Paraneoplastic cerebellar degeneration
Encyclopedia
Paraneoplastic cerebellar degeneration (PCD) is a paraneoplastic syndrome
associated with lung
, ovarian, breast
, and other cancer
s.
As is the case with other paraneoplastic syndromes, PCD is believed to be due to an autoimmune reaction targeted against components of the central nervous system
(in PCD, this is specifically Purkinje cells). It is thought to be triggered when tumor cells (in PCD, most commonly ovarian or breast cancer) express a protein normally expressed in the brain (in PCD, this is the Purkinje neuronal protein termed cdr2). This is believed to trigger an anti-tumor immune response that may be clinically significant, but also an anti-neuronal immune response. PCD patients harbor an anti-neuronal antibody known as anti-Yo (named after the first two letters of the index patient). PCD may be associated with other tumors--when associated with small cell lung cancer, it is associated with an antibody termed "anti-Hu" (more commonly associated with paraneoplastic subacute sensory neuropathy and/or limbic encephalitis
).
The clinical cerebellar ataxia
evident in patients with PCD are caused by Purkinje neuronal loss in the cerebellum; it is manifested by dysarthria, limb and gait ataxia, and nystagmus. Radiologic imaging occasionally reveals cerebellar atrophy. Other paraneoplastic antibodies may be associated with PCD symptoms, including anti-Tr and antibodies to glutamate receptor.
. However, when the antibody was used to clone the cDNA encoding the cdr2 antigen, it was found to be an intracellular protein. This led to the suggestion that there might be a cell-mediated component (T cell) in disease pathogenesis. cdr2 antigen-specific CD8+ T cells were subsequently described in all PCD patients, making them a hallmark of the disease, and likely components in both the anti-tumor immune response and in the neuronal degeneration.
Paraneoplastic syndrome
A paraneoplastic syndrome is a disease or symptom that is the consequence of the presence of cancer in the body, but is not due to the local presence of cancer cells. These phenomena are mediated by humoral factors excreted by tumor cells or by an immune response against the tumor...
associated with lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
, ovarian, breast
Breast
The breast is the upper ventral region of the torso of a primate, in left and right sides, which in a female contains the mammary gland that secretes milk used to feed infants.Both men and women develop breasts from the same embryological tissues...
, and other cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
s.
As is the case with other paraneoplastic syndromes, PCD is believed to be due to an autoimmune reaction targeted against components of the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
(in PCD, this is specifically Purkinje cells). It is thought to be triggered when tumor cells (in PCD, most commonly ovarian or breast cancer) express a protein normally expressed in the brain (in PCD, this is the Purkinje neuronal protein termed cdr2). This is believed to trigger an anti-tumor immune response that may be clinically significant, but also an anti-neuronal immune response. PCD patients harbor an anti-neuronal antibody known as anti-Yo (named after the first two letters of the index patient). PCD may be associated with other tumors--when associated with small cell lung cancer, it is associated with an antibody termed "anti-Hu" (more commonly associated with paraneoplastic subacute sensory neuropathy and/or limbic encephalitis
Limbic encephalitis
Limbic encephalitis is a form of encephalitis.In a small number of cases, the pathogens responsible for encephalitis attack primarily the limbic system , often causing memory deficits similar to those observed in Alzheimer's disease or Creutzfeldt-Jakob disease Limbic encephalitis is a form of...
).
The clinical cerebellar ataxia
Cerebellar ataxia
Cerebellar ataxia is a form of ataxia originating in the cerebellum.-References:...
evident in patients with PCD are caused by Purkinje neuronal loss in the cerebellum; it is manifested by dysarthria, limb and gait ataxia, and nystagmus. Radiologic imaging occasionally reveals cerebellar atrophy. Other paraneoplastic antibodies may be associated with PCD symptoms, including anti-Tr and antibodies to glutamate receptor.
Pathophysiology
The anti-Purkinje cell antibodies originally described in PCD led to the hypothesis that the antibody might be pathogenic, much as earlier studies had demonstrated pathogenicity of anti-acetylcholine receptor antibodies in myasthenia gravisMyasthenia gravis
Myasthenia gravis is an autoimmune neuromuscular disease leading to fluctuating muscle weakness and fatiguability...
. However, when the antibody was used to clone the cDNA encoding the cdr2 antigen, it was found to be an intracellular protein. This led to the suggestion that there might be a cell-mediated component (T cell) in disease pathogenesis. cdr2 antigen-specific CD8+ T cells were subsequently described in all PCD patients, making them a hallmark of the disease, and likely components in both the anti-tumor immune response and in the neuronal degeneration.