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We report a case of a patient aged 66 years, with spontaneous intracranial hypotension presenting initially with postural headache, complicated by subdural haematomas and followed by progressive decline of his clinical condition evolving in obtundation state, cranial nerve involvement and gaze paralysis. The patient underwent a long course of different therapeutical approaches: medical and surgical treatment, intrathecal saline infusion and epidural blood patching (EBP). Rapid and dramatic relief of the patient’s symptoms was obtained after a third lumbar EBP and he was discharged asymptomatic two weeks later.

The association of decreased cerebral blood flow with the development of Alzheimer's disease (AD) has been a recent target of interest. By using neuroimaging techniques, growing attention has been devoted to the identification of preclinical AD. In this study, color duplex sonography of cervical arteries was used to measure mean cerebral blood flow (CBF) on 55 amnestic Mild Cognitive Impairment (MCI) patients. Two years after enrollment, excluding patients who progressed to dementia other than AD, two subgroups were identified, patients who developed AD (MCI converters) and patients with preserved cognitive and functional level (MCI non-converters). Examining the mean difference of CBF measured at baseline in the two subgroups obtained, a significant difference was noticed (MCI converters 539.3 +/- 114.3 vs MCI non converters 636.0 +/- 143.9, p0.05). MCI patients with CBF higher than median value (558 ml/min) had lower risk of developing AD (specificity 72.2%, sensitivity 68.4%) within a two year follow-up. Ultrasonography of the cervical arteries is a simple, non invasive and widespread technique useful in detecting CBF decline during the MCI stage, thus identifying patients who later will convert to AD.

Transient Global Amnesia (TGA) is a common condition of unknown aetiology characterised by the abrupt onset of severe anterograde amnesia, which lasts less than 24 hours. Some authors have suggested that subclinical impairment of memory functions may persist for much longer, but neuropsychological assessment lasting years after TGA attack has not been performed so far. The aim of this study was to evaluate longterm cognitive functions in patients with a previous TGA episode. Fifty-five patients underwent a standardised neuropsychological assessment after at least one-year from the TGA attack, and were compared with 80 age-matched controls. TGA patients showed worse performances on tests evaluating verbal and nonverbal long-term memory and attention, with comparable global cognitive functions. By applying current criteria for amnestic Mild Cognitive Impairment (MCI-a) on TGA subjects, a group consisting of 18/55 (32.7%) MCI-a subjects was identified. There was no association between the presence of MCI-a and demographic variables, vascular risk factors, years since the TGA episode, or ApoE genotype. This study demonstrates that TGA appears to be a relatively benign syndrome although objective memory deficits fulfilling MCI-a criteria persist over time, as detected by multidimensional neuropsychological tasks performed at long-term follow-up.

There is emerging evidence that psychosis in Alzheimer Disease (AD) represents a clinically relevant phenotype with a distinct biological process. It has been reported that a functional polymorphism of the catechol-O-methyltransferase (COMT) gene predisposes to an increased risk for schizophrenia and likely to psychosis susceptibility. Aim of this study was to evaluate functional COMT genetic variation as a risk factor for psychosis in Alzheimer Disease. One hundred eighty-one AD patients and 208 age-matched controls underwent clinical and neuropsychological examination, behavioural and psychiatric disturbances evaluation, and ApoE and COMT genotyping. The distribution of COMT genotypes did not significantly differ in AD compared to controls. Among patients with psychosis (32.6%), 88.1% were COMT*H carriers (COMT H/H or COMT H/L, p.01). The Odds Ratio (OR) for risk of psychosis in COMT*H carriers was 2.66 (confidence interval, CI 95%: 1.6-6.62), taking into account possible confounding factors. A comparable influence of COMT polymorphism on psychosis over the course of the disease was reported. These findings suggest that COMT polymorphism influences on the risk of psychosis since the early stages, and claims for the possibility to identify distinct phenotypes on genetic basis among AD patients.

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.

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.

