Limbic Encephalitis – Causes, Symptoms, treatment

Limbic Encephalitis (LE) is characterized by a rapidly progressive, non-infective inflammation with short-term memory loss, psychiatric symptoms, and seizures.[] Limbic encephalitis¬†is a rare, subacute process involving the¬†limbic system¬†and¬†hypothalamus. The term LE described memory loss and dementia in association with bronchial carcinoma.[] Initially LE was considered a rare disorder in association with cancer; most commonly associated with small cell lung cancer (SCLC), breast cancer, testicular tumors, teratomas, Hodgkin’s lymphoma, and thymomas but can occur in the absence of malignancy also.[,,]

Limbic encephalitis represents a group of autoimmune conditions characterized by inflammation of the limbic system and other parts of the brain. The cardinal sign of limbic encephalitis is a severe impairment of short-term memory; however, symptoms may also include confusion, psychiatric symptoms, and seizures. The symptoms typically develop over a few weeks or months, but they may evolve over a few days. Limbic encephalitis is often associated with an underlying neoplasm (paraneoplastic limbic encephalitis); however, some cases never have a neoplasm identified (non-paraneoplastic limbic encephalitis). Delayed diagnosis is common, but improvements are being made to assist in early detection. Various tests including imaging studies (MRI, PET) laboratory tests (CSF analysis), and tests that measure the electrical activity of the brain (EEG) may be utilized to confirm a diagnosis. Treatment includes removal of the neoplasm (if identified) and immunotherapy.[rx][rx][rx]

Types include encephalitis

  • Acute disseminated encephalomyelitis (ADEM)
  • Anti-NMDAR receptor encephalitis
  • Hashimoto‚Äôs encephalopathy
  • LG11/CASPR2-antibody encephalitis
  • Limbic encephalitis
  • Rasmussen‚Äôs encephalitis
  • Autoimmune limbic encephalitis,
  • Experimental allergic encephalomyelitis (EAE)
  • Experimental autoimmune encephalomyelitis

Types of Limbic Encephalitis

Autoimmune encephalitis can be divided broadly into two groups, based on whether or not antibodies are the result of an underlying tumor

  • Paraneoplastic limbic encephalitis – usually antibodies are against intracellular antigens poor response to immunotherapy
  • Non-neoplastic autoimmune limbic encephalitis – antibodies are against extracellular antigens, usually with a reversible neuronal dysfunction and better outcomes

Limbic encephalitis is classified according to the auto-antibody that causes the disease. The most common types are

  • Anti-Hu – which is associated with small-cell carcinoma¬†of the lungs.
  • Anti-Ma2 –¬†associated with¬†germ-cell tumors¬†of the¬†testis.
  • Anti-NMDAR – associated with tumors of the ovaries, commonly teratomata.

Causes of Limbic Encephalitis

1. Infectious causes – Many infections of the brain can potentially cause inflammation of the limbic areas. A number of viruses, such as the herpes simplex virus (HSV) seem to preferentially target this area. Some people may therefore be given the diagnosis of LE whilst others are given the diagnosis herpes simplex encephalitis for the same condition. A clearer way for people would be to say that the person has ‚Äėherpes simplex virus encephalitis affecting mainly the limbic areas of the brain‚Äô, but this is rather long-winded.

2. Autoimmune causes – A major role of our immune system is to recognize and eliminate an infection. But sometimes parts of the immune system called ‚Äėantibodies‚Äô may instead react with proteins of our own body to cause autoimmune diseases. When this reaction is against proteins of the limbic areas of the brain, this is called ‚Äėautoimmune limbic encephalitis.

There are broadly two forms of autoimmune limbic encephalitis: paraneoplastic limbic encephalitis (PLE) and non-paraneoplastic limbic encephalitis (NPLE).

a) Paraneoplastic limbic encephalitis (PLE)

Sometimes when the immune system starts to react with the limbic areas, this happens because the person has a tumor in their body that activates the immune system. This activated immune system can, in turn, attack the brain. Doctors call this paraneoplastic limbic encephalitis the tumor (neoplasm) that affects the brain from a distance, via the immune system.

