Catatonia associated with pediatric postoperative cerebellar mutism syndrome.

OBJECTIVE: To ascertain the presence of catatonia in cases of pediatric postoperative cerebellar mutism syndrome (PPCMS). METHOD: A systematic review of PPCMS case reports of patients aged 0-17 years with sufficient clinical information to extract catatonic phenomena was undertaken following PRISMA guidelines. Standardized catatonia rating scales were applied to selected cases retrospectively to ascertain whether diagnostic criteria for catatonia were met. A case known to the authors is also presented. RESULTS: Two hundred twenty-one suitable full-text articles were identified. Following screening and application of inclusion criteria, 51 articles were selected plus seven more from their references, reporting on 119 subjects. All cases met Bush and Francis (BF) diagnostic criteria for catatonia, 92.5% Pediatric Catatonia Rating Scale (PCRS), 52.9% ICD-11, and 44.5% DSM-5. All patients presented with mutism. The next most frequent signs were immobility/stupor (77.3%), withdrawal (35.3%), mannerisms (23.5%), and excitement/agitation (18.5%). Most cases presented with stuporous catatonia (75.6%). Catatonia most frequently occurred following resection of medulloblastoma (64.7%). Preoperative hydrocephalus occurred in 89 patients (74.8%). CONCLUSION: Catatonia was frequent in this PPCMS sample, with a predominant stuporous variant; it should be considered in patients with PPCMS and assessed with reliable and validated instruments for prompt diagnosis and management.

Absence of Long-Lasting Morning Stiffness at the Time of Diagnosis as Paraneoplastic Warning in Patients with Polymyalgia Rheumatica (PMR): Data from Italian Single-Center Study.

BACKGROUND: There is little literature on the paraneoplastic value of the absence of long-lasting morning stiffness (MS) at the time of diagnosis of polymyalgia rheumatica (PMR). We investigated whether and to what extent this finding was related to the probability of diagnosing a neoplasia. PATIENTS AND METHODS: This was an observational, retrospective, single-center cohort study. We enrolled all patients consecutively referred to our rheumatologic outpatient clinic between January 2015 and December 2020, who could be classified as PMR according to 2012 EULAR/ACR criteria. In particular, we assessed all patients scoring a minimum of five points with a combination of clinical and ultrasound (US) criteria. The exclusion criteria were as follows: (a) follow-up duration

Presence of subclinical giant cell arteritis in patients with morning stiffness of duration less than 45 minutes at the time of diagnosis of polymyalgia rheumatica.

Introduction: In some patients with polymyalgia rheumatica (PMR), giant cell arteritis (GCA) is subclinical as underlying inflammation of large vessels (LV) is present without evidence of related clinical manifestations. Different factors have been proposed as predictive of subclinical GCA in PMR patients. To date, the literature reports scant data about the association between subclinical GCA and long-lasting morning stiffness (MS) in patients at the time of diagnosis of PMR. Given this background, the aim of this study was to assess the association between subclinical GCA and MS < 45 min in patients with newly diagnosed PMR. Material and methods: We performed an observational, retrospective, single-centre cohort study of patients consecutively referred to our public out-of-hospital rheumatologic clinic between January 2015 and December 2020, who could be classified as having PMR according to the 2012 EULAR/ACR criteria. Subclinical GCA was investigated through ultrasound examination of a core set of arteries (temporal, axillary, common carotid, and subclavian arteries), in accordance with the EULAR recommendations for the use of imaging in LV vasculitis. Patients who did not have GCA symptoms but showed halo sign in at least one of these arteries were described as having subclinical GCA. Results: We included a total of 143 patients (35 men and 108 women). Their median age was of 71.5 years. Thirty-five had MS duration < 45 min at the time of PMR diagnosis. Subclinical GCA was found in 23 PMR patients (16.1%); 18 had a cranial and 5 an extracranial GCA. A univariate analysis highlighted that MS < 45 min was associated with a lower prevalence of GCA (OR = 0.11, 95% CI: 0.04-0.29; p < 0.0001). This association was retained in a multivariable analysis that accounted for 6 different potential covariates (OR = 0.06, 95% CI: 0.01-0.26; p < 0.0001. Conclusions: In our study MS < 45 min at the time of PMR diagnosis was associated with a significantly lower risk of subclinical GCA, when patients were screened by ultrasound, of approximately 90%. Identification of a more accurate MS cut-off value could improve the accuracy for subclinical GCA in patients with newly diagnosed PMR.

