Lorenzo Ugga

Mid-term and long-term follow-up of intracranial aneurysms treated by the p64 Flow Modulation Device: a multicenter experience

Background Experience with the endovascular treatment of cerebral aneurysms using the p64 Flow Modulation Device is still limited. This study discusses the results and complications of this new flow diverter device. Methods 40 patients (30 women, 10 men) with 50 cerebral aneurysms treated in six Italian neurointerventional centers with the p64 Flow Modulation Device between April 2013 and September 2015 were retrospectively reviewed. Results Complete occlusion was obtained in 44/50 aneurysms (88%) and partial occlusion in 3 (6%). In the other three aneurysms (6%), two cases of asymptomatic in-stent thrombosis and one intraprocedural occlusion of the parent vessel occurred. Technical complications were observed in eight procedures (16%). Permanent morbidity due to acute in-stent thrombosis and consequent ischemic stroke occurred in one patient (2.5%). No delayed aneurysm rupture, subarachnoid or intraparenchymal hemorrhage, or ischemic complications occurred and there were no deaths. Conclusions Endovascular treatment with the p64 Flow Modulation Device is a safe treatment for unruptured cerebral aneurysms, resulting in a high rate of occlusion. As with other flow diverter devices, we recommend this treatment mainly for large-necked aneurysms of the internal carotid artery siphon. However, endovascular treatment with the p64 device should also be encouraged in difficult cases such as aneurysms of the posterior circulation and beyond the circle of Willis.

Alterations of functional connectivity of the motor cortex in Fabry disease An RS-fMRI study

Objective: To evaluate the presence of functional connectivity (FC) alterations of the motor circuits in patients with Fabry disease (FD) and their possible correlation with clinical variables with a resting-state (RS) fMRI analysis. Methods: In our cross-sectional study, 32 patients with FD with genetically confirmed classic diagnosis of FD (12 men, mean age 43.3 ± 12.2 years) were enrolled along with 35 healthy controls (HCs) of comparable age and sex (14 men, mean age 42.1 ± 14.5 years). RS-fMRI data were analyzed with a seed-based approach, with 2 different seeds for right and left motor cortex. Patients with FD underwent a clinical examination for the assessment of different motor functions. Correlations with clinical variables were probed with the Spearman correlation coefficient. Results: A reduction of FC was found in patients with FD compared to HCs between both motor cortices and 2 clusters encompassing, for each side, the caudate and lenticular nucleus (p < 5 × 10−4 and p < 10−8 for right and left motor cortex, respectively) and between the left motor cortex and dentate nuclei (p = 0.01) and Crus 1 in the right cerebellar hemisphere (p = 0.001). No significant results emerged in tests for possible correlations of FC with clinical scores. Conclusions: An alteration of the corticostriatal pathway is present in FD, in line with the recently suggested subclinical involvement of motor circuits in this disease. These results shed new light on the pattern of cerebral involvement in FD.

White matter changes and the development of motor phenotypes in de novo Parkinson's Disease

BACKGROUND Parkinsons Disease (PD) patients are usually divided into Tremor Dominant (TD) and Postural Instability/Gait Difficulty (PIGD) subtypes. The latter is characterized by axial motor symptoms and worse outcomes, possibly also because of comorbid white matter disease. Therefore, the current study investigated the importance of Age-Related White Matter Changes (ARWMCs) in the development of different PD motor phenotypes. METHODS The present 4-year longitudinal study recruited 63 de novo PD patients, who underwent MRI at the time of the diagnosis to rate ARWMCs. Motor subtypes (PIGD or TD) were evaluated at baseline visit, and after 2 and 4years. Age, gender, UPDRS part III total score, comorbidities and ARWMC total score were included in a mixed effect logistic regression model for repeated measures. RESULTS The likelihood of being PIGD subtype during the study period was associated with higher ARWMC total score (OR=2.743; 95%CI=1.137-7.802), but not with age (OR=0.967; 95%CI=0.818-1.143), female gender (OR=0.169; 95%CI=0.014-1.970), UPDRS part III total score (OR=1.942; 95%CI=0.888-13.470), and comorbidities (OR=2.979; 95%CI=0.560-15.849). CONCLUSION Motor dysfunction in PD is apparently multifactorial and, in particular, comorbid white matter disease might concur in the development of axial impairment.

