Luigi A. Vignolo

Inherited Thrombophilic Disorders in Young Adults With Ischemic Stroke and Patent Foramen Ovale

Background and Purpose— The pathogenic link between patent foramen ovale (PFO) and stroke remains unknown in most cases. We investigated the association between inherited thrombophilic disorders and PFO-related strokes in a series of young adults in the setting of a case-control study. Methods— We investigated 125 consecutive subjects (age, 34.7±7.3 years) with ischemic stroke and 149 age- and sex-matched control subjects. PFO was assessed in all patients with transcranial Doppler sonography with intravenous injection of agitated saline according to a standardized protocol. Genetic analyses for the factor V (FV)G1691A mutation, the prothrombin (PT)G20210A variant, and the TT 677 genotype of methylenetetrahydrofolate reductase (MTHFR) were performed in all subjects. Results— A pathogenic role of PFO was presumed in 36 patients (PFO+). Interatrial right-to-left shunt either was not detected or was considered unrelated to stroke occurrence in the remaining 89 patients (PFO−). The PTG20210A variant was more frequent in the PFO+ group compared with control subjects and the PFO− group (PFO+ versus control subjects, 11% versus 2%; 95% CI, 0.04 to 0.94; PFO+ versus PFO−, 11% versus 1.1%; 95% CI, 1.09 to 109;P =0.047). A similar distribution was observed for subjects carrying either the PTG20210A variant or the FVG1691A mutation (PFO+ versus control subjects, 19.4% versus 5.3%; 95% CI, 0.08 to 0.75; PFO+ versus PFO−, 19.4% versus 3.3%; 95% CI, 1.45 to 26.1;P =0.021). Combined thrombophilic defects were observed in 3 subjects of the PFO+ group, in 2 control subjects (8.3% versus 1.3%; 95% CI, 0.01 to 0.66;P =0.015), and in 0 subjects in the PFO− group. A trend toward a difference in the frequency of the FVG1691A mutation between PFO+ and control subjects was found after bivariate analysis (11% versus 3.3%;P =0.068) but not after multinomial logistic regression analysis. No significant association was found in the distribution of the TT MTHFR genotype in the 3 groups. Conclusions— In young adults, the PTG20210A variant and, to a lesser extent, the FVG1691A mutation may represent risk factors for PFO-related cerebral infarcts. A role of systemic thrombophilic disorders in the pathogenesis of this specific subtype of stroke may be hypothesized.

Combined 99mTc-ECD SPECT and neuropsychological studies in MCI for the assessment of conversion to AD

Identifying pre-clinical Alzheimers disease (AD) in subjects with mild cognitive impairment (MCI) is a major issue in clinical diagnosis. Establishing a combination of predictive markers from different fields of research might help in increasing the diagnostic accuracy. Aim of this study was to evaluate the potential role of 99mTc-ECD single photon emission computed tomography (SPECT) and memory scores in predicting conversion to AD in MCI subjects. Thirty-one MCI subjects underwent a clinical and neuropsychological examination, and a regional cerebral blood flow (rCBF) SPECT scan at baseline. Subjects had been followed periodically through 2 years in order to monitor the progression of cognitive symptoms. Canonical variate analysis of principal components was able to separate all subjects who converted to AD from those who remained stable, the former being characterized by a specific hypometabolic pattern, involving the parietal and temporal lobes, precuneus, and posterior cingulate cortex. Canonical correlation analysis of combined baseline memory deficits and rCBF SPECT images identified pre-clinical AD with a sensitivity and specificity of 77.8%. The pattern of hypoperfusion 99mTc-ECD SPECT and the severity of memory deficits predict the risk of progression to probable AD dementia in MCI subjects.

