Systemic lupus erythematosus (SLE) is a multisystem major collagenosis of unknown etiology with autoimmune pathogenesis and unpredictable evolution. The prevalence of neuropsychiatric manifestations as a complication of SLE is reported in the literature of 14-95% in pediatric patients. The study presents the case of a patient with SLE, whom after a month of the onset, the illness is complicated with an impairment of the nervous system. Clinical manifestations were: headache syndrome, memory impairment, hemianopsia, hemiplegia. The brain MRI was found multiple areas of ischemia. Aimd immunosuppressive treatment, there was clinical and laboratory improvement. Although the lupus prognosis has improved significantly in recent years, the neuropsychiatric involvement represents one of the main causes of major disabilities, morbidity and mortality in SLE. Introduction. Systemic lupus erythematosus (SLE) is a multisystem inflammatory disorder of unknown etiology with various clinical and laboratory manifestations due to an imperfect genetically determined immunoregulation, associated with autoantibody hyperproduction and unpredictable evolution. The prevalence of neuropsychiatric manifestations as a complication of SLE is reported in the literature of 14-95% in pediatric patients. The neuropsychiatric involvement represents one of the main causes of morbidity and mortality in SLE. Aim: to study the particularities of clinical manifestations of the neurolupus in children. Material and Method: is presented a clinical case of a patient with SLE with clinical and laboratory signs of neuropsychiatric impairment and the methodology of investigations. Results and Conclusions: The patient, aged 14, is a primary diagnosed with SLE. One month after onset of illness appears one of the major complications of this disease- the impairment of the nervous system. Clinical manifestations were: headache syndrome, memory impairment, hemianopsia, hemiplegia. The brain MRI found multiple areas of ischemia. There was clinical and laboratory improvement amid an immunosuppressive treatment, though the prognosis remains reserved one.
Systemic lupus erythematosus (SLE) is a multisystem inflammatory disorder of unknown etiology with various clinical and laboratory manifestations due to an imperfect genetically determined immunoregulation, associated with autoantibody hyperproduction and unpredictable evolution . SLE with onset in childhood is more severe than in adult, with a higher incidence of multisystem damage and lower survival rates [1,2]. The prevalence of neuropsychiatric manifestations (NPSLE) as a complication of SLE is reported in different studies literature from 14-95% in pediatric patients [5,9]. The manifestations of the involvement of the nervous system vary widely from life threatening presentation, such as transverse myelitis or stroke to subtle and subclinical abnormalities in neurocognitive function such as memory, intellect and learning . The neuropsychiatric involvement represents one of the main causes of morbidity and mortality in SLE .
Material and Methods
Clinical case presentation:
The patient A., aged 14, is hospitalized in september 2014 with symptoms of urinary tract infection (pain, fever 38-39°C, leucocyturia). In evolution over a week it was joined an inflammatory joint syndrome, an anemic syndrome, the urinary picture worsens until renal impairment.
The laboratory analysis reveals anemia (Hb- 93x1012g/l), ESR = 58mm/h, increased blood creatinine 157 mmol/l, hematuria covering the microscopic field. The acute phase reactants increased (ASL-A ≥ 200 IU/ml, CRP ≥ 24 mg / l), the presence of antinuclear antibodies in titers increased (1,7 U/ml), increased antibody titers anticardiolipin IgM (> 81,6) and IgG (53,8 U / ml), very major titre IgM antiphospholipid antibodies (262,3 U/ml) and IgG (66,7 U/ml). EcoCG: I degree MVP (5,0), endured mitral valve, mitral valve insufficiency I degree. The established clinical diagnosis was systemic lupus erythematosus, acute evolution. Lupus nephritis. Antiphospholipid syndrome. Acute renal failure.
In the third week of illness a headache syndrome, increased blood pressure values (up to 210/100 mmHg), anorexia and myalgia in the legs is associated. In the treatment it added antihypertensive and vasodilators drugs. However, over time (over 1 month of illness onset) the general state of the child is getting worse: there is a delayed response with slowness in the thinking, it appear tingling in the fingers of both hands, hyperkines in right upper limb, muscle weakness in all members R>L, gait disturbance, poor memory. The general state with continued aggravation, hemodynamically unstable, periodic hypotension (70/30 mm Hg), shortness of breath and marked fatigue, homonyme hemianopsia and later the patient becomes drowsy and can be awakened only to strong stimuli. The neurological examination determine a state of sopor, reduced muscle strength upper left limb-4, right upper limb-3p, left leg- 4p, right leg- 3p, decreased muscle tone Rigt> Left, low sensitivity, focusing on the right.
