Prognostic value of changes in resting-state functional connectivity patterns in cognitive recovery after stroke: A 3T fMRI pilot study.

Resting-state studies conducted with stroke patients are scarce. First objective was to explore whether patients with good cognitive recovery showed differences in resting-state functional patterns of brain activity when compared to patients with poor cognitive recovery. Second objective was to determine whether such patterns were correlated with cognitive performance. Third objective was to assess the existence of prognostic factors for cognitive recovery. Eighteen right-handed stroke patients and eighteen healthy controls were included in the study. Stroke patients were divided into two groups according to their cognitive improvement observed at three months after stroke. Probabilistic independent component analysis was used to identify resting-state brain activity patterns. The analysis identified six networks: frontal, fronto-temporal, default mode network, secondary visual, parietal, and basal ganglia. Stroke patients showed significant decrease in brain activity in parietal and basal ganglia networks and a widespread increase in brain activity in the remaining ones when compared with healthy controls. When analyzed separately, patients with poor cognitive recovery (n=10) showed the same pattern as the whole stroke patient group, while patients with good cognitive recovery (n=8) showed increased activity only in the default mode network and fronto-temporal network, and decreased activity in the basal ganglia. We observe negative correlations between basal ganglia network activity and performance in Semantic Fluency test and Part A of the Trail Making Test for patients with poor cognitive recovery. A reverse pattern was observed between frontal network activity and the above mentioned tests for the same group. .

Is there progressive cognitive dysfunction in Sjögren Syndrome? A preliminary study.

OBJECTIVE: The aim of this study was to determine the progression of cognitive dysfunction in primary Sjögren Syndrome (SS). METHODS: Twelve subjects with SS were compared with ten subjects with migraine and ten healthy controls on neuropsychological, mood and fatigue tests at baseline and 8 years later. RESULTS: At follow-up, SS subjects performed below subjects with migraine on the Continuous Performance Test (CPT) but did not differ on other tasks. Compared with controls, both clinical groups obtained lower scores on simple reaction time, patients with SS obtained lower scores on the Wisconsin Card Sorting Test (WCST) and patients with migraine performed below controls on the Benton's Judgment of Line Orientation Test (JOLO). Clinical groups did not differ on cognitive changes over time, except that migraine subjects improved on verbal fluency. Compared with baseline, both SS and migraine patients were more impaired on simple reaction time, Trail Making Test part B, Stroop and JOLO. However, they showed higher scores on verbal and visual memory, WCST and CPT reaction time. SS also showed higher levels of depression and fatigue than migraine and controls, with no significant changes over time. DISCUSSION: Preliminary evidence indicates some cognitive deficits in both SS and migraine following a pattern of fronto-subcortical dysfunction without a significant cognitive decline over time.

The Barcelona-Asymptomatic Intracranial Atherosclerosis (AsIA) study: Subclinical cervico-cerebral stenosis and middle cerebral artery pulsatility index as predictors of long-term incident cognitive impairment.

BACKGROUND AND AIMS: We aimed to study subclinical non-invasive vascular markers as predictors of incident long-term cognitive impairment in a longitudinal population-based study. METHODS: The Barcelona-Asymptomatic Intracranial Atherosclerosis (AsIA) study is a population-based study that included a random sample of 933 Caucasian subjects (mean age 66 years, 64% male) with a moderate-high vascular risk and without history of stroke or dementia. Subclinical carotid and intracranial stenosis was assessed at baseline visit by cervical and transcranial color-coded duplex (TCCD) and confirmed by magnetic resonance angiography. Cervico-cerebral stenosis (CCS) was defined as the presence of extra and/or intracranial stenosis >50%. Baseline middle cerebral artery pulsatility index (MCA-PI) was measured bilaterally by TCCD, and mean PI of both sides was considered for analyses. Subjects were followed-up to determine incident long-term cognitive impairment (mild cognitive impairment or dementia). RESULTS: After a median of 7.16 [6.91-7.75] years of follow-up, 91 subjects (9.7%) developed cognitive impairment, 27 of them mild cognitive impairment, and 64 dementia. Incidence of cognitive impairment was significantly higher among subjects with subclinical CCS (21.4% versus 9% in those without CCS) and among those with mean MCA-PI>1 (13.5% versus 7.4% in those with MCA-PI<1). In multivariate Cox regression analyses, both CCS and MCA-PI>1 were independently associated with incident cognitive impairment with HR of 2.07 [1.11-3.88] and 1.58 [1.02-2.46], respectively. CONCLUSIONS: Subclinical cervico-cerebral stenosis and higher MCA-PI are non-invasive neurosonological markers of incident long-term cognitive impairment in our population.

