Cases Of Refractory Epilepsy Research Articles

T06. Outcome of brain responsive neurostimulation in refractory epilepsy cases from a single tertiary epilepsy centre

Introduction Responsive Neurostimulation (RNS) provides an alternative treatment for medication-refractory epilepsy cases which are not a candidate for resective epilepsy surgery. It has been shown effective with complication rates comparable to similar procedures. This study reports the data on responsive neurostimulation patients from Massachusetts General Hospital (MGH) for the first time. Methods We retrospectively studied all patients who were implanted with RNS at MGH, which was from October 2006 to July 2017. We collected data on age of implantation, sex, and the localization of epileptogenic zone. The seizure reduction was calculated by subtracting the frequency of seizures per month in the last visit after implantation (report of past 6 months) from the seizure frequency before implantation. This was divided by seizure frequency before RNS implantation and reported in percentage. For calculating the responder rate, we excluded the three cases that received stimulation less than 6 months. Also we reviewed the rate of different complications associated with RNS. Results 25 patients (12 female and 13 male) ranging from 20 to 65 years old (mean ± std: 37.4 ± 12.6) were implanted with RNS from October 2006 to July 2017. One patient was explanted after 2 months due to wound infection so it was excluded from seizure outcome analyses. In terms of epileptogenic zone, 11 cases were neocortical, 9 cases were bilateral mesiotemporal, 2 cases were left mesiotemporal, 2 cases were left mesiotemporal and neocortical and 1 case was thalamic. The seizure reduction percentage ranged between 0% and 100% with median reduction of 88%. The responder rate (patients with >50% seizure reduction) was 76.19% (16 out of 21 patients) and the super-responder rate (patients with >90% seizure reduction) was 57.14% (12 out of 21 patients). There was a positive correlation between seizure reduction and time from implantation which means patients who had the RNS for longer showed better outcome (Spearman correlation: r = 0.43, p = 0.067).There was no significant difference in average seizure reduction percentage between neocortical (mean: 45.75 %) and bilateral mesiotemporal (mean: 70.00%) cases (p: 0.351). Seventeen patients had no post-operative complication (68%), 4 patients had intracranial hemorrhage (16%), 2 patients had wound infection (8%), 1 patient had headache (4%) and 1 patient had wound dehiscence (4%). Conclusion This study shows that RNS has been an effective treatment modality in medication refractory epilepsy cases at MGH, with minimal complications. The improvement of outcome over time supports the hypothesis that RNS may function through seizure network modulation. Future works are needed to find optimal frequency and length of stimulation to achieve faster and more efficacious network modulation.

Posterior Quadrant Disconnection: A Fiber Dissection Study.

Posterior quadrant disconnection can be highly effective in the surgical treatment of selected cases of refractory epilepsy. The technique aims to deafferent extensive areas of epileptogenic posterior cortex from the rest of the brain by isolating the temporoparietooccipital cortex. To describe this procedure and relevant white matter tracts with a specific emphasis on the extent of callosotomy in an anatomic study. Twenty hemispheres were dissected according to Klingler's fiber dissection technique illustrating the peri-insular (temporal stem, superior longitudinal fasciculus, corona radiata) and mesial disconnection (mesiotemporal cortex, cingulum, and corpus callosum). Extensive white matter tract disconnection is obtained after posterior quadrant disconnection. Callosal fibers connecting the anterior most part of the parietal cortex invariably ran through the isthmus of the corpus callosum and need to be disconnected, while frontal lobe connections including the corticospinal tract and the anterior two-thirds of the corpus callosum are spared during the procedure. Our findings suggest the involvement of both the splenium and the isthmus in interhemispheric propagation in posterior cortex epilepsies. Sectioning the total extent of the posterior one-third of the corpus callosum might therefore be necessary to achieve optimal outcomes in posterior quadrant epilepsy surgery.

