Neuropsychiatric Neuropsychiatric Systemic Lupus Systemic Lupus

Erythematosus (NPSLE)Erythematosus (NPSLE)Case presentations and topic Case presentations and topic

discussiondiscussionThe Rheumatology Unit UMMC The Rheumatology Unit UMMC

experienceexperience

ReferencesReferences Sanna G, Bertolaccini ML. Neuropsychiatric Sanna G, Bertolaccini ML. Neuropsychiatric

manifestations in systemic lupus erythematosus: manifestations in systemic lupus erythematosus: prevalence and association with antiphospholipid prevalence and association with antiphospholipid antibodies. antibodies. J Rheumatology 2003; 30: 985-992.J Rheumatology 2003; 30: 985-992.

The AmericanThe American College of Rheumatology College of Rheumatology nomenclature and case definitions for nomenclature and case definitions for neuropsychiatric lupus syndromes. neuropsychiatric lupus syndromes. Arthritis Arthritis Rheum 1999;42:599-608Rheum 1999;42:599-608

Bruyn GA. Controversies in lupus: Nervous system Bruyn GA. Controversies in lupus: Nervous system involvement. involvement. Rheum Dis 1995: 54: 159-167Rheum Dis 1995: 54: 159-167

CNS Lupus – Current scenario in CNS Lupus – Current scenario in UMMCUMMC

From the beginning of 2005 an From the beginning of 2005 an average of 1 admission a month average of 1 admission a month (new case).(new case).

Varied presentations closely Varied presentations closely following the revised ACR criteria following the revised ACR criteria ( 19 NPSLE definitions)( 19 NPSLE definitions)

Problems with establishing a Problems with establishing a concrete diagnosis and we lack a concrete diagnosis and we lack a clear treatment protocol.clear treatment protocol.

CNS Lupus CNS Lupus

Nervous system manifestations are Nervous system manifestations are present in up to 70% of patients with present in up to 70% of patients with SLE.SLE.

There are 19 definitions which are There are 19 definitions which are components of NPSLE. The earlier components of NPSLE. The earlier classifications only recognized 2 classifications only recognized 2 clinical entities – clinical entities – seizuresseizures and and psychosespsychoses

NPSLE based on the revised ACR NPSLE based on the revised ACR criteriacriteria

Acute confusional Acute confusional statestate

Anxiety disordersAnxiety disorders Cognitive function Cognitive function

impairmentimpairment Affective disordersAffective disorders psychosespsychoses

Cranial nerve Cranial nerve disordersdisorders

MononeuropathyMononeuropathy Plexus neuropathyPlexus neuropathy Vegetative Vegetative

neuropathyneuropathy MyastheniaMyasthenia AIDPAIDP PolyneuropathyPolyneuropathy

NPSLE component entitiesNPSLE component entities

Epileptic attacksEpileptic attacks Headaches and migrainesHeadaches and migraines Cereberovascular diseasesCereberovascular diseases Demyelinating syndromesDemyelinating syndromes Aseptic meningitisAseptic meningitis ChoreaChorea myelopathymyelopathy

CNS Lupus – problems in CNS Lupus – problems in diagnosisdiagnosis

Subtle presentations – wouldn’t I be Subtle presentations – wouldn’t I be depressed or anxious (or both) if I depressed or anxious (or both) if I was diagnosed with SLE ?was diagnosed with SLE ?

Effect of corticosteroidsEffect of corticosteroids Other differential diagnoses? Other differential diagnoses?

Infections and metabolic diseasesInfections and metabolic diseases access to imaging facilitiesaccess to imaging facilities

NPSLE specific antibodiesNPSLE specific antibodies

Anti ribosomal P antibodyAnti ribosomal P antibody Anti neuronal antibodiesAnti neuronal antibodies

ImagingImaging

MRI by far the most superiorMRI by far the most superior SPECT scans have also been found SPECT scans have also been found

to be usefulto be useful In the UMMC experience the MRI has In the UMMC experience the MRI has

shown to be of great diagnostic valueshown to be of great diagnostic value

MRI Images of 2 patientsMRI Images of 2 patients

Case 1 – 14 years old Indian girl who Case 1 – 14 years old Indian girl who presented to Kuantan with dense presented to Kuantan with dense right sided hemiplegia who showed right sided hemiplegia who showed remarkable recovery with remarkable recovery with intravenous Methyl Prednisolone.intravenous Methyl Prednisolone.

