Neurologist, neuroradiologist, MD, PhD. My main areas of expertise and research are Advanced and Quantitative Techniques in Brain Magnetic Resonance Imaging, Medical Education, Health Humanities.
To test if chronic calcificed neurocysticercosis (cNCC) and hippocampal sclerosis occur more ofte... more To test if chronic calcificed neurocysticercosis (cNCC) and hippocampal sclerosis occur more often than by chance ipsilateral to the same brain hemisphere or brain region in mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS) plus neurocysticercosis. This proof-of-concept would provide important evidence of a direct pathogenic relationship between neurocysticercosis and MTLE-HS. A cohort of 290 consecutive MTLE-HS surgical patients was studied. A test of proportions was used to analyze if the proportion of patients with a single cNCC lesion matching the same brain hemisphere or region of hippocampal sclerosis was significantly greater than 50%, as expected by the chance. Neuroimaging findings of cNCC were observed in 112 (38.6%) of 290 MTLE-HS patients and a single cNCC lesion occurred in 58 (51.8%) of them. There were no differences in main basal clinical characteristics of MTLE-HS patients with single or multiple cNCC lesions. In patients with single cNCC lesions, the lesion matched the side in which hippocampal sclerosis was observed in 43 (74.1%) patients, a proportion significantly greater than that expected to occur by chance (p=0.008). Neurocysticercosis in temporal lobe was ipsilateral to hippocampal sclerosis in 85.0% of patients and accounted mostly for this result. This work is a proof-of-concept that the association of neurocysticercosis and MTLE-HS cannot be explained exclusively by patients sharing common biological or socio-economic predisposing variables. Instead, our results suggest the involvement of more direct pathogenic mechanisms like regional inflammation, repetitive seizures or both. Neurocysticercosis within temporal lobes was particularly related with ipsilateral hippocampal sclerosis in MTLE-HS, a finding adding new contributions for understanding MTLE-HS plus cNCC or perhaps to other forms of dual pathology in MTLE-HS.
Recent observations suggest that neurocysticercosis (NCC) might act as an initial precipitating i... more Recent observations suggest that neurocysticercosis (NCC) might act as an initial precipitating injury (IPI) causing mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS). A total of 191 patients from Brazil, a country in which NCC is endemic, were surgically treated for MTLE-HS, and subsequent findings for patients with MTLE-HS were compared with those of patients with MTLE-HS plus NCC. Seventy-one patients (37,2%) presented chronic findings of NCC (cNCC). MTLE-HS plus cNCC was significantly more common in women (O.R.=2.45; 95%CI=1.30-4.60; p=0.005), in patients with no history of classical forms of IPI (O.R.=2.67; 95%CI=1.37-5.18; p=0.004), and in those with bi-temporal interictal spikes on video-EEG (O.R.=2.00; 95%CI=1.07-3.73; p=0.03). Single cNCC lesions were observed to occur significantly more often on the same side as hippocampal sclerosis, a finding suggesting an anatomical relationship between NCC and MTLE-HS. Taken together, our results suggest that NCC may be a marker, or contributes to or even causes MTLE-HS. Based on our findings, we propose two distinct, non-excluding, and potentially synergistic mechanisms involved in the development of MTLE-HS in NCC, one of them being inflammatory-mediated, while the other is electrogenic-mediated. Taken together, our observations may provide further evidence suggesting a role of NCC in the genesis or development of MTLE-HS.
Ependymoma is a central nervous system neoplasm that is often managed with surgery and radiothera... more Ependymoma is a central nervous system neoplasm that is often managed with surgery and radiotherapy. The benefits of chemotherapy in treating this tumor remain poorly defined. The use of a platinum-based chemotherapy as a neoadjuvant treatment to permit complete surgical resection of a supratentorial anaplastic ependymoma recurring for the third time is described. This paper also discusses the possible use of chemotherapy as a strategy that may allow tumor shrinkage and ease tumor resection in giant recurring ependymomas.
Summary: Purpose: We sought to analyze the contralateral volumes of the temporal pole, posterior... more Summary: Purpose: We sought to analyze the contralateral volumes of the temporal pole, posterior segment of the temporal lobe, amygdala, hippocampus, and parahippocampal gyrus in patients with temporal lobe epilepsy (TLE) due to histologically proven mesial temporal lobe sclerosis (MTLS), seizure free for ≥4 years of postsurgical follow‐up. Methods: Forty‐six (23 male) TLE patients, operated on between 1996 and 2001, with histopathologic diagnosis of MTLS, and a postsurgical follow‐up of ≥4 years, had their temporal lobe structures manually segmented, measured, and compared with those of 23 normal volunteers, paired as groups for sex, age, and handedness. Results: The mean volumes of the contralateral temporal pole, hippocampus, and parahippocampal gyrus in TLE patients were significantly lower than those in controls. Conclusions: MRI volumetric data show that the damage in TLE due to MTS may be more widespread and bilateral, even in patients with unilateral TLE by clinical and neurophysiological criteria. Our results are relevant to the discussion of epileptogenic mechanisms in TLE.
