Neuroimmunology Lecture Notes PDF

Neuroimmunology Clinical and Chemical Pathology Department Dear students &  learning outcomes At the end of this session, you should be able to: 1. Define neuroimmunology 2. Understand the relation of CNS and immunology system 3. Know the different CNS cells 4. Classify...

Neuroimmunology Clinical and Chemical Pathology Department Dear students &  learning outcomes At the end of this session, you should be able to: 1. Define neuroimmunology 2. Understand the relation of CNS and immunology system 3. Know the different CNS cells 4. Classify the autoimmune neurological diseases. 5. Identify the pathophysiological mechanisms of the different autoimmune neurological diseases 6. Demonstrate the laboratory workout of the different autoimmune neurological diseases  What is meant by neuroimmunology It is the study of the interaction between the nervous system and immune system.  Sympathe tic nernous system as IL1,IL6,TNFα B- adrenergic signalling So the complex mechanisms of survival does not performs alone by our immune system but the high developed neurons of the nervous system in the brain and spinal cord also integrate with it.  The innate and adaptive immune Cells of immune system responses work in concert to restrict the invasion space of the pathogenic agent (innate immunity) either reduce its numbers or eradicate it altogether (innate and adaptive immunity). The adaptive immune response has a second feature which is to survey the body continually for possible invasion by the same pathogenic agent. Upon encounter with the same pathogenic agent a second time, the immune response occurs much more quickly since the  Sometimes Family Family history history Sometimes none of of autoimmune autoimmune none Coexisting Coexisting What disease disease or or autoimmune are the cancer cancer autoimmune disease, disease, e.g. e.g. thyroid risk thyroid disease, disease, Smoking Smoking type type 1 1 diabetes diabetes factors? history history mellitus mellitus Recent Recent Cancer Cancer infection infection history history Subacute Subacute onset onset Multifocal Multifocal symptoms symptoms disorders disorders How do patients Rapid Rapid Atypical Atypical progression progression present? phenotypes phenotypes Fluctuating Fluctuating Classic Classic course course phenotypes phenotypes Can Can affect affect any any neurological neurological 02/09/2025 domain domain  l u a a t t e e e e v vaa l u w t t o o H w rtth H o o h e e r r ? ? ur ffu Serum testing CSF testing Thyroid abs Protein Connective tissue Cell count Abs Neural Abs IgG index/synthesis rate  Autoimmune Neurological diseases CNS PNS Autoimmune Autoimmune Autoimmune Multiple diseases of disease of disease of sclerosis peripheral neuromuscular muscles nerves junction Myasthenia Dermatomyosit Gullian Barre Gravis is  CNS autoimmune diseases MS the autoimmune response to unknown target antigens has traditionally been driven by T cells, and recently it was found that B cell antigen presentation plays an important role in T cell activation in MS Pathogenesis of Multiple sclerosis (MS) nitial symptoms of multiple sclerosis (MS) Serum testing Prevalence (%) Sensory symptoms 35–40 Weakness in one or more 25–40 limbs Visual loss 17–29 Diplopia 12 Altered balance and gait 18 Vertigo 5 Bladder and bowel 5  Diagnosis/Laboratory Data No No single single laboratory of laboratory test MS test diagnostic diagnostic for for MS; MS; 1-Cerebrospinal 1-Cerebrospinal fluid fluid analysis analysis demonstrates demonstrates oligoclonal oligoclonal IgG IgG bands, bands, which which indicate indicate intrathecal intrathecal synthesis synthesis of of immunoglobulins immunoglobulins and and inflammatory inflammatory pathology pathology in in more more than than 90% 90% of of the the patients. patients. 2-The Diagnosis/Laboratory 2-The immunoglobulin immunoglobulin G G (IgG) (IgG) index Data index may may also also be be assessed assessed to to identify of MS synthesis identify intrathecal intrathecal synthesis of of IgG. IgG. It It is is increased increased in in 75% 75% of of patients patients with with multiple multiple sclerosis sclerosis (MS) (MS) IgG IgG Index Index = = (CSF/Serum (CSF/Serum IgG IgG ratio)/(CSF/Serum ratio)/(CSF/Serum Albumin Albumin ratio) ratio) 3-CSF 3-CSF cell cell count, count, protein, protein, and and glucose glucose are are often often normal normal in in patients patients with with MS, MS, or or there there may may be be aa mild mild pleocytosis pleocytosis Blood tests Blood tests are are usually usually used used to to rule rule out out other other diseases diseases that that may may mimic mimic MS. MS. No No autoantibodies autoantibodies areare present present in in MS MS  PNS autoimmune diseases 1-Autoimmune diseases of peripheral Guillain Barre syndrome : nerves Guillain–Barré syndrome (GBS) is the most frequent cause of acute flaccid paralysis worldwide. Are due to autoantibodies to gangliosides (glycosphingolipids) which are abundant in peripheral nerves. Autoantibodies cause segmental demyelination and disruption