Masnammany et al. WW Med 2020 Vol 2 issue: 1 12-23

Original Article

Clinical features and treatment outcome of neuropsychiatric systemic lupus erythematosus (NPSLE) : A single centre experience.

Adrian Mark Masnammany, Avreena Kaur Bhullar, Ooi Seok Ling, Asmahan Mohamed Ismail

Rheumatology Unit, Hospital Raja Perempuan Zainab II, Kota Bharu, Kelantan, Malaysia.

Received: 28 February 2020 / Accepted: 15 March 2020

Abstract

Background: Neuropsychiatry (NP) syndromes of SLE (NPSLE) encompass a wide range of neurologic and psychiatric manifestations including cognitive dysfunction, mood disorder, psychosis, seizure, headache, and peripheral neuropathies.

Objective: To identify patient characteristics, clinical features, SLEDAI , treatment protocol and outcome of patients with NPSLE.

Method: A retrospective ,observational single centre study of all patients ( n = 20) admitted for NSPLE from Dec 2017 to Dec 2019 in Hospital Raja Perempuan Zainab II, Kota Bharu, Kelantan, a tertiary referral centre. Patient neurological

outcome was determined based on 3 and 6 months follow after initial diagnosis of NPSLE.

Results: There were a total of 20 patients with NPSLE ; 3(15%) with thrombotic NPSLE , 14(70%) with inflammatory central nervous system NPSLE and 3(15%) with peripheral nervous system involvement. 17 (85%) patients had high

disease activity ( SLEDAI >12) and 3(15%) had moderate activity ( SLEDAI 6-12) with mean SLEDAI score of 22.65 8.37 .

Keywords: SLE, lupus, neuropsychiatry, neuropsychiatric, NPSLE, management, outcome

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Worldwide Medicine

Corresponding Author: Adrian Mark Masnammany - Rheumatology Unit, Hospital Raja Perempuan Zainab II, Kota Bharu, Kelantan, Malaysia. DOI: 10.5455/ww.89583 This is an Open Access article under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/)

Masnammany et al. WW Med 2020 Vol 2 issue: 1 12-23

Introduction

Systemic lupus erythematosus (SLE) is a prototypical multisystemic autoimmune disease. Neuropsychiatry (NP) syndromes of SLE (NPSLE) encompass a wide range of neurologic and psychiatric manifestations including cognitive dysfunction, mood disorder, psychosis, seizure, headache, and peripheral neuropathies. The prevalence reported for NPSLE ranges from 9-75% of SLE patients in various series, due to the lack of standard definition and no confirmative

method for the diagnosis. NPSLE has been shown to be a predictor of high frequency of disease flare and is associated with high mortality rate.

American College of Rheumatology (ACR) ad hoc committee1 defined 19 NPSLE features or syndromes categorized as

either central or peripheral nervous system. Diagnosis is often challenging and involves exclusion of other causes for the neurological symptoms. Treatment includes immunosuppressive therapy and anticoagulation in selected patients.

In this retrospective analysis, we identified NP events in 20 patients, based on American College of Rheumatology (ACR) ad hoc committee 1999 NP lupus definitions. The clinical features, disease activity, treatment and outcome of

our patients were analyzed.

Materials and methods

All new and established cases of SLE hospitalized from Dec 2017 to Dec 2019 in our centre were identified. All

patients fulfilled SLICC 2012 classification criteria for SLE. Based on the case definitions published by the ACR Ad Hoc committee on NP lupus syndromes, 20 patients were classified as NPSLE. Patients with neurological symptoms secondary to other factors such as hypertension, hypoxia, uremia, electrolyte imbalance or intracranial infection were excluded. Medical records were reviewed with attention to age, gender, disease activity, clinical manifestations,

treatment and outcome, including patient follow up at 3 and 6 months after NPSLE.