According the neurologic status it recommended brain MRI: diffuse cerebral vasculitis, multiple areas of ischemia with a haemorrhagical component in the parietal-occipital lobes bilaterally and in the left the thalamus (8,16mm). Subacute, chronic subdural hematoma in the right hemisphere, with transverse diameter up to 18mm parietal-occipital in the midline. Multiple microbleeds (fig. 1).
Fig.1. Brain MRI over 1,5 months of SLE onset
Over four months of disease onset, aimd individualized therapy with cyclophosphamide, glucocorticosteroids, erythropoietin, anticoagulants, barbiturates, the child’s state is evident improving. As accuse: joint pains of the knees Right>Left, which are swelling with movement limitation, fatigue, general weakness, headaches regularly. Muscle tone is 4p in the left limbs and 5p in the right limbs.
In laboratory tests remains anemia, which is decreasing (Hb-78 g / l), accelerated ESR (68 mm/h), CPR ³ 6 mg/l. The kidney tests are normal. Cardiac ultrasound: normal function of LV. I degree MVP, II degree mitral regurgitation, I degree tricuspid insufficiency.
Repeated brain MRI was performed, which is with diminishing and resorption of cerebral hematoma: right basal occipital (15-5 mm) and parasagittal right parietal-occipital. Restructuring encephalomalacia type of parietal-oocipital lobes (fig.2).
Fig.2. Brain MRI at 4 months of SLE onset, amid individualized therapy
Systemic lupus erythematosus in children is a rare and severe disease associated with high morbidity. Neurological impairment in systemic lupus erythematosus (NPSLE) is a major complication and is an adverse prognostic factor in the development of the patients with SLE. The NPSLE prevalence varies considerably in the literature from 14 to 95%, the stroke prevalence in children with SLE is 12%. A retrospective NPSLE study on 185 children in a period of 20 years found that 11% had symptoms at diagnosis NPSLE and 16% developed these symptoms within a year of disease onset. The mortality rate in this study was 45% in children NPSLE and 17,4% in those without these symptoms .
The pathophysiology of NPSLE in a specific individual depends on genetic, environmental, and hormonal factors. . The pathophysiological mechanisms are diverse: antibody-mediated neurotoxicity, vasculopathy due to anti-phospholipid (aPL) antibodies and other mechanisms, cytokine-induced neurotoxicity, and loss of neuroplasticity (fig. 3) .
Fig.3. Proposed pathogenesis of neuropsychiatric lupus [by Muscal et al,2010].
NPSLE causes impairment of the central (CNS) and of the peripheral nervous system (PNS), the cases definiton which are based on the recommendations of the American College of Rheumatology (tab. 1) . The frequency of CNS organ damage in SLE was estimated between 35-75%. The peripheral nervous system is affected in 18% of cases.
A recent study from Colombia in children with SLE for five years  reported NPSLE events in 40% of them. Seizures were the most frequent neuropsychiatric manifestation in 50% of patients, followed by headache and depression in 36% of patients, stroke in 26% of patients, vasculitis and chorea in 16% of patients, psychosis and neuropathy in 13% of patients, and myelitis in 6% of patients.
Table 1. Neuropsychiatric syndromes associated with SLE
Another retrospective study of NPSLE in 185 chinese children over a 20-year period  found that 11% had NPSLE manifestations at the time of diagnosis and an additional 16% developed them within one year. In this study, the mortality rate was 45% in children with NPSLE and 17,4% in those without these manifestations. Estimates of the prevalence of NPSLE have ranged from 22% to 95% in children.