Influence of APOE polymorphism on cognitive and behavioural outcome in moderate and severe traumatic brain injury.

AIM: To analyse the influence of apolipoprotein (APOE) epsilon4 status on the cognitive and behavioural functions usually impaired after moderate and severe traumatic brain injury (TBI). METHODS: In all, 77 patients with TBI selected from 140 consecutive admissions were genotyped for APOE. Each patient was subjected to neuropsychological and neurobehavioural assessment at least 6 months after injury. RESULTS: Performance of participants carrying the epsilon4 allele was notably worse on verbal memory (Auditory Verbal Learning Test), motor speed, fine motor coordination, visual scanning, attention and mental flexibility (Grooved Pegboard, Symbol Digit Modalities Test and part B of the Trail Making Test) and showed considerably more neurobehavioural disturbances (Neurobehavioral Rating Scale-Revised) than the group without the epsilon4 allele. CONCLUSIONS: In particular, performance on neuropsychological tasks that are presumed to be related to temporal lobe, frontal lobe and white matter integrity is worse in patients with the APOE epsilon4 allele than in those without it. More neurobehavioural disturbances are observed in APOE epsilon4 carriers than in APOE epsilon2 and epsilon3 carriers.

Magnetic resonance imaging measurement of the caudate nucleus in adolescents with attention-deficit hyperactivity disorder and its relationship with neuropsychological and behavioral measures.

OBJECTIVE: To investigate structural basal ganglia abnormalities in attention-deficit hyperactivity disorder (ADHD) and their relationship with the neuropsychological deficits and behavioral problems found in ADHD. DESIGN: Case-control study. SETTING: Adolescents were recruited from a local polytechnic institute of secondary education. SUBJECTS: Eleven adolescents with ADHD and 19 healthy control subjects. Subjects with ADHD were diagnosed by the school psychologist from a total population of 450 students according to the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised. Diagnosis was confirmed by the Conners Teachers Rating Scale and a structured family interview. MAIN OUTCOME MEASURES: Magnetic resonance imaging single-slice transversal measurements of the head of the caudate nucleus and a comprehensive neuropsychological evaluation, which was specially designed to assess frontal-striatal functioning. RESULTS: The ADHD group had a larger right caudate nucleus area than the control group. In control adolescents, larger caudate nucleus areas were associated with poorer performance on tests of attention and higher ratings on the Conners Teachers Rating Scale. CONCLUSIONS: These findings provide further evidence of the involvement of the caudate nucleus in the neuropsychological deficits and behavioral problems found in ADHD. The larger caudate nucleus found in the ADHD group could be related to a failure of the maturational processes that normally result in volume reduction.

Long-term effects of bilateral frontal brain lesion: 60 years after injury with an iron bar.

BACKGROUND: Harlow's report of the case of Phineas P. Gage in 1848 was one of the earliest description of the personality and behavioral changes following frontal lobe damage. Since Harlow's articles, a few more case reports of frontal lobe damage have been published. As standard neuropsychological and neurologic evaluations may reveal subtle defects, case reports have been particularly useful in characterizing the behavioral changes that follow frontal lobe damage. OBJECTIVE: To describe the long-term outcome of an 81-year-old patient who sustained a severe frontal brain lesion 60 years ago caused by the passage of an iron spike through his head. RESULTS: The patient has bilateral damage affecting the orbital and dorsolateral frontal regions. He displays many of the typical frontal behavioral disturbances described in the literature. His conduct is characterized by dependence on others, cheerfulness, planning difficulties, problems establishing realistic goals, lack of drive, and difficulties in initiating, continuing, and finishing activities. Although gross cognitive functioning is intact, neuropsychological deficits are present in the executive functioning, memory, and visuoconstructive domains. CONCLUSIONS: In contrast with the antisocial conduct pattern usually associated with frontal damage in the literature, this case suggests that large frontal lesions can produce behavioral and personality changes that are compatible with stable functioning in family, professional, and social settings. In addition to the localization of the lesion, many other factors should be considered in the long-term prognosis of frontal brain injured patients.

