Experimental study on radioactive pathways of hypodermically injected technetium-99m

The objective of this study was to investigate the biological substrate of radioactive pathways of migration of hypodermically injected 99mTc into points of low electrical resistance. Sixteen anesthetized adult male beagles were used. Control and test points were defined by comparing their electrical resistance to that of the pinna. Seventy-three experiments of three different types were performed: (1) separate hypodermic injections of [99mTc] sodium pertechnetate, 201Tl-chloride, 131INa and 99mTc-rhenium sulfide into control and test points; (2) simultaneous injections of [99mTc]sodium pertechnetate and 201Tl chloride into control and test points; and (3) intravascular injections of 99mTcO4 into blood vessels underlying test points. Only the hypodermic injection of 99mTc into points of low electrical resistance gave rise to a specific radioactive pathway characterized by rapid and longitudinal migration, clearly independent of background activity. The specific radioactive pathway detected is not the result of diffusion of the radiotracer through nerves, veins or lymphatic vessels, but its trajectory coincides with that described for one of the acupuncture meridians in the dog

Evaluating the performance of Bayesian and frequentist approaches for longitudinal modeling: application to Alzheimers disease

Linear mixed effects (LME) modelling under both frequentist and Bayesian frameworks can be used to study longitudinal trajectories. We studied the performance of both frameworks on different dataset configurations using hippocampal volumes from longitudinal MRI data across groups-healthy controls (HC), mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients, including subjects that converted from MCI to AD. We started from a big database of 1250 subjects from the Alzheimer's disease neuroimaging initiative (ADNI), and we created different reduced datasets simulating real-life situations using a random-removal permutation-based approach. The number of subjects needed to differentiate groups and to detect conversion to AD was 147 and 115 respectively. The Bayesian approach allowed estimating the LME model even with very sparse databases, with high number of missing points, which was not possible with the frequentist approach. Our results indicate that the frequentist approach is computationally simpler, but it fails in modelling data with high number of missing values

Clinical role of subtraction ictal SPECT coregistered to MR Imaging and 18F-FDG PET in pediatric epilepsy

A precise assessment of the drug-resistant epileptic pediatric population for surgical candidacy is often challenging, and to date there are no evidence-based guidelines for presurgical identification of the epileptogenic zone. To evaluate the usefulness of radionuclide imaging techniques for presurgical evaluation of epileptic pediatric patients, we compared the results of video-electroencephalography (EEG), brain MR imaging, interictal SPECT, ictal SPECT, subtraction ictal SPECT coregistered to MR imaging (SISCOM), and interictal PET with (18)F-FDG. METHODS: Fifty-four children with drug-resistant epilepsy who had undergone video-EEG monitoring, brain MR imaging, interictal and ictal brain perfusion SPECT, SISCOM, and (18)F-FDG PET were included in this study. All abnormal findings revealed by these neuroimaging techniques were compared with the presumed location of the epileptogenic zone (PEZ) as determined by video-EEG and clinical data. The proportion of localizing studies for each technique was statistically compared. In the 18 patients who underwent resective brain surgery, neuroimaging results were compared with histopathology results and surgical outcome. RESULTS: SISCOM and (18)F-FDG PET concordance with the PEZ was significantly higher than MR imaging (P < 0.05). MR imaging showed localizing results in 21 of 54 cases (39%), SISCOM in 36 of 54 cases (67%), and (18)F-FDG PET in 31 of 54 cases (57%). If we consider SISCOM and (18)F-FDG PET results together, nuclear medicine imaging techniques showed coinciding video-EEG results in 76% of patients (41/54). In those cases in which MR imaging failed to identify any epileptogenic lesion (61% [33/54]), SISCOM or (18)F-FDG PET findings matched PEZ in 67% (22/33) of cases. CONCLUSION: SISCOM and (18)F-FDG PET provide complementary presurgical information that matched video-EEG results and clinical data in three fourths of our sample. SISCOM was particularly useful in those cases in which MR imaging findings were abnormal but no epileptogenic lesion was identified. Radionuclide imaging techniques are both useful and reliable, extending the possibility of surgical treatment to patients who may have been discouraged without a nuclear medicine approach

Epileptogenic zone localization with (18)FDG PET using a new dynamic parametric analysis