In a prospective study of NPSLE in children, the nervous system manifestations were more common over a 6-year study period than glomerulonephritis (95% versus 55%, p≤0.0001). The most prevalent NPSLE syndromes in this longitudinal study included: headaches in 72 % of children, mood disorder in 57%, cognitive dysfunction in 55%, seizure disorder in 51%, acute confusional disorder in 35%, peripheral nervous system impairment in 15%, psychosis in 12%, and stroke in 12% . Stroke in SLE occurs through several mechanisms: immune-mediated vasculitis, antiphospholipid antibodies, cardiogenic embolism (Libman-Sacks endocarditis) .
The management of patients with neurolupus counts in an immunosuppressive and a symptomatic therapy (anticonvulsants, antidepressants, drugs for anxiety) [4,7,13]. Initially, the treatment starts with an intensive induction therapy with glucocorticosteroids, followed by a maintenance phase for a long time. The cyclophosphamide, a powerful immunosuppressive induce apoptosis of the cells with high proliferation, administered i/v monthly, has beneficial effects in severe manifestations of the NPSLE. And in the case watched in our hospital the cyclophosphamide had beneficial effects and improved the clinical and laboratory state of the patient.
At the same time there are studies that show that pediatric patients treated with other immunosuppressant preparations (mucofenolat and azathioprine) or biological preparations (rituximab) have a more favorable prognosis [9,13].
According to EULAR criteria if antiphospholipidic syndrome is present the patients need anticoagulants or antiplatelet drugs . From the adjuvant drugs is hydroxychloroquine, which reduces long-term risk of acute episodes of disease and thrombotic events.
Systemic lupus erythematosus in children is a rare and severe disease, associated with high morbidity. Neuropsychiatric impairment in SLE is a major complication. Making a timely diagnosis requires imaging investigations (brain MRI), which can establish outbreaks of ischemia. However, if the nervous system is affected, SLE is associated with a poorer prognosis and more complications.
Although the prognosis in lupus has improved significantly in recent years, the affecting of the specific organs, particularly the neuropsychiatric, it remains an important cause of morbidity and mortality in these patients.
- Barsalou J et al. An update on childhood-onset systemic lupus erythematosus. Curr Opin Rheumatol, 2013, 25:616–622.
- Rajiv S, Raut S. Pediatric lupus nephritis: Management update. World J Nephrol, 2014, 3(2): 16-23.
- Revenco N. Reumatologie, in: Revenco (Ed). Esențialul în pediatrie . Editura NovalInprint, Chișinău, 2014, 315-321.
- Midgley A et al. New insights into the pathogenesis and management of lupus in children. Arch Dis Child, 2014,99:563–567.
- Robin L. Neuropsychiatric Lupus. Clinical and Imaging Aspects. Bull NYU Hosp Jt Dis, 2007,65(3):194-9.
- Muscal E et al. Neurological Manifestations of Systemic Lupus Erythematosus in Children and Adults. Neurol Clin, 2010, 28(1): 61–73.
- Reynolds JA, Bruce IN. Overview of the management of systemic lupus erythematosus. Reports on the Rheumatic Diseases, 2013, 7(2):1-11.
- Bertsias G et al. EULAR recommendations for the management of systemic lupus erythematosus. Report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics. Ann Rheum Dis, 2008, 67:195–205.
- Zambrano ZYC, Ramos JDG, Vargas NEP and al. Risk Factors for Neuropsychiatric Manifestations in Children With Systemic Lupus Erythematosus: Case-Control Study. Pediatric Neurology, 2014, 51: 403-409.
- Gehan AM, Dalia HI, Abeer AS, Azza KM. The role of measurement of serum autoantibodies in prediction of pediatric neuropsychiatric systemic lupus erythematosus. Journal of Neuroimmunology, 2010, 227: 195–201.
- Jeltsch-David H, Muller S. Neuropsychiatric systemic lupus erythematosus: pathogenesis and biomarkers. Nat. Rev. Neurol,2014, 10: 579–596.
- Kivity S, Agmon-Levin N, Zandman-Goddard G. Neuropsychiatric lupus: a mosaic of clinical presentations. BMC Medicine, 2015, 13:43.
- Arici ZS, Batu ED, Ozen S. Reviewing the Recommendations for Lupus in Children. Curr Rheumatol Rep, 2015, 17: 17.
- Joseph FG, Scolding NJ. Neurolupus. Pract Neurol 2010; 10: 4–15.