中1.5T核磁共振,术前常规行T1、T2及T1加强,及弥散张量成像,术中切除(切开)后行T1、T2及T1加强及弥散张量成像检查,以确定切除范围及功能区定位,其中5例术中MR检查后扩大切除。结果左侧枕叶局灶性皮质发育异常2例,左侧颞叶海绵状血管瘤4例,左侧颞叶海马硬化1例,右侧额叶胚胎发育不良性神经上皮肿瘤1例,右侧中央前回局灶性皮质发育不良1例,右侧颞叶海马硬化1例,右侧颞叶海绵状血管瘤1例,右侧颞叶胶质瘤1级1例,右侧中央后回海绵状血管瘤1例,胼胝体切开2例,engle分级:Ⅰ级11例,Ⅱ级4例。结论术中1.5T核磁共振对切除(切开)病灶及功能保护有指导意义。     

A comprehensive clinico‐pathological and genetic evaluation of bottom‐of‐sulcus focal cortical dysplasia in patients with difficult‐to‐localize focal epilepsy

Aims. We comprehensively studied the clinical presentation, stereo‐EEG and MRI findings, histopathological diagnosis, and brain somatic mutations in a retrospective series of drug‐resistant patients with difficult‐to‐localize epilepsy due to focal cortical dysplasia at the bottom of a sulcus (BOS‐FCD). Methods. We identified 10 patients with BOS‐FCD from the Cleveland Clinic epilepsy surgery database submitted for intracranial video‐EEG monitoring. Brain MRI, including voxel‐based morphometric analysis and surgical tissue submitted for histopathology, was reviewed. Paraffin tissue samples from five patients were made available for targeted next‐generation sequencing. Postsurgical follow‐up was available in nine patients. Results. BOS‐FCD was identified in the superior frontal sulcus in six patients, inferior frontal sulcus in one patient, central sulcus in one patient, and intraparietal sulcus in two patients. All patients had stereotyped seizures. Intracranial EEG recordings identified ictal onset at the BOS‐FCD in all 10 patients, whereas ictal scalp EEG had a localizing value in only six patients. Complete resection was achieved by lesionectomy or focal corticectomy in nine patients. Histopathologically, six patients had FCD type IIb and three had FCD type IIa. Next‐generation sequencing analysis of DNA extracted from lesion‐enriched (micro‐dissected) tissue from five patients with FCD type II led to the identification of a germline frameshift insertion in DEPDC5, introducing a premature stop in one patient. Eight out of nine patients with available follow‐up were completely seizure‐free (Engel Class IA) after a mean follow‐up period of six years. Conclusion. Our results confirm previous studies classifying difficult‐to‐localize BOS‐FCD into the emerging spectrum of FCD ILAE type II mTORopathies. Further studies with large patient numbers and ultra‐deep genetic testing may help to bridge the current knowledge gap in genetic aetiologies of FCD.     

A case of focal cortical dysplasia type IIa with pathologically suspected bilateral Rasmussen syndrome

BackgroundRasmussen syndrome (RS) is a rare neurological disorder characterized by unilateral chronic inflammation, drug-resistant epilepsy, and progressive neurological and cognitive deterioration. There has been no detailed pathological evaluation or finding, including focal cortical dysplasia, for bilateral RS.Case reportA 13-year-old boy presented with status epilepticus with focal to bilateral tonic clonic seizure starting from the left upper limb. At the age of 15, epilepsia partialis continua of the right face and upper extremities appeared, and MRI showed hemispheric abnormal signal intensities with left frontal lobe predominance. Three months later, MRI showed extensive abnormal signal intensities in the right occipitoparietal and left temporal lobes. Tacrolimus was useful in preventing recurrence. Because the seizures were intractable, a corpus callosotomy was performed at 16 years along with a concurrent brain biopsy from the bilateral lateral frontal cortices. We detected dysmorphic neurons in addition to inflammatory changes suspicious for RS, leading to a diagnosis of focal cortical dysplasia (FCD) type Ⅱa and suspected bilateral RS. Total callosotomy and vagus nerve stimulation were not sufficiently effective.ConclusionsIn bilateral RS, FCD may be present in both cerebral hemispheres. In the current case, an autoimmune response to dysmorphic neurons may have contributed to the pathogenesis of intense inflammation.     

A case of focal epilepsy associated with focal cortical dysplasia and crossed cerebellar diaschisis]

We here reported a 24-year-old woman who presented complex partial seizure from 15 years of age. Her brain MRI showed the right perirolandic focal cortical dysplasia (FCD) corresponding to the orofacial division of the primary sensori-motor area. On SPECT (Tc-99 mECD) study, hypoperfusion was demonstrated at the FCD, the right pons and the left cerebellum (crossed cerebellar diaschisis (CCD)). Magnetoencephalography disclosed the current source of the focal spikes was localized on the FCD. To our knowledge, no previous report of a case associated with FCD and CCD was found. We speculated the pathomechanism of the CCD might be related to the persistent epileptogenic firing which inhibited the cerebellar metabolism transsynaptically through cortico (FCD)-ponto-cerebellar pathway.     

