Atypical parkinsonism: An Update.

Purpose of review: This update discusses novel aspects on genetics, diagnosis, and treatments of atypical parkinsonism published over the past 2 years. Recent findings: A genome-wide association study identified new genetic risk factors for progressive supranuclear palsy and new genetic conditions presenting with atypical parkinsonism have been described. The clinical criteria for diagnosis of corticobasal degeneration have been revised, and for progressive supranuclear palsy are under revision. Novel molecular techniques to identify possible biomarkers, as in other neurodegenerative disorders, have started being studied on atypical parkinsonian conditions, and although preliminary results seem promising, further studies are urgently warranted. Therapeutic trials based on disease-specific targets have shown no clinical improvement. Summary: The knowledge obtained recently on atypical parkinsonian conditions points out the major deficits in this field. With the expanding phenotypical spectrum of atypical parkinsonian conditions, the early identification of patients has become difficult. The inability of conventional methods to identify these disorders earlier and better than clinicians, and the recent failure of promising therapeutic compounds, highlight the fact that the lack of biomarkers is probably the greatest limitation for developing treatments for these disorders. Thus, current and future research in this direction will be crucial

The differential diagnosis of Huntington's disease-like syndromes: 'red flags' for the clinician

A growing number of progressive heredodegenerative conditions mimic the presentation of Huntington's disease (HD). Differentiating among these HD-like syndromes is necessary when a patient with a combination of movement disorders, cognitive decline, behavioural abnormalities and progressive disease course proves negative to the genetic testing for HD causative mutations, that is, IT15 gene trinucleotide-repeat expansion. The differential diagnosis of HD-like syndromes is complex and may lead to unnecessary and costly investigations. We propose here a guide to this differential diagnosis focusing on a limited number of clinical features (‘red flags’) that can be identified through accurate clinical examination, collection of historical data and a few routine ancillary investigations. These features include the ethnic background of the patient, the involvement of the facio-bucco-lingual and cervical district by the movement disorder, the co-occurrence of cerebellar features and seizures, the presence of peculiar gait patterns and eye movement abnormalities, and an atypical progression of illness. Additional help may derive from the cognitive–behavioural presentation of the patient, as well as by a restricted number of ancillary investigations, mainly MRI and routine blood tests. These red flags should be constantly updated as the phenotypic characterisation and identification of more reliable diagnostic markers for HD-like syndromes progress over the following years

Tremor in motor neuron disease may be central rather than peripheral in origin

BACKGROUND AND PURPOSE: Motor neuron disease (MND) refers to a spectrum of degenerative diseases affecting motor neurons. Recent clinical and post-mortem observations have revealed considerable variability in the phenotype. Rhythmic involuntary oscillations of the hands during action, resembling tremor, can occur in MND, but their pathophysiology has not yet been investigated. METHODS: A total of 120 consecutive patients with MND were screened for tremor. Twelve patients with action tremor and no other movement disorders were found. Ten took part in the study. Tremor was recorded bilaterally using surface electromyography (EMG) and triaxial accelerometer, with and without a variable weight load. Power spectra of rectified EMG and accelerometric signal were calculated. To investigate a possible cerebellar involvement, eyeblink classic conditioning was performed in five patients. RESULTS: Action tremor was present in about 10% of our population. All patients showed distal postural tremor of low amplitude and constant frequency, bilateral with a small degree of asymmetry. Two also showed simple kinetic tremor. A peak at the EMG and accelerometric recordings ranging from 4 to 12 Hz was found in all patients. Loading did not change peak frequency in either the electromyographic or accelerometric power spectra. Compared with healthy volunteers, patients had a smaller number of conditioned responses during eyeblink classic conditioning. CONCLUSIONS: Our data suggest that patients with MND can present with action tremor of a central origin, possibly due to a cerebellar dysfunction. This evidence supports the novel idea of MND as a multisystem neurodegenerative disease and that action tremor can be part of this condition

Regulatory measures to address the risk from the shadow banking system in the E.U. and the U.S.A.