of Na channel clustering and axonal degeneration It comprises subtypes like acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor/sensory axonal neuropathy (AMAN/AMSAN), and Miller Fisher syndrome (MFS) Guillain Barre syndrome : Diagnosis of Gullian Barré 1-The identification of “albuminocytologic dissociation” in the CSF, indicating elevated protein levels with a normal or mildly increased cell count, supports GBS diagnosis. However, normal CSF protein level is observed in a considerable proportion of patients, particularly when tested within the first 3 days from symptom onset, whereas 84% of the patients have albumin-cytological dissociation after 7 days. 2-The identification of serum anti-ganglioside antibodies, such as IgG against GQ1b, is also valuable in identifying GBS subtypes 3- Nerve conduction studies, findings may be normal in early GBS stages, requiring repeat testing after 1–2 weeks with demyelinating or axonal patterns  PNS autoimmune diseases 2-Autoimmune diseases of neuromuscular junction  Myasthenia Gravis A A chronic chronic autoimmune autoimmune disease disease affecting affecting neuromuscular neuromuscular transmission. transmission. Characterized Characterized by by painless painless muscular muscular weakness, weakness, which which develops develops or or becomes becomes more more pronounced pronounced upon upon physical physical exertion. exertion. 26 Myasthenia gravis caused by autoantibodies to the: (i) post synaptic Acetylcholine receptor (AChR); IgG1 and IgG3 autoantibodies activate the complement cascade leading to structural damage to postsynaptic membrane and loss of AChR. (ii) Muscle skeletal receptor tyrosine protein kinase (MUSK). MUSK autoantibodies (Fab- arm exchanged monovalent IgG4) block agrin (released from motor nerve terminals) induced MUSK—LRP4 (low density lipoprotein receptor related protein 4) interaction, and disrupt clustering of AChR.  Presenting symptoms at the onset of MG. Prevalence (%) Ocular only 40% Ocular and bulbar 11% Ocular and generalized 17% Bulbar only 17% Total bulbar 43% Extremities 17% Generalized 14% Respiratory dysfunction 0.7% Diagnosis of Myasthenia Gravis 1-Serologic Tests: The anti-AChR Ab test is very specific, and it confirms the diagnosis in patients with classical clinical findings. It is present in four-fifths of patients with generalized MG and only in half of the patients with pure ocular MG. The rest of the patients, about 5% to 10%, will demonstrate anti-MuSK antibodies. Only in a few sporadic cases, both anti-AChR and anti-MuSK antibodies are present in the same patient. The 3% to 50% of the remaining patients who are seronegative to either of these antibodies will demonstrate anti-LRP4 antibodies. Anti-striated muscle antibodies are present in 30% of MG patients. They are more useful as a serologic marker for thymoma, especially in younger patients.  Diagnosis of Myasthenia Gravis 2-Electrophysiologic Tests: These are relevant in patients who are seronegative for antibody testing. Commonly employed tests for MG are the repetitive nerve stimulation (RNS) test and single-fiber electromyography (SFEMG). Both the tests assess for conduction delays in the NMJ 3-Edrophonium (Tensilon) Test: Edrophonium is a short-acting acetylcholinesterase inhibitor that increases the availability of ACh in the NMJ. This is particularly useful for ocular MG, where electrophysiologic testing cannot be performed. It is administered intravenously, and the patient is observed for improvement in the symptoms of ptosis or diplopia. It has a sensitivity of 71% to 95% for MG diagnosis. 4-Ice-pack Test: When edrophonium testing is contraindicated, an ice-pack test can be performed. This test requires an ice-pack placed over the eye for 2-5 minutes. Then, an assessment for any improvement in ptosis is done. This test cannot be used for the evaluation of extraocular muscles.  3-Immune-Mediated Myopathies are a group of acquired muscle disorders which include dermatomyositis, necrotizing autoimmune myopathy, overlap myositis, and inclusion body myositis  Summary or take-home message The interaction between immune and nervous system take place through molecular components and cells. The neuronal cell includes various receptors such as cytokine receptors, (PRR) pattern recognition receptors and various others that are expressed on the neurons. Tests Done for Evaluation (1) CSF analysis in autoimmune encephalitis may be normal or non-specific with mild lymphocytosis and elevation of CSF protein (2) Both serum and CSF should be tested for IgG autoantibodies. (3)Tests for CSF oligoclonal bands and CSF IgG index should be done as an indication of intra-thecal synthesis of antibodies.  Lecture notes Bhagavati S. Autoimmune Disorders of the Nervous System: Pathophysiology, Clinical Features, and Therapy. Front Neurol. 2021;12:664664. Published 2021 Apr 14. doi:10.3389/fneur.2021.664664  Dear Student: Don’t forget to complete your KWL chart And reflect on your learning experience by writing down what do you learnt from the lecture (3 points at least)