Prevalence and pattern of cognitive impairment in systemic lupus erythematosus patients with and without overt neuropsychiatric manifestations

The prevalence and pattern of cognitive impairment in systemic lupus erythematosus (SLE) patients with (NPSLE) and without (nSLE) overt neuropsychiatric manifestations were investigated. Fifty-two nSLE patients, 23 NPSLE patients and 27 healthy controls were evaluated with a battery of standardized neuropsychological and psychological tests. Disease duration, disease activity index, and current corticosteroid therapy were collected. Cognitive impairment was identified in 14 (26.9%) and in 12 (52.2%) of subjects with nSLE and NPSLE, respectively. Both SLE groups showed a significant impairment compared with controls on tasks assessing verbal and non-verbal long-term memory, and visuoconstructional abilities. In addition, NPSLE patients reported worse performances than both nSLE patients and controls on task evaluating short-term visuospatial memory. NPSLE subjects were significantly more anxious and depressed compared to both nSLE subjects and controls. By multivariate analysis, only depression levels, among clinical variables, significantly predicted cognitive performance. This study shows that cognitive impairment occurs frequently in both nSLE and NPSLE subjects. The higher frequency in NPSLE may be related to coexisting depressive disturbances.

Transient Global Amnesia: A Clinical and Sonographic Study

Background: The aetiology of transient global amnesia (TGA) is still unknown. The aim of this study was to identify potential risk factors for TGA, vascular risk factors, the role of patent foramen ovale (PFO) and of retrograde jugular venous flow. Methods: 138 subjects entered the study, including 48 patients with TGA, 42 age-matched patients with transient ischaemic attack (TIA) and 48 controls. PFO was studied by contrast transcranial duplex sonography. Retrograde jugular venous flow was tested with air contrast ultrasound venography (ACUV). Results: TGA patients and controls showed a lower prevalence for vascular risk factors than TIA patients. No statistical difference was found between the 3 groups with regard to PFO. ACUV detected jugular valve incompetence in 72.9% TGA, 35.7% TIA and 39.5% controls (TGA vs. TIA and TGA vs. controls p < 0.01). Conclusions: TGA patients have fewer vascular risk factors than TIA patients. Paradoxical embolism due to PFO as a cause of TGA is not confirmed in our study. Cerebral venous hypertension due to incompetence of the internal jugular valve may play a role in the pathogenesis of TGA.

Unexpected CT-scan findings in global aphasia.

The clinical-CT scan correlation was studied in 37 stroke patients with global aphasia. The time between stroke and language examination was between 21 and 60 days; the time between stroke and CT scan was equal to or longer than 21 days. It was found that while 22 patients harboured the expected large lesions including Brocas and Wernickes areas, 8 had anterior lesions sparing Wernickes area, 3 had posterior lesions sparing Brocas area, and 4 had deep lesions centered on the insula and lenticular nucleus. These findings suggest that global aphasia, albeit apparently simple from the semeiological viewpoint (also due to its severity), does in fact include different clinical entities. However, no clear-cut correlation was found between either subtype of speech production or severity, and locus of the lesion (except that deep lesions were associated with somewhat milder forms). An interesting finding, i.e. that all 8 patients with anterior lesions were females, while the 3 posterior ones were male, is briefly discussed in terms of possible differential organization of language functions in the two sexes.

Adult crossed aphasia in dextrals revisited.

The clinical study of crossed aphasia in dextrals (CAD) may shed light on the discreteness and modularity of several cognitive functions, such as language, gestures and visual spatial abilities, with respect to hemispheric lateralisation. Since 1975 over 180 cases have been described, employing, however, different criteria of assessment and classification. The purpose of this paper is to review them and to propose a set of diagnostic criteria that may be useful to single out a series of reliable CAD cases on which research can be safely carried out. A detailed analysis of such series is dealt with in terms of a number of characteristics concerning both the language disorder and the associated nonverbal cognitive impairments.