Correlation between resection of high frequency oscillation region and outcomes of epilepsy surgery

Objective To explore the relationship between removal of areas where high frequency oscillations (HFOs) were detected by a new automatic detector and the prognosis of epilepsy surgical. Methods In this study, 7 patients with intractable epilepsy were enrolled and their clinical data were retrospectively studied, who underwent intracranial electroencephalography (EEG) monitoring and subsequent epileptogenic zone resection from January 2013 and December 2014 at Epilepsy Center of Beijing Haidian Hospital. An automatic detector of HFOs was employed using maximum distributed peak points to calculate baseline. Then the relationship between the removal ratio of HFOs and surgical outcomes was investigated. Results Among the 7 cases of refractory epilepsy, the resection ratio of ripple area was 19.4% ~ 96.4% and that of fast ripple area was 29.3% ~ 96.0% . The surgical removal ratio of HFO areas was higher than 50% in 5 cases, 4 out of whom achieved good outcomes after surgery. In the other 2 patients whose removal ratio of HFO area was lower than 50%, poor surgical outcome was reported in 1 and good outcome was obtained in the other who had extensive area demonstrating suspicious physiological HFOs in the occipital lobe. Conclusions The automatic detector of HFOs using maximum distributed peak points to calculate baseline seems to be accurate for detection of HFOs. The ratio of resection in areas with HFOs might be closely related to the surgical outcomes. Key words: Epilepsy; Neurosurgical procedures; Maximum distributed peak points; High frequency oscillations; Prognosis

A case of refractary epilepsy and related pain due to dysmenorrhea solved with loading dose of lacosamide: clinical and neurophysiological correlates

In most cases, the etiology of epilepsy is unknown, although some individuals may develop epilepsy as a result of certain brain injuries, following a stroke, a brain tumor or because of drugs and alcohol. Even some rare genetic mutations may be related to the onset of the condition. Seizures are the result of excessive and abnormal activity of neurons in the cerebral cortex. In this case report we show a clinical case of refractory epilepsy due to pain related to uncontrolled dysmenorrhea. The patient, 43 yrs old, had a history of epilepsy of 20 years and ovarian cancer. She was treated with lamotrigine, clonazepam and levomepromazina maleato. At admission the patient shew seizures due to pain related to dysmenorrhea. In emergency we treated with verapamil hydrochloride 10 mg ev, subsequently verapamil hydrochloride 20 mg in 250 ml of saline solution as maintenance dose. Then we decided to administer a loading dose of 100 mg cpr of Lacosamide to stop the treatment with verapamil hydrochloride. With Lacosamide we solved the seizures in 24 hours. (www. actabiomedica.it)

Movement disorder and epilepsy in subependymal nodular heterotopia

Subependymal nodular heterotopia is a cortical development malformation that is commonly associated with refractory epilepsy. Patients with heterotopia show a wide spectrum of clinical manifestations, from being asymptomatic to presenting with intractable seizures and intellectual impairment.We report a case of refractory epilepsy with normal intelligence, having bilateral subependymal heterotopic nodules in brain, presenting to us with a movement disorder in the form of myoclonus of bilateral lower limbs which is an unusual manifestation of gray matter heterotopias.Though rare, gray matter heterotopias may present as movement disorder and should be considered in differential diagnosis while work up of movement disorders.

Caracterización de los pacientes con epilepsia refractaria de un hospital de tercer nivel en Costa Rica

Thirty percent of patients with epilepsy have recurrent seizures, representing fifteen million people in the world. This population has been scarcely described. To characterize sociodemographic and clinically the patients diagnosed with refractory epilepsy in a tertiary referral hospital of the Costa Rican social security. This study presents an analysis of all cases of refractory epilepsy evaluated at the epilepsy unit of San Juan de Dios Hospital from August, 2012 to October, 2014. Clinical records of 91 patients were studied; patients with psychogenic seizures were analyzed separately. The mean age of onset was 13.1 ± 11.1 years, secondary generalized seizures were the predominant type (81.3%), the most frequent etiology was mesial temporal sclerosis (48.3%) and the majority had normal neurological exams and normal or low neuropsychological assessments. Around half (48.8%) of the patients had been medicated with a range of 4-6 antiepileptic drugs, being lamotrigine, carbamazepine, valproic acid and phenytoin the most prescribed. Treatment optimization, neurosurgery, and further analysis were standard recommendations. Sociodemographic characteristics, patient management, and antiepileptic drugs used are similar to the described in other latitudes. Differences between the age of onset and gender; seizure frequency and gender; age of onset and failed treatments and time of evolution of the disease and employment were observed. The percentage and characteristics of recurrent seizures of psychogenic nature found are comparable to other refractory epilepsy studies. Sociodemographic characteristics, management of patients, antiepileptic drugs used and the differences observed are similar to those previously described.