Neuropsychological outcome in relation to the traumatic coma data bank classification of computed tomography imaging.

The Traumatic Coma Data Bank (TCDB) classification of CT (computed tomography) scan has been related to the general outcome and intracranial pressure evolution. Our aim was to analyse the relationship of this classification with neuropsychological outcome and late indices of ventricular dilatation. Fifty-seven patients with a moderate or severe head injury (mean admission Glasgow Coma Scale Score, 7.7) were studied from 122 consecutive cases. There were 49 males and 8 females (mean age, 27.7 years). Subjects were classified into TCDB categories on the basis of their most serious acute CT scan finding. From the last control CT scan image, performed at a mean of 6.12 months postinjury, several measures of ventricular dilatation were calculated. Neuropsychological assessment at 6-month included tests of verbal and visual memory, visuoconstructive functions, fine motor speed, and frontal lobe functions. Patients with diffuse injury type I showed better neuropsychological outcome than patients with more severe diffuse injuries and those with mass lesions. Within the diffuse injury groups, the degree of diffuse damage was related to measures of verbal memory and attention and cognitive flexibility. Ventricular enlargement was more evident in patients with mass lesions and it decreased in the remaining groups as the severity of diffuse injury diminished. These results show that there is a relationship between acute intracranial lesion diagnosis according to TCDB classification and neuropsychological results and ventricular dilatation indices at 6 months postinjury.

Agreement between CSF flow dynamics in MRI and ICP monitoring in the diagnosis of normal pressure hydrocephalus. Sensitivity and specificity of CSF dynamics to predict outcome.

OBJECTIVES: The aims of the study were 1) to assess the degree of agreement between CSF flow dynamics determined by MR and ICP monitoring in the diagnosis of NPH, and 2) to determine the sensitivity and specificity of CSF flow dynamics studied by MR in predicting improvement after shunting. PATIENTS AND METHODS: A prospective study was carried out in 35 consecutive patients with suspected NPH. CSF velocity (Phase Contrast) through the aqueduct was determined in sagittal plane. Patients were classified as "normal" or hyperdynamic in comparison with a control group of 27 healthy volunteers. Continuous extradural ICP monitoring was performed for at least 72 hours and patients were classified as having active, compensated, or ex-vacuo hydrocephalus. Patients with active or compensated hydrocephalus were shunted. RESULTS: The degree of agreement between MR dynamics and ICP monitoring was 82%. Sensitivity of CSF velocity was 90% and specificity was 50%. CONCLUSIONS: The degree of agreement between ICP monitoring and CSF velocity is high. High CSF velocity through the aqueduct is a good predictor of improvement after surgery. However, patients with normal velocity in MR required additional tests before a diagnosis of NPH is ruled out.

[Study of cerebral activity with functional magnetic resonance]. / Estudio de la actividad cerebral con resonancia magnética funcional.

BACKGROUND: Functional magnetic resonance is a new imaging method which allows the incruent observation of human cerebral activity. The authors describe their method of functional magnetic resonance and the results of cerebral activation. METHODS: A total of 364 functional sequences were performed in 52 volunteers with a magnetic resonance system of 1.5 Tesla. A gradient echo sequence with a long echo time sensitive to the changes in oxygenation of venous blood was used. Different cortical areas were stimulated by visual, motor and language maneuvers and by complex mental operations. RESULTS: Different cerebral areas representative of different levels of cerebral functional complexity were consistently activated and reproduced. Experiments of activation of primary cerebral cortex (visual and motor), premotor regions, specific area of language and areas of cortical association for cognitive operations are described. CONCLUSIONS: Functional magnetic resonance imaging is a sensitive method for the observation of cerebral activity and provides functional images with great spatial and temporal resolution. This may be useful in both clinical and basic investigation.

