Clinical characteristics of pathological confirmed prodromal dementia with Lewy bodies.

INTRODUCTION: Misdiagnosis rate of Dementia with Lewy Bodies (DLB) remains high despite being second most common cause of neurodegenerative dementia. To date, understanding of clinical profile of pathologically confirmed prodromal DLB remains limited. The main objective of this study was to describe and compare it with pathologically confirmed Alzheimer's disease (AD). METHODS: We accessed the National Alzheimer's Coordinating Center database from 2005 to December 2022 data freeze and included 111 and 501 prodromal DLB and AD patients respectively. First visit data was analyzed. RESULTS: Clinician-determined memory impairment is common in prodromal DLB (>70%) but associated with higher risk for AD diagnosis (OR 0.355, p = 0.0003). DLB had a higher proportion of non-amnestic mild cognitive impairment (MCI) diagnoses but statistically insignificance in differentiating the two. Inattention (OR 2.273, p = 0.0015), and neuropsychiatric features, such as visual hallucinations (OR 11.98, p < 0.0001), depressed mood (OR1.709, p = 0.0292), apathy (1.824, p = 0.0345), and night/REM sleep behaviors, are associated with DLB diagnosis. Hallucinations are infrequent (7-11%). Motor symptoms, particularly gait disorders (OR 4.570, p < 0.001), falls (OR3.939, p = 0.0003), tremors (OR2.237, p = 0.0154), slowness (OR3.573, p < 0.0001), and parkinsonism signs (OR2.443, p < 0.0001), are common. 32% showed no parkinsonism during initial presentation. Neuropsychological examination revealed less impaired memory and language but impaired executive function in DLB. CONCLUSION: In clinical practice, it is important to note that memory symptoms although being higher risk associated with AD diagnosis, are prominent in prodromal DLB. Psychosis is infrequent, and non-amnestic MCI is not necessarily associated with higher risk of DLB diagnosis. A careful clinical approach is key to improve the diagnosis of prodromal DLB.

C9orf72 expansions are the most common cause of genetic frontotemporal dementia in a Southeast Asian cohort.

OBJECTIVE: Frontotemporal dementia (FTD) encompasses a spectrum of neurodegenerative disorders, including behavioural variant FTD (bvFTD), semantic variant primary progressive aphasia (svPPA) and non-fluent variant PPA (nfvPPA). While a strong genetic component is implicated in FTD, genetic FTD in Asia is less frequently reported. We aimed to investigate the frequency of Southeast Asian FTD patients harbouring known genetic FTD variants. METHODS: A total of 60 FTD-spectrum patients (25 familial and 35 sporadic) from Singapore and the Philippines were included. All underwent next-generation sequencing and repeat-primed PCR for C9orf72 expansion testing. Neurofilament light chain (NfL) levels were measured in a subset of patients. RESULTS: Overall, 26.6% (16/60 cases) carried pathogenic or likely pathogenic variants in a FTD-related gene, including: MAPT Gln351Arg (n = 1); GRN Cys92Ter (n = 1), Ser301Ter (n = 2), c.462 + 1G > C (n = 1); C9orf72 expansion (35-70 repeats; n = 8); TREM2 Arg47Cys (n = 1); and OPTN frameshift insertion (n = 2). Genetic mutations accounted for 48% (12/25) of patients with familial FTD, and 11.4% (4/35) of patients with sporadic FTD. C9orf72 repeat expansions were the most common genetic mutation (13.3%, 8/60), followed by GRN (6.7%, 4/60) variants. Within mutation carriers, plasma NfL was highest in a C9orf72 expansion carrier, and CSF NfL was highest in a GRN splice variant carrier. INTERPRETATION: In our cohort, genetic mutations are present in one-quarter of FTD-spectrum cases, and up to half of those with family history. Our findings highlight the importance of wider implementation of genetic testing in FTD patients from Southeast Asia.

Amyloid-Tau-Neurodegeneration Profiles and Longitudinal Cognition in Sporadic Young-Onset Dementia.

