Autoimmune Causes of Dementia

Several autoimmune conditions can cause both typical and rapidly progressive dementia. The rapidly progressive forms can occur as paraneoplastic disorders.

Dementia is a condition of diminished brain function. It can impair memory, cognition and reason to a degree not seen in normal aging. Most conditions of dementia develop slowly over time. It is important to identify autoimmune forms of dementia because these conditions are highly reversible with immunosuppressant treatment. For instance in one case of amyloid cerebral angiopathy, a single dose of dexamethasone caused the patient to make a rapid and nearly completely recovery over the course of a few months.

Rapidly Progressive Dementia

Unlike the slow developing forms of dementia caused by Alzheimer’s disease or vitamin B12 deficiency, some forms of dementia are rapidly progressive and potentially fatal. Researchers at the University of California, San Francisco, report that the rapidly progressive forms of dementia can be caused by Jakob-Creutzfeldt and other prion disorders, neurodegenerative disorders, autoimmune conditions, toxic/metabolic disorders, malignancies and vascular disorders.

Autoimmune Dementia

About 15 percent of all cases of rapidly progressive dementia are caused by autoimmune disorders. Some of these conditions may occur as paraneoplastic conditions, which means that they are related to malignancies. These conditions may occur before the malignancies are apparent.

Dementia with a slower onset may also occur in the autoimmune conditions Hashimoto’s encephalopathy and in pernicious anemia and other causes of vitamin B 12 deficiency. The following autoimmune conditions are known to cause rapidly progressive dementia.

Autoimmune Encephalopathies

Autoimmune encephalopathies may occur as paraneoplastic and non-paraneoplastic conditions. Initially, these conditions were all thought to be paraneoplastic caused by an immune response to various types of cancer that cross-reacted with nervous system antigens. In recent years it’s been found that many of these conditions are not associated with cancer.

Paraneoplastic autoimmune encephalopathies are often divided into two subtypes. One type causes isolated involvement of one part of the central nervous system (e.g. limbic encephalitis or encephalopathy, cerebellar syndromes, retinal degeneration). The other subtype causes more diffuse, multifocal symptoms and is sometimes referred to as paraneoplastic encephalomyelitis (PEM).

Paraneoplastic limbic encephalopathy (PLE) can occur as an isolated syndrome or as PEM with involvement of the brainstem, cerebellum or peripheral nerves. Symptoms include problems with short-term memory, variable amnesia, depression, personality changes, anxiety and emotional lability and eventual cognitive dysfunction. These disorders can occur in patients with cancer or they can precede the detection of cancer by weeks, months, or years.

The most common associated tumors are small cell lung cancer, ovarian cancer, testicular cancer, thymoma, Hodgkin’s lymphoma, and breast cancer. Laboratory indicators include evidence of inflammation in spinal fluid, elevated tumor markers (e.g., CEA, CA-125, PSA, CA15-3), and the presence of certain paraneoplastic antibodies (e,g., anti-Hu, anti-CV2, anti-Ma2, anti-Ta) in the serum or spinal fluid.

Non-paraneoplastic autoimmune limbic encephalopathies are sometimes associated with anti-voltage-gated potassium channels antibodies (VGKC) and to anti-neuropil antibodies. Patients with anti-VGKC antibodies show signs of peripheral and central nervous system involvement. Peripheral nervous system involvement alone may manifest as neuromyotonia (Isaac’s Syndrome). Isolated central nervous system involvement may occur as seizure disorders and limbic encephalopathy. Anti-GAD antibodies, which are common in Stiff-Person syndrome, can also cause subacute ataxia accompanied by mild cognitive impairment.

Other Autoimmune Causes of Progressive Dementia

Cerebral amyloid inflammatory vasculopathy is a newly identified autoimmune condition responsible for rapidly progressive dementia. MRI studies show evidence of hemorrhage that is amyloid-related and occasional white matter hyperintensities. Collagen vascular and granulomatous diseases may also cause encephalopathy including primary angiitis of the central nervous system, polyarteritis nodosa, sarcoidosis, systemic lupus erythematosus, celiac disease, CNS vasculitis, Behcet’s disease, hypereosinophilic syndrome, Waldenstrom's macroglobulinemia, thrombotic thrombocytopenic purpura, and Sjogren’s encephalopathy. ♦

© Oct 5 2010 Copyrighted by Elaine Moore

Resources:

Michael Geschwind, Aissa Haman, and Bruce Miller (2007). "Rapidly Progressive Dementia, Clinical Neurology and Neurosurgery," August: 25(3) 783-807.

Mayo Clinic Laboratories Test Catalog (August, 2010). "Paraneoplastic Autoantibody Evaluation, Serum Unit Code 83380."