From Psoriasis to Psoriatic Arthritis: Insights from Imaging on the Transition to Psoriatic Arthritis and Implications for Arthritis Prevention

Purpose of Review: To describe the recent advances in the field towards the prevention and early recognition of Psoriatic Arthritis (PsA). Recent Findings: Defining the preclinical phase of PsA remains challenging since up to 50% of subjects with psoriasis have subclinical imaging enthesopathy, but many of these do not progress to PsA. Nevertheless, there is evidence that subjects with subclinical imaging enthesopathy are at increased risk of developing PsA. In recent years, it has been shown that both PsA and anti-citrullinated protein antibodies (ACPA) positive rheumatoid arthritis (RA) are characterized by a subclinical phase of non-specific or brief duration arthralgia with shared imaging features accounting for joint symptomatology. Sonographically determined tenosynovitis and enthesitis are the key imaging features present in non-specific PsO arthralgia that are at risk of future PsA development. Furthermore, the early phases of PsA are complicated by factors including body mass index (BMI), which is a risk factor for PsA, but BMI is also associated with imaging abnormalities on enthesopathy. Fully disentangling these clinical and imaging factors will be important for enrichment for imminent PsA so that disease prevention strategies can be investigated. Summary: Psoriasis patients with arthralgia have a higher prevalence of tenosynovitis and imaging enthesopathy is at higher risk of transitioning to overt PsA

How to understand it: Neuropsychological testing

Neuropsychological testing is a key diagnostic tool for assessing people with dementia and mild cognitive impairment, but can also help in other neurological conditions such as Parkinson’s disease, stroke, multiple sclerosis, traumatic brain injury and epilepsy. While cognitive screening tests offer gross information, detailed neuropsychological evaluation can provide data on different cognitive domains (visuospatial function, memory, attention, executive function, language and praxis) as well as neuropsychiatric and behavioural features. We should regard neuropsychological testing as an extension of the neurological examination applied to higher order cortical function, since each cognitive domain has an anatomical substrate. Ideally, neurologists should discuss the indications and results of neuropsychological assessment with a clinical neuropsychologist. This paper summarises the rationale, indications, main features, most common tests and pitfalls in neuropsychological evaluation

The impact of recurrent Covid-19 waves on patients with Functional Movement Disorders: A follow-up study

Background: Functional Movement Disorders (FMDs) might exacerbate in stressful conditions. As the global health emergency due to Covid-19 rise and multiple waves hit the Italian population, the recurrent severe restrictions' periods imposed could represent important triggers and worsen the symptoms of FMDs. Through a follow-up study, we compare results on Motor Symptoms (MS), Non-Motor Symptoms (NMS), and Global Health Status (GHS) of two surveys, one referred to the first Covid-19 wave and the other to the third Covid-19 wave. Methods: 60 FMDs patients responded to an online survey after the first and the third Covid-19 waves in Italy. Questions regarding sociodemographic, clinical and Covid-19 information, MS, NMS, and GHS were collected to assess severity of symptoms and changes in comparison to a period with less severe social restrictions. Results: Patients showed minimal to mild motor symptoms' severity, and substantial stability through time in all collected measures, both for severity and changes of MS, NMS, and GHS in comparison at two time points (p > 0.050). The worsening of pain resulted as predictor factor for the worsening of Motor Symptoms (p = 0.042). Conclusions: Patients did not show a vulnerability due to the recurrent restrictions' periods: MS, NMS and GHS did not vary in comparison to the first wave, confirming the previous results and highlighting the role of the social context in those disorders. Further investigations are required to better disentangle the relationship between stressful events, motor symptoms, and pain

Functional neurological disorders as seen by a cohort of general practitioners in northern italy: Evidence from an online survey

General practitioners (GPs) provide primary care and advise their patients on which diagnostic and therapeutic pathways they judge most appropriate. For patients with functional neurological disorders (FND), receiving a proper explanation of diagnosis by their GP from the very beginning may drastically improve prognosis. Novel approaches to the diagnosis and treatment of FND have important implications for effective management. The aim of this study was to investigate Italian GP opinion and knowledge about FND in light of new approaches to the illness. To do this, we evaluated the responses to a 13-item web-based survey completed by 133 GPs practicing in northern Italy. Psychological terms to describe FND were more frequently used than functional neurological disorder and mental illness was considered an important predictor of diagnosis. Referral to a neurologist rather than to a psychiatrist was largely preferred, while physiotherapy consultation was seldom recognized as a valuable approach to treating FND. Overall, the survey findings suggest that knowledge about novel approaches to FND is somewhat lacking. Currently, GPs appear to be transitioning from a classical psychological view of the disorder toward a more modern conceptualization, in which neurobiological, psychological, and social factors all play an important role. Professional education during this transition would be an advantageous way to optimize physician management of FND and to enhance diagnosis, explanation, and management across primary and secondary care pathways

Impaired temporal processing of tactile and proprioceptive stimuli in cerebellar degeneration.

