Table 3 Diagnostic investigations for the detection of autoimmune causes of obsessive-compulsive disorders and other psychiatric syndromes (compare with [34, 108, 121]).

From: Immunological causes of obsessive-compulsive disorder: is it time for the concept of an “autoimmune OCD” subtype?

Patient history

 

Onset/course of OCD

• Acute onset (< 3 months)?

• Treatment resistance or poor response to standard treatment according to OCD guidelines?

• Neurological symptoms such as seizures or focal neurological signs?

• Autonomic instability? Infectious prodromic symptoms? Systemic signs?

Family history

• Psychiatric/neurological/immunological/malignant disorders?

Comorbidity

• Psychiatric co-morbidity (Psychosis? Depression? Dementia? Autism? Tics?)

• Peripheral or central nervous neurological disorders (Encephalitis? Multiple sclerosis?)

• Systemic autoimmune disorders (Systemic lupus erythematosus? Sjögren’s Syndrome?)

• Malignancies?

Physical examination

 

Internal

• Tonsillopharyngitis? Heart involvement? Skin? Fever? Gastrointestinal symptoms? Changes in body weight? Etc.?

Neurological

• Movement disorders? Focal neurological signs? Kayser–Fleisher rings? Etc.?

Blood analyses

 

Basic blood analyses

• Differential blood count

• Electrolytes (sodium, potassium, calcium, magnesium)

• Metabolic markers (Creatinine, CK, GOT, GPT, AP, γ-GT, lipase)

• Thyroid hormones (TSH, free T3, free T4)

• Coagulation (INR, Quick, PTT)

• Caeruloplasmin and copper

Serologies or PCR analyses

• When suspected association to streptococcal infection: Anti-streptolysin O and anti-DNAse B antibodies (throat culture for Group A streptococcal infection)

• Borrelia burgdorferi (Lyme disease), mycoplasma pneumonia, Influenza, Epstein Barr virus, Herpes simplex, varicella zoster, toxoplasmosis gondii, Borna Disease Virus etc.

Rheumatic/immunological screening

• CRP, IgG/IgA/IgM levels, immune fixation

• CH50, C3, C4, C3d

• Rheumatoid factor

• ANA (dsDNA, ENA-differentiation), ANCA (MPO/PR3), antiphospholipid antibodies (lupus anticoagulant, anti-cardiolipin antibodies, anti-β2-glycoprotein I antibodies)

• Anti-thyroid antibodies (TPO/TG/TRAK)

Neuronal antibodies

• Against well-characterized cell surface antigens: NMDA-R, AMPA-1/2-R, GABAA/B-R, LGI1, CASPR2

• Against well-characterized intracellular antigens: Yo, Hu, CV2/CRMP5, Ri, Ma1/2, SOX1, Tr, Zic4, GAD65, amphiphysin

• When available: “Tissue tests” (indirect immunofluorescence on murine brain sections) for novel neuronal antibodies

• “Suspected PANDAS antibodies”: Antibodies against basal ganglia or dopamine D1/D2 receptor, perhaps also antibodies directed against lysoganglioside, tubulin, as well as antibody produced activation of calcium calmodulin protein kinase II

Urine

 

Instrument-based diagnostics

• Urine status/culture, drug screening, pregnancy test (for women)

EEG

• Resting state EEG including hyperventilation period, in special cases: “sleep EEG”

Brain MRI

• T1-weighted/MPRAGE, FLAIR, DWI sequences etc. (https://generate-net.de/generate-sops.html)

Cerebrospinal fluid analyses

 

Routine analyses

• White blood cell count, total protein, albumin quotient, IgG index, OCBs in serum/CSF, lactate

• Damage markers optionally (such as NfL, GFAP, tau; https://07525720-0688-4380-840d-0a4af942fef7.filesusr.com/ugd/92c932_af60b043468c4969b48f3c46bfc9b30f.pdf)

Antibody testing

• Against different well-characterized cell surface antigens: NMDA-R, AMPA-1/2-R, GABAA/B-R, LGI1, CASPR, basal ganglia, dopamine D1/D2 receptor

• Against well-characterized intracellular antigens: Yo, Hu, CV2/CRMP5, Ri, Ma1/2, SOX1, Tr, Zic4, GAD65, amphiphysin

• When available: “Tissue tests” for novel neuronal antibodies

• Antibody indices: For neuronal antibodies or pathogens (e.g., for antibodies against Borrelia burgdorferi); MRZ-reaction

Other investigations (for selected cases)

 

Psychometric/ neuropsychological testing

• Yale-Brown Obsessive-Compulsive Scale

• Test battery for attentional performance and for other executive functions (https://generate-net.de/generate-sops.html)

Positron emission tomography (PET)

• FDG- or TSPO-PET

Screening for malignancies

• According to the tumor-specific guidelines (in patients with paraneoplastic antibodies)

  1. OCD obsessive-compulsive disorder, CK creatine kinase, GOT glutamate oxaloacetate transaminase, GPT glutamate pyruvate transaminase, AP alkaline phosphatase, γ-GT gamma-glutamyltransferase, TSH thyroid-stimulating hormone, T3 triiodothyronine, T4 thyroxine, INR international normalized ratio, PTT partial thromboplastin time, CRP C-reactive protein, Ig immunoglobulin, CH50 total hemolytic complement activity, C3/C4/C3d complement factors, ANA antinuclear antibody, ENA extractable nuclear antigens, ANCA anti-neutrophil cytoplasmic antibodies, MPO myeloperoxidase, PR3 proteinase-3, TPO thyroid peroxidase, TG thyroglobulin, TRAK TSH receptor autoantibodies, NMDA-R N-methyl-d-aspartate type glutamate receptor, AMPA-1/2-R α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-1/2-receptor, GABAA/B-R γ-aminobutyric acid-A/B-receptor, LGI1 leucine-rich, glioma inactivated 1, CASPR2 contactin-associated protein-like 2, Yo/Hu initials of the first described patient, CV2/CRMP5 collapsin response mediator protein 5, Ri initials of the first described patient, SOX1 sry-like high mobility group Box 1, Zic4 zinc-finger of the cerebellum protein, GAD65 glutamate-decarboxylase 65kD, PANDAS Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infection, EEG electroencephalography, MRI magnetic resonance imaging, MPRAGE magnetization prepared - rapid gradient echo, FLAIR fluid-attenuated inversion recovery, DWI diffusion-weighted imaging, OCBs oligoclonal bands, CSF cerebrospinal fluid, GFAP glial fibrillary acidic protein, NfL neurofilament light chain, FDG-PET [18F]fluorodeoxyglucose positron emission tomography, TSPO-PET 18-kDa translocator protein positron emission tomography.
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