Polymyalgia rheumatica and polymyalgia-like syndromes as adverse events following COVID-19 vaccines: working notes from a narrative review of published literature.

Since the 1990s, polymyalgia rheumatica (PMR) has been reported as a possible adverse event following immunization (AEFI). The aim of this narrative review is to provide an overview of PMR (and PMR-like syndromes) following the most common types of COVID-19 vaccines, namely mRNA (tozinameran and mRNA-1273) and adenovirus-vectored (ChAdOx1-S) vaccines. To date, published literature reports few cases of PMR as vaccine-linked AEFI. Yet Vigibase, the WHO pharmacovigilance database, reports a few hundred cases. Based on these data, we address the question whether PMR/PMR-like syndromes following COVID-19 vaccines can be a true adverse or a coincidental event, and discuss its possible pathogenetic mechanisms.

Catatonia in older adults: A systematic review.

BACKGROUND: Catatonia is a complex psychomotor syndrome that often goes unrecognized and untreated, even though its classification has evolved in recent years. Prompt and correct identification of catatonia allows for highly effective treatment and prevention of possible complications. The underrecognition of catatonia in older patients is also frequent, and research in this population is scarce. AIM: To conduct a systematic review of the literature on catatonia in older people to ascertain its clinical characteristics across settings. METHODS: Following the PRISMA guidelines, MEDLINE, EMBASE, and PsycINFO databases were searched from inception to December 2021, with a strategy aimed at identifying all articles published on catatonia in older adults. Titles and abstracts were scanned and selected independently by two authors. Papers investigating issues related to catatonia and/or catatonic symptoms in older people, with English abstracts available, were included. References of selected articles were revised to identify other relevant studies. RESULTS: In total, 1355 articles were retrieved. After removing duplicates, 879 remained. Of the 879 identified abstracts, 669 were excluded because they did not meet the inclusion criteria. A total of 210 articles underwent full text review, and 51 were eliminated for various reasons. Fourteen more articles were selected from the references. Overall, 173 articles were reviewed: 108 case reports, 35 case series, 11 prospective cohort studies, 6 case-control studies, 3 retrospective cohort studies and 10 reviews. We found several particular aspects of catatonia in this population. Catatonia in older patients is highly prevalent and tends to have a multifactorial etiology. Older patients, compared to younger patients, have a higher risk of developing catatonia with benzodiazepine (BZD) withdrawal, in bipolar disorder, and in the general hospital. Age, together with other risk factors, was significantly associated with the incidence of deep venous thrombosis, neuroleptic malignant syndrome poor outcome, other complications and mortality. Treatment with BZDs and electroconvulsive therapy is safe and effective. Prompt treatment of its cause is essential to ensure a good prognosis. CONCLUSION: Catatonia in older patients is highly prevalent and tends to have a multifactorial etiology. The risk of developing catatonia in some settings and conditions, as well as of developing complications, is high in this population. Symptomatic treatment is safe and effective, and timely etiologic treatment is fundamental.

The Role of Tumor Necrosis Factor Alpha Antagonists (Anti TNF-α) in Personalized Treatment of Patients with Isolated Polymyalgia Rheumatica (PMR): Past and Possible Future Scenarios.

BACKGROUND: Glucocorticoids (GCs) are the cornerstone of polymyalgia rheumatica (PMR) therapy, but their long-term use (as is usually necessary in PMR patients) can induce many adverse events. Alternatives have long been sought. The primary aim of our narrative review is to provide an overview about the use of anti-tumor necrosis factor alpha (TNF-α) drugs in patients with PMR, and discuss advantages and disadvantages. MATERIALS AND METHODS: we performed a non-systematic literature search (PRISMA protocol not followed) on PubMed and Medline (OVID interface). RESULTS AND CONCLUSIONS: only two anti TNF-α drugs have been prescribed to PMR patients: infliximab in 62 patients and etanercept in 28 patients. These drugs were normally used in addition to GCs when significant comorbidities and/or relapsing PMR were present; less commonly, they were used as first-line therapy. In general, they have been scarcely successful in patients with PMR. Indeed, randomized controlled trials did not confirm the positive results reported in case reports and/or case series. However, an administration schedule and study design different from those proposed in the past could favour new scenarios in the interest of PMR patients.

Catatonia in pediatric obsessive-compulsive disorder: report of two cases.

