Inmunosenescencia: el rol de la edad en la esclerosis múltiple / Immunosenescence: the role of age in multiple sclerosis

Introducción: Junto con el envejecimiento de la población general, la prevalencia de ancianos con esclerosis múltiple (EM) se encuentra en aumento. El sistema inmunológico sufre profundos cambios a lo largo de la vida, por lo que parece imprescindible conocer qué diferencias presentan respecto a pacientes más jóvenes. Desarrollo: La inmunosenescencia, definida como la alteración del sistema inmunológico en relación con el envejecimiento natural, juega un papel esencial en la tolerancia, efectos adversos y respuesta a los tratamientos modificadores de la enfermedad. Entre las principales características de este fenómeno, la involución que sufre el timo es la más destacable. Este hecho genera una reducción en la producción de células T vírgenes. Además, se observa una ratio de linfocitos CD4 + /CD8 + invertido, alteraciones severas en el funcionamiento de las células NK o una disminución en la capacidad de reparación tisular cerebral. Conclusiones: El número de personas de edad avanzada con EM se encuentra en aumento en coincidencia con el envejecimiento de la población general y gracias al avance en los tratamientos modificadores de la enfermedad, así como a la mejora en la asistencia sociosanitaria de estos pacientes. El envejecimiento del sistema inmunitario conlleva un mayor riesgo de infecciones, tumores y enfermedades autoinmunes en los ancianos. En la EM, además, tiene lugar una aceleración en la neurodegeneración por la pérdida de capacidad de remielinización del sistema nervioso. Conocer los cambios que tienen lugar en el sistema inmunológico de la población de edad avanzada es esencial para mejorar la atención de este grupo de pacientes cada vez más prevalente.(AU)

Introduction: The number of elderly people with multiple sclerosis (MS) has increased in line with population ageing. As the immune system presents profound changes over an individual's lifetime, it is important to understand the differences between these patients and younger patients. Development: Immunosenescence, defined as age-related alterations naturally occurring in the immune system, particularly influences tolerance, response, and adverse effects of disease-modifying treatments for MS. Thymic involution is the most noteworthy characteristic of this phenomenon. This process leads to a reduction in the number of virgin T cells. Other effects include an inverted CD4 + /CD8 + cell ratio, severe alterations in NK cell functioning, and reduced tissue repair capacity in the brain. Conclusions: The number of older people with MS is increasing due to population ageing, advances in disease-modifying treatments, and improved health and social care of these patients. Ageing of the immune system increases the risk of infections, tumours, and autoimmune diseases in elderly individuals. Furthermore, neurodegeneration is accelerated in patients with MS due to the nervous system's loss of remyelination capacity. Understanding of the changes affecting the immune system in the elderly population is essential to improving the care provided to this ever-growing patient group.(AU)

Immunosenescence: the role of age in multiple sclerosis.

INTRODUCTION: The number of elderly people with multiple sclerosis (MS) has increased in line with population ageing. As the immune system presents profound changes over an individual's lifetime, it is important to understand the differences between these patients and younger patients. DEVELOPMENT: Immunosenescence, defined as age-related alterations naturally occurring in the immune system, particularly influences tolerance, response, and adverse effects of disease-modifying treatments for MS. Thymic involution is the most noteworthy characteristic of this phenomenon. This process leads to a reduction in the number of virgin T cells. Other effects include an inverted CD4+/CD8+ cell ratio, severe alterations in NK cell functioning, and reduced tissue repair capacity in the brain. CONCLUSIONS: The number of older people with MS is increasing due to population ageing, advances in disease-modifying treatments, and improved health and social care of these patients. Ageing of the immune system increases the risk of infections, tumours, and autoimmune diseases in elderly individuals. Furthermore, neurodegeneration is accelerated in patients with MS due to the nervous system's loss of remyelination capacity. Understanding of the changes affecting the immune system in the elderly population is essential to improving the care provided to this ever-growing patient group.

Immunosenescence: the role of age in multiple sclerosis. / Inmunosenescencia: el rol de la edad en la esclerosis múltiple.