We examined amyloid-tau-neurodegeneration biomarker effects on cognition in a Southeast-Asian cohort of 84 sporadic young-onset dementia (YOD; age-at-onset <65 years) patients. They were stratified into A+N+, A- N+, and A- N- profiles via cerebrospinal fluid amyloid-ß1-42 (A), phosphorylated-tau (T), MRI medial temporal atrophy (neurodegeneration- N), and confluent white matter hyperintensities cerebrovascular disease (CVD). A, T, and CVD effects on longitudinal Mini-Mental State Examination (MMSE) were evaluated. A+N+ patients demonstrated steeper MMSE decline than A- N+ (ß = 1.53; p = 0.036; CI 0.15:2.92) and A- N- (ß = 4.68; p = 0.001; CI 1.98:7.38) over a mean follow-up of 1.24 years. Within A- N+, T- CVD+ patients showed greater MMSE decline compared to T+CVD- patients (ß = - 2.37; p = 0.030; CI - 4.41:- 0.39). A+ results in significant cognitive decline, while CVD influences longitudinal cognition in the A- sub-group.

Incidence of Cerebral Venous Thrombosis Following SARS-CoV-2 Infection vs mRNA SARS-CoV-2 Vaccination in Singapore.

Importance: Reports of cerebral venous thrombosis (CVT) after messenger RNA (mRNA)-based SARS-CoV-2 vaccination has caused safety concerns, but CVT is also known to occur after SARS-CoV-2 infection. Comparing the relative incidence of CVT after infection vs vaccination may provide a better perspective of this complication. Objective: To compare the incidence rates and clinical characteristics of CVT following either SARS-CoV-2 infection or mRNA-based SARS-CoV-2 vaccines. Design, Setting, and Participants: Between January 23, 2020, and August 3, 2021, this observational cohort study was conducted at all public acute hospitals in Singapore, where patients hospitalized with CVT within 6 weeks of SARS-CoV-2 infection or after mRNA-based SARS-CoV-2 vaccination (BNT162b2 [Pfizer-BioNTech] or mRNA-1273 [Moderna]) were identified. Diagnosis of SARS-CoV-2 infection was based on quantitative reverse transcription-polymerase chain reaction or positive serology. National SARS-CoV-2 infection data were obtained from the National Centre for Infectious Disease, Singapore, and vaccination data were obtained from the National Immunisation Registry, Singapore. Exposures: SARS-CoV-2 infection or mRNA-based SARS-CoV-2 vaccines. Main Outcomes and Measures: Clinical characteristics, crude incidence rate (IR), and incidence rate ratio (IRR) of CVT after SARS-CoV-2 infection and after mRNA SARS-CoV-2 vaccination. Results: Among 62 447 individuals diagnosed with SARS-CoV-2 infections included in this study, 58 989 (94.5%) were male; the median (range) age was 34 (0-102) years; 6 CVT cases were identified (all were male; median [range] age was 33.5 [27-40] years). Among 3 006 662 individuals who received at least 1 dose of mRNA-based SARS-CoV-2 vaccine, 1 626 623 (54.1%) were male; the median (range) age was 50 (12-121) years; 9 CVT cases were identified (7 male individuals [77.8%]; median [range] age: 60 [46-76] years). The crude IR of CVT after SARS-CoV-2 infections was 83.3 per 100 000 person-years (95% CI, 30.6-181.2 per 100 000 person-years) and 2.59 per 100 000 person-years (95% CI, 1.19-4.92 per 100 000 person-years) after mRNA-based SARS-CoV-2 vaccination. Six (66.7%) received BNT162b2 (Pfizer-BioNTech) vaccine and 3 (33.3%) received mRNA-1273 (Moderna) vaccine. The crude IRR of CVT hospitalizations with SARS-CoV-2 infection compared with those who received mRNA SARS-CoV-2 vaccination was 32.1 (95% CI, 9.40-101; P < .001). Conclusions and Relevance: The incidence rate of CVT after SARS-CoV-2 infection was significantly higher compared with after mRNA-based SARS-CoV-2 vaccination. CVT remained rare after mRNA-based SARS-CoV-2 vaccines, reinforcing its safety.

Safety and Usefulness of Lumbar Puncture for the Diagnosis and Management of Young-Onset Cognitive Disorders.

