Limbic encephalitis: Difference between revisions
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}}</ref> Limbic encephalitis is caused by auto-immunity: that is an abnormal state where the body produces antibodies against itself. Some cases are associated with cancer and some are not.<ref name="Tuzun2007"/> Although the disease is known as "limbic" encephalitis, the fact is that disease is seldom limited to the [[limbic system]] and post-mortem studies usually show involvement of other parts of the brain also.<ref>{{cite journal |
}}</ref> Limbic encephalitis is caused by auto-immunity: that is an abnormal state where the body produces antibodies against itself. Some cases are associated with cancer and some are not.<ref name="Tuzun2007"/> Although the disease is known as "limbic" encephalitis, the fact is that disease is seldom limited to the [[limbic system]] and post-mortem studies usually show involvement of other parts of the brain also.<ref>{{cite journal |
||
| author = Brierley JB, Corsellis JAN, Hierons R, ''et al.'' |
| author = Brierley JB, Corsellis JAN, Hierons R, ''et al.'' |
||
| title = Subacute encephalitis of later adult life. Mainly affecting the limbic areas |
| title = Subacute encephalitis of later adult life. Mainly affecting the limbic areas |
||
| journal = Brain |
| journal = Brain |
||
| year = 1960 |
| year = 1960 |
||
| volume = 83 |
| volume = 83 |
||
| pages = 357–368}}</ref><ref name="Corsellis1968">{{cite journal |
| pages = 357–368 |
||
| doi = 10.1093/brain/83.3.357 |
|||
| issue = 3}}</ref><ref name="Corsellis1968">{{cite journal |
|||
| author = Corsellis JA, Goldberg GJ, Norton AR |
| author = Corsellis JA, Goldberg GJ, Norton AR |
||
| title = |
| title = "Limbic encephalitis" and its association with carcinoma |
||
| journal = Brain |
| journal = Brain |
||
| year = 1968 |
| year = 1968 |
||
| volume = 91 |
| volume = 91 |
||
| pages = 481–496 |
| pages = 481–496 |
||
| doi = 10.1093/brain/91.3.481 |
|||
| issue = 3}}</ref><ref>{{cite journal |
|||
| author = Bakheit AM, Kennedy PG, Behan PO |
| author = Bakheit AM, Kennedy PG, Behan PO |
||
| title = Paraneoplastic limbic encephalitis: clinico-pathological correlations |
| title = Paraneoplastic limbic encephalitis: clinico-pathological correlations |
||
Line 38: | Line 42: | ||
| year = 1990 |
| year = 1990 |
||
| volume = 53 |
| volume = 53 |
||
| pages = 1084–1088 |
|||
⚫ | |||
| doi = 10.1136/jnnp.53.12.1084 |
|||
⚫ | |||
| author = Henson RA, Hoffman HL, Urich H |
| author = Henson RA, Hoffman HL, Urich H |
||
| title = Encephalomyelitis with carcinoma |
| title = Encephalomyelitis with carcinoma |
||
| journal = Brain |
| journal = Brain |
||
| year = 1965 |
| year = 1965 |
||
| volume = 88 |
| volume = 88 |
||
| pages = 449–464 |
| pages = 449–464 |
||
| doi = 10.1093/brain/88.3.449 |
|||
| issue = 3}}</ref> |
|||
The majority of cases of limbic encephalitis are associated with a tumour (diagnosed or undiagnosed). In cases caused by tumour, cure is only achieved when the tumour is removed completely (this is not always possible). Limbic encephalitis is classified according to the auto-antibody that causes the disease. |
The majority of cases of limbic encephalitis are associated with a tumour (diagnosed or undiagnosed). In cases caused by tumour, cure is only achieved when the tumour is removed completely (this is not always possible). Limbic encephalitis is classified according to the auto-antibody that causes the disease. |
||
Line 58: | Line 66: | ||
Examination of cerebrospinal fluid (CSF) shows elevated numbers of lymphocytes (but usually < 100 cells/µl); 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.<ref>{{cite journal |
Examination of cerebrospinal fluid (CSF) shows elevated numbers of lymphocytes (but usually < 100 cells/µl); 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.<ref>{{cite journal |