In many cases, PLE can be diagnosed by testing for one of the paraneoplastic autoantibodies in the patient’s blood and spinal fluid. Most individuals with PLE have cancer of the lung, thymus gland, ovary, breast, or testes. More rarely, other cancers can initiate the condition. The outcome is very dependent on the underlying tumor and the precise condition, often classified by the antibody. In some cases, the condition may improve or at least stabilize if the cancer is detected and treated effectively. However, unfortunately, in many cases treatment does not improve the patient’s neurological symptoms, probably because the immune system has irreversibly damaged the brain cells and the tumor cannot be controlled successfully.

b) Non-paraneoplastic limbic encephalitis (NPLE)

NPLE has only been clearly recognized in the last few years when doctors began to identify patients with symptoms similar to those with PLE but who did not have any of the marker paraneoplastic antibodies in their blood and never developed a tumor. NPLE is far more common than PLE.

It is becoming increasingly clear that NPLE is caused, at least in part, by specific antibodies in the patient’s blood that targets the patient’s brain, particularly the hippocampus and other limbic areas. Many of these patients improve if they are treated with drugs that suppress the immune system and reduce the levels of the antibodies. These drugs include steroids, intravenous immunoglobulins, and plasma exchange.

Limbic encephalitis is associated with an autoimmune reaction.[rx] In non-paraneoplastic limbic encephalitis, this is typically due to infection (commonly herpes simplex virus) or as a systemic autoimmune disorder.[rx] Limbic encephalitis associated with cancer or tumors is called paraneoplastic limbic encephalitis.

  • Exposure to certain bacteria and viruses, including streptococcus and herpes simplex virus.
  • A type of tumor called a teratoma, generally in the ovaries, causes the immune system to produce specific antibodies.
  • Rarely, some cancers that can trigger an autoimmune response (when the immune system attacks the body‚Äôs own tissues).
  • Aseptic Meningitis
  • Bell palsy
  • Brain metastasis
  • Brucellosis
  • Cardioembolic stroke
  • Cauda Equina and Conus Medullaris syndrome
  • Cavernous sinus syndromes
  • Central nervous system complications in HIV
  • Cerebral venous thrombosis
  • Churg-Strauss disease
  • Another autoimmune encephalitis
  • Primary psychiatric disorder
  • Viral encephalitis
  • Neuroleptic malignant syndrome
  • Catatonia
  • Acute disseminated encephalomyelitis
  • Mitochondrial encephalitis
  • Cerebral space-occupying lesions
  • Exposure to¬†drugs, toxins, or withdrawal symptoms
  • Intracranial hemorrhage
  • Subdural hemorrhage
  • Subarachnoid hemorrhage
  • Cerebral sinus venous thrombosis
  • Posterior circulation ischemic or hemorrhagic stroke
  • Thrombosis of the basilar artery
  • Vasculitis of the central nervous system
  • Herpes simplex encephalitis
  • Autoimmune encephalitis
  • Uremic encephalopathy
  • Hypoglycemia

Symptoms of Limbic Encephalitis

Symptoms develop over days or weeks. The subacute development of short-term memory deficits is considered the hallmark of this disease,[1] but this symptom is often overlooked because it is overshadowed by other more obvious symptoms such as headache, irritability, sleep disturbance, delusions, hallucinations, agitation, seizures, and psychosis, or because the other symptoms mean the patient has to be sedated, and it is not possible to test memory in a sedated patient.