Introduction: [18F]fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) is part of the regular preoperative work-up in medically refractory epilepsy. As a complement to visual evaluation of PET, statistical parametric maps can help in the detection of the epileptogenic zone (EZ). However, software packages currently available are time-consuming and little intuitive for physicians. We develop a user-friendly software (referred as PET-analysis) for EZ localization in PET studies that allows dynamic real-time statistical parametric analysis. To evaluate its performance, the outcome of PET-analysis was compared with the results obtained by visual assessment and Statistical Parametric Mapping (SPM). Methods: Thirty patients with medically refractory epilepsy who underwent presurgical 18F-FDG PET with good post-operative outcomes were included. The 18F-FDG PET studies were evaluated by visual assessment, with SPM8 and PET-analysis. In SPM, parametric T-maps were thresholded at corrected p < 0.05 and cluster size k = 50 and at uncorrected p < 0.001 and k = 100 (the most used parameters in the literature). Since PET-analysis rapidly processes different threshold combinations, T-maps were thresholded with multiple p-value and different clusters sizes. The presurgical EZ identified by visual assessment, SPM and PET-analysis was compared to the confirmed EZ according to post-surgical follow-up. Results: PET-analysis obtained 66.7% (20/30) of correctly localizing studies, comparable to the 70.0% (21/30) achieved by visual assessment and significantly higher (p < 0.05) than that obtained with the SPM threshold p < 0.001/k = 100, of 36.7% (11/30). Only one study was positive, albeit non-localizing, with the SPM threshold corrected p < 0.05/k = 50. Concordance was substantial for PET-analysis (κ = 0.643) and visual interpretation (κ = 0.622), being fair for SPM (κ = 0.242). Conclusion: Compared to SPM with the fixed standard parameters, PET-analysis may be superior in EZ localization with its easy and rapid processing of different threshold combinations. The results of this initial proof-of-concept study validate the clinical use of PET-analysis as a robust objective complementary tool to visual assessment for EZ localization

Epilepsy surgery in drug resistant temporal lobe epilepsy associated with neuronal antibodies

We assessed the outcome of patients with drug resistant epilepsy and neuronal antibodies who underwent epilepsy surgery. Retrospective study, information collected with a questionnaire sent to epilepsy surgery centers. Thirteen patients identified, with antibodies to GAD (8), Ma2 (2), Hu (1), LGI1 (1) or CASPR2 (1). Mean age at seizure onset: 23 years. Five patients had an encephalitic phase. Three had testicular tumors and five had autoimmune diseases. All had drug resistant temporal lobe epilepsy (median: 20 seizures/month). MRI showed unilateral temporal lobe abnormalities (mainly hippocampal sclerosis) in 9 patients, bilateral abnormalities in 3, and was normal in 1. Surgical procedures included anteromesial temporal lobectomy (10 patients), selective amygdalohippocampectomy (1), temporal pole resection (1) and radiofrequency ablation of mesial structures (1). Perivascular lymphocytic infiltrates were seen in 7/12 patients. One year outcome available in all patients, at 3 years in 9. At last visit 5/13 patients (38.5%) (with Ma2, Hu, LGI1, and 2 GAD antibodies) were in Engel's classes I or II. Epilepsy surgery may be an option for patients with drug resistant seizures associated with neuronal antibodies. Outcome seems to be worse than that expected in other etiologies, even in the presence of unilateral HS. Intracranial EEG may be required in some patients