Catatonia is a psychomotor syndrome which may occur in a wide variety of medical, neurological, and psychiatric conditions. In pediatrics, this condition is rare and is associated with high morbidity and mortality if not correctly diagnosed and treated. Catatonia in obsessive-compulsive disorder is an infrequent association that has been understudied and underdiagnosed. To add to the knowledge on this unusual clinical presentation, two pediatric patients are reported and discussed together with the other two cases described in the literature. These four cases in total of catatonia associated with OCD confirm that it is a relationship that is infrequently reported, possibly because of lack of awareness in clinicians that catatonia can also be caused by OCD, and because the similarity between some catatonic signs and some compulsive phenomena may compound the identification of the former. Most cases of catatonia in this small series seemed to have responded to the optimization of the treatment for OCD. This highlights the clinical importance of an accurate diagnosis of catatonia when associated with OCD.

Recognition and Management of Antipsychotic-Induced Parkinsonism in Older Adults: A Narrative Review.

BACKGROUND: Parkinsonism is a common side-effect of antipsychotic drugs especially in older adults, who also present with a higher frequency of neurodegenerative disorders like Idiopathic Parkinson's disease (IPD). Distinguishing between antipsychotic-induced parkinsonism (AIP) and IPD is challenging due to clinical similarities. Up to 20% of older adults may suffer from persisting parkinsonism months after discontinuation of antipsychotics, suggesting underlying neurodegeneration. A review of the literature on AIP in older adults is presented, focusing on epidemiology, clinical aspects, and management. METHODS: A literature search was undertaken on EMBASE, MEDLINE and PsycINFO, for articles on parkinsonism induced by antipsychotic drugs or other dopamine 2 receptor antagonists in subjects aged 65 or older. RESULTS: AIP in older adults is the second most common cause of parkinsonism after IPD. Older age, female gender, exposure to high-potency first generation antipsychotics, and antipsychotic dosage are the main risk factors. The clinical presentation of AIP resembles that of IPD, but is more symmetrical, affects upper limbs more, and tends to have associated motor phenomena such as orofacial dyskinesias and akathisia. Presence of olfactory dysfunction in AIP suggests neurodegeneration. Imaging of striatal dopamine transporters is widely used in IPD diagnosis and could help to distinguish it from AIP. There is little evidence base for recommending pharmacological interventions for AIP, the best options being dose-reduction/withdrawal, or switching to a second-generation drug. CONCLUSIONS: AIP is a common occurrence in older adults and it is possible to differentiate it from IPD. Further research is needed into its pathophysiology and on its treatment.

Back to the future: identification and classification of polymyalgia rheumatica and polymyalgia rheumatica-like syndromes following cancer immunotherapy with checkpoint inhibitors.

Polymyalgia rheumatica (PMR) and PMR-like syndromes are among the most frequent rheumatologic immuno-related adverse events (IRAEs) induced by cancer immunotherapy with "checkpoint inhibitors" (ICIs). Our short communication addresses two key methodological issues laid bare by published literature : 1) how to diagnose PMR and PMR-like syndromes following ICI therapy, 2) how PMR/PMR-like syndromes following ICI therapy are described as adverse drug reactions (ADRs).

Could COVID-19 anosmia and olfactory dysfunction trigger an increased risk of future dementia in patients with ApoE4?

The association of the coronavirus disease 2019 (COVID-19) with significant neurological and neuropsychiatric complications has been increasingly reported, both during the acute illness and in its aftermath. However, due to the short duration of patient follow up until now, it is not clear whether this infection will be associated with longer-term neurological and/or neuropsychiatric sequelae. In particular, the question of whether COVID-19 will be associated with an increased risk and rate of future dementia remains open and subject to speculation. During the course of the COVID-19 pandemic, an increasing number of patients have reported sudden anosmia or other olfactory dysfunction as concurrent symptoms. The possibility that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may reach the brain via the olfactory nerve or an upper nasal trancribrial route is an interesting working hypothesis. Among the identified genetic risk factors for Late-onset Alzheimer's disease (LOAD), Apo E4 is one of the strongest and most frequent. People carrying one or two copies of the e4 allele of Apo E4 have significant odor recognition deficits in comparison to those not carrying this haplotype. The hypothesis invoked in this paper is that anosmia/olfactory dysfunctions induced by SARS-CoV-2 may cause an increased a risk of future neurodegenerative dementia in ApoE4 carriers, and that this risk would be higher than in Apo E4 carriers affected by anosmia not induced by SARS-CoV-2. This would be associated with virus-induced chronic modifications in the central nervous system. It is proposed that COVID-19 patients with anosmia and no other serious symptoms should be followed up as part of specifically designed and approved studies in order to identify the early stages of dementia (especially LOAD and Dementia with Lewy Bodies), thereby improving our knowledge of the mechanisms involved in pre-cognitive stages of neurodegenerative dementia and making best use of any available therapies. This latter opportunity is unique and should not be lost.

