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Garcia H.H.,Instituto Nacional Of Ciencias Neurologicas | Garcia H.H.,Cayetano Heredia Peruvian University | Gonzales I.,Instituto Nacional Of Ciencias Neurologicas | Lescano A.G.,Cayetano Heredia Peruvian University | And 10 more authors.
The Lancet Infectious Diseases | Year: 2014

Background: Neurocysticercosis causes a substantial burden of seizure disorders worldwide. Treatment with either praziquantel or albendazole has suboptimum efficacy. We aimed to establish whether combination of these drugs would increase cysticidal efficacy and whether complete cyst resolution results in fewer seizures. We added an increased dose albendazole group to establish a potential effect of increased albendazole concentrations. Methods: In this double-blind, placebo-controlled, phase 3 trial, patients with viable intraparenchymal neurocysticercosis were randomly assigned to receive 10 days of combined albendazole (15 mg/kg per day) plus praziquantel (50 mg/kg per day), standard albendazole (15 mg/kg per day), or increased dose albendazole (22·5 mg/kg per day). Randomisation was done with a computer generated schedule balanced within four strata based on number of cysts and concomitant antiepileptic drug. Patients and investigators were masked to group assignment. The primary outcome was complete cyst resolution on 6-month MRI. Enrolment was stopped after interim analysis because of parasiticidal superiority of one treatment group. Analysis excluded patients lost to follow-up before the 6-month MRI. This trial is registered with ClinicalTrials.gov, number NCT00441285. Findings: Between March 3, 2010 and Nov 14, 2011, 124 patients were randomly assigned to study groups (41 to receive combined albendazole plus praziquantel [39 analysed], 43 standard albendazole [41 analysed], and 40 increased albendazole [38 analysed]). 25 (64%) of 39 patients in the combined treatment group had complete resolution of brain cysts compared with 15 (37%) of 41 patients in the standard albendazole group (rate ratio [RR] 1·75, 95% CI 1·10-2·79, p=0·014). 20 (53%) of 38 patients in the increased albendazole group had complete cyst resolution at 6-month MRI compared with 15 (37%) of 41 patients in the standard albendazole group (RR 1·44, 95% CI 0·87-2·38, p=0·151). No significant differences in adverse events were reported between treatment groups (18 in combined treatment group, 11 in standard albendazole group, and 19 in increased albendazole group). Interpretation: Combination of albendazole plus praziquantel increases the parasiticidal effect in patients with multiple brain cysticercosis cysts without increased side-effects. A more efficacious parasiticidal regime without increased treatment-associated side-effects should improve the treatment and long term prognosis of patients with neurocysticercosis. Funding: National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health. © 2014 Elsevier Ltd.


PubMed | Instituto Nacional Of Ciencias Neurologicas, Magnetic Resonance Imaging Center, Hospital Nacional Edgardo Rebagliati, Hospital Nacional Alberto Sabogal and 3 more.
Type: Clinical Trial, Phase III | Journal: The Lancet. Infectious diseases | Year: 2014

Neurocysticercosis causes a substantial burden of seizure disorders worldwide. Treatment with either praziquantel or albendazole has suboptimum efficacy. We aimed to establish whether combination of these drugs would increase cysticidal efficacy and whether complete cyst resolution results in fewer seizures. We added an increased dose albendazole group to establish a potential effect of increased albendazole concentrations.In this double-blind, placebo-controlled, phase 3 trial, patients with viable intraparenchymal neurocysticercosis were randomly assigned to receive 10 days of combined albendazole (15 mg/kg per day) plus praziquantel (50 mg/kg per day), standard albendazole (15 mg/kg per day), or increased dose albendazole (225 mg/kg per day). Randomisation was done with a computer generated schedule balanced within four strata based on number of cysts and concomitant antiepileptic drug. Patients and investigators were masked to group assignment. The primary outcome was complete cyst resolution on 6-month MRI. Enrolment was stopped after interim analysis because of parasiticidal superiority of one treatment group. Analysis excluded patients lost to follow-up before the 6-month MRI. This trial is registered with ClinicalTrials.gov, number NCT00441285.Between March 3, 2010 and Nov 14, 2011, 124 patients were randomly assigned to study groups (41 to receive combined albendazole plus praziquantel [39 analysed], 43 standard albendazole [41 analysed], and 40 increased albendazole [38 analysed]). 25 (64%) of 39 patients in the combined treatment group had complete resolution of brain cysts compared with 15 (37%) of 41 patients in the standard albendazole group (rate ratio [RR] 175, 95% CI 110-279, p=0014). 20 (53%) of 38 patients in the increased albendazole group had complete cyst resolution at 6-month MRI compared with 15 (37%) of 41 patients in the standard albendazole group (RR 144, 95% CI 087-238, p=0151). No significant differences in adverse events were reported between treatment groups (18 in combined treatment group, 11 in standard albendazole group, and 19 in increased albendazole group).Combination of albendazole plus praziquantel increases the parasiticidal effect in patients with multiple brain cysticercosis cysts without increased side-effects. A more efficacious parasiticidal regime without increased treatment-associated side-effects should improve the treatment and long term prognosis of patients with neurocysticercosis.National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health.