Frontal lobe epilepsy with atypical seizure semiology resembling shuddering attacks or wet dog shake seizures

We report a girl with a drug-resistant frontal lobe epilepsy caused by focal cortical dysplasia, who exhibited uncommon seizures. The seizures consisted of shoulder or whole body shuddering after a short psychic aura and face grimacing. Consciousness was fully preserved. The seizures resembled "wet dog shake" seizures described in rat models of epilepsy or shuddering attacks in infants. EEG findings were inconclusive, however, MRI showed a clear dysplastic lesion in the right frontal mesial and polar structures. The patient underwent an extended lesionectomy guided by neuronavigation and intraoperative electrocorticography. Focal cortical dysplasia type Ib was histologically confirmed and the patient has been seizure-free for the three years following resection. [Published with video sequences].     

Contralateral temporal hypometabolism on positron emission tomography in temporal lobe epilepsy

Introduction — No detailed case studies report lateralised hypometabolism on positron emission tomography (PET) contralateral to the epileptogenic focus in temporal lobe epilepsy (TLE). Material and methods — We performed ¹⁸F fluorodeoxyglucose (FDG) PET in two intractable TLE patients. Results — One had right temporal interictal spikes on electroencephalography (EEG) and a right medial temporal lobe lesion on magnetic resonance imaging (MRI). FDG-PET showed decreased uptake in the left temporal lobe. Right temporal ictal onset, with bilateral interictal epileptiform activity, occurred on intracranial EEG. He is seizure free after right temporal lobectomy and ganglioglioma resection. The second had right temporal lobe interictal and ictal EEG activity. MRI demonstrated right anteriomedial temporal increased T2 signal. Neuropsychology revealed bilateral cognitive dysfunction. FDG-PET showed left anterior temporal and lateral frontal hypometabolism. He is seizure free after right temporal lobectomy. Conclusion — These findings suggest that regional uptake asymmetry on FDG-PET may be give misleading lateralising information in TLE.     

Focal cortical dysplasia and intractable epilepsy in adults: clinical,EEG, imaging,and surgical features

PURPOSE: The clinical features of focal cortical dysplasia (FCD) in adults are poorly understood. The purpose of this report is to describe the clinical, electrographic, and neuroimaging characteristics of adults with FCD undergoing surgical resection for intractable epilepsy. METHODS: Case series of 55 patients, aged 17-57 years, with a histopathological diagnosis of FCD. Medical history, neurological examination, non-invasive video-EEG, neuroimaging, and surgical outcome data were analyzed retrospectively. RESULTS: There were 36 patients with temporal, 19 with extra-temporal lobe resections. Mean age at surgery was 29 years. Mean age at epilepsy onset was 10 years. Dual pathology was seen in 56% of patients, with 68% of these having hippocampal sclerosis (HS). Epilepsy risk factors included febrile seizures (16%), head trauma (16%), CNS infections (11%), and perinatal stroke (4%). Interictal EEG showed regional epileptiform activity in 89% of patients. Only 24% were diagnosed with FCD pre-operatively. Of those with dual pathology, only 6% were suspected of having FCD pre-operatively. Of those patients with >12 months follow-up, surgical outcomes were as follows: 65% seizure-free, 19% significant improvement, 16% without significant improvement. CONCLUSIONS: In this series of adult patients with intractable epilepsy and FCD, a significant number have other seizure risk factors, normal neurological examinations and neuroimaging, and regional EEG findings. Dual pathology was common in patients with FCD. FCD should be considered as an etiology of epilepsy even in patients whose evaluation suggests other mechanisms.     

Intraoperative ultrasound to define focal cortical dysplasia in epilepsy surgery

Focal cortical dyplasia (FCD) is a frequent cause of medication-resistant focal epilepsy. Patients with FCD may benefit from epilepsy surgery. However, it is difficult to intraoperatively define lesion boundaries. In this case report we present a novel tool to identify FCD intraoperatively. A patient with frontal lobe epilepsy underwent resection of a left frontomesial FCD. Image guidance was achieved by intraoperative ultrasound, which depicted the lesion with a higher resolution than preoperative MRI. Postoperatively the patient remained seizure free. Intraoperative ultrasound may be helpful in identifying and targeting subtle epileptogenic lesions, which are difficult to visualize.     