Low complements, anti dsDNA 276 Low complements, anti dsDNA 276 iu/mL, Ig ACL 4 units, LA negativeiu/mL, Ig ACL 4 units, LA negative

MRI Images of 2 patientsMRI Images of 2 patients

12 years old Chinese girl presented 12 years old Chinese girl presented with seizures while under treatment with seizures while under treatment for class IV lupus nephritis.for class IV lupus nephritis.

Low complements anti dsDNA 167 Low complements anti dsDNA 167 iu/mL, IgG ACL 4 units, LA negative.iu/mL, IgG ACL 4 units, LA negative.

Cases presented today had CT scans Cases presented today had CT scans with contrast which were normal but with contrast which were normal but with low complements and anti ds with low complements and anti ds DNA in the thousandsDNA in the thousands

NPSLE - CSFNPSLE - CSF

Varied findings among samples from Varied findings among samples from our cases, an indicator which we use our cases, an indicator which we use is the CSF proteins (tend to be higher is the CSF proteins (tend to be higher then 0.45)then 0.45)

More useful to rule out infections. More useful to rule out infections. AlwaysAlways send for TB culture. send for TB culture.

Therapeutic approach in CNS lupus Therapeutic approach in CNS lupus – mild disease– mild disease

Symptomatic therapySymptomatic therapy AnalgesicsAnalgesics AnxiolyticsAnxiolytics AntidepressantsAntidepressants TricyclicsTricyclics FluoxetineFluoxetine Anti convulsantsAnti convulsants Anti psychoticsAnti psychotics Low dose corticosteroidsLow dose corticosteroids

Therapeutic approach in CNS Lupus – Therapeutic approach in CNS Lupus – severe CNS disease: diffuse/nonthrombotic severe CNS disease: diffuse/nonthrombotic

diseasedisease Acute treatmentAcute treatment High dose corticosteroidsHigh dose corticosteroids Iv pulse methylprednisoloneIv pulse methylprednisolone Iv pulse cyclophosphamideIv pulse cyclophosphamide PlasmapharesisPlasmapharesis Iv immunoglobulinsIv immunoglobulins Intrathecal methotrexateIntrathecal methotrexate AzathioprineAzathioprine Mycophenolate mofetilMycophenolate mofetil

Therapeutic approach in CNS Lupus – Therapeutic approach in CNS Lupus – severe CNS disease: diffuse/nonthrombotic severe CNS disease: diffuse/nonthrombotic

diseasedisease Chronic treatmentChronic treatment Taper corticosteroidsTaper corticosteroids Iv pulse cyclophosphamideIv pulse cyclophosphamide MethotrexateMethotrexate AzathioprineAzathioprine Mycophenolate mofetilMycophenolate mofetil

Current practice at UMMCCurrent practice at UMMC

Intravenous methylprednisolone Intravenous methylprednisolone 500mg daily for 3 days followed by 500mg daily for 3 days followed by one of 2 cyclophosphamide regimesone of 2 cyclophosphamide regimes

1) monthly courses of 1.0grams/BSA 1) monthly courses of 1.0grams/BSA for 6 months followed by 3 monthly for 6 months followed by 3 monthly courses.courses.

2) 2 weekly courses of 500mg total 2) 2 weekly courses of 500mg total of 6 doses (3 grams in total)of 6 doses (3 grams in total)

Current practice at UMMCCurrent practice at UMMC

Symptomatic treatment is accompanied by Symptomatic treatment is accompanied by intravenous methylprednisolone and high intravenous methylprednisolone and high dose 1mg/kg of oral prednisolone daily dose 1mg/kg of oral prednisolone daily which is tapered. Usually a steroid sparing which is tapered. Usually a steroid sparing agent such as azathioprine is added.agent such as azathioprine is added.

HydroxychloroquineHydroxychloroquine Role for cyclophosphamide in such Role for cyclophosphamide in such

patients? At which doses – 1 or 2?patients? At which doses – 1 or 2?