Giovanni Grillea

Ischaemic stroke following tranexamic acid in young patients carrying heterozygosity of MTHFR C677T

The objective of this study is to report a new manifestation of acute stroke following antifibrinolytic agent administration in young women carrying heterozygosity for methylene-tetrahydrofolate reductase (MTHFR) C677T. The study included two young women who developed an acute ischaemic stroke following three days of tranexamic acid administration for bleeding gynaecological disorders. Case 1, a 44-year-old woman, presented left hemiplegia, mild dysarthria and anosognosia. Brain magnetic resonance imaging showed right ischaemic fronto-temporal lesion due to subocclusion of the right middle cerebral artery. Case 2, a 49-year-old woman, developed aphasia and right hemiplegia. Neuroimaging showed left capsular and periventricular infarcts due to near occlusion of the left internal carotid artery. Thrombophilia screening, coagulation parameters, homocysteine testing, 12-lead electrocardiography, and transthoracic and transoesophageal echocardiography were unremarkable. Genetic assay showed that both patients carried heterozygosity for MTHFR C677T, in which cytosine (C) is replaced by thymidine (T) at base position 677. To our knowledge, this is the first report describing the association between genetic factors and the onset of stroke following antifibrinolytic drugs intake. These data suggest a synergic effect of plasminogen activator inhibitor and heterozygosity for MTHFR C677T on the pathogenetic mechanisms leading to ischaemic stroke in young people.

In vitro and in vivo effect of human lactoferrin on glioblastoma growth

OBJECT Human lactoferrin (HLF) is a natural protein with antitumor activity. The aim of this study was to investigate the effects of HLF alone and in combination with temozolomide (TMZ), a conventional chemotherapeutic, on human glioblastoma (GBM) cells. METHODS The authors cultured fresh human primary cell lines NMD and FN and the continuous cell line U87MG to evaluate proliferation in the presence of HLF alone at different doses (1, 10, and 100 mg/ml, and 1 mg/ml) and in combination with TMZ. In in vivo experiments they assessed tumor size reduction in CD1 nude mice carrying an orthotopic GBM xenograft and orally treated with HLF. RESULTS Lactoferrin causes growth inhibition in the NMD and FN primary cell lines and in the U87MG continuous cell line. This inhibition seemed to be modulated by the downregulation of cyclin D1 and D4. Western blot and fluorescence-activated cell sorting analysis showed inhibition of the cell cycle in G0/G1 and G2 phases. When administered in nude mice, HLF (60 mg/kg/day) decreased tumor size about 30%, as shown in both histological analyses and high-field brain MRI. Administration of HLF with TMZ enhanced the effect of chemotherapy both in vitro and in vivo. CONCLUSIONS This study demonstrated that HLF can inhibit GBM cell growth, suggesting that this nontoxic substance may have a role in potentiating the effect of current TMZ treatment of GBM.

Lhermitte-Duclos disease presenting with positron emission tomography-magnetic resonance fusion imaging: a case report

IntroductionLhermitte-Duclos disease or dysplastic gangliocytoma of the cerebellum is an extremely rare tumor. It is a slowly enlarging mass within the cerebellar cortex. The majority of cases are diagnosed in the third or fourth decade of life.Case presentationWe report the case of a 37-year-old Caucasian woman who underwent positron emission tomography-computed tomography with fluorine-18-fluorodeoxyglucose for evaluation of a solitary lung node. No pathological uptake was detected in the solitary lung node but the positron emission tomography-computed tomography of her brain showed intense tracer uptake, suggestive of a malignant neoplasm, in a mass in her left cerebellar lobe. Our patient had experienced two years of occipital headache and movement disorder. Subsequently, magnetic resonance imaging was performed with contrast agent administration, showing a large subtentorial mass in her left cerebellar hemisphere, with compression and dislocation of the fourth ventricle. Metabolic data provided by positron emission tomography and morphological magnetic resonance imaging views were fused in post-processing, allowing a diagnosis of dysplastic gangliocytoma with increased glucose metabolism. Total resection of the tumor was performed and histological examination confirmed the diagnosis of Lhermitte-Duclos disease.ConclusionsOur case indicates that increased uptake of fluorine-18-fluorodeoxyglucose may be misinterpreted as a neoplastic process in the evaluation of patients with Lhermitte-Duclos disease, but supports the usefulness of integrated positron emission tomography-magnetic resonance imaging in the exact pathophysiologic explanation of this disease and in making the correct diagnosis. However, an accurate physical examination and exact knowledge of clinical data is of the utmost importance.