Dyke-Davidoff-Masson Syndrome: An Uncommon Cause of Refractory Epilepsy

A rare syndrome, Dyke-Davidoff-Masson Syndrome (DDMS), with a diagnostic conundrum, and the way it was solved is presented. DDMS is one among the syndromes associated with refractory epilepsy. We have come across a case of Dyke-Davidoff-Masson syndrome while investigating a case of refractory epilepsy. When cerebral hemi atrophy is associated with the radiological features of osseous hypertrophy of calvarium, hyper-pneumatisation of sinuses dilatation, DDMS is to be considered.Bangladesh J Medicine Jan 2014; 25 (1) : 31-34

Induction of Fear by Intraoperative Stimulation During Awake Craniotomy: Case Presentation and Systematic Review of the Literature

A case is presented and a systematic review of the literature is provided to update our current knowledge of induction of fear by cortical stimulation. We present a case of refractory epilepsy associated with a lesion where fear could be induced by intraoperative electrical stimulation of the posterior inner part of the superior temporal gyrus. We performed a systematic review of the literature using PubMed with the key words "epilepsy AND emotion", "cortical stimulation AND emotion," and "human brain stimulation AND behavior". Intraoperative cortical stimulation of the inner part of the posterior superior temporal gyrus reliably induced fear and progressive screaming behavior. Stimulation through subdural grid electrodes did not induce this phenomenon. A systematic review of the literature identified fear induction by stimulation of different widespread cortical areas including the temporal pole, the insula, and the anterior cingulate cortex. The posterior part of the superior temporal gyrus has so far not been associated with fear induction after electrical stimulation. Although our observation suggests that this area of the brain could be part of a network involved in the elicitation of fear, dysfunction of this network induced by epilepsy could also explain the observed phenomenon. Electrophysiologic and imaging studies must be conducted to improve our understanding of the cortical networks forming the neuroanatomical substrate of higher brain functions and experiences such as fear.

Dyke-Davidoff-Masson Syndrome: A Cause of Recurrent Seizures

Objective: Dyke-Davidoff-Masson Syndrome (DDMS) is one of the rare causes of recurrent seizures and can be missed in adults. It is associated with contralateral hemiplegia, mental retardation and facial asymmetry. Confirmed diagnosis can be made with characteristic radiological picture. Hemi-spherectomy is the treatment of choice. Case: DDMS is usually diagnosed in childhood. Here a rare case of refractory epilepsy is being reported in a 23 years old pregnant woman which was diagnosed as DDMS on radiological findings of cerebral atrophy, ventricle enlargement, dilatation of sulci and osseous hypertrophy of calvarium with increased width of diploic space. Conclusion: A proper history, thorough clinical examination and characteristic radiological findings provide the correct diagnosis of DDMS. CT/MRI must be performed in patients presenting with recurrent seizures.

Novel Method to Identify the Precentral Gyrus and Its Detailed Functional Distribution in Real Brain Surfaces Using Reconstructed 3D Brain Surface Imaging

Objective: To study the use of reconstructed 3D brain surface imaging (RBSI) to identify the precentral gyrus and its detailed functional distribution in epileptic patients. Method: A total of 12 refractory epilepsy cases that need intracranial electrode implantation were studied. In these patients, pre-operative magnetic resonance imaging (MRI) and functional MRI (fMRI) were conducted, and a cranial computed tomography (CT) scan was performed after electrode implantation. The RBSI was accomplished using Brain Voyager software based on MRI data, and then the 3D brain surface was integrated with the subdural electrode CT scan. The precentral gyrus was found in the reconstructed brain surface imaging according to their anatomical shape, and then were identified in the surgical field by comparing the exposed gyrus in the RBSI with the help of intraoperative photographs. Results: Total 12 cases of precentral gyrus was found and marked in the RBSI. There were 101 electrodes covering the precentral gyrus and 73 (72%) of them had motor response to electrical stimulation. In the contrast, (the area which is 1 cm ahead of the precentral gyrus), the motor response rate was 13% (17/130) (p < 0.05). During fMRI, 100% of the precentral gyrus and 58% (7/12) of post central gyrus was activated during hand movement. Whereas, no activation of the areas ahead of precentral gyrus was seen showing a significant difference between precentral gyrus and gyrus ahead. Conclusion: Our results demonstrated that using RBSI technique, it is possible to identify the precentral gyrus with precision.

