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Papers by Rafael González Redondo
Cephalalgia, 2009
Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (S... more Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) syndrome is characterized by short-lived (5-240 s), strictly unilateral, periorbital, severe pain attacks, accompanied by ipsilateral conjunctival injection and lacrimation (1). SUNCT syndrome has been considered to be refractory to treatment, although recent small case series have suggested benefit from different antiepileptic drugs (2, 3). In some cases surgical intervention may be advocated, particularly when the pain is medically intractable or the medications are not tolerated. We present a patient with chronic SUNCT syndrome who was successfully treated with posterior fossa vascular decompression 19 years after the onset of symptoms.
Parkinson's disease, 2012
Dyskinetic disorders are characterized by excess of motor activity that may interfere with normal... more Dyskinetic disorders are characterized by excess of motor activity that may interfere with normal movement control. In patients with Parkinson's disease, the chronic levodopa treatment induces dyskinetic movements known as levodopa-induced dyskinesias (LID). This paper analyzed the pathophysiology, clinical manifestations, pharmacological treatments, and surgical procedures to treat hyperkinetic disorders. Surgery is currently the only treatment available for Parkinson's disease that may improve both parkinsonian motor syndrome and LID. However, this paper shows the different mechanisms involved are not well understood.
Brain imaging and behavior, 2022
Recent imaging studies with the stop-signal task in healthy individuals indicate that the subthal... more Recent imaging studies with the stop-signal task in healthy individuals indicate that the subthalamic nucleus, the pre-supplementary motor area and the inferior frontal gyrus are key components of the right hemisphere "inhibitory network". Limited information is available regarding neural substrates of inhibitory processing in patients with asymmetric Parkinson's disease. The aim of the current fMRI study was to identify the neural changes underlying deficient inhibitory processing on the stop-signal task in patients with predominantly left-sided Parkinson's disease. Fourteen patients and 23 healthy controls performed a stop-signal task with the left and right hands. Behaviorally, patients showed delayed response inhibition with either hand compared to controls. We found small imaging differences for the right hand, however for the more affected left hand when behavior was successfully inhibited we found reduced activation of the inferior frontal gyrus bilaterally ...
Forty-two patients, mean 40 yo (19-66), followed up from 2015 (C017 open label-extension beginnin... more Forty-two patients, mean 40 yo (19-66), followed up from 2015 (C017 open label-extension beginning; n=8) and 2017 (C021; n=34) until 2020. A significant clinical response was obtained in 73.8% with a 1-year remission rate of 21.4% (Graph #1). The seizure frequency evolution with cenobamate (pre vs post) for focal impaired awareness seizures was (Graph #2): dailyweekly (81.0% vs 28.5%), monthly-sporadic (19.0% vs 57.1%), seizure-free (0% vs 14.3%). Focal to bilateral tonic-clonic seizures were present pre and post cenobamate treatment in a 45.2% vs 11.9%. Cenobamate introduction allowed the withdrawal of 0, 1 or 2 adjuvant AED in 11.9%, 42.9%, 45.2%, respectively (Graph #3). Main AE consisted of somnolence, dizziness and instability (Graph #4), which globally caused a cease of treatment in 8 patients (50% within first 6 months); and were mild-transient in 22 patients. No biochemical, hematic or idiosyncratic disorders were found. In 2020, 57.1% of the total continued cenobamate treatment with benefit, achieving optimal seizure control (11.9% 1-year terminal remission) with a median daily dose of 200 (100-300) mg/d (Graph #5).
La demencia es un problema incapacitante y frecuente en la enfermedad de Parkinson (EP) avanzada.... more La demencia es un problema incapacitante y frecuente en la enfermedad de Parkinson (EP) avanzada. El deterioro cognitivo leve (DCL) también es prevalente (27% de pacientes con EP sin demencia) e implica un factor de riesgo para la demencia. De normales (EPCN), con deterioro cognitivo leve (EP-DCL) y con demencia (EPD).