The disease activity of SLE was evaluated based on SLE disease activity index (SLEDAI). The score was evaluated before initiation of treatment. Clinical outcome was classified based on Neuwelt’s classification with modification. The

first group (improved) included patients with complete recovery or minor residual deficits. The second group (unchanged) had no new clinical events but old abnormalities remained. The third group (progressed or death), the NP symptoms exacerbated, or new symptoms developed or patients died during hospitalization. We defined those patients in the second or third group as having unfavorable outcomes.

Statistical analysis

Data obtained was organized in tables. Results with continuous data were expressed as mean ± standard deviation (SD). For comparison of categorical data, statistical analysis using contingency table Chi square statistical test was applied.

Statistical significance was defined as p value < 0.05.

Results

Baseline characteristics, manifestation, investigation, treatment and outcomes are summarized

in Table 1.

Patient characteristics

All patients fulfilled SLICC 2012 classification criteria for SLE. There were a total of 20 patients with NPSLE, 18 (90%) females and 2(10%) males. The mean age at the onset of NPSLE was 28.4 ± 10.01( ± SD) years old. NPSLE

occurred within 1 year of lupus diagnosis in all patients except for 2. All 17 patients with central nervous system 13

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symptoms underwent neuroimaging, either contrast enhanced computed tomography ( CECT) brain or MRI or both. 15

patients had CSF analysis done, which all had normal biochemistry and negative cultures, except for 1 patient with AIDP who had elevated protein.

Neuropsychiatric manifestations

There was a total of 34 NPSLE manifestation among the patients (Table 1). 65% (13) patients presented with singular

NP symptom, while 35% (7) patients had more than one, ranging from 2 to 3 manifestations. Central nervous system involvement was 85% (17) and while 15% (3) had peripheral nervous system manifestation. The most frequent manifestations were psychosis, followed by seizure , cerebrovascular disease ( radiological evidence) and acute

confusional state (Table 2). 85% (17) patients had inflammatory NPSLE and 15% (3) had thrombotic NPSLE.

SLE disease activity index (SLEDAI) score

85% (17) patients had high disease activity ( SLEDAI >12) and 15% (3) had moderate activity ( SLEDAI 6-12).

The lowest SLEDAI score was 9 (2 patients) and the highest was 41. The mean SLEDAI score was 22.65 ± 8.37. The

mean SLEDAI score for those who succumbed was 25 +/- 3.162, while those who had favorable outcome had a mean SLEDAI of 22.06 +/- 9.212.

Mean SLEDAI score of patients with only one NPSLE manifestation was 20.15 +/-8.75, while mean SLEDAI score for

those with 2 or more manifestation was 27.29 +/- 5.50. Most patients also had associated lupus nephritis, hematological and mucocutaneous involvement during the episode of NPSLE.

Immunological features

ANA was detected in all patients, while dsDNA in 80% (16) patients. 20% (4) patients had positive ENA ; 2 with both

anti-Ro and anti-La , 2 with anti-ribosomal P antibodies. 25%(5) patients had positive lupus anticoagulant antibody and 5%(1) with positive anticardiolipin antibody. All 20 patients had hypocomplementaemia.

Imaging

Neuroimaging was performed using CT, MRI or both (17 CT and 2 MRI). Contrast enhanced CT brain was the initial neuroimaging of choice due to limited resources for MRI.

Out of 17 patients with neuroimaging, abnormalities were found in 64.7% (11) patients, while 35.3%(6) other patients had normal findings.

Abnormalities found were infarcts 45.5% (5/11), cerebral atrophy 36.4% (4/11), venous thrombosis 27.3%(3/11), hypodensities suggestive of cerebritis 18.2%(2/11) and 9.1% (1/11) with areas of calcification. Although radiological evidence of infarcts was seen, clinically these patients did not have localizing focal neurological deficits.

