Decreased striatal monoaminergic terminals in Huntington disease

Neurology. 2000 May 9;54(9):1753-9. doi: 10.1212/wnl.54.9.1753.


Objective: To evaluate the integrity of the dorsal striatal dopaminergic innervation in rigid and choreic Huntington disease (HD).

Background: Some patients with HD have an akinetic-rigid phenotype. It has been suggested that nigrostriatal in addition to striatal pathology is present in this subgroup. The authors sought to determine whether in vivo measures of striatal vesicular monoamine transporter type-2 (VMAT2) binding could distinguish patients with akinetic-rigid (HDr) from typical choreiform (HDc) HD.

Methods: Nineteen patients with HD (mean age 48 +/- 16 years) and 64 normal controls (mean age 50 +/- 14 years) underwent (+)-alpha-[11C]dihydrotetrabenazine (DTBZ) PET imaging. DTBZ blood to brain ligand transport (K1) and tissue to plasma distribution volume (DV) in the caudate nucleus, anterior putamen, and posterior putamen were normalized to the occipital cortex.

Results: The normalized striatal specific DV was reduced in HDr (n = 6) when compared with controls: caudate nucleus -33% (p < 0.001), anterior putamen -56% (p < 0.0001), and posterior putamen -75% (p < 0.0001). Patients with HDc (n = 13) also had reduced striatal DV: caudate nucleus -6% (NS), anterior putamen -19% (p < 0.01), and posterior putamen -35% (p < 0.0001). Patients with HDr had significantly lower striatal (+)-alpha-[11C]DTBZ binding than HDc patients. After correction for tissue atrophy effects, normalized DV differences were less significant, with values somewhat increased in the caudate, slightly reduced in the anterior putamen, and moderately decreased in the posterior putamen. There were no significant regional differences in K1 reductions among caudate, anterior, and posterior putamen in HD.

Conclusions: Reduced striatal VMAT2 binding suggests nigrostriatal pathology in HD, most severely in the HDr phenotype. Striatal DV reductions were most prominent in the posterior putamen, similar to PD.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Brain Mapping
  • Corpus Striatum / physiopathology*
  • Female
  • Humans
  • Huntington Disease / diagnosis*
  • Huntington Disease / genetics
  • Huntington Disease / physiopathology
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology*
  • Membrane Transport Proteins*
  • Middle Aged
  • Neuropeptides*
  • Neurotransmitter Agents / genetics
  • Neurotransmitter Agents / physiology*
  • Predictive Value of Tests
  • Substantia Nigra / physiopathology
  • Tetrabenazine / analogs & derivatives
  • Tetrabenazine / pharmacokinetics
  • Tomography, Emission-Computed
  • Vesicular Biogenic Amine Transport Proteins
  • Vesicular Monoamine Transport Proteins


  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Neuropeptides
  • Neurotransmitter Agents
  • SLC18A2 protein, human
  • Vesicular Biogenic Amine Transport Proteins
  • Vesicular Monoamine Transport Proteins
  • dihydrotetrabenazine
  • Tetrabenazine