Presentation is loading. Please wait.

Presentation is loading. Please wait.

Kathryn Hazel C. Trinidad M.D. First Year Medical Resident.

Similar presentations

Presentation on theme: "Kathryn Hazel C. Trinidad M.D. First Year Medical Resident."— Presentation transcript:

1 Kathryn Hazel C. Trinidad M.D. First Year Medical Resident

2 To be able to present a known case of SLE who developed seizure during the course of illness To be able to know the diagnosis, treatment, and prognosis of NPSLE To be able to know the latest updates with regards to NPSLE

3 H.M 35 year old G3P2 (1112) female right-handed known case of SLE maintained on Prednisone 20mg 2x/day known case of APAS, maintained on ASA 80mg OD housewife

4 Seizure

5 May 2002 experienced on-off fever (Tmax 40C), malar rash, joint pains, vomiting, photosensitivity, and oral ulcers. diagnosed with SLE; started on Prednisone 5mg OD; regular OPD follow-up Nov 2007 (+) miscarriage; OPD follow-up for clearance prior to dilatation and curettage

6 TestResultsN.V. Kaolin Clotting Time79 sec50 – 90 sec APTT32 sec25 – 40 sec DRVVT37 sec31 – 44 sec ACA IgG18.8 GPL units/mLup to 15.0 GPL units/mL ACA IgM11.72 MPL units/mLup to 12.5MPL units/mL Feb 2008 diagnosed with APAS based on history and lab results: She was started on ASA 80mg OD

7 9 months PTA(July 2008) 1st prenatal check- up at 7wks AOG. No rashes, joint pains, and oral ulcers; Started on Heparin 5,000 IU SQ OD Prednisone 5mg OD and ASA 80mg OD continued. Monthly prenatal check-up with both Rheumatology and OB-GYN services

8 2 months PTA(March 2009) gave birth to a live preterm male via LTCS; Discharged with ASA 80mg OD and Heparin 5,000 IU/mL; Prednisone was not resumed

9 11days PTA, OPD ff up with (+)occasional upper back pain, grade I bipedal edema, raised macules on both face and upper extremities. Prednisone 5mg OD was resumed. CBC, urinalysis and ESR were requested.

10 4 days PTA (+) diffuse headache & joint pains; (+) fever; inc. rashes in face & extremities; consult done Prednisone inc. to 20mg BID; Advised ff up of lab requests 3 days PTA pancytopenia: (Hgb-9.5 hct wbc-2,640 plt-120,000) and proteinuria(+4) hematuria(1171/hpf), pyuria(335/hpf) bacteriuria(404); ESR was elevated at 111. Ciprofloxacin 500mg BID

11 7 hrs PTA severe headache (10/10)slightly relieved by Paracetamol. (-) vomiting nor blurring of vision 30 mins PTA tonic-clonic seizure ~ 30 minutes MMC ER Admission

12 Non-hypertensive Non-diabetic s/p CS (2001) s/p dilation and curettage November 2007 No history of travel outside of Metro Manila.

13 Family History: No hypertension No diabetes No connective tissue disease. Personal and Social History: Non-smoker Non-alcoholic beverage drinker Worked as a bank teller prior to being diagnosed with SLE Currently stays at home and takes care of her children; can do light household chores

14 Gen. Survey: Drowsy, not in cardio-respiratory distress Vital signs: BP = 200/ /100 HR 81 RR 20 Temp 36.7C Skin: raised macules on the face and both upper extremities HEENT: Anicteric sclerae, pink palpebral conjunctivae, (+) subconjunctival effusion, no tonsillopharyngeal discharge, no cervical lymphadenopathy Chest: Symmetrical chest expansion, no retractions, clear breath sounds

15 Heart: Adynamic precordium, distinct S1 and S2, normal rate and rhythm, no murmurs Abdomen: Flabby abdomen, soft, non-tender, normoactive bowel sounds Extremities: Full and equal pulses, no cyanosis and no edema

16 MSE: Drowsy, opens eyes to verbal stimulation but non-sustained, does not follow commands Cranial Nerves: Pupils 3mm EBRTL; Full EOMS; (+) visual threat on all planes; (-) facial asymmetry; (+) gag Sensory: Withdraws to pain in all extremities MMT: Moves all extremities non-purposely Reflexes: +2 in all reflexes Pathologic Reflexes: No Babinski Meninges: Supple neck

