CASE PRESENTATION Combined Monthly Rheumatology Meeting 27/02/2009

Transcription

1 CASE PRESENTATION Combined Monthly Rheumatology Meeting 27/02/2009

2 Case Madam I.M,28 year old Malay lady, First presentation on 21/3/2008 with: Altered behaviour for 2 weeks Fever for 1 week H/o incomplete abortion at 16/52 POA in March 2007-D&C done No significant family history Married with 3 children-6,4,2 yrs Assistant teacher in kindergarten Husband prison warden

3 Examination Opens eyes to call Not obeying commands GCS E4,V1,M5-10/15 Pupils 4mm bilateral, reactive Neck stiffness present and generalised hypertonicity all 4 limbs Febrile-39 deg C Mild malar rash present, petechial rash both lower limbs Alopecia present with sparse hair Single hard palate ulcer present Oral candidiasis present Fundoscopy-no cytoid bodies

4 Lungs-clear Heart-Drnm Per Abdomen-soft,spleen tipped C.N.S-Unable to assess higher functions Power 5/5 all 4 limbs Plantars downgoing

5 Provisional Diagnosis Acute Meningoencephalitis To rule out connective tissue disease such as SLE

6 Investigations For cause: CT Brain-subtle density in right frontotemporal region representing focal oedema MRI Brain-white matter cellular oedema-?variant multiple sclerosis,? viral/toxic encephalopathy,?neuropsychiatric SLE CSF biochem &feme normal S.C3/C4-0.55/0.1 ANA- pending Anti dsdna-pending Thrombophilia screening- pending

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10 anti HIV-Negative HbsAg-negative Anti HCV-negative, CXR-Normal 2DECHO HT-Normal U/S Abdomen-splenomegaly

11 Management Treated as acute meningoencephalitis with IV Ceftriaxone,later iv Tienam,IV Acyclovir,IV fluconazole followed 7 days later by IV Methylprednisolone x 3 days and by T Prednisolone,tapering doses Referred to visiting neurologist from HKL as patient still stiff in limbs although fully conscious and afebrile,on 3/4/2008- Impression: Acute demyelinating encephalomyelitis secondary to viral infection Transferred to HKL on 3/4/2008 for further management in HKL,discharged on 30/4/2008 EEG,Repeat Lumbar puncture and reporting of MRI Brain at Neurology conference

12 Investigations From HKL: CSF-glucose 2.8 protein-0.31 globulin negative feme-acellular S Ceruloplasmin-normal BMA:reactive changes Urine organic acid:non diagnostic S Amino acid:further testing required ASOT:normal G6PD:normal

13 Latex agglutination negative Blood cultures no growth Cryptococcal antigen negative ANA reactive->1 :2560,speckled Anti ds DNA negative Thrombophilia screening- negative C3/C4-low Antibodies to Smith/RNP/sm/Histone/Ribosomal P- positive MRI Brain-periventricular encephalopaty Repeat MRI Brain-same changes EEG-Normal

14 Final Diagnosis: Acute Parkinsonism secondary to SLE Medication from HKL: T Artane-2mgs bd T Rocaltriol -0.25microgms dly T Calcium Lactate-600mgs bd T Madopar-125mgs tds T Ranitidine 150mgs on T Prednisolone 40mgs dly T Alprazolam 0.5 mgs on T Sertraline 25mgm dly

15 Progress Defaulted both Neurology and Psychiatry follow ups at HKL Given referral letter to Rheumatologist,HTJS Seen at Rheumatology clinic,htjs on 13/5/2008 with referral letter from Neurologist,HKL Final Impression: Acute Parkinsonism secondary to neuropsychiatric SLE with possible

16 Progress MRI Brain-white matter changes Clinically had cogwheel rigidity, resting tremor and bradykinesia Defaulted all medications since May 2008 and defaulted follow-up

17 Progress Brought in Rheumatology clinic by father on 29/10/2008 Pregnant,LMP-29/6/2008,POA 16/52 complaints of inability to squat,incontinent of faeces, absent from work Examination: Slow,scanning speech, mask like facies Alopecia present Mild malar rash No oral ulcers BP 100/79,PR 84/MT Cogwheel rigidity upper limbs, more on right

18 Progress Admitted for termination of pregnancy on 8/11/2008 Advised on contraception Discharged on 10/11/2008 with T Prednisolone 30mgs dly T Hydroxychloroquin-200mgs dly and T Fa/BCO/Fe Fumarate/vit c

19 Progress Seen next in Rheumatology clinic on 10/12/2008,23/12/2008 and latest on 28/01/2009 for IV Cyclophosphamide infusions Received 3 courses of IV Cyclophosphamide on 12/12/2008,12/01/2009 &12/02/2009 At present well with no malar rash,alopecia or hypertonicity of limbs Plan:For 6 courses of Iv Cyclophosphamide-500mgs monthly with

