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{{ | __NOTOC__ | ||
{{SI}} | |||
{{CMG}} {{AE}} {{MV}} | |||
{{SK}} Cerebellar ataxia due to neoplasia; | |||
==Overview== | |||
Paraneoplastic cerebellar degeneration (PCD) is a rare [[paraneoplastic syndrome]] associated with [[lung]], [[ovarian]], [[breast]], [[Hodgkin’s lymphoma]], and other types of [[Tumor|tumors]]. Paraneoplastic cerebellar degeneration occurs in less than 1 to 3% of [[cancer]] [[Patient|patients]]. The [[pathogenesis]] of paraneoplastic cerebellar degeneration is due to an [[Autoimmunity|autoimmune reaction]] targeted against components of the [[central nervous system]]. The presence of anti-[[Purkinje cell]] is triggered by [[Tumor cell|tumor cells]], that normally express a Purkinje [[Neuron|neuronal]] [[protein]] termed CDR2 [[antibodies]]. The [[antibodies]] that have been associated with the development of paraneoplastic cerebellar degeneration include anti-P/Q type [[calcium channel]] [[antibodies]], anti-Tr [[antibodies]], anti-Ri (ANNA-2), anti-CV2, [[antibodies]] to Ma [[Protein|proteins]], and [[antibodies]] to the Zic4. Paraneoplastic cerebellar degeneration is more commonly observed among [[Patient|patients]] between 40 to 60 years old. Paraneoplastic cerebellar degeneration affects [[Female|females]] more commonly than [[Male|males]]. The majority of [[Patient|patients]] with paraneoplastic cerebellar degeneration are typically [[symptomatic]]. Early clinical features include [[dizziness]], [[nausea]], and [[vomiting]]. The [[diagnosis]] of paraneoplastic cerebellar degeneration is made with the following criteria: positive [[antibody]]-mediated [[immune response]], diffuse [[Cerebellum|cerebellar]] [[atrophy]] on [[imaging]], and positive [[Medicine|medical]] history of [[cancer]]. Common [[Medicine|medical]] [[Therapy|therapies]] for paraneoplastic cerebellar degeneration include [[intravenous]] [[immunoglobulins]], [[cyclophosphamide]], and [[methylprednisolone]]. There are no [[Prevention|primary and secondary preventive]] measures available for paraneoplastic cerebellar degeneration. | |||
==Historical Perspective== | |||
*Paraneoplastic cerebellar degeneration was first described in early 1980. | |||
}} | ==Classification== | ||
{{ | * Paraneoplastic cerebellar degeneration may be [[Classification|classified]] according to the presence or absence of an [[antibody]]. | ||
==Pathophysiology== | |||
*The [[pathogenesis]] of paraneoplastic cerebellar degeneration is characterized by the presence of anti-[[Purkinje cell]] [[antibodies]]. | |||
*The [[pathogenesis]] of paraneoplastic cerebellar degeneration is due to an [[Autoimmunity|autoimmune reaction]] targeted against components of the [[central nervous system]]. | |||
*The [[pathogenesis]] of paraneoplastic cerebellar degeneration is triggered by [[Tumor cell|tumor cells]], that normally express a [[protein]] (Purkinje [[Neuron|neuronal]] [[protein]] termed cdr2). This [[protein]] is believed to trigger an anti-[[tumor]] [[Immunity (medical)|immune]] and anti-[[Neuron|neuronal]] [[Immunity (medical)|immune]] response. | |||
*The [[antibodies]] that have been associated with the development of paraneoplastic cerebellar degeneration include:<ref name="pmid18339348">{{cite journal |vauthors=Dalmau J, Rosenfeld MR |title=Paraneoplastic syndromes of the CNS |journal=Lancet Neurol |volume=7 |issue=4 |pages=327–40 |year=2008 |pmid=18339348 |pmc=2367117 |doi=10.1016/S1474-4422(08)70060-7 |url=}}</ref> | |||
:*Anti - P/Q type [[calcium channel]] [[antibodies]] | |||
:*Anti -Tr [[antibodies]] | |||
:*Anti - Ri (ANNA-2) | |||
:*Anti - CV2 | |||
:*[[Antibodies]] to Ma [[Protein|proteins]] | |||
:*[[Antibodies]] to the Zic4 | |||
==Causes== | |||
* Causes of paraneoplastic cerebellar degeneration include:<ref name="wiki">Paraneoplastic cerebellar degeneration. Wikipedia. https://en.wikipedia.org/wiki/Paraneoplastic_cerebellar_degeneration Accessed on April 13, 2016</ref> | |||