17 35 year old G3P2 (1112) female known case of SLE on Oral steroids Steroids on hold for 1 month; resumed ~ 1 week prior to onset of symptoms known case of APAS, maintained on ASA 80mg OD Came in for tonic-clonic seizure History of fever, headache, rashes, and joint pains few days prior to seizure

18 Proteinuria, pyuria on urinalysis sample done few days PTA On PE: Drowsy, does not follow commands, opens eyes to verbal stimulation (GCS ~ 9 – 10) Elevated BP upon admission Raised macules on the face and both upper extremities Withdraws to pain on stimulation Moves extremities non-purposely Intact reflexes Supple neck

19 Neuropsychiatric SLE R/O CNS infection Lupus nephritis Hypertension, secondary UTI APAS


21 CBC, Urinalysis, C3, 24hour urine, ESR, antiSmith, antidsDNA Complete Blood Count revealed improvement in pancytopenia Complete Blood Count Hydrocortisone 100mg IV q8 Referral to neurology service NGT feeding started

22 3 episodes of seizures at ER – Midazolam 5mg IV Loading dose Phenytoin 300mg IV x 2 doses 1 hour apart Phenytoin 100mg IV q8 Citicholine 1g IV q12 Mannitol 20% 75ml IV q6

23 Urinalysis Co- amoxiclav 1.2 g IV every 8 hours

24 Lumbar tap done Lumbar CT Scan revealed normal EEG Methylprednisolone 1 g IV in D5W 500mL x 4hours for 3 days

25 BP /100 Cardiology referral Nicardipine drip started ECG, CXR, 2Decho were normal

26 (-)seizures (-)headache still drowsy but opens eyes to verbal stimuli, moves all extremities spontaneously BP was /100mmHg Phenytoin was shifted to Leviteracetam(Keppra) 500mg ½ tablet BID Nicardipine overlapped w/ Amlodipine 5mg OD

27 (-) seizures/headache Awake, conversant Mannitol was tapered down to 50mL Q8 then later D/C Last dose Methylprednisolone pulse therapy Hydrocortisone 100mg IV q8

28 24 hr urine collection proteinuria with a creatinine clearance of 83.5mL/min. 24 hr Serum complement C3, anti-SM and anti-dsDNA were requested which showed low C3 levels and positive anti-SM and anti-dsDNA Urine culture – no growth Nephrology referral Imidapril 5mg OD UTZ guided kidney biopsy contemplated

29 (-) seizures/headache Awake, conscious, coherent Tolerated soft diet, NGT removed Placed on full diet Hydrocortisone shifted to Prednisone 25mg BID

30 No recurrence of seizures, headache, no fever Co- Amoxiclav IV was shifted to oral Co- Amoxiclav 625mg BID ASA discontinued anticipating kidney biopsy Leviteracetam continued

31 No recurrence of seizures, headache, no fever Decrease in raised macules on face and UE CBC showed decrease in platelet to 80,000 Prednisone increased to 30mg BID Kidney biopsy to be done as outpatient

32 No recurrence of seizures, headache, no fever, significant decrease in malar rash and macules on upper extremities Patient cleared for discharge from all services

33 Patient discharged improved and stable

34 NPSLE Lupus Nephritis Hypertension, secondary Urinary Tract Infection, resolved APAS


36 Systemic lupus erythematosus (SLE) multisystem autoimmune connective tissue disorder with various clinical presentations Affects many organ systems, including the central and peripheral nervous systems and muscles. 90% of patients are women of childbearing age Incidence is cases per 100,000 people With full access to medical care, overall survival for SLE is 85% at 5 years and 63% at 15 years Harrisons Principles of Internal Medicine 17 th Ed.

37 SLE is caused by interactions between susceptible genes and environmental factor resulting in abnormal immune response 1. Hyper-reactivity and hypersensitivity of T and B lymphocytes 2. Ineffective regulation of antigen availability and ongoing antibody response Harrisons Principles of Internal Medicine 17 th Ed.