Corpus callosum involvement: a useful clue for differentiating Fabry Disease from Multiple Sclerosis

PurposeMultiple sclerosis (MS) has been proposed as a possible differential diagnosis for Fabry disease (FD). The aim of this work was to evaluate the involvement of corpus callosum (CC) on MR images and its possible role as a radiological sign to differentiate between FD and MS.MethodsIn this multicentric study, we retrospectively evaluated the presence of white matter lesions (WMLs) on the FLAIR images of 104 patients with FD and 117 patients with MS. The incidence of CC-WML was assessed in the two groups and also in a subgroup of 37 FD patients showing neurological symptoms.ResultsWMLs were detected in 50 of 104 FD patients (48.1%) and in all MS patients. However, a lesion in the CC was detected in only 3 FD patients (2.9%) and in 106 MS patients (90.6%). In the FD subgroup with neurological symptoms, WMLs were present in 26 of 37 patients (70.3%), with two subjects (5.4%) showing a definite callosal lesion.ConclusionFD patients have a very low incidence of CC involvement on conventional MR images compared to MS, independently from the clinical presentation and the overall degree of WM involvement. Evaluating the presence of CC lesions on brain MR scans can be used as a radiological sign for a differential diagnosis between MS and FD, rapidly addressing the physician toward a correct diagnosis and subsequent treatment options.

Longitudinal assessment of dentate nuclei relaxometry during massive gadobutrol exposure

We report the assessment of Dentate Nuclei (DN) R1 (1/T1) and R2* (1/T2*) values in a patient with relapsing-remitting Multiple Sclerosis, exposed to 22 standard (0.1 mmol/kg) doses of gadobutrol, who underwent eight relaxometric MR measurements within 2 years. DN R1 did not significantly increase nor correlated with cumulative gadobutrol administration, even after a total dose of 130 ml. Likewise, DN R2* relaxometry remained unchanged. In conclusion, massive gadobutrol exposure did not induce significant DN relaxometry changes.

Intracranial extension of orbital inflammatory pseudotumor: a case report and literature review

BackgroundOrbital inflammatory pseudotumor is a rare inflammatory condition of unknown cause that may extend intracranially, usually as a dural-based infiltrate. Here we report the first case of orbital pseudotumor presenting with intra-axial Magnetic Resonance Imaging (MRI) changes.Case presentationA 57-year-old white female, with a 3-month history of headache and right palpebral edema, presented with marked right temporal lobe edema with ominous MRI appearance, and ipsilateral alterations of orbital and periorbital structures. Following steroid therapy, both intracranial and orbital involvement dramatically improved.ConclusionOrbital inflammatory pseudotumor with chronic inflammation may infrequently present with intracranial involvement, mimicking more aggressive diseases, even showing intra-axial enhancement after i.v. contrast administration in brain MRI. Awareness of this possibility may help neurologists to choose the appropriate therapeutic approach.

Motor involvement in Fabry disease

We have read with great interest the article published by Wise and colleagues on the last issue of Molecular Genetics and Metabolism Reports [1]. The Authors performed a survey study investigating the prevalence of Parkinson Disease (PD) in individuals affected by Fabry Disease (FD), and found that 2 patients out of 90 (2.2%) were diagnosed with PD. Although considering all the limitations of their study design, the Authors conclude that there might be an increased risk of developing PD in individuals with α-galactosidase A mutations. The present work is not the first study exploring and suggesting a possible motor involvement in FD. Indeed, as reported in the manuscript, the presence of subtle motor symptoms in FD, with slower gait and transfer speed, poorer fine manual dexterity and lower hand speed, has been reported [2]. In line with these evidences, both electrophysiology and advanced MRI studies showed an involvement of the primary motor cortex in this condition. In particular, with transcranial magnetic stimulation an increase of excitatory neurotransmission in motor cortex circuits of FD patients was found [3], while a reduction of the functional connectivity between motor cortices and both basal ganglia and cerebellum was proved by a resting-state functional MRI study, resembling findings present in early phases of PD [4]. Finally, pathology studies demonstrated the presence of abnormal globotriaosylceramide accumulation in the substantia nigra of FD patients, a central hub of the basal ganglia motor circuit [5]. We think that all these evidences, together with the results of this study, further support the hypothesis of a possible extrapyramidal involvement in FD. However, only future prospective studies, conducted on large samples of FD patients with the integration of different modalities, as well as a direct comparisons between FD and PD patients, can further confirm or dismiss this pathophysiological hypothesis.

