Impulse control disorder in PD: A lateralized monoaminergic frontostriatal disconnection syndrome?

BACKGROUND: Impulse Control Disorder symptoms (ICD) in Parkinson's disease (PD) has been recently associated by magnetic Resonance imaging with impaired cortico-striatal connectivity, especially between left putamen and frontal associative areas. METHODS: 84 patients entered the study (21 PD-ICD+ and 64 PD-ICD-) and underwent DATSCAN imaging. The striatal tracer uptake was evaluated using BRASS software (Hermes, Sweden). The whole-brain analysis was performed with Statistical Parametric Mapping (SPM). RESULTS: PD-ICD+ showed a significant reduction of left putaminal and left inferior frontal gyrus tracer uptake compared to PD-ICD-. Functional covariance analysis using left putamen as the seed point showed that, in contrast to ICD-patients, ICD+ patients had no functional covariance with contralateral basal ganglia and ipsilateral cingulate cortex, as index of an impaired inter- and intra-hemispheric dopamine binding in PD-ICD+. DISCUSSION: the results support and expand the concept of a functional disconnection syndrome linked to ICD symptoms in PD patients through an asymmetric molecular frontostriatal network breakdown with left basal ganglia as central hub.

Disease-modifying therapies in frontotemporal lobar degeneration.

Frontotemporal Lobar Degeneration (FTLD) is characterized by behavioral changes, executive dysfunctions, and language impairment, sustained by different neuropathological patterns. The collective efforts of clinical, pathological and genetic studies have recently opened new insights into the underpinnings of pathological mechanisms of this complex disorder. Different types of inclusions define the new conceptual framework for FTLD classification. Up to now, Tau (FTLDTau-positive), TAR DNA-binding protein (TDP43, FTLD Tau-negative TDP43-positive) have been recognized as the most frequent neuropathological hallmarks of FTLD. In some clinical cases, monogenic forms are identified, mainly due to Microtubule Associated Protein (MAPT) or Granulin (GRN) mutations. No treatments for FTLD are available yet, and off-label medications studies testing potential modifying treatments on the basis of neuropathological positive, inhibitors of Tau kinases or manipulation of Tau-processing haploinsuffciency associated with GRN mutations, has been counteracted into pathological processing of TDP-43 and other key-molecules involved and their consequent translocation from nucleus to cytoplasm, and growing number of potential therapeutic targets. In this continuously new findings on molecular targets and modifying therapies in FTLD.