The Limbic encephalitis Is a disease that occurs due to an inflammation of the brain that is usually characterized by sub-acute involvement of memory, psychiatric symptoms and seizures.
This pathology occurs due to the involvement of the medial region of the Temporal lobes . Especially, cerebral inflammation seems to be performed on the hippocampus, a fact that results in multiple failures of mnemic function.
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Limbic encephalitis may be caused by two major conditions: infections and autoimmune diseases. With regard to this latter factor, two main types have been described: limaneous paraaneoplastic encephalitis and non-paraneoplastic limbic encephalitis.
Of all types, limaneoplastic limbic encephalitis appears to be the most prevalent. The clinical presentation of this pathology is characterized by incorporating cognitive and neuropsychiatric manifestations (mood changes, irritability, anxiety, depression, disorientation, hallucinations and behavioral alterations).
This article reviews the main features of this disease. The different types of limbic encephalitis are explained and the factors that may give rise to this neurological clinical entity are discussed.
Characteristics of limbic encephalitis
Limbic encephalitis (EL) is a neurological entity that was first described in 1960 by Brierly and his colleagues.
The diagnosis of this pathology was made by describing three cases of patients with subacute encephalitis who had predominant involvement in the limbic region.
However, the limbic encephalitis nomenclature with which these conditions are known today was adjudicated by Corsellis and his collaborators three years after the description of the pathology.
The main clinical features of EL are subacute loss of short-term memory, the development of a dementia syndrome and the inflammatory involvement of the limbic gray matter in association with bronchial carcinoma.
The interest in EL has increased considerably in recent years, which has led to the establishment of a more detailed clinical picture.
In this sense, at the present time different scientific investigations have consensuated that the main alterations of this pathology are:
- Cognitive alterations, especially in short-term memory.
- Feeling of seizures.
- State of general confusion.
- Suffering from sleep disorders and various psychiatric disorders such as depression, irritability or hallucinations.
However, of these major symptoms of EL, the only clinical finding that is characteristic of the entity is the sub-acute development of short-term memory deficit.
Types of limbic encephalitis
Encephalitis is a set of diseases that are caused by an inflammation of the brain. They are pathologies quite frequent in certain regions of the world that can be caused by different factors.
In the case of limbic encephalitis, two main categories have now been established: EL caused by infectious factors and EL caused by autoimmune elements.
Limbic infectious encephalitis may be caused by a broad spectrum of viral, bacterial, and fungal germs that affect the brain's brain regions.
On the other hand, autoimmune limbic encephalitis are disorders caused by inflammation of the central nervous system initially caused by the interaction of autoantibodies. The main features of each are reviewed below.
Limbic infectious encephalitis
Both general Central Nervous System Like concrete limbic encephalitis, may be caused by a variety of viral, bacterial, and fungal germs. In fact, viral etiology is the most frequent of encephalitis.
However, among all viral factors there is one that is especially important in the case of EL, herpes simplex virus type 1 (HSV-1). This germ is most commonly implicated as causing not only viral encephalitis in general, but also of EL.
Specifically, several investigations indicate that 70% of cases of infectious EL are caused by HSV-1. Especially, this germ plays a highly important role in the development of infectious limbic encephalitis in immunocompetent subjects.
In contrast, in immunocompromised individuals, especially individuals suffering from human immunodeficiency virus (HIV) or subjects who have received bone marrow transplantation, may present a more varied etiology of limbic encephalitis.
In these latter cases, infectious EL can also be caused by herpes simplex virus type 2 (HSV-2) and human herpesvirus 6 and 7, with none of them being much more prevalent than the rest.
Irrespective of the germ involved in the etiology of pathology, limbic infectious encephalitis is characterized by presenting a series of common manifestations. These are:
- Sub-acute presentation of seizures.
- Experimentation of body temperature rise or fever frequently.
- Loss of memory and confusion.
Likewise, infectious ELs are characterized by a progression of symptomatology somewhat faster than the other types of limbic encephalitis. This fact provokes the experimentation of a rapid and progressive deterioration.
At the time of establishing the presence of this pathology, two main factors appear: the pathogenesis of infection and the diagnostic procedure.
Pathogenesis of infection
The pathogenesis of infection, in the case of primary infection, depends mainly on the direct contact of mucous membranes or injured skin with drops from the respiratory tract.
Specifically, the pathogenesis of infection depends on contact with the oral mucosa in the case of HSV-1 infection or contact of genital mucosa in the case of HSV.2.
Once infectious contact has been made, the virus is transported through the neural pathways to the nerve ganglia. Especially, it appears that viruses are transported to the lymph nodes in the dorsal roots, where they remain dormant.
The most common is that in adults, cases of herpes encephalitis occur secondary to a reactivation of the disease. That is, the virus remains latent in the ganglion of the trigeminal nerve until it is spread intracranially.
The virus travels along the meninges of the trigeminal nerve along the leptomeninges and thus reaches the neurons of the limbic region of the cortex, where they generate Atrophy And cerebral degeneration.