Cognitive impairment has long been recognized in people with medically refractory epilepsies. Mes... more Cognitive impairment has long been recognized in people with medically refractory epilepsies. Mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS), the most common surgically remediable epileptic syndrome, has been associated with a cellular prion protein (PrPc) gene (Prnp) variant allele at codon 171. The polymorphism consisting of a methionine-for-valine substitution at codon 129 has been associated with early cognitive deterioration in elderly people and patients with Down syndrome. The same variant allele in homozygosis (V129V) has been associated to a lower long-term memory in healthy humans. PrPc mediates several processes related to neuroplasticity, and its role in cognitive processes remains unknown. In this study, we evaluated the genetic contribution of Prnp alleles to cognitive performance in patients with MTLE-HS. Cognitive performance, measured with 19 neuropsychological tests, of patients with refractory MTLE-HS with the normal Prnp genotypes was compared with that of patients with the variant alleles at codons 129 and 171. With the effects of clinical, demographic, electrophysiological, and neuroimaging variable interactions controlled by multiple linear regression analysis and adjustment for multiple test comparisons, the presence of Prnp variant alleles was found not to be significantly associated to cognitive performance of patients with MTLE-HS. The presence of variant alleles at codons 129 and 171 is not associated to cognitive performance of patients with refractory MTLE-HS.
Background: Paramagnetic rim lesions (PRLs) and slowly expanding lesions (SELs) have been posited... more Background: Paramagnetic rim lesions (PRLs) and slowly expanding lesions (SELs) have been posited as markers of chronic active lesions (CALs). Objective: To assess the lesion-level concordance of PRLs and SELs in MS and to characterize changes in brain tissue integrity in CALs over time. Methods: MRIs were analyzed from a substudy of AFFINITY [NCT03222973], a phase 2 trial of opicinumab in relapsing MS. Assessments included (1) identification of SELs based on longitudinal MRIs over 72 weeks, and identification of PRLs on susceptibility-weighted imaging (SWI) filtered phase images at week 72; (2) evaluation of subject-level correlation of SEL and PRL counts, volumes, and degree of lesion-level overlap between SELs and PRLs; and (3) characterization of tissue integrity over time in overlapping and non-overlapping SELs and PRLs. Results: In 41 subjects, 119 chronic PRLs and 267 SELs were detected. Of 119 (39.5%) chronic PRLs, 47 co-localized with a SEL; 46/267 (17.2%) SELs co-localized with a PRL. PRLs co-localized with SELs showed expansion and worsening microstructural damage over time. SELs with and without co-localization with PRLs showed ongoing tissue damage. Conclusions: Chronic MS lesions identified as both PRL and SEL were associated with the most severe accumulation of tissue damage. Trial Registration: AFFINITY [NCT03222973].
To determine the frequency of cortical lesions (CLs) in patients with pediatric-onset multiple sc... more To determine the frequency of cortical lesions (CLs) in patients with pediatric-onset multiple sclerosis (POMS) using multi-contrast magnetic resonance imaging (MRI), and the relationship between frontal CL load and upper limb dexterity assessed with the Nine-Hole Peg Test (9-HPT). Participants completed the 9-HPT and were imaged on a 3T MRI scanner to collect T1-weighted three-dimensional (3D) magnetization prepared rapid gradient echo (MPRAGE), proton density-weighted, T2-weighted and fluid-attenuated inversion recovery (FLAIR) images. CLs were manually segmented using all MRI contrasts. We enrolled 24 participants with POMS (mean (standard deviation) age at first symptom: 13.3 (±2.7) years; mean age at scan: 18.8 (±3) years; mean disease duration of 5 (±3.2) years). A total of 391 CLs (mean, 16.3 ± 27.2; median, 7) were identified in 19 of 24 POMS patients (79%). The total number of CLs was positively associated with white matter lesion volume ( p = 0.04) but not with thalamic vo...