Identification and Classification of Polymyalgia Rheumatica (PMR) and PMR-Like Syndromes Following Immune Checkpoint Inhibitors (ICIs) Therapy: Discussion Points and Grey Areas Emerging from a Systematic Review of Published Literature.

Background: Polymyalgia Rheumatica (PMR) is one of the most frequent rheumatologic immune-related adverse effects (IRAEs) in cancer patients following therapy with immune checkpoint inhibitors (ICIs). Atypical findings in many patients often lead to diagnosing PMR-like syndromes. Materials and methods: The aim of our research was to review reported diagnoses of PMR and PMR-like syndromes following ICIs therapy, and assess whether they can be redefined as adverse drug reaction (ADR). In line with PRISMA guidelines, we carried out a systematic search on three main bibliographic databases, based on a combination of subject headings and free text. We included all studies and case-reports published after 2011 (when FDA approved the use of the first ICI) describing the association of PMR or PMR-like syndromes with all types of ICIs therapy. We excluded reviews, conference abstracts, comments, secondary articles, and non-English language studies. Results: We reviewed data from seven studies and eight case-reports, involving a total of 54 patients. Limitations included: the small size of all studies; only one retrospective study used validated criteria for PMR; most reports assessed IRAEs by clinical judgment only and did not seek validation through assessment scales. To date, it remains a conundrum whether IRAEs-PMR is identical to the idiopathic form of the disease, or whether it should be considered a subset of the disease or a new entity. Conclusions: Our review indicates that the relationship between PMR and ICIs therapy is yet to be clearly understood and defined and that future research should remedy the current limits in study design.

Catatonia in N-methyl-d-aspartate receptor antibody encephalitis: Phenomenological characteristics from a systematic review of case reports.

OBJECTIVE: To ascertain the phenomenological characterisation of catatonia in N-methyl-d-aspartate receptor antibody encephalitis (NMDAr-AbE). METHODS: A systematic review of case reports was undertaken in accordance with PRISMA guidelines. Case reports of NMDAr-AbE containing sufficient information on the cases' clinical presentation and meeting the study's inclusion criteria were selected. Cases were searched for clinical data in keeping with core catatonic signs by applying the screening instrument of the Bush-Francis Catatonia Rating Scale. When two or more core signs were ascertained catatonia was considered to be present. RESULTS: 2645 records were identified through the database search. Following screening and application of eligibility/inclusion criteria 139 articles were selected reporting on 189 individual subjects. Catatonia was present in 60% of these cases. The most prevalent signs were immobility/stupor (70%), mutism (67%), excitement (50%), posturing/catalepsy (34%), stereotypies (31%), and rigidity (30%). Immobility/stupor and excitement co-occurred in the same patient in 33% of cases. CONCLUSION: The phenomenological profile of catatonia in this sample of cases of NMDAr-AbE was characterised by a preponderance of signs in the hypokinetic spectrum. However, excitement often co-occurred in these patients suggesting that fluctuations in catatonic semiology may be frequent.

Depression and depressive symptoms in patients with polymyalgia rheumatica: discussion points, grey areas and unmet needs emerging from a systematic review of published literature.

OBJECTIVES: In 1979, Bird et al. proposed depression as a diagnostic criterion for polymyalgia rheumatica (PMR). More recently, the significance of depression in PMR patients has been re-proposed, , and some researchers have suggested that PMR may increase the risk of depression. The aim of our article is to evaluate the relationship between PMR and depression. MATERIAL AND METHODS: Systematic literature searches were performed on 19th and 20th May 2020 based on Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The search was restricted to all studies and case reports with English abstract, published in any language, since 1979 (when depression was first proposed as a diagnostic criterion for PMR) describing the association of PMR with depression. Exclusion criteria were as follows: reviews, conference abstracts, comments, non-original articles; and articles discussing giant cell arteritis (GCA) and PMR when data and observations for the two conditions were not clearly subdivided. RESULTS: The initial search yielded 812 papers, of which 115 duplicates were removed. A total of 697 articles had a first screening and 506 were excluded based on title and abstract reviews; 117 articles underwent full-length scrutiny, and 99 full-text articles were excluded because they did not meet the inclusion and exclusion criteria (reviews and comments = 58; articles with outcome of interest not reported = 34; low-quality articles = 7). At least, 18 articles were included in this review. CONCLUSIONS: The review did not find any studies that clarified the prevalence rates of depression in patients with PMR. Furthermore, the studies reviewed did not offer any clarity as to whether patients suffered from just depressive symptoms or clinical depression, and that accepted diagnostic criteria for depression had not been employed, indicating that a robust method for diagnosing depression had not been employed. Collaboration of different professionals should be improved through shared guidelines.

