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Letter to the Editor
Haemophagocytic syndrome as a cause of subacute encephalopathy
Síndrome hemofagocítico como causa de encefalopatía subaguda
Francisco José Hernández Ramos
Corresponding author
, Alfredo Palomino García, María Dolores Jiménez Hernández
Consulta de Enfermedades Neurosistémicas. Unidad de Gestión Clínica de Neurología y Neurofisiología, Hospital Regional Universitario, Virgen del Rocío de Sevilla, Sevilla, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Hemophagocytic syndrome is a rare entity with an annual incidence of one case per 800&#44;000 people<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a>&#46; There is a genetic form&#44; and it is more common in Japan and in children&#46; Its pathogenesis is unknown&#46; It is an entity with a high mortality rate and affects multiple organs&#44; including the nervous system<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a>&#46; It has been associated with infections&#44; neoplasms&#44; autoimmune diseases&#44; immunomodulatory treatment of multiple sclerosis&#44; haematological transplants&#44; and there is an idiopathic form&#46; The diagnosis is based on clinical&#44; laboratory and immunological markers and it is pathologically confirmed&#46; The diagnostic criteria have been defined by the Histiocytosis Society &#40;2004&#41;&#46; Management consists of life support measures&#44; concomitant disease treatment and specific treatment &#40;salvage and induction&#41;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">We report the case of a 56-year-old man&#44; with no relevant family&#44; personal&#44; and epidemiological history&#44; whose symptoms began in March 2018 with fever&#44; generalized weakness&#44; toxic syndrome&#44; dry cough&#44; evanescent hives-like skin lesions&#44; drowsiness and seizures&#44; reason why he was admitted to the infectious disease department&#44; ruling out microbiological causes and haematological causes after a bone marrow study&#46; A brain MRI scan showed anomalies in white matter&#44; resulting in admission to the neurology department&#46; The examination showed&#58; general malaise&#44; pyretic&#44; paleness&#44; hepatosplenomegaly and from a neurological point of view&#44; tendency to sleep&#44; with ocular opening to verbal stimuli&#44; disorientation to time and place&#44; bradypsychia&#44; understands simple commands responding with disyllables and motor perseveration&#46; There appears to be cortical blindness&#44; ocular tracking in horizontal rapid eye movements&#44; bilateral lower facial weakness&#44; spastic tetraparesis with extensor plantar reflexes&#44; attitude tremor in hands with occasional myoclonic jerks&#46; Among the anomalies found in the complementary tests performed&#44; the following stand out&#58; pancytopenia&#44; LDH 1&#44;926<span class="elsevierStyleHsp" style=""></span>U&#47;l&#44; ferritin 1&#46;309<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;l&#44; CD25 18&#46;64<span class="elsevierStyleHsp" style=""></span>U&#47;mL&#44; and negative autoimmunity&#46; Body PET&#47;CT scan with splenomegaly&#44; electroencephalogram with diffuse slowing in theta frequency range&#44; cerebrospinal fluid with elevated protein count and negative cultures&#44; serologies&#44; PCR and flow cytometry&#46; A new brain MRI was performed which showed progression of the white matter abnormality with activity data in diffusion sequences&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">From a topographic and syndromic point of view&#44; we propose a subacute encephalopathy with white matter damage&#44; elevated protein count in cerebrospinal fluid&#44; diffuse slowing in the electroencephalogram&#44; together with the systemic and analytical clinical data described&#46; In the differential diagnosis&#44; the demyelinating aetiology of the hemorrhagic leukoencephalitis was considered&#44; but the lack of red blood cells&#44; negative oligoclonal banding in cerebrospinal fluid&#44; absence of oedema and hemorrhagic component in the MRI rule out this aetiology&#46; There are no epidemiological data for the toxic aetiology&#44; and the infectious cause is ruled out after the extensive study in this regard&#46; We ruled out inflammatory amyloid angiopathy due to the lack of bleeding and hemosiderin deposits in <span class="elsevierStyleItalic">spin-echo</span> sequences on MRI&#46; Vasculitis of the nervous system&#44; in this case secondary to the accompanying systemic symptoms&#44; is ruled out because it does not present pleocytosis or data on autoimmune or infectious diseases&#46; Fever&#44; pancytopenia&#44; and white matter involvement would work in favour of lymphoma with nervous system involvement&#44; but a negative cerebrospinal fluid flow cytometry would work against it&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Despite a first negative bone marrow biopsy&#44; the clinical and laboratory findings pointed to the hemophagocytic syndrome as the cause of the patient&#39;s symptoms&#46; We insisted on the need for a second bone marrow biopsy showing hemophagocytosis and abnormal lymphocytes compatible with germinal centre B-cell non-Hodgkin lymphoma in a percentage lower than 5&#37; on cytometry&#46; Despite starting treatment with corticosteroid pulse therapy and subsequently cyclophosphamide&#44; the patient died in the ICU&#44; unable to perform autopsy due to family refusal&#44; being the final diagnosis that of idiopathic hemophagocytic syndrome&#44; not ruling out that it was secondary to lymphoma&#44; although a percentage of abnormal lymphocytes below 5&#37; do not allow its confirmation&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">When the hemophagocytic syndrome affects the nervous system&#44; it can manifest as subacute encephalopathy&#44; meningoencephalomyelitis&#44; hematomas&#44; Guillain-Barr&#233; or cauda equina syndrome&#46; The differential diagnosis is narrowed if it is accompanied by systemic data such as fever&#44; lymphadenopathy&#44; hepatosplenomegaly&#44; skin lesions&#44; and laboratory abnormalities such as pancytopenia and elevated LDH&#44; triglycerides&#44; ferritin&#44; and CD25&#46; It is a disease with a high mortality rate&#44; but it can respond to treatment&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">This case has the peculiarity that&#44; despite a first negative bone marrow biopsy&#44; the neurological manifestations&#44; ancillary tests&#44; systemic data and laboratory abnormalities allowed us to suspect the hemophagocytic syndrome&#44; which was confirmed in the second bone marrow biopsy&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">It is important to bear in mind that we&#44; neurologists&#44; should not only assess &#34;pure&#34; neurological manifestations&#44; but also those that are accompanied by systemic manifestations&#44; since we provide insight into the diagnosis and treatment of diseases such as hemophagocytic syndrome&#44; which can enable us to increase our knowledge of these diseases&#46;</p></span>"
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ISSN: 23870206
Original language: English
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