TREATMENT & OUTCOME

Thrombotic NPSLE

There were 3 (15%) patients with cerebral venous thrombosis. 2 patients were diagnosed as secondary antiphospholipid

syndrome due to presence of lupus anticoagulant antibody ,and planned for lifelong anticoagulation (warfarin). The third patient however, was negative for antiphospholipid study and his thrombosis was attributed to his generalized high

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disease activity and anticoagulated ( dabigatran 150mg BD) for 6 months. Repeated neuroimaging at 6 months of

anticoagulation showed resolution of thrombosis in all 3 patients.

Peripheral Nervous System NPSLE

There were 3(15%) patients with NPSLE affecting the peripheral nervous system. First patient, was a 31-year-old lady presenting with acute lower motor neuron paraparesis, areflexia with associated lupus nephritis and photodermatitis.

Nerve conduction study was consistent with demyelination and CSF showed cytoalbuminergic dissociation. She was diagnosed as acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and was give intravenous immunoglobulin 0.4gm/kg daily for 5 days. She received mycophenolate mofetil 1gm BD with prednisolone 1mg/kg for

her concurrent lupus nephritis. She made full neurological recovery within 6 months with physiotherapy and rehabilitation.

2nd patient was a 13-year-old girl presenting with left foot drop and associated hematological, mucocutaneous and musculoskeletal flare. Nerve conduction study showed axonal pattern suggestive of mononeuritis multiplex. She was

given pulsed methylprednisolone 500mg daily for 3 days followed by oral prednisolone 1mg/kg daily, and intravenous cyclophosphamide 15mg/kg 2 weekly x 3, and 3 weekly x 3 ( EUVAS protocol) and subsequently placed on azathioprine 2mg/kg OD maintenance. She made significant improvement at 3 months, and full recovery at 6 months.

3rd patient was a 26-year-old SLE patient with leucopenia and low complements, developed bilateral eye ptosis and diplopia. No fatiguability demonstrable over other muscles. Her serum acetylcholinesterase antibody was positive and was diagnosed as ocular myasthenia gravis. Pyridostigmine was added and her symptoms resolved.

Central Nervous System NPSLE

There were 14 (70%) patients with inflammatory central nervous system NPSLE with manifestations including psychosis, seizure, acute confusional state and cognitive impairment. All patients received oral corticosteroids

(prednisolone 1mg/kg/day). 1 patient succumbed from sepsis and did not receive immunosuppressive therapy while remaining 13 (92.9%) patients received pulsed methylprednisolone 500mg daily for 3 days. 1 patient refused for cyclophosphamide, while remaining 12(85.7%) received intravenous cyclophosphamide , on average 3 to 6 cycles ( 6 cycles = 4patients, 3 cycles = 6 patients, 2 cycles =1;died , 1 cycle = 1;died ). The intravenous cyclophosphamide

dosing regimens were given as either as fixed dose of 500mg at 2 weekly intervals 3 – 6 cycles ( adapted from EUROLUPUS protocol) or 750mg/m2 monthly for 3 – 6 cycles ( adapted from NIH protocol).

All 10 patients who received intravenous cyclophosphamide for 3 to 6 cycles had complete resolution of neurological

symptoms at 3 months. A 30year old lady who presented with seizure, psychosis and cognitive impairment only received pulsed methlypredisolone and refused cyclophosphamide, however had complete resolution of her neurological symptoms with prednisolone alone at 3 months.

Total of 10/14 patients received remission maintenance therapy with azathioprine 2mg/kg daily ( 7patients) or

mycophenolate mofetil 1gm BD ( 3 patients). Mycophenolate mofetil was chosen in these 3 patients due to concurrent lupus nephritis. All patients were planned for maintenance therapy of at least 3 years in remission. Anticonvulsants and antipsychotics were prescribed as necessary.

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Mortality

In our case series, mortality rate was 20% (4/20) attributed to overwhelming sepsis. 3 patients received pulsed methylprednisolone and intravenous cyclophosphamide 1 -3 cycles before developing infection, whereas one patient succumbed during admission for NPSLE from infection even without immunosuppressive therapy ( Table 3).