Sudden post-traumatic sciatica caused by a thoracic spinal meningioma

Spinal meningiomas usually present with slowly progressive symptoms of cord and root compression, while a sudden clinical onset is very rare. A 35-year-old previously symptom-free woman presented sudden right sciatica and weakness of her right leg following a fall with impact to her left foot. A neurological examination showed paresis of the right quadriceps, tibial and sural muscles, increased bilateral knee and ankle reflexes and positive Babinski sign. Magnetic resonance imaging (MRI) revealed the presence of a spinal T11 meningioma in the left postero-lateral compartment of the spinal canal; at this level, the spinal cord was displaced to the contralateral side with the conus in the normal position. At surgery, a meningioma with dural attachment of the left postero-lateral dural surface was removed. The intervention resulted in rapid remission of both pain and neurological deficits. Spinal meningiomas may exceptionally present with sudden pain and neurological deficits as result of tumour bleeding or post-traumatic injury of the already compressed nervous structures, both in normal patients and in those with conus displacement or tethered cord. In this case, the traumatic impact of the left foot was transmitted to the spine, resulting in stretching of the already compressed cord and of the contralateral lombosacral roots. This case suggests that low thoracic cord compression should be suspected in patients with post-traumatic radicular leg pain with normal lumbar spine MRI.

Simultaneous PET/MRI in assessing the response to chemo/radiotherapy in head and neck carcinoma: initial experience

The purpose of the study was to assess by simultaneous positron emission tomography/magnetic resonance imaging (PET/MRI) the response to chemotherapy (CHT) and/or radiotherapy (RT) in patients with head and neck squamous cell carcinoma (HNSCC). Five patients with HNSCC underwent simultaneous PET/MRI examination before and after CHT and/or RT. Standard uptake volume (SUV), apparent diffusion coefficient (ADC), Ktrans, Kep, Ve, and iAUC pre- and post-treatment values were extracted and compared. The response to treatment was assessed according to RECIST criteria and classified as complete response (CR), partial response (PR), stable disease (SD), and progression disease (PD). In patient 1, PR was observed with increased ADC, Ktrans, and Ve values and reduction of SUV, iAUC, and Kep values; during clinical and instrumental follow-up, the patient experienced disease progression. Patient 2, classified as PR, showed increased ADC values and reduction of SUV and all perfusion parameters; follow-up demonstrated disease stability. Patient 3, considered as SD, showed increase of ADC and all perfusion values with a mild decrease of SUV; PD was observed during clinical and instrumental follow-up. Patients 4 and 5 showed a CR with no detectable tumor lesions at post-treatment PET/MRI examination, confirmed by 1-year follow-up. Multiparametric evaluation with simultaneous PET/MRI could be a useful tool to assess and predict the response to CHT and/or RT in patients with HNSCC.

Superparamagnetic iron oxide nanocolloids in MRI studies of neuroinflammation

Iron oxide (IO) nanocolloids are being increasingly used to image cellular contribution to neuroinflammation using MRI, as these particles are capable of labeling circulating cells with phagocytic activity, allowing to assess cell trafficking from the blood to neuroinflammation sites. The use of IOs relies on the natural phagocytic properties of immune cells, allowing their labeling either in vitro or directly in vivo, following intravenous injection. Despite concerns on the specificity of the latter approach, the widespread availability and relatively low cost of these techniques, coupled to a sensitivity that allows to reach single cell detection, have promoted their use in several preclinical and clinical studies. In this review, we discuss the results of currently available preclinical and clinical IO-enhanced MRI studies of immune cell trafficking in neuroinflammation, examining the specificity of the existing findings, in view of the different possible mechanisms underlying IO accumulation in the brain. From this standpoint, we assess the implications of the temporal and spatial differences in the enhancement pattern of IOs, compared to gadolinium-based contrast agents, a clinically established MRI marker blood-brain barrier breakdown. While concerns on the specificity of cell labeling obtained using the in-vivo labeling approach still need to be fully addressed, these techniques have indeed proved able to provide additional information on neuroinflammatory phenomena, as compared to conventional Gadolinium-enhanced MRI.