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the hallmark of systemic lupus erythematosus ( sle ) is its autoimmunity and protean clinical manifestations that can affect virtually every organ and can vary perilously living up to its name as  the disease with thousand faces  .
the extent of cns manifestations can vary broadly , from less severe subclinical abnormalities in neurocognitive function , such as memory , intellect and learning to more grueling presentations , such as seizure , stroke or transverse myelitis .
the incidence of epilepsy among sle patients increases three times more than the general population and patients with both sle and epilepsy are more prone to experience neuropsychiatric disorders .
we present a case of a 70-year - old male who presented with a 17-year history of epilepsy and cognitive decline diagnosed with sle and subsequently responded well to immunotherapy .
a 70-year - old middle eastern male with a past medical history of poorly controlled seizure disorder , htn , and atrial fibrillation was admitted to the hospital due to worsening cognitive decline and leukopenia noticed on outpatient lab work .
patient was diagnosed with epilepsy 17 years ago and family members note it is poorly controlled on his current regimen of clobazam 5 and 10 mg , levetiracetam 1,000 and 1,500 mg , and lacosamide 200 and 250 mg ( morning and evening , respectively ) .
his seizures were generalized , jerky movements of extremities , pronounced on the right side , with post - ictal confusion and incoherent speech .
initial blood workup revealed significant leukopenia , proteinuria on urine analysis and bilateral hilar , mesenteric and inguinal lymphadenopathy on ct .
right inguinal node biopsy showed no evidence of malignancy . during the hospital course , patient developed swelling and tenderness of the bilateral wrist joints making us consider a rheumatologic etiology for his symptoms . on further questioning ,
the family noted that the patient frequently developed pain and swelling of the joints , predominantly in knee and hands .
rheumatological workup revealed a high ana titer of 1:640 , dsdna strongly positive , c3/c4 was low and rf , anti - ccp was negative .
patient was put on oral prednisone 60 mg once daily resulting in improvement of joint swelling and cognition .
patient was discharged on oral prednisone and hydroxychloroquine 200 mg twice daily with outpatient follow - up . as an outpatient , the benefits and disadvantage of renal biopsy to work up proteinuria were discussed with the family and finally it was decided not to perform renal biopsy due to high bleeding risk expected due to anticoagulation ( warfarin ) , and the patient was put on mycophenolate mofetil ( mmf ) 100 mg twice daily , for likely lupus nephritis .
eventually , steroids were gradually tapered off and patient was continued with hydroxychloroquine and mmf ( 200 and 1,000 mg twice daily , respectively ) on outpatient course .
patient s mental status has significantly improved and is now able to perform activities of daily living independently which he could not previously .
sle is a chronic , relapsing remitting systemic disease characterized by loss of immune tolerance resulting in autoantibody production with immune complex deposition .
it has a predisposition towards females of a childbearing age with a female to male ratio that ranges from 7:1 to 15:1 .
hence , this case of sle diagnosed in a 70-year - old male shows the variable presentations of this disease and why it is rightly called the disease with a thousand faces .
the american college of rheumatology ( acr ) has designed specific diagnostic criteria requiring at least 4 out of 11 to yield a sensitivity of 85% and a specificity of 95% .
this fact is well validated in our case of a 70-year - old man with a score of 6 out of 11 projecting a diagnosis of sle with even more greater statistical strength - arthritis , leukopenia , seizures , persistent proteinuria with positive ana , and anti - dsdna .
neuropsychiatric manifestations of sle have been divided by the acr into cerebrovascular disease , cognitive dysfunction , seizures and psychosis , and peripheral nervous system disorders .
the manifestation of this neuropsychiatric lupus can take place in absence of either serologic activity or other metabolic disorders .
prevalence of neuropsychiatric manifestations of sle ranges from 11% to 90% with large variation among cohort studies .
review of the literature presents certain hypothesis of the pathogenesis of seizures and cognitive dysfunction in patients with sle .
antiphospholipid antibody inhibiting y - aminobutyric acid receptor - ion channel complex has been shown to increase neuronal excitability [ 4 , 5 ] .