Diagnostic procedure
The diagnostic procedure to be performed for establishing the presence of infectious EL consists of amplifying the HSV genome by polymerase chain reaction (PCR) in a sample of cerebrospinal fluid (CSF).
The specificity and sensitivity of CRP and CSF is very high, with indices of 94 and 98% respectively. However, this medical test may also incorporate some drawbacks.
In fact, the amplification test of the HSV genome may be negative during the first 72 hours of symptomatology and after 10 days of onset of the pathology, so the temporal factor plays an important role in the diagnosis of this pathology.
On the other hand, other diagnostic tests frequently used in infectious EL are magnetic resonance imaging. This test allows the observation of cerebral alterations in 90% of the cases of subjects with limbic encephalitis caused by HSV-1.
More specifically, magnetic resonance imaging often shows hypertensive lesions in enhanced sequences that result in edema, hemorrhage, or necrosis in the infero-medial region of the temporal lobes. Likewise, the orbital surface of the frontal lobes and the insult cortex can also be compromised.
Autoimmune limbic encephalitis
Autoimmune limbic encephalitis is a disorder caused by inflammation of the central nervous system due to an interaction of autoantibodies. These autoantibodies are present in the CSF or in the serum, and interact with specific neuronal antigens.
Autoimmune limbic encephalitis was described during the 1980s and 1990s, when the presence of antibodies against neuronal antigens expressed by a tumor in the serum of subjects with a neurological syndrome and a peripheral tumor was demonstrated.
Thus, this type of EL demonstrates the association between limbic encephalitis and tumors, a fact that had been postulated years before when Corsellis and his colleagues described limbic encephalitis disease.
Specifically, in autoimmune EL, autoantibodies act on two major categories of antigens: intracellular antigens and cell membrane antigens.
The immune response against intracellular antigens is usually associated with cytotoxic T cell mechanisms and a limited response to inmonumodulator treatment. In contrast, the antigen response of the membrane is measured by antibodies and responds satisfactorily to the treatment.
On the other hand, the multiple investigations that have been carried out on this type of EL have allowed the establishment of two main antibodies that would lead to the development of the pathology: the onconeuronal antibodies and the neural autoantibodies.
This classification of antibodies has led to the description of two different autoimmune limbic encephalitis: the paraneoplastic and the nonparaneoplastic.
Paraneoplastic limbic encephalitis
Paraneoplastic limbic encephalitis is characterized by the expression of antigens by neoplasias outside the central nervous system that are coincidentally expressed by neuronal cells.
Because of this interaction, the immune response performs an antibody production that targets tumor and specific sites in the brain .
In order to establish the presence of this type of EL, it is first necessary to reject the viral etiology of the condition. Subsequently, it is necessary to establish whether the condition is paraneoplastic or not (detection of a tumor involved).
The majority of cases of autoimmune limbic encephalitis are characterized by being paraneoplastic. Approximately, between 60 and 70% of the cases are. In these cases, the neurological picture precedes the detection of the tumor.
In general, the tumors most commonly associated with limaneoplastic limbic encephalitis are lung carcinoma (in 50% of cases), testicular tumors (in 20%), breast carcinoma (in 8% %) And non-Hodgkin's lymphoma.
On the other hand, the membrane antigens usually associated with this type of EL are:
- Anti-NMDA : It is a receptor of the cellular membrane that performs functions in the synaptic transmission and in the Neuronal plasticity of the brain. In these cases, the subject usually presents with headache, fever, agitation, hallucinations, mania, seizures, deterioration of consciousness, mutism and catatonia.
- Anti-AMPA : Is a subtype of glutamate receptor that modulates the excitatory neuronal transmission. This entity mainly affects elderly women, is usually associated with breast carcinoma and usually causes confusion, memory loss, changes in behavior and, in some cases, seizures.
- Anti-GABAB-R : Consists of a GABA receptor that modulates the synaptic inhibition of the brain. These cases are usually associated with tumors and generate a clinical picture characterized by classical seizures and symptoms of EL.
- Liminal non-paraneoplastic encephalitis.
Non-paraneoplastic EL is characterized by a clinical picture and a neuronal condition typical of limbic encephalitis, in which there is no tumor underlying the pathology.
In these cases, limbic encephalitis is usually caused by antigens of the voltage-dependent potassium channel complex or by glutamic acid decarboxylase antigens.
As regards the anti-antigens of the voltage-dependent potassium channel complex, it has been shown that the anti-body is directed against the protein associated with said channels.
In this sense, the protein involved in limbic encephalitis would be the LG / 1 protein. Subjects with this type of EL usually present the classic triad of symptoms characterized by: loss of memory, confusion and convulsions.
In the case of Acid-glutamic decarboxylase (GAD) is affected this intracellular enzyme that is responsible for transmitting the excitatory neurotransmitter glutamate in the inhibitory neurotransmitter GABA.
These antibodies are often seen in other pathologies beyond EL, such as rigid person syndrome, Cerebellar ataxia wave Epilepsy of the temporal lobe .
References
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