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we present the case of a 20-year-old patient who started out with RPGN&#44; accompanied by haemoptoic sputum and two episodes of generalized tonic-clonic convulsive seizures&#44; with high anti-BM Ab titres&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Clinical case</span></p><p class="elsevierStylePara">20-year old man&#44; smoker and former cocaine and cannabis user&#44; who was admitted to the hospital with macroscopic haematuria and acute oliguric renal failure &#40;AORF&#41;&#46; 12 days before admission&#44; the patient presented with asthenia&#44; anorexia&#44; vomiting&#44; and dysuria&#44; for which he visited a general practitioner who diagnosed him with a urinary infection and prescribed ciprofloxacin treatment&#46; Four days later&#44; he referred a fever of 38&#186;C&#44; macroscopic haematuria&#44; and a subjective decrease in diuresis&#46;</p><p class="elsevierStylePara">The physical examination revealed the following&#58; blood pressure&#58; 140&#47;90 mmHg&#44; temperature&#58; 37 &#186;C&#46; Deteriorated general health&#44; pallor of skin and mucosae&#44; and bibasal hypoventilation&#46; Upon admission&#44; AORF was observed&#44; requiring haemodialysis during the first 24 hours&#46; 48 hours later&#44; the patient presented haemoptoic sputum&#44; followed by two episodes of generalised tonic-clonic convulsive seizures&#46;</p><p class="elsevierStylePara">The laboratory results from the time of admission revealed&#58; haematocrit&#44; 25&#46;5&#37;&#44; haemoglobin&#44; 8&#46;9 g&#47;L&#44; leukocytes&#44; 16&#44;700&#47;mm<span class="elsevierStyleSup">3</span>&#44; platelets&#44; 344&#44;000&#47;mm<span class="elsevierStyleSup">3</span>&#44; ESR&#44; 96 mm&#47;h&#44; creatinine&#44; 11&#46;8 mg&#47;dL&#44; BUN&#44; 90 mg&#47;dL&#44; glucose&#44; 97 mg&#47;dL&#44; total protein&#44; 5&#46;3 g&#47;dL&#44;&#160;albumin&#44; 4&#46;5 g&#47;dL&#44; calcium&#44; 8&#46;2 mg&#47;dL&#44; sodium&#44; 134 mEq&#47;L&#44; potassium&#44; 5&#46;2 mEq&#47;L&#46; Proteinogram&#44; immunoglobulins&#44; and kappa&#47;lambda light chains were normal&#46; Serology for hepatotropic virus&#44; HIV&#44; and liver function tests revealed no abnormalities&#46; Blood and urine toxin screens&#44; including tests for cocaine metabolites&#44; were negative&#46; The immunological study&#44; which consisted of ANA&#44; ANCA&#44; antiphospholipid and anticardiolipin Ab&#44; and complement levels were all negative&#46; However&#44; anti-BM Ab were positive &#40;72&#46;5 ug&#47;mL&#44; normal range &#60;10 U&#41;&#46; The urine analysis &#40;24 hrs&#41; revealed a proteinuria of 850 mg&#46; An intense haematuria in the urine sediments was also observed&#46; The chest radiograph showed bilateral alveolar&#47;interstitial infiltrates&#44; indicative of alveolar haemorrhage&#46; The renal ultrasound revealed normal sized kidneys with increased cortical echogenicity&#46; The electroencephalogram&#44; cerebral magnetic nuclear resonance &#40;NMR&#41; and the cerebral angio-NMR were all normal&#46;</p><p class="elsevierStylePara">Four days after the patient was admitted&#44; we performed a percoetaneous renal biopsy&#44; in which we observed an extracapillary glomerulonephritis &#40;100&#37;&#160;of crescents&#41;&#44; with collapsed glomerular tufts&#44; areas of fibrinoid necrosis&#44; moderate inflammatory infiltration and incipient interstitial fibrosis and tubular atrophy &#40;Figure 1&#41;&#46; The immunofluorescence scan showed linear deposits of immunoglobulin G &#40;IgG&#41; along the glomerular basement membrane&#46;</p><p class="elsevierStylePara">The patient was diagnosed with GPS associated with a probable ANCA negative CNS vasculitis&#46; Upon admission&#44; the patient was treated with 3 500mg boluses of methylprednisolone for 3 consecutive days&#46; Subsequently&#44; oral cyclophosphamide was added in a daily dose of 1&#46;5 mg&#47;kg along with 15 sessions of plasmapheresis&#46; Furthermore&#44; the patient received treatment with valproic acid&#46; The respiratory and neurological symptoms disappeared with the prescribed treatment&#44; but unfortunately&#44; the renal function did not recover&#44; and the patient remained on a haemodialysis program upon discharge&#46;</p><p class="elsevierStylePara">Twenty five days after being admitted&#44; the patient was discharged from the hospital with negative anti-BM Ab titres&#44; allowing a slow reduction in the immunosuppressant treatment&#44; with no indications of relapse&#46; Cyclophosphamide was ended 3 months after admission&#44; but the patient remained on low doses of steroids &#40;2&#46;5 mg&#47;day&#41; and on a haemodialysis program &#40;Figure 2&#41;&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Subsequent evolution</span></p><p class="elsevierStylePara">Six months after being discharged&#44; and after non-compliance for antihypertensive treatment&#44; the patient was readmitted