Brain volume change measured from magnetic resonance imaging (MRI) provides a widely used and use... more Brain volume change measured from magnetic resonance imaging (MRI) provides a widely used and useful in vivo measure of irreversible tissue loss. These measurements, however, can be influenced by reversible factors such as shifts in brain water content. Given the strong effect of water on T2 relaxation, we investigated whether an estimate of T2 relaxation time would correlate with brain volume changes induced by physiologically manipulating hydration status. We used a clinically feasible estimate of T2 ("pseudo-T2") computed from a dual turbo spin-echo MRI sequence and correlated pseudo-T2 changes to percent brain volume changes in 12 healthy subjects after dehydration overnight (16-hour thirsting) and rehydration (drinking 1.5 L of water). We found that the brain volume significantly increased between the dehydrated and rehydrated states (mean brain volume change = 0.36%, p = 0.0001) but did not change significantly during the dehydration interval (mean brain volume chang...
Hemispheric brain lesions are commonly associated with early onset of catastrophic epilepsies and... more Hemispheric brain lesions are commonly associated with early onset of catastrophic epilepsies and multiple seizure types. Hemispheric surgery is indicated for patients with unilateral intractable epilepsy. Although described more than 50 years ago, several new techniques for hemispherectomy have only recently been proposed aiming to reduce operatory risks and morbidity. We present the clinical characteristics, presurgical workup, and postoperative outcome of a series of pediatric patients who underwent hemispherectomy for medically intractable epileptic seizures. Thirty-nine patients with medically intractable epilepsy underwent surgery from 1996 to 2005. We analyzed demographic data, interictal and ictal EEG findings, age at surgery, surgical technique and complications, and postsurgical seizure outcome. There were 74.4% males. Tonic and focal motor seizures occurred in 30.8 and 20.5% of the patients. Most frequent etiologies were Rasmussen encephalitis (30.8%) and malformation of cortical development (23.1%). Postsurgical outcomes were Engel classes I and II for 61.5% of the patients. In general, 89.5% of the patients exhibited at least a 90% reduction in seizure frequency. All patients had acute worsening of hemiparesis after surgery. Basically, two surgical techniques have been employed, both with similar results, although a trend has been noted toward one of the procedures which produced consistently complete disconnection. Patients with hemispheric brain lesions usually have abnormal neurological development and intractable epilepsy. When video-EEG monitoring and magnetic resonance imaging show unilateral disease, the patient may evolve with a good surgical outcome. We showed that a marked reduction in seizure frequency may be achieved, with acceptable neurological impairments.
To test if chronic calcificed neurocysticercosis (cNCC) and hippocampal sclerosis occur more ofte... more To test if chronic calcificed neurocysticercosis (cNCC) and hippocampal sclerosis occur more often than by chance ipsilateral to the same brain hemisphere or brain region in mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS) plus neurocysticercosis. This proof-of-concept would provide important evidence of a direct pathogenic relationship between neurocysticercosis and MTLE-HS. A cohort of 290 consecutive MTLE-HS surgical patients was studied. A test of proportions was used to analyze if the proportion of patients with a single cNCC lesion matching the same brain hemisphere or region of hippocampal sclerosis was significantly greater than 50%, as expected by the chance. Neuroimaging findings of cNCC were observed in 112 (38.6%) of 290 MTLE-HS patients and a single cNCC lesion occurred in 58 (51.8%) of them. There were no differences in main basal clinical characteristics of MTLE-HS patients with single or multiple cNCC lesions. In patients with single cNCC lesions, the lesion matched the side in which hippocampal sclerosis was observed in 43 (74.1%) patients, a proportion significantly greater than that expected to occur by chance (p=0.008). Neurocysticercosis in temporal lobe was ipsilateral to hippocampal sclerosis in 85.0% of patients and accounted mostly for this result. This work is a proof-of-concept that the association of neurocysticercosis and MTLE-HS cannot be explained exclusively by patients sharing common biological or socio-economic predisposing variables. Instead, our results suggest the involvement of more direct pathogenic mechanisms like regional inflammation, repetitive seizures or both. Neurocysticercosis within temporal lobes was particularly related with ipsilateral hippocampal sclerosis in MTLE-HS, a finding adding new contributions for understanding MTLE-HS plus cNCC or perhaps to other forms of dual pathology in MTLE-HS.