||
| author = Buckley C, Oger J, Clover L, ''et al.'' |
| author = Buckley C, Oger J, Clover L, ''et al.'' |
||
| title = Potassium channel antibodies in two patients with reversible limbic encephalitis |
| title = Potassium channel antibodies in two patients with reversible limbic encephalitis |
||
| journal = Ann Neurol |
| journal = Ann Neurol |
||
| year = 2001 |
| year = 2001 |
||
| volume = 50 |
| volume = 50 |
||
| pages = 73–78}}</ref><ref>{{cite journal |
| pages = 73–78 |
||
| doi = 10.1002/ana.1097}}</ref><ref>{{cite journal |
|||
| author = Vincent A, Buckley C, Schott JM, ''et al.'' |
| author = Vincent A, Buckley C, Schott JM, ''et al.'' |
||
| title = Potassium channel antibody-associated encephalopathy: a potentially immunotherapy-responsive form of limbic encephalitis |
| title = Potassium channel antibody-associated encephalopathy: a potentially immunotherapy-responsive form of limbic encephalitis |
||
| journal = Brain |
| journal = Brain |
||
| year = 2004 |
| year = 2004 |
||
| volume = 127 |
| volume = 127 |
||
| pages = 701–712 |
| pages = 701–712 |
||
| doi = 10.1093/brain/awh077 |
|||
| issue = 3}}</ref><ref>{{cite journal |
|||
| author = Thieben MJ, Lennon VA, Boeve BF, ''et al.'' |
| author = Thieben MJ, Lennon VA, Boeve BF, ''et al.'' |
||
| title = Potentially reversible auto-immune limbic encephalitis with neuronal potassium channel antibody |
| title = Potentially reversible auto-immune limbic encephalitis with neuronal potassium channel antibody |
||
| journal = Neurology |
| journal = Neurology |
||
| year = 2004 |
| year = 2004 |
||
| volume = 62 |
| volume = 62 |
||
| pages = 1177–1182 |
| pages = 1177–1182 |
||
| doi = 10.1212/01.WNL.0000122648.19196.02 |
|||
| issue = 7}}</ref> |
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==Diagnosis== |
==Diagnosis== |
||
Line 82: | Line 95: | ||
There are two sets of diagnostic criteria used. The oldest are those proposed by Gultekin ''et al.'' in 2000.<ref>{{cite journal |
There are two sets of diagnostic criteria used. The oldest are those proposed by Gultekin ''et al.'' in 2000.<ref>{{cite journal |
||
| author = Gultekin SH, Rosenfeld MR, Voltz R, ''et al.'' |
| author = Gultekin SH, Rosenfeld MR, Voltz R, ''et al.'' |
||
| title = Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients |
| title = Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients |
||
| journal = Brain |
| journal = Brain |
||
| year = 2000 |
| year = 2000 |
||
| volume = 123 |
| volume = 123 |
||
| pages = 1481–1494 |
| pages = 1481–1494 |
||
| doi = 10.1093/brain/123.7.1481 |
|||
| issue = 7}}</ref> |
|||
{| class="wikitable" |
{| class="wikitable" |
||
|- |
|- |
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Line 104: | Line 119: | ||
A revised set of criteria were proposed by Graus and Saiz in 2005.<ref>{{cite journal |
A revised set of criteria were proposed by Graus and Saiz in 2005.<ref>{{cite journal |
||
| author = Graus F, Saiz A |
| author = Graus F, Saiz A |
||
| title = Limbic encephalitis: a probably under-recognized syndrome |
| title = Limbic encephalitis: a probably under-recognized syndrome |
||
| journal = Neurologia |
| journal = Neurologia |
||
| year = 2005 |
| year = 2005 |
||
Line 125: | Line 140: | ||
The main antibodies within this group are those against Hu, Ma2, CV2, amphiphysin and Ri. The syndrome of anti-Ma2 encephalitis may be clinically mistaken for Whipple's disease.<ref>{{cite journal |
The main antibodies within this group are those against Hu, Ma2, CV2, amphiphysin and Ri. The syndrome of anti-Ma2 encephalitis may be clinically mistaken for Whipple's disease.<ref>{{cite journal |
||
| author = Castle J, Sakonju A, Dalmau J, ''et al.'' |
| author = Castle J, Sakonju A, Dalmau J, ''et al.'' |
||
| title = Anti-Ma2-associated encephalitis with normal FDG-PET: a case of pseudo- |
