title: Reduced Number of Pigmented Neurons in the Substantia Nigra of Dystonia Patients? Findings from Extensive Neuropathologic, Immunohistochemistry, and Quantitative Analyses.
abstract: BACKGROUND
  Dystonias (Dys) represent the third most common movement disorder after essential tremor (ET) and Parkinson's disease (PD). While some pathogenetic mechanisms and genetic causes of Dys have been identified, little is known about their neuropathologic features. Previous neuropathologic studies have reported generically defined neuronal loss in various cerebral regions of Dys brains, mostly in the basal ganglia (BG), and specifically in the substantia nigra (SN). Enlarged pigmented neurons in the SN of Dys patients with and without specific genetic mutations (e.g., GAG deletions in DYT1 dystonia) have also been described. Whether or not Dys brains are associated with decreased numbers or other morphometric changes of specific neuronal types is unknown and has never been addressed with quantitative methodologies.
  
  
  METHODS
  Quantitative immunohistochemistry protocols were used to estimate neuronal counts and volumes of nigral pigmented neurons in 13 SN of Dys patients and 13 SN of age-matched control subjects (C).
  
  
  RESULTS
  We observed a significant reduction (∼20%) of pigmented neurons in the SN of Dys compared to C (p<0.01). Neither significant volumetric changes nor evident neurodegenerative signs were observed in the remaining pool of nigral pigmented neurons in Dys brains. These novel quantitative findings were confirmed after exclusion of possible co-occurring SN pathologies including Lewy pathology, tau-neurofibrillary tangles, β-amyloid deposits, ubiquitin (ubiq), and phosphorylated-TAR DNA-binding protein 43 (pTDP43)-positive inclusions.
  
  
  CONCLUSIONS
  A reduced number of nigral pigmented neurons in the absence of evident neurodegenerative signs in Dys brains could indicate previously unconsidered pathogenetic mechanisms of Dys such as neurodevelopmental defects in the SN.
authors.affiliation: Neuropathology Research, Biomedical Research Institute of New Jersey, BRInj, Cedar Knolls, NJ, USA ; Movement Disorders Program, Atlantic Neuroscience Institute, Overlook Medical Center, Summit, NJ, USA ; Department of Neurology, Icahn School of Medicine at Mount Sinai, Mount Sinai Hospital, New York City, NY, USA.
authors.forename: Diego
authors.initials: D
authors.lastname: Iacono
authors.affiliation: Neuropathology Research, Biomedical Research Institute of New Jersey, BRInj, Cedar Knolls, NJ, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Geraci-Erck
authors.affiliation: Neuropathology Research, Biomedical Research Institute of New Jersey, BRInj, Cedar Knolls, NJ, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Peng
authors.affiliation: Movement Disorders Program, Atlantic Neuroscience Institute, Overlook Medical Center, Summit, NJ, USA.
authors.forename: Marcie L
authors.initials: ML
authors.lastname: Rabin
authors.affiliation: Movement Disorders Program, Atlantic Neuroscience Institute, Overlook Medical Center, Summit, NJ, USA ; Department of Neurology, Icahn School of Medicine at Mount Sinai, Mount Sinai Hospital, New York City, NY, USA.
authors.forename: Roger
authors.initials: R
authors.lastname: Kurlan
keywords: Substantia nigra; neurodegenerative disorder; neurodevelopmental disorder; neuronal loss; neuronal reduction; pigmented neurons