Το σκιώδες τραπεζικό σύστημα ορίζεται από το Συμβούλιο Χρηματοπιστωτικής Σταθερότητας (FSB) ως "σύστημα πιστωτικής διαμεσολάβησης που περιλαμβάνει οντότητες και δραστηριότητες εκτός του κανονικού τραπεζικού συστήματος". Αυτό σημαίνει ότι ο μόνος τρόπος για τον εντοπισμό της σκιώδους τραπεζικής δραστηριότητας βασίζεται σε δύο αλληλένδετους πυλώνες: τις οντότητες που λειτουργούν εκτός του κανονικού τραπεζικού συστήματος, που εξετάζονται μέσω των δραστηριοτήτων που εκτελούν και των δραστηριοτήτων που λειτουργούν ως σημαντικές πηγές χρηματοδότησης αυτών των μη τραπεζικών οντοτήτων. Σε αυτό το πλαίσιο, μόνο οι μη τραπεζικοί μεσάζοντες, οι οποίοι λειτουργούν με φαινομενικά παρόμοιο τρόπο με τις εμπορικές τράπεζες ,δηλαδή αυτόν της τραπεζικής διαμεσολάβησης, δημιουργώντας υπερβολική μόχλευση, μετασχηματισμούς διάρκειας και ρευστότητας και μετακύλιση του πιστωτικού κινδύνου, μπορούν να θεωρηθούν ως σκιώδεις τράπεζες, λόγω του γεγονότος ότι θέτουν απειλές, κινδύνους και δυσμενείς επιπτώσεις στη χρηματοπιστωτική σταθερότητα, και ιδίως, λόγω του κινδύνου να συμβεί ρυθμιστικό αρμπιτράζ. Για αυτό το λόγο συνέβαλαν στο ξέσπασμα της παγκόσμιας χρηματοπιστωτικής κρίσης το 2007-2009, ειδικά στις ΗΠΑ, όπου κατηγορήθηκαν από τον υπουργό Οικονομικών των ΗΠΑ, Timothy Geithner, μετέπειτα πρόεδρο και διευθύνοντα σύμβουλο της Federal Reserve Bank της Νέας Υόρκης, ως ο κύριος λόγος για το «πάγωμα» των πιστωτικών αγορών. Πράγματι, οι σκιώδεις τράπεζες δεν είναι παραδοσιακές, εμπορικές τράπεζες και επομένως δεν υπόκεινται στις ίδιες ρυθμίσεις και στην ίδια εποπτεία, ούτε στις διευκολύνσεις της κεντρικής τράπεζας ή προβλέψεις του τραπεζικού «διχτυού ασφαλείας», και αυτό οδηγεί σε υψηλή πιθανότητα κινδύνων και ευπάθειας. Ειδικότερα, οι μεσάζοντες χρηματοπιστωτικοί οργανισμοί (π.χ. Αμοιβαία κεφάλαια της χρηματαγοράς , ιδιωτικά επενδυτικά κεφάλαια, αμοιβαία κεφάλαια αντιστάθμισης κινδύνου, οντότητες για τιτλοποίησεις , δανειστές κινητών αξιών και φορείς για δομημένες επενδύσεις, τράπεζες επενδύσεων και μεσίτες στεγαστικών δανείων) που παρέχουν πίστωση και ρευστότητα, ασκούν δραστηριότητες σκιώδους τραπεζικής, κυρίως σε «φορολογικούς παραδείσους», διευκολύνοντας τη δημιουργία τεράστιου ποσού πίστωσης σε όλο το παγκόσμιο χρηματοπιστωτικό σύστημα. Σε αντίθεση με τις εμπορικές τράπεζες, δεν λαμβάνουν καταθέσεις ώστε να χρηματοδοτούν τις πιστώσεις, αλλά οι πιστώσεις που δίνουν βασίζονται σε βραχυπρόθεσμα κεφάλαια που προέρχονται από επενδυτές. Εκεί ξεκινά το πρόβλημα. Δεδομένου ότι τα χρήματά τους παρέχονται από χρεόγραφα εξασφαλισμένα με περιουσιακά στοιχεία ή από την αγορά συμφωνιών επαναγοράς, είναι σαφές ότι οι πιστωτικοί κίνδυνοι και οι κίνδυνοι ρευστότητας είναι υψηλοί και, εάν δεν ρυθμίζονται και διαχειρίζονται, μπορούν να προκαλέσουν σημαντική ζημιά στο χρηματοπιστωτικό σύστημα και, φυσικά, στους δανειολήπτες του σκιώδους τραπεζικού συστήματος. Ωστόσο, οι οντότητες και οι συμμετέχοντες σε αυτό το σύστημα είναι πολυάριθμοι, το ποσοστό του συνολικού χρηματοπιστωτικού συστήματος είναι αξιοσημείωτο, η αξία του ενεργητικού του υπολογίζεται σε τρισεκατομμύρια και ταυτόχρονα είναι εξαιρετικά ανεξέλεγκτη, καθιστώντας το ελκυστικό και επικίνδυνο ταυτόχρονα. Ωστόσο, ευθύνεται δίκαια αυτή η διαβόητη αλλά κερδοφόρα βιομηχανία για όλες τις αποτυχίες και τις αναποτελεσματικότητες; Πώς μπορούμε