Tau as a Biomarker of Neurodegeneration.

Less than 50 years since tau was first isolated from a porcine brain, its detection in femtolitre concentrations in biological fluids is revolutionizing the diagnosis of neurodegenerative diseases. This review highlights the molecular and technological advances that have catapulted tau from obscurity to the forefront of biomarker diagnostics. Comprehensive updates are provided describing the burgeoning clinical applications of tau as a biomarker of neurodegeneration. For the clinician, tau not only enhances diagnostic accuracy, but holds promise as a predictor of clinical progression, phenotype, and response to drug therapy. For patients living with neurodegenerative disorders, characterization of tau dysregulation could provide much-needed clarity to a notoriously murky diagnostic landscape.

Clinical predictors of discordance between screening tests and psychiatric assessment for depressive and anxiety disorders among patients being evaluated for seizure disorders.

OBJECTIVE: This study was undertaken to identify factors that predict discordance between the screening instruments Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and Generalized Anxiety Disorder scale (GAD-7), and diagnoses made by qualified psychiatrists among patients with seizure disorders. Importantly, this is not a validation study; rather, it investigates clinicodemographic predictors of discordance between screening tests and psychiatric assessment. METHODS: Adult patients admitted for inpatient video-electroencephalographic monitoring completed eight psychometric instruments, including the NDDI-E and GAD-7, and psychiatric assessment. Patients were grouped according to agreement between the screening instrument and psychiatrists' diagnoses. Screening was "discordant" if the outcome differed from the psychiatrist's diagnosis, including both false positive and false negative results. Bayesian statistical analyses were used to identify factors associated with discordance. RESULTS: A total of 411 patients met inclusion criteria; mean age was 39.6 years, and 55.5% (n = 228) were female. Depression screening was discordant in 33% of cases (n = 136/411), driven by false positives (n = 76/136, 56%) rather than false negatives (n = 60/136, 44%). Likewise, anxiety screening was discordant in one third of cases (n = 121/411, 29%) due to false positives (n = 60/121, 50%) and false negatives (n = 61/121, 50%). Seven clinical factors were predictive of discordant screening for both depression and anxiety: greater dissociative symptoms, greater patient-reported adverse events, subjective cognitive impairment, negative affect, detachment, disinhibition, and psychoticism. When the analyses were restricted to only patients with psychogenic nonepileptic seizures (PNES) or epilepsy, the rate of discordant depression screening was higher in the PNES group (n = 29, 47%) compared to the epilepsy group (n = 70, 30%, Bayes factor for the alternative hypothesis = 4.65). SIGNIFICANCE: Patients with seizure disorders who self-report a variety of psychiatric and other symptoms should be evaluated more thoroughly for depression and anxiety, regardless of screening test results, especially if they have PNES and not epilepsy. Clinical assessment by a qualified psychiatrist remains essential in diagnosing depressive and anxiety disorders among such patients.

Ambiguous medical abbreviation study: challenges and opportunities.

BACKGROUND: Healthcare workers often abbreviate for convenience, but ambiguous abbreviations may cause miscommunication, which jeopardises patient care. Robust large-scale research to quantify abbreviation frequency and ambiguity in medical documents is lacking. AIMS: To calculate the frequency of abbreviations used in discharge summaries, the proportion of these abbreviations that are ambiguous and the potential utility of auto-expansion software. METHODS: We designed a software programme to extract all instances of abbreviations from every General Medical Unit discharge summary from the Royal Melbourne Hospital in 2015. We manually expanded abbreviations using published inventories and clinical experience, logging multiple expansions for any abbreviation if identified. Abbreviations were classified based on well defined criteria as standardised and likely to be well understood, or ambiguous. Outcome measures included the range and frequency of standardised and ambiguous abbreviations, and the feasibility of electronic auto-expansion software based on these measures. RESULTS: Of the 1 551 537 words analysed from 2336 documents, 137 997 (8.9%) were abbreviations with 1741 distinct abbreviations identified. Most abbreviations (88.7%) had a single expansion. The most common abbreviation was PO (per os/orally), followed by BD (bis in die/twice daily) and 68.1% of abbreviations were standardised, largely pertaining to pathology/chemicals. This meant, however, that a large proportion (31.9%) of abbreviations (2.8% of all words) were ambiguous. The most common ambiguous abbreviation was Pt (patient/physiotherapy), followed by LFT (liver function test/lung function test). CONCLUSIONS: Close to one-third of abbreviations used in general medical discharge summaries were ambiguous. Electronic auto-expansion of ambiguous abbreviations is likely to reduce miscommunication and improve patient safety.

Anti-melanoma differentiation-associated gene 5 (anti-MDA5) positive dermatomyositis: early detection is crucial.

Anti-melanoma differentiation-associated gene 5-positive (Anti-MDA5) dermatomyositis (DM) is an aggressive phenotype of DM associated with rapidly progressive interstitial lung disease (RP-ILD). It is a rare condition that carries high mortality. Diagnosis and management of patients with anti-MDA5 DM RP-ILD presents several challenges, including uncertainty around treatment algorithms and a lack of evidence to inform practice. This case report of a patient with anti-MDA5 DM RP-ILD highlights these challenges, emphasising the fulminant course of this disease despite aggressive immunosuppression. Further research is required to guide management and to minimise morbidity and mortality, and greater awareness of the condition is required to minimise delays in diagnosis.

Prevalence of cerebral microbleeds in Alzheimer's disease, dementia with Lewy bodies and Parkinson's disease dementia: A systematic review and meta-analysis.

