Scientific Letter
Limbic encephalitis: The great unknown
Encefalitis límbica: la gran desconocida
B. Sosa-Torres
, M.J. Prieto-Bragado, L.Á. Domínguez-Quintero, P. Fernández-Arroyo, E. Blasco-Ciscar, R. Cantó-Pérez
Corresponding author
Servicio de Cuidados Intensivos, Hospital Marina Baixa, Alicante, La Vila Joiosa, Spain
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Sosa-Torres, M.J. Prieto-Bragado, L.Á. Domínguez-Quintero, P. Fernández-Arroyo, E. Blasco-Ciscar, R. Cantó-Pérez" "autores" => array:6 [ 0 => array:4 [ "nombre" => "B." "apellidos" => "Sosa-Torres" "email" => array:1 [ 0 => "bsosatorres@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "M.J." "apellidos" => "Prieto-Bragado" ] 2 => array:2 [ "nombre" => "L.Á." "apellidos" => "Domínguez-Quintero" ] 3 => array:2 [ "nombre" => "P." "apellidos" => "Fernández-Arroyo" ] 4 => array:2 [ "nombre" => "E." "apellidos" => "Blasco-Ciscar" ] 5 => array:2 [ "nombre" => "R." "apellidos" => "Cantó-Pérez" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Cuidados Intensivos, Hospital Marina Baixa, Alicante, La Vila Joiosa, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Encefalitis límbica: la gran desconocida" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 812 "Ancho" => 1501 "Tamanyo" => 115765 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">NMR of the brain ([A]: diffusion study, and [B]: ADC coefficient). The diffusion study shows hyperintensity with discrete decrease of the ADC coefficient in the hypocampic region of the left temporal lobe.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Limbic encephalitis (LE), described in 1960 by Brierley et al.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> is a rare neurological clinical entity of subacute course that causes neuropsychiatric symptoms.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Hereby we present the clinical case of a seventy one year old female with dyslipidemia, hypothyroidism and breast ductal carcinoma with radical exeresis and treated with chemotherapy. She was admitted in the hospital following an event of sepsis due to methicillin-sensitive Staphylococcus aureus (due to reservoir infection). She suffers from progressive disorientation, repetitive talking, and sleepiness with progression towards status epilepticus, which is why she was admitted in the unit of intensive care medicine (ICM). The urgent cranial computed tomography (CT) scan performed did not show any significant findings. At admission her state is post-critical after the administration of intravenous (IV) benzodiazepines and her temperature is 38<span class="elsevierStyleHsp" style=""></span>°C; the rest of the device based-medical examination was normal. The blood sample showed platelet levels of 22<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/l, creatinine levels of 3.5<span class="elsevierStyleHsp" style=""></span>mg/dl, urea levels of 95<span class="elsevierStyleHsp" style=""></span>mg/dl, C-reactive protein (CRP) levels of 15.6<span class="elsevierStyleHsp" style=""></span>mg/dl, the rest being normal. Doctors proceeded with orotracheal intubation and lumbar puncture (LP) followed by secretion of cerebrospinal fluid (CSF) colourless at normal-pressure without cells, glucose levels of 68<span class="elsevierStyleHsp" style=""></span>mg/gl and protein levels of 64<span class="elsevierStyleHsp" style=""></span>mg/dl (plasma proteins 5.2<span class="elsevierStyleHsp" style=""></span>g/dl). Doctors proceeded with sedoanalgesia, fluid therapy, levetiracetam, and broad-spectrum IV antimicrobial treatment including acyclovir. They were isolated in bronchoaspiration and one hemoculture of the extended-spectrum-beta-lactamase-producing Klebsiella pneumonia without condensation in the chest X-ray was collected; both the urine culture and the CSF culture tested negative. CSF with polymerase chain reaction (PCR) for herpes simplex virus (HSV), cytomegalovirus (CMV), varicella zoster virus (VZV) and Epstein–Barr virus (EBV) all tested negative, and the cytology to rule out malignant cells tested negative too. Serologies for human immunodeficiency virus (HIV), hepatitis, HSV, CMV and VZV tested negative for active infections. Elevated CA 125 level (180.3<span class="elsevierStyleHsp" style=""></span>U/ml); remaining tumour markers normal. Negative test results for the anti-DNA antibodies, antinuclear antibodies, c-ANCA and p-ANCA. Thyroid hormones in normal ranges with replacement therapy and negative test results for the antiperoxidase and antithyroglobulin antibodies. One second CT scan with the administration contrast is performed and it rules out structural disease, and also another control LP with secretion of colourless fluid at normal pressure with normal biochemical profile without cells, and negative for malignancy. Given the low level of consciousness, one electroencephalogram (EEG) is performed that is consistent with the effects of sedation and the nuclear magnetic resonance (NMR) of the brain with the following results: in the T2-weighted sequence of the hypocampic region, there is hyperintensity of left predominance, in the diffusion-weighted sequence, there is hyperintensity and a mild decrease of the apparent diffusion coefficient (ADC) in the hypocampic region of the left temporal lobe. After the administration of paramagnetic contrast there is no presence of any uptakes (<a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1 and 2</a>A and B).