να το κάνουμε να λειτουργήσει έτσι ώστε να έχουμε όλο το κέρδος και να καταφέρουμε να διαχειριστούμε και να ελαχιστοποιήσουμε τους κινδύνους; Πώς μπορεί ο χρηματοοικονομικός τομέας και οι συμμετέχοντες του να εμπιστεύονται ένα σύστημα που ούτως ή άλλως ονομάζεται «σκιώδες»; Όλα αυτά θα τα εξετάσουμε στις επόμενες σελίδες.The shadow banking system is defined by the Financial Stability Board (FSB) as “a system of credit intermediation that involves entities and activities outside the regular banking system”. This means that the only way to identify the shadow banking activity is based on two intertwined pillars: entities operating outside the regular banking system, examined through the activities they perform and activities that act as important sources of funding of these non-bank entities. In this spectrum, only non-bank intermediaries, which operate in a seemingly similar way with traditional banks meaning performing banking intermediation, creating excessive leverage, maturity and liquidity transformation, and credit risk transfer, can be considered as shadow banks because of the fact that they pose threats, risks and adverse effects to financial stability, and especially, because of the danger of a regulatory arbitrage happening. That is why these activities contributed in the outbreak of the Global Financial Crisis in 2007-2009, especially in the USA, where it was blamed by the U.S. Treasury Secretary Timothy Geithner, later President and CEO of the New York Federal Reserve Bank, as the main reason for the “freezing” of the credit markets. Indeed, shadow banks are not traditional, commercial banks and thus are not subject to the same regulation and supervision, nor central bank facilities or safety net arrangements, and that leads to high potentiality of risks and vulnerability. In particular, these financial intermediaries (i.e. money market funds, private equity funds, hedge funds, securitization vehicles, securities lenders, and structured investment vehicles, investment banks and mortgage brokers) which operate the shadow-banking activities, mostly in tax heavens, facilitate the creation of huge amount of credit across the global financial system. In contrast with commercial banks, they do not take deposits to lend out to borrowers, but the credit they give is based on short –term funds that come from investors. That is where the problem begins. Since their funds are provided by asset-backed commercial paper or by the repo market, it is clear that credit and liquidity risks are high and if not regulated and managed, can cause significant damage to the financial system and ,of course, to the borrowers of the shadow banking system. However, the entities and participants of this system are numerous, the percentage of the total financial system is remarkable, its assets’ worth is counted in trillions and at the same time is highly unregulated, making it appealing and dangerous at the same time. However, is this infamous yet profiting industry fairly blamed for all the failures and inefficiencies? How can we make it work so that we gain all the profit and succeed to manage and minimize the risks? How can the financial sector and its participants trust a system that is called “shadow” anyway? We are going to examine all these in the following pages