Tuberous sclerosis: Clinical characteristics and their relationship to genotype/phenotype

Abstract Introduction Tuberous sclerosis (TS) is an inherited disorder with multisystemic involvement and a high phenotypic variability. There are two genes that cause this condition: TSC1 and TSC2. Objectives Our goal was to clinically characterise patients with TS followed up in the Pediatric Neurology Clinic of a tertiary hospital during the last 10 years, and correlate the genotype with the severity of neurological manifestations and imaging studies. Patients and methods Retrospective analysis of patients with TS, including review of medical records and available MRI imaging. Results We studied 35 cases with a median age at diagnosis of 10 months. Seizures were the first manifestation in 91.4% of cases, with a predominance of epileptic spasms. Over 50% had cognitive impairment and 49% behavioural disorders. A genetic study was performed on 24 children, and TSC2 mutations identified in 58.3% of them. Of the 11 cases of refractory epilepsy, six had the TSC2 gene mutation. In the group of eight patients with moderate/severe cognitive deficits, five had TSC2 mutations. We reviewed 26 MRI scans, in which it was observed that 76.9% had diffuse involvement of cerebral lobes, which reflects a greater burden of injury. Of the patients who had an MRI scan performed and had TSC2 mutations, all had a high tuber load, and 5 of them had refractory epilepsy. Discussion In our sample we observe a high percentage of mutations in the TSC2 gene. This mutation carries a worse neurological prognosis, with drug-resistant epilepsy and a more severe cognitive impairment.

Esclerosis tuberosa: caracterización clínica e intento de correlación fenotipo/genotipo

IntroductionTuberous sclerosis (TS) is an inherited disorder with multisystemic involvement and a high phenotypic variability. There are two genes that cause this condition: TSC1 and TSC2. ObjectivesOur goal was to clinically characterize patients with TS followed up in the Pediatric Neurology Clinic of a tertiary hospital during the last 10 years, and correlate the genotype with the severity of neurological manifestations and imaging studies. Patients and methodsRetrospective analysis of patients with TS, including review of medical records and available MRI imaging. ResultsWe studied 35 cases with a median age at diagnosis of ten months. Seizures were the first manifestation in 91.4% of cases, with a predominance of epileptic spasms. Over 50% had cognitive impairment and 49% behavioral disorders.A genetic study was performed on 24 children, and TSC2 mutations identified in 58.3% of them. Of the 11 cases of refractory epilepsy, six had the TSC2 gene mutation. In the group of eight patients with moderate/severe cognitive deficits, five had TSC2 mutations.We reviewed 26 MRI scans, in which it was observed that 76.9% had diffuse involvement of cerebral lobes, which reflects a greater burden of injury. Of the patients who had an MRI scan performed and had TSC2 mutations, all had a high tuber load, and5 of them had refractory epilepsy. DiscussionIn our sample we observe a high percentage of mutations in the TSC2 gene. This mutation carries a worse neurological prognosis, with drug-resistant epilepsy and a more severe cognitive impairment.

The value of gamma probe in the detection of epileptogenic focus

Radiol Bras. 2014 Jan/Fev;47(1):IX Even though epilepsy is known since the antiquity and, despite the great developments in the diagnosis and clinical treatment of this disease, there are still cases of refractory epilepsy to conventional antiepileptic drugs. In such cases of refractory epilepsy when an epileptogenic focus has been defined, surgery may be indicated for focus resection, if it is not located in an eloquent area. Imaging methods are routinely utilized to detect lesions that may be the cause for refractory epilepsy. In such patients, the identification of an epileptogenic focus represents a decisive factor for the indication or not of a surgery for management of the seizure. The association of structural imaging methods, such as magnetic resonance imaging, with functional methods such as SPECT (ictal and interictal) and PET plays a significant role in the identification of such lesions, allowing that many cases previously diagnosed as cryptogenic epilepsy have the disease origin defined and surgery indicated. Additionally, electroencephalography and video-encephalography data are essential to confirm the presence of abnormal electrical activity coinciding with the focal lesions identified at the imaging studies. The utilization of nuclear medicine with a gamma probe (portable gamma ray detector) is known as radioguided surgery. Such procedure modality already has its use recognized in oncology, and has changed the approach to several types of malignant neoplasms (breast, melanoma, colorectal cancer), neuroendocrine neoplasms and parathyroid surgery. The gamma probe allows the real-time obtention of essential information for the surgeon regarding the disease location and its extent besides information about margin resection.

