LIMBIC ENCEPHALITIS: SYMPTOMS, TYPES AND CAUSES - GEOGRAFÍA - 2024

The limbic encephalitis is a disease that occurs due to inflammation of the brain, which usually subacute memory, seizures and psychiatric symptoms characterized by the commitment.

This pathology occurs due to the involvement of the medial region of the temporal lobes. Especially, brain inflammation seems to take place on the hippocampus, a fact that results in multiple memory failures.

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Limbic encephalitis can be caused by two main conditions: infections and autoimmune conditions. With regard to this last factor, two main types have been described: paraneoplastic limbic encephalitis and non-paraneoplastic limbic encephalitis.

Paraneoplastic 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).

Limbic encephalitis characteristics

Limbic encephalitis is a neurological clinical entity that was first described in 1960 by Brierly and his collaborators.

The diagnostic establishment of this pathology was carried out by describing three cases of patients with subacute encephalitis who presented a predominantly involvement in the limbic region.

However, the limbic encephalitis nomenclature with which these conditions are known today was awarded by Corsellis and his collaborators three years after the description of the pathology.

The main clinical features of limbic encephalitis are subacute loss of short-term memory, the development of a dementia syndrome, and inflammatory involvement of the limbic gray matter in association with bronchial carcinoma.

Interest in limbic encephalitis has increased sharply in recent years, which has allowed the establishment of a slightly more detailed clinical picture.

At present, different scientific investigations have agreed that the main alterations of this pathology are:

1. Cognitive disturbances, especially in short-term memory.
2. Suffering from seizures.
3. Generalized state of confusion.
4. Suffering from sleep disorders and psychiatric disorders of various kinds such as depression, irritability or hallucinations.

However, of these main symptoms of limbic encephalitis, the only clinical finding that is characteristic of the entity is the subacute development of short-term memory deficit.

Classification

Encephalitis is a group of diseases that are caused by an inflammation of the brain. They are quite frequent pathologies 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: those caused by infectious factors and those caused by autoimmune elements.

Infectious limbic encephalitis can be caused by a wide spectrum of viral, bacterial, and fungal germs that affect the brain regions of the body.

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 characteristics of each of them are reviewed below.

Infectious limbic encephalitis

Both general infections of the central nervous system and limbic encephalitis in particular, can be caused by a wide variety of viral, bacterial and fungal germs. In fact, the viral etiology is the most common of encephalitis.

However, among all the viral factors there is one that is especially important in the case of limbic encephalitis, the herpes simplex virus type 1 (HSV-1). This germ is the most commonly implicated as the cause not only of viral encephalitis in general, but also of limbic encephalitis.

Specifically, various investigations indicate that 70% of cases of infectious limbic encephalitis are caused by HSV-1. Especially, this germ plays a highly important role in the development of infectious limbic encephalitis in immunocompetent subjects.

On the other hand, in immunocompromised people, especially individuals suffering from the human immunodeficiency virus (HIV) or subjects who have received a bone marrow transplant, they can present a more varied etiology of limbic encephalitis.

In the latter cases, infectious limbic encephalitis can also be caused by herpes simplex virus type 2 (HSV-2) and human herpes viruses 6 and 7, with none of them being much more prevalent than the rest.

Regardless of the germ involved in the etiology of the pathology, infectious limbic encephalitis are characterized by presenting a series of common manifestations. These are:

1. Sub-acute presentation of seizures.
2. Experiencing a rise in body temperature or fever on a frequent basis.
3. Memory loss and confusion

Likewise, infectious limbic encephalitis is characterized by a somewhat faster progression of symptoms than other types of limbic encephalitis. This fact causes the experimentation of a rapid and progressive deterioration.

When establishing the presence of this pathology, two main factors appear: the pathogenesis of the infection and the diagnostic procedure.

Pathogenesis of infection

The pathogenesis of the infection, in the case of primary infection, depends mainly on direct contact of mucous membranes or injured skin with drops from the respiratory tract.

Specifically, the pathogenesis of the infection depends on contact with the oral mucosa in the case of HSV-1 infection or by contact with the 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. In particular, it appears that viruses are transported to the ganglia in the dorsal roots, where they remain dormant.

Most commonly, in adults, cases of herpes encephalitis occur secondary to a reactivation of the disease. That is, the virus remains latent in the trigeminal nerve ganglion until it spreads intracranially.