Limbic encephalitis symptoms are

  • Cognitive, and particularly memory, impairment predominantly due to the involvement of the limbic system
  • Frequent but not invariable seizure activity arising from one or both temporal lobes
  • Frequent but not invariable MRI signal change within limbic structures, particularly the hippocampus.
  • Personality changes
  • Aggression
  • Delusional behavior
  • Concentration and memory problems
  • Coma
  • Disorientation
  • Headaches
  • Jerks in the muscles (myoclonus¬†‚Äď 65% of cases)
  • Lack of coordination (ataxia¬†‚Äď 65% of cases)
  • Partial¬†paralysis¬†on the right side
  • Psychosis
  • Seizures¬†(60% of cases)
  • Sleep abnormalities (55% of cases)
  • Speech problems (transient aphasia ‚Äď 80% of cases)
  • Status epilepticus¬†(20% of cases)
  • Tremors (80% of cases)

Common symptoms include

  • Impaired memory and understanding
  • Unusual and involuntary movements
  • Involuntary movements of the face (facial dyskinesia)
  • Difficulty with balance, speech, or vision
  • Insomnia
  • Weakness or numbness
  • Seizures
  • Severe anxiety or panic attacks
  • Compulsive behaviors
  • Altered sexual behaviors
  • Behavior changes such as agitation, fear or euphoria
  • Loss of inhibition
  • Hallucinations
  • Paranoid thoughts
  • Loss of consciousness or coma

Associated Symptoms

Neurologic symptoms

  • Problems with memory and the process of thinking (also known as cognition)
  • Abnormal movements
  • Seizures
  • Problems with balance or coordination (or ataxia)
  • Having trouble speaking
  • Changes in vision
  • Loss of consciousness or coma

Psychiatric symptoms

  • Hallucinations, delusions, or paranoia (or psychosis)
  • Aggressive behavior
  • Inappropriate sexual behaviors
  • Anxiety or panic attacks
  • Compulsive behaviors
  • Agitation, fear
  • Difficulty sleeping

Brain-related symptoms include

  • Short-term memory loss
  • Confusion
  • Slow thinking
  • Slurred speech
  • Personality changes
  • Severe headaches, often with vomiting.

Vision-related symptoms include

  • A dark area in one part of your visual field
  • Visual disturbances such as loss of side vision or a dark shade drawn over part of your vision

Inner-ear symptoms include

  • Hearing loss
  • Dizziness
  • Ringing in your ears

Diagnosis of Limbic Encephalitis

History and Physical

It is a rare paraneoplastic syndrome that affects the medial temporal lobe and may be presented with cognitive dysfunction with a subacute beginning, change in the personality, seizure in partial and generalized type, irritability, hallucinations, disorientation, limbic paresis, and disruption of consciousness and short-term memory loss,,. A study of patients with this syndrome showed that most of the patients presented with an altered level of consciousness. Usually, early manifestations are psychiatric symptoms, so many patients may be treated in the psychiatric ward before making the diagnosis of paraneoplastic limbic encephalitis.

Symptoms of this syndrome usually precede the diagnosis of the tumor. It may appear to be complications of chemotherapy, so when this syndrome is suspected, a complete history and physical examination should be done to determine which cancer is the cause. Cognitive function may be accessed through a mini mental-state examination, clock test, or instrumental activity of daily living. Also, this syndrome may be a part of the larger syndrome in which the brain stem and spinal cord are also involved in the inflammatory process.

Any patient who is suspected to have paraneoplastic limbic encephalitis should undergo the following tests:

  • Exclusion of other neuro-oncological complications
  • CSF with inflammatory changes but negative cytology
  • MRI showing abnormalities in the temporal lobe
  • EEG showing epileptic activities in the temporal lobe

Not all of the patients will fulfill these criteria, but the diagnosis of paraneoplastic limbic encephalitis also may be done in the presence of a neuropathological examination.

