title: Parkinsonism is a late, not rare, feature of CADASIL: a study on Italian patients carrying the R1006C mutation.
abstract: OBJECTIVE
  To describe parkinsonism as a clinical manifestation of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.
  
  
  METHODS
  We report 5 patients carrying the R1006C mutation in the exon 19 of NOTCH3 gene. All cases presented late onset, slowly progressive parkinsonism, not responsive to l-dopa. We performed brain MRI and (123)I-FP-CIT SPECT in all and in 3 additional patients carrying the same mutation but without parkinsonism. Four patients with parkinsonism underwent myocardial (123)I-meta-iodobenzylguanidine scintigraphy.
  
  
  RESULTS
  In all patients, brain MRI showed widespread ischemic lesions in the periventricular white matter, the internal and external capsules, the basal ganglia, and thalami. (123)I-FP-CIT SPECT showed symmetrical or asymmetrical reduction of tracer uptake in the putamen, with inconstant caudate involvement. Myocardial (123)I-meta-iodobenzylguanidine scintigraphy resulted normal. Nigrostriatal denervation was also demonstrated in 2 patients without parkinsonism.
  
  
  CONCLUSIONS
  In cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, parkinsonism may be a not rare, late onset manifestation. The clinical picture, the lack of response to dopaminergic treatment, and MRI findings suggest a vascular parkinsonism, which may be preceded by a protracted presymptomatic phase.
authors: Neurology Division, Mazzoni Hospital, Ascoli Piceno, Italy. Michele.Ragno@sanita.marche.it
authors: Michele
authors: M
authors: Ragno
authors: Alfonso
authors: A
authors: Berbellini
authors: Gabriella
authors: G
authors: Cacchiò
authors: Antonio
authors: A
authors: Manca
authors: Fabio
authors: F
authors: Di Marzio
authors: Luigi
authors: L
authors: Pianese
authors: Anna
authors: A
authors: De Rosa
authors: Serena
authors: S
authors: Silvestri
authors: Maria
authors: M
authors: Scarcella
authors: Giuseppe
authors: G
authors: De Michele
mesh_terms: D000368:Aged; D001921:Brain / Q000473:pathology; D046589:CADASIL / Q000150:complications* / Q000235:genetics / Q000503:physiopathology*; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007558:Italy; D056784:Leukoencephalopathies / Q000235:genetics; D007980:Levodopa / Q000494:pharmacology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009154:Mutation; D020734:Parkinsonian Disorders / Q000150:complications* / Q000235:genetics*; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000235:genetics*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
chemical_list: C499374:NOTCH3 protein, human; D000071656:Receptor, Notch3; D051880:Receptors, Notch; D007980:Levodopa