Cerebral correlates of declarative memory dysfunctions in early traumatic brain injury.

We investigated residual brain damage in subjects who suffered severe traumatic brain injury (TBI) in childhood, and its relationship with declarative memory impairment. Magnetic resonance imaging (MRI) volumetric data and memory performance were compared between 16 adolescents with antecedents of severe TBI and 16 matched normal controls. Volumes of grey matter, white matter, cerebrospinal fluid (CSF), hippocampus, and caudate nuclei were measured. Verbal memory was assessed by the Rey's Auditory Verbal Learning test and visual memory by the Rey's Complex Figure. TBI patients performed significantly worse than controls in both verbal and visual memory. Patients presented decreased white matter volume and increased CSF. The hippocampus was reduced, but not the caudate nuclei. Memory performance correlated with CSF. Plasticity is incomplete for structural and functional deficits in children with TBI. Hippocampal atrophy, white matter loss, and memory impairment remain until adolescence. Memory sequelae are related more to diffuse brain injury, as reflected by MRI findings of increased CSF, than to hippocampal injury.

Effects of gabapentin on the motor response to levodopa: a double-blind, placebo-controlled, crossover study in patients with complicated Parkinson disease.

BACKGROUND: Motor fluctuations and dyskinesias affect many parkinsonian patients chronically treated with levodopa. Imbalance between gabaergic direct and indirect striatopallidal pathways may originate them. Manipulating GABA neurotransmission may be effective in the treatment of these patients. Gabapentin is an antiepileptic drug that increases the synthesis and release of GABA. Previous studies suggest that gabapentin may be useful in Parkinson disease (PD). OBJECTIVE: To know the effects of gabapentin on the motor response to levodopa in PD patients with motor complications. DESIGN: A randomized double-blind, placebo-controlled, cross-over trial with four weeks of treatment. SETTING: A tertiary referral center. PARTICIPANTS: Twenty subjects with PD and motor fluctuations and dyskinesias on stable antiparkinsonian treatment, took gabapentin up to a maximum dose of 2.400 mg/d in three doses and placebo. METHODS: Three levodopa challenges were performed: at the beginning of the study and at the end of each period of treatment (4 weeks). Basal (off) and best (on) motor status were assessed by the UPDRS III. Latency to peak effect, magnitude of motor response (difference between "on" and "off" scores in the UPDRS III), duration of motor response and severity and duration of dyskinesias after each levodopa challenge were assessed. Patients' diaries were administered. RESULTS: : Fifteen patients completed the study. A significant improvement in the basal UPDRS III resulting in a significant reduction in the magnitude of the motor response after gabapentin was obtained (P < 0.001). No other changes were observed, either on pharmacological parameters or in levodopa-induced dyskinesias. Number of daily hours spent in "on," "on with dyskinesias" and "off" also remained unchanged. Tolerance was good, dizziness being the most common side effect. CONCLUSION: Gabapentin improved parkinsonian symptoms (basal UPDRS III and magnitude of the motor response) following levodopa. This improvement was not reflected in the daily motor situation of patients. Dyskinesias remained unchanged. Gabapentin was well tolerated. Further studies are needed to know the impact of these results in the long-term.

Treatment of restless legs syndrome with gabapentin: a double-blind, cross-over study.

OBJECTIVE: To assess the effects of gabapentin on sensory and motor symptoms in patients with restless legs syndrome (RLS). METHODS: Patients with RLS (22 idiopathic, 2 secondary to iron deficiency) were randomized and treated for 6 weeks with either gabapentin or placebo. After a 1-week washout they crossed over to the alternative treatment for 6 weeks. Patients were rated at baseline and at scheduled intervals by the RLS Rating Scale, Clinical Global Impression, pain analogue scale, and Pittsburgh Sleep Quality Index. At the end of each treatment period, all-night polysomnography was performed. RESULTS: Compared to placebo, gabapentin was associated with reduced symptoms on all rating scales. In addition, sleep studies showed a significantly reduced periodic leg movements during sleep (PLMS) index and improved sleep architecture (increased total sleep time, sleep efficiency, and slow wave sleep, and decreased stage 1 sleep). Patients whose symptoms included pain benefited most from gabapentin. The mean effective dosage at the end of the 6-week treatment period was 1,855 mg, although therapeutic effects were already observed at the end of week 4 (1,391 mg). CONCLUSIONS: Gabapentin improves sensory and motor symptoms in RLS and also improves sleep architecture and PLMS.