| title = Anti-Ma2-associated encephalitis with normal FDG-PET: a case of pseudo-Whipple's disease |
||
| journal = Nat Clin Pract Neurol |
| journal = Nat Clin Pract Neurol |
||
| year = 2006 |
| year = 2006 |
||
| volume = 2 |
| volume = 2 |
||
| pages = 566–572 |
| pages = 566–572 |
||
| doi = 10.1038/ncpneuro0287 |
|||
| issue = 10}}</ref> |
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==Antibodies against cell membrane antigens== |
==Antibodies against cell membrane antigens== |
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Line 137: | Line 154: | ||
Patients with [[Anti-NMDA receptor encephalitis|NMDAR encephalitis]] are frequently young women who present with fever, headache and fatigue. This is often misdiagnosed as influenza, but progresses to severe behavioural and personality disturbance, delusions, paranoia and hallucinations.<ref>{{cite journal |
Patients with [[Anti-NMDA receptor encephalitis|NMDAR encephalitis]] are frequently young women who present with fever, headache and fatigue. This is often misdiagnosed as influenza, but progresses to severe behavioural and personality disturbance, delusions, paranoia and hallucinations.<ref>{{cite journal |
||
| author = Koide R, Shimizu T, Koike K, ''et al.'' |
| author = Koide R, Shimizu T, Koike K, ''et al.'' |
||
| title = EFA6A-like antibodies in paraneoplastic encephalitis associated with immature ovarian teratoma: a case report |
| title = EFA6A-like antibodies in paraneoplastic encephalitis associated with immature ovarian teratoma: a case report |
||
| journal = J Neurooncol |
| journal = J Neurooncol |
||
| year = 2007 |
| year = 2007 |
||
| volume = 81 |
| volume = 81 |
||
| pages = 71–74 |
|||
| |
| doi = 10.1007/s11060-006-9200-7 }}</ref> Patients may therefore initially be admitted to a psychiatric ward for acute psychosis or schizophrenia. The disease then progresses to catatonia, seizures and loss of consciousness. The next stage is hypoventilation requiring intubation, orofacial dyskinesia and autonomic instability (dramatic fluctuations in blood pressure, temperature and heart rate).<ref>{{cite journal |
||
| author = Dalmau J, Tuzun E, Wu HY, ''et al.'' |
| author = Dalmau J, Tuzun E, Wu HY, ''et al.'' |
||
| title = Paraneoplastic anti-''N''-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma |
| title = Paraneoplastic anti-''N''-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma |
||
| journal = Ann Neurol |
| journal = Ann Neurol |
||
| year = 2007 |
| year = 2007 |
||
| volume = 61 |
| volume = 61 |
||
| pages = 25–36}}</ref> Treatment is removal of the associated ovarian tumour. |
| pages = 25–36 |
||
| doi = 10.1002/ana.21050}}</ref> Treatment is removal of the associated ovarian tumour. |
|||
==Treatment== |
==Treatment== |
Revision as of 10:50, 7 February 2013
Limbic encephalitis | |
---|---|
Specialty | Neurology |
Limbic encephalitis is a form of encephalitis, which is to say, it is a disease characterised by inflammation of the brain.[1] Limbic encephalitis is caused by auto-immunity: that is an abnormal state where the body produces antibodies against itself. Some cases are associated with cancer and some are not.[1] Although the disease is known as "limbic" encephalitis, the fact is that disease is seldom limited to the limbic system and post-mortem studies usually show involvement of other parts of the brain also.[2][3][4] The disease was first described by Brierley and others in 1960 as a series of three cases. The link to cancer was first noted in 1968[3] and confirmed by later investigators.[5]
The majority of cases of limbic encephalitis are associated with a tumour (diagnosed or undiagnosed). In cases caused by tumour, cure is only achieved when the tumour is removed completely (this is not always possible). 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 tumours of the testis.