denburg and colleagues illustrated antiphospholipid antibody was associated with cognitive decline in certain aspects ( verbal memory , cognitive flexibility , and psychomotor speed ) .
however , it is important to note that antiphospholipid antibody was negative in this patient .
blood - brain barrier integrity dysfunction due to autoantibodies in sle patients may also play a role in cognitive decline .
kowal et al demonstrated in animal model that anti - glutamate receptor antibodies are associated with cognitive dysfunction and hippocampal apoptosis in the presence of blood - brain barrier disruption [ 7 , 8 ] .
a cohort study by huang et al showed 56 ( 26.3% ) out of 213 patients with a history of seizures had the first seizures more than 1 year before diagnosis of sle .
appenzeller et al illustrated the frequency and risk factors of epileptic seizures in a large cohort of patients with sle which showed 19 of 60 ( 31.6% ) had epileptic seizure at the onset of sle disease activity , 41 of 60 ( 68% ) had epileptic seizures after disease onset and seven of 60 ( 11.7% ) had recurrence .
therefore , seizure can occur at any time either before , at , or after sle diagnosis .
ramsey - goldman et al stated in the study that seizures are a relatively early event in the disease course of sle .
hence , we believe that early diagnosis of sle by neuropsychiatric manifestations will not only lead to better control of cns symptoms but early immunosuppressive therapy could control the progression of the underlying autoimmune disease .
we postulate that the reduced frequency of confusional episodes reflecting subclinical seizures and significant improvement in cognitive function in our patient are attributable to the immunosuppressive effect of hydroxychloroquine and mmf .
this is validated by sommerlad et al who concluded immuno - modulating therapy significantly improves both subjective and objective clinical presentations of neuropsychiatric sle . considering toxicity profile current view favors mmf to cyclophosphamide , which has much better side effect profile for maintenance and initial treatment of neuropsychiatric lupus .
also , mmf demonstrated a significantly higher remission rate than intravenous cyclophosphamide in renal lupus in the randomized , open label , non - inferiority trial conducted by ginzler et al .
above evidence convinced us to start the patient on mmf . in conclusion , this case highlights the fact that seizures and other neuropsychiatric manifestations of sle can often pre - date other symptoms making the diagnosis of cns lupus a challenging one due to the lack of specific laboratory tests , non - specific neuroimaging findings , and inaccessible brain parenchyma for histological confirmation and overall non - specific nature of the disease .
we also believe that early diagnosis and initiation of immunosuppressive therapy will not only lead to better control of cns symptoms but early immunosuppressive therapy could defer the progression of the underlying autoimmune disease .
in conclusion , this case highlights the fact that seizures and other neuropsychiatric manifestations of sle can often pre - date other symptoms making the diagnosis of cns lupus a challenging one due to the lack of specific laboratory tests , non - specific neuroimaging findings , and inaccessible brain parenchyma for histological confirmation and overall non - specific nature of the disease .
we also believe that early diagnosis and initiation of immunosuppressive therapy will not only lead to better control of cns symptoms but early immunosuppressive therapy could defer the progression of the underlying autoimmune disease .
a 70-year - old man presented with complaints of rapid cognitive decline and new onset leukopenia . 
 the patient had a 17-year history of refractory seizures . 
 detailed review of symptoms and investigations revealed the patient met american college of rheumatology ( acr ) diagnostic criteria for systemic lupus erythematosus ( sle ) . 
 the patient had high titer ana with a strongly positive dsdna . 
 immunosuppressive therapy with hydroxychloroquine and mycophenolate mofetil led to significant improvement in cognition and seizures . 
 neuropsychiatric sle should be considered a potential differential diagnosis for patients presenting with seizures or cognitive decline . moreover , 
 neuropsychiatric manifestations especially seizures are an early event in the disease course of sle . hence , we believe that early diagnosis of sle by neuropsychiatric manifestations will not only lead to better control of cns symptoms but early immunosuppressive therapy could control the progression of the underlying autoimmune disease .