Nódulo brillante en la frente de un adulto / A Shiny Nodule on the Forehead of a Man

No disponible

The role of infections in autoimmune encephalitides.

Autoimmune encephalitides are autoimmune neurological disorders characterized by rapidly progressive central nervous system symptoms associated with specific auto-antibodies targeting neuronal cell-surface proteins. The clinical features of encephalitis are frequently preceded by symptoms suggesting an infectious process, and specific pathogens have been detected at the early phase of the disease in some patients, suggesting that it can be triggered by infections. Moreover, recent data have shown an association with specific HLA haplotypes, suggesting a genetic susceptibility to develop at least some subtypes of autoimmune encephalitis. Nonetheless, the immunological mechanisms leading from an adequate response to infection to autoimmunity against neuronal self-antigens remain highly hypothetical. Molecular mimicry, inborn errors of the host immune system, as well as epitope spreading and chronic activation of innate immunity actors, may be involved. Importantly, the frequency of prodromal infectious symptoms and association with HLA haplotypes differ among autoimmune encephalitides, suggesting that depending on the subtype distinct immunopathogenic mechanisms are involved. A direct link between infection and autoimmune encephalitis was recently provided by the demonstration that most of the so-called relapsing neurological symptoms post-herpes simplex virus encephalitis corresponded to viral-induced autoimmune encephalitis with antibodies against NMDA receptors or other, yet unknown, neuronal surface antigens. Although this association has also been demonstrated experimentally in mice, the underlying immunological mechanisms remain unknown. Overall, a body of clinical, epidemiological and experimental data suggests infections are involved in the pathogenesis of autoimmune encephalitides. Further studies, focusing on the interplays between pathogens, genetic determinants of the host immune response, and brain inflammation, are needed to clarify the immunological mechanisms that lead to autoimmune encephalitis after infection.

Milia, una reacción infrecuente tras terapia fotodinámica / Milia: An Uncommon Reaction to Photodynamic Therapy

No disponible

[Autoimmune encephalitis]. / Encefalitis autoinmunes.

Autoimmune encephalitis are a new category of inflammatory diseases of the central nervous system mediated by antibodies that attack neurotransmitter or protein receptors on the surface of neurons. The clinical syndromes are complex and are associated with manifestations that vary according to the type of antibody that is associated. The autoimmune response can start due to the presence of a tumour or viral infection, but in many case the cause remains unknown. In paediatrics, the most frequent autoimmune encephalitis is that associated with NMDA glutamate receptor antibodies (or anti-NMDA encephalitis). In children and teenagers, the initial symptoms are usually different from those of adults and the disease is rarely associated with tumours. In this article, in addition to anti-NMDA encephalitis, the general aspects of autoimmune encephalitis are reviewed and the most common questions asked about treatment of these diseases are addressed.

TITLE: Encefalitis autoinmunes.Las encefalitis autoinmunes constituyen una nueva categoria de enfermedades inflamatorias del sistema nervioso central mediadas por anticuerpos contra receptores de neurotransmisores o proteinas de la superficie neuronal. Los sindromes clinicos son complejos y se asocian a manifestaciones que varian en funcion del tipo de anticuerpo asociado. La respuesta autoinmune puede iniciarse por la presencia de un tumor o infeccion virica, pero en muchos casos se desconoce la causa. En pediatria, la encefalitis autoinmune mas frecuente es la que se asocia a anticuerpos contra el receptor de glutamato NMDA (o encefalitis anti-NMDAR). En niños y adolescentes, los sintomas iniciales suelen ser diferentes a los de los adultos y la enfermedad raramente se asocia a tumores. En este articulo, ademas de la encefalitis anti-NMDAR, se revisan los aspectos generales de las encefalitis autoinmunes y se abordan las preguntas mas frecuentes que suscita el tratamiento de estas enfermedades.

Syndrome and outcome of antibody-negative limbic encephalitis.