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

Huntington9s disease (HD), MIM 143100, is a dominantly inherited progressive neurodegenerative disorder characterised by motor, behavioural and cognitive dysfunction, caused by an expanded CAG repeat region in exon 1 of the HTT gene. This mutation results in the presence of an abnormally long polyglutamine tract in the encoded protein, huntingtin. Research into this disorder has conventionally focused on neurological symptoms and brain pathology, particularly neurodegeneration in the basal ganglia and cerebral cortex. Mutant huntingtin is, however, ubiquitously expressed throughout the body. Contrary to earlier thinking, HD is also associated with abnormalities in peripheral tissues. Due to obvious problems in obtaining brain tissue, these peripheral tissues can be studied to elucidate pathogenetic mechanism (still not well understood) of the disease as well as identifying disease biomarkers. Peripheral tissue dermal fibroblasts, which have the same ectodermal origin as CNS cells, may represent an alternative source for biological studies. Furthermore, contrary to peripheral blood cells, this cell type is not directly exposed to drugs. We performed gene expression profile analysis of human fibroblasts obtained from HD patients and healthy controls matched by age and sex. The study was performed using the whole genome Affymetrix HG U133 plus 2.0 arrays. Preliminary data obtained indicate that 451 genes are upregulated twofold or greater in patients compared with controls while 17 are downregulated. This study allowed us to evidence the modulation at the transcriptional level of a discrete number of genes relevant in biological processes which are altered in the disease—processes such as transcription and its regulation, apoptosis, regulation of actin cytoskeleton, inositol phosphate metabolism and vesicle mediated transport. We plan to extend this type of analysis to a larger number of cases and controls and to confirm the differential expression of interesting genes both at the RNA and protein levels. The data generated by this study could provide novel clues on the Huntington pathogenesis and lead to the identification of a set of mRNAs that appear to be useful as biomarkers of the disease.

Context: Patients affected by sporadic Alzheimer disease (AD) show a significant alteration of amyloid precursor protein (APP) forms in platelets when compared with patients with dementia but without AD and agematched controls. Objective: To evaluate the ratio of platelet APP forms (APPr) in early-stage AD and mild cognitive impairment (MCI) and its potential as a biomarker for the early identification of AD. Setting: Community population-based sample of patients admitted to 4 AD centers for investigation of cognitive disturbances. Design and Methods: Thirty-five patients with mild AD (mAD), 21 patients with very mild AD (vmAD), 30 subjects with MCI, and 25 age-matched controls were included. The APPr was evaluated by Western blot analysis in platelet homogenate. Results: Compared with controls (mean±SD, 0.93±0.3), the mean APPr was decreased in patients with mAD (0.44±0.24; P.001) and patients with vmAD (0.49±0.3; P.001). Regarding the MCI group, a significant decrease in APPr was found compared with controls (0.62±0.33; P.001). Fixing a cutoff score of 0.6, sensitivity was 88.6% (31/35) for patients with mAD and 85.7% (18/21) for patients with vmAD, whereas specificity was 88% (22/25) for controls. Among patients with MCI, 18 (60%) of 30 individuals displayed APPr values below the cutoff. Conclusions: Alteration of platelet APP forms is an early event in AD, and the measurement of APPr may be useful for the identification of preclinical AD in patients with MCI.

Background It has been recently demonstrated that in Frontotemporal Lobar Degeneration (FTLD) memory deficits at presentation are commoner than previously thought. Apolipoprotein E (ApoE) genotype, the major genetic risk factor in sporadic late-onset Alzheimer Disease (AD), modulates cerebral perfusion in late middle-age cognitively normal subjects. ApoE ε4 homozygous have reduced glucose metabolism in the same regions involved in AD. The aim of this study was to determine whether ApoE genotype might play a key-role in influencing the cerebral functional pattern as well as the degree of memory deficits in FTLD patients. Methods Fifty-two unrelated FTLD patients entered the study and underwent a somatic and neurological evaluation, laboratory examinations, a brain structural imaging study, and a brain functional Single Photon Emission Tomography study. ApoE genotype was determined. Results ApoE genotype influenced both clinical and functional features in FTLD. ApoE ε4-carriers were more impaired in long-term memory function (ApoE ε4 vs. ApoE non ε4, 6.3 ± 3.9 vs. 10.1 ± 4.2, p = 0.004) and more hypoperfused in uncus and parahippocampal regions (x,y,z = 38,-6,-20, T = 2.82, cluster size = 100 voxels; -32,-12,-28, T= 2.77, cluster size = 40 voxels). Conclusion The present findings support the view that ApoE genotype might be considered a disease-modifying factor in FTLD, thus contributing to define a specific clinical presentation, and might be of relevance for pharmacological approaches.