Frontal and subcortical contribution to visual hallucinations in dementia with Lewy bodies and Parkinson’s disease

Objectives: Visual hallucinations (VH) are common in Lewy body disease (LBD), and have been associated with cognitive and structural brain alterations. Evidence so far concerns mainly Parkinson’s disease (PD), but little is known about symptom-specific pathophysiological mechanisms across the LBD spectrum, especially related to the presence of dementia. The aim of the present pilot study was to investigate the neuroanatomical, and neuropsychological characteristics related to VH in two forms of LBD, namely dementia with Lewy bodies (DLB) and PD without dementia.

Methods: Whole brain voxel-based morphometry (VBM) analyses on 3D MRI acquired structural brain scans, and neuropsychological testing were performed on 28 clinically diagnosed DLB (11 with VH, 17 NVH), and 24 PD (9 with VH, and 15 NVH) patients. In order to assess differences in gray matter (GM) regional volumes, and cognitive performance, hallucinating patients for each group were compared with corresponding non-hallucinating ones.

Results: DLB patients with VH presented significantly worse visual attention deficits compared to those without, which persisted even when controlling for visual perception. Whole brain VBM analysis revealed decreased GM volume in DLB with VH in the right superior and medial frontal gyri, putamen, caudate nucleus and insula. Subcortical regional volumes were also significantly associated with visual attention performance. Hallucinating PD patients, instead, presented more severe executive dysfunction, but VBM showed no volumetric differences between the two PD subgroups. Post hoc region of interest analyses revealed striatal GM loss in PD with VH.

Conclusion: Frontal and striatal GM atrophy may contribute to the emergence of VH in DLB, which may be fostered by the more severe attention deficits. Striatal GM loss and executive dysfunction, instead, appeared to underlie VH in PD without dementia.     

Efficacy of Haemate-P as prophylaxis of recurrent bleeding in a patient with type 2B von Willebrand's disease.

We report the case of a 58-year-old woman with type 2B von Willebrand's disease who received regular infusions of the factor VIII/von Willebrand factor concentrate Haemate-P (2000 IU every other day) for 4 months to prevent recurrent bleeding from a malignant esophageal ulcer. Prophylaxis with Haemate-P was shown to be safe and effective in this patient, thus enabling completion of radiochemotherapy.     

Cerebral amyloid load determination in a clinical setting: interpretation of amyloid biomarker discordances aided by tau and neurodegeneration measurements

Neurological Sciences - Alzheimer’s disease (AD) diagnosis can be hindered by amyloid biomarkers discordances. We aim to interpret discordances between amyloid positron emission tomography...     

Long‐term preclinical magnetic resonance imaging alterations in sporadic Creutzfeldt–Jakob disease

An asymptomatic 74‐year‐old woman, on follow‐up for a carotid body tumor, showed magnetic resonance imaging (MRI) focal restricted diffusion confined to the left temporal and occipital cortices. Thirteen months later, diffusion‐weighted images revealed a bilateral cortical ribbon sign involving all lobes. After 1 month, the patient developed gait instability and cognitive decline rapidly evolving to severe dementia and death within 3 months. Prion protein gene sequence, molecular, and neuropathological studies confirmed the diagnosis of sporadic Creutzfeldt–Jakob disease (sCJD) MM1 subtype. Here we show the kinetics of MRI changes and prion spreading in preclinical sCJD MM1. Ann Neurol 2016;80:629–632     

Multiple myeloma involving the cavernous sinus: a report of 3 cases and response to bortezomib

Intracranial multiple myeloma is uncommon. Cavernous sinus involvement has rarely been reported, generally associated with treatment-refractory disease and poor outcome. We report clinical data and neuroradiologic findings of 3 patients with multiple myeloma and unilateral cavernous sinus involvement. At neuroradiology, this resulted from diffuse bone involvement as disease relapse (n=2) or focal dural disease (n=1) as the presenting sign. Interestingly, bortezomib treatment resulted in complete clinical resolution in 1 patient and partial clinical and significant magnetic resonance response in another, whereas in the literature, local radiation therapy has been reported as the only efficient treatment.     