BACKGROUND AND PURPOSE: The aim was to report the clinical characteristics of 12 patients with limbic encephalitis (LE) who were antibody-negative after a comprehensive immunological study. METHODS: The clinical records of 163 patients with LE were reviewed. Immunohistochemistry on rat brain, cultured neurons and cell-based assays were used to identify neuronal autoantibodies. Patients were included if (i) there was adequate clinical, cerebrospinal fluid (CSF) and magnetic resonance imaging information to classify the syndrome as LE, (ii) magnetic resonance images were accessible for central review and (iii) serum and CSF were available and were confirmed negative for neuronal antibodies. RESULTS: Twelve (7%) of 163 LE patients [median age 62 years; range 40-79; 9 (75%) male] without neuronal autoantibodies were identified. The most frequent initial complaints were deficits in short-term memory leading to hospital admission in a few weeks (median time 2 weeks; range 0.5-12). In four patients the short-term memory dysfunction remained as an isolated symptom during the entire course of the disease. Seizures, drowsiness and psychiatric problems were unusual. Four patients had solid tumors (one lung, one esophagus, two metastatic cervical adenopathies of unknown primary tumor) and one chronic lymphocytic leukemia. CSF showed pleocytosis in seven (58%) with a median of 13 white blood cells/mm3 (range 9-25). Immunotherapy included corticosteroids, intravenous immunoglobulins and combinations of both drugs or with rituximab. Clinical improvement occurred in six (54%) of 11 assessable patients. CONCLUSIONS: Despite the discovery of new antibodies, 7% of LE patients remain seronegative. Antibody-negative LE is more frequent in older males and usually develops with predominant or isolated short-term memory loss. Despite the absence of antibodies, patients may have an underlying cancer and respond to immunotherapy.

Dietary practices in propionic acidemia: A European survey.

BACKGROUND: The definitive dietary management of propionic acidaemia (PA) is unknown although natural protein restriction with adequate energy provision is of key importance. AIM: To describe European dietary practices in the management of patients with PA prior to the publication of the European PA guidelines. METHODS: This was a cross-sectional survey consisting of 27 questions about the dietary practices in PA patients circulated to European IMD dietitians and health professionals in 2014. RESULTS: Information on protein restricted diets of 186 PA patients from 47 centres, representing 14 European countries was collected. Total protein intake [PA precursor-free L-amino acid supplements (PFAA) and natural protein] met WHO/FAO/UNU (2007) safe protein requirements for age in 36 centres (77%). PFAA were used to supplement natural protein intake in 81% (n = 38) of centres, providing a median of 44% (14-83%) of total protein requirement. Seventy-four per cent of patients were prescribed natural protein intakes below WHO/FAO/UNU (2007) safe levels in one or more of the following age groups: 0-6 m, 7-12 m, 1-10 y, 11-16 y and > 16 y. Sixty-three per cent (n = 117) of patients were tube fed (74% gastrostomy), but only 22% received nocturnal feeds. CONCLUSIONS: There was high use of PFAA with intakes of natural protein commonly below WHO/FAO/UNU (2007) safe levels. Optimal dietary management can only be determined by longitudinal, multi-centre, prospective case controlled studies. The metabolic instability of PA and small patient cohorts in each centre ensure that this is a challenging undertaking.

Dietary practices in isovaleric acidemia: A European survey.

