Silvia Vazquez

Neuropsychological, Psychiatric, and Cerebral Blood Flow Findings in Vascular Dementia and Alzheimer’s Disease

BACKGROUND AND PURPOSE Psychiatric, neuropsychological, and cerebral blood flow differences between patients with ischemic vascular dementia (IVD) or Alzheimers disease (AD) were examined. METHODS A consecutive series of patients who met either the criteria of the National Institute of Neurological Disorders and Stroke and the Alzheimers Disease and Related Disorders Association for probable AD or the State of California AD Diagnostic and Treatment Centers criteria for probable IVD were included in the study. Twenty consecutive patients with IVD were matched for age, sex, and Mini-Mental State Examination scores with 40 consecutive patients with probable AD. Patients underwent a psychiatric interview, a neuropsychological assessment, and single-photon emission CT imaging with 99mTc-hexamethylpropyleneamine oxime. RESULTS Patients with IVD showed significantly more severe anosognosia (P<.05) and emotional lability (P<.01) than AD patients, but no significant between-group differences were found in the frequency and severity of depression. IVD patients showed significantly more severe deficits in tests of planning, sequencing (P<.05), and verbal fluency (P<.05) as well as significantly more severe cerebral blood flow deficits in the basal ganglia (P<.01) and the frontal lobes (P<.001) than AD patients. CONCLUSIONS Patients with IVD showed a relatively more severe dysfunction of the frontal lobes as demonstrated by single-photon emission CT and expressed in specific psychiatric and neuropsychological changes than AD patients matched for age, sex, and severity of dementia.

ABC Transporters during Epilepsy and Mechanisms Underlying Multidrug Resistance in Refractory Epilepsy

Summary:  It is estimated 20–25% of the epileptic patients fails to achieve good control with the different antiepileptic drugs (AEDs) treatments, developing refractory epilepsy (RE). Discovered first in cancer, the activity of P‐glycoprotein (P‐gp) and others ABC transporters as multidrug‐resistance‐associated proteins (MRPs) and breast cancer resistant protein (BCRP) are directly related with the refractoriness. We have observed the overexpression of these all transporters in the brain of patients with RE, and according with other authors, all these data suggests an active drug efflux from brain. Both constitutive and seizure induced brain P‐gp overexpression was also suggested. As confirmation of these clinical evidences, different models of experimental epilepsy have demonstrated P‐gp overexpression on blood brain barrier (BBB) and brain parenchyma cells, as astrocytes and neurons. In our model, early P‐pg detection in vessel‐related cells and later additional P‐gp detection in neurons, correlated with the gradual loss of protective effect of phenytoin. The progressive neuronal P‐gp expression, depending on intensity and time‐constancy of seizure‐injury, was in agreement with the development of “P‐gp‐positive seizure‐axis” proposed by Kwan & Brodie, who also showed that the development of RE directly correlated with the number and frequency of seizures before initiation of drug therapy. P‐gp expression in excretory organs suggests that P‐gp have a central role in drug elimination. Persistent low levels of AEDs in plasma and P‐gp brain overexpression in several RE pediatric patients were reported. We also observed in adult RE patients, an increased liver clearance of 99mTc‐hexakis‐2‐methoxyisobutylisonitrile (99mTc‐MIBI) (a P‐gp substrate), and the surgically treated cases showed P‐gp brain overexpression. These results suggest the systemic hyperactivity of P‐gp in RE patients, including brain P‐gp over‐expression should be suspected when persistent subtherapeutic levels of AEDs in plasma are detected. P‐gp neuronal expression described in both clinical and experimental reports indicates that additional mechanisms could be operative from seizure‐affected P‐gp‐positive neurons, due to AEDs targets are expressed at membrane level. An alternative mechanism was demonstrated in P‐gp‐expressed cells that exhibit lower membrane potential (Δψ0=−10 to –20) compared to normal physiological Δψ0 of –60 mV. Under this situation and irrespective to the P‐gp pharmacoresistant property or type of drug treatment selected, P‐gp‐expressed neurons could increase their sensitivity to new seizures perhaps as an epileptogenic mechanism. The understanding of properties of these ABC transporters can offer new tools for better selection of more effective preventive or therapeutic strategies and avoid the invasive surgical treatments for RE.

A SPECT study of delusions in Alzheimer's disease

Although delusions are a frequent finding in patients with Alzheimers disease (AD), their mechanism is not well known. We carried out Tc 99m HMPAO single-photon emission computed tomography studies in 16 AD patients with delusions and 29 AD patients without delusions comparable in age, years of education, duration of illness, and severity of dementia. Although we found no significant between-group differences in performance on neuropsychological tasks, AD patients with delusions had significantly lower mean cerebral blood flow in both the left and right temporal lobes.

Neuropsychological, psychiatric, and cerebral perfusion correlates of leukoaraiosis in Alzheimer’s disease

OBJECTIVE To examine neurological, neuropsychological, psychiatric, and cerebral perfusion correlates of leukoaraiosis in Alzheimer’s disease. METHODS A consecutive series of patients with probable Alzheimer’s disease was assessed with a comprehensive neuropsychological battery, a structured psychiatric evaluation, the unified Parkinson’s disease rating scale, MRI, and single photon emission computed tomography with technetium 99m hexamethylpropylene-amine oxime (HMPAO) and regional cerebral perfusion measurements. RESULTS Patients with Alzheimer’s disease and leukoaraiosis were significantly more apathetic and had significantly more extrapyramidal signs than patients with Alzheimer’s disease without leukoaraiosis. Patients with Alzheimer’s disease with leukoaraiosis also had significantly lower bilateral perfusion in the basal ganglia, thalamus, and frontal lobes than patients with Alzheimer’s disease without leukoaraiosis. On the other hand, there were no significant differences between groups in age, duration of illness, depression scores, severity of delusions, or deficits on specific neuropsychological tasks. CONCLUSIONS Leukoaraiosis in Alzheimer’s disease may produce significant basal ganglia, and thalamic and frontal lobe dysfunction, which may be associated with more severe apathy and extrapyramidal signs.