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22 Uncommon Neurological Syndromes Movement disorders Cranial neuropathies Eye involvement Transverse myelitis Meningitis

23 Case Presentations of uncommon neurologic Manifestations of SLE 1.Myoclonus of Tongue in SLE 2.Acute cortical blindness in SLE 3.Acute Parkinsonism in SLE

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25 Case Reports of Acute Parkinsonism in SLE 1)Rheumatology 2002;41: Observed in at least two women with well defined SLE,varying in age from 16 to 42 years and in one other case with undefined SLE 2)Lupus : Unusual neurologic manifestations:parkinsonism in juvenile SLE A girl with neuropsychitric lupus demonstrated Parkinsonism features soon after commencing risperidone 3)Movement Disorders.17(6): ,2002,Nov Juvenile parkinsonism as a manifestation of SLE:case report and review of literature A case of juvenile parkinsonism as a manifestation of SLE and review the literature 4)Parkisonism & Related Disorders;14(4): ,2008 Stroke of the substance nigra and parkinsonism as first manifestation of SLE Authors report one case of parkinsonism associated with SLE in a 45 year old women who presenred with a strategic infarct of the right substance nigra secondary to vasculitis and contralaeral symptoms

26 Case Reports of acute parkinsonism in SLE 5)Journal of the Neurological Sciences:193(1),2001 Dec 15 Reversible parkinsonism in SLE Report on first patient with SLE who developed a reversible parkinsonian syndrome associated with enhancing subcortical lesions on MRI 6)Lupus,9(6):4-7,2000 Parkinsonism as unusual neurological complication in childhood SLE Report on two girls with SLE who developed extrapyramidal parkinsonian after an initial stormy course with seizures

27 Discussion Diagnosis of Parkinsonism complicating SLE may be delayed because of its extreme rarity Even in adult-onset SLE,parkinsonian syndrome is rare Pathologic examiation of brain tissue for patients with CNS lupus has revealed vasculopathy,infarcts,haemorrhage and vasculitis Pathogenesis of neuropsychitric SLE is multifactorial Vasculopathy is major factor in evolution of Parkinsonism Diagnosis of CNS lupus is hampered by the lack of sensitivity and specificity of current tests Combination of diagnostic approaches using radiology,serolgy and csf analysis yield the best result

28 No controlled trials of any treatment for neuropsychiatric SLE Uncontrolled studies using high dose intravenous steroids and cyclophosphamide showed benefit Use of IVIG in SLE related Parkinsonism has not been reported

29 Treatment of Neuropsychiatric Sequelae Treatment of cerebral lupus is empiric Best available evidence is based on retrospective series,case reports and expert opinion Inflammatory brain lesions are treated with corticosteroids and immunosuppressive drugs e.g cyclophosphamide Anticoagulant therapy with coumarins is recommended in cases of thrombotic events associated with antiphospholipid antibodies

30 Symptomatic treatment is justified in cases in which depression,mania,psychosis,delirium or dementia persisits despite treatment Antipsychotics and antidepressants that may lower seizure threshold are avoided Conventional antipsychotics avoided Risperidone and olanzapine preferred

31 Use of more aggressive therapy in CNS Lupus Role of cyclophosphamide and/or plasmapheresis in management of CNS lupus not well defined Consider these modalities in patients with following characteristics: 1)Acute or recent onset of neurologic symptoms such as seizures or organic brain syndromes in absence of another cause 2)Evidence of active inflammation in the brain such as increased cells and protein in csf,brain swelling on MRI or CT scan,vascular injury on MR angiography and high titre antibrain antibodies 3)Failure to respond to one to two week course of high dose oral corticosteroids in dose of 1 to 2 mg/kg per day or to pulse methylprednisolone- 1000mgs/day for 3 days

32 Stem cell transplant Phase 1 study administered high dose chemotherapy followed by autologous stem cell transplantation to 7 patients with active diffuse proliferative glomerulonephritis,cerebritis,myelitis,and/ or vasculitis despite 6 cycles of intravenous cyclophosphamide At median follow up of 25 months,all patients were free from signs of active lupus and renal,cardiac and pulmonary function and serologic markers had improved Proposed mechanism of action is a period free from memory T cell influence,during which maturation of new lyphocyte progenitors can occur without recruitment to anti-self activity

33 References: 1)2004 UpToDate,Neurologic&Psychiatric SLE 2)Arthritis &Rheumatism,Vol 42,No 4,April 1999,pp ,Neuropsychitric maifestations of SLE 3)Rheumatology 2002;41: ,The central nervous system in SLE,Part 1.Clinical syndromes:a literature investigation 4)Neuropsychiatric manifestations of SLE:Dr Ng Ben Yong,Senior Consultant Psychiatrist & Head,Singapore General Hospital 5)Lupus 2007:Unusual neurologic manifestations:parkinsonism in juvenile SLE 6)Lupus 2000:Parkinsonism as unusual neurological complication in chilhood SLE

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