An association of Hutchinson-Gilford progeria and malignancy

Mutations in the LMNA gene encoding lamins A/C are responsible for a variety of disorders, commonly referred to as "laminopathies," including the segmental premature aging syndrome Hutchinson-Gilford progeria. We describe in this report the rare association of osteosarcoma and slowly progressing progeria in an 11-year-old girl carrying a truncating heterozygous c.1868C > G (p.T623S) prelamin A mutation. These findings are discussed in light of recent data on the pathophysiological mechanisms underlying progeria and "physiological" aging in human, as well as previous data on other well-known segmental aging syndromes.     

Metabolic disorders induced by highly active antiretroviral therapy and their relationship with vascular remodeling of the brachial artery in a population of HIV-infected patients

Antiretroviral therapy has positively modified the natural history of HIV infection; but this treatment can induce metabolic abnormalities, including dyslipidemia, fat redistribution, high blood pressure, and insulin resistance. The metabolic syndrome, a clustering of the metabolic disorders, is frequently detected among HIV patients, especially those on antiretroviral treatment. All the arteries can modify their diameter in response to a chronic injury. This process, defined vascular remodeling, was demonstrated for the brachial artery. It is well known that the diameter of the brachial artery was correlated with the number of the elements of the metabolic syndrome and was associated with the severity of coronary artery disease. On this basis, we postulate that brachial arterial enlargement may be a process potentially correlated with the metabolic disorders induced by antiretroviral therapy. We tested this hypothesis in a large population of HIV-infected patients in which we measured brachial artery diameter, as an indicator of artery remodeling, by noninvasive, ultrasonographic technique. Our population consisted of 570 patients, with a mean age of 46.3 ± 7.1 years. All the patients were chronically treated with highly active antiretroviral therapy. Brachial artery diameter was correlated with insulin resistance, evaluated by the homeostasis model assessment of insulin resistance index (r = 0.18, P < .0001). There was a significant linear increase in brachial artery diameter as the number of components of the metabolic syndrome increased: brachial artery diameter for those with 0, 1, 2, 3, or + characteristics was 39.3 ± 7.2, 41.0 ± 6.8, 42.0 ± 7.3, and 43.8 ± 7.9 mm, respectively (P < .001 for trend). In multivariable logistic regression analysis, brachial artery diameter was independently correlated with the presence of metabolic syndrome. Our results are in line with the hypothesis that, among HIV-infected patients chronically treated with antiretroviral therapy, those with a larger brachial artery diameter are at high risk for metabolic disorders, including a more severe insulin resistance and the presence of metabolic syndrome.     

Diagnostic tools for the study of vascular cognitive dysfunction in hypertension and antihypertensive drug research

Arterial hypertension is one of the main risk factors for cerebrovascular diseases, and antihypertensive treatment has significantly reduced their associated mortality. However, morbidity has not been reduced to a similar extent and a still increasing number of patients suffers from recurring strokes and from the disabling consequences of cerebrovascular diseases and develops progressive cognitive impairment. It is still debated to what extent antihypertensive treatment may prevent the development of cognitive dysfunction, due to the lack of a focused approach to vascular cognitive impairment, to the lack of a systematic study of the early phases of dementia, and to the use of diagnostic tests that are not sensitive and specific for a slow onset clinical condition, such as dementia. The aim of the present expert consensus report is to enlist the diagnostic tools that are currently available to assess mild cognitive impairment (MCI) and early dementia and that are sensitive and specific enough to be used in observational, longitudinal, and interventional clinical research studies, aiming to investigate the impact of antihypertensive drugs on vascular dementia (VD).     

HGPS and related premature aging disorders: from genomic identification to the first therapeutic approaches

Progeroid syndromes are heritable human disorders displaying features that recall premature ageing. In these syndromes, premature aging is defined as "segmental" since only some of its features are accelerated. A number of cellular biological pathways have been linked to aging, including regulation of the insulin/growth hormone axis, pathways involving ROS metabolism, caloric restriction, and DNA repair. The number of identified genes associated with progeroid syndromes has increased in recent years, possibly shedding light as well on mechanisms underlying ageing in general. Among these, premature aging syndromes related to alterations of the LMNA gene have recently been identified. This review focuses on Hutchinson-Gilford Progeria syndrome and Restrictive Dermopathy, two well-characterized Lamin-associated premature aging syndromes, pointing out the current knowledge concerning their pathophysiology and the development of possible therapeutic approaches.