INTRODUCTION: The number of elderly people with multiple sclerosis (MS) has increased in line with population ageing. As the immune system presents profound changes over an individual's lifetime, it is important to understand the differences between these patients and younger patients. DEVELOPMENT: Immunosenescence, defined as age-related alterations naturally occurring in the immune system, particularly influences tolerance, response, and adverse effects of disease-modifying treatments for MS. Thymic involution is the most noteworthy characteristic of this phenomenon. This process leads to a reduction in the number of virgin T cells. Other effects include an inverted CD4 + /CD8 + cell ratio, severe alterations in NK cell functioning, and reduced tissue repair capacity in the brain. CONCLUSIONS: The number of older people with MS is increasing due to population ageing, advances in disease-modifying treatments, and improved health and social care of these patients. Ageing of the immune system increases the risk of infections, tumours, and autoimmune diseases in elderly individuals. Furthermore, neurodegeneration is accelerated in patients with MS due to the nervous system's loss of remyelination capacity. Understanding of the changes affecting the immune system in the elderly population is essential to improving the care provided to this ever-growing patient group.

Modificaciones epigenéticas en neurología: alteraciones en la metilación del ADN en la esclerosis múltiple / Epigenetic changes in neurology: DNA methylation in multiple sclerosis

Introducción: La epigenética se define como el estudio de los mecanismos que regulan la expresión génica sin modificar la secuencia de ADN, siendo entre ellos el más conocido la metilación del ADN. La esclerosis múltiple (EM) es una enfermedad de etiología no del todo conocida, en la que se plantea que la participación de factores ambientales sobre individuos con una determinada predisposición genética, pueden resultar claves para el desarrollo de la enfermedad. Es en esta intersección entre la predisposición genética y los factores ambientales donde la metilación del ADN puede desempeñar un papel patogénico. Desarrollo: Realizamos una revisión bibliográfica de los efectos que los factores de riesgo ambiental para el desarrollo de EM pueden ejercer sobre los distintos mecanismos epigenéticos, así como la implicación que presentan dichas modificaciones en el desarrollo de la enfermedad. Conclusión: El conocimiento de las modificaciones epigenéticas involucradas en la patogenia de la EM abre una nueva vía de investigación para la identificación de potenciales biomarcadores, así como para la búsqueda de nuevas dianas terapéuticas (AU)

Introduction: Epigenetics is defined as the study of the mechanisms that regulate gene expression without altering the underlying DNA sequence. The best known is DNA methylation. Multiple Sclerosis (MS) is a disease with no entirely known etiology, in which it is stated that the involvement of environmental factors on people with a genetic predisposition, may be key to the development of the disease. It is at this intersection between genetic predisposition and environmental factors where DNA methylation may play a pathogenic role. Development: A literature review of the effects of environmental risk factors for the development of MS can have on the different epigenetic mechanisms as well as the implication that such changes have on the development of the disease. Conclusion: Knowledge of epigenetic modifications involved in the pathogenesis of MS, opens a new avenue of research for identification of potential biomarkers, as well as finding new therapeutic targets (AU)

Epigenetic changes in neurology: DNA methylation in multiple sclerosis. / Modificaciones epigenéticas en neurología: alteraciones en la metilación del ADN en la esclerosis múltiple.

INTRODUCTION: Epigenetics is defined as the study of the mechanisms that regulate gene expression without altering the underlying DNA sequence. The best known is DNA methylation. Multiple Sclerosis (MS) is a disease with no entirely known etiology, in which it is stated that the involvement of environmental factors on people with a genetic predisposition, may be key to the development of the disease. It is at this intersection between genetic predisposition and environmental factors where DNA methylation may play a pathogenic role. DEVELOPMENT: A literature review of the effects of environmental risk factors for the development of MS can have on the different epigenetic mechanisms as well as the implication that such changes have on the development of the disease. CONCLUSION: Knowledge of epigenetic modifications involved in the pathogenesis of MS, opens a new avenue of research for identification of potential biomarkers, as well as finding new therapeutic targets.