[Study of the long term sequelae of traumatic brain injury: evaluation of declarative and procedural memory, and its neuroanatomic substrate]. / Estudio de las secuelas a largo plazo de los traumatismos craneoencefálicos: evaluación de la memoria declarativa y procedimental y de su sustrato neuroanatómico.

INTRODUCTION AND OBJECTIVES: The hippocampus and the striatum have been proposed as respectively cerebral substrates of declarative and procedural memory. Both structures are vulnerable to traumatic brain injury. Although declarative and procedural memory have been reported to be impaired in traumatic brain injury (TBI), volumetric measures have so far failed to associate this impairment with atrophy of hippocampal and striatal structures. In our study, we investigated the profile of declarative and procedural memory in children who suffered from moderate to severe traumatic brain injury during childhood (injury test interval: 9.42+/-1.98 years). PATIENTS AND METHODS: Nineteen patients and matched controls were evaluated on tests of declarative memory and motor learning. Results showed that TBI subjects exhibit poorer performance in both tasks. Moreover, structural magnetic resonance images were obtained from TBI subjects. In order to relate neuropsychological performance with hippocampal and neostriatal volumetric data, correlation analyses were performed. RESULTS: Significant positive correlations were obtained between hippocampal volume and memory for objects. Striatal volume correlated positively with motor learning and with verbal memory. CONCLUSIONS: It thus seems that plasticity does not completely compensate for the memory deficits resultant from neural loss in the immature brain.

Estudio de las secuelas a largo plazo de los traumatismos craneoencefálicos: evaluación de la memoria declarativay procedimental y de su sustrato neuroanatómico / Study of the long term sequelae of traumatic brain injury: evaluation of declarative and procedural memory, and its neuroanatomic substrate

Introducción y objectivos. Los estudios realizados hasta la actualidad permiten considerar el hipocampo y el estriado como el sustrato neural de las memorias declarativa y procedimental, respectivamente. Si bien ambas estructuras son vulnerables al traumatismo craneoencefálico, y diversos estudios han observado que tanto la memoria declarativa como la procedimental también decaen a consecuencia de traumatismo craneoencefálico, los estudios volumétricos realizados hasta ahora no muestran evidencia de la relación entre la atrofia de ambas estructuras y el grado de alteración de la memoria. El presente estudio se centra en investigar el grado de alteración de las memorias declarativa y procedimental en niños que, de pequeños, sufrieron traumatismo craneoencefálico de moderado a grave. Pacientes y métodos. Diecinueve pacientes y sus respectivos controles fueron evaluados en tareas de memoria declarativa y aprendizaje motor. Los resultados mostraron que los sujetos con traumatismo craneoencefálico exhibían un peor rendimiento en ambas tareas. Además, para relacionar el rendimiento neuropsicológico con los datos volumétricos del hipocampo y el estriado, se realizaron análisis de correlaciones. Resultados. Se encontraron correlaciones positivas entre el volumen del hipocampo y la memoria para objetos del test `objeto-localización'. Por su parte, el volumen del estriado correlacionaba positivamente con el aprendizaje motor y la memoria verbal. Conclusión. Los resultados obtenidos sugieren que los mecanismos de plasticidad no compensan completamente los déficit de memoria resultantes de la pérdida neural en el cerebro immaduro (AU)

Correlation of atrophy measures on MRI with neuropsychological sequelae in children and adolescents with traumatic brain injury.

To examine the relationship between neuropsychological sequelae and atrophy parameters from magnetic resonance imaging (MRI) following paediatric moderate-to-severe traumatic brain injury (TBI), 19 head injured children and adolescents were studied at least 6 years after injury. Three-dimensional MRI scans were obtained. A semi-automatic computerized method was used to estimate ventricular volumes and the corpus callosum area. Tests of intellectual, memory, visuospatial, frontal lobe, and motor speed functioning were administered to all patients and to 19 matched normal control subjects. Patients' performance significantly differed from controls in general intellectual function, visual memory, visuospatial and frontal lobe tests. The corpus callosum area correlated strongly with several measures involving processing speed and visuospatial function. Ventricular enlargement was less related to neuropsychological outcome. In conclusion, quantitative measurement of the corpus callosum on MRI reflects neuropsychological outcome better than ventricular dilation in paediatric patients.

Phonemic and semantic fluencies in traumatic brain injury patients with focal frontal lesions.