Recent observations suggest that neurocysticercosis (NCC) might act as an initial precipitating i... more Recent observations suggest that neurocysticercosis (NCC) might act as an initial precipitating injury (IPI) causing mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS). A total of 191 patients from Brazil, a country in which NCC is endemic, were surgically treated for MTLE-HS, and subsequent findings for patients with MTLE-HS were compared with those of patients with MTLE-HS plus NCC. Seventy-one patients (37,2%) presented chronic findings of NCC (cNCC). MTLE-HS plus cNCC was significantly more common in women (O.R.=2.45; 95%CI=1.30-4.60; p=0.005), in patients with no history of classical forms of IPI (O.R.=2.67; 95%CI=1.37-5.18; p=0.004), and in those with bi-temporal interictal spikes on video-EEG (O.R.=2.00; 95%CI=1.07-3.73; p=0.03). Single cNCC lesions were observed to occur significantly more often on the same side as hippocampal sclerosis, a finding suggesting an anatomical relationship between NCC and MTLE-HS. Taken together, our results suggest that NCC may be a marker, or contributes to or even causes MTLE-HS. Based on our findings, we propose two distinct, non-excluding, and potentially synergistic mechanisms involved in the development of MTLE-HS in NCC, one of them being inflammatory-mediated, while the other is electrogenic-mediated. Taken together, our observations may provide further evidence suggesting a role of NCC in the genesis or development of MTLE-HS.
Ependymoma is a central nervous system neoplasm that is often managed with surgery and radiothera... more Ependymoma is a central nervous system neoplasm that is often managed with surgery and radiotherapy. The benefits of chemotherapy in treating this tumor remain poorly defined. The use of a platinum-based chemotherapy as a neoadjuvant treatment to permit complete surgical resection of a supratentorial anaplastic ependymoma recurring for the third time is described. This paper also discusses the possible use of chemotherapy as a strategy that may allow tumor shrinkage and ease tumor resection in giant recurring ependymomas.
Summary: Purpose: We sought to analyze the contralateral volumes of the temporal pole, posterior... more Summary: Purpose: We sought to analyze the contralateral volumes of the temporal pole, posterior segment of the temporal lobe, amygdala, hippocampus, and parahippocampal gyrus in patients with temporal lobe epilepsy (TLE) due to histologically proven mesial temporal lobe sclerosis (MTLS), seizure free for ≥4 years of postsurgical follow‐up. Methods: Forty‐six (23 male) TLE patients, operated on between 1996 and 2001, with histopathologic diagnosis of MTLS, and a postsurgical follow‐up of ≥4 years, had their temporal lobe structures manually segmented, measured, and compared with those of 23 normal volunteers, paired as groups for sex, age, and handedness. Results: The mean volumes of the contralateral temporal pole, hippocampus, and parahippocampal gyrus in TLE patients were significantly lower than those in controls. Conclusions: MRI volumetric data show that the damage in TLE due to MTS may be more widespread and bilateral, even in patients with unilateral TLE by clinical and neurophysiological criteria. Our results are relevant to the discussion of epileptogenic mechanisms in TLE.
Cognitive impairment has long been recognized in people with medically refractory epilepsies. Mes... more Cognitive impairment has long been recognized in people with medically refractory epilepsies. Mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS), the most common surgically remediable epileptic syndrome, has been associated with a cellular prion protein (PrPc) gene (Prnp) variant allele at codon 171. The polymorphism consisting of a methionine-for-valine substitution at codon 129 has been associated with early cognitive deterioration in elderly people and patients with Down syndrome. The same variant allele in homozygosis (V129V) has been associated to a lower long-term memory in healthy humans. PrPc mediates several processes related to neuroplasticity, and its role in cognitive processes remains unknown. In this study, we evaluated the genetic contribution of Prnp alleles to cognitive performance in patients with MTLE-HS. Cognitive performance, measured with 19 neuropsychological tests, of patients with refractory MTLE-HS with the normal Prnp genotypes was compared with that of patients with the variant alleles at codons 129 and 171. With the effects of clinical, demographic, electrophysiological, and neuroimaging variable interactions controlled by multiple linear regression analysis and adjustment for multiple test comparisons, the presence of Prnp variant alleles was found not to be significantly associated to cognitive performance of patients with MTLE-HS. The presence of variant alleles at codons 129 and 171 is not associated to cognitive performance of patients with refractory MTLE-HS.
