دمانس های اتوایمون دکتر رضائی طلب نورولوژیست آذر 95

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1 دمانس های اتوایمون دکتر رضائی طلب نورولوژیست آذر 95

2 Definition: Dementia According the DSM-5, dementia is defined as significant acquired cognitive impairment in one or more cognitive domains (eg, learning and memory, language, executive function, complex attention, perceptual-motor function, social cognition) that represents a significant decline from previous baseline and interferes with independence in daily activities

3 Role of Autoantibodies in Alzheimer disease Compelling evidence suggests that the immune system plays a critical role in the pathophysiology of AD. Autoantibodies against a variety of molecules have been associated with AD. Wu J, Li L. Autoantibodies in Alzheimer's disease: potential biomarkers, pathogenic roles, and therapeutic implications. J Biomed Research Sep;30(5):

4 Role of Autoantibodies in Alzheimer disease Active amyloid-β (Aβ) immunotherapy is effective in preventing Aβ deposition, facilitating plaque clearance, and improving cognitive functions in mouse models of Alzheimer's disease (AD). Ding L, Meng Y, Zhang HY, Yin WC, Yan Y, Cao YP. Active immunization with the peptide epitope vaccine Aβ3-10-KLH induces a Th2-polarized anti-aβ antibody response and decreases amyloid plaques in APP/PS1 transgenic mice. Neurosci Lett Nov 10;634:1-6. doi: /j.neulet Epub 2016 Sep 28.

5 Post-stroke cognitive decline and dementia pose a significant public health problem, with 30% of stroke survivors suffering from dementia. Pathogenic B cell responses to the damaged CNS are one possible contributing factor. B- lymphocytes and antibodies are present in and around the stroke core of some human subjects who die with stroke and dementia, and mice that develop delayed cognitive dysfunction after stroke have clusters of B- lymphocytes in the stroke lesion, and antibody infiltration in the stroked hemisphere. Doyle KP, Buckwalter MS. Does B lymphocyte-mediated autoimmunity contribute to post-stroke dementia? Brain Behav Immun Aug 13. pii: S

6 Inflammatory and autoimmune diseases Paraneoplastic and autoimmune limbic encephalitis Other nonparaneoplastic autoimmune encephalopathies Encephalopathy associated with systemic autoimmune Multiple sclerosis (MS)

7 Paraneoplastic limbic encephalitis is characterized by acute or subacute mood and behavioral changes, short-term memory problems, complex-partial seizures, and cognitive dysfunction The most common cause of paraneoplastic limbic encephalitis is small cell lung carcinoma

8 Autoimmune limbic encephalitis (LE) Rapid development of confusion, working memory deficit, mood changes and often seizures. The subacute memory loss is a hallmark of the disorder but it can be overlooked easily because of the presence of other symptoms Grabs F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T, Cortese I, Dale RC, Gelfand JM, Geschwind M, Glaser CA, Honnorat J, Hoftberger R, Iizuka T, Irani SR, Lancaster E, Leypoldt F, Pruss H, Rae-Grant A, Reindl M, Rosenfeld MR, Rostasy K, Saiz A, Venkatesan A, Vincent A, Wandinger KP, Waters P, Dalmau J. Autoimmune encephalitis. Lancet Neurology 2016 Apr; 15(4):

9 CSF analysis shows mild to moderate lymphocytic pleocytosis in 60-80% of patients (usually less than 100 white cells per mm3) and elevated IgG index or oligoclonal bands in 50%.

10 MRI often shows increased signal on T2 FLAIR in the medial aspect of the temporal lobes. LE can present with unilateral involvement or with normal MRI and then the diagnosis requires positive antibodies

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12 Panel 2. Diagnostic criteria for definite autoimmune limbic encephalitis All four of the following criteria: 1.- Subacute onset (less than 3 months) of working memory deficits, seizures or psychiatric symptoms. 2.- Bilateral MRI brain abnormalities on medial temporal lobes (PET may be more sensitive) 3.- At least one of the following: - CSF pleocytosis (more than 5 white cells per mm3) - EEG with epileptic or slow wave activity in temporal lobes 4.- Reasonable exclusion of alternative causes: Lupus, Sjogren's, Kikuchi, Behcet, glioma, herpes, syphilis, Whipple. If one of the first three criteria is not met diagnosis of definite LE can be made only by the detection of antibodies against cell-surface, synaptic or onconeural proteins.

13 Other nonparaneoplastic autoimmune encephalopathies Autoimmune dementia is a term that has been used to describe a steroidresponsive autoimmune disorder characterized by a rapidly progressive dementia with a fluctuating course. This condition, unlike paraneoplastic encephalopathy, is more common in females. The condition has been referred to by many names (including Hashimoto encephalopathy), but in the end represents a steroid-responsive autoimmune disorder causing a dementing disorder.

14 Hashimoto's encephalitis or encephalopathy (HE) is a rare autoimmune disease often under diagnosed. It can present as rapidly progressive dementia (RPD) or dementia of unknown origin which is treatable with high dose steroids. Kuljeet Singh Anand, Jyoti Garg, Rohit Verma, and Anirban Chakraborty. Hashimoto's Encephalitis: Unusual Cause of Reversible Dementia. J Family Med Prim Care Jul-Sep; 3(3):

15 Hashimoto's encephalopathy (HE), which carries kaleidoscopic clinical presentations, is easily misdiagnosed in clinical practice. Early diagnosis and prompt initiation of steroid therapy are associated with good prognosis. Goh KK, Chiu YH, Shen WW. Hashimoto's encephalopathy mimicking presenile dementia. Gen Hosp Psychiatry May-Jun;36(3):360.e9-11.

16 Encephalopathy associated with systemic autoimmune disease Progressive cognitive impairment has been described in association with systemic lupus erythematosis, Sjogren syndrome, and Behcet disease. These conditions typically produce a nonvasculitic encephalitis. Bhangle SD, Kramer N, Rosenstein ED. Corticosteroid-induced neuropsychiatric disorders: review and contrast with neuropsychiatric lupus. Rheumatol Int 2013; 33:1923.

17 Multiple sclerosis Cognitive dysfunction on neuropsychological testing can be detected in 45 to 65 percent of patients with multiple sclerosis. Cortical lesion burden and brain atrophy, rather than the T2 hyperintense white matter lesion volume, correlate most strongly with degree of cognitive impairment. Staff NP, Lucchinetti CF, Keegan BM. Multiple sclerosis with predominant, severe cognitive impairment. Arch Neurol 2009; 66:1139.

18 Thank you