Limitation

The main limitation of this study was the small sample of 20 patients. Larger pool of patient would likely yield difference in terms of outcome and mortality. Only 2 patients had MRI done, hence those with normal CT brain findings

may have had different abnormalities in MRI study.

Discussion

NPSLE can be seen in 30-40% of patients with SLE based on cohort studies. In general, 50-60 % of these cases occur at the time of onset of lupus or within 1 year of diagnosis. It is associated with generalized lupus activity in 40-50% of

patients.

Risk factors that have been associated with NPSLE are presence of antiphospholipid antibodies, generalized lupus activity and prior history of NPSLE . The pathophysiology of NPSLE is complex and includes autoantibody mediated

neuronal or vascular injury, production of inflammatory mediators and accelerated atherosclerosis.

Based on our study, there was a total of 20 patients with NPSLE ; 3 (15%) with thrombotic NPSLE, 3(15%) with peripheral nervous system, and 14(70%) with inflammatory central nervous system NPSLE. 17(85%) patients had high disease activity ( SLEDAI >12) and 3(15%) had moderate activity ( SLEDAI 6-12) with mean SLEDAI score of 22.65

± 8.37 .NPSLE occurred within 1 year of lupus diagnosis in all our patients except for 2.

There were 2(10%) patients with anti-ribosomal P antibodies, 5(25%) with lupus anticoagulant antibody and 1(5%) with positive anticardiolipin antibody. All 20(100%) patients had hypocomplementaemia.

The most frequent manifestations in our study were psychosis 8(23.5%), followed by seizure 7 (20.6%) , cerebrovascular disease ( radiological evidence) 5 (14.7%, acute confusional state 5 (14.70%), cognitive impairment 4 (11.8%), headache 2 (5.9%) and peripheral nervous system manifestations 3(8.8%).

Diagnosis of NPSLE can be challenging and is predominantly a diagnosis of exclusion of other conditions that can

cause such neurological symptoms including infection and metabolic causes. The standard approach in evaluating NPSLE should be the same as a non-lupus patient presenting with neurological complaint. Main investigation includes neuroimaging, CSF study and EEG in selected patients.

17 patients with central nervous system symptoms underwent neuroimaging, either contrast enhanced computed tomography ( CECT) brain or MRI or both. Abnormal neuroimaging was found in 11( 64.7%) patients , and these include infarcts 45.5% (5/11), cerebral atrophy 36.4% (4/11), venous thrombosis 27.3%(3/11), hypodensities suggestive of cerebritis 18.2%(2/11) and 9.1% (1/11) with areas of calcification.

In general, the neuroimaging of choice in NPSLE is MRI with a sensitivity of 57%.

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Frequent MRI finding includes small punctate hyperintense T2-weighted focal lesions in subcortical and periventricular

white matter (WM), usually in the frontal-parietal regions. However, it is important to note that these MRI lesions are also present in many patients without NPSLE ( specificity 60–82%). 2

Other advanced neuroimaging modalities include quantitative MRI magnetic resonance spectroscopy, magnetisation transfer imaging, diffusion tensor MRI, perfusion-weighted imaging) or radionuclide brain scanning (single photon

emission computed tomography (SPECT), or positron emission tomography ). 2

15 patients had CSF analysis done, which all had normal biochemistry and negative cultures, except for 1 patient with

AIDP who had elevated protein. The main importance of CSF study is to exclude intracranial infections. CSF findings can be normal or have mild abnormalities in 40-50% of cases. EEG can be useful to diagnose underlying seizure disorder.

Principle of treatment would depend on whether the manifestation is predominantly inflammatory , thrombotic or a

combination of both. Inflammatory NPSLE requires pulsed methylprednisolone 500-1000mg daily for 3 days followed by consideration for intravenous cyclophosphamide for at least 3 to 6 cycles. This should be followed by remission maintenance agents like azathioprine, cyclosporin or even mycophenolate mofetil. For thrombotic NPSLE, mainstay of

treatment will be anticoagulation for a minimum period of 6 months, and indefinitely in the presence of antiphospholipid antibodies. Adjunctive therapies include antipsychotics, antidepressants and antiepileptics.