:*[[Lung cancer]] | |||
:*[[Ovarian cancer]] | |||
:*[[Breast cancer]] | |||
:*[[Hodgkin's lymphoma]] | |||
==Differentiating Paraneoplastic Cerebellar Degeneration from Other Diseases== | |||
*Paraneoplastic cerebellar degeneration must be differentiated from other diseases that cause [[ataxia]], [[dizziness]], and [[nausea]] such as: | |||
**[[Cerebellum|Cerebellar]] [[metastasis]] | |||
**[[Brain stem|Brainstem]] [[metastasis]] | |||
**[[Metabolic]] derangement | |||
**[[Intoxication]] | |||
==Epidemiology and Demographics== | |||
* Paraneoplastic cerebellar degeneration affects approximately 1 - 3% of all [[cancer]] [[Patient|patients]].<ref name="wiki">Paraneoplastic cerebellar degeneration. Wikipedia. https://en.wikipedia.org/wiki/Paraneoplastic_cerebellar_degeneration Accessed on April 13, 2016</ref> | |||
===Age=== | |||
*Paraneoplastic cerebellar degeneration is more commonly observed among [[Patient|patients]] between 40 to 60 years old. | |||
*Paraneoplastic cerebellar degeneration is more commonly observed among middle aged [[Adult|adults]]. | |||
===Gender=== | |||
*Paraneoplastic cerebellar degeneration affects [[Female|females]] more commonly than [[Male|males]]. | |||
===Race=== | |||
*There is no racial predilection to paraneoplastic cerebellar degeneration. | |||
==Risk Factors== | |||
*There are no known [[Risk factor|risk factors]] for paraneoplastic cerebellar degeneration.<ref name="pmid16543537">{{cite journal |vauthors=Scheid R, Voltz R, Briest S, Kluge R, von Cramon DY |title=Clinical insights into paraneoplastic cerebellar degeneration |journal=J. Neurol. Neurosurg. Psychiatr. |volume=77 |issue=4 |pages=529–30 |year=2006 |pmid=16543537 |pmc=2077487 |doi=10.1136/jnnp.2005.082206 |url=}}</ref> | |||
== Screening == | |||
* There is insufficient evidence to recommend routine [[Screening (medicine)|screening]] for paraneoplastic cerebellar degeneration. | |||
== Natural History, Complications, and Prognosis== | |||
*The majority of [[Patient|patients]] with paraneoplastic cerebellar degeneration are typically [[symptomatic]]. | |||
*Early clinical features include [[dizziness]], [[nausea]], and [[vomiting]].<ref name="pmid16543537">{{cite journal |vauthors=Scheid R, Voltz R, Briest S, Kluge R, von Cramon DY |title=Clinical insights into paraneoplastic cerebellar degeneration |journal=J. Neurol. Neurosurg. Psychiatr. |volume=77 |issue=4 |pages=529–30 |year=2006 |pmid=16543537 |pmc=2077487 |doi=10.1136/jnnp.2005.082206 |url=}}</ref> | |||
*If left untreated, the majority of [[Patient|patients]] with paraneoplastic cerebellar degeneration may progress to develop severe [[disability]] with inability to walk. | |||
*The most common [[Complication (medicine)|complication]] of paraneoplastic cerebellar degeneration is [[Cerebellum|cerebellar]] [[dysfunction]]. | |||
*[[Prognosis]] is generally poor, and the [[median]] [[survival rate]] of [[Patient|patients]] with paraneoplastic cerebellar degeneration is approximately 13 months.<ref name="pmid18339348">{{cite journal |vauthors=Dalmau J, Rosenfeld MR |title=Paraneoplastic syndromes of the CNS |journal=Lancet Neurol |volume=7 |issue=4 |pages=327–40 |year=2008 |pmid=18339348 |pmc=2367117 |doi=10.1016/S1474-4422(08)70060-7 |url=}}</ref> | |||
== Diagnosis == | |||
===Diagnostic Study of Choice=== | |||
*The [[diagnosis]] of paraneoplastic cerebellar degeneration is made with the following criteria:<ref name="pmid18339348">{{cite journal |vauthors=Dalmau J, Rosenfeld MR |title=Paraneoplastic syndromes of the CNS |journal=Lancet Neurol |volume=7 |issue=4 |pages=327–40 |year=2008 |pmid=18339348 |pmc=2367117 |doi=10.1016/S1474-4422(08)70060-7 |url=}}</ref> | |||
:*Positive [[antibody]]-mediated [[immune response]] | |||
:*Diffuse [[Cerebellum|cerebellar]] [[atrophy]] on [[imaging]] | |||
:*Positive [[Medicine|medical]] history of [[cancer]] | |||
=== History and Symptoms === | |||