for a hypertensive emergency &#40;blood pressure at 220&#47;120 mmHg and a right temporal intraparenchymal haematoma that required surgical drainage&#41;&#46; At this point&#44; serial measurements of anti-BM Ab levels were negative&#44; and in spite of the severity of the damage&#44; the patient presented with no neurological deficit upon discharge&#46;</p><p class="elsevierStylePara">Twenty months later&#44; the patient received a kidney transplant from an organ donor&#44; as well as immunosuppressant treatment with tacrolimus&#44; mycophenolate mofetil&#44; and prednisone&#46; The kidney transplant has been satisfactory so far&#44; and the patient has referred no recurrence of the disease &#40;Table 1&#41;&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara">GPS is a rare immunological disorder characterized by the triad of RPGN&#44; the presence of circulating anti-BM Ab&#44; and pulmonary haemorrhage&#46; Although genetic factors have been associated with an increased likelihood to develop this syndrome&#44; other factors such as environmental exposure &#40;viral infections&#44; exposure to volatile hydrocarbons and tobacco smoke&#41; could trigger the disease in predisposed individuals&#44; particularly in those with underlying pulmonary lesions&#46;<span class="elsevierStyleSup">5</span> Additionally&#44; the consumption of cocaine has also been related to anti-BM Ab disease&#46;<span class="elsevierStyleSup">6</span> Our patient was a smoker&#44; as well as a previous cocaine user&#44; factors that could have influenced in triggering the disease&#46;</p><p class="elsevierStylePara">In 10 to 30&#37; of cases&#44; anti-BM Ab disease is associated with ANCA&#44; and the majority of patients have low titres of anti-myeloperoxidase &#40;MPO&#41;&#46; This subgroup of patients probably presents a variant of associated vasculitis&#46;<span class="elsevierStyleSup">7</span> However&#44; although the exact cause of the development of ANCA in anti-BM Ab disease has not been clarified&#44; some authors suggest that a polyclonal activation mechanism could be responsible&#46;<span class="elsevierStyleSup">8</span></p><p class="elsevierStylePara">GPS is characterized by the presence of autoantibodies against the epitope of the alpha 3 chain of type IV collagen &#40;alfa-3 &#91;IV&#93; NCI&#41;&#44; labelled the Goodpasture antigen&#46;<span class="elsevierStyleSup">9</span> Although this antigen has a wide distribution&#44; it is primarily expressed in the glomerular and alveolar basement membranes&#44; and less frequently in tubular&#44; cochlear&#44; retinal&#44; and choroid plexus basement membranes&#46;</p><p class="elsevierStylePara">Cerebral involvement in GPS is extremely rare in the absence of ANCA&#44; and only 4 cases have been described in the medical literature&#46;<span class="elsevierStyleSup">1-4</span> All of the cases that have been communicated presented with recurrent convulsive seizures related to cerebral vasculitis with or without haemoptysis&#46; Rydel et al&#46;<span class="elsevierStyleSup">1</span> described the first case of ANCA-negative cerebral vasculitis associated with GPS&#44; demonstrating vasculitic infiltrates in the meningeal biopsy&#46; Although cerebral and meningeal biopsies constitute the gold standard for the diagnosis of cerebral vasculitis&#44; their use is currently limited to patients with doubtful diagnosis due to the aggressive nature of the procedure&#46; Furthermore&#44; in most of the described cases of GPS with cerebral involvement&#44; the diagnoses of ANCA-negative cerebral vasculitis associated with GPS were performed based on the clinical presentation of the patient and the findings from imaging tests&#46;<span class="elsevierStyleSup">2-4</span> Our patient started with RPGN requiring dialysis from the beginning&#44; followed by pulmonary haemorrhage and two events of tonic-clonic convulsive seizures&#44; together with elevated anti-BM Ab levels&#46; The repeated ANCA measurements were negative&#44; and other possible causes that could have triggered the convulsive seizures&#44; such as metabolic disorders&#44; drug deprivation-induced hypertensive seizures&#44; etc&#46; were excluded&#46; Although the cerebral NMR came up normal in our patient&#44; we cannot rule out that small vessel vasculitic lesions could have contributed to the cerebral damage that was caused&#46; Indeed&#44; cerebral NMR scans come up negative in as much as 35&#37; of patients with cerebral vasculitis&#46;<span class="elsevierStyleSup">10</span> Cerebral angiography was not performed because the neurological symptoms disappeared with the previously described treatment&#46; Furthermore&#44; we also observed an improvement in respiratory symptoms&#44; although renal function never recovered&#46; Levy et al&#46; showed that renal insufficiency as estimated by plasma creatinine levels &#40;&#62;5&#46;7 mg&#47;dL&#41; or the need for dialysis at the onset of the disease&#44; as