Other diagnostic criteria which may be used include Graus and Saiz criteria. These include the following:

  • Subacute onset of seizure or confusion (less than 12 weeks)
  • Neuropathological or radiological involvement of limbic system
  • Exclusion of other causes
  • Diagnosing the tumor within 5 years of diagnosing the syndrome¬†

Laboratory and radiological findings

  • Increased¬†liver¬†enzyme levels (55% cases)
  • Increased thyroid-stimulating hormone (55% cases)
  • Increased erythrocyte sedimentation rate (25% cases)

Cerebrospinal fluid findings

  • Raised protein (25% cases)
  • Negative for 14‚Äď3‚Äď3 protein
  • May contain antithyroid antibodies
  • Magnetic resonance imaging¬†abnormalities consistent with encephalopathy (26% f cases)
  • Single-photon emission computed tomography¬†shows focal and global hypoperfusion (75% of cases)
  • Cerebral¬†angiography¬†is normal

Thyroid hormone abnormalities are common (>80% of cases)

  • Subclinical hypothyroidism (35% of cases)
  • Overt hypothyroidism (20% of cases)
  • Hyperthyroidism (5% of cases)
  • Euthyroid on levothyroxine (10% of cases)
  • Euthyroid not on levothyroxine (20% of cases)

Adult Guidelines

In adults, a diagnosis of ‚Äúpossible AE‚ÄĚ is made when all three of the criteria listed below have been met:

  • Subacute onset (rapid progression of symptoms over less than 3 months) of working memory problems (short-term memory loss), altered mental state (such as confusion or decreased ability to interact with other people or surroundings), or psychiatric symptoms¬†(such as hallucinations)
  • At least one of these findings:
    Abnormal findings on the physical examination that suggest a problem in the brain or spinal cord (such as arm or leg weakness, abnormal reflexes, or problems with coordination)
    ‚ÄĘ Seizures¬†that are not explained by a previously known seizure disorder
    ‚ÄĘ High levels of white blood cells in the spinal fluid
    ‚ÄĘ MRI¬†abnormalities that fit with AE
  • A reasonable number of test results show that symptoms are not caused by more common conditions, such as infections or cancers

Pediatric Guidelines

In children and teenagers, a diagnosis of ‚Äúpossible AE‚ÄĚ is made when all three of the criteria listed below have been met:

  1. New neurological and/or psychiatric symptoms developing over less than three months in a previously healthy child
  2. At least two of these symptoms or findings:
  • Reduced ability to interact with other people or surroundings (or slowing on EEG)
  • Abnormal findings on the physical examination that suggest a problem in the brain or spinal cord (such as arm or leg weakness, abnormal reflexes, or problems with coordination)
  • Problems with memory and the process of thinking
  • Loss of developmental milestones
  • Abnormal movements (except tics)
  • Psychiatric symptoms (such as low mood or hallucinations)
  • Seizures that are not explained by a previously known seizure disorder or other condition
  1. A reasonable number of test results show that symptoms are not caused by more common conditions, such as infections or cancers

Antibodies related to autoimmune encephalitis [onconeuronal antibodies are excluded; summarized from (, , ].