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Given the clinical data and the characteristic neuroimaging obtained, a diagnosis of LE was suggested; onconeuronal antibodies tests in blood and CSF (against NMDA, IA-2, GAD, Hu, Yo, Ri, PNMA2, CV2, antiphysine, titin, recoverin and SOX1) were conducted and they tested negative. Treatment with 1<span class="elsevierStyleHsp" style=""></span>mg/kg/d of IV methylprednisolone was initiated that resulted in a slow but favourable neurological recovery. The patient was discharged from the ICM unit after 35 days, then from the hospital after 20 days, and then administered 1<span class="elsevierStyleHsp" style=""></span>mg/kg/d of oral prednisone for the next three<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> months after which she achieved ad integrum neurological recovery.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The clinical manifestations of LE are the subacute<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> appearance of several neuropsychiatric alterations including, among others, cognitive impairment, seizures, depression, irritability, hallucinations, and loss of short term memory.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3,4</span></a> In most cases, the CSF<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> shows inflammatory changes with discrete proteinorrachia and/or pleocytosis without pathognomonic findings. The CT scan<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> is usually normal, without contrast uptake, while in 70% of the cases, the NMR of the brain<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> is asymmetrically hyperintense in both temporal lobes, especially the T2 and the FLAIR-weighted sequences, while remains unenhanced after the administration of contrast. The EEG can show temporal or diffuse slowness, temporal spikes, and temporal or generalized focal seizure activity.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Today we can distinguish three<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> types of LE:<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> paraneoplastic, viral and idiopathic (non-paraneoplastic autoimmune).</p><p id="par0030" class="elsevierStylePara elsevierViewall">Our patient shows clinical data associated with additional tests that are highly suggestive of LE. In the context of immunosuppression and since the most common cause of LE is viral, we ruled out a diagnosis of viral LE since the CRP in the CSF tested negative for HSV, CMV, VZV, and EBV (sensitivity and specificity over 95%).<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> Differential diagnosis was conducted with other causes of encephalopathy with affectation of the temporal lobe such as mesial sclerosis, ischaemic stroke, cerebral neoplasm, Hashimoto encephalopathy and lupus encephalopathy.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Taking these data into consideration, the most probable clinical diagnosis is paraneoplastic LE<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> (PLE). This is a rare entity (occurring in <1% of patients with cancer) and in between 60 and 70% of the cases, the neurological clinical manifestations can occur even years before the identification of the neoplasm; the tumours more commonly associated with PLE are small cell lung carcinomas (50%), testicular cancers (20%), and breast cancers (8%).</p><p id="par0040" class="elsevierStylePara elsevierViewall">The diagnosis of this entity requires meeting the four<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> following criteria:<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> a compatible clinical picture, absence of neuro-oncological complications, <4 years-interval between symptom onset and the diagnosis of the tumour, and at least, one of the following: (a) inflammatory changes in the CSF with a negative cytology, (b) one NMR of the brain with changes in the temporal lobe, (c) the identification of onconeuronal antibodies<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6,10</span></a> in blood or the CSF–present in between 50 and 60% of cases whose specificity is over 90%.