BACKGROUND: In Europe, dietary management of isovaleric acidemia (IVA) may vary widely. There is limited collective information about dietetic management. AIM: To describe European practice regarding the dietary management of IVA, prior to the availability of the E-IMD IVA guidelines (E-IMD 2014). METHODS: A cross-sectional questionnaire was sent to all European dietitians who were either members of the Society for the Study of Inborn Errors of Metabolism Dietitians Group (SSIEM-DG) or whom had responded to previous questionnaires on dietetic practice (n = 53). The questionnaire comprised 27 questions about the dietary management of IVA. RESULTS: Information on 140 patients with IVA from 39 centres was reported. 133 patients (38 centres) were given a protein restricted diet. Leucine-free amino acid supplements (LFAA) were routinely used to supplement protein intake in 58% of centres. The median total protein intake prescribed achieved the WHO/FAO/UNU [2007] safe levels of protein intake in all age groups. Centres that prescribed LFAA had lower natural protein intakes in most age groups except 1 to 10 y. In contrast, when centres were not using LFAA, the median natural protein intake met WHO/FAO/UNU [2007] safe levels of protein intake in all age groups. Enteral tube feeding was rarely prescribed. CONCLUSIONS: This survey demonstrates wide differences in dietary practice in the management of IVA across European centres. It provides unique dietary data collectively representing European practices in IVA which can be used as a foundation to compare dietary management changes as a consequence of the first E-IMD IVA guidelines availability.

Anti-N-Methyl-D-Aspartate Receptor Encephalitis: A New Challenging Entity for Consultation-Liaison Psychiatrist.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a relatively newly identified autoimmune neuropsychiatric disorder that predominantly affects children and young adults. Although psychiatric symptoms are highly prevalent and frequently severe, it has mainly been reported in neurological, but not psychiatric, literature. Understanding this form of encephalitis, its quick diagnosis and which treatment to provide are of utmost importance for consultation-liaison (C-L) psychiatrists. The aim of this paper was to describe a case of anti-NMDAR encephalitis with severe psychiatric manifestations, who showed impressive recovery but required intensive involvement of the C-L psychiatry team. We emphasise the behavioural aspects, psychiatric symptoms and challenges faced by the CL consultant across the different phases of the treatment. METHODS: We report the different treatment phases for a young woman with anti-NMDAR encephalitis who developed severe neuropsychiatric symptoms, with a focus on the role and challenges faced by the C-L psychiatrist. The literature is reviewed for each of these challenges. RESULTS: This case illustrated that even extremely severely affected patients may show impressive recovery, but require long lasting psychiatric care. C-L psychiatrists are faced with numerous challenges where only little literature is available. CONCLUSION: C-L psychiatrists play a pivotal role throughout the multidisciplinary care of patients with anti-NMDAR encephalitis and should be informed about this entity.

Residual enzymatic activity as a prognostic factor in patients with Gaucher disease type 1: correlation with Zimran and GAUSS-I index and the severity of bone disease.

BACKGROUND: Gaucher disease (GD) is an autosomal recessive disorder produced by mutations in the glucocerebrosidase gene (GBA), causing storage of glucosylceramide in reticuloendothelial cells in multiple organs. Traditionally, the prediction of the phenotype based on the genotype has been reported to be limited. SUBJECTS AND METHODS: We investigated the correlation between the enzymatic residual activity (ERA) and the phenotype at diagnosis of the disease in 45 GD Spanish patients (44 with type I and 1 with type III GD). The genotype involved two of the following previously expressed proteins: c.517A > C (T134P), 1%; c.721G > A (G202R), 17%; c.1090G > T (G325W), 13.9%; c.1208G > A (S364N), 4.1%; c.1226A > G (N370S), 17.8%; c.1246G > A (G377S), 17.6%; c.1289C > T (P391L), 8.5%; c.1448T > C (L444P), 3%; and c.1504C > T (R463C), 24.5%. Recombinant alleles, deletion of 55 bp in exon 9 and 84GG mutation were considered as mutations with no residual enzymatic activity. RESULTS: The ERA showed a statistically significant correlation with chitotriosidase (P < 0.001), age (P < 0.001), spleen size (P < 0.001), 'Zimran's Severity Score Index' (P < 0.01) and the 'Gaucher Disease Severity Score Index-Type I' (P < 0.0001) at diagnosis of the disorder. Previous to any medical intervention, a comparison between the ERA and bone involvement, demonstrated a statistically significant relationship (P < 0.01) between the two variables. CONCLUSIONS: This study data allowed us to define a new criterion for prognostic assessment of the disease at diagnosis, called Protein Severity Index, which expresses the theoretical severity of the genotype presented by patients, according to the corresponding ERA.