Antibody Syndromes MRI: T2/Flair Sequences Tumor F/M Age (Median)
NMDA-R Prodromal stage, global encephalopathy Normal or transient non-region specific changes (~33%) 10‚Äď50%, (age dependent) ovarian teratoma 4:1 1‚Äď85 (21)
LGI1 Faciobrachial dystonic seizures, limbic encephalitis, hyponatremia, sleep disorders, myoclonia Hyperintense signal in medial temporal lobes and basal ganglia (>80%) <10‚Äď20% Bronchial carcinoma, thymoma 1:2 30‚Äď80 (60)
AMPA-R Limbic encephalitis (predominant psychosis), seizures Hyperintense signal in medial temporal lobes (90%) 70% Bronchial- or Mamma carcinoma, Thymoma 9:1 38‚Äď87 (60)
GABAb-R Limbic encephalitis, seizures Hyperintense signal in medial temporal lobes (>60%) 60% Bronchial carcinoma, neuroendocrine tumors 1:1 24‚Äď75 (62)
CASPR2 Morvan syndrome, neuromyotonia, polyneuropathy, bulbar weakness, limbic encephalitis Normal or Hyperintense signal in medial temporal lobes (~40%) <20‚Äď40% bronchial carcinoma, thymoma 1:4 46‚Äď77 (60)
Glycine-R PERM, Myelopathy, Stiff person syndrome Normal or nonspecific changes (~10%) ~10% Lymphoma, thymoma 6:5 5‚Äď69 (43)
mGLUR5 Ophelia syndrome Normal or hyperintense signal in various brain regions (~50%) Hodgkin lymphoma 1:2 35
GAD* Stiff person syndrome, limbic encephalitis, seizures, cerebellar ataxia n/k 25% Thymoma, small cell lung carcinoma n/k n/k
GABAa-R Encephalitis with refractory seizures Hyperintense signal in multiple cortical and subcortical regions 25% Thymoma n/k n/k
DPPX Encephalitis, diarrhea, hyperplexia Normal or nonspecific changes <10% Lymphoma n/k n/k
Dopamine-2-R Basal ganglia encephalitis with abnormal movements, gait disturbance Hyperintense signal in basal ganglia n/k 1:1 2‚Äď15 (6)
Neurexin-3 őĪ Encephalitis Normal n/k n/k n/k
IgLON5 NREM and REM sleep disorder, brain stem dysfunction Normal n/k n/k n/k
mGLUR1 Cerebellar ataxia Normal or cerebellar atrophy A few cases described, Hodgkin disease n/k n/k
nACH-R Encephalitis, postural tachycardia syndrome, Chronic intestinal pseudo-obstruction Not applicable 30% thymoma, mamma/bladder/rectum/bronchial carcinoma, lymphoma 2:1 20‚Äď76 (58)
MOG Acute disseminated encephalomyelitis Diffuse, poorly demarcated, large (>1‚Äď2 cm) lesions predominantly in the white matter 0% n/k n/k
Adenylate-kinase 5 Isolated severe short-term memory loss, no seizures Not applicable No association n/k n/k

Specific antibodies

Another way of dividing autoimmune encephalitis is on the grounds of whether the antibodies are against intracellular antigens or cell surface antigens. The antibodies, in turn, correlate both to an underlying cause and pattern of involvement. As a general rule, antibodies targeted to intracellular antigens are more frequently associated with an underlying tumor.

  • group I¬†– antibodies to intracellular antigens
    • anti-Hu antibodies
      • most common
      • small cell carcinoma of the lung¬†in 75% of cases
      • anti-Hu syndrome consists of paraneoplastic encephalomyelitis, paraneoplastic sub-acute sensory neuropathy, and paraneoplastic cerebellar degeneration
    • anti-Ma/Ta antibodies
      • better prognosis than anti-Hu
      • testicular tumors
      • diencephalic and brainstem involvement more common
      • ophthalmoplegia is common
    • anti-CV2 antibodies
      • small cell carcinoma of the lung¬†and¬†malignant thymoma
      • involvement of the striatum prominent
      • choreiform movement disorders common
    • anti-GAD (glutamic acid decarboxylase) antibodies
      • usually not associated with tumors
      • usually classical limbic involvement with prominent seizures and¬†stiff person syndrome
    • anti-amphiphysin antibodies
      • small cell carcinoma of the lung¬†and¬†breast cancer
      • myelopathy, myoclonus and¬†stiff person syndrome
    • anti-Ri antibodies
      • small cell carcinoma of the lung¬†and¬†breast cancer
      • brain stem involvement
      • opsoclonus-myoclonus syndrome
    • anti-Yo antibodies
      • ovarian cancer¬†and¬†breast cancer
      • typically presents with paraneoplastic cerebellar degeneration
  • group II¬†– antibodies to surface antigens
    • anti-NMDA antibodies
      • common
      • usually in children and young women with no underlying tumor
      • older patients may have underlying tumors (e.g.¬†ovarian teratoma)
      • typically present with psychiatric symptoms
      • mild or often absent imaging changes
    • anti-VGKC (voltage-gated potassium channel)¬†antibodies
      • common
      • classic features of “limbic encephalitis” with prominent seizures
      • extra-limbic involvement very uncommon
    • anti-GABA (gamma-aminobutyric acid) antibodies
      • similar to VGKC but less common
      • two subtypes:
        • GABA-A
          • frequent extralimbic involvement
        • GABA-B
          • not infrequent underlying cancer (pulmonary neuroendocrine tumors)
    • anti-AMPA (őĪ-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) antibodies
      • predominantly psychiatric symptoms
      • imaging changes limited to the hippocampi
    • anti-D2 dopamine antibodies
      • basal ganglia encephalitis
    • anti-GlyR1 (glyoxylate reductase) antibodies
      • stiff leg syndrome or¬†stiff person syndrome, or progressive encephalomyelitis with rigidity and myoclonus
    • anti-mGluR1(metabotropic glutamate receptor) antibodies
      • lymphoma with cerebellar ataxia
    • anti-mGluR5 antibodies
      • associated with¬†Ophelia syndrome
    • anti-GluR3 (glutamate receptor)¬†antibodies
      • associated with¬†Rasmussen encephalitis