[Attention deficit hyperactivity disorder. Cerebral asymmetry observed on magnetic resonance]. / Trastorno por déficit de atención con hiperactividad. Asimetrías cerebrales observadas en resonancia magnética.

INTRODUCTION: Anatomical and functional neuroimaging data from subjects with Attention Deficit Hyperactivity Disorder (ADHD) have consistently implicated a reversal of cerebral asymmetry and suggested a fronto-striatal dysfunction in this disorder. OBJECTIVE: The aim of this study is to investigate the brain asymmetries in a homogeneous and non-medicated sample of adolescents with ADHD who had been previously studied in our laboratory. PATIENTS AND METHODS: T1-weighted magnetic resonance images were obtained for 11 adolescents with ADHD and 19 control subjects. Frontal and posterior brain regions, caudate nucleus, and ventricular system were quantitatively measured. RESULTS: A reversed pattern of asymmetry for the caudate nucleus (right > left) was found in ADHD when compared to the control group. We also found a reversed pattern of asymmetry for the frontal lobe (right < left) and a smaller right frontal volume (prefrontal specifically) in the ADHD subjects most severely impaired. Right caudate and frontal measures were inversely correlated. CONCLUSIONS: ADHD is associated with fronto-striatal abnormalities, which may be explicable via extant neurodevelopmental theories. Enlargement of the right caudate nucleus may suggest the failure of a process of synaptic 'pruning' by which attentional functions could be improperly transferred from the basal ganglia to frontal regions during development.

[Cognitive event-related brain potentials (P300) in patients with normal pressure hydrocephalus. Results of a prospective study]. / Potenciales evocados cognitivos (P300) en pacientes con hidrocefalia de presión normal.

OBJECTIVE: To determine the response to cognitive event-related potentials (P300) in patients with normal-pressure hydrocephalus (NPH) and their relationship with clinical and cognitive status before and after shunt surgery. METHODS: We performed a prospective study in a series of 26 patients with NPH who underwent clinical and cognitive assessment before surgery and 6 months afterwards. Visual P300 potentials obtained before and after treatment were also compared with those obtained in 18 healthy volunteers. RESULTS: Before shunting, the P300 wave was detected in 11 (42.3%) NPH patients, compared with the 18 (100%) volunteers. Six months after shunting, the P300 wave was found in 20 (76.9%) NPH patients. P300 latency was significantly longer in NPH patients than in the control group before surgery, but not at 6 months after surgery. No significant differences in neuropsychological studies or in the level of dependence for daily life activities were found between the subgroups of NPH patients with and without pre-surgical P300 waves, or between changes in P300 parameters and clinical and cognitive changes. CONCLUSIONS: The P300 wave was delayed or undetectable in a substantial percentage of patients with NPH before surgery. These alterations can be reversed by shunting. P300 analysis and neuropsychological tests could be complementary measures to evaluate functional status in patients with NPH.

[Vascular risk factors and cognitive performance in patients 50 to 65 years-old]. / Factores de riesgo vascular y rendimiento cognitivo en personas de 50 a 65 años.

INTRODUCTION: Vascular risk factors (VRF) have been related to cognitive deficits and an increased risk of dementia. Cognitive impairment is considered to be one of the earliest manifestations of cerebrovascular disease. In Spain there is a high prevalence of VRF, but also one of the lowest incidences of cerebrovascular disease in Europe. This is the first study that investigates the relationship between VRF and cognition in a Spanish sample. METHODS: A total of 90 people aged between 50-65 years with a low-to-moderate cardiovascular risk underwent a neuropsychological evaluation. None of them had a history of cardiovascular disease. The battery included tests assessing executive, attentional, mnesic, visuospatial and motor-speed/coordination functions. We used correlation and inter-groups comparison to relate VRF to multiple cognitive domains0120. RESULTS: Higher stroke risk was significantly related to a lowered profile in visuo-constructive functions and motor-speed/coordination. Moreover, the group with moderate cardiovascular risk showed a lower performance in visuoconstructive functions compared to the low-risk group. After statistical adjustment for age, sex and years of scholarship VRF were only related to motor-speed/coordination. CONCLUSIONS: In healthy, middle-aged adults, VRF are related with impairment in two cognitive domains. This effect is slight and tends to appear in people with moderate cardiovascular risk.

