Review
CSF diagnostics in psychiatry – present status – future projects

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Abstract

Introduction

In today’s psychiatry only a minority of psychiatry inpatients with severe mental illness (SMI) undergo CSF diagnostics.

Autoimmune encephalitis and mild encephalitis

There is increasing evidence that refined differential diagnosis is advantageous for a subgroup of patients before beginning psychopharmacological treatment. In any clinical case of suspected autoimmune encephalitis or classical encephalitis of any etiology CSF investigation is required. Evidence for the mild encephalitis hypothesis comes from recent CSF studies.

Basics of CSF analysis in psychiatric disorders

Cytology, protein analysis (albumin, IgG, IgA, IgM) and oligoclonal IgG and lactate. Parallel analysis of the CSF with serum samples and calculation of CSF/serum quotients is base for interpretation of immunoglobulin patterns in Reibergrams, data compilation in cumulative CSF data report for the individual patient.

Immune and cytokine findings in SMI

Many markers of immune activation/inflammation have been found. The scenario matches with the known triangle in autoimmune disorders: genes, agents, environment.

Actual CSF studies in severe mental illness

About 79% of therapy resistant cases with affective or schizophrenic spectrum disorders showed low level CSF abnormalities

Conclusion

There is strong support for the view that CSF analysis should be performed in routine differential diagnosis at the onset of SMI more often than presently done in clinical routine in psychiatric hospitals.

Outlook

CSF research will gain increasing relevance for psychiatric research. Preliminary definitions/descriptions of ME or mild neuroinflammation can be found, but no consensus definition is available yet.

Section snippets

Introduction (related to personal communication with Hansotto Reiber)

In the nineties (20th century) Prof. Felgenhauer, then head of the Neurology Department in Göttingen University, gave a lecture in the neighboring Psychiatry department about the potential relevance of CSF analysis in psychiatry. He mourned infrequent indication of CSF lumbar puncture for psychiatric patients. This cooperation in diagnosis and education of assistant doctors was an old agreement from the seventies between the departments of psychiatry (Prof. E. Maier) and neurology (Prof. H.

Autoimmune encephalitis (AE) and mild encephalitis (ME)

There is increasing evidence now that refined differential diagnosis including modern CSF diagnostics is advantageous at least for a subgroup of patients before beginning psychopharmacological treatment. Most relevant herein is the recent discovery of various antineural autoantibodies. Patients in initial stages of autoimmune encephalitis (AE) typically present with exclusive psychiatric syndromes (Dalmau, Lancaster, Martinez-Hernandez, Rosenfeld, & Balice-Gordon, 2011). AE is a treatable

Basics of CSF analysis in psychiatric disorders

Basic CSF analysis includes cytology, protein analysis (albumin, IgG, IgA, IgM) and numbers of complementary parameters of diagnostic relevance like oligoclonal IgG and lactate (Wildemann et al., 2010). The parallel analysis of the CSF with serum samples and calculation of CSF/serum quotients is the base for the evaluation and interpretation of the immunoglobulin patterns in Reibergrams (Reiber & Peter, 2001). These diagrams eventually present disease-related, sometimes typical patterns and are

Actual CSF studies in severe mental illness

In schizophrenia spectrum psychoses, and also in severe depression, number of studies indicated CSF protein increases in subgroup of cases. Over the last decennia we performed several CSF studies and confirmed high prevalence of minor CSF abnormalities in both, in therapy resistant affective and in schizophrenia spectrum groups, which presented: about 20% CSF albumin increase, indicating moderate blood CSF barrier dysfunction; 15% slightly increased CSF cell numbers; 14% intrathecal humoral

Immune and cytokine findings in severe mental illness

The role of infectious agents is difficult to define in the ME scenario but agents likely play a contributive role (Bechter, 2013). Evidence has accumulated for several agents (Houenou et al., 2014, Leypoldt et al., 2013), also inflammatory metabolites may play a role (Bay-Richter et al., 2015). Many markers of immune activation/inflammation have been found (Davis, Moylan, Harvey, Maes, & Berk, 2014; Fillmann, Sinclair, Fung, Webster, & Weickert, 2014; Leboyer, Tamouza, Charron, Faucard, &

