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. 2020 Jun 16;10(6):375. doi: 10.3390/brainsci10060375

Table 1.

Diagnostic findings approximately 1.5 years after symptom exacerbation. Abbreviation: FDG-PET, [18F] fluorodeoxyglucose positron emission tomography.

Neuropsychiatric examination
  • Severe formal thought disorder and attention, concentration and memory deficits, flattened mood. Strongly reduced energy level and apathy. Abulia, loss of interests, dramatically reduced activity, delusions, severe insomnia, disinhibition. No hallucinations, no suicidal tendencies, normal appetite.

  • Scanning speech, mild dysarthria, at the upper extremity slightly left-emphasized muscle reflexes, patellar tendon reflex with widened reflex zone on both sides. In addition, inconspicuous neurological examination.

Blood analyses
  • Blood cell count, liver/kidney/pancreas values, and C-reactive protein were normal. Calcium levels were intermediately discreetly elevated and normalized themselves in the course of time.

  • Hyponatremia in the prehistory (i.e., 130 mmol/L a half year before; reference range: 136–145 mmol/L), during the clarification as an inpatient the sodium values were normal.

  • Folic acid and Vitamin B12 levels were normal. Selenium (52 µg/L; reference: 75–140 µg/L) and Vitamin D (9.9 ng/mL; optimal: >30 ng/mL) were reduced.

  • Thyroid-stimulating hormone, triiodothyronine, and thyroxine levels were in normal ranges. Autoantibodies against thyroglobulin, TSH receptor and thyroid peroxidase were not detectable.

  • Antibody testing for Lyme borreliosis, syphilis and HIV were negative. Toxoplasmosis IgG antibodies were positive (IgM antibodies and PCR in CSF were negative). The Bartonella henselae and Hepatisis B/C/E serologies were negative. A quantiferon test was also negative.

  • No IgG autoantibodies against the following intracellular onconeural antigens Yo, Hu, CV2/CRMP5, Ri, Ma1/2, SOX1, Tr, Zic4 or the intracellular synaptic antigens GAD65/amphiphysin were found using Ravo line assay®. No IgG autoantibodies against the following intracellular onconeural antigens—amphiphysin, CV2/CRMP5, Ma2/Ta, Ri, Yo, Hu, recoverin, Sox1, Titin, Zic4 and DNER/Tr—were found using the immunoblot method (laboratory Krone, Bad Salzufflen, Germany).

  • In the serum, anti-LGI1 IgG autoantibodies were repeatedly slightly positive (using fixed cell biochip assays from Euroimmun®). A titer of 1:80 (reference <1:20) was discovered using cell-based assays (laboratory Krone, Bad Salzufflen, Germany). RIA showed no increased anti-VGKC autoantibody levels.

  • IgG autoantibodies against other neuronal cell surface antigens (NMDA-R, AMPA-1/2-R, GABAB-R, DPPX, CASPR2) were negative (using fixed cell biochip assays from Euroimmun®). No IgG autoantibodies against different other neuronal cell surface antigens (GAD65, NMDAR, GABAB-R, IgLON5, AMPAR2, DPPX, CASPR2, Glycin-R, mGluR5/1) were found using cell-based assays (laboratory Krone, Bad Salzufflen, Germany). Aquaporin 4 and MOG antibodies were negative.

  • “Tissue-based assay” using indirect immunofluorescence on unfixed murine brain tissue (Prof. Prüss, Berlin) showed an unspecific nuclear pattern of IgG binding.

  • Screening for serum antinuclear antibodies using indirect immunofluorescence on HEp-2000® cells was negative. Anti-neutrophil cytoplasmic, antiphospholipid, and anti-mitochondrial antibodies were negative.

  • Rheumatoid factor was negative. Analyses of the complement system (C3, C4, CH50 and C3d) showed no relevant findings.

  • Traceable evidence of a Bence Jones proteinuria of the Kappa type. The kappa and lambda chains in the serum were negative.

Cerebrospinal fluid analyses (was performed three times after in-patient admission)
  • Normal to slightly increased white blood cell counts (3–5/µL; reference <5/µL).

  • Normal to slightly increased protein concentrations (362–569 mg/L; reference <450 mg/L).

  • Normal to slightly increased age-corrected albumin quotients (6.4–9.5; reference: <8).

  • No CSF specific oligoclonal bands; IgG index not increased. No intrathecal IgG, IgM or IgA synthesis.

  • No IgG autoantibodies against the following intracellular onconeural antigens—amphiphysin, CV2/CRMP5, Ma2/Ta, Ri, Yo, Hu, recoverin, Sox1, Titin, Zic4, DNER/Tr—were found using the immunoblot method (laboratory Krone, Bad Salzufflen, Germany).

  • IgG autoantibodies against neuronal cell surface antigens (NMDA-R, AMPA-1/2-R, GABAB-R, DPPX, LGI1, CASPR2) were negative (using fixed cell biochip assays from Euroimmun®). No IgG autoantibodies against different neuronal cell surface antigens (GAD65, NMDAR, GABAB-R, IgLON5, AMPAR2, DPPX, LGI1, CASPR2, Glycin-R, mGluR5/1) were found using cell-based assays (laboratory Krone, Bad Salzufflen, Germany). RIA showed no increased anti-VGKC antibody levels.

  • “Tissue-based assay” using indirect immunofluorescence on unfixed murine brain tissue (Prof. Prüss, Berlin) showed antibodies against many blood vessels of different sizes, but with relatively low signal.

  • 14-3-3 protein was not increased.

Cerebral magnetic resonance imaging
  • Right-sided FLAIR hyperintensities mesio-temporally and in the amygdala without contrast enhancement.

  • In the left thalamus, a small, possibly microangiopathic lesion was detected.

  • Discrete grey–white matter blurring.

Electroencephalo-graphy
  • Normal alpha-electroencephalography. No slow wave activity. No epileptic activity. No dysrhythmia. Two years ago, after status epilepticus, epileptic activity was reported.

FDG-PET
  • Moderate hypometabolism of the bilateral mesial to medial frontal cortices.

  • No lesions or metabolic changes suspicious of malignancy on whole-body FDG-PET/computer tomography.

Heart examination
  • Inconspicuous resting electrocardiography (but intermittent T-wave changes during clozapine-induced myocarditis).

  • Transthoracic echocardiography showed normal findings (but intermittent left-ventricular hypokinesia during clozapine induced myocarditis). In long-term electrocardiography, continuous normocardial to tachycardial sinus rhythm.

Computer tomography and x-ray thorax
  • Smaller nodulus in the anterior left lower lobe. No evidence of malignant thoraco-abdominal lesions in left diaphragm elevation. Triangularly configured compression in the apicoventral lower lobe primarily non-specifically scarred.

Bronchoscopy
  • Slight acute tracheobronchitis.In the biopsy, signs of chronic bronchitis with submucosal fibrosis and deep hyaline bronchial cartilage as well as only very sparse alveolar parenchyma were detected. No evidence of malignancy. No growth of legionella.

Sonography of the abdomen
  • Small cyst in the liver.

  • On the left, rather large kidney, three cysts.

Electromyography
  • Fasciculations of the legs, which can occur in the context of polyneuropathy, neuromyotonia or also as “benign fasciculations”.

Altered findings are written in bold.