[Inflammatory optic neuritis]. / Neuritis óptica inflamatoria.

Inflammatory Optic Neuritis (ON) is the most frequent cause of acute visual loss in young adults. Although the visual prognosis is excellent in the majority of cases, many patients develop pathology, such as multiple sclerosis, in its subsequent evolution. The natural history of ON has been studied in numerous works in recent years; one of the most important of which is Optic Neuritis Treatment Trial. Magnetic Resonance plays a fundamental role in the etiological diagnosis of ON and in predicting the risk of conversion into multiple sclerosis. New exploratory techniques have recently been incorporated, such as optical coherence tomography, useful for diagnosis and prognosis; serum biomarkers have been identified in the diagnosis of other pathologies with an autoimmune nature that produce ON. A better understanding of the clinical and exploratory data of typical ON will make a more rapid and accurate diagnostic study possible. Treatment of ON with steroids must be individualised bearing in mind that they do not alter the long-term prognosis and an immunomodulating therapy must be proposed for patients with a high risk of conversion into multiple sclerosis. This article reviews the existing data in the literature on its clinical manifestations, its etiological and differential diagnosis, and the treatment of inflammatory ON.

[Cocaine-induced brain stem stroke associated to craneal midline destructive lesions]. / Ictus de tronco asociado a lesiones destructivas de línea media craneal inducidas por cocaína.

INTRODUCTION: Abuse of cocaine and other sympathomimetic drugs has been reported as a significant risk factor for stroke. The physiopathologic mechanisms implicated are multifactorial. Chronic cocaine use leads to extensive destruction of osteocartilaginous structures of nose, sinuses and palate. CASE REPORT: We report the case of a 56 years-old woman with hypertension and smoke abuse who was admitted with a pontine paramedian infarction. Cranial resonance findings of midline destructive lesions lead to the suspicion of chronic cocaine consumption. The initial outcome was good but she was re-admitted nine months later with an extent pontomesencephalic infarction. CONCLUSIONS: Abuse of cocaine is a risk factor for stroke that should be considered not only in young patients. The pathogenic relationship between stroke and midline cocaine related destructive lesions is discussed.

Ictus de tronco asociado a lesiones destructivas de línea media craneal inducidas por cocaína / Cocaine-induced brain stem stroke associated to craneal midline destructive lesions

Introducción. La asociación entre enfermedad cerebrovascular y consumo de cocaína y otras drogas simpaticomiméticas ha sido ampliamente reflejada en la literatura y son múltiples los mecanismos fisiopatológicos que pueden explicar esta asociación. Por otro lado, el consumo crónico de cocaína produce lesiones destructivas de estructuras osteocartilaginosas de nariz, senos nasales y paladar. Caso clínico. Se describe el caso de una paciente de 56 años, hipertensa y fumadora que ingresa por un infarto pontino paramediano y en la que fue el hallazgo en neuroimagen de lesiones destructivas de línea media craneal lo que hizo sospechar el consumo crónico de cocaína. Tras una evolución inicial satisfactoria, sufrió una recurrencia a los 9 meses en forma de extenso infarto pontomesencefálico. Conclusiones. El consumo de cocaína debe tenerse en cuenta como factor de riesgo de enfermedad cerebrovascular, no sólo entre la población joven. Discutimos la relación fisiopatológica entre las lesiones destructivas de línea media craneal y los infartos de tronco recurrentes

Introduction. Abuse of cocaine and other sympathomimetic drugs has been reported as a significant risk factor for stroke. The physiopathologic mechanisms implicated are multifactorial. Chronic cocaine use leads to extensive destruction of osteocartilaginous structures of nose, sinuses and palate. Case report. We report the case of a 56 years-old woman with hypertension and smoke abuse who was admitted with a pontine paramedian infarction. Cranial resonance findings of midline destructive lesions lead to the suspicion of chronic cocaine consumption. The initial outcome was good but she was re-admitted nine months later with an extent pontomesencephalic infarction. Conclusions. Abuse of cocaine is a risk factor for stroke that should be considered not only in young patients. The pathogenic relationship between stroke and midline cocaine related destructive lesions is discussed

[Fatal familiar insomnia: clinical, neurophysiological and histopathological study of two cases]. / Insomnio letal familiar: estudio clínico, neurofisiológico e histopatológico de dos casos.