38 End result: sustained production of pathogenic auto- antibodies and formation of immune complexes that bind target tissues, resulting in: 1. Sequestration and destruction of Ig-coated circulating cells 2. Fixation and cleaving of complement proteins 3. Release of chemotaxins, vasoactive peptides, and destructive enzymes into tissues

39 Malar rashFixed erythema, flat or raised, over malar eminence Discoid rashErythematous circular raised patches with adherent keratotic scaling and follicular plugging; atropic scarring may occur PhotosensitivityExposure to UV light causes rashes Oral ulcersOral or nasopharyngeal ArthritisNonerosive, involving 2 or more joints SerositisPleuritis: + pleuritic pain or rub, OR pleural effusion, OR pericardial effusion Renal disorderPersistent proteinuria OR cellular casts Neurologic disorderSeizures or psychosis Hematologic disorderHemolytic anemia with reticulocytosis OR Leukopenia < 4000 OR lymphopenia < 1,500 OR thrombocytopenia < 100,000 ANAPositive; if negative, check for anti-SSA (Ro) antibodies Anti-dsDNA or anti- smith antibody Positive; highly specific for SLE Harrisons Principles of Internal Medicine 17 th Ed.


41 Hebra and Kaposi (1875) Noted first neurologic involvement in SLE Baum (1904) Related active delirium, aphasia and hemiparesis to probable disseminated LE Daly (1945) conducted 1 st modern study of NP-SLE Lewis (1954) 1 st to focus on importance of EEG findings and psychometric testing in patients with NP-SLE Over the last 3 decades, appreciation of Clinical significance of antineuronal, antiribosomal P, and antiphospholipid antibodies as well as advances in brain Imaging have again altered our concept of NP-SLE Joseph FG, Lammie AG, Scolding NG. CNS lupus: A study of 41 patients. Neurology. 2007

42 Incidence of neuropsychiatric manifestations in SLE ranges from 14 – 75% Patients with NP-SLE can present with a myriad of diffuse and/or focal symptoms and signs involving the brain, spinal cord, or peripheral nervous system

43 Vasculopathy Hyalinization Peripheral inflammation w/o infection Endothelial proliferation w/o infection Thrombosis Vasculitis Hemorrhage Subarachnoid Microhemorrhages Subdural Intracerebral Infarction Microinfarcts Large infarcts Infection Meningitis Perivascular inflammation with infection Septic hemorrhages Focal cerebritis Vasculitis with infection Joseph FG, Lammie AG, Scolding NG. CNS lupus: A study of 41 patients. Neurology. 2007

44 1. Vasculopathy 2. Auto-antibodies 3. Others Schur PH, Khoshbin S. Neurologic manifestations of systemic lupus erythematosus.

45 characterized by small to moderate perivascular accumulation of mononuclear cells, without destruction of the blood vessel. May have small infarcts Pathogenesis not known Antiphospholipid antibodies may play a role Accelerated atherosclerosis may contribute to the risk of stroke in patients with SLE Schur PH, Khoshbin S. Neurologic manifestations of systemic lupus erythematosus. Joseph FG, Lammie AG, Scolding NG. CNS lupus: A study of 41 patients. Neurology. 2007

46 (+) Antineuronal antibodies found in one report in 45 percent of patients with CNS lupus Cognitive dysfunction associated with lymphocytotoxic antibodies Antiphospholipid antibodies increase the risk of stroke syndromes, recurrent seizures and abnormal findings on MRI Schur PH, Khoshbin S. Neurologic manifestations of systemic lupus erythematosus.

47 Antiribosomal P protein antibodies associated with lupus psychosis and depression but not with cognitive dysfunction or psychologic distress High levels of autoantibodies to a 50 kDa antigen located in the plasma membrane of brain synaptic terminals in 19 of 20 patients with SLE who had CNS involvement Antiribosomal-P autoantibodies from psychiatric lupus target a novel neuronal surface protein causing calcium influx and apoptosis Soledad Matus, 1,2,4 Patricia V. Burgos, 1,2,4 Marcela Bravo-Zehnder, 1,2,4 Regine Kraft, 6 Omar H. Porras, 5

48 Cytokines Neuropeptides Oxidative stress Nitric oxide Interference with neurotransmission Genetic heterogeneity Schur PH, Khoshbin S. Neurologic manifestations of systemic lupus erythematosus.

49 Primary Vascular occlusion/hemorrhage Auto-antibody- mediated Choroid Plexus dysfunction Cytokine effects Other mechanisms Secondary Infection Medications TTP Hypertension Uremia Electrolyte imbalances Fever Thyroid disease Atherosclerotic strokes Subdural hematoma Cerebral lymphoma Reactive depression Schur PH, Khoshbin S. Neurologic manifestations of systemic lupus erythematosus.