Lab Test

A brain scan, can determine inflammation and differentiate it from other possible causes.

  • Blood test¬† – for monoclonal antibodies (anti-Hu, anti-Ta, anti-Ma, anti-GABA B receptor, and anti NMDA receptor) but the absence of these antibodies does not exclude the disease. A¬†complete blood count with differential is a general index of health. It checks the number of red and white blood cells in your blood. White blood cells fight infection. The count is usually elevated in¬†meningitis.
  • MRI – may show hyperintense signals in the temporal lobe, hippocampal areas, insula, amygdala, or cingulate gyrus. T2-weighted images and fluid-attenuated inversion recovery will support the diagnosis, but signs may appear later than the initial neurological symptom of the syndrome.
  • Lumbar puncture – should be negative for malignant cells or infection and may show pleocytosis, the elevation of protein levels, and intensification of immunoglobulin synthesis and oligoclonal bands. Lumbar puncture (spinal tap) helps determine via a test using the cerebral-spinal fluid, obtained from the lumbar region.
  • PET-CT – which will show abnormal metabolic activities in the limbic system. Diagnosis is difficult and should be by exclusion because clinical markers are often absent. A study on 1047 patients used the following criteria to diagnose paraneoplastic limbic encephalitis.
  • An¬†electroencephalogram (EEG)¬†‚Äď small electrodes are placed on your scalp, which picks up the electrical signals from your brain and shows abnormal brain activity
  • Spinal fluid analysis ‚ÄstBy doing a¬†lumbar puncture¬†(also called a¬†spinal tap), your doctor can check the spinal fluid for an increase in white blood cells and protein. The bacteria, virus, parasite, or fungus causing the encephalitis also may be found in the spinal fluid. Examination of cerebrospinal fluid (CSF) shows elevated numbers of lymphocytes (but usually < 100 cells/őľl); elevated CSF protein (but usually <1.5 g/l), normal glucose, elevated IgG index, and oligoclonal bands. Patients with antibodies to voltage-gated potassium channels may have a completely normal CSF examination.[rx][rx][rx]
  • Urine analysis –¬†¬†A urinalysis is a simple¬†test¬†that looks at a small sample of your¬†urine. It can help find problems that need treatment, including infections or kidney problems. It can also help find serious diseases in the early stages, like kidney disease, diabetes, or liver disease. A urinalysis is also called a ‚Äúurine test.
  • Polymerase chain reaction¬†(PCR) testing – of the cerebrospinal fluid, to detect the presence of viral DNA which is a sign of viral encephalitis.
  • Blood cultures¬†identify bacteria in the blood¬†‚ÄstBacteria can travel from the blood to the brain.¬†N. meningitides¬†and¬†S. pneumonia¬†can cause both¬†sepsis¬†and meningitis.
  • Cerebrospinal fluid (CSF)¬†‚Äď CSF is the fluid that surrounds your brain and spinal cord. It helps to support and protect the brain and spinal cord from trauma.
  • Chest X-rays¬†‚Äst can reveal the¬†presence of¬†pneumonia,¬†tuberculosis,¬†or fungal infections. Meningitis¬†can occur after¬†pneumonia. A chest radiograph called a chest X-ray, or chest film is a projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures. Chest radiographs are the most common film taken in medicine
  • Thyroid antibodies ‚Äď both antithyroid peroxidase antibodies (anti-TPO, antithyroid microsomal antibodies, anti-M) and antithyroglobulin antibodies (anti-Tg) ‚Äď in the disease are elevated, but their levels do not correlate with the severity.