BACKGROUND: Young-onset cognitive disorders (YOCD) often manifests with complex and atypical presentations due to underlying heterogenous pathologies. Therefore, a biomarker-based evaluation will allow for timely diagnosis and definitive management. OBJECTIVE: Here, we evaluated the safety and usefulness of cerebrospinal fluid (CSF) sampling through lumbar puncture (LP) in YOCD patients in a tertiary clinical setting. METHODS: Patients with mild cognitive impairment (MCI) and mild dementia with age of onset between 45-64 years were evaluated. Patients underwent magnetic resonance imaging and their medial temporal lobe atrophy (MTA) was rated. LP side-effects and the impact of the CSF findings on diagnosis and management were analyzed. RESULTS: 142 patients (53 (37.32%) MCI, 51 (35.92%) dementia of the Alzheimer's disease [DAT] type, and 38 (26.76%) non-AD type dementia) who underwent LP between 2015 to 2021 were analyzed. Using post-LP results and MTA ratings, 74 (52.11%) patients met the AT(N) criteria for AD. 56 (39.44%) patients (28 out of 53 (50.0%) MCI, 12 out of 51 (21.43%) DAT, and 16 out of 38 (28.57%) non-AD dementia) had a change in diagnosis following LP. 13 (9.15%) patients developed side-effects post-LP (11 (84.62%) patients had headache, 1 (7.69%) patient had backache, and 1 (7.69%) patient had headache and backache). 32 (22.54%) patients had a change in management post-LP, 24 (75.0%) had medication changes, 10 (31.30%) had referrals to other specialists, and 3 (9.40%) was referred for clinical trial with disease modifying interventions. CONCLUSION: LP is well-tolerated in YOCD and can bring about relevant clinical decisions with regards to the diagnosis and management of this complex clinical condition.

Dementia in Southeast Asia: influence of onset-type, education, and cerebrovascular disease.

BACKGROUND: Southeast Asia represents 10% of the global population, yet little is known about regional clinical characteristics of dementia and risk factors for dementia progression. This study aims to describe the clinico-demographic profiles of dementia in Southeast Asia and investigate the association of onset-type, education, and cerebrovascular disease (CVD) on dementia progression in a real-world clinic setting. METHODS: In this longitudinal study, participants were consecutive series of 1606 patients with dementia from 2010 to 2019 from a tertiary memory clinic from Singapore. The frequency of dementia subtypes stratified into young-onset (YOD; <65 years age-at-onset) and late-onset dementia (LOD; ≥65 years age-at-onset) was studied. Association of onset-type (YOD or LOD), years of lifespan education, and CVD on the trajectory of cognition was evaluated using linear mixed models. The time to significant cognitive decline was investigated using Kaplan-Meier analysis. RESULTS: Dementia of the Alzheimer's type (DAT) was the most common diagnosis (59.8%), followed by vascular dementia (14.9%) and frontotemporal dementia (11.1%). YOD patients accounted for 28.5% of all dementia patients. Patients with higher lifespan education had a steeper decline in global cognition (p<0.001), with this finding being more pronounced in YOD (p=0.0006). Older patients with a moderate-to-severe burden of CVD demonstrated a trend for a faster decline in global cognition compared to those with a mild burden. CONCLUSIONS: There is a high frequency of YOD with DAT being most common in our Southeast Asian memory clinic cohort. YOD patients with higher lifespan education and LOD patients with moderate-to-severe CVD experience a steep decline in cognition.

Hospital-based observational study of neurological disorders in patients recently vaccinated with COVID-19 mRNA vaccines.

PURPOSE: We describe the spectrum of acute neurological disorders among hospitalized patients who recently had COVID-19 mRNA vaccination. METHOD: We performed a prospective study at 7 acute hospitals in Singapore. Hospitalized patients who were referred for neurological complaints and had COVID-19 mRNA vaccines, BNT162b2 and mRNA-1273, in the last 6 weeks were classified into central nervous system (CNS) syndromes, cerebrovascular disorders, peripheral nervous system (PNS) disorders, autonomic nervous system (ANS) disorders and immunization stress-related responses (ISRR). RESULTS: From 30 December 2020 to 20 April 2021, 1,398,074 persons (median age 59 years, 54.5% males) received COVID-19 mRNA vaccine (86.7% BNT162b2, 13.3% mRNA-1273); 915,344(65.5%) completed 2 doses. Four hundred and fifty-seven(0.03%) patients were referred for neurological complaints [median age 67(20-97) years, 281(61.5%) males; 95.8% received BNT162b2 and 4.2% mRNA-1273], classified into 73(16.0%) CNS syndromes, 286(62.6%) cerebrovascular disorders, 59(12.9%) PNS disorders, 0 ANS disorders and 39(8.5%) ISRRs. Eleven of 27 patients with cranial mononeuropathy had Bell's palsy. Of 33 patients with seizures, only 4 were unprovoked and occurred within 2 weeks of vaccination. All strokes occurred among individuals with pre-existing cardiovascular risk factors. We recorded 2 cases of cerebral venous thrombosis; none were vaccine-induced thrombotic thrombocytopenia. Five had mild flares of immune-mediated diseases. CONCLUSION: Our observational study does not establish causality of the described disorders to vaccines. Though limited by the lack of baseline incidence data of several conditions, we observed no obvious signal of serious neurological morbidity associated with mRNA vaccination. The benefits of COVID-19 vaccination outweigh concerns over neurological adverse events.