50 Confirm diagnosis of lupus according to ARA criteria Careful history and PE Diagnostics Monitoring: If patient improves: monitor history and PE If patient gets worse: PET scan/MRI, LP Schur PH, Khoshbin S. Diagnostic approach to the neuropsychiatric manifestations of systemic lupus erythematosus.

51 1. Blood tests: a. Complete blood cell count including platelet count and smear may demonstrate a hemolytic anemia with reticulocytosis or reductions of neutrophils, lymphocytes, or platelets b. Creatinine or creatinine clearance c. Urinalysis d. Liver function tests e. Electrolytes f. C3, C4, or CH50 g. Anti-dsDNA antibodies h. Erythrocyte sedimentation rate or C- reactive protein i. Antiphospholipid antibodies j. Lipid profile, glucose Ramachandran T, Grisola JS. Systemic Lupus Erythematosus.

52 2. CSF Studies: a. Cell count b. Protein c. Glucose d. Cultures e. Gram stain and other special stains f. VDRL g. IgG index h. Oligoclonal bands Ramachandran T, Grisola JS. Systemic Lupus Erythematosus.

53 3. Imaging: a. CT Scan indicated for suspected acute hemorrhage and in patients with contraindications to MRI (intracranial metal, pacemakers, etc.) b. MRI more sensitive and used to define site and extent of lesions. A negative MRI result does not rule out CNS lupus, and MRI abnormalities may not be diagnostic of NPSLE. Follow-up MRIs may be indicated to document progression, improvement, or significance of lesions Ramachandran T, Grisola JS. Systemic Lupus Erythematosus.

54 Positron emission tomography (PET) and single photon emission computed tomography (SPECT) have also been explored as functional imaging tools in lupus and both appear to be more sensitive in detecting subtle brain changes in NPSLE

55 4. EEG Standard EEG indicated in seizures and encephalopathies. Evoked potentials are performed for suspected demyelinating disease. 5. Psychologic Testing 6. Others: 2D echo Ramachandran T, Grisola JS. Systemic Lupus Erythematosus.

56 Stroke - CT scan, blood tests for coagulopathy (including lupus anticoagulant), MRI, echocardiogram, carotids ultrasonography Seizures – EEG Neuropathy – EMG Psychosis - MRI, EEG, lumbar puncture Cognitive abnormalities - Psychometric testing, MRI, EEG, blood tests for coagulopathy, antibrain antibody Anxiety or depression - Psychometric testing Meningitis/fever - lumbar puncture Schur PH, Khoshbin S. Diagnostic approach to the neuropsychiatric manifestations of systemic lupus erythematosus.

57 High-dose IV corticosteroid regimens consist of methylprednisolone 1-2 g daily for 3-6 doses, followed by oral prednisone 60 mg daily, then tapering according to clinical recovery Various steroid-sparing strategies have evolved for long-term use, including cyclophosphamide mg/kg/d, azathioprine 1-2 mg/kg/d,, permitting gradual reduction or elimination of chronic steroid therapy. Ramachandran T, Grisola JS. Systemic Lupus Erythematosus.

58 Intravenous cyclophosphamide (at an initial dose of 500 mg per square meter of body surface area) is given in the ff: 1. Acute or recent onset of neurologic symptoms such as seizures or organic brain syndromes in the absence of another cause. 2. Evidence of active inflammation in the brain such as increased cells and protein in the cerebrospinal fluid, brain swelling on MRI or CT scan. 3. Failure to respond to a one to two week course of high dose oral corticosteroids (eg, prednisone in a dose of 1 to 2 mg/kg per day) or to pulse methylprednisolone (1000 mg/day for three days). Ramachandran T, Grisola JS. Systemic Lupus Erythematosus.


60 Patients and methods: RCT at two tertiary care centres of patients with SLE with severe NP manifestations such as seizures, optic neuritis, peripheral or cranial neuropathy, coma, brainstem disease, or transverse myelitis. Induction treatment with 3 g of IV methylprednisolone (MP) followed by either IV monthly cyclophosphamide (Cy) versus IV MP bimonthly every 4 months for 1 year and then IV Cy or IV MP every 3 months for another year. The primary end point was response to treatment: at least 20% improvement from basal conditions on clinical, laboratory, or specific neurological testing variables.