There were 14 (70%) patients with inflammatory central nervous system NPSLE in our study. All patients received oral

corticosteroids (prednisolone 1mg/kg/day). 13 patients received pulsed methylprednisolone 500mg daily for 3 days and 12 received intravenous cyclophosphamide , on average 3 to 6 cycles . All patients who received intravenous cyclophosphamide for 3 to 6 cycles had complete resolution of neurological symptoms at 3 months. Complete

neurological recovery was also see in in a patient with seizure, psychosis and cognitive impairment who received only pulsed methylprednisolone without additional cyclophosphamide.

Total of 10 out of 14 patients received remission maintenance therapy with azathioprine 2mg/kg daily ( 7patients) and mycophenolate mofetil 1gm BD ( 3 patients with concurrent lupus nephritis). All patients were planned for maintenance

therapy of at least 3 years in remission. Anticonvulsants and antipsychotics were prescribed as necessary.

In our case series, mortality rate was 20% ( 4/20) attributed to overwhelming sepsis. 3 patients received pulsed methylprednisolone and intravenous cyclophosphamide before developing infection, whereas one patient succumbed

during admission for NPSLE from infection even without immunosuppressive therapy.

Conclusion: NPSLE is a major manifestation in lupus that can be challenging to diagnose and manage, and associated with

generalized lupus activity. It is an important contributing factor for mortality in SLE. Mainstay of treatment will be immunosuppressive therapy for inflammatory manifestation and anticoagulation for thrombotic events.

Conflict of interest All authors declare that they have no conflict of interest

Funding There was no funding received for this paper.

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Acknowledgement We would like to thank the Director General of Health of Malaysia for his permission to publish this article.

References

1) Ad hoc Committee on Neuropsychatric Lupus Nomenclature 1999, the ACR nomenclature and case definitions for neuropsychiatric lupus syndromes. Ad & Chairman, & Liang, Matthew. Arthritis Rheum 1999;42:599-608

2) EULAR recommendations for the management of systemic lupus erythematosus with neuropsychiatric manifestations: report of a task force of the EULAR standing committee for clinical affairs. Bertsias GK, Ioannidis JPA, Aringer M, et alAnnals of the Rheumatic Diseases 2010;69:2074-2082.

Age/

Sex

Presenta.on

SLEDAI

Immunological

Inves.ga.on / Imaging

Treatment Neurological

Outcome

1 33 M

Acute confusional state

41 ANA 1:160, DsDNA neg ENA neg ,ACL pos LA neg, Low C3

CT scan : Normal

CSF study Normal

IV MTP 500mg OD x 3 IV CYC 500mg , 2 weekly x 6 MMF 1gm BD maintenance ( for lupus nephriQs)

Complete recovery

2

39 F Acute confusional state

26 ANA 1:80, dsDNA pos, ENA neg, ACL/LA neg, Low c3/c4

CT scan hypodensiQes suggesQve of infarcts over corona radiata and basal ganglia

CSF study: Normal

IV MTP 500mg OD x 3 IV CYC 500mg ,2 weekly x 2 Succumbed

Succumbed

3

37 F CogniQve impairment

22ANA 1:160, dsDNA pos ENA neg, ACL/LA neg Low C3/C4

CT scan: Normal

CSF study: Normal

No immunosuppressive therapy due to infecQon

Succumbed

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4

45 F CogniQve impairment, Psychosis

18 ANA 1:320, dsDNA pos ENA neg, ACL/LA neg Low C3/C4

CT scan: mulQfocal hypodensiQes over biparietal and occipital region suggesQve of cerebriQs