Recomendaciones para el diagnóstico y el tratamiento de la enfermedad de Gaucher durante la infancia / Recommendations for diagnosis and treatment of pediatric Gaucher disease

El diagnóstico y el tratamiento de la enfermedad de Gaucher infantil presentan dificultades debido a su variabilidad clínica. Tres pediatras expertos en la enfermedad han propuesto una serie de recomendaciones generales al respecto. El paciente debe ser asistido por un equipo multidisciplinario, en un centro pediátrico con experiencia en el tratamiento de enfermedades metabólicas. El diagnóstico del paciente sintomático se garantiza con la anamnesis, el examen físico (afectación visceral, hematológica, esquelética y/o del sistema nervioso central), los exámenes complementarios y la confirmación mediante un estudio enzimático y genético. Los objetivos terapéuticos son recuperar al paciente de los síntomas que presenta, modificar beneficiosamente la evolución natural de la enfermedad y evitar el desarrollo de asociaciones patológicas. En los pacientes sin patología neurológica menores de 20 años de edad es obligado el tratamiento enzimático sustitutivo i.v., pero en patología neurológica no ejerce efecto sobre el sistema nervioso central, aunque puede utilizarse en la forma tipo III para mejorar las manifestaciones viscerales y óseas (AU)

The diagnosis and treatment of pediatric Gaucher disease is difficult due to its clinical variability. Three pediatricians, experts in the disease, have proposed a series of recommendations regarding the subject. The patient must be taken care of by a multidisciplinary team, in a pediatric center with experience in metabolic diseases. The diagnosis of the symptomatic patient is guaranteed by the anamnesis, physical exam (visceral, hematologic, skeletal and/or CNS involvement), complementary exams and confirmation by means of enzymatic and genetic studies. The therapeutic objectives are recovery from exhibited symptoms, beneficial modification of the natural course of the disease and avoidance of development of associated pathology. In patients with no neurologic pathology <20 years old, iv enzymatic replacement therapy is mandatory but in case of neurologic pathology it does not exert an effect on SNC, although it may be used in type III to improve visceral and bone manifestations (AU)

The expanding field of IgG4-mediated neurological autoimmune disorders.

At least 13 different disease entities affecting the central nervous system, peripheral nervous system and connective tissue of the skin or kidneys are associated with immunoglobulin G4 (IgG4) immune reactivity. IgG4 has always been considered a benign, non-inflammatory subclass of IgG, in contrast to the well-known complement-activating pro-inflammatory IgG1 subclass. A comprehensive review of these IgG4 autoimmune disorders reveals striking similarities in epitope binding and human leukocyte antigen (HLA) associations. Mechanical interference of extracellular ligand-receptor interactions by the associated IgG4 antibodies seems to be the common/converging disease mechanism in these disorders.

Espectro clínico y valor diagnóstico de los anticuerpos contra el complejo proteico asociado a canales de potasio / Clinical spectrum and diagnostic value of antibodies against the potassium channel related protein complex