INTRODUCTION: Family prion diseases are caused by mutations in the gene coding the prion protein (PrP), originating an altered isoform called prion. One of the most uncommon is the fatal familial insomnia (FFI), an entity characterized by sleep disorders and that is associated to a mutation in codon 178. METHODS: We have studied two male patients, aged 43 and 49 years respectively, from the same family. RESULTS: The most significant symptoms were sleep disorders with agitation, fractionated sleep, snoring and daytime sleepiness. The evolution was brief, the patient dying at a few months of the clinical debut. Sleep registries showed destructuration with total loss of the normal cycle of the phases and great decrease of the sleep spindles and K complexes in both cases. The polygraphy showed tachycardia and apnea pauses. In the molecular study, a mutation in the codon 178 was detected, both being methionine/methionine homozygotes at position 129. The most outstanding neuropathological abnormalities were located in the thalamus with gliosis and neuronal loss of anterior and dorsomedial ventral nuclei and also intense neuronal loss in olive of the first case. CONCLUSIONS: This study describes two new cases of FFI with genotype D178N-129M and short course classical phenotype. The polysomnography is essential in the diagnostic strategy of this disease whose neuropathological substrate is the thalamic alterations and of the inferior olive. Molecular biology permits an exact diagnosis of FFI although there is still controversy on the phenotypal variability and physiopathogenic mechanisms.

Insomnio letal familiar: estudio clínico, neurofisiológico e histopatológico de dos casos / Fatal familiar insomnia: clinical, neurophysiological and histopathological study of two cases

Introducción. Las enfermedades priónicas familiares son causadas por mutaciones en el gen que codifica la proteína priónica (PrP), originando una isoforma alterada denominada prión; una de las más infrecuentes es el insomnio letal familiar (ILF), entidad caracterizada por alteraciones en el sueño y que se asocia a una mutación en el codón 178. Métodos. Estudiamos dos pacientes varones de una misma familia de 43 y 49 años, respectivamente. Resultados. Los síntomas más relevantes fueron los trastornos del sueño con agitación, sueño fraccionado, ronquido e hipersomnia diurna; el curso evolutivo fue breve, falleciendo a los pocos meses del inicio clínico. En los registros de sueño se apreció en los dos casos desestructuración del mismo con pérdida total del ciclo normal de las fases y gran disminución de husos de sueño y complejos K. La poligrafía evidenció taquicardia y pausas de apnea. En el estudio molecular se detectó una mutación en el codón 178, siendo ambos homocigotos metionina/metionina en la posición 129. Las alteraciones neuropatológicas más llamativas se localizaron en el tálamo con gliosis y pérdida neuronal de núcleos ventral anterior y dorsomedial; además, intensa pérdida neuronal en la oliva bulbar del primer caso. Conclusiones. Este estudio describe dos nuevos casos de ILF con genotipo D178N-129M y fenotipo clásico de corta evolución. La polisomnografía es esencial en la estrategia diagnóstica de esta enfermedad, cuyo sustrato neuropatológico son las alteraciones talámicas y de la oliva inferior. La biología molecular permite un diagnóstico preciso del ILF, aunque sigue habiendo controversias sobre la variabilidad fenotípica y los mecanismos fisiopatogénicos (AU)