Cognitive Function in Primary Sjögren's Syndrome: A Systematic Review.

BACKGROUND: Cognitive disorders are reported to be common in patients with primary Sjogren's syndrome (pSS). In some cases, they are the first clinical manifestation, preceding the diagnosis of pSS by two years on average. AIM: A systematic review was conducted to explore cognitive impairment in pSS, with reference to diagnostic methods and their relationship with laboratory data and clinical manifestations. MATERIALS AND METHODS: According to the PRISMA 2009 checklist, we carried out a comprehensive literature search in the three main bibliographic databases: MEDLINE, EMBASE, and PsycINFO (NICE HDAS interface). The following main search terms were used: primary Sjogren syndrome, neurological manifestations, fatigue, cognitive functions, psychiatric manifestations, mild cognitive impairment, dementia, and neurocognitive disorder. The search was made on 14 September, 2018. References from all selected studies were also examined. Inclusion criteria were: all studies and case-reports published in any language from 2002 that assessed the association of pSS (according to classification criteria proposed by the 2002 American/European collaborative group (AECG)) with all types of cognitive impairment (including dementia). Exclusion criteria were: reviews, abstracts, secondary Sjögren's syndrome (SS), and all articles in which other classification criteria were used. RESULTS: The initial search yielded 352 articles, of which 253 were excluded based on the title and abstract review. A total of 54 articles underwent a full-length review, and 32 articles were excluded. Data were extracted from 18 studies and three case-reports involving a total of 6196 participants. In most cases, cognitive dysfunction was a brain fog or a mild cognitive impairment (MCI). Occasionally, an autoimmune dementia was present. The relationship between pSS and degenerative dementias, such as Alzheimer's disease (AD), was a controversial issue, even if some investigators hypothesized that pSS could be a risk factor. Several unmet needs were highlighted. First, some of the included studies had not reported the severity of pSS; hence, few correlations between disease severity and cognitive function were possible. Secondly, the evaluation of the pathogenetic role of comorbid diseases was often absent. The lack of information on the type of dementia represented a third critical point in the majority of the included studies. CONCLUSIONS: This systematic review confirmed that adequate studies on cognitive function in pSS are scarce, mostly performed on small-sized samples, and often conflicting. The routine assessment of cognitive function in patients with pSS seems advisable and it will help to elucidate some of the unmet needs highlighted by this review in future appropriately designed studies.

Behavioral, Psychiatric, and Cognitive Adverse Events in Older Persons Treated with Glucocorticoids.

Background: Since the introduction of glucocorticoids (GCs) in the physician's pharmacological arsenal, it has been known that they are a cause of behavioral or psychiatric adverse events (BPAE), as well as of cognitive problems. To the best of our knowledge, the relationship between these adverse events and GCs in older persons has never been evaluated, except through case-reports or series with few cases. In this paper, a review of the literature regarding BPAEs and cognitive disorders in older people treated with CSs is undertaken. Methods: A comprehensive literature search for BPAEs was carried out on the three main bibliographic databases: EMBASE, MEDLINE and PsycINFO (NICE HDAS interface). Emtree terms were: Steroid, steroid therapy, mental disease, mania, delirium, agitation, depression, behavior change, dementia, major cognitive impairment, elderly. The search was restricted to all clinical studies and case reports with focus on the aged (65+ years) published in any language since 1998. Results: Data on the prevalence of the various BPAEs in older patients treated with GCs were very scarse, consisting mainly of case reports and of series with small numbers of patients. It was hence not possible to perform any statistical evaluation of the data (including meta-analysis). Amongst BPAEs, he possibility that delirium can be induced by GCs has been recently been questioned. Co-morbidities and polypharmacy were additional risk factors for BPAEs in older persons. Conclusions: Data on BPAEs in older persons treated with GCs, have several unmet needs that need to be further evaluated with appropriately designed studies.