Performance of timed motor sequences relies on the cerebellum and basal ganglia, which integrate proprioceptive information during the motor task and set internal timing mechanisms. Accordingly, these structures are also involved in other temporal processes, such as the discrimination of the different afferent information in the domain of time. In the present study we tested temporal processing of proprioceptive and tactile stimuli in 20 patients with neurodegenerative cerebellar ataxia and 20 age- and sex-matched healthy subjects. Tactile temporal discrimination threshold was defined as the value at which subjects recognized the two stimuli as asynchronous. Temporal discrimination movement threshold of the first dorsal interosseous and flexor carpi radialis was defined as the shortest interval between two paired electrical stimuli in which the subjects blindfolded perceived two separate index finger abductions and wrist flexions. Both tactile and movement temporal discrimination thresholds were higher in patients with cerebellar ataxia. No correlation was found with disease duration and severity. Our study demonstrates that temporal processing of tactile and proprioceptive stimuli is impaired in patients with cerebellar neurodegeneration and highlights the involvement of cerebellum in temporal processing of somatosensory stimuli of different type

Restless Legs Syndrome: Known Knowns and Known Unknowns

Although restless legs syndrome (RLS) is a common neurological disorder, it remains poorly understood from both clinical and pathophysiological perspectives. RLS is classified among sleep-related movement disorders, namely, conditions characterized by simple, often stereotyped movements occurring during sleep. However, several clinical, neurophysiological and neuroimaging observations question this view. The aim of the present review is to summarize and query some of the current concepts (known knowns) and to identify open questions (known unknowns) on RLS pathophysiology. Based on several lines of evidence, we propose that RLS should be viewed as a disorder of sensorimotor interaction with a typical circadian pattern of occurrence, possibly arising from neurochemical dysfunction and abnormal excitability in different brain structures

Tactile and proprioceptive temporal discrimination are impaired in functional tremor

Background and Methods: In order to obtain further information on the pathophysiology of functional tremor, we assessed tactile discrimination threshold and proprioceptive temporal discrimination motor threshold values in 11 patients with functional tremor, 11 age- and sex-matched patients with essential tremor and 13 healthy controls. Results: Tactile discrimination threshold in both the right and left side was significantly higher in patients with functional tremor than in the other groups. Proprioceptive temporal discrimination threshold for both right and left side was significantly higher in patients with functional and essential tremor than in healthy controls. No significant correlation between discrimination thresholds and duration or severity of tremor was found. Conclusions: Temporal processing of tactile and proprioceptive stimuli is impaired in patients with functional tremor. The mechanisms underlying this impaired somatosensory processing and possible ways to apply these findings clinically merit further research

Long non-coding RNAs play a role in the pathogenesis of psoriatic arthritis by regulating microRNAs and genes involved in inflammation and metabolic syndrome

Psoriatic arthritis (PsA) is an inflammatory arthritis, characterized by inflammation of entheses and synovium, leading to joint erosions and new bone formation. It affects 10-30% of patients with psoriasis, and has an estimated prevalence of approximately 1%. PsA is considered to be primarily an autoimmune disease, driven by autoreactive T cells directed against autoantigens present in the skin and in the joints. However, an autoinflammatory origin has recently been proposed. Long noncoding RNAs (lncRNAs) are RNAs more than 200 nucleotides in length that do not encode proteins. LncRNAs play important roles in several biological processes, including chromatin remodeling, transcription control, and post-transcriptional processing. Several studies have shown that lncRNAs are expressed in a stage-specific or lineage-specific manner in immune cells that have a role in the development, activation, and effector functions of immune cells. LncRNAs are thought to play a role in several diseases, including autoimmune disorders. Indeed, a few lncRNAs have been identified in systemic lupus erythematosus, rheumatoid arthritis, and psoriasis. Although several high-throughput studies have been performed to identify lncRNAs, their biological and pathological relevance are still unknown, and most transcriptome studies in autoimmune diseases have only assessed protein-coding transcripts. No data are currently available on lncRNAs in PsA. Therefore, by microarray analysis, we have investigated the expression profiles of more than 50,000 human lncRNAs in blood samples from PsA patients and healthy controls using Human Clariom D Affymetrix chips, suitable to detect rare and low-expressing transcripts otherwise unnoticed by common sequencing methodologies. Network analysis identified lncRNAs targeting highly connected genes in the PsA transcriptome. Such genes are involved in molecular pathways crucial for PsA pathogenesis, including immune response, glycolipid metabolism, bone remodeling, type 1 interferon, wingless related integration site, and tumor necrosis factor signaling. Selected lncRNAs were validated by RT-PCR in an expanded cohort of patients. Moreover, modulated genes belonging to meaningful pathways were validated by RT-PCR in PsA PBMCs and/or by ELISA in PsA sera. The findings indicate that lncRNAs are involved in PsA pathogenesis by regulating both microRNAs and genes and open new avenues for the identification of new biomarkers and therapeutical targets

Performance validity tests in nonlitigant patients with functional motor disorder

Background: Performance Validity Tests (PVTs) are used in neuropsychological assessments to detect patterns of performance suggesting that the broader evaluation may be an invalid reflection of an individual's abilities. Data on Functional motor disorder (FMD) are currently poor and conflicting. Objectives: We aimed to examine the rate of failure at three different PVTs of non-litigant, non-compensation seeking FMD patients, and we compared their performance to that of healthy controls and controls asked to simulate malingering (healthy simulators). Methods: We enrolled 29 non-litigant, non-compensation seeking patients with a clinical diagnosis of FMD, 29 healthy controls and 29 healthy simulators. Three PVTs, the Coin in the Hand Test (CIH), the Rey 15-item Test (REY) and the Finger Tapping Test (FTT), were employed. Results: FMD Patients showed low rates of failure at the CIH and REY tests (7% and 10%, respectively) and slightly higher at the FTT (15%, n=26) test, which implies a motor task. Their performance was statistically comparable to that of healthy controls but statistically different from that of healthy simulators (p<0.001). 93% of FMD patients, 7% of healthy simulators, and 100% of healthy controls passed at least two of the three tests. Conclusions: PVT performance of non-litigant, non-compensation seeking patients with FMD ranged from 7 to 15%. Patient's performance was comparable to controls and significantly differed from that of simulators. This simple battery of three PVTs could be of practical utility and routinely used in clinical practice