Brain : a journal of neurology, 2014
The pathophysiological process underlying cognitive decline in Parkinson's disease is not wel... more The pathophysiological process underlying cognitive decline in Parkinson's disease is not well understood. Cerebral atrophy and hypometabolism have been described in patients with Parkinson's disease and dementia or mild cognitive impairment with respect to control subjects. However, the exact relationships between atrophy and hypometabolism are still unclear. To determine the extension and topographical distribution of hypometabolism and atrophy in the different cognitive states of Parkinson's disease, we examined 46 patients with Parkinson's disease (19 female, 27 male; 71.7 ± 5.9 years old; 14.6 ± 4.2 years of disease evolution; modified Hoehn and Yahr mean stage 3.1 ± 0.7). Cognitive status was diagnosed as normal in 14 patients, as mild cognitive impairment in 17 and as dementia in 15 patients. Nineteen normal subjects (eight female, 11 male; 68.1 ± 3.2 years old) were included as controls. (18)F-fluorodeoxyglucose positron emission tomography and magnetic reson...
Neuroscience Letters, 2009
Deep brain stimulation of the subthalamic nucleus (STN-DBS) reduces motor fluctuations in Parkins... more Deep brain stimulation of the subthalamic nucleus (STN-DBS) reduces motor fluctuations in Parkinson's disease (PD) but its effect on non-motor fluctuations (NMF) is not well known. In this study we assess the efficacy of STN-DBS on NMF two years after surgery. Autonomic, cognitive, psychiatric and sensory NMF in 20 patients were evaluated using a questionnaire designed to assess the frequency and severity of the NMF preoperatively and after two years of follow-up. The UPDRS scale was used for assessing the motor state. Compared with the preoperative situation, STN-DBS at 2 years of follow-up was associated with a significant reduction in the number and severity of autonomic and psychiatric NMF in the "off" state (without medication), and in the severity of sensory NMF, which were not observed in the "on" state (with medication). A cross-sectional analysis at the two-year time-point of the four possible motor conditions (combining medication and stimulation) showed a reduction in the total number of NMF and in the severity of autonomic and sensory NMF after switching on the stimulation in the "on" state. Improvement of the UPDRS-motor score was correlated with a reduction in the severity but not in the frequency of NMF. A worsening of motor function after suppressing stimulation in the "off" state was not paralleled by a worsening of NMF. After two years of follow-up, STN-DBS in the "off" medication was associated with a reduction in the frequency and severity of NMF. These results will need to be confirmed in controlled studies.
European Journal of Neurology, 2012
BACKGROUND AND PURPOSE White matter hyperintensities (WMHs) detected by magnetic resonance imagin... more BACKGROUND AND PURPOSE White matter hyperintensities (WMHs) detected by magnetic resonance imaging (MRI) of the brain are associated with dementia and cognitive impairment in the general population and in Alzheimer's disease. Their effect in cognitive decline and dementia associated with Parkinson's disease (PD) is still unclear. METHODS We studied the relationship between WMHs and cognitive state in 111 patients with PD classified as cognitively normal (n = 39), with a mild cognitive impairment (MCI) (n = 46) or dementia (n = 26), in a cross-sectional and follow-up study. Cognitive state was evaluated with a comprehensive neuropsychological battery, and WMHs were identified in FLAIR and T2-weighted MRI. The burden of WMHs was rated using the Scheltens scale. RESULTS No differences in WMHs were found between the three groups in the cross-sectional study. A negative correlation was observed between semantic fluency and the subscore for WMHs in the frontal lobe. Of the 36 non-demented patients re-evaluated after a mean follow-up of 30 months, three patients converted into MCI and 5 into dementia. Progression of periventricular WMHs was associated with an increased conversion to dementia. A marginal association between the increase in total WMHs burden and worsening in the Mini Mental State Examination was encountered. CONCLUSIONS White matter hyperintensities do not influence the cognitive status of patients with PD. Frontal WMHs have a negative impact on semantic fluency. Brain vascular burden may have an effect on cognitive impairment in patients with PD as WMHs increase overtime might increase the risk of conversion to dementia. This finding needs further confirmation in larger prospective studies.