well as a percentage greater than 50&#37; of crescents found in the renal biopsy&#44; are all negative prognostic factors for the recovery of kidney function&#46;<span class="elsevierStyleSup">11</span></p><p class="elsevierStylePara">Kidney transplants are possible to perform in this disease&#44; although there does exist a risk of recurrence in the new organ&#44; leading to the recommendation that at least a 6-month waiting period be necessary for the transplantation and only when anti-BM Ab titres are undetectable&#46; This is a promising strategy in the majority of cases&#44; as in our patient&#44; who received an organ donor transplant 20 months later&#44; presenting with a positive clinical evolution and no signs of recurrence of the disease&#46;</p><p class="elsevierStylePara">Finally&#44; we conclude that GPS with neurological involvement is extremely infrequent&#44; especially with negative ANCA&#46; Normal cerebral NMR findings do not exclude the possibility of small vessel cerebral vasculitis&#44; requiring an aggressive and early diagnosis and treatment of GPS in order to improve the prognosis of the patient&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">ACKNOWLEDGEMENTS</span></p><p class="elsevierStylePara">The authors would like to thank Dr&#46; Eduardo Salido for his advice on renal pathology and review of the manuscript&#46;</p><p class="elsevierStylePara"><a href="grande&#47;10237&#95;108&#95;8376&#95;en&#95;w4777103918fig1&#95;en&#46;jpg" class="elsevierStyleCrossRefs"><img src="10237_108_8376_en_w4777103918fig1_en.jpg" alt="Extracapillary glomerulonephritis &#40;red arrows&#41; with centres of fibrinoid necrosis&#46; Yellow arrow&#44; PAS stain&#44; 400x&#46;"></img></a></p><p class="elsevierStylePara">Figure 1&#46; Extracapillary glomerulonephritis &#40;red arrows&#41; with centres of fibrinoid necrosis&#46; Yellow arrow&#44; PAS stain&#44; 400x&#46;</p><p class="elsevierStylePara"><a href="10237&#95;108&#95;8375&#95;en&#95;w4777103917table1&#95;en&#46;doc" class="elsevierStyleCrossRefs">10237&#95;108&#95;8375&#95;en&#95;w4777103917table1&#95;en&#46;doc</a></p><p class="elsevierStylePara">Table 1&#46; Data on the patient&#191;s evolution from the onset of GPS&#46;</p><p class="elsevierStylePara"><a href="10237&#95;108&#95;8377&#95;en&#95;w4777103918fig2&#95;en&#46;ppt" class="elsevierStyleCrossRefs">10237&#95;108&#95;8377&#95;en&#95;w4777103918fig2&#95;en&#46;ppt</a></p><p class="elsevierStylePara">Figure 2&#46; Evolution of Anti-BM antibodies and renal function following the initiation of treatment with steroids&#44; oral cyclophosphamide&#44; and plasmapheresis</p>"
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        "resumen" => "<p class="elsevierStylePara">El s&#237;ndrome de Goodpasture &#40;SGP&#41; es una rara entidad de base inmunol&#243;gica&#44; caracterizada por la asociaci&#243;n de una glomerulonefritis r&#225;pidamente progresiva &#40;GNRP&#41; y hemorragia alveolar en presencia de anticuerpos antimembrana basal&#46; La afectaci&#243;n del sistema nervioso central &#40;SNC&#41; en el SGP es extremadamente infrecuente en ausencia de ANCA&#46; Presentamos el caso de un paciente de 20 a&#241;os que comenz&#243; con una GNRP acompa&#241;ada de esputos hemoptoicos y dos episodios de crisis convulsivas t&#243;nico-cl&#243;nicas generalizadas&#44; en presencia de elevados t&#237;tulos de anticuerpos antimembrana basal glomerular &#40;Ac-anti-MBG&#41;&#46; Tras tratamiento inmunosupresor asociado con plasmaf&#233;resis&#44; el paciente present&#243; descenso de los t&#237;tulos de Ac-anti-MBG&#44; as&#237; como mejor&#237;a de los s&#237;ntomas neurol&#243;gicos y respiratorios&#44; aunque sin recuperaci&#243;n de la funci&#243;n renal&#44; permaneciendo en programa de hemodi&#225;lisis&#46; Veinte meses m&#225;s tarde&#44; con la enfermedad en remisi&#243;n&#44; el paciente recibi&#243; un trasplante renal de cad&#225;ver&#46;</p>"
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        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleItalic">Goodpasture&#180;s syndrome is a rare autoimmune disorder characterized by rapidly progressive glomerulonephritis &#40;RPGN&#41; and alveolar hemorrhage in the presence of anti-glomerular basement membrane &#40;anti-GBM&#41; antibodies&#46; Central nervous system involvement is highly unusual in the absence of anti-neutrophil cytoplasmic antibodies&#46; We report the case of a 20-year-old man with RPGN accompanied by bloody sputum&#44; tonic-clonic seizure and high titers of anti-GBM antibody&#46; After treatment with immunosuppressants and plasmapheresis&#44; the patient showed reduced anti-GBM antibody titers and improved neurologic and respiratory symptoms&#44; but renal failure persisted&#44; requiring hemodialysis&#46; Twenty months later&#44; with the disease in remission&#44; he underwent deceased-donor renal transplantation&#46;</span></p>"
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