- Anti-NMDAR, associated tumours of the ovary.
Symptoms and signs
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. Examination of cerebrospinal fluid (CSF) shows elevated numbers of lymphocytes (but usually < 100 cells/µl); 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.[6][7][8]
Diagnosis
The diagnosis of limbic encephalitis is extremely difficult and it is usual for the diagnosis to be delayed for weeks. The key diagnostic test (detection of specific auto-antibodies in cerebrospinal fluid) is not routinely available offered by most immunology laboratories. Some of the rarer anti-antibodies (e.g., NDMAR) have no commercially available assay and can only be measured by a very small number of research laboratories worldwide, further delaying diagnosis by weeks or months. Most patients with limbic encephalitis are initially diagnosed with herpes simplex encephalitis, because the two syndromes cannot be distinguished clinically.[1] HHV-6 (human herpes virus 6) encephalitis is also clinically indistinguishable from limbic encephalitis.[1]
There are two sets of diagnostic criteria used. The oldest are those proposed by Gultekin et al. in 2000.[9]
Gultekin criteria |
---|
EITHER, Pathological demonstration of limbic encephalitis |
OR, All four of:
|
A revised set of criteria were proposed by Graus and Saiz in 2005.[10]
Graus and Saiz criteria |
---|
All four of
|
The main distinction between the two sets of criteria is whether or not the detection of a paraneoplastic antibody is needed for diagnosis.
Antibodies against intracellular neuronal antigens
The main antibodies within this group are those against Hu, Ma2, CV2, amphiphysin and Ri. The syndrome of anti-Ma2 encephalitis may be clinically mistaken for Whipple's disease.[11]
Antibodies against cell membrane antigens
The main antibodies within this group are those again voltage-gated potassium channels (VGKC) and anti-N-methyl-D-aspartate receptors (NMDAR). They are associated with tumours of the thymus and ovary. Anti-NDMAR encephalitis is strongly associated with benign tumours of the ovary (usually teratomas or dermoid cysts).
Patients with NMDAR encephalitis are frequently young women who present with fever, headache and fatigue. This is often misdiagnosed as influenza, but progresses to severe behavioural and personality disturbance, delusions, paranoia and hallucinations.[12] Patients may therefore initially be admitted to a psychiatric ward for acute psychosis or schizophrenia. The disease then progresses to catatonia, seizures and loss of consciousness. The next stage is hypoventilation requiring intubation, orofacial dyskinesia and autonomic instability (dramatic fluctuations in blood pressure, temperature and heart rate).[13] Treatment is removal of the associated ovarian tumour.
Treatment
Limbic encephalitis is a rare condition with no randomised-controlled trials to guide treatment. Treatments that have been tried include intravenous immunoglobulin, plasma exchange, corticosteroids, cyclophosphamide and rituximab.[1] None of these treatments have been proven to work. If an associated tumour is found, then recovery is not possible until the tumour is removed. Unfortunately, this is not always possible, especially if the tumour is malignant and advanced.
References
- ^ a b c d e f Tüzün E, Dalmau J (2007). "Limbic encephalitis and variants: classification, diagnosis and treatment". The Neurologist. 13 (5).