The virus travels along the meningeas of the trigeminal nerve along the leptomeninges and, in this way, reaches the neurons of the limbic region of the cortex, where they generate brain atrophy and degeneration.

Diagnostic procedure

The diagnostic procedure to be performed for the establishment of the presence of infectious limbic encephalitis consists of amplifying the HSV genome by means of polymerase chain reaction (PCR) in a sample of cerebrospinal fluid (CSF).

The specified and the sensitivity of CRP and CSF is very high, reporting rates of 94 and 98% respectively. However, this medical test can also have some drawbacks.

In fact, the HSV genome amplification test can be negative during the first 72 hours of symptoms and after 10 days after the onset of the disease, so the time factor plays an important role in the diagnosis of this disease.

On the other hand, other diagnostic tests frequently used in infectious EL is magnetic resonance imaging. This test allows the observation of brain alterations in 90% of the cases of subjects with limbic encephalitis caused by HSV-1.

More specifically, magnetic resonance imaging usually shows hyper-intense lesions in enhanced sequences that translate into edema, hemorrhage, or necrosis in the inferomedial region of the temporal lobes. Likewise, the orbital surface of the frontal lobes and the insulting 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 CSF or serum, and interact with specific neuronal antigens.

Autoimmune limbic encephalitis was described during the 80s and 90s of the last century, when the presence of antibodies against neuronal antigens expressed by a tumor was demonstrated in the serum of subjects with a neurological syndrome and a peripheral tumor.

In this way, this type of limbic encephalitis reveals the association between limbic encephalitis and tumors, a fact that had already been postulated years before when Corsellis and his collaborators described the disease of limbic encephalitis.

Specifically, in autoimmune EL, autoantibodies act on two main 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 immunumodulatory therapy. Instead, the response against membrane antigens is measured through antibodies and responds satisfactorily to treatment.

On the other hand, the multiple investigations that have been carried out on this type of limbic encephalitis have allowed the establishment of two main antibodies that would lead to the development of the pathology: onconeuronal antibodies and neuronal autoantibodies.

This antibody classification has led to the description of two different autoimmune limbic encephalitis: paraneoplastic and non-paraneoplastic.

Paraneoplastic limbic encephalitis

Paraneoplastic limbic encephalitis is characterized by the expression of antigens by neoplasms outside the central nervous system that are coincidentally expressed by neuronal cells.

Due to this interaction, the immune response makes an antibody production that targets the tumor and specific sites in the brain.

In order to establish the presence of this type of limbic encephalitis, it is first necessary to disregard the viral etiology of the condition. Subsequently, it is necessary to establish whether the picture is paraneoplastic or not (detection of an involved tumor).

Most 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 frequently associated with paraneoplastic limbic encephalitis are lung carcinoma (in 50% of cases), testicular tumors (in 20%), breast carcinoma (in 8 %) and non-Hodgkin lymphoma.

On the other hand, the membrane antigens that are usually associated with this type of limbic encephalitis are:

• Anti-NMDA: it is a cell membrane receptor that performs functions in synaptic transmission and neuronal plasticity in the brain. In these cases, the subject usually has headache, fever, agitation, hallucinations, mania, seizures, impaired consciousness, mutism, and catatonia.
• Anti-AMPA: It is a glutamate receptor subtype that modulates 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: it consists of a GABA receptor that is responsible for modulating synaptic inhibition in the brain. These cases are usually associated with tumors and generate a clinical picture characterized by seizures and classic symptoms of limbic encephalitis.

Nonparaneoplastic limbic encephalitis

Non-paraneoplastic limbic encephalitis is characterized by the suffering of 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-gated potassium channel complex or by antigens of glutamic acid decarboxylase.

Regarding the antigens of the complex of voltage-gated potassium channels, it has been shown that the anti-body targets the protein associated with these channels.

In this sense, the protein involved in limbic encephalitis would be the LG / 1 protein. Patients with this type of limbic encephalitis usually present with the classic triad of symptoms characterized by: memory loss, confusion, and seizures.

In the case of glutamic acid decarboxylase (GAD), this intracellular enzyme that is responsible for transmitting the excitatory neurotransmitter glutamate in the inhibitory neurotransmitter GABA is affected.

These antibodies are usually present in other pathologies beyond limbic encephalitis, such as stiff person syndrome, cerebellar ataxia or temporal lobe epilepsy.

References

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