Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

The relation between person identity nodes, familiarity judgment and biographical information. Evidence from two patients with right and left anterior temporal atrophy

The aim of this study consisted of using neuropsychological data obtained in two patients (VL and StG) showing a selective atrophy of the anterior parts of the right (VL) and left (StG) temporal lobes to check current cognitive models of familiar people identification. According to these models, information coming from modality-specific "face", "voice" and "name" recognition units converge into "Person Identity Nodes" (PINs) where familiarity feelings are generated and which provide a modality-free gateway to a unitary semantic system, where information about people is stored in an amodal format. Data obtained in patient VL (and to a lesser degree in StG) were at variance with this model because VL showed: (1) a very impaired familiarity for faces, contrasting with a spared familiarity for names, indicating that familiarity judgments are generated at the level of modality-specific recognition units and not at a supramodal PIN; (2) a prevalent impairment of person-specific information available from faces rather than from names also for people that (being recognized as familiar from both their face and their name) should be normally represented at the PINs level. This last finding is at variance with the hypothesis assuming that the PINs may provide a modality-free gateway to a unitary semantic system, where information about people is stored in an amodal format

Cross-modal recognition disorders for persons and other unique entities in a patient with right fronto-temporal degeneration

We describe a patient (CD), with a right fronto-temporal degeneration, who showed massive defects in the recognition of familiar people and severe behavioural disorders. CD scored in the normal range on tests of episodic memory, attention and visual-spatial abilities, and obtained mildly abnormal scores on naming and executive functions tests. CD was then studied and matched with a left brain-damaged patient (IG), comparable to her as for education, naming score and general cognitive impairment, on several tasks, exploring recognition of familiar people and of other instances of 'unique entities'. On specific tasks of face recognition, she obtained normal results on perceptual tests, but highly pathological scores on mnesic-associative tasks. A similar defect was found when identification was based on the person's voice or on a verbal definition. The cross-modal nature of CD's disorder was confirmed by results of a test, in which person-specific information available from photographs and from names was directly compared. In order to evaluate if CD's recognition disorder: (a) was the consequence of a general semantic defect, (b) was specific for people, or (c) also concerned other instances of 'unique entities', we matched her capacity to name and recognize the pictures of items belonging to various categories of knowledge with those concerning famous monuments and famous people. CD identified items belonging to semantic categories much better than those considered as 'unique entities' and, within the latter, obtained slightly better results with famous monuments than with famous persons. MRI showed a bilateral atrophy of the antero-inferior parts of the temporal lobes, more pronounced in the right side. About 2 years after the onset of the symptomatology, CD became untestable, due to the development of a severe motor neuron disease

Patterns of Cognitive Decline and Rates of Conversion to Dementia in Patients with Degenerative and Vascular Forms of MCI

According to recent criteria, Mild Cognitive Impairment (MCI) represents a clinical condition with multiple cognitive presentations (amnesic and non amnesic) that can be supported by different types of brain lesions (mainly vascular and atrophic). In order to asses if the cognitive presentation and the rate of progression differ according to the type of brain pathology, two populations of MCI patients, characterized by hippocampal atrophy (n: 39) and vascular subcortical pathology (n: 36) respectively, on the basis of MRI findings, were investigated. Patients underwent an extensive neuropsychological test battery twice (at baseline and at two years follow-up), which is made up of the MMSE and various tests of episodic memory, short-term memory, visual-spatial abilities, executive functions, language, attention, praxis and psychomotor speed. Atrophic and vascular MCI patients showed a remarkably different pattern of impairment at the baseline. The former were significantly more impaired in episodic memory tasks. The latter were more impaired in an action naming task. At the follow up examination, the rate of progression to dementia was higher in atrophic (14/39) than in vascular (5/36) MCI patients. The comparison between neuropsychological scores obtained at the baseline and at the follow-up showed that atrophic MCI patients underwent a severe decline in several cognitive domains, whereas vascular MCI patients showed a significant decline only in those tasks requiring executive abilities. Our results confirm that a selective and severe defect of episodic memory is associated with hippocampal atrophy and that MCI patients with atrophic lesions are more likely to convert to Alzheimer's type dementia while MCI patients with vascular lesions are characterized by a slight decline in executive function over time and by a tendency to develop probable vascular forms of dementia

The profiling of axial spondyloarthritis patient candidate to a biologic therapy: Consensus from a Delphi-panel of Italian experts

Objective: The project aimed to collect expert consensus statements for the profiling of patients with axial spondyloarthritis (axSpA) candidate to biologic agents (bDMARDs) treatment, in order to better define the drivers for the best treatment choice. Methods: The 6 more interesting topics about axSpA patient profiling were identified by the project steering committee and a panel of axSpA Italian experts. A systematic literature review (SLR) was performed for each of the selected topics according to the PICO format. Two rounds of a modified Delphi process were conducted. In the 1st round, the steering committee evaluated the results of the SLR in order to formulate statements for each topic. In the 2nd round, the experts panel discussed, rephrased when needed, and voted the level of agreement (on a 5-point Likert-type scale) for each statement. Consensus was defined as ≥66% agreement. Results: The topics selected for the analysis were the differential efficacy of available bDMARDs on enthesitis/dactylitis, uveitis, radiographic progression and cardiovascular involvement, and the clinical response in non radiographic-axSpA and in patients receiving a second-line bDMARD. The Delphi rounds formulated 19 statements, all reaching the defined level of consensus in a second round including 25 rheumatologists highly skilled in the management of axSpA. Conclusion: Identified consensus statements can help clinicians to apply to routine-care settings the results from clinical studies and international recommendations, providing a guide for individualization of treatment strategy in axSpA patients