Introducción: Los anticuerpos contra un complejo proteico que incluye a los canales de potasio dependientes de voltaje (CKVD) se han descrito en pacientes con encefalitis límbica, hiperexcitabilidad del nervio periférico, síndrome de Morvan, así como en un creciente grupo de síndromes neurológicos. Desarrollo: En este artículo revisamos los síndromes asociados a anticuerpos contra proteínas relacionadas con los CKVD y los 2 antígenos principales de este complejo, las proteínas leucine rich glioma inactivated protein 1 (LGI1) y contactin-associated protein-like 2 (Caspr2). Así mismo describimos los problemas conceptuales y las implicaciones diagnósticas de la descripción de anticuerpos contra CKVD diferentes de LGI1 y Caspr2. Aunque inicialmente se consideró que existían anticuerpos dirigidos contra CKVD, recientemente se ha identificado que, en la mayor parte de los casos, los antígenos son una proteína neuronal secretada denominada LGI1, involucrada en el control de la excitabilidad sináptica, y la proteína Caspr2, localizada en la superficie neuronal de varias regiones cerebrales y en la región yuxtaparanodal de axones mielinizados. Mientras que los anticuerpos contra LGI1 se asocian preferentemente a un cuadro clásico de encefalitis límbica, los anticuerpos contra Caspr2 muestran un espectro clínico más amplio, incluyendo el síndrome de Morvan, la hiperexcitabilidad del nervio periférico o neuromiotonía, o una encefalitis límbica o difusa. Existen además casos descritos de pacientes con anticuerpos contra el complejo CKVD que no tienen anticuerpos contra LGI1 o Caspr2. En estos casos, la identidad y la localización de los antígenos es desconocida, la asociación sindrómica inespecífica y la respuesta al tratamiento, incierta. Conclusiones: El descubrimiento de los antígenos LG1 y Caspr2 ha permitido delimitar clínica y molecularmente el amplio grupo de síndromes previamente atribuidos a anticuerpos contra CKVD. Frente a la literatura que describe la presencia de anticuerpos contra CKVD diferentes a LGI1 y Caspr2, proponemos un algoritmo práctico para el diagnóstico y el tratamiento de estos pacientes

Introduction: Antibodies against a protein complex that includes voltage-gated potassium channels (VGKC) have been reported in patients with limbic encephalitis, peripheral nerve hyperexcitability, Morvan's syndrome, and a large variety of neurological syndromes. Review summary: In this article, a review is presented of the syndromes associated with antibodies against VGKC-related proteins and the main antigens of this protein complex, the proteins LGI1 (leucine rich glioma inactivated protein 1) and Caspr2 (contactin-associated protein-like 2). The conceptual problems and clinical implications of the description of antibodies against VGKC-related proteins other than LGI1 and Caspr2 are also discussed. Although initial studies indicated the occurrence of antibodies against VGKC, recent investigations have shown that the main antigens are a neuronal secreted protein known as LGI1 which modulates synaptic excitability, and a protein called Caspr2 located on the cell surface and processes of neurons of different brain regions, and at the juxtaparanodal region of myelinated axons. While antibodies against LGI1 preferentially associate with classical limbic encephalitis, antibodies against Caspr2 associate with a wider spectrum of symptoms, including Morvan's syndrome, peripheral nerve hyperexcitability or neuromyotonia, and limbic or more extensive encephalitis. In addition there are reports of patients with antibodies against VGKC-related proteins that are different from LGI1 or Caspr2. In these cases, the identity and location of the antigens are unknown, the syndrome association is not specific, and the response to treatment uncertain. Conclusions: The discovery of antigens such as LGI1 and Caspr2 has resulted in a clinical and molecular definition of the broad group of diseases previously attributed to antibodies against VGKC. Considering the literature that describes the presence of antibodies against VGKC other than LGI1 and Caspr2 proteins, we propose a practical algorithm for the diagnosis and treatment of these patients

Bipolar disorder and antibodies against the N-methyl-d-aspartate receptor: A gate to the involvement of autoimmunity in the pathophysiology of bipolar illness.

The high prevalence of comorbidity between bipolar disorder (BD) and other medical conditions, including autoimmune diseases, supports the hypothesis of the nature of BD as a biological illness category. Hence, an immune dysregulation process may play an important role in the development of at least certain subtypes of BD. Increasing evidence also suggests that the N-methyl-d-aspartate receptor (NMDAR) may be relevant in the pathophysiology of BD. A possible key mechanism underlying the physiopathology of certain autoimmune diseases that may present with affective symptoms might be the production of anti-NMDAR auto-antibodies (auto-Abs). The best characterized autoimmune anti-NMDAR disease is the anti-NMDAR encephalitis. It has been found that 4% of these patients present isolated, mostly affective, psychiatric manifestations during their illness. An interesting suggestion emerged from this overview is that the same mechanisms that trigger affective symptoms in patients with increased anti-NMDAR auto-Abs levels could be involved in the physiopathology of at least a subgroup of BD. Future studies are needed to characterize the relationship between anti-NMDAR auto-Abs and BD.