Cryptogenic West syndrome and subsequent mesial temporal lobe epilepsy

We report on a male patient who experienced a previously unreported sequence of cryptogenic West syndrome in infancy and subsequent mesial temporal lobe epilepsy. His complex partial seizures were consistently characterised by motionless staring with brief right eye blinking. Scalp electroencephalography (EEG) showed bilateral temporal spikes which were dominant on the right side. Magnetic resonance imaging (MRI) revealed no organic brain lesion. Invasive EEG recording captured seizures with right hippocampal onset. The patient became seizure-free following right temporal lobectomy at 27 years, 8 months of age. Pathological examination of the resected specimen revealed corpora amylacea and gliosis in the temporal cortex but no clear findings of hippocampal sclerosis. It is suggested that an epileptogenic lesion causing MRI-negative mesial temporal lobe epilepsy may give rise to apparent cryptogenic West syndrome in infancy.     

Frontal lobe epilepsy may present as myoclonic seizures

We describe a patient with seizures arising from right anterior–inferior frontal lobe presenting as myoclonic epilepsy. A 19-year-old man had experienced frequent paroxysmal bilateral myoclonic jerks involving his upper arms, shoulders, neck, and upper trunk since the age of 10. His baseline EEG showed intermittent right frontal spikes, and his ictal EEG showed rhythmic sharp theta discharges in the same area. MRI revealed cortical dysplasia in the right inferior frontal gyrus, and ictal–interictal SPECT analysis by SPM showed increased signal abnormality in this region. Diffusion tensor imaging (DTI) showed defects in fasciculi in the same area. These findings suggest that frontal lobe epilepsy should be considered in some patients with myoclonic seizures.     

Prognostic factors for surgery of neocortical temporal lobe epilepsy.

OBJECTIVES: In the current classification of epilepsies two forms of temporal lobe epilepsy (TLE) were included: mesial and lateral (neocortical) TLE. We aimed at identifying prognostic factors for the surgical outcome of lesional neocortical TLE. METHODS: We included consecutive patients who had undergone presurgical evaluation including ictal video-EEG and high-resolution MRI, who had TLE due to neocortical lateral epileptogenic lesions, who had a lesionectomy and who had >2-year follow-up. RESULTS: There were 29 patients who met the inclusion criteria. Twenty of them became postoperatively seizure-free. Patients' mean age was 34.8+/-9 years (range 18-52). The age at epilepsy onset was 20.1+/-8 years. We found that left-sided surgery (p=0.048) and focal cortical dysplasia (FCD) on MRI (p=0.005) were associated with non-seizure-free outcome, while lateralized/localized EEG seizure pattern (p=0.032), tumors on the MRI (p=0.013), and a favorable seizure situation at the 6-month postoperative evaluation were associated with 2-year postoperative seizure-freedom (p<0.001). Multivariate analysis indicated that the side of surgery was not an independent predictor. CONCLUSION: More than two-thirds of the patients with neocortical TLE became seizure-free postoperatively. Lateralized/localized EEG seizure pattern and tumors on the MRI were associated with postoperative seizure-freedom, while FCD were associated with a poor outcome. The 6-month postoperative outcome is a reliable predictor for the long-term outcome.     

Somatic mutations involving TSC 1 and TSC2 genes in two children with focal cortical dysplasia

BackgroundThe role of PI3K/AKT/mTOR pathway hyperactivation in localized brain overgrowth is evolving. We describe two patients with focal cortical dysplasia (FCD) who demonstrated somatic mutations in TSC1 and TSC2 genes in the dysplastic brain tissue but not peripheral blood.MethodsPaired whole-exome sequencing was performed on genomic DNA extracted from blood and excised brain tissue in two children with FCD who underwent excision of dysplastic tissue.ResultsPatient 1, a 14-year boy, had drug-resistant focal epilepsy with onset at 20 months. His brain MRI showed abnormalities suggestive of FCD in the left superior and middle frontal lobes. Patient 2 presented at the age of 10 years with pharmaco-resistant focal epilepsy (onset at six years). His MRI suggested FCD in the left insular lobe. Both patients underwent surgical excision of FCD, and excised tissues were pathologically confirmed to have type IIb FCD. For patient 1, a missense mutation (c.64C > T; p.Arg22Trp) was detected in the TSC1 gene in DNA of dysplastic brain tissue but not peripheral blood lymphocytes. Similarly, for patient 2, a frameshift mutation (c.4258_4261delCAGT; p.Ser1420GlyfsTer55) in the TSC2 gene was identified in the brain tissue but not blood. Both gene variants are likely pathogenic and cause mTOR pathway activation.ConclusionOur report of TSC1/TSC2 somatic mutations in patients with non-syndromic FCD suggests that localized hyperactivation of the mTOR pathway can cause focal malformations during cortical development and presents pharmacological targets for precision therapy in FCD management.