Cerebral microbleeds (CMB) are often associated with vascular risk factors and/or cerebral amyloid angiopathy and are frequently identified in people with dementia. The present study therefore aimed to estimate the pooled prevalence and associations of CMB in Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), using meta-analytic methods. Sixty-five MRI studies were included after a systematic search on major electronic databases. We found that the prevalence of CMB was comparable across the three dementia subtypes (31-36%) and was highly influenced by the MRI techniques used. CMB in AD were associated with a history of hypertension and amyloid-ß burden. In contrast, CMB in DLB, despite being predominantly lobar, were associated with hypertension, but not amyloid-ß burden. These findings suggest that the underlying pathophysiology of CMB in DLB might differ from that of AD. There was substantially larger number of AD studies identified and more studies evaluating CMB in Lewy body dementias are warranted.

Comprehensive clinical, radiological, pathological and biochemical analysis required to differentiate VV1 sporadic Creutzfeldt-Jakob disease from suspected variant CJD.

Background: A diagnosis of variant Creutzfeldt-Jakob disease (vCJD), the zoonotic prion disease related to transmission of bovine spongiform encephalopathy, can carry enormous public health ramifications. Until recently, all vCJD clinical cases were confined to patients displaying methionine homozygosity (MM) at codon 129 of the prion protein gene (PRNP). The recent diagnosis of vCJD in a patient heterozygous (MV) at codon 129 reignited concerns regarding a second wave of vCJD cases, with the possibility of phenotypic divergence from MM vCJD and greater overlap with sporadic CJD (sCJD) molecular subtypes. Method and results: We present a case of CJD with clinico-epidemiological and radiological characteristics creating initial concerns for vCJD. Thorough case evaluation, including data provided by genetic testing, autopsy and neuropathological histological analyses, provided a definitive diagnosis of the rare VV1 molecular subtype of sCJD. Conclusion: Distinguishing vCJD from sCJD is of vital public health importance and potentially more problematic with the development of non-MM vCJD cases. The patient described herein demonstrates that in addition to the clinico-epidemiological profile, combined supplementary pathological, biochemical and critical radiological analysis may be necessary for confident discrimination of sCJD, especially rare sub-types, from vCJD.

Emergency presentation of new onset versus recurrent undiagnosed seizures: A retrospective review.

OBJECTIVES: To identify clinical factors that may assist emergency physicians to delineate between patients with new onset seizures (NOS) versus patients with recurrent undiagnosed seizures (RUS) among those presenting with apparent 'first seizures' to EDs. In addition, to provide a summary of current evidence-based guidelines regarding the workup of seizure presentations to ED. METHODS: This retrospective cohort study included patients aged over 17 years who presented to a tertiary hospital ED between 1 January 2008 and 30 November 2016 with seizure-related ICD-10-AM discharge codes. Exclusion criteria included pre-existing epilepsy and non-seizure diagnoses. Medical records were reviewed and relevant data extracted. RESULTS: Seventy-five patients had NOS (54.7% [41/75] female, median age 71 years) and 22 patients had RUS (59.1% [13/22] female, median age 64 years). Non-motor index seizures were more than four times as common among RUS patients (27.3% [6/22] RUS vs 6.7% [5/75] NOS; P = 0.015). 95.5% (21/22) of RUS patients met epilepsy diagnostic criteria compared to 44.0% (33/75) of NOS patients (P < 0.001). No differences in patient demographics, seizure aetiology or seizure risk factors were identified. CONCLUSIONS: Emergency physicians should be wary of patients presenting with non-motor 'first seizures': they are more likely to have experienced prior seizures (the 'recurrent untreated seizure' group), and thus meet epilepsy diagnostic criteria. Almost half of those with actual NOS may also meet epilepsy criteria, largely driven by abnormal neuroimaging. Distinguishing RUS from NOS patients in the ED allows accurate prognostication and timely initiation of appropriate therapy.

Presentation and management of community-onset vs hospital-onset first seizures.

BACKGROUND: New-onset seizures are frequently encountered in community and hospital settings. It is likely that seizures presenting in these distinct settings have different etiologies and prognoses, requiring different investigation and treatment approaches. We directly compare the presentation and management of patients with community- and hospital-onset first seizures attending the same hospital. METHODS: We reviewed the medical records of patients aged 18 years or older with discharge International Classification of Diseases, Australian Classification (ICD-10-AM) codes of G40 (epilepsy), G41 (status epilepticus), and R56.8 (unspecified convulsions), who attended a general hospital in Melbourne, Australia, from January 1, 2008, through November 30, 2016. Patients with new-onset seizures were included for analysis. RESULTS: A total of 367 patients were discharged with a relevant ICD-10-AM code. Among them, 151 patients met the inclusion criteria: 97 presented to the emergency department with community-onset seizure (median age 70 years), and 54 experienced seizures during hospitalization for other indications (median age 80.5 years). Provoked seizures were more common in the latter group (26.8% vs 63.0%, p < 0.001), with exposure to proconvulsant drugs a major risk factor. Despite not fulfilling the International League Against Epilepsy (ILAE) diagnostic criteria, 72.5% (58/80) who survived to discharge were prescribed antiepileptic drug (AED) therapy, whereas 19.0% (12/63) of those who met the ILAE criteria were not. CONCLUSIONS: Hospitalized elderly patients are at an increased risk of provoked seizures, and caution should be exercised when prescribing potential proconvulsant medications and procedures. A more standardized approach to AED prescribing is needed. Further studies should consider morbidity, mortality, and health economic effects of first seizures and assess optimal management to improve outcomes in this cohort.