Practices in prescribing protein substitutes for PKU in Europe: No uniformity of approach.

BACKGROUND: There appears little consensus concerning protein requirements in phenylketonuria (PKU). METHODS: A questionnaire completed by 63 European and Turkish IMD centres from 18 countries collected data on prescribed total protein intake (natural/intact protein and phenylalanine-free protein substitute [PS]) by age, administration frequency and method, monitoring, and type of protein substitute. Data were analysed by European region using descriptive statistics. RESULTS: The amount of total protein (from PS and natural/intact protein) varied according to the European region. Higher median amounts of total protein were prescribed in infants and children in Northern Europe (n=24 centres) (infants <1 year, >2-3g/kg/day; 1-3 years of age, >2-3 g/kg/day; 4-10 years of age, >1.5-2.5 g/kg/day) and Southern Europe (n=10 centres) (infants <1 year, 2.5 g/kg/day, 1-3 years of age, 2 g/kg/day; 4-10 years of age, 1.5-2 g/kg/day), than by Eastern Europe (n=4 centres) (infants <1 year, 2.5 g/kg/day, 1-3 years of age, >2-2.5 g/kg/day; 4-10 years of age, >1.5-2 g/kg/day) and with Western Europe (n=25 centres) giving the least (infants <1 year, >2-2.5 g/kg/day, 1-3 years of age, 1.5-2 g/kg/day; 4-10 years of age, 1-1.5 g/kg/day). Total protein prescription was similar in patients aged >10 years (1-1.5 g/kg/day) and maternal patients (1-1.5 g/kg/day). CONCLUSIONS: The amounts of total protein prescribed varied between European countries and appeared to be influenced by geographical region. In PKU, all gave higher than the recommended 2007 WHO/FAO/UNU safe levels of protein intake for the general population.

How strict is galactose restriction in adults with galactosaemia? International practice.

Dietary management of 418 adult patients with galactosaemia (from 39 centres/12 countries) was compared. All centres advised lactose restriction, 6 restricted galactose from galactosides ± fruits and vegetables and 12 offal. 38% (n=15) relaxed diet by: 1) allowing traces of lactose in manufactured foods (n=13) or 2) giving fruits, vegetables and galactosides (n=2). Only 15% (n=6) calculated dietary galactose. 32% of patients were lost to dietetic follow-up. In adult galactosaemia, there is limited diet relaxation.

Análisis cuantitativo de la ingesta de nutrientes en niños menores de 3 años. Estudio ALSALMA / Quantitative analysis of nutrient intake in children under 3 years old. ALSALMA study

OBJETIVO: El objetivo del estudio fue analizar el patrón de alimentación de niños menores de 3 años y comparar los resultados con las recomendaciones de consumo energético y de nutrientes. PACIENTES Y MÉTODOS: En este estudio epidemiológico transversal, los padres completaron un diario dietético sobre el consumo de alimentos de sus hijos, durante 4 días no consecutivos. Se analizó la proporción de niños con ingestas medias inferiores a las recomendaciones para cada edad y nutriente, mediante el método «Estimated Average Requirement (EAR) cut-point method». RESULTADOS: Participaron 186 pediatras, que incluyeron a 1.701 niños. El 95,9% (n=1320) de los niños de 7 a 36 meses consumieron proteínas por encima del doble de las Recommended Dietary Allowances. Las deficiencias observadas (% < EAR) en los grupos de edad de 13-24 meses y 25-36 meses, respectivamente, fueron: vitamina D en el 81,7 y el 92,1%; vitamina E en el 39,3 y el 53,4%; ácido fólico en el el 12,5 y el 14,8%; calcio en el 10,1 y el 5,5%; yodo en el 27,1 y el 31%. Se observó que una mayor proporción en el consumo diario de proteínas (p = 0,013) y de hidratos de carbono (p < 0,0001), y una menor proporción de lípidos totales (p < 0,0001), estaban relacionadas con un mayor índice de masa corporal, independientemente del consumo energético. CONCLUSIONES: El estudio mostró una visión muy detallada de los patrones de alimentación de los niños españoles menores de 3 años. La promoción de una alimentación saludable debería ir dirigida a la corrección de los desequilibrios dietéticos detectados, para favorecer la salud futura de los niños