Changes in Regional Cerebral Blood Flow Beyond the Temporal Lobe in Unilateral Temporal Lobe Epilepsy

Summary: Purpose: Single photon emission computed tomography (SPECT) is widely used to evaluate functional abnormalities during the epileptic event. Changes in regional cerebral blood flow (rCBF) are well defined in patients with temporal lobe epilepsy (TLE) undergoing surgical resection. Nonetheless, the interpretation of ictal abnormalities in CBF beyond the temporal lobes has not been carefully addressed.

SPECT Findings in Mentally Retarded Autistic Individuals

The authors examined specific deficits of cerebral blood perfusion in autistic patients as measured with [(99m)Tc]HMPAO single-photon emission computed tomography (SPECT). The study, conducted in an outpatient clinic setting, included a consecutive series of 30 patients with autism and 14 patients with mental retardation but no autism comparable in chronological age, mental age, height, weight, and head circumference. All participants were examined with a comprehensive psychiatric and neuropsychological battery and received a [(99m)Tc]HMPAO SPECT scan. Autistic patients had significantly lower perfusion than the control group in the following brain regions: right temporal lobe (basal and inferior areas), occipital lobes, thalami, and left basal ganglia. The study demonstrated significant perfusion deficits in specific brain areas of moderately to severely mentally retarded autistic patients.

Creation of the Argentina-Alzheimer's Disease Neuroimaging Initiative

The Alzheimers Disease Neuroimaging Initiative (ADNI) is a multisite, longitudinal study that assesses clinical, imaging, genetic, and biospecimen biomarkers through the process of normal aging to mild cognitive impairment and dementia. We present the creation of the Argentina‐ADNI—the first South American ADNI—and its effort to acquire data comparable with those gathered in other worldwide ADNI centers.

Ictal SPECT in paroxysmal non-kinesigenic dyskinesia. Case report and review of the literature

Purpose: Paroxysmal non-kinesigenic dyskinesia (PNKD) should be included in the list of differential diagnosis in patients with refractory epilepsy. Although the pathophysiological mechanisms that underlie this disorder remain controversial, it is now accepted that the basal ganglia are the anatomical substrate responsible for it.Material and methods: We report a 16-year-old mentally retarded male with PNKD admitted for video-EEG monitoring and ictal SPECT, which showed hyperperfusion on the right caudate and thalamus.Conclusion: This case supports more evidence for the involvement of the caudate nucleus and thalamus in the mechanisms responsible for the production of PNKD.

Sphenoid wing meningioma behavior on 11C-PiB and 18F-FDG PET.

Two patients with mild cognitive impairment underwent C-PiB and F-FDG brain PET. Both patients had previously gone through a contrast-enhanced MRI scan that revealed extra-axial tumors next to the sphenoid wing, suggestive of meningiomas. C-PiB PET images showed a highly increased uptake by the extra-axial masses. These 2 cases represent 1.2% of our C-PiB population (n = 163). No meningioma was found with negative C-PiB uptake. The F-FDG concentration was not increased within the lesions. C-PiB could be used as a meningioma marker.

Predicting episodic memory performance using different biomarkers: results from Argentina-Alzheimer's Disease Neuroimaging Initiative.

Purpose Argentina-Alzheimer’s Disease Neuroimaging Initiative (Arg-ADNI) is the first ADNI study to be performed in Latin America at a medical center with the appropriate infrastructure. Our objective was to describe baseline characteristics and to examine whether biomarkers related to Alzheimer’s disease (AD) physiopathology were associated with worse memory performance. Patients and methods Fifteen controls and 28 mild cognitive impairment and 13 AD dementia subjects were included. For Arg-ADNI, all biomarker parameters and neuropsychological tests of ADNI-II were adopted. Results of positron emission tomography (PET) with fluorodeoxyglucose and 11C-Pittsburgh compound-B (PIB-PET) were available from all participants. Cerebrospinal fluid biomarker results were available from 39 subjects. Results A total of 56 participants were included and underwent baseline evaluation. The three groups were similar with respect to years of education and sex, and they differed in age (F=5.10, P=0.01). Mean scores for the baseline measurements of the neuropsychological evaluation differed significantly among the three groups at P<0.001, showing a continuum in their neuropsychological performance. No significant correlations were found between the principal measures (long-delay recall, C-Pittsburgh compound-B scan, left hippocampal volume, and APOEε4) and either age, sex, or education (P>0.1). Baseline amyloid deposition and left hippocampal volume separated the three diagnostic groups and correlated with the memory performance (P<0.001). Conclusion Cross-sectional analysis of baseline data revealed links between cognition, structural changes, and biomarkers. Follow-up of a larger and more representative cohort, particularly analyzing cerebrospinal fluid and brain biomarkers, will allow better characterization of AD in our country.