Dopaminergic reward system: a short integrative review

Memory is an essential element to adaptive behavior since it allows consolidation of past experience guiding the subject to consider them in future experiences. Among the endogenous molecules that participate in the consolidation of memory, including the drug-seeking reward, considered as a form of learning, is dopamine. This neurotransmitter modulates the activity of specific brain nucleus such as nuclei accumbens, putamen, ventral tegmental area (VTA), among others and synchronizes the activity of these nuclei to establish the neurobiological mechanism to set the hedonic element of learning. We review the experimental evidence that highlights the activity of different brain nuclei modulating the mechanisms whereby dopamine biases memory towards events that are of motivational significance

Psychogenic palatal tremor may be underrecognized: reappraisal of a large series of cases.

Palatal tremor is characterized by rhythmic movements of the soft palate and can be essential or symptomatic. Some patients can have palatal movements as a special skill or due to palatal tics. Psychogenic palatal tremor is recognized but rarely reported in the literature

Psychogenic paroxysmal movement disorders – Clinical features and diagnostic clues

AbstractBackgroundThe diagnosis of psychogenic paroxysmal movement disorders (PPMD) can be challenging, in particular their distinction from the primary paroxysmal dyskinesias (PxD) remains difficult.MethodsHere we present a large series of 26 PPMD cases, describe their characteristics, contrast them with primary PxD and focus on their distinguishing diagnostic features.ResultsMean age at onset was 38.6 years, i.e. much later than primary PxD. Women were predominantly affected (73%). Most subjects (88.4%) had long attacks, and unlike primary PxD there was a very high within-subject variability for attack phenomenology, duration and frequency. Dystonia was the most common single movement disorder presentation, but 69.2% of the patients had mixed or complex PxD. In 50% of PPMD cases attack triggers could be identified but these were unusual for primary PxD. 42.3% of patients employed unusual strategies to alleviate or stop the attacks. Response to typical medication used for primary PxD was poor. Precipitation of the disorder due to physical or emotional life events and stressors were documented in 57.6% and 65.3% of the cases respectively. Additional interictal psychogenic signs were documented in 34.6% and further medically unexplained somatic symptoms were present in 50% of the cases. 19.2% of patients had a comorbid organic movement disorder and 26.9% had pre-existing psychiatric comorbidities.ConclusionAlthough the phenotypic presentation of PPMD can be highly diverse, certain clinical characteristics help in distinguishing this condition from the primary forms of PxD. Recognition is important as multidisciplinary treatment approaches led to significant improvement in most cases

Dystonic opisthotonus: A "red flag" for neurodegeneration with brain iron accumulation syndromes?

Back arching was reported in one of the very first patients with neurodegeneration with brain iron accumulation syndrome (NBIAs) published in 1936. However, recent reports have mainly focused on the genetic and imaging aspects of these disorders, and the phenotypic characterization of the dystonia has been lost. In evaluating patients with NBIAs in our centers, we have observed that action-induced dystonic opisthotonus is a common and characteristic feature of NBIAs. Here, we present a case series of patients with NBIAs presenting this feature demonstrated by videos. We suggest that dystonic opisthotonus could be a useful "red flag" for clinicians to suspect NBIAs, and we discuss the differential diagnosis of this feature. This would be particularly useful in identifying patients with NBIAs and no iron accumulation as yet on brain imaging (for example, as in phospholipase A2, group IV (cytosolic, calcium-independent) [PLA2G6]-related disorders), and it has management implications.© 2013 International Parkinson and Movement Disorder Society

Validation of mobile eye-tracking as novel and efficient means for differentiating progressive supranuclear palsy from Parkinson's disease

Background: The decreased ability to carry out vertical saccades is a key symptom of Progressive Supranuclear Palsy (PSP). Objective measurement devices can help to reliably detect subtle eye movement disturbances to improve sensitivity and specificity of the clinical diagnosis. The present study aims at transferring findings from restricted stationary video-oculography (VOG) to a wearable head-mounted device, which can be readily applied in clinical practice. Methods: We investigated the eye movements in 10 possible or probable PSP patients, 11 Parkinson's disease (PD) patients, and 10 age-matched healthy controls (HCs) using a mobile, gaze-driven video camera setup (EyeSeeCam). Ocular movements were analyzed during a standardized fixation protocol and in an unrestricted real-life scenario while walking along a corridor. Results: The EyeSeeCam detected prominent impairment of both saccade velocity and amplitude in PSP patients, differentiating them from PD and HCs. Differences were particularly evident for saccades in the vertical plane, and stronger for saccades than for other eye movements. Differences were more pronounced during the standardized protocol than in the real-life scenario. Conclusions: Combined analysis of saccade velocity and saccade amplitude during the fixation protocol with the EyeSeeCam provides a simple, rapid (<20 s), and reliable tool to differentiate clinically established PSP patients from PD and HCs. As such, our findings prepare the ground for using wearable eye-tracking in patients with uncertain diagnoses