Diffusion tensor imaging applications in multiple sclerosis patients using 3T magnetic resonance: a preliminary study

ObjectivesThis study evaluated patients with multiple sclerosis using diffusion tensor imaging (DTI) to obtain fractional anisotropy (FA) and mean diffusivity (MD) values.MethodsWe investigated the possible statistically significant variation of MD and FA in different MS patients, compared simultaneously, putting in comparison their normal appearing white matter (NAWM) and white matter affected by disease (plaques), both during activity and in remission, with normal white matter (NWM) of control subjects.ResultsStatistical analysis using Levene’s test for comparison of variances revealed significant (P < 0.05) differences between FA values of the NWM of the controls and those of NAWM and active or inactive lesions, of the patients in the study. However, the differences between MD values of the NWM of the controls and those of NAWM and active or inactive lesions of the patients in the study were judged not significant (P > 0.05).ConclusionImaging of MS using MRI techniques is constantly searching for reproducible quantitative parameter. This study shows how these parameters can be identified in the MD and FA values, and thus suggests the implementation of MRI routine protocols for diagnosing MS with the DTI analysis, since it can provide valuable information otherwise unobtainable.Key PointsMagnetic resonance imaging is widely performed in multiple sclerosis (MS) patientsDiffusion tensor imaging (DTI) can be implemented using a 3T magnetDTI provides quantitative parameters as mean diffusivity (MD) and fractional anisotropy (FA)MD and, especially, FA can help evaluate the lesion load in MS patients and also assess variation in normal appearing white matter (NAWM) in MS

Hybrid Y Stenting with the Waffle-Cone A Technical Note

Endovascular treatment of wide-neck bifurcation aneurysms is challenging and often requires adjunctive techniques and devices. We report our experience with the hybrid Y stenting with the waffle-cone technique, combining Y stent-assisted coiling and waffle-cone stenting techniques. This approach has been described only in a single case report using a combination of open and closed cell stents. We describe four cases treated by hybrid Y stenting with the waffle-cone procedure with a variation from the originally reported technique, consisting in deploying two closed cell stents. All patients were successfully treated without complications. We propose hybrid Y stenting with the waffle-cone for the treatment of wide-neck bifurcation aneurysms as a bailout technique after failure of Y stent-assisted coiling.

Third-generation percutaneous vertebral augmentation systems

Currently, there is no general consensus about the management of osteoporotic vertebral fractures (OVF). In the past, conservative treatment for at least one month was deemed appropriate for the majority of vertebral fractures. When pain persisted after conservative treatment, it was necessary to consider surgical interventions including: vertebroplasty for vertebral fractures with less than 30% loss of height of the affected vertebral body and kyphoplasty for vertebral fractures with greater than 30% loss of height. Currently, this type of treatment is not feasible. Herein we review the characteristics and methods of operation of three of the most common percutaneous vertebral augmentation systems (PVAS) for the treatment of OVF: Vertebral Body Stenting(®) (VBS), OsseoFix(®) and Spine Jack(®). VBS is a titanium device accompanied by a hydraulic (as opposed to mechanical) working system which allows a partial and not immediate possibility to control the opening of the device. On the other hand, OsseoFix(®) and Spine Jack(®) are accompanied by a mechanical working system which allows a progressive and controlled reduction of the vertebral fracture. Another important aspect to consider is the vertebral body height recovery. OsseoFix(®) has an indirect mechanism of action: the compaction of the trabecular bone causes an increase in the vertebral body height. Unlike the Vertebral Body Stenting(®) and Spine Jack(®), the OsseoFix(®) has no direct lift mechanism. Therefore, for these characteristics and for the force that this device is able to provide. In our opinion, Spine Jack(®) is the only device also suitable for the treatment OVF, traumatic fracture (recent, old or inveterate) and primary or secondary bone tumors.

Molecular imaging of brain tumors with radiolabeled choline PET.

Several positron emission tomography (PET) radiopharmaceuticals have been emerged in the last decade as feasible in the management of brain lesions, due to the low performance in this field of the 18F-fluoro-deoxyglucose (18F-FDG), for its high physiological gradient of distribution in the brain. Beyond its usefulness in prostate cancer imaging, the radiolabeled choline is becoming a promising tool in diagnosing benign and malignant lesions of the brain, due to a very low rate of distribution in normal white and grey matters. The aim of our review was to assess the real impact of the radiolabeled choline PET/CT in the management of brain benign lesions, brain tumors, and metastases. Furthermore, emphasis was given to the comparison between the radiolabeled choline and the other radiopharmaceuticals in this field. A literature review was performed. The radiolabeled choline is useful in the management of patients with suspected brain tumor relapse, especially in association with magnetic resonance imaging (MRI), with caution regarding its intrinsic characteristic of non-tumor-specific tracer. For the same reason, it is not useful in the early evaluation of brain lesions. Similar results are reported for other radiopharmaceuticals. The inclusion of the head in the whole-body scans for somatic tumors is necessary to ensure metastases in the brain or choline-avid benign lesions.