*[[Symptom|Symptoms]] of paraneoplastic cerebellar degeneration may include the following:<ref name="pmid18339348">{{cite journal |vauthors=Dalmau J, Rosenfeld MR |title=Paraneoplastic syndromes of the CNS |journal=Lancet Neurol |volume=7 |issue=4 |pages=327–40 |year=2008 |pmid=18339348 |pmc=2367117 |doi=10.1016/S1474-4422(08)70060-7 |url=}}</ref> | |||
:*[[Dysarthria]] | |||
:*[[Trunk|Truncal]], [[Limb (anatomy)|limb]] and [[Gait (human)|gait]] [[ataxia]] | |||
:*[[Vertigo]] | |||
:*[[Nausea]] | |||
:*[[Vomiting]] | |||
:*[[Diplopia|Double vision]] | |||
:*[[Slurred speech]] | |||
:*[[Dysphagia|Difficulty swallowing]] | |||
:*[[Nystagmus]] | |||
=== Physical Examination === | |||
*[[Patient|Patients]] with paraneoplastic cerebellar degeneration usually appear [[Confusion|confused]], or [[Fatigue|lethargic]].<ref name="pmid16543537">{{cite journal |vauthors=Scheid R, Voltz R, Briest S, Kluge R, von Cramon DY |title=Clinical insights into paraneoplastic cerebellar degeneration |journal=J. Neurol. Neurosurg. Psychiatr. |volume=77 |issue=4 |pages=529–30 |year=2006 |pmid=16543537 |pmc=2077487 |doi=10.1136/jnnp.2005.082206 |url=}}</ref> | |||
*[[Neurological examination]] may be remarkable for:<ref name="pmid18339348">{{cite journal |vauthors=Dalmau J, Rosenfeld MR |title=Paraneoplastic syndromes of the CNS |journal=Lancet Neurol |volume=7 |issue=4 |pages=327–40 |year=2008 |pmid=18339348 |pmc=2367117 |doi=10.1016/S1474-4422(08)70060-7 |url=}}</ref> | |||
:*[[Hyperactive reflexes]] | |||
:*[[Gait disturbance]] | |||
:*[[Babinski sign]] | |||
:*[[Speech disturbances|Speech disturbance]] | |||
:*[[Lack of coordination of muscle movement|Lack of coordination]] | |||
:*[[Nystagmus]] | |||
=== Laboratory Findings === | |||
*There are no specific [[Medical laboratory|laboratory]] findings associated with paraneoplastic cerebellar degeneration. | |||
*[[Medical laboratory|Laboratory]] [[Test|testing]] may include [[thyroid function tests]], [[vitamin]] levels, and [[antibody]] [[Titer|titers]] ([[Anti-gliadin antibodies|anti-gliadin]], or anti-GAD [[antibodies]]). | |||
=== Electrocardiogram === | |||
* There are no [[The electrocardiogram|ECG]] findings associated with paraneoplastic cerebellar degeneration. | |||
=== X-ray === | |||
* There are no [[X-rays|x-ray]] findings associated with paraneoplastic cerebellar degeneration. | |||
=== Echocardiography or Ultrasound === | |||
* There are no [[echocardiography]]/[[ultrasound]] findings associated with paraneoplastic cerebellar degeneration. | |||
=== CT scan === | |||
== | * There are no [[Computed tomography|CT scan]] findings associated with paraneoplastic cerebellar degeneration. | ||
===MRI=== | |||
*[[Magnetic resonance imaging|MRI]] is the [[imaging]] modality of choice for paraneoplastic cerebellar degeneration. | |||
*On [[Magnetic resonance imaging|MRI]], findings of paraneoplastic cerebellar degeneration include:<ref name="pmid18339348">{{cite journal |vauthors=Dalmau J, Rosenfeld MR |title=Paraneoplastic syndromes of the CNS |journal=Lancet Neurol |volume=7 |issue=4 |pages=327–40 |year=2008 |pmid=18339348 |pmc=2367117 |doi=10.1016/S1474-4422(08)70060-7 |url=}}</ref> | |||
:* Diffuse [[Cerebellum|cerebellar]] [[atrophy]] | |||
:* No [[atrophy]] of the [[cerebral cortex]], [[Mesencephalon|midbrain]], [[pons]], or [[Medulla oblongata|medulla]] | |||
=== Other Imaging Findings === | |||
* There are no other [[imaging]] findings associated with paraneoplastic cerebellar degeneration. | |||
=== Other Diagnostic Studies === | |||
*Paraneoplastic cerebellar degeneration may also be [[Diagnosis|diagnosed]] using [[Positron emission tomography|PET scan]]. | |||
*Findings on [[Positron emission tomography|PET scan]] are often unspecific, but may include [[hypermetabolism]].<ref name="wiki">Paraneoplastic cerebellar degeneration. Wikipedia. https://en.wikipedia.org/wiki/Paraneoplastic_cerebellar_degeneration Accessed on April 13, 2016</ref> | |||