Recent imaging studies with the stop-signal task in healthy individuals indicate that the subthal... more Recent imaging studies with the stop-signal task in healthy individuals indicate that the subthalamic nucleus, the presupplementary motor area and the inferior frontal gyrus are key components of the right hemisphere "inhibitory network". Limited information is available regarding neural substrates of inhibitory processing in patients with asymmetric Parkinson's disease. The aim of the current fMRI study was to identify the neural changes underlying deficient inhibitory processing on the stop-signal task in patients with predominantly left-sided Parkinson's disease. Fourteen patients and 23 healthy controls performed a stop-signal task with the left and right hands. Behaviorally, patients showed delayed response inhibition with either hand compared to controls. We found small imaging differences for the right hand, however for the more affected left hand when behavior was successfully inhibited we found reduced activation of the inferior frontal gyrus bilaterally and the insula. Using the stop-signal delay as regressor, contralateral underactivation in the right dorsolateral prefrontal cortex, inferior frontal and anterior putamen were found in patients. This finding indicates dysfunction of the right inhibitory network in left-sided Parkinson's disease. Functional connectivity analysis of the left subthalamic nucleus showed a significant increase of connectivity with bilateral insula. In contrast, the right subthalamic nucleus showed increased connectivity with visuomotor and sensorimotor regions of the cerebellum. We conclude that altered inhibitory control in left-sided Parkinson's disease is associated with reduced activation in regions dedicated to inhibition in healthy controls, which requires engagement of additional regions, not observed in controls, to successfully stop ongoing actions.
Recent imaging studies with the stop-signal task in healthy individuals indicate that the subthal... more Recent imaging studies with the stop-signal task in healthy individuals indicate that the subthalamic nucleus, the presupplementary motor area and the inferior frontal gyrus are key components of the right hemisphere "inhibitory network". Limited information is available regarding neural substrates of inhibitory processing in patients with asymmetric Parkinson's disease. The aim of the current fMRI study was to identify the neural changes underlying deficient inhibitory processing on the stop-signal task in patients with predominantly left-sided Parkinson's disease. Fourteen patients and 23 healthy controls performed a stop-signal task with the left and right hands. Behaviorally, patients showed delayed response inhibition with either hand compared to controls. We found small imaging differences for the right hand, however for the more affected left hand when behavior was successfully inhibited we found reduced activation of the inferior frontal gyrus bilaterally and the insula. Using the stop-signal delay as regressor, contralateral underactivation in the right dorsolateral prefrontal cortex, inferior frontal and anterior putamen were found in patients. This finding indicates dysfunction of the right inhibitory network in left-sided Parkinson's disease. Functional connectivity analysis of the left subthalamic nucleus showed a significant increase of connectivity with bilateral insula. In contrast, the right subthalamic nucleus showed increased connectivity with visuomotor and sensorimotor regions of the cerebellum. We conclude that altered inhibitory control in left-sided Parkinson's disease is associated with reduced activation in regions dedicated to inhibition in healthy controls, which requires engagement of additional regions, not observed in controls, to successfully stop ongoing actions.
Objetivo General de la tesis: Caracterizar la relacion entre la atrofia y el hipometabolismo PET-... more Objetivo General de la tesis: Caracterizar la relacion entre la atrofia y el hipometabolismo PET-FDG de la corteza cerebral y sus respectivos patrones bioquimicos mediante espectroscopia en los distintos estadios cognitivos de la EP. Objetivos especificos: 1) Realizar una comparacion directa entre el grado de atrofia de RM de la sustancia gris y el hipometabolismo PET-FDG en pacientes con EP con demencia, con deterioro cognitivo leve y cognitivamente normales. 2) Caracterizar mediante RME1H las intensidades de la senal de resonancia de los picos tipicos del espectro cerebral (N-acetilaspartato, creatina, colina, mioinositol y lactato) para cada una de las regiones categorizadas mediante PET-FDG y RM como atroficas, hipometabolicas y normales (sin hipometabolismo ni atrofia). 3) Analizar los datos de espectroscopia mediante un metodo moderno que permita evaluar el espectro al completo, mas alla de los picos tipicos, con el fin de investigar el papel de otros metabolitos que pudieran ...
Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques, 2016
Cephalalgia, 2009
Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (S... more Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) syndrome is characterized by short-lived (5-240 s), strictly unilateral, periorbital, severe pain attacks, accompanied by ipsilateral conjunctival injection and lacrimation (1). SUNCT syndrome has been considered to be refractory to treatment, although recent small case series have suggested benefit from different antiepileptic drugs (2, 3). In some cases surgical intervention may be advocated, particularly when the pain is medically intractable or the medications are not tolerated. We present a patient with chronic SUNCT syndrome who was successfully treated with posterior fossa vascular decompression 19 years after the onset of symptoms.
Parkinson's disease, 2012
Dyskinetic disorders are characterized by excess of motor activity that may interfere with normal... more Dyskinetic disorders are characterized by excess of motor activity that may interfere with normal movement control. In patients with Parkinson's disease, the chronic levodopa treatment induces dyskinetic movements known as levodopa-induced dyskinesias (LID). This paper analyzed the pathophysiology, clinical manifestations, pharmacological treatments, and surgical procedures to treat hyperkinetic disorders. Surgery is currently the only treatment available for Parkinson's disease that may improve both parkinsonian motor syndrome and LID. However, this paper shows the different mechanisms involved are not well understood.
Brain imaging and behavior, 2022
Recent imaging studies with the stop-signal task in healthy individuals indicate that the subthal... more Recent imaging studies with the stop-signal task in healthy individuals indicate that the subthalamic nucleus, the pre-supplementary motor area and the inferior frontal gyrus are key components of the right hemisphere "inhibitory network". Limited information is available regarding neural substrates of inhibitory processing in patients with asymmetric Parkinson's disease. The aim of the current fMRI study was to identify the neural changes underlying deficient inhibitory processing on the stop-signal task in patients with predominantly left-sided Parkinson's disease. Fourteen patients and 23 healthy controls performed a stop-signal task with the left and right hands. Behaviorally, patients showed delayed response inhibition with either hand compared to controls. We found small imaging differences for the right hand, however for the more affected left hand when behavior was successfully inhibited we found reduced activation of the inferior frontal gyrus bilaterally ...
Forty-two patients, mean 40 yo (19-66), followed up from 2015 (C017 open label-extension beginnin... more Forty-two patients, mean 40 yo (19-66), followed up from 2015 (C017 open label-extension beginning; n=8) and 2017 (C021; n=34) until 2020. A significant clinical response was obtained in 73.8% with a 1-year remission rate of 21.4% (Graph #1). The seizure frequency evolution with cenobamate (pre vs post) for focal impaired awareness seizures was (Graph #2): dailyweekly (81.0% vs 28.5%), monthly-sporadic (19.0% vs 57.1%), seizure-free (0% vs 14.3%). Focal to bilateral tonic-clonic seizures were present pre and post cenobamate treatment in a 45.2% vs 11.9%. Cenobamate introduction allowed the withdrawal of 0, 1 or 2 adjuvant AED in 11.9%, 42.9%, 45.2%, respectively (Graph #3). Main AE consisted of somnolence, dizziness and instability (Graph #4), which globally caused a cease of treatment in 8 patients (50% within first 6 months); and were mild-transient in 22 patients. No biochemical, hematic or idiosyncratic disorders were found. In 2020, 57.1% of the total continued cenobamate treatment with benefit, achieving optimal seizure control (11.9% 1-year terminal remission) with a median daily dose of 200 (100-300) mg/d (Graph #5).
La demencia es un problema incapacitante y frecuente en la enfermedad de Parkinson (EP) avanzada.... more La demencia es un problema incapacitante y frecuente en la enfermedad de Parkinson (EP) avanzada. El deterioro cognitivo leve (DCL) también es prevalente (27% de pacientes con EP sin demencia) e implica un factor de riesgo para la demencia. De normales (EPCN), con deterioro cognitivo leve (EP-DCL) y con demencia (EPD).