Background: Paramagnetic rim lesions (PRLs) and slowly expanding lesions (SELs) have been posited... more Background: Paramagnetic rim lesions (PRLs) and slowly expanding lesions (SELs) have been posited as markers of chronic active lesions (CALs). Objective: To assess the lesion-level concordance of PRLs and SELs in MS and to characterize changes in brain tissue integrity in CALs over time. Methods: MRIs were analyzed from a substudy of AFFINITY [NCT03222973], a phase 2 trial of opicinumab in relapsing MS. Assessments included (1) identification of SELs based on longitudinal MRIs over 72 weeks, and identification of PRLs on susceptibility-weighted imaging (SWI) filtered phase images at week 72; (2) evaluation of subject-level correlation of SEL and PRL counts, volumes, and degree of lesion-level overlap between SELs and PRLs; and (3) characterization of tissue integrity over time in overlapping and non-overlapping SELs and PRLs. Results: In 41 subjects, 119 chronic PRLs and 267 SELs were detected. Of 119 (39.5%) chronic PRLs, 47 co-localized with a SEL; 46/267 (17.2%) SELs co-localized with a PRL. PRLs co-localized with SELs showed expansion and worsening microstructural damage over time. SELs with and without co-localization with PRLs showed ongoing tissue damage. Conclusions: Chronic MS lesions identified as both PRL and SEL were associated with the most severe accumulation of tissue damage. Trial Registration: AFFINITY [NCT03222973].
To determine the frequency of cortical lesions (CLs) in patients with pediatric-onset multiple sc... more To determine the frequency of cortical lesions (CLs) in patients with pediatric-onset multiple sclerosis (POMS) using multi-contrast magnetic resonance imaging (MRI), and the relationship between frontal CL load and upper limb dexterity assessed with the Nine-Hole Peg Test (9-HPT). Participants completed the 9-HPT and were imaged on a 3T MRI scanner to collect T1-weighted three-dimensional (3D) magnetization prepared rapid gradient echo (MPRAGE), proton density-weighted, T2-weighted and fluid-attenuated inversion recovery (FLAIR) images. CLs were manually segmented using all MRI contrasts. We enrolled 24 participants with POMS (mean (standard deviation) age at first symptom: 13.3 (±2.7) years; mean age at scan: 18.8 (±3) years; mean disease duration of 5 (±3.2) years). A total of 391 CLs (mean, 16.3 ± 27.2; median, 7) were identified in 19 of 24 POMS patients (79%). The total number of CLs was positively associated with white matter lesion volume ( p = 0.04) but not with thalamic vo...
Brain volume change measured from magnetic resonance imaging (MRI) provides a widely used and use... more Brain volume change measured from magnetic resonance imaging (MRI) provides a widely used and useful in vivo measure of irreversible tissue loss. These measurements, however, can be influenced by reversible factors such as shifts in brain water content. Given the strong effect of water on T2 relaxation, we investigated whether an estimate of T2 relaxation time would correlate with brain volume changes induced by physiologically manipulating hydration status. We used a clinically feasible estimate of T2 ("pseudo-T2") computed from a dual turbo spin-echo MRI sequence and correlated pseudo-T2 changes to percent brain volume changes in 12 healthy subjects after dehydration overnight (16-hour thirsting) and rehydration (drinking 1.5 L of water). We found that the brain volume significantly increased between the dehydrated and rehydrated states (mean brain volume change = 0.36%, p = 0.0001) but did not change significantly during the dehydration interval (mean brain volume chang...
Hemispheric brain lesions are commonly associated with early onset of catastrophic epilepsies and... more Hemispheric brain lesions are commonly associated with early onset of catastrophic epilepsies and multiple seizure types. Hemispheric surgery is indicated for patients with unilateral intractable epilepsy. Although described more than 50 years ago, several new techniques for hemispherectomy have only recently been proposed aiming to reduce operatory risks and morbidity. We present the clinical characteristics, presurgical workup, and postoperative outcome of a series of pediatric patients who underwent hemispherectomy for medically intractable epileptic seizures. Thirty-nine patients with medically intractable epilepsy underwent surgery from 1996 to 2005. We analyzed demographic data, interictal and ictal EEG findings, age at surgery, surgical technique and complications, and postsurgical seizure outcome. There were 74.4% males. Tonic and focal motor seizures occurred in 30.8 and 20.5% of the patients. Most frequent etiologies were Rasmussen encephalitis (30.8%) and malformation of cortical development (23.1%). Postsurgical outcomes were Engel classes I and II for 61.5% of the patients. In general, 89.5% of the patients exhibited at least a 90% reduction in seizure frequency. All patients had acute worsening of hemiparesis after surgery. Basically, two surgical techniques have been employed, both with similar results, although a trend has been noted toward one of the procedures which produced consistently complete disconnection. Patients with hemispheric brain lesions usually have abnormal neurological development and intractable epilepsy. When video-EEG monitoring and magnetic resonance imaging show unilateral disease, the patient may evolve with a good surgical outcome. We showed that a marked reduction in seizure frequency may be achieved, with acceptable neurological impairments.
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