Conclusion

The current rapid development in neurology to detect more sensitively limbic encephalitis (LE) or autoimmune encephalitis (AE), is of great relevance for clinical psychiatry, as a number of cases present with exclusive psychiatric syndromes. Overall rare, these psychiatric patients may considerably profit from early immune suppressive or immune modulatory treatment (see redflags in Table 3), which was recommended to perform in neurology departments (Lennox, Coles, & Vincent, 2012). Other cases

Outlook

CSF research probably will gain increasing relevance for psychiatric research in the clinic in the near future and such perspective matches with the long standing experience in neurology, CSF analysis representing a most sensitive and specific method to detect neuroinflammation in the individual patient. Such perspective matches also with new insights into the role of the CSF spaces in physiology and pathophysiology, as the intrathecal spaces represent a compartment of its own with a specific

References (58)

  • H.G. Maxeiner

    Flow cytometric analysis of T cell subsets in paired samples of cerebrospinal fluid and peripheral blood from patients with neurological and psychiatric disorders

    Brain, Behavior, and Immunity

    (2009)
  • H.G. Maxeiner et al.

    Cerebrospinal fluid and serum cytokine profiling to detect immune control of infectious and inflammatory neurological and psychiatric diseases

    Cytokine

    (2014)
  • H. Reiber

    Flow rate of cerebrospinal fluid (CSF)—a concept common to normal blood-CSF barrier function and to dysfunction in neurological diseases

    Journal of the Neurological Sciences

    (1994)
  • H. Reiber et al.

    Antibody patterns vary arbitrarily between cerebrospinal fluid and aqueous humor of the individual multiple sclerosis patient: specificity-independent pathological B cell function

    Journal of Neuroimmunology

    (2015)
  • H. Reiber et al.

    Cerebrospinal fluid analysis—disease-related data patterns and evaluation programs

    Journal of the Neurological Sciences

    (2001)
  • R. Tandon et al.

    Definition and description of schizophrenia in the DSM-5

    Schizophrenia Research

    (2013)
  • J. Arnedo et al.

    Uncovering the hidden risk architecture of the schizophrenias: confirmation in three independent genome-wide association studies

    American Journal of Psychiatry

    (2015)
  • S. Bachmann et al.

    Neurological soft signs in the clinical course of schizophrenia: results of a meta-analysis

    Front Psychiatry

    (2014)
  • K. Baruch et al.

    Aging-induce type I interferon response at the choroid plexus negatively affects brain function

    Science

    (2014)
  • B. Bechter et al.

    Editorial_Quinckes’ pioneering 19th centuries CSF studies may inform 21th centuries research

    NPBR

    (2015)
  • K. Bechter

    Mild encephalitis underlying psychiatrc disorder—a reconsideration and hypothesis exemplified on borna disease

    NPBR

    (2001)
  • K. Bechter et al.

    A case of therapy resistant depression with fatigue—seemingly streptococcal associated autoimmune disorder

    Nervenarzt

    (2007)
  • M. Benros et al.

    Autoimmune diseases and severe infections as risk factors for schizophrenia—a 30-year population-based register study

    American Journal of Psychiatry

    (2011)
  • M.E. Benros et al.

    Autoimmune diseases and infections as risk factors for schizophrenia

    Annals of the New York Academy of Sciences

    (2012)
  • M.E. Benros et al.

    Autoimmune diseases and severe infections as risk factors for mood disorders: a nationwide study

    JAMA Psychiatry

    (2013)
  • S. Bigi et al.

    The growing spectrum of antibody-associated inflammatory brain diseases in children

    Neurology Neuroimmunology & Neuroinflammation

    (2015)
  • D.O. Borroto-Escuela et al.

    The role of transmitter diffusion and flow versus extracellular vesicles in volume transmission in the brain neural–glial networks

    Philosophical Transactions of the Royal Society B

    (2015)
  • P.N. Britton et al.

    Consensus guidelines for the investigation and management of encephalitis in adults and children in Austrialia and New Zealand

    Internal Medicine Journal

    (2015)
  • M.R. Bseikri et al.

    Anti-N-methyl-d-aspartate receptor encephalitis mimics viral encephalitis

    Pediatric Infectious Disease Journal

    (2012)
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