Acute Ischemic Stroke During the Convalescent Phase of Asymptomatic COVID-2019 Infection in Men.

Importance: Acute ischemic stroke (AIS) is a known neurological complication in patients with respiratory symptoms of COVID-19 infection. However, AIS has not been described as a late sequelae in patients without respiratory symptoms of COVID-19. Objective: To assess AIS experienced by adults 50 years or younger in the convalescent phase of asymptomatic COVID-19 infection. Design, Setting, and Participants: This case series prospectively identified consecutive male patients who received care for AIS from public health hospitals in Singapore between May 21, 2020, and October 14, 2020. All of these patients had laboratory-confirmed asymptomatic COVID-19 infection based on a positive SARS-CoV-2 serological (antibodies) test result. These patients were individuals from South Asian countries (India and Bangladesh) who were working in Singapore and living in dormitories. The total number of COVID-19 cases (54 485) in the worker dormitory population was the population at risk. Patients with ongoing respiratory symptoms or positive SARS-CoV-2 serological test results confirmed through reverse transcriptase-polymerase chain reaction nasopharyngeal swabs were excluded. Main Outcomes and Measures: Clinical course, imaging, and laboratory findings were retrieved from the electronic medical records of each participating hospital. The incidence rate of AIS in the case series was compared with that of a historical age-, sex-, and ethnicity-matched national cohort. Results: A total of 18 male patients, with a median (range) age of 41 (35-50) years and South Asian ethnicity, were included. The median (range) time from a positive serological test result to AIS was 54.5 (0-130) days. The median (range) National Institutes of Health Stroke Scale score was 5 (1-25). Ten patients (56%) presented with a large vessel occlusion, of whom 6 patients underwent intravenous thrombolysis and/or endovascular therapy. Only 3 patients (17%) had a possible cardiac source of embolus. The estimated annual incidence rate of AIS was 82.6 cases per 100 000 people in this study compared with 38.2 cases per 100 000 people in the historical age-, sex-, and ethnicity-matched cohort (rate ratio, 2.16; 95% CI, 1.36-3.48; P < .001). Conclusions and Relevance: This case series suggests that the risk for AIS is higher in adults 50 years or younger during the convalescent period of a COVID-19 infection without respiratory symptoms. Acute ischemic stroke could be part of the next wave of complications of COVID-19, and stroke units should be on alert and use serological testing, especially in younger patients or in the absence of traditional risk factors.

Syphilitic Spinal Disease: An Old Nemesis Revisited. A Case Series and Review of Literature.

ABSTRACT: Syphilitic spinal disease is a rare condition caused by the spirochete Treponema pallidum, either from direct spirochete involvement of the cord or as a consequence of indirect spirochete involvement of the meninges, blood vessels, or the vertebral column. After the introduction of penicillin therapy in the 1940s, it has become an increasingly rare condition. We report 3 challenging cases of syphilitic spinal disease presenting as myelopathy-1 with an extra-axial gumma of tertiary syphilis causing cord compression and 2 with tabes dorsalis complicated by tabetic spinal neuroarthropathy-each presenting a diagnostic dilemma to their treating physicians. We also review the literature for updates on modern investigative modalities and discuss pitfalls physicians need to avoid to arrive at the diagnosis.

Neurology of COVID-19 in Singapore.