SPECT cerebral intervencionista en la valoración prequirúrgica de la epilepsia

[spa] Los pacientes con crisis parciales complejas farmacorresistentes localizadas en el lóbulo temporal, pueden beneficiarse del tratamiento quirúrgico mediante una lobectomía temporal parcial. Por la exéresis del hipocampo, la principal secuela a evitar de esta intervención es la pérdida de memoria. Por ello, antes de la cirugía se les realiza el test de Wada o test del Amobarbital sódico (TAS) para lateralizar las funciones de memoria y lenguaje. El TAS precisa de una arteriografía carotidea, para la administración intracarotidea del amobarbital sódico, que provoca una anestesia cerebral transitoria de un hemisferio cerebral. Esto permite valorar la capacidad de memoria del hipocampo contralateral y permitirá predecir el riesgo de amnesia antes de la intervención. Sin embargo, se ha visto que el test es poco fiable para predecir el riesgo de amnesia postquirúrgica, probablemente porque en algunos pacientes no se produce la inactivación del hipocampo durante el TAS. Esto puede provocar falsos negativos del TAS para predecir el riesgo de amnesia. Los objetivos de este trabajo han sido realizar un SPECT cerebral con HMPAO - Tc99m durante el TAS para conocer la distribución intracerebral del amobarbital y compararlo con la angiografía. Demostrar con un SPECT, que los falsos negativos del TAS para predecir el riesgo de amnesia son debidos a una escasa inactivación del hipocampo. Se han estudiado 40 pacientes con crisis parciales complejas del lóbulo temporal, a los que se les ha realizado un TAS, una angiografía digital, dos SPECTs cerebrales (uno basal y otro durante el TAS) y una lobectomía temporal. Se ha desarrollado un programa informático para realinear y cuantificar en porcentaje los cambios de la perfusión entre los dos SPECTs. Un estudio neuropsicológico de todos los pacientes con la escala de memoria de Whechler antes y durante un seguimiento de un año tras la intervención quirúrgica ha demostrado los falsos negativos del TAS, que son los pacientes que han desarrollado pérdida de memoria tras la intervención. Los resultados demuestran que el SPECT cerebral realizado durante el TAS permite conocer la distribución intracerebral del amobarbital y, por tanto, determinar las regiones que han quedado anestesiadas o inactivadas durante el test. Por la inyección del amobarbital a través de la arteria carótida interna, en los territorios cerebrales dependientes del flujo carotideo el SPECT demostró una disminución de la perfusión hemicerebral (del 12%) que indica que se han inactivado durante el TAS. Pero no ocurre lo mismo en los territorios cerebrales tributarios del flujo vertebrobasilar, donde el SPECT no mostró disminución de la perfusión, lo que indica que no se inactivaron durante el TAS. Además, la disminución de la perfusión en la región temporal interna permite determinar la inactivación funcional del hipocampo durante el TAS, lo que se observó únicamente en el 35% de pacientes según el SPECT y en un 27% según la angiografía. El seguimiento de la evolución de la memoria demostró que 6 pacientes (el 16%) desarrolló pérdida de memoria tras la intervención y son los falsos negativos del TAS. De ello, según el SPECT cerebral, 5/6 habían realizado el TAS con el hipocampo funcionante, por lo que el SPECT demostró que el riesgo de amnesia es mayor en los pacientes que realizaron el TAS con el hipocampo funcionante. El SPECT discrimina mejor que la angiografía la inactivación funcional del hipocampo. La angiografía detectó flujo cruzado a través de la arteria cerebral anterior en el 42% de casos, mientras que el SPECT cerebral demostró esta situación en un porcentaje menor de pacientes (25%)

Validation of an automatic dose injection system for Ictal SPECT in epilepsy

The purpose of our study was to evaluate the performance and clinical usefulness of an automated injector system (AIS) that administers an automated injection for ictal SPECT after calculating the volume of tracer to be injected over time. Methods: To test the AIS, repeated injections were performed at different times after tracer preparation. The clinical study consisted of 56 patients with drug-resistant, complex partial seizures. Tracer for ictal SPECT was injected using automated injection in 27 patients and manual injection (MI) in the remaining 29. Injection time (TI) was measured in seconds from seizure onset to the end of volume injection. The SISCOM (Subtraction Ictal Spect Co-registered to MRI) procedure was used to locate the epileptogenic seizure focus with SPECT. The definition of seizure focus was made by consensus of the epilepsy unit using conventional diagnostic methods. Results: During the experimental phase, there were no system failures, and the error in injected doses when using automated injection was lower than with MI. During the clinical phase, TI using manual injection was 41 s with a range of 14-103 s, compared with an AIS average of 33 s with a range of 19-63 s (P , 0.05). Ictal SPECT and SISCOM successfully localized the seizure focus in 21 of the 27 patients (78%) by AIS and in 19 of the 29 patients (65%) by MI (P 5 0.14). Furthermore, nursing staff found the AIS method more convenient than the MI method. Conclusion: An AIS can improve the quality of work of the nursing staff in the neurology ward and allow a finer adjustment of the injection dose. Early results using an AIS would indicate a reduction in injection time and improved SPECT accuracy

Clinical role of subtraction ictal SPECT coregistered to MR Imaging and 18F-FDG PET in pediatric epilepsy