  • Electroencephalogram studies – while almost always abnormal (98% of cases), are usually not diagnostic. The most common findings are diffuse or generalized slowing or frontal intermittent rhythmic delta activity. Prominent triphasic waves, focal slowing, epileptiform abnormalities, and photo paroxysmal and photogenic responses may be seen.[rx]
  • A¬†CT scan¬†¬†‚Äď of the head may show problems like a brain abscess or sinusitis. Bacteria can spread from the sinuses to the meninges. A computerized tomography (CT)¬†scan combines a series of X-ray images taken from different angles around your body and uses computer processing to create cross-sectional images (slices) of the bones, blood vessels, and soft tissues inside your body.¬†CT scan images provide more detailed information than plain X-rays do.
  • MRI¬†‚Äď to be oversure about meningitis. Magnetic resonance imaging¬†(MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body.¬†MRI¬†scanners use strong magnetic fields, magnetic field gradients, and radio waves to generate images of the organs in the body.
  • Anti NMDAR IgG antibodies – detected by indirect immunofluorescence assay in the serum and the CSF, are diagnostic for the disease. Antibody titers are higher in the CSF, and in some cases, diagnosis is possible after CSF testing with concurrent negative serum reports. CSF also can have low-grade hypercellularity and oligoclonal bands.¬†Brain MRI can be normal, but nonspecific white and gray matter T2/FLAIR¬† signal hyperintensity can be present, most commonly in the hippocampus. Diffusion restriction positivity has been reported, as well as cerebellar atrophy, as the only irreversible radiologic finding with this encephalitis.
  • Transvaginal ultrasonography – is the most crucial test for young women presenting with the illness due to the high incidence of underlying ovarian teratoma. If these tests are unrevealing, PET scans and exploratory laparotomy are options. In cases of negative initial screening, follow-up MRI of abdomen and pelvis should be repeated every six months for at least four years.
  • Electroencephalography – Patients with ALE may occasionally have a normal EEG, which does not rule out the diagnosis.[rx] Usually, however, EEG shows slow-wave activity or epileptiform discharges from the temporal lobes of patients with ALE ‚ÄĒ a clue to brain inflammation. In a retrospective analysis of 19 patients with autoimmune encephalitis and seizures, 10 of 16 patients with ictal EEGs (63%) had seizure onset over the temporal lobe region, which closely mirrored the medial temporal lobe abnormalities seen on MRI in three-quarters of those studied.[rx] Importantly, EEG abnormalities of the temporal lobes without any observed changes on imaging are not sufficient to make a diagnosis of ALE in the absence of a positive antibody. In clinical practice, an EEG that shows slow-wave activity or epileptiform discharges from the temporal lobes in a patient with possible ALE should raise suspicion of the condition even if the initial MRI is normal; in such cases, repeat MRI may be considered, to look for the interval development of medial temporal lobe abnormalities.[rx]

Treatment Of Limbic Encephalitis 

Treatment (which is based on supportive care) is as follows

Medications

Limbic encephalitis is a rare condition with no randomized controlled trials to guide treatment. Treatments that have been tried include intravenous immunoglobulin, plasmapheresis, corticosteroids, cyclophosphamide and rituximab.[rx]