PURPOSE: To describe the spectrum of COVID-19 neurology in Singapore. METHOD: We prospectively studied all microbiologically-confirmed COVID-19 patients in Singapore, who were referred for any neurological complaint within three months of COVID-19 onset. Neurological diagnoses and relationship to COVID-19 was made by consensus guided by contemporaneous literature, refined using recent case definitions. RESULTS: 47,572 patients (median age 34 years, 98% males) were diagnosed with COVID-19 in Singapore between 19 March to 19 July 2020. We identified 90 patients (median age 38, 98.9% males) with neurological disorders; 39 with varying certainty of relationship to COVID-19 categorised as: i) Central nervous system syndromes-4 acute disseminated encephalomyelitis (ADEM) and encephalitis, ii) Cerebrovascular disorders-19 acute ischaemic stroke and transient ischaemic attack (AIS/TIA), 4 cerebral venous thrombosis (CVT), 2 intracerebral haemorrhage, iii) Peripheral nervous system-7 mono/polyneuropathies, and a novel group, iv) Autonomic nervous system-4 limited dysautonomic syndromes. Fifty-one other patients had pre/co-existent neurological conditions unrelated to COVID-19. Encephalitis/ADEM is delayed, occurring in critical COVID-19, while CVT and dysautonomia occurred relatively early, and largely in mild infections. AIS/TIA was variable in onset, occurring in patients with differing COVID-19 severity; remarkably 63.2% were asymptomatic. CVT was more frequent than expected and occurred in mild/asymptomatic patients. There were no neurological complications in all 81 paediatric COVID-19 cases. CONCLUSION: COVID-19 neurology has a wide spectrum of dysimmune-thrombotic disorders. We encountered relatively few neurological complications, probably because our outbreak involved largely young men with mild/asymptomatic COVID-19. It is also widely perceived that the pandemic did not unduly affect the Singapore healthcare system.

Frontotemporal dementia and COVID-19: Hypothesis generation and roadmap for future research.

The COVID-19 pandemic has caused tremendous suffering for patients with dementia and their caregivers. We conducted a survey to study the impact of the pandemic on patients with mild frontotemporal dementia (FTD). Our preliminary findings demonstrate that patients with FTD have significant worsening in behavior and social cognition, as well as suffer greater negative consequences from disruption to health-care services compared to patients with AD. The reduced ability to cope with sudden changes to social environments places patients with FTD at increased vulnerability to COVID-19 infection as well as to poorer clinical and social outcomes. Caregivers of FTD patients also demonstrate high burden during crisis situations. A proportion of patients with FTD benefitted from use of web-based interactive platforms. In this article, we outline the priority areas for research as well as a roadmap for future collaborative research to ensure greatest benefit for patients with FTD and their caregivers.

Brain Metabolic Dysfunction in Early Neuropsychiatric Symptoms of Dementia.

Neuropsychiatric symptoms (NPS) including behavioral and psychiatric symptoms are common in the dementia stages of Alzheimer's disease (AD) and are associated with poorer outcomes in cognition, functional states, quality of life, and accelerated progression to severe dementia or death. NPS are also increasingly observed in the mild cognitive impairment stage of AD and may predict incipient dementia. As such, there is an emerging conceptual framework, which support NPS as early non-cognitive symptoms of dementia. [18F]fluorodeoxyglucosepositron emission tomography is a technique that is sensitive in detecting resting metabolism associated with NPS in neuropsychiatric conditions, and there is a growing body of literature evaluating the role of NPS as early indicators of brain metabolic dysfunctions in AD. In this mini-review, we examine the frequency and associations of NPS with metabolic dysfunction in the AD continuum, including preclinical, prodromal, and dementia stages of AD. We will also present the validated neurobehavioral syndrome, mild behavioral impairment describes the later life emergence of sustained NPS as an at-risk state for incident cognitive decline and dementia, and an early presentation of neurodegenerative diseases in some. Lastly, we will discuss future directions in the field so as to better understand the neurobiological basis of NPS in the early stages of the AD continuum, and their role in predicting AD pathophysiological progression and incident dementia.

The influence of language and culture on cognitive assessment tools in the diagnosis of early cognitive impairment and dementia.

