Neurosarcoidosis (NS) occurs in 5–15 % of patients with systemic sarcoidosis and may affect the brain, spinal cord, meninges, cranial nerves, and peripheral nervous system (Oksanen 1986; Wengert et al. 2013). Sarcoidosis is a systemic disease histologically characterized by noncaseating epithelioid granulomas, most often localized in the lungs and mediastinal lymph nodes (Zajicek et al. 1999). Neurological symptoms are the primary manifestation of the disease in ca. two-thirds of cases of NS (Zajicek et al. 1999; Ferriby et al. 2001). Thus most patients with NS only develop systemic symptoms after presenting with neurological signs of the disease. The clinical course may be acute, subacute, or chronic with insidious onset. The diagnosis of NS is based on demonstration of variable combination of neurological deficits, CNS imaging and CSF abnormalities, histological findings consistent with sarcoidosis, a positive Kveim–Siltzbach test, and positive results for at least two of the following tests: gallium scan, serum angiotensin-converting enzyme (ACE) level, and chest radiology including high-resolution computed tomography of the chest and bronchoalveolar lavage fluid analysis (Zajicek et al. 1999; Marangoni et al. 2006). The most typical MRI abnormalities include diffuse leptomeningeal enhancement in the brain and/or spinal cord and parenchymal hyperintense lesions with contrast enhancement (Wengert et al. 2013). In spite of this complexity, histological evidence of systemic disease together with compatible alterations in the CNS is sufficient for diagnosis in most cases (Marangoni et al. 2006). Other etiologies have to be ruled out.

CSF in patients with neurosarcoidosis may show several abnormalities: elevated leukocyte counts (≥50 × 10⁶/l cells), increased protein concentration (≥2 g/l), elevated level of lactate, and decreased level of glucose (Wengert et al. 2013). Intrathecal synthesis of IgG, IgA, and IgG has been detected in ca. one-fifth to one-third of the cases. Such CSF abnormalities were most pronounced in patients with active disease and correlated with changes on MRI.

Angiotensin-converting enzyme activity in sarcoidosis is regarded both as a diagnostic feature and as an index of disease activity that is elevated in the serum of patients with sarcoidosis (Parrish et al. 1982). Increase of its activity in the CSF has been reported in half of the patients with NS (Oksanen et al. 1985). Increased activity of this enzyme is thought to parallel macrophage and epithelioid cell activity. Also increase of the levels of lysozyme and beta-2 microglobulin, a low-molecular-weight protein associated with the histocompatibility antigens, has been reported in both the CSF and serum of majority of patients with NS (Oksanen et al. 1986). Notably, both CSF lysozyme and beta-2 microglobulin correlated to CSF leukocytes but not to CSF albumin suggesting that these markers were secreted from cells within the CNS. Elevations of CSF lysozyme and beta-2 microglobulin reveal disease activity in the CNS, and therefore both analyses are useful in monitoring disease activity in this illness.

Systemic lupus erythematosus (SLE) is a chronic, relapsing–remitting autoimmune disease of unknown etiology with a broad spectrum of clinical and immunologic manifestations affecting multiple organ systems. Neuropsychiatric SLE (NPSLE) encompasses central, peripheral, and autonomic nervous system as well as psychiatric manifestations observed in SLE patients. These features are classified using the American College of Rheumatology case definitions for 19 neuropsychiatric syndromes, which are listed in Table 17.2 (American College of Rheumatology 1999). The prevalence of NPSLE is highly variable, ranging from 21 to 95 % (Hanly 2014). However, only one-third of neuropsychiatric events can be directly attributed to SLE (Hanly 2014). These events can also be a consequence of complications of the disease or its treatment or totally unrelated to SLE.

Cornerstones of NPSLE diagnosis are (1) serum autoantibody profiling, (2) CSF examination, (3) neuroimaging (mainly MRI) in evaluation of brain structural abnormalities, (4) electrophysiological assessment (EEG to exclude underlying seizure disorder), and (5) neuropsychological assessment (Hanly 2014). The most important autoantibodies are antineuronal, antiribosomal P, and antiphospholipid antibodies (aPL). Antiribosomal P antibodies are mainly associated with SLE psychosis and aPL with stroke and seizure disorders.

In practice, the examination of CSF is primarily done to exclude CNS infections as a secondary cause of neuropsychiatric events and rarely in differential diagnosis of MS. In general, mild CSF abnormalities are common (40–50 %) but not specific to NPSLE (Bertsias et al. 2010). CSF findings include lymphocytic pleocytosis and OCBs, which may be detected in 25–80 % of cases (Ernerudh et al. 1983; Winfield et al. 1983; McLean et al. 1995; Reske et al. 2005). Unlike in MS, OCBs are not stable: they may disappear after treatment with corticosteroids (McLean et al. 1995).

Anti-NR2 antibodies are directed against the NR2 subtype of N-methyl-D-aspartate (NMDA) receptors, which are important in memory and learning functions. A Japanese study of 80 SLE patients found a strong association between CSF anti-NR2 antibodies and neuropsychiatric events (Yoshio et al. 2006). In another study, antiNR2 antibodies were detected in CSF of 44 and 82 % of patients with focal and diffuse NPSLE, respectively (Arinuma et al. 2008). These antibodies are also associated with hippocampal atrophy (Lauvsnes et al. 2014).

Primary Sjögren’s syndrome (PSS) is a relatively common autoimmune disease affecting approximately 3–4 % of adults (Thomas et al. 1998). It is characterized by chronic inflammation of exocrine glands, specifically the salivary and lacrimal glands, often leading to the dryness of the mouth and eyes. The diagnosis of PSS is based on (1) ocular and oral symptoms; (2) autoantibody testing; (3) objective measures of dry eyes by Schirmer’s test and Rose Bengal testing; (4) objective evidence of salivary gland involvement by unstimulated whole salivary flow, parotid sialography, or salivary scintigraphy; and (5) demonstration of focal lymphocytic infiltration in lip minor salivary gland biopsy (Vitali et al. 2002). The nuclear autoantibodies associated with but not specific for PSS are anti-SSA (formerly known as anti-Ro) and anti-SSB (anti-La). Their occurrence in patients with PSS is 33–74 % and 23–52 %, respectively (Bournia and Vlachoyiannopoulos 2012).