== Treatment == | |||
=== Medical Therapy === | |||
*The mainstay of [[therapy]] for paraneoplastic cerebellar degeneration is supportive care. | |||
*Common [[Medicine|medical]] [[Therapy|therapies]] for paraneoplastic cerebellar degeneration include:<ref name="pmid18339348">{{cite journal |vauthors=Dalmau J, Rosenfeld MR |title=Paraneoplastic syndromes of the CNS |journal=Lancet Neurol |volume=7 |issue=4 |pages=327–40 |year=2008 |pmid=18339348 |pmc=2367117 |doi=10.1016/S1474-4422(08)70060-7 |url=}}</ref> | |||
:*[[Intravenous]] [[Antibody|immunoglobulins]] | |||
:*[[Cyclophosphamide]] | |||
:*[[Methylprednisolone]] | |||
== | === Surgery === | ||
*[ | *[[Surgery]] is not recommended for [[Patient|patients]] with paraneoplastic cerebellar degeneration. | ||
=== Primary Prevention === | |||
*There are no [[Prevention (medical)|primary preventive]] measures available for paraneoplastic cerebellar degeneration. | |||
=== Secondary Prevention === | |||
* There are no [[Prevention (medical)|secondary preventive]] measures available for paraneoplastic cerebellar degeneration. | |||
==References== | |||
{{Reflist|2}} | |||
[[Category: Oncology]] | |||
[[Category:Rheumatology]] | |||
[[Category:Up-To-Date]] | |||
[[Category:Oncology]] | |||
[[Category:Medicine]] | |||
[[Category:Neurology]] | [[Category:Neurology]] | ||
Latest revision as of 18:00, 20 May 2019
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Maria Fernanda Villarreal, M.D. [2]
Synonyms and keywords: Cerebellar ataxia due to neoplasia;
Overview
Paraneoplastic cerebellar degeneration (PCD) is a rare paraneoplastic syndrome associated with lung, ovarian, breast, Hodgkin’s lymphoma, and other types of tumors. Paraneoplastic cerebellar degeneration occurs in less than 1 to 3% of cancer patients. The pathogenesis of paraneoplastic cerebellar degeneration is due to an autoimmune reaction targeted against components of the central nervous system. The presence of anti-Purkinje cell is triggered by tumor cells, that normally express a Purkinje neuronal protein termed CDR2 antibodies. The antibodies that have been associated with the development of paraneoplastic cerebellar degeneration include anti-P/Q type calcium channel antibodies, anti-Tr antibodies, anti-Ri (ANNA-2), anti-CV2, antibodies to Ma proteins, and antibodies to the Zic4. Paraneoplastic cerebellar degeneration is more commonly observed among patients between 40 to 60 years old. Paraneoplastic cerebellar degeneration affects females more commonly than males. The majority of patients with paraneoplastic cerebellar degeneration are typically symptomatic. Early clinical features include dizziness, nausea, and vomiting. The diagnosis of paraneoplastic cerebellar degeneration is made with the following criteria: positive antibody-mediated immune response, diffuse cerebellar atrophy on imaging, and positive medical history of cancer. Common medical therapies for paraneoplastic cerebellar degeneration include intravenous immunoglobulins, cyclophosphamide, and methylprednisolone. There are no primary and secondary preventive measures available for paraneoplastic cerebellar degeneration.
Historical Perspective
- Paraneoplastic cerebellar degeneration was first described in early 1980.
Classification
- Paraneoplastic cerebellar degeneration may be classified according to the presence or absence of an antibody.
Pathophysiology
- The pathogenesis of paraneoplastic cerebellar degeneration is characterized by the presence of anti-Purkinje cell antibodies.
- The pathogenesis of paraneoplastic cerebellar degeneration is due to an autoimmune reaction targeted against components of the central nervous system.
- The pathogenesis of paraneoplastic cerebellar degeneration is triggered by tumor cells, that normally express a protein (Purkinje neuronal protein termed cdr2). This protein is believed to trigger an anti-tumor immune and anti-neuronal immune response.
