Parkinsonian Syndrome with Frontal Lobe Involvement and Anti-Glycine Receptor Antibodies.

Blood cell count, liver/kidney/pancreas values, and C-reactive protein were normal. Sodium and potassium were normal, calcium levels were borderline high (from 2.54–2.57 mmol/l; reference 2.15–2.5 mmol/l). Normal HbA1c.

Folic acid and Vitamin B12 levels were normal. Selenium (48 µg/l; reference: 75–140 µg/l) and Vitamin D (15 ng/mL; optimal: >30 ng/mL) were reduced.

Thyroid-stimulating hormone, triiodothyronine, and thyroxine levels were in normal ranges. Autoantibodies against and thyroid peroxidase were increased (48.1 IU/mL; reference < 34 IU/mL). Autoantibodies against thyroglobulin and TSH receptor were not increased.

Antibody testing for Lyme borreliosis, syphilis, and HIV were negative. Toxoplasmosis IgG antibodies were positive, for IgM were negative. The Bartonella henselae and Hepatisis B/C/E serologies were negative. A quantiferon test was 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, DNER/Tr, were found using immune blot method (Laboratory Krone, Bad Salzuflen, Germany).

In the serum IgG anti-GlyR autoantibodies with a titer of 1:80 (reference < 1:20) were discovered using cell-based assays (Laboratory Krone, Bad Salzuflen, Germany). IgG autoantibodies against different other neuronal cell surface antigens (NMDA-R, AMPA-1/2-R, GABA_B-R, DPPX, CASPR2, LGI1) were negative (using fixed cell biochip assays from Euroimmun^®). No antibodies against IgLON5 or mGluR5/1 were detected using cell-based assays (Laboratory Krone, Bad Salzuflen, Germany). Aquaporin 4 and MOG antibodies were negative.

“Tissue-based assay” using indirect immunofluorescence on unfixed murine brain tissue (Prof. Prüss, Berlin) showed a perinuclear signal in many neurons, likely reflecting ANAs.

Traceable ANAs. ENA differentiation and testing for ds-DNA antibodies remained negative. ANCAs, antiphospholipid, and AMAs/SMAs were negative. Rheumatoid factor was negative. Analyses of the complement system showed normal findings for C3, C4, and CH50. C3d was slightly increased (9.6 mg/l, reference: < 9 mg/l). Serum IgG and IgA levels normal, IgM was slightly decreased (0.34 g/l; reference 0.7–4.0 g/l).

Normal white blood cell count (1/µL; reference < 5/µL).

Increased protein concentration (563 mg/L; reference < 450 mg/L).

Normal age-corrected albumin quotient: 8 (age-dependent reference < 9.3 × 10⁻³).

No intrahtecal IgG, IgA or IgM synthesis. No CSF specific oligoclonal bands; IgG index not increased (0.53; reference < 0.7).

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®).

IgG antibodies against the GlyR were negative (cell-based assay; Laboratory Krone, Bad-Salzuflen, Germany). No antibodies against IgLON5 or mGluR5/1 were detected using cell-based assays (Laboratory Krone, Bad Salzuflen, Germany). 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 immune blot method (Laboratory Krone, Bad Salzuflen, Germany).

Tau/phospho-Tau levels and ß-amyloid quotient were normal.

“Tissue-based assay” using indirect immunofluorescence on unfixed murine brain tissue (Prof. Prüss, Berlin) showed a perinuclear signal in many neurons, likely reflecting ANAs.

Combined voxel- and region-based morphometry shows decreased gray matter volumes of the medial frontal lobes (z-scores < −2).

On visual analysis the midbrain is atrophic, however the midbrain to pons ratio is with 0.61 in the normal range.

No evidence of myelopathy, no evidence of intraspinal contrast-affine lesions.

Visual assessment: No slow wave activity. No epileptic activity. No dysrhythmia.

Independent component analysis: Alpha at 10.1 Hz, no abnormal activity.

Brain: Moderate bilateral hypometabolism of the frontal lobes, midbrain and, to a lesser extent, caudate nuclei.

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

Severely reduced dopamine transporter availability in both striata, indicating pronounced nigrostriatal degeneration.

The approximated binding potential values were: Caudate nucleus right/left 0.38/0.42 (asymmetry index −10%) and putamen right/left 0.22/0.18 (21%).