Introduction: Family prion diseases are caused by mutations in the gene coding the prion protein (PrP), originating an altered isoform called prion. One of the most uncommon is the fatal familial insomnia (FFI), an entity characterized by sleep disorders and that is associated to a mutation in codon 178. Methods: We have studied two male patients, aged 43 and 49 years respectively, from the same family. Results: The most significant symptoms were sleep disorders with agitation, fractionated sleep, snoring and daytime sleepiness. The evolution was brief, the patient dying at a few months of the clinical debut. Sleep registries showed destructuration with total loss of the normal cycle of the phases and great decrease of the sleep spindles and K complexes in both cases. The polygraphy showed tachycardia and apnea pauses. In the molecular study, a mutation in the codon 178 was detected, both being methionine/methionine homozygotes at position 129. The most outstanding neuropathological abnormalities were located in the thalamus with gliosis and neuronal loss of anterior and dorsomedial ventral nuclei and also intense neuronal loss in olive of the first case. Conclusions: This study describes two new cases of FFI with genotype D178N-129M and short course classical phenotype. The polysomnography is essential in the diagnostic strategy of this disease whose neuropathological substrate is the thalamic alterations and of the inferior olive. Molecular biology permits an exact diagnosis of FFI although there is still controversy on the phenotypal variability and physiopathogenic mechanisms (AU)

[Neurobrucellosis. A report of 13 cases]. / Neurobrucelosis. Aportación de 13 casos.

Thirteen patients with nervous system brucellosis are described. The clinical signs were heterogeneous: meningoencephalitis in 5 cases, meningoradiculitis in another 5, meningomyelitis with cranial neuropathy in 1 and of a vascular nature in 2 others. Neurologic signs appeared during the active phase in 5 patients and later in 8. Diagnosis was based on clinical manifestations, serum and cerebrospinal fluid (CSF) serology, quantitative changes in CSF and favorable response to treatment. Therapy consisted of a combination of 2 or 3 of the following drugs: rifampin, doxycycline, streptomycin and trimethoprim sulfamethoxazole. In spite of favorable evolution, 5 patients suffered sequelae. We suggest that brucellosis be investigated when neurologic deficit ensues with no known etiology, especially in endemic countries.

[Wernicke encephalopathy in patients given parenteral nutrition]. / Encefalopatía de Wernicke en pacientes sometidos a nutrición parenteral.

Wernicke's encephalopathy is caused by thiamin deficiency and can be recognized by severe neurological symptoms that are occasionally accompanied by systemic signs. The syndrome is often found in alcoholics, although other causes have also been identified, such as intravenous feeding, in which the main pathogenic mechanisms are the administration of carbohydrates and the low standard dose of vitamin B1--in relation to the increase in metabolic load--delivered in a medium of substances that favor inactivation of the vitamin. We present 3 intravenously fed patients who developed the syndrome, even though in 2 cases they were given thiamin. Only the third patient's history included chronic alcoholism, and this patient also suffered severe cardiac symptoms and amaurosis. We believe that the amount of thiamin provided through parenteral nutrition, as well as the medium in which it is delivered, must be reviewed.

[Involvement of cranial pairs as manifestation of prostatic cancer]. / Afectación de pares craneales como manifestación de cáncer de próstata.

Two cases of prostate cancer (PC) which presented clinically with affectation of the cranial pairs due to skull base metastasis. In both cases, existence of intraparenchimatous brain metastasis was excluded. Initial improvement with hormonal therapy was followed by clinical, analytical and radiological relapse due to spread of process until death, at 11 and 36 months from diagnosis. Although PC's bone metastasis are frequent, their location at the skull base is uncommon. Even more rare are the cases which present with changes in the cranial pairs in the absence of signs and symptoms of prostatism.

[Chronic polyneuropathy due to vitamin E deficiency]. / Polineuropatía crónica secundaria a deficiencia de vitamina E.

Vitamin E deficiency has been implicated as a causal factor in neurological disease for some time. Nevertheless, only in the last 10 years have we begun to understand the role this vitamin plays in the normal functioning and structure of the nervous system. Chronic fat malabsorption syndromes are the most common causes of low levels of this highly fat-soluble vitamin. We present a case of chronic polyneuropathy due to vitamin E deficiency caused by malabsorption in which a biliary-cholonic fistula was present. Plasma tocopherol levels were normalized by parenteral substitution, leading to substantial clinical improvement. We suggest that vitamin E levels be determined in cases of digestive disorders involving malabsorption of fats and in chronic neurological diseases, particularly spinal-cerebral degenerative and polyneuropathic diseases that are mainly sensory or motor-sensory in nature, given the potential reversibility of these disorders when caused by vitamin E deficiency.