Ketogenic Diet For Refractory Epilepsy In Children- An Institutional Experience

Introduction: Ketogenic diet consists in a adequate protein diet (1 qram/kg), low in carbohydrates and rich in lipids, which induces a prolonged state of ketosis that modifies the cerebral energetic metabolism. This study aims to characterize the children with refractory epilepsy treated with ketogenic diet, enrolled in a Child Development Center in Portugal. It intends to evaluate the efficacy and tolerability of the diet and to identify in which epilepsy syndromes and etiologies the diet is effective. Methods: Retrospective analysis of the cases of refractory epilepsy treated with ketogenic diet. Results: Sixteen children were included, eleven boys. The mean age of seizures onset was 13,9 months (0-72 months) and of ketogenic diet onset was 4,4 years (5 months-16 years). At the end of the first month, 62,5% had a seizure reduction of more than 50%. The efficacy reached 43,8% at the end of third month and 31,3% at the end of the sixth month. In 31,3% there was a reduction of the number of anti-epileptic drugs and 56,3% had an improvement in the behavior/ cognition. The diet was more effective in infantile spasms, Lennox-Gastaut and Dravet syndromes and genetic and structural epilepsies, particularly in malformations of the cortical development. The mean time to a clinical response was 1,4 months. The diet had a good tolerability, with side effects only in 31,2%, none with clinical severity. Conclusion: In this study, ketogenic diet has proven to be safe and effective and should be considered in children with severe and refractory epilepsies.

Expression of PI3K pathway proteins in refractory epilepsy associated with cortical malformation development

To investigate the expression of TSC1, TSC2, p-mTOR, p-4E-BP1, p-p70S6K and p-S6 in refractory epilepsy associated malformation of cortical development (MCD) tissues. A total of 43 cases of refractory epilepsy were involved in the study, and all the patients were treated in Xuanwu Hospital during 2005 - 2008, including focal cortical dysplasia type IIa (11 cases) and type IIb (11 cases), tuberous sclerosis complex (10 cases) and ganalioglioma (11 cases), and other 12 cases were used as control. These cases were divided into 7 study groups and immunohistochemical EnVision method was used. To detect the location and intensity of TSC1, TSC2, p-mTOR, p-4E-BP1, p-p70S6K and p-S6 expression in every group. Then the Image-Pro Plus 6.0 image processing and analysis software were used to measure the number, area, integrating absorbance (IA) of positive cells in every samples. The statistical software SPSS 16.0 was used to analyze the data. The immunolocalization of TSC1 and TSC2 was similar. It could be observed the expression of various levels in the cytoplasm of dysmorphic neurons, balloon cells, giant cells, ganglioglioma cells and normal neurons. TSC1 staining in normal neurons was more notably than others but TSC2 staining in giant cells was weaker than other samples. p-mTOR mainly presented in giant cells, which could also be observed in astrocyte. P-4E-BP1 presented in the cytoplasm and nuclear membrane of balloon cells, giant cells and ganglioglioma cells, the staining of giant cells was stronger than balloon cells, but their staining were weaker than ganglioglioma cells. P-p70S6K mainly expressed in giant cells and less commonly presented in balloon cells. P-S6 typically presented in all abnormal glioneuronal cells and it nearly did not present in the normal neurons of N-CTX group. PI3K pathway, at least in part, involves in the occurrence of MCD, and may play an important role in the pathogenesis.