OBJECTIVE: The objective of the study was to analyze the nutritional patterns of children under three years of age and to compare the results against the recommendations for energy and nutrient intake. PATIENTS AND METHODS: In this cross-sectional epidemiological study, parents completed a dietary diary on their food intake of their children on 4 non-consecutive days. The percentage of children with mean intakes below the recommendations for each age and nutrient was analyzed using the 'Estimated Average Requirement (EAR) cut-point method.' RESULTS: A total of 186 pediatricians included 1701 children in the study. A total of 95.9% (n=1320) of the children between 7 and 36 months had a protein consumption more than twice that of the Recommended Daily Allowances. The deficiencies observed (% < EAR) in the age groups 13-24 months and 25-36 months, respectively, were: vitamin D in 81.7% and 92.1%; vitamin E in 39.3% and 53.4%; folic acid in 12.5% and 14.8%; calcium in 10.1% and 5.5%; iodine in 27.1% and 31%. It was observed that a higher percentage in the daily intake of proteins (P = .013) and of carbohydrates (P < .0001), and a lower percentage of total lipids (P < .0001), were related to a greater body mass index, regardless of energy intake. CONCLUSIONS: The study presents a very detailed view of the eating patterns of Spanish children less than three years of age. The encouragement of healthy feeding should be directed towards the correction of the dietary imbalances detected, in order to promote the future health of children

Clinical spectrum and diagnostic value of antibodies against the potassium channel related protein complex.

INTRODUCTION: Antibodies against a protein complex that includes voltage-gated potassium channels (VGKC) have been reported in patients with limbic encephalitis, peripheral nerve hyperexcitability, Morvan's syndrome, and a large variety of neurological syndromes. REVIEW SUMMARY: In this article, a review is presented of the syndromes associated with antibodies against VGKC-related proteins and the main antigens of this protein complex, the proteins LGI1 (leucine rich glioma inactivated protein 1) and Caspr2 (contactin-associated protein-like 2). The conceptual problems and clinical implications of the description of antibodies against VGKC-related proteins other than LGI1 and Caspr2 are also discussed. Although initial studies indicated the occurrence of antibodies against VGKC, recent investigations have shown that the main antigens are a neuronal secreted protein known as LGI1 which modulates synaptic excitability, and a protein called Caspr2 located on the cell surface and processes of neurons of different brain regions, and at the juxtaparanodal region of myelinated axons. While antibodies against LGI1 preferentially associate with classical limbic encephalitis, antibodies against Caspr2 associate with a wider spectrum of symptoms, including Morvan's syndrome, peripheral nerve hyperexcitability or neuromyotonia, and limbic or more extensive encephalitis. In addition there are reports of patients with antibodies against VGKC-related proteins that are different from LGI1 or Caspr2. In these cases, the identity and location of the antigens are unknown, the syndrome association is not specific, and the response to treatment uncertain. CONCLUSIONS: The discovery of antigens such as LGI1 and Caspr2 has resulted in a clinical and molecular definition of the broad group of diseases previously attributed to antibodies against VGKC. Considering the literature that describes the presence of antibodies against VGKC other than LGI1 and Caspr2 proteins, we propose a practical algorithm for the diagnosis and treatment of these patients.