  • Corticosteroids – are a class of drug that lowers inflammation in the body. They also reduce immune system activity. Because corticosteroids ease swelling, itching, redness, and allergic reactions, doctors often prescribe them to help treat diseases like asthma. Because most patients respond to corticosteroids¬†or¬†immunosuppressant treatment, this condition is now also referred to as steroid-responsive encephalopathy. Initial treatment is usually with oral prednisone¬†(50‚Äď150¬†mg/day) or high-dose intravenous¬†methylprednisolone¬†(1 g/day) for 3‚Äď7 days.
  • Pyrimethamine-based maintenance therapy – is often used to treat Toxoplasmic Encephalitis (TE), which is caused by Toxoplasma gondii and can be life-threatening for people with weak immune systems. The use of highly active antiretroviral therapy,
  • Immunoglobulin infusion(IVIG)¬† – Prompt treatment can be initiated before the final diagnosis in case of a reasonable degree of suspicion after collecting serum and CSF samples for confirmation of autoimmune encephalitis.¬†Expeditious immunomodulatory/immunosuppressive therapies with corticosteroids, immunoglobulin infusion(IVIG), and plasmapheresis (PLEX) are first-line therapies, as well as tumor removal if applicable, with robust supportive therapies.
  • Plasmapheresis – can remove autoantibodies of the blood. Plasmapheresis is a method for removing unwanted substances (toxins, metabolic substances, autoantibodies) from the blood. During plasmapheresis, blood is removed from the affected individual and blood cells are separated from plasma. The plasma is then replaced with other human plasma and the blood is transfused back into the affected individual.
  • Biological Drugs – Rituximab, cyclophosphamide, azathioprine, mycophenolate mofetil have been used as second-line therapies if clinical improvement does not occur after four weeks of treatment with first-line therapy. Some experts recommended the use of rituximab early in the disease process as first-line therapy. For refractory patients, bortezomib(proteasome inhibitor), alemtuzumab(humanized monoclonal antibody against CD52), intrathecal methotrexate, and tocilizumab(a monoclonal antibody against interleukin-6 receptor) can work in a small number of patients with success.
  • Anti Seizure Drugs – management in the acute phase can be difficult and requires AEDs along with immunotherapy. However, these patients do not develop epilepsy as the seizure improves with the improvement of encephalitis. A retrospective series reported that valproate, levetiracetam, and carbamazepine had been similarly effective, but carbamazepine was associated with fewer side effects. Gradual reduction of AEDs is possible during follow-up, and most can be discontinued in 2 years without seizure recurrence. Antipsychotic agents are frequently used to treat behavioral symptoms, but the neuroleptic malignant syndrome can occur.
  • Benzodiazepines and electroconvulsive therapy – have been utilized to treat catatonia. Abnormal movements associated with this encephalitis are challenging to control and require a high dose of sedative medications, botulinum toxin, or tetrabenazine.ICU management is essential during the severe phase of the disease for several reasons: airway protection, altered cognition, dyskinesias, seizures, abnormal behavior, temperature instability, heart rate variability, and arrhythmia.
  • Antiviral Medication – Herpes simplex encephalitis is the commonest sporadic encephalitis. Any patient who presented with clinical features of acute encephalitis should be treated empirically with IV acyclovir, pending the result of HSV PCR results. Acyclovir will be continued or stopped depending on the outcome of the PCR test. It is essential to recognize the fact that early recurrence of HSV encephalitis within 2 to 3 weeks of the encephalitis is often due to anti-NMDAR encephalitis triggered by the viral encephalitis. It is reasonable and understandable that HSV is a neurotropic virus with predominant involvement of the limbic gray matter, which has a high concentration of NMDA receptors. The viral infection may lead to a higher likelihood of release of the receptor and subsequent antibody formation and secondary immune encephalitis.

References

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