Brain : a journal of neurology, 2014
The pathophysiological process underlying cognitive decline in Parkinson's disease is not wel... more The pathophysiological process underlying cognitive decline in Parkinson's disease is not well understood. Cerebral atrophy and hypometabolism have been described in patients with Parkinson's disease and dementia or mild cognitive impairment with respect to control subjects. However, the exact relationships between atrophy and hypometabolism are still unclear. To determine the extension and topographical distribution of hypometabolism and atrophy in the different cognitive states of Parkinson's disease, we examined 46 patients with Parkinson's disease (19 female, 27 male; 71.7 ± 5.9 years old; 14.6 ± 4.2 years of disease evolution; modified Hoehn and Yahr mean stage 3.1 ± 0.7). Cognitive status was diagnosed as normal in 14 patients, as mild cognitive impairment in 17 and as dementia in 15 patients. Nineteen normal subjects (eight female, 11 male; 68.1 ± 3.2 years old) were included as controls. (18)F-fluorodeoxyglucose positron emission tomography and magnetic reson...
Neuroscience Letters, 2009
Deep brain stimulation of the subthalamic nucleus (STN-DBS) reduces motor fluctuations in Parkins... more Deep brain stimulation of the subthalamic nucleus (STN-DBS) reduces motor fluctuations in Parkinson's disease (PD) but its effect on non-motor fluctuations (NMF) is not well known. In this study we assess the efficacy of STN-DBS on NMF two years after surgery. Autonomic, cognitive, psychiatric and sensory NMF in 20 patients were evaluated using a questionnaire designed to assess the frequency and severity of the NMF preoperatively and after two years of follow-up. The UPDRS scale was used for assessing the motor state. Compared with the preoperative situation, STN-DBS at 2 years of follow-up was associated with a significant reduction in the number and severity of autonomic and psychiatric NMF in the "off" state (without medication), and in the severity of sensory NMF, which were not observed in the "on" state (with medication). A cross-sectional analysis at the two-year time-point of the four possible motor conditions (combining medication and stimulation) showed a reduction in the total number of NMF and in the severity of autonomic and sensory NMF after switching on the stimulation in the "on" state. Improvement of the UPDRS-motor score was correlated with a reduction in the severity but not in the frequency of NMF. A worsening of motor function after suppressing stimulation in the "off" state was not paralleled by a worsening of NMF. After two years of follow-up, STN-DBS in the "off" medication was associated with a reduction in the frequency and severity of NMF. These results will need to be confirmed in controlled studies.
European Journal of Neurology, 2012
BACKGROUND AND PURPOSE White matter hyperintensities (WMHs) detected by magnetic resonance imagin... more BACKGROUND AND PURPOSE White matter hyperintensities (WMHs) detected by magnetic resonance imaging (MRI) of the brain are associated with dementia and cognitive impairment in the general population and in Alzheimer's disease. Their effect in cognitive decline and dementia associated with Parkinson's disease (PD) is still unclear. METHODS We studied the relationship between WMHs and cognitive state in 111 patients with PD classified as cognitively normal (n = 39), with a mild cognitive impairment (MCI) (n = 46) or dementia (n = 26), in a cross-sectional and follow-up study. Cognitive state was evaluated with a comprehensive neuropsychological battery, and WMHs were identified in FLAIR and T2-weighted MRI. The burden of WMHs was rated using the Scheltens scale. RESULTS No differences in WMHs were found between the three groups in the cross-sectional study. A negative correlation was observed between semantic fluency and the subscore for WMHs in the frontal lobe. Of the 36 non-demented patients re-evaluated after a mean follow-up of 30 months, three patients converted into MCI and 5 into dementia. Progression of periventricular WMHs was associated with an increased conversion to dementia. A marginal association between the increase in total WMHs burden and worsening in the Mini Mental State Examination was encountered. CONCLUSIONS White matter hyperintensities do not influence the cognitive status of patients with PD. Frontal WMHs have a negative impact on semantic fluency. Brain vascular burden may have an effect on cognitive impairment in patients with PD as WMHs increase overtime might increase the risk of conversion to dementia. This finding needs further confirmation in larger prospective studies.