Information needs of the traumatic brain injury patient's family members regarding the consequences of the injury and associated perception of physical, cognitive, emotional and quality of life changes.

We studied physical, cognitive, emotional and quality-of-life changes noted by relatives in a sample of 65 severely traumatic brain injured (TBI) patients several years after injury. The purpose of the present study was to evaluate the families perception of these changes and their need for information concerning the consequences of TBI. Our results indicated that the perceived changes in behavioural and affective symptoms and in the patient's quality of life were most closely associated with the need expressed by family members for information concerning, TBI. We also found that family relationships were especially affected by problems in the behavioral and affective domain, and the decrease in patient quality of life, as reported by relatives. These findings underline the importance of providing the relatives of TBI patients with information about the consequences of the injury with particular emphasis on behavioural and emotional disturbances, in order that they might cope better with these problems.

[Learning and memory skills in patients with cryptogenic epilepsy]. / Capacidad de aprendizaje y memoria en los pacientes con epilepsia criptogénica y crisis parciales.

The purpose of this investigation was to determine the nature of memory deficits in patients with cryptogenic epilepsy and partial seizures. Sixty-two patients were compared to forty-four controls on several verbal and visual memory tests (short-term memory, learning, long-term recall, and recognition). Performance in the patients group was significantly impaired only on the test of verbal delayed recall.

Neuropsychological differences in epileptic patients with seizures of frontal and temporal lobe origin.

This investigation studied the neuropsychological differences in nonsurgical cryptogenic epileptic patients with seizures of frontal and temporal lobe origin, which were classified according to clinical criteria. Fifty-one patients with partial seizures of frontal (n = 15) or temporal (n = 36) lobe origin and 2 matched control groups were administered a battery of neuropsychological tests assessing intelligence, memory, perceptual, and frontal functions. Patients with seizures of temporal lobe onset performed worse than patients with seizures of frontal lobe origin, even in frontal functions. The findings of this study corroborate the low specificity of tasks regarded as frontal lobe tests and the difficulty in detecting frontal lobe neuropsychological focalities.

[Update on diagnosis and treatment of normotensive hydrocephalus (chronic hydrocephalus of the adult)]. / Actualizaciones en el diagnóstico y tratamiento de la hidrocefalia "normotensiva" (hidrocefalia crónica del adulto).

Normal pressure hydrocephalus, or adult chronic hydrocephalus, is a relatively unknown entity. Classically, this disease is characterized by progressive dementia, gait disturbance, and urinary incontinence. Despite an increase in the prevalence of this type of dementia due to longer life expectancy, its diagnosis and treatment remain controversial. Recent studies have reported that the percentage of patients who show clinical improvement after shunting is still low and that the complication rate is excessively high. However, our experience and that of other authors indicates that the percentage of improvement after shunting can be greater than 80% and the complication rate can be low if a strict diagnostic protocol is applied and if the most appropriate valve is selected, based on the hydrodynamic characteristics of the shunt. The aim of this review is to provide an update of the clinical features, diagnosis and treatment of adult chronic hydrocephalus. We also discuss the diagnostic and treatment protocols applied in our centre in patients with suspected adult chronic hydrocephalus.

Neuropsychological findings in congenital and acquired childhood hydrocephalus.

