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Review
. 2024 Apr 18;13(8):2365.
doi: 10.3390/jcm13082365.

Infectious Diseases and Basal Ganglia Calcifications: A Cross-Sectional Study in Patients with Fahr's Disease and Systematic Review

Birgitta M G Snijders  1 , Mike J L Peters  1   2 , Susanne van den Brink  3 , Marijke J C A van Trijp  4 , Pim A de Jong  5 , Laurens A T M Vissers  2 , Frans M Verduyn Lunel  6 , Marielle H Emmelot-Vonk  1 , Huiberdina L Koek  1
Affiliations
Review

Infectious Diseases and Basal Ganglia Calcifications: A Cross-Sectional Study in Patients with Fahr's Disease and Systematic Review

Birgitta M G Snijders et al. J Clin Med. .

Abstract

Background: It is unclear whether patients with basal ganglia calcifications (BGC) should undergo infectious disease testing as part of their diagnostic work-up. We investigated the occurrence of possibly associated infections in patients with BGC diagnosed with Fahr's disease or syndrome and consecutively performed a systematic review of published infectious diseases associated with BGC. Methods: In a cross-sectional study, we evaluated infections in non-immunocompromised patients aged ≥ 18 years with BGC in the Netherlands, who were diagnosed with Fahr's disease or syndrome after an extensive multidisciplinary diagnostic work-up. Pathogens that were assessed included the following: Brucella sp., cytomegalovirus, human herpesvirus type 6/8, human immunodeficiency virus (HIV), Mycobacterium tuberculosis, rubella virus, and Toxoplasma gondii. Next, a systematic review was performed using MEDLINE and Embase (2002-2023). Results: The cross-sectional study included 54 patients (median age 65 years). We did not observe any possible related infections to the BGC in this population. Prior infection with Toxoplasma gondii occurred in 28%, and in 94%, IgG rubella antibodies were present. The positive tests were considered to be incidental findings by the multidisciplinary team since these infections are only associated with BGC when congenitally contracted and all patients presented with adult-onset symptoms. The systematic search yielded 47 articles, including 24 narrative reviews/textbooks and 23 original studies (11 case series, 6 cross-sectional and 4 cohort studies, and 2 systematic reviews). Most studies reported congenital infections associated with BGC (cytomegalovirus, HIV, rubella virus, Zika virus). Only two studies reported acquired pathogens (chronic active Epstein-Barr virus and Mycobacterium tuberculosis). The quality of evidence was low. Conclusions: In our cross-sectional study and systematic review, we found no convincing evidence that acquired infections are causing BGC in adults. Therefore, we argue against routine testing for infections in non-immunocompromised adults with BGC in Western countries.

Keywords: Fahr’s disease; basal ganglia; calcification; infection; primary familial brain calcification; systematic review.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure A1
Figure A1
Flow chart of patients included in cross-sectional study. Abbreviations: UMCU = University Medical Center Utrecht.
Figure A2
Figure A2
Quality assessment of included systematic reviews [33,35].
Figure A3
Figure A3
Quality assessment of included cohort studies [23,27,34,36].
Figure A4
Figure A4
Quality assessment of included cross-sectional studies [18,22,25,29,30,31].
Figure A5
Figure A5
Quality assessment of included case series [14,15,16,17,19,20,21,24,26,28,32].
Figure 1
Figure 1
Flow chart of study selection.
Figure 2
Figure 2
Flow chart for the assessment of infectious diseases in patients with basal ganglia calcifications. Pathogens in grey boxes should always be ruled out. Pathogens in yellow boxes should be ruled out on indication.
See this image and copyright information in PMC

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