CSF study :Normal

IV MTP 500mg OD x 3 IV CYC 750mg/m2 monthly x 3 , Subsequently changed to MMF 1gm BD for lupus nephriQs

Complete recovery

5 30 F Seizure, Psychosis, CogniQve impairment

27 ANA 1:80, dsDNA pos RO/LA pos, ACL/LA neg Low C4

CT scan: Normal

CSF study Normal

IV MTP 500mg OD x 3 Refused CYC Sodium Valproate 200mg BD

Complete recovery

6 15 F Seizure 17

ANA 1:640,dsDNA pos RO/LA pos,ACL/LA neg Low C3

CT scan: Normal

CSF study: Normal

IV MTP 500mg OD x 3 IV CYC 500mg ,2 weekly x 6 Azathioprine maintenance Sodium Valproate 200mg BD

Complete recovery

7 20 M

Seizures19

ANA 1:640 dsDNA pos ENA negaQve ACL/LA/B2glycoprotein-1 negaQve Low C3/C4

MRI/MRA/MRV: Le] parasagi^al corQcal vein thrombosis EEG Normal

AnQcoagulaQon 6 months Prednisolone Epilim 200mg BD

Complete recovery

8 23 F Status epilepQcus

18 ANA 1:80,DsDNA neg ENA neg,ACL/LA neg Low c3/c4

CT scan: areas of hypodensiQes suggesQve of cerebriQs CSF study: Normal

IV MTP 500mg OD x 3 IV CYC 750mg/m2 monthly x 3 Azathioprine maintenance LeveQracetam 500mg BD

Complete recovery

9 14 F Status epilepQcus, Psychosis

31 ANA 1:160,dsDNA pos ENA neg,ACL/LA neg Low c3/c4

CT scan: Normal

CSF study Normal

IV MTP 500mg OD x 3 IV CYC 500 mg ,2weekly x 6 AnQpsychoQcs Sodium Valproate 200mg BD Azathioprine maintenance

Complete Recovery

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10 22 FSeizure, Psychosis, CogniQve impairment

35 ANA 1:320,DsDNA pos AnQribosomal pos, LA pos, ACL neg Low c3/c4

CT scan : Normal

CSF study : Normal

IV MTP 500mg OD x 3 IV CYC 500mg ,2 weekly x 3 Azathioprine maintenance LeveQracetam 500mg BD

Complete recovery

11

17 F Status epilepQcus & Acute confusional state

29 ANA 1:320, dsDNA pos ENA neg, LA pos ACL neg, Low c3/c4

MRI: mild generalized cerebral atrophy, mulQple hypodensiQes suggesQve of microangiopathic infarcts, periventricular deep white ma^er changes

CSF study: Normal

IV MTP 500mg OD x 3 IV CYC 500mg x 1 Refused further CYC Started MMF 1gm BD for lupus nephriQs LeveQracetam 500mg BD

Succumbed

1228 F Psychosis

,Acute confusional state

28ANA 1: 80, dsDNA pos ENA neg, ACL/LA neg Low c3/c4

CT scan: cerebral atrophy with hypodensiQes possible lacunar infarcts

CSF Study Normal

IV MTP 500mg OD x 3 IV CYC 750mg/m2 monthly x 6 Azathioprine maintenance

Complete Recovery

1327 F Psychosis

, Acute confusional state

23 ANA : 160, DsDNA pos ENA neg, ACL/LA neg Low c3/c4

CT scan: Patchy linear calcificaQon within the parenchyma of frontal and cerebellum bilaterally

CSF study: Normal

IVIG 1gm/kg OD x 2 IV MTP 500mg OD x 3 IV CYC 500 mg ,2 weekly x 3 AnQpsychoQcs

Succumbed

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30 F Psychosis 18

A N A 1:160,dsDNA pos ENA neg,ACL/LA neg Low c3/c4

CT scan :cerebral atrophy & old infarcts

C S F s t u d y : Normal

IV MTP 500mg OD x 3 IV CYC 500mg, 2 weekly x3 AnQpsychoQcs Azathioprine maintenance