Hydrocephalus is an increase in cerebrospinal fluid volume that can be caused by a variety of etiologies. The most common connatal and acquired causes of hydrocephalus are spina bifida, aqueduct stenosis, and preterm low birthweight infants with ventricular hemorrhage. In general, the literature suggests mild neuropsychological deficits associated with hydrocephalus, which are predominant in visuospatial and motor functions, and other nonlanguage skills. Although the precise nature of the neuropsychological deficits in hydrocephalus are not completely known, several factors such as etiology, raised intracranial pressure, ventricular size, and changes in gray and white matter tissue composition as well as shunt treatment complications have been shown to influence cognition. In fact, the presence of complications and other brain abnormalities in addition to hydrocephalus such as infections, trauma, intraventricular hemorrhage, low birthweight, and asphyxia are important determinants of the ultimate cognitive status, placing the child at a high risk of cognitive impairment.

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.

Initial disturbances of consciousness and resultant impaired awareness in Spanish patients with traumatic brain injury.

The purpose of this prospective, between-subjects study was to look at impaired awareness cross-culturally in patients with traumatic brain injury (TBI) and to relate impaired awareness after injury to the initial estimates of disturbed consciousness at time of injury. The study was conducted in community and inpatient and outpatient rehabilitation centers in Barcelona and Madrid. Participants were 30 persons with primarily moderate to severe TBI who could complete a written questionnaire concerning their functioning and 28 age- and gender-matched controls. A Spanish translation of the Patient Competency Rating Scale (PCRS) was administered to each participant. Relatives or significant others also completed this scale on each participant using the relative's version (PCRS-R). Difference scores, obtained by subtracting PCRS-R from PCRS-P (PCRS-P minus PCRS-R), were used as a marker of impaired awareness. Individuals with TBI were rated (by self and significant others) as being less competent than controls. Forty percent of Spanish patients with TBI who suffered severe injuries tended to overestimate their behavioral competencies. The PCRS-P minus the PCRS-R difference scores tended to correlate with admitting Glasgow Coma Scale (GCS) scores and retrospective estimates of posttraumatic amnesia (PTA). Initial disturbances of consciousness, one measure of severity of brain injury, appeared to relate to later measures of impaired self-awareness in Spanish patients with TBI. Non-brain-injured controls did not tend to report levels of competency that differed from their relatives' reports.

Shunt related changes in somatostatin, neuropeptide Y, and corticotropin releasing factor concentrations in patients with normal pressure hydrocephalus.

OBJECTIVES: Recent data indicate that alterations in brain neuropeptides may play a pathogenic role in dementia. Neuropeptide Y (NPY), somastostatin (SOM), and corticotropin releasing factor (CRF) are neuropeptides involved in cognitive performance. Decreased SOM and NPY concentrations have been found in patients with normal pressure hydrocephalus and are probably the result of neuronal dysfunction, which could potentially be restored by shunting. The effects of shunt surgery on preoperative SOM, NPY, and CRF concentrations were studied. Any improvements in neuropeptide concentrations that could lead to clinically significant neuropsychological and functional changes were also investigated. METHODS: A prospective study was performed in 14 patients with normal pressure hydrocephalus syndrome with a duration of symptoms between 3 months and 12 years. Diagnosis was based on intracranial pressure (ICP) monitoring and CSF dynamics. Concentrations of SOM, NPY, and CRF in lumbar CSF were determined before shunting and again 6-9 months after surgery. A battery of neuropsychological tests and several rating functional scales were also given to patients before and after shunting. RESULTS: After shunting, SOM and CRF concentrations were significantly increased in all patients. Concentrations of NPY were increased in 12 of the 14 patients studied. The clinical condition of 13 of the 14 patients was significantly improved 6 months after surgery. This improvement was more pronounced in gait disturbances and sphincter dysfunction than in cognitive impairment. No significant differences in any of the neuropsychological tests were seen for the group of patients as a whole despite the increased neuropeptide concentrations. CONCLUSIONS: Shunting can restore SOM, NPY, and CRF concentrations even in patients with longstanding normal pressure hydrocephalus. However, despite the biochemical and clinical improvement in some areas such as ambulation and daily life activities, cognitive performance did not significantly improve. The role of neuropeptides in the diagnosis and treatment of patients with normal pressure hydrocephalus syndrome is discussed.