61 CONCLUSIONS Cy was significantly more effective than MP. Cy was clearly better in patients with seizures, peripheral neuropathy, optic neuritis, and brainstem disease, while differences were not clear in coma and transverse myelitis RESULTS Of the 32 patients studied, 18/19 receiving Cy and 7/13 receiving MP responded to treatment (p,0.03)


63 Study describes the results of treatment of patients with NPSLE who had previously failed to respond to various immunosuppressants. Rituximab anti-CD20 antibody a chimeric antibody that directly targets B cells a biological preparation that eliminates B cells through a variety of mechanisms such as antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity and apoptosis. has recently been used for the treatment of a variety of SLE disease conditions and good therapeutic response has been reported

64 Inclusion Criteria: 1. Presence of a highly active disease 2. CNS lesions resistant to conventional treatment. such as intravenous cyclophosphamide pulse treatment (IV-CY), cyclosporine A (CsA), PE and immunoadsorption therapy Treatment Protocol: Patients 1–5 and 10 treated with 375 mg/m2 rituximab once a week for 2 weeks Patient 9 treated with single dose of 375 mg/m2 rituximab Patients 6 and 7 treated with 500 mg rituximab once a week for 4 weeks Patient 8 treated with 1000 mg once biweekly for 4 weeks.

65 Treatment with rituximab resulted in rapid improvement of central nervous system-related manifestations, particularly acute confusional state. Rituximab also improved cognitive dysfunction, psychosis and seizure, and reduced the SLE Disease Activity Index Score at day 28 in all 10 patients. These effects lasted for >1 year in five patients. Flow cytometric analysis showed that rituximab down regulated CD40 and CD80 on B cells and CD40L, CD69 and inducible costimulator on CD4+ T cells.


67 Rituximab rapidly improved refractory NPSLE, as evident by resolution of various clinical signs and symptoms and improvement of radiographic findings. The down regulation of functional molecules on B and T cells suggests that rituximab modulates the interaction of activated B and T cells through costimulatory molecules. These results warrant further analysis of rituximab as treatment for NPSLE


69 4/24/094/28/095/4/09 Hgb Hct WBC2,6405,1607,730 Seg Lym Mono9118 Platelet Count 120,000140,00080,000

70 4/24/094/28/095/4/09 Hgb Hct WBC2,6405,1607,730 Seg Lym Mono9118 Platelet Count 120,000140,00080,000

71 4/24/094/28/094/29/094/30/095/4/09 ESR11177 Na K BUN Crea RBS120 CRPNeg C330.3 Anti-SM+ dsDNA+ Albumin2.3

72 4/24/094/28/09 ColorYellow TransparencyHazy pH Spec. Grav1.02 SugarNegative CHON+4+3 KetonesNegative NitritesNegative Leucocyte Esterase Negative RBC1,171.50/uL2,123.00/uL WBC335.50/uL236.50/uL Epithelial Cells16.50/uL11.0/uL Bacteria404.06/uL245.16/uL

73 CSF Analysis CSF CSF GS/CSNo microorganism seen; Pus cells 0 – 1/OIF AFBNo acid fast bacilli seen VDRLNon-reactive Phadebact Negative for Streptococcus Group B, Streptococcus pneumoniae, Haemophilus influenzae type B, Neisseria meningitides ABCY W135 and E. coli K1 antigens CALASNegative India InkNegative KOHNo fungal elements seen ColorNon-xanthochromic TransparencyClear RBC13/uL WBC Lymphocytes 1/uL 1% ProteinTotal CHON: 88.8 mg% (NV 15 – 45) SugarGlucose 59 mg% (NV 40 – 75) Urine CSNo growth in 48 hours

74 Urine chemistry Urine Protein535.2 mg% = /24 hours (Ref Value: 0 – 149.1mg/24hrs) Urine Creatinine90.2 mg% = mg /24 hours (Ref Value: 600 – 2500 mgs/24hrs) Total Volume1600mL / 24hrs

75 IMAGING STUDIES CXRnormal Cranial CT ScanNormal non-contrast CT 2D EchoNormal LV dimension with normal wall thickness, motion and contractility. Color flow and Doppler study showed trace MR and PR with mild TR. There was also a note of decreased relaxation based on prolonged IVRT. EEG Abnormal EEG due to epileptiform discharges on the right frontocentrotemporal region suggestive of a tenderncy towards localization related seizure, on top of mild diffuse slowing of background activity at 7 – 8 Hz


Download ppt "Kathryn Hazel C. Trinidad M.D. First Year Medical Resident."

Similar presentations

Ads by Google