Trojsi F.,The Second University of Naples | Trojsi F.,Neurological Institute for Diagnosis and Care Hermitage Capodimonte | Trojsi F.,Magnetic Resonance Imaging Center | Monsurr M.R.,The Second University of Naples | And 6 more authors.
Neural Plasticity | Year: 2012

Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease principally affecting motor neurons. Besides motor symptoms, a subset of patients develop cognitive disturbances or even frontotemporal dementia (FTD), indicating that ALS may also involve extramotor brain regions. Both neuropathological and neuroimaging findings have provided further insight on the widespread effect of the neurodegeneration on brain connectivity and the underlying neurobiology of motor neurons degeneration. However, associated effects on motor and extramotor brain networks are largely unknown. Particularly, neuropathological findings suggest that ALS not only affects the frontotemporal network but rather is part of a wide clinicopathological spectrum of brain disorders known as TAR-DNA binding protein 43 (TDP-43) proteinopathies. This paper reviews the current state of knowledge concerning the neuropsychological and neuropathological sequelae of TDP-43 proteinopathies, with special focus on the neuroimaging findings associated with cognitive change in ALS. Copyright © 2012 Francesca Trojsi et al.


Cirillo M.,The Second University of Naples | Cirillo M.,Magnetic Resonance Imaging Center | Esposito F.,Magnetic Resonance Imaging Center | Esposito F.,Neurological Institute for Diagnosis and Care Hermitage Capodimonte | And 17 more authors.
American Journal of Neuroradiology | Year: 2012

BACKGROUND AND PURPOSE: The extensive application of advanced MR imaging techniques to the study of ALS has undoubtedly improved our knowledge of disease pathophysiology, even if the actual spread of the neurodegenerative process throughout the central nervous system is not fully understood. The present study aimed to detect WM patterns of microstructural abnormalities to better investigate the pathologic process in ALS, within but also beyond CSTs, in a whole-brain analysis. MATERIALS AND METHODS: DTI was performed in 19 patients with ALS and 20 matched healthy controls, by using whole-brain TBSS and VOI analyses. RESULTS: We observed a significant decrease of FA in the body of CC of the ALS group (P < .05). At the VOI level, both FA decrease and RD increase in the body of CC significantly correlated with the UMN score (P = .003 and P = .02). Additionally, significant voxelwise positive correlations between FA and the ALSFRS-R were detected in the WM tracts underneath the left premotor cortex (P < .05). CONCLUSIONS: The correlations between reduction of FA and increase of RD in the body of CC with the UMN score indicate that the WM degeneration in the CC is strictly related to the ALS pyramidal impairment, while the correlation between FA and ALSFRS-R in the associative tracts underneath the left premotor cortex might reflect the progressive spread of the disease from the motor toward the extramotor areas.


Tedeschi G.,The Second University of Naples | Tedeschi G.,Neurological Institute for Diagnosis and Care Hermitage Capodimonte | Tedeschi G.,Magnetic Resonance Imaging Center | Trojsi F.,The Second University of Naples | And 20 more authors.
Neurobiology of Aging | Year: 2012

We assessed the spontaneous blood-oxygen-level-dependent signal fluctuations in the resting-state brain networks of amyotrophic lateral sclerosis patients and their relation to physiologically sensitive and disease modified functional magnetic resonance imaging parameters.Resting-state functional magnetic resonance imaging was performed at 3 Tesla on 20 amyotrophic lateral sclerosis patients with minimal frontal cognitive dysfunction and 20 age- and sex-matched healthy volunteers. Resting-state network maps were extracted with independent component analysis and group-level statistical analyses were performed to detect disease and disease-by-age interaction effects. Whole-brain global and regional atrophy measures were obtained from same-session structural scans.The sensori-motor network showed significant disease effects, with signals suppressed in patients bilaterally in the primary motor cortex. The default-mode network showed a significant disease-by-age interaction in the posterior cingulate cortex, where signals correlated with age positively in patients and negatively in controls. Both disease and disease-by-age interaction effects were detected in the right fronto-parietal network. Although global atrophy did not show significant differences, regions of reduced gray matter volume were detected in patients compared with controls adjacent to regions of reduced functional connectivity.Our results confirm that resting-state functional magnetic resonance imaging signals in the sensori-motor network are suppressed in amyotrophic lateral sclerosis. A similar suppression is evident in the right fronto-parietal network, possibly reflecting the patients' frontal dysfunction and right-lateralized patterns of regional atrophy. The interaction between disease and aging in the default-mode network unravels a possible mechanism of compensation between motor and extramotor systems emerging as a supplementary functional push to help motor disturbances. © 2012 Elsevier Inc.

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