- ^ Brierley JB, Corsellis JAN, Hierons R; et al. (1960). "Subacute encephalitis of later adult life. Mainly affecting the limbic areas". Brain. 83 (3): 357–368. doi:10.1093/brain/83.3.357.
{{cite journal}}
: Explicit use of et al. in:|author=
(help)CS1 maint: multiple names: authors list (link) - ^ a b Corsellis JA, Goldberg GJ, Norton AR (1968). ""Limbic encephalitis" and its association with carcinoma". Brain. 91 (3): 481–496. doi:10.1093/brain/91.3.481.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Bakheit AM, Kennedy PG, Behan PO (1990). "Paraneoplastic limbic encephalitis: clinico-pathological correlations". J Neurol Neurosurg Psychiatry. 53 (12): 1084–1088. doi:10.1136/jnnp.53.12.1084.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Henson RA, Hoffman HL, Urich H (1965). "Encephalomyelitis with carcinoma". Brain. 88 (3): 449–464. doi:10.1093/brain/88.3.449.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Buckley C, Oger J, Clover L; et al. (2001). "Potassium channel antibodies in two patients with reversible limbic encephalitis". Ann Neurol. 50: 73–78. doi:10.1002/ana.1097.
{{cite journal}}
: Explicit use of et al. in:|author=
(help)CS1 maint: multiple names: authors list (link) - ^ Vincent A, Buckley C, Schott JM; et al. (2004). "Potassium channel antibody-associated encephalopathy: a potentially immunotherapy-responsive form of limbic encephalitis". Brain. 127 (3): 701–712. doi:10.1093/brain/awh077.
{{cite journal}}
: Explicit use of et al. in:|author=
(help)CS1 maint: multiple names: authors list (link) - ^ Thieben MJ, Lennon VA, Boeve BF; et al. (2004). "Potentially reversible auto-immune limbic encephalitis with neuronal potassium channel antibody". Neurology. 62 (7): 1177–1182. doi:10.1212/01.WNL.0000122648.19196.02.
{{cite journal}}
: Explicit use of et al. in:|author=
(help)CS1 maint: multiple names: authors list (link) - ^ Gultekin SH, Rosenfeld MR, Voltz R; et al. (2000). "Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients". Brain. 123 (7): 1481–1494. doi:10.1093/brain/123.7.1481.
{{cite journal}}
: Explicit use of et al. in:|author=
(help)CS1 maint: multiple names: authors list (link) - ^ Graus F, Saiz A (2005). "Limbic encephalitis: a probably under-recognized syndrome". Neurologia. 20: 24–30.
- ^ Castle J, Sakonju A, Dalmau J; et al. (2006). "Anti-Ma2-associated encephalitis with normal FDG-PET: a case of pseudo-Whipple's disease". Nat Clin Pract Neurol. 2 (10): 566–572. doi:10.1038/ncpneuro0287.
{{cite journal}}
: Explicit use of et al. in:|author=
(help)CS1 maint: multiple names: authors list (link) - ^ Koide R, Shimizu T, Koike K; et al. (2007). "EFA6A-like antibodies in paraneoplastic encephalitis associated with immature ovarian teratoma: a case report". J Neurooncol. 81: 71–74. doi:10.1007/s11060-006-9200-7.
{{cite journal}}
: Explicit use of et al. in:|author=
(help)CS1 maint: multiple names: authors list (link) - ^ Dalmau J, Tuzun E, Wu HY; et al. (2007). "Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma". Ann Neurol. 61: 25–36. doi:10.1002/ana.21050.
{{cite journal}}
: Explicit use of et al. in:|author=
(help)CS1 maint: multiple names: authors list (link)
External links
- Template:Medcyclopaedia
- PNSEURONET: the PNSEURONET group provides information on paraneoplastic neurological syndromes for medical specialists worldwide.
- [1]: "Diagnosis: 'Forgetting Everything'", New York Times, November 11, 2007.