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Our patient meets all diagnostic criteria except for testing positive for onconeuronal antibodies.</p><p id="par0050" class="elsevierStylePara elsevierViewall">The LE is a rare and misdiagnosed clinical entity that should be taken into consideration when conducting the differential diagnosis of confusional state of subacute onset. In medical literature there are very few cases of PLE reported, and it is an exceptional diagnosis after the neoplastic process.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Management of PLE is based on symptom control and the initiation of oncospecific and/or immunomodulating therapy. Up to 50% of the patients do not respond to first line immunomodulating therapies (corticoids, IV immunoglobulins or plasma exchange–alone or combined). In the management of refractory cases, the administration of second-line therapies (rituximab and cyclophosphamide – alone or combined)<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> enables full recoveries or with minimal deficits in 80% of the cases.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Sosa-Torres B, Prieto-Bragado MJ, Domínguez-Quintero LÁ, Fernández-Arroyo P, Blasco-Ciscar E, Cantó-Pérez R. Encefalitis límbica: la gran desconocida. Med Intensiva. 2017;41:319–321.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1105 "Ancho" => 882 "Tamanyo" => 133556 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">NMR of the brain, FLAIR sequence. Signal hyperintensity in the hypocampic region of both temporal lobes of left predominance.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 812 "Ancho" => 1501 "Tamanyo" => 115765 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">NMR of the brain ([A]: diffusion study, and [B]: ADC coefficient). 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 7 | 5 | 12 |
| 2024 October | 69 | 57 | 126 |
| 2024 September | 70 | 40 | 110 |
| 2024 August | 60 | 71 | 131 |
| 2024 July | 62 | 40 | 102 |
| 2024 June | 66 | 92 | 158 |
| 2024 May | 55 | 52 | 107 |
| 2024 April | 64 | 34 | 98 |
| 2024 March | 71 | 32 | 103 |
| 2024 February | 59 | 37 | 96 |
| 2024 January | 50 | 39 | 89 |
| 2023 December | 48 | 35 | 83 |
| 2023 November | 75 | 57 | 132 |
| 2023 October | 79 | 41 | 120 |
| 2023 September | 66 | 69 | 135 |
| 2023 August | 46 | 22 | 68 |
| 2023 July | 48 | 41 | 89 |
| 2023 June | 46 | 25 | 71 |
| 2023 May | 85 | 48 | 133 |
| 2023 April | 55 | 27 | 82 |
| 2023 March | 119 | 36 | 155 |
| 2023 February | 87 | 36 | 123 |
| 2023 January | 69 | 24 | 93 |
| 2022 December | 87 | 50 | 137 |
| 2022 November | 74 | 47 | 121 |
| 2022 October | 112 | 55 | 167 |
| 2022 September | 96 | 38 | 134 |
| 2022 August | 89 | 46 | 135 |
| 2022 July | 73 | 46 | 119 |
| 2022 June | 59 | 24 | 83 |
| 2022 May | 56 | 38 | 94 |
| 2022 April | 73 | 50 | 123 |
| 2022 March | 93 | 60 | 153 |
| 2022 February | 101 | 42 | 143 |
| 2022 January | 108 | 41 | 149 |
| 2021 December | 125 | 43 | 168 |
| 2021 November | 104 | 53 | 157 |
| 2021 October | 147 | 77 | 224 |
| 2021 September | 76 | 48 | 124 |
| 2021 August | 63 | 47 | 110 |
| 2021 July | 37 | 42 | 79 |
| 2021 June | 66 | 34 | 100 |
| 2021 May | 57 | 45 | 102 |
| 2021 April | 129 | 91 | 220 |
| 2021 March | 120 | 33 | 153 |
| 2021 February | 77 | 23 | 100 |
| 2021 January | 80 | 31 | 111 |
| 2020 December | 71 | 28 | 99 |
| 2020 November | 61 | 22 | 83 |
| 2020 October | 95 | 29 | 124 |
| 2020 September | 119 | 23 | 142 |
| 2020 August | 56 | 25 | 81 |
| 2020 July | 78 | 28 | 106 |
| 2020 June | 55 | 19 | 74 |
| 2020 May | 42 | 16 | 58 |
| 2020 April | 39 | 20 | 59 |
| 2020 March | 24 | 12 | 36 |
| 2020 February | 93 | 46 | 139 |
| 2020 January | 62 | 24 | 86 |
| 2019 December | 80 | 36 | 116 |
| 2019 November | 75 | 25 | 100 |
| 2019 October | 62 | 32 | 94 |
| 2019 September | 49 | 18 | 67 |
| 2019 August | 32 | 19 | 51 |
| 2019 July | 34 | 26 | 60 |
| 2019 June | 35 | 25 | 60 |
| 2019 May | 52 | 39 | 91 |
| 2019 April | 19 | 20 | 39 |
| 2019 March | 44 | 34 | 78 |
| 2019 February | 52 | 31 | 83 |
| 2019 January | 33 | 25 | 58 |
| 2018 December | 45 | 38 | 83 |
| 2018 November | 56 | 37 | 93 |
| 2018 October | 43 | 23 | 66 |
| 2018 September | 42 | 15 | 57 |
| 2018 August | 26 | 9 | 35 |
| 2018 July | 35 | 18 | 53 |
| 2018 June | 40 | 11 | 51 |
| 2018 May | 24 | 9 | 33 |
| 2018 April | 33 | 14 | 47 |
| 2018 March | 37 | 12 | 49 |
| 2018 February | 24 | 11 | 35 |
| 2018 January | 46 | 24 | 70 |
| 2017 December | 31 | 11 | 42 |
| 2017 November | 48 | 22 | 70 |
| 2017 October | 46 | 0 | 46 |
| 2017 September | 2 | 0 | 2 |
| 2017 July | 2 | 3 | 5 |
| 2017 May | 0 | 3 | 3 |
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