INTRODUCTION: Cognitive assessment tools measure cognitive impairment and complement biomarkers to link cognitive symptoms with pathophysiological processes underlying dementia. However, language and cultural differences in multilingual populations can influence the interpretation of cognitive assessment tools when applied in cross-cultural and multinational studies. Areas covered: This article examines the influence of culture and language on the interpretation of the Mini-Mental State Examination, Montreal Cognitive Assessment, and Alzheimer's Disease Assessment Scale-cognitive subscale, which are more commonly used worldwide. It discusses how this impacted multinational studies. Lastly, it presents language-neutral tools such as the Visual Cognitive Assessment Test, which do not require translation when applied in multilingual populations. Expert commentary: Linguistic and cultural variation within tools due to translation and differences in administration introduce method bias and differential item functioning, which influence the interpretation of cognitive scores in multinational studies. The ultimate goal is to have a tool that accurately measures cognitive impairment, yet with minimal influence from linguistic, cultural, educational, and demographic differences, through concerted international efforts to harmonize the development and validation of tools. While recently developed visual-based language-neutral tools show promise in the early detection of cognitive impairment, further validation will be required for these tools to be applied internationally.

Diffusion-weighted MRI abnormalities in an outbreak of Streptococcus agalactiae Serotype III, multilocus sequence type 283 meningitis.

PURPOSE: In 2015, an outbreak of group B streptococcal (GBS) infection caused by Streptococcus agalactiae Serotype III, multilocus sequence type 283, related to consuming infected raw freshwater fish, affected more than 200 patients in Singapore. We describe the clinical, laboratory, and neuroimaging features of a subgroup of adults with central nervous system (CNS) infections caused by GBS. MATERIALS AND METHODS: The database of the Singapore Neurologic Infections Program (SNIP), a national multicenter study for surveillance of infectious neurologic disease, was reviewed to select patients with GBS CNS infection during the outbreak. Cases were diagnosed on the basis of clinical features, cerebrospinal fluid (CSF) findings and identification or isolation of Streptococcus agalactiae in the blood or CSF. Demographic, clinical and neuroradiological information was obtained prospectively and retrospectively abstracted. RESULTS: Fourteen patients (6 male, 8 female; median age, 58 years) presented with fever, meningism, headache, encephalopathy, focal neurological deficits, and/or seizures. All except two were previously healthy. Diffusion-weighted imaging (DWI) on admission was abnormal in 13 patients, showing tiny hyperintensities in the subarachnoid space (7 patients), ventricles (6 patients) and brain parenchyma (8 patients); 5 patients had cerebellar abnormalities. CONCLUSION: Among healthy non-pregnant adults infected with Serotype III, multilocus sequence type 283 GBS meningitis linked to eating infected raw freshwater fish, DWI detected small pus collections and unusual cerebellar involvement. A collaborative national surveillance system that includes MRI can be helpful during unusual food-borne zoonotic infectious disease outbreaks. LEVEL OF EVIDENCE: 4 J. Magn. Reson. Imaging 2017;45:507-514.

Global trend of survival and damage of systemic lupus erythematosus: meta-analysis and meta-regression of observational studies from the 1950s to 2000s.

OBJECTIVE: To assess systemically with meta-analysis the trend of survival and its determinants, which are hindering further improvement of survival of patients with systemic lupus erythematosus (SLE) over the past 5 decades. METHODS: Retrospective, cross-sectional, and prospective observational studies addressing survival and damage in SLE patients published between 1 January 1950 and 31 July 2010 were identified in electronic databases. Using the random-effects model, effect size was calculated based on the logit of the overall 5- and 10-year survival rates. The pooled logit and its robust 95% confidence interval were transformed back into the 5- and 10-year survival rates, after adjusting for potential dependence on the data. Potential factors predicting the pooled survival rates were explored by meta-regression. RESULTS: Seventy-seven studies involving 18,998 SLE patients were analyzed. Between the 1950s and the 2000s, their overall survival significantly increased, from 74.8% to 94.8% and 63.2% to 91.4% for the overall 5-year and 10-year survival, respectively (P < 0.001). The survival improvement, however, appeared to slow down between 1980 and 1990. Meta-regression revealed that neuropsychiatric and renal damage negatively affected the overall 5-year survival, whereas neuropsychiatric damage remained so for the 10-year survival for the past 50 years. Furthermore, the prevalence of neuropsychiatric damage has been significantly increasing over the past 5 decades. CONCLUSIONS: For the past 50 years, damage involving the renal and neuropsychiatric systems has been negatively affecting survival of SLE patients. Early detection and aggressive management of renal and neuropsychiatric involvement may potentially improve further the survival of lupus patients.