Complete Recovery

15

31 F Psychosis 22 ANA 1:320,dsDNA neg ENA neg,ACL/LA neg Low c3/c4

CT scan :mild cerebral atrophy

CSF study: Normal

IV MTP 500mg OD x 3 IV CYC 500mg, 2 weekly x 3 Azathioprine maintenance

Complete recovery

1635 F Headach

e 9 ANA 1: 160,

dsDNA pos ENA neg, LA pos, ACL neg, Low C4

CT scan :transverse sinus thrombosis

AnQcoagulaQon lifelong Complete recovery

1752 F Headach

e 23

ANA 1:80,dsDNA pos AnQribosomal pos, LA pos,ACL neg Low C3/C4

CT scan :thrombosis of le] straight sinus, inferior sagi^al and great vein of Galen with lacunar infarcts

AnQcoagulaQon lifelong Complete recovery

18

31 F AIDP ( Paraparesis with areflexia)

28 ANA 1: 320, dsDNA pos, ENA neg, ACL/LA neg, Low C3/C4

Nerve ConducQon Study: DemyelinaQon

CSF high protein, acellular

IVIG 0.4gm/kg OD x 5 Prednisolone 1mg/kg OD

Started MMF 1gm BD for Lupus NephriQs

Complete recovery

19 13 F MononeuriQs MulQplex ( Right Foot Drop)

10 ANA 1:320, dsDNA pos, ENA neg, ACL/LA neg, Low c3/c4

Nerve ConducQon Study : MononeuriQs mulQplex

IV MTP 500mg OD x 3 IV CYC 15mg/kg ,2 weekly x3, then 3 weekly x3 Azathioprine maintenance

Complete recovery

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Table 2 :Neuropsychiatric manifestation of 20 patients with NPSLE

Table 3: Predictor analysis of outcome

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26 F Myasthenia Gravis ( Ocular)

9 ANA 1: 320, dsDNA neg, ENA neg, ACL/LA neg, Low C3/C4

AnQ- Acetylcholine Receptor AnQbody pos

Prednisolone PyridosQgmine

Complete Recovery

ANA = AnQ nuclear anQbody, dsDNA = AnQ double stranded DNA, ENA = Extractable nuclear anQgens, ACL = AnQ-cardiolipin anQbody, LA = Lupus anQcoagulant anQbody, IV MTP = Intravenous methylprednisolone, IV CYC = Intravenous cyclophosphamide, CSF = Cerebrospinal Fluid study, CT = Computed tomography brain, MRI = MagneQc resonance imaging, neg = negaQve, pos = posiQve

Table 1:Summary of all patients, characteristics, manifestation and treatment outcome

Neuropsychiatric manifestation Number of patients (%) ( n= 20, 34 events)

Psychosis 8 (23.53%)

Seizure 7 (20.59%)

Acute confusional state 5 (14.70%)

Cerebrovascular disease 5(14.70%)

Cognitive Impairment 4 (11.76%)

Headache 2 (5.88%)

AIDP 1 (2.94%)

Mononeuritis multiplex 1(2.94%)

Myasthenia Gravis 1(2.94%)

Predictor Unfavourable outcome (n=4) Favourable outcome (n=16)

Age 30 +/- 10.3 28 +/- 10.6

Thrombotic NPSLE ( n=3) 0 3

Peripheral Nervous System NPSLE ( n = 3)

0 3

Central Nervous System NPSLE ( n =14)

4 10

Manifestations >1 2 5

SLEDAI Score mean 25 +/- 3.16 22.06 +/- 9.212

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Cyc Treatment ( n = 12) 3 9

Pulse IV MTP ( n= 13) 3 10

Antiphospholipid Antibody ( n = 6)

1 5

Anti-ribosomomal p Antibody(n = 2)

0 2

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