Recent imaging studies with the stop-signal task in healthy individuals indicate that the subthal... more Recent imaging studies with the stop-signal task in healthy individuals indicate that the subthalamic nucleus, the presupplementary motor area and the inferior frontal gyrus are key components of the right hemisphere "inhibitory network". Limited information is available regarding neural substrates of inhibitory processing in patients with asymmetric Parkinson's disease. The aim of the current fMRI study was to identify the neural changes underlying deficient inhibitory processing on the stop-signal task in patients with predominantly left-sided Parkinson's disease. Fourteen patients and 23 healthy controls performed a stop-signal task with the left and right hands. Behaviorally, patients showed delayed response inhibition with either hand compared to controls. We found small imaging differences for the right hand, however for the more affected left hand when behavior was successfully inhibited we found reduced activation of the inferior frontal gyrus bilaterally and the insula. Using the stop-signal delay as regressor, contralateral underactivation in the right dorsolateral prefrontal cortex, inferior frontal and anterior putamen were found in patients. This finding indicates dysfunction of the right inhibitory network in left-sided Parkinson's disease. Functional connectivity analysis of the left subthalamic nucleus showed a significant increase of connectivity with bilateral insula. In contrast, the right subthalamic nucleus showed increased connectivity with visuomotor and sensorimotor regions of the cerebellum. We conclude that altered inhibitory control in left-sided Parkinson's disease is associated with reduced activation in regions dedicated to inhibition in healthy controls, which requires engagement of additional regions, not observed in controls, to successfully stop ongoing actions.
Recent imaging studies with the stop-signal task in healthy individuals indicate that the subthal... more Recent imaging studies with the stop-signal task in healthy individuals indicate that the subthalamic nucleus, the presupplementary motor area and the inferior frontal gyrus are key components of the right hemisphere "inhibitory network". Limited information is available regarding neural substrates of inhibitory processing in patients with asymmetric Parkinson's disease. The aim of the current fMRI study was to identify the neural changes underlying deficient inhibitory processing on the stop-signal task in patients with predominantly left-sided Parkinson's disease. Fourteen patients and 23 healthy controls performed a stop-signal task with the left and right hands. Behaviorally, patients showed delayed response inhibition with either hand compared to controls. We found small imaging differences for the right hand, however for the more affected left hand when behavior was successfully inhibited we found reduced activation of the inferior frontal gyrus bilaterally and the insula. Using the stop-signal delay as regressor, contralateral underactivation in the right dorsolateral prefrontal cortex, inferior frontal and anterior putamen were found in patients. This finding indicates dysfunction of the right inhibitory network in left-sided Parkinson's disease. Functional connectivity analysis of the left subthalamic nucleus showed a significant increase of connectivity with bilateral insula. In contrast, the right subthalamic nucleus showed increased connectivity with visuomotor and sensorimotor regions of the cerebellum. We conclude that altered inhibitory control in left-sided Parkinson's disease is associated with reduced activation in regions dedicated to inhibition in healthy controls, which requires engagement of additional regions, not observed in controls, to successfully stop ongoing actions.
Objetivo General de la tesis: Caracterizar la relacion entre la atrofia y el hipometabolismo PET-... more Objetivo General de la tesis: Caracterizar la relacion entre la atrofia y el hipometabolismo PET-FDG de la corteza cerebral y sus respectivos patrones bioquimicos mediante espectroscopia en los distintos estadios cognitivos de la EP. Objetivos especificos: 1) Realizar una comparacion directa entre el grado de atrofia de RM de la sustancia gris y el hipometabolismo PET-FDG en pacientes con EP con demencia, con deterioro cognitivo leve y cognitivamente normales. 2) Caracterizar mediante RME1H las intensidades de la senal de resonancia de los picos tipicos del espectro cerebral (N-acetilaspartato, creatina, colina, mioinositol y lactato) para cada una de las regiones categorizadas mediante PET-FDG y RM como atroficas, hipometabolicas y normales (sin hipometabolismo ni atrofia). 3) Analizar los datos de espectroscopia mediante un metodo moderno que permita evaluar el espectro al completo, mas alla de los picos tipicos, con el fin de investigar el papel de otros metabolitos que pudieran ...
Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques, 2016