Jugular Valve Incompetence A Study Using Air Contrast Ultrasonography on a General Population

Objective. Internal jugular valves are the only venous valves between the heart and the brain. Conditions such as coughing and other precipitating activities may result in retrograde cerebral venous flow because of the absence or presence of internal jugular valve incompetence, allowing brief transmission of high venous pressure and resulting in brain disturbance. Knowledge of these valves and their noninvasive evaluation might be useful in clinical practice. Methods. We applied air contrast ultrasonographic venography to a large sample of healthy subjects (n = 125) to evaluate the ultrasonographic aspects of internal jugular valves and their competence. Results. The valves were observed in 121 (96.8%) of 125 subjects and were present bilaterally in 107 (85.6%) and unilaterally in 14 (11.2%). In 4 subjects we did not detect the valves. Retrograde venous flow was present in 48 (38.4%) of 125 subjects. The frequency of internal jugular valve incompetence was significantly higher on the right side (36 [30.2%] of 119) than on the left (7 [6.4%] of 109; P < .0001). Retrograde venous flow due to incompetence of jugular valves was significantly more frequent at older ages (<50 years, 20%; and ≥50 years, 38.75%; P < .03) and was more frequent in men (33 [25%] of 132) than in women (10 [10.41%] of 96; P < .02). Conclusions. Air contrast ultrasonographic venography is a noninvasive method for evaluating internal jugular valves and identifying retrograde venous flow. This information may be useful in clinical and interventional care.

Music Agnosia and Auditory Agnosia

Abstract: A review and an experimantal study were carried out in search of dissociations between the recognition of music (music agnosia) and that of environmental sounds (auditory agnosia) in stroke patients. The review focused on 45 adequately studied cases published since 1883. The experimental study consisted of administering standard tests of music and environmental sound recognition to 40 unselected patients with unilateral stroke. Among case reports, music was selectively impaired more frequently than environmental sounds, whereas the reverse occurred in the experimantal study. In this, right hemisphere lesions tended either to disrupt the apperception of environmental sounds, sparing music entirely, or to disrupt both environmental sounds and melody, sparing rhythm, whereas left hemisphere lesions tended to spare melody and to disrupt rhythm, either selectively or in association with the semantic identification of environmental sounds.

The many faces of crossed aphasia in dextrals: report of nine cases and review of the literature.

A substantial body of the aphasia literature has been devoted to the topic of crossed aphasia in dextrals (CAD) over the past century but still no theory exists that explains the anomalous organization of neurocognitive functions in this population. However, if strict selection criteria are applied only some cases of vascular CAD are reported in which the correlation between neurocognitive disturbances and the locus of the brain lesion is studied. This study describes nine new cases of vascular CAD who underwent in‐depth neurolinguistic and neuropsychological investigations. Our analysis shows the semiological variability of CAD phenomena and the many faces of the lesion‐behaviour relationships of this exceptional neurobiological condition.

Volume Reduction in Cerebral Blood Flow in Patients with Alzheimer’s Disease: A Sonographic Study

Neuroimaging techniques such as PET and SPECT demonstrated a consistent reduction of cerebral blood flow (CBF) in Alzheimer’s disease (AD). The aim of the study was to assess the potential role of ultrasonography for CBF measurement in AD patients and whether the CBF volume correlates positively with disease severity. Fifty patients who met the diagnostic criteria of probable AD (NINDS-ADRDA) were compared to 50 age-matched healthy elderly volunteers. The extracranial internal carotid arteries (ICAs) and the vertebral arteries (VAs) of the patients and controls were examined. Angle-corrected time-averaged flow velocity (TAV) and the diameter of the vessel were measured. Intravascular flow volumes were calculated as the product of TAV and the cross-sectional area of the circular vessel. CBF volume was calculated as the sum of flow volumes in the ICAs and VAs of both sides. All subjects underwent the MMSE. The mean global CBF (474.87 ± 94.085 vs. 744.26 ± 94.082 ml/min; p < 0.0001) was lower in AD patients than in healthy volunteers. A significant decline in global flow volumes (r = 0.48; p < 0.0007) with the degree of cognitive impairment was also present. The ability of ultrasonography to characterize flow decreases makes such a technique an attractive tool for the study of AD, for the evaluation of pharmacological therapies and, possibly, for early diagnosis.