The purpose of this study was to investigate the effect of focal frontal lesions, identified by magnetic resonance imaging (MRI), in a group of traumatic brain injured (TBI) patients, in order to clarify the sensitivity of phonemic and semantic fluency tasks as tests of frontal lobe functioning. Thirteen TBI patients were included and matched with a normal control group of 26 subjects. Frontal lobe patients produced significantly fewer words than the control group in the phonemic fluency condition. Semantic performance correlated with lesion size, but phonemic performance did not, corroborating the idea that the two have different brain-based substrates. Although, as a group effect, frontal lesions impaired fluency, not all patients were impaired, even in the presence of large bilateral frontal lesions.

Age effects on long-term neuropsychological outcome in paediatric traumatic brain injury.

In order to investigate the relationship between age at injury and long-term neuropsychological impairment, 29 children and adolescents who sustained traumatic brain injury (TBI) were studied at least 6 years post-trauma. Tests of intellectual, memory, visuospatial and frontal lobe functions were administered to patients and 29 normal matched control subjects. Correlations between performance on neuropsychological tests and age showed the following direction: the younger the child when TBI was sustained, the worse the cognitive outcome. After controlling for injury severity, visuospatial functions remained related to age. Patients' performance differed significantly from that of controls in half of the neuropsychological variables analysed. To further investigate the effects of age at injury, the sample was divided in two groups (TBI before and after age of 8) and then compared with their respective controls. Patients damaged earlier presented impaired intellectual and visuospatial functions. The results suggest that neuropsychological sequelae remain after at least 6 years of evolution, and that there is an age at injury effect.

Neuropsychological functioning in a subclinical obsessive-compulsive sample.

BACKGROUND: Previous neuropsychological research has suggested that the study of psychometrically defined subclinical samples might be a valid approach to understand the underlying pathophysiology of obsessive-compulsive disorder (OCD). This approach has the potential benefit of overcoming some of the methodological problems linked to the use of clinical samples. METHODS: A group of subclinical obsessive-compulsive (OC) subjects (n = 35), selected on the basis of their scores on the Padua Inventory, and a control group were assessed on executive functioning tasks and other neuropsychological tests which have been demonstrated to be impaired in clinical OCD patients and/or in those with several basal ganglia disorders. RESULTS: Subclinical OC subjects needed significantly more moves than controls to reach the solution criteria on the Tower of Hanoi puzzle, and performance on this test was positively correlated with total score and the Checking factor of the Padua Inventory. There were no between-group differences on the other frontal lobe tests. CONCLUSIONS: The results suggest that deficits in manipulating spatial information might be basic in OCD, and are congruent with the involvement of the frontostriatal circuits in the disorder.

Hemispheric functional imbalance in a sub-clinical obsessive-compulsive sample assessed by the Continuous Performance Test, Identical Pairs version.

Obsessive-compulsive disorder (OCD) sufferers have long been observed to give excessive consideration to normally ignored exogenous and endogenous stimuli. This over-focused attention concerning their symptoms has led researchers to experimentally investigate the attentional mechanisms involved in this disorder and its psychobiological basis. Previous psychometric and neuropsychological research has demonstrated the validity of the sub-clinical analogue in the study of the mechanisms underlying OCD. In this study, 71 introductory university students were recruited from an original pool of 450 people on the basis of their scores on the Spanish version of the Padua Inventory. A high obsessive group (n = 35) was compared with a control group (n = 36) on a standard sustained attention task: the Continuous Performance Test, Identical Pairs version (CPT-IP). The results showed a significant interaction effect between CPT-IP subscales (verbal and spatial) and group membership. This effect was more evident among men. The results were unrelated to general intelligence, depression, anxiety, personality or motivational factors. These findings support the hypothesis that neuropsychological deficits in OCD may be related to a hemispheric functional imbalance rather than to a lateralised dysfunction of a particular hemisphere.

[Neuropsychological disorders due to left fronto-striatal lesions: a longitudinal study of an adolescent]. / Trastornos neuropsicológicos por lesión en el sistema fronto-estriado izquierdo. Estudio longitudinal de un adolescente.

Relatively little is known of the neuropsychological consequences of isolated frontal-striatal lesions in children. We study the case of an adolescent boy who suffered a stroke in the left hemisphere at the age of 11. In addition to the expected frontal dysfunctions, the patient at first suffered lowered IQ and attention disorder with hyperactivity. Four years after the stroke, only frontal lobe dysfunctions (difficulties in planning, anticipating, responding, generating words, attending, and sequencing with loss of mental flexibility) persisted. The functional recovery might have come about because the right hemisphere striate assumed functions of the left hemisphere. The persistence of frontal dysfunctions favors specialization of the left frontal lobe and the relatively early maturity of this cortical structure.