A precise assessment of the drug-resistant epileptic pediatric population for surgical candidacy is often challenging, and to date there are no evidence-based guidelines for presurgical identification of the epileptogenic zone. To evaluate the usefulness of radionuclide imaging techniques for presurgical evaluation of epileptic pediatric patients, we compared the results of video-electroencephalography (EEG), brain MR imaging, interictal SPECT, ictal SPECT, subtraction ictal SPECT coregistered to MR imaging (SISCOM), and interictal PET with (18)F-FDG. METHODS: Fifty-four children with drug-resistant epilepsy who had undergone video-EEG monitoring, brain MR imaging, interictal and ictal brain perfusion SPECT, SISCOM, and (18)F-FDG PET were included in this study. All abnormal findings revealed by these neuroimaging techniques were compared with the presumed location of the epileptogenic zone (PEZ) as determined by video-EEG and clinical data. The proportion of localizing studies for each technique was statistically compared. In the 18 patients who underwent resective brain surgery, neuroimaging results were compared with histopathology results and surgical outcome. RESULTS: SISCOM and (18)F-FDG PET concordance with the PEZ was significantly higher than MR imaging (P < 0.05). MR imaging showed localizing results in 21 of 54 cases (39%), SISCOM in 36 of 54 cases (67%), and (18)F-FDG PET in 31 of 54 cases (57%). If we consider SISCOM and (18)F-FDG PET results together, nuclear medicine imaging techniques showed coinciding video-EEG results in 76% of patients (41/54). In those cases in which MR imaging failed to identify any epileptogenic lesion (61% [33/54]), SISCOM or (18)F-FDG PET findings matched PEZ in 67% (22/33) of cases. CONCLUSION: SISCOM and (18)F-FDG PET provide complementary presurgical information that matched video-EEG results and clinical data in three fourths of our sample. SISCOM was particularly useful in those cases in which MR imaging findings were abnormal but no epileptogenic lesion was identified. Radionuclide imaging techniques are both useful and reliable, extending the possibility of surgical treatment to patients who may have been discouraged without a nuclear medicine approach

Validation of an automatic dose injection system for Ictal SPECT in epilepsy

The purpose of our study was to evaluate the performance and clinical usefulness of an automated injector system (AIS) that administers an automated injection for ictal SPECT after calculating the volume of tracer to be injected over time. Methods: To test the AIS, repeated injections were performed at different times after tracer preparation. The clinical study consisted of 56 patients with drug-resistant, complex partial seizures. Tracer for ictal SPECT was injected using automated injection in 27 patients and manual injection (MI) in the remaining 29. Injection time (TI) was measured in seconds from seizure onset to the end of volume injection. The SISCOM (Subtraction Ictal Spect Co-registered to MRI) procedure was used to locate the epileptogenic seizure focus with SPECT. The definition of seizure focus was made by consensus of the epilepsy unit using conventional diagnostic methods. Results: During the experimental phase, there were no system failures, and the error in injected doses when using automated injection was lower than with MI. During the clinical phase, TI using manual injection was 41 s with a range of 14-103 s, compared with an AIS average of 33 s with a range of 19-63 s (P , 0.05). Ictal SPECT and SISCOM successfully localized the seizure focus in 21 of the 27 patients (78%) by AIS and in 19 of the 29 patients (65%) by MI (P 5 0.14). Furthermore, nursing staff found the AIS method more convenient than the MI method. Conclusion: An AIS can improve the quality of work of the nursing staff in the neurology ward and allow a finer adjustment of the injection dose. Early results using an AIS would indicate a reduction in injection time and improved SPECT accuracy

Epilepsy surgery in drug resistant temporal lobe epilepsy associated with neuronal antibodies

We assessed the outcome of patients with drug resistant epilepsy and neuronal antibodies who underwent epilepsy surgery. Retrospective study, information collected with a questionnaire sent to epilepsy surgery centers. Thirteen patients identified, with antibodies to GAD (8), Ma2 (2), Hu (1), LGI1 (1) or CASPR2 (1). Mean age at seizure onset: 23 years. Five patients had an encephalitic phase. Three had testicular tumors and five had autoimmune diseases. All had drug resistant temporal lobe epilepsy (median: 20 seizures/month). MRI showed unilateral temporal lobe abnormalities (mainly hippocampal sclerosis) in 9 patients, bilateral abnormalities in 3, and was normal in 1. Surgical procedures included anteromesial temporal lobectomy (10 patients), selective amygdalohippocampectomy (1), temporal pole resection (1) and radiofrequency ablation of mesial structures (1). Perivascular lymphocytic infiltrates were seen in 7/12 patients. One year outcome available in all patients, at 3 years in 9. At last visit 5/13 patients (38.5%) (with Ma2, Hu, LGI1, and 2 GAD antibodies) were in Engel's classes I or II. Epilepsy surgery may be an option for patients with drug resistant seizures associated with neuronal antibodies. Outcome seems to be worse than that expected in other etiologies, even in the presence of unilateral HS. Intracranial EEG may be required in some patients