- The antibodies that have been associated with the development of paraneoplastic cerebellar degeneration include:[1]
- Anti - P/Q type calcium channel antibodies
- Anti -Tr antibodies
- Anti - Ri (ANNA-2)
- Anti - CV2
- Antibodies to Ma proteins
- Antibodies to the Zic4
Causes
- Causes of paraneoplastic cerebellar degeneration include:[2]
Differentiating Paraneoplastic Cerebellar Degeneration from Other Diseases
- Paraneoplastic cerebellar degeneration must be differentiated from other diseases that cause ataxia, dizziness, and nausea such as:
- Cerebellar metastasis
- Brainstem metastasis
- Metabolic derangement
- Intoxication
Epidemiology and Demographics
Age
- Paraneoplastic cerebellar degeneration is more commonly observed among patients between 40 to 60 years old.
- Paraneoplastic cerebellar degeneration is more commonly observed among middle aged adults.
Gender
Race
- There is no racial predilection to paraneoplastic cerebellar degeneration.
Risk Factors
- There are no known risk factors for paraneoplastic cerebellar degeneration.[3]
Screening
- There is insufficient evidence to recommend routine screening for paraneoplastic cerebellar degeneration.
Natural History, Complications, and Prognosis
- The majority of patients with paraneoplastic cerebellar degeneration are typically symptomatic.
- Early clinical features include dizziness, nausea, and vomiting.[3]
- If left untreated, the majority of patients with paraneoplastic cerebellar degeneration may progress to develop severe disability with inability to walk.
- The most common complication of paraneoplastic cerebellar degeneration is cerebellar dysfunction.
- Prognosis is generally poor, and the median survival rate of patients with paraneoplastic cerebellar degeneration is approximately 13 months.[1]
Diagnosis
Diagnostic Study of Choice
- Positive antibody-mediated immune response
- Diffuse cerebellar atrophy on imaging
- Positive medical history of cancer
History and Symptoms
Physical Examination
- Patients with paraneoplastic cerebellar degeneration usually appear confused, or lethargic.[3]
- Neurological examination may be remarkable for:[1]
Laboratory Findings
- There are no specific laboratory findings associated with paraneoplastic cerebellar degeneration.
- Laboratory testing may include thyroid function tests, vitamin levels, and antibody titers (anti-gliadin, or anti-GAD antibodies).
Electrocardiogram
- There are no ECG findings associated with paraneoplastic cerebellar degeneration.
X-ray
- There are no x-ray findings associated with paraneoplastic cerebellar degeneration.
Echocardiography or Ultrasound
- There are no echocardiography/ultrasound findings associated with paraneoplastic cerebellar degeneration.
CT scan
- There are no CT scan findings associated with paraneoplastic cerebellar degeneration.
MRI
- MRI is the imaging modality of choice for paraneoplastic cerebellar degeneration.
- On MRI, findings of paraneoplastic cerebellar degeneration include:[1]
- Diffuse cerebellar atrophy
- No atrophy of the cerebral cortex, midbrain, pons, or medulla
Other Imaging Findings
- There are no other imaging findings associated with paraneoplastic cerebellar degeneration.
Other Diagnostic Studies
- Paraneoplastic cerebellar degeneration may also be diagnosed using PET scan.
- Findings on PET scan are often unspecific, but may include hypermetabolism.[2]
Treatment
Medical Therapy
- The mainstay of therapy for paraneoplastic cerebellar degeneration is supportive care.
- Common medical therapies for paraneoplastic cerebellar degeneration include:[1]
Surgery
Primary Prevention
- There are no primary preventive measures available for paraneoplastic cerebellar degeneration.
Secondary Prevention
- There are no secondary preventive measures available for paraneoplastic cerebellar degeneration.
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Dalmau J, Rosenfeld MR (2008). "Paraneoplastic syndromes of the CNS". Lancet Neurol. 7 (4): 327–40. doi:10.1016/S1474-4422(08)70060-7. PMC 2367117. PMID 18339348.
- ↑ 2.0 2.1 2.2 Paraneoplastic cerebellar degeneration. Wikipedia. https://en.wikipedia.org/wiki/Paraneoplastic_cerebellar_degeneration Accessed on April 13, 2016
- ↑ 3.0 3.1 3.2 Scheid R, Voltz R, Briest S, Kluge R, von Cramon DY (2006). "Clinical insights into paraneoplastic cerebellar degeneration". J. Neurol. Neurosurg. Psychiatr. 77 (4): 529–30. doi:10.1136/jnnp.2005.082206. PMC 2077487. PMID 16543537.