Neuropathology of Seizure Disorders

Epilepsy is a common neurological disorder characterized by an enduring predisposition to generate recurrent seizures. Pathologists may be called upon to evaluate brain tissue from patients with a history of seizures, and it is important to keep in mind the diversity of histopathologic findings associated with this disorder and the limitations imposed by both, limited sampling and neuroanatomy. Review of the literature has shown that the three most common clinicopathological entities in surgically resected medically refractory epilepsy are mesial temporal sclerosis (MTS), long-term epilepsy-associated tumors (LEAT), and malformations of cortical development (MCD) which includes focal cortical dysplasia (FCD). Here, we will review the most common clinicopathological entities seen in surgically resected cases of refractory epilepsy, such as MTS, MCD, LEAT, as well as vascular and encephalitic lesions. We will also touch upon traumatic brain injuries and SUDEP, and the role of the forensic pathologist. A better understanding of the etiopathology, recent classifications, and underlying molecular mechanisms involved in each entity will be helpful in order to identify the cause of death in patients with seizure disorders, candidates who will benefit from tailored surgical resection strategies, as well as to develop new and targeted drug treatment.

Benign mesial temporal lobe epilepsy

Benign mesial temporal lobe epilepsy (bMTLE), which is defined as at least 24 months of seizure freedom with or without antiepileptic medication, has probably been under-recognized because of a literature bias toward refractory epilepsy cases. Seizure onset in bMTLE tends to be in adolescence or adulthood, and patients frequently have a family history of febrile seizures and epilepsy. Long-term seizure freedom is observed with or without antiepileptic medication. On brain MRI, nearly 40% of patients with long-standing bMTLE show evidence of hippocampal sclerosis, a feature usually associated with refractory temporal lobe epilepsy. Prospective studies are needed to determine the features that allow prediction of a benign course, and to clarify the significance of hippocampal MRI changes.

Neuroimaging in epilepsy

Epilepsy is a common neurological disorder with diverse etiologies. Neuroimaging plays an important role in workup of patients with epilepsy. It helps to identify brain pathologies that require specific treatment; and also in formulating syndromic and etiological diagnoses so as to give patients and their relatives an accurate prognosis. Magnetic resonance imaging, specially the 3 tesla MRI is the imaging of choice because of its ability to detect small lesions like mesial temporal sclerosis, cortical dysplasias, small tumors, etc that are not detected by conventional MR or CT scan of brain. Identification of these lesions often helps in managing refractory epilepsies more effectively. However, cost and non-availability of MR in large part of the country necessitate the use of CT as an alternative. CT is often the initial investigation and also useful in acute situations. Functional imagings are used for pre-surgical work-up of refractory epilepsy cases with an aim to identify the epileptogenic focus and to delineate functional areas nearing the focus.

Rufinamide for refractory epilepsy in a pediatric and young adult population

This chart review investigated the efficacy and safety of rufinamide in 45 children and young adults who experienced a broad spectrum of partial and generalized seizure/epilepsy types which have been refractory to therapy. Of these patients, 19 (46%) achieved a >50% decrease in seizure frequency on rufinamide, and 7 patients achieved a >75% decrease in seizure frequency. While 17 (37.8%) patients stopped their trial of rufinamide prior to the end of the review period, only 2 (4.4%) were due to adverse effects. Although additional research must be done, this data shows promise that rufinamide is a safe and efficacious adjunct for cases of refractory epilepsy.

Ultrastructure observation of refractory epilepsy with cortical dysplasia

Objective To study the relationship between the ultrasturcture changes and pathogenesis of refractory epilepsy with cortical dysplasia.Method To analyze the clinical data of 7 cases of refractory epilepsy retrospectively.The electron microscope was used to observe specimens of brain tissue got from surgical excision.ResultsMacrogyria,gray matter heterotopia,cortex underdevelopment and cortex derangement were observed in the brain tissue of refractory epileptic patients with cortical dysplasia.The electron microscopic examination showed nerve tissue degeneration,decreased or increased number of neurons,swelling astrocytes,synaptic number changes,increased presynaptic terminal round clear excitatory transmitters.Conclisions Ultrastructural pathological changes including less neurons,pyknosis and degeneration,cortex architecture disorders,changes of synaptic numbers and structures could be found in dysplasia cortex of refractory epilepsy patients. Key words: Cortical dysplasia; Refractory epilepsy; Ultramicropathology