Freezing of gait in Parkinson’s disease: gray and white matter abnormalities

Freezing of gait (FOG) is a disabling disorder that often affects Parkinson’s disease (PD) patients in advanced stages of the disease. To study structural gray matter (GM) and white matter (WM) changes in PD patients with and without FOG, twenty-one PD patients with FOG (PD-FOG), 16 PD patients without FOG (PD-nFOG) and 19 healthy subjects (HS) underwent a standardized MRI protocol. For the gray matter evaluation, cortical volume (CV), cortical thickness (CTh), and surface area (SA) were analyzed using the FreeSurfer pipeline. For the white matter evaluation, DTI images were analyzed using tracts constrained by underlying anatomy (TRACULA) toolbox in FreeSurfer. PD-FOG patients exhibited lower CTh than HS in the mesial surface of both cerebral hemispheres, including the superior frontal gyrus, paracentral lobule, posterior cingulate cortex, precuneus and pericalcarine cortex, and in the right dorsolateral prefrontal cortex. Moreover, significant WM changes were observed in PD-FOG patients in comparison with HS in the superior longitudinal fasciculus, uncinate fasciculus, cingulum cingulate gyrus and inferior longitudinal fasciculus (prevalently in the right hemisphere) and in the frontal radiations of the corpus callosum. DTI abnormalities in specific WM bundles correlated significantly with cognitive measures. The damage of multiple cortical areas involved in high-level gait control together with WM disruption between motor, cognitive and limbic structures may represent the anatomical correlate of FOG.

Scintigraphic, neuroradiological and clinical comparison in two patients with primary sporadic and two with secondary Fahr’s disease

Bilateral striopallidodentate calcification, usually termed Fahr’s disease, can give rise to various clinical manifestations including hyperkinetic movement disorders or a hypokinetic Parkinsonian syndrome, behavioural and mood changes, cognitive deficits and even frank dementia. We describe four patients all of whom underwent a detailed scintigraphic, neuroradiological and clinical work-up: two had primary, sporadic Fahr’s disease and two had Fahr’s disease secondary to hypoparathyroidism. The neuroradiological and clinical studies disclosed similar anatomical and pathological changes in the four patients but variable and sometimes unexpected clinical manifestations. Both patients with primary forms had hypokinetic Parkinsonian syndrome, both patients with secondary forms had hyperkinetic movements. Dopamine autotransporter scan brain scintigraphy disclosed an unexpected unilateral putamen involvement despite substantially symmetric calcifications.

Brain MRI fiber-tracking reveals white matter alterations in hypertensive patients without damage at conventional neuroimaging

Aims Hypertension is one of the main risk factor for dementia. The subtle damage provoked by chronic high blood pressure in the brain is usually evidenced by conventional magnetic resonance imaging (MRI), in terms of white matter (WM) hyperintensities or cerebral atrophy. However, it is clear that by the time brain damage is visible, it may be too late hampering neurodegeneration. Aim of this study was to characterize a signature of early brain damage induced by hypertension, before the neurodegenerative injury manifests. Methods and results This work was conducted on hypertensive and normotensive subjects with no sign of structural damage at conventional neuroimaging and no diagnosis of dementia revealed by neuropsychological assessment. All individuals underwent cardiological clinical examination in order to define the hypertensive status and the related target organ damage. Additionally, patients were subjected to DTI-MRI scan to identify microstructural damage of WM by probabilistic fiber-tracking. To gain insights in the neurocognitive profile of patients a specific battery of tests was administered. As primary outcome of the study we aimed at finding any specific signature of fiber-tracts alterations in hypertensive patients, associated with an impairment of the related cognitive functions. Hypertensive patients showed significant alterations in three specific WM fiber-tracts: the anterior thalamic radiation, the superior longitudinal fasciculus and the forceps minor. Hypertensive patients also scored significantly worse in the cognitive domains ascribable to brain regions connected through those WM fiber-tracts, showing decreased performances in executive functions, processing speed, memory, and paired associative learning tasks. Conclusions Overall, WM fiber-tracking on MRI evidenced an early signature of damage in hypertensive patients when otherwise undetectable by conventional neuroimaging. In perspective, this approach could allow identifying those patients that are in initial stages of brain damage and could benefit of therapies aimed at limiting the transition to dementia and neurodegeneration.