[A iatrogenic pathology study in an internal medicine service]. / Estudio de la patología iatrógena en un servicio de Medicina Interna.

BASIS: It's obvious that the current medicine practice generates iatrogenesis . However, we are unaware about its magnitude and severity, specially in Spain, where this item has been scarcely studied. METHODS: All the patients admitted to the Department of Internal Medicine were prospectively studied during a 13 months period, selecting among the patients those fulfilling criteria for an iatrogenic problem both of pharmacological origin and not pharmacological. The kind of iatrogenesis, its severity, related mortality, gravity of the basic illness, affected organ and avoidability of the iatrogenesis were evaluated. Infusion phlebitis were recorded only during 6 months. RESULTS: Iatrogenic pathology was found in 228 cases over 1.549 patients admissions, accounting for 14.7% of incidence. Iatrogenic pathology was the reason for admission in 65 cases. The average stay was significantly increased in patients with iatrogenic pathology (p < 0.01). Adverse reactions to drugs accounted for 62% of the total account with 141 cases. The non-steroids antiinflammatory (NSA) drugs were the most frequently troublesome pharmacological agents. The GI tract was the more affected system (84 cases). Infusion phlebitis are not included in the total account of cases. CONCLUSIONS: a) iatrogenic pathology is an illness of very high incidence in our surroundings; b) NSA is a group of drugs generating frequently adverse reactions in off-hospital environment; c) GI hemorrhage is an iatrogenic illness accounting for high percentage of cases; d) many of the iatrogenic events can be catalogued as avoidable and with more accurate attention to some factors the more of them could be prevented.

[Brain stem encephalitis due to herpes simplex]. / Encefalitis de troncoencéfalo por herpes simple.

Brainstem encephalitis is an unusual infection caused by a variety of agents, among them the herpes simplex (HS) virus. The difficulty of establishing a diagnosis by neurophysiological and radiological examination is greater in this type of encephalitis than in the usual form produced by HS. We describe a fatal case of brainstem encephalitis. Inflammatory and necrotic lesions in the pous and medulla confirmed the clinical diagnosis, while the etiology was determined by immuno-histo-chemical techniques and viral culture of the cerebral parenchyma. Early diagnosis of this form of encephalitis, based on new virological techniques, allows more effective antiviral treatment.

[Neurological disease due to the varicella-zoster virus without a skin lesion]. / Afección neurológica por virus varicela-zoster sin lesión cutánea.

We studied three cases of inflammatory neurological disease and serological evidence of varicella-zoster viral (VZV) infection without cutaneous manifestation. They corresponded to a case of cranial multi-neuritis, a case of aseptic meningitis, and another case of meningoencephalitis. Despite the infrequency of any such association, the spectrum of the neurological diseases associated with VZV without skin lesions is quite wide. We are motivated to present our experience by the belief that it is important to think about this possible etiology based on inflammatory areas at different levels of the Nervous System in patients who are still immunocompetent.

[Neck-tongue syndrome secondary to abrupt head movements. Clinical study and conservative treatment]. / Síndrome cuello-lengua secundario a giros bruscos de la cabeza. Estudio clínico y tratamiento conservador.

The neck-tongue syndrome is an extremely rare entity consisting of the compression of the second cervical root in the atloaxoid space in relation to certain brusque movements of the neck. Given the infrequency of this syndrome, the authors present a diagnosed and controlled case of the same in the Reina Sofia Hospital in Tudela. A 25 year old patient was consulted who, for some time, had presented paresthesia in the right half of the tongue and contraction of the cervical musculature related to certain neck postures made during sports activities. Clinical examination was completely normal. Radiography only demonstrated a defect in the segmentation between the posterior C2, C3 arches. Herewith, the authors have revised the literature concerning the topic, discuss the physiopathological theories made in other studies and analyze the therapeutic possibilities of the disease inclinning towards conservative treatment.