BackgroundCocaine use is associated with an increased risk of cerebrovascular accidents. Small vessel pathology has been linked to the risk of stroke in cocaine users, but can be challenging to detect on conventional magnetic resonance (MR) scans. Fluid-attenuated inversion recovery (FLAIR) scans permit better resolution of small vessel lesions.ObjectivesFLAIR scans are currently only acquired based on the subjective judgement of abnormalities on MR scans at face value. We sought to evaluate this practice and the added value of FLAIR scans for patients with cocaine use disorder (CUD), by comparing microbleeds detected by MR and FLAIR scans. We hypothesised that microbleeds are more pronounced in CUD patients, particularly so in participants who had been selected for a FLAIR scan by radiographers.MethodsSixty-four patients with CUD and 60 control participants underwent a brain scan. The MR of 20 CUD patients and 16 control participants showed indicators of cerebral infarction at face value and were followed up by a FLAIR scan. We determined the volume of microbleeds in both MR and FLAIR scans and examined associations with various risk factors.ResultsWhile MR lesion volumes were significantly increased in CUD patients, no significant differences in lesion volume were found in the subgroup of individuals who received a FLAIR.ConclusionThe current practice of subjectively evaluating MR scans as a basis for the follow-up FLAIR scans to detect vascular pathology may miss vulnerable individuals. Hence, FLAIR scans should be included as a routine part of research studies.
The study of consanguineous families has provided novel insights into genetic causes of monogenic parkinsonism. Here, we present a family from the rural Khyber Pakhtunkhwa province, Pakistan, where three siblings were diagnosed with early-onset parkinsonism. Homozygosity mapping of two affected siblings and three unaffected family members identified two candidate autozygous loci segregating with disease, 8q24.12-8q24.13 and 9q31.2-q33.1. Whole-exome sequence analysis identified a single rare homozygous missense sequence variant within this region, CCN3 p.D82G. Although unaffected family members were heterozygous for this putative causal mutation, it was absent in 3,222 non-Parkinson's disease (PD) subjects of Pakistani heritage. Screening of 353 Australian PD cases, including 104 early-onset cases and 57 probands from multi-incident families, also did not identify additional carriers. Overexpression of wild-type and the variant CCN3 constructs in HEK293T cells identified an impaired section of the variant protein, alluding to potential mechanisms for disease. Further, qPCR analysis complemented previous microarray data suggesting mRNA expression of CCN3 was downregulated in unrelated sporadic PD cases when compared to unaffected subjects. These data indicate a role for CCN3 in parkinsonism, both in this family as well as sporadic PD cases; however, the specific mechanisms require further investigation. Additionally, further screening of the rural community where the family resided is warranted to assess the local frequency of the variant. Overall, this study highlights the value of investigating underrepresented and isolated affected families for novel putative parkinsonism genes.
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