Single photon emission computed tomographic blood flow and magnetic resonance volume imaging of basal ganglia in Huntington's disease.

OBJECTIVE To examine basal ganglia dysfunction and atrophy in patients with mild to moderate Huntington's disease, with correlation of imaging measures with clinical and neuropsychological measures. DESIGN Survey study in patients with Huntington's disease and matched controls, with imaging measures being evaluated by investigators unaware of the diagnosis. SETTING Baltimore Huntington's Disease Project, The Johns Hopkins Hospital, Baltimore, Md. PATIENTS AND OTHER PARTICIPANTS Subjects included 10 patients with mild to moderate Huntington's disease and nine healthy age-matched control subjects. MAIN OUTCOME MEASURES Imaging measures included single photon emission computed tomographic regional cerebral blood flow in caudate, putamen, and thalamus, and magnetic resonance imaging measures of caudate and putamen volumes and bicaudate ratios. Patients underwent neurologic and mental status examinations and neuropsychological tests. RESULTS The measure with the greatest difference between patients and control subjects was mean putamen volume, reduced 54.3% in patients, with no overlap between groups (P<.001). Of the cerebral blood flow measures, caudate showed the greatest difference (21.5% decrease; P<.001). Quantitative neurologic indexes of disease severity correlated with both putamen measures (P<.03), while Mini-Mental State Examination scores correlated with caudate volume (P<.02). Bicaudate ratio correlated with both clinical measures and was the best index of neurologic deterioration (r=.95; P<.001), while global atrophy (measured by cerebrospinal fluid percentage) was the best correlate of several neuropsychological tests, such as the Trail Making Test (r=93; P<.001). CONCLUSIONS Volumetric measurement of putamen best discriminated patients with Huntington's disease from healthy subjects. Measures of caudate atrophy or single photon emission computed tomographic measures performed less well. Neurologic decline correlated best with subcortical atrophy measured by the bicaudate ratio, but neuropsychological performance best corresponded to cerebrospinal fluid percentage, a measure of global atrophy.

[1]  H. Nelson.  A Modified Card Sorting Test Sensitive to Frontal Lobe Defects , 1976, Cortex.

[2]  J. Barrio,et al.  Quantifying local cerebral blood flow by N-isopropyl-p-[123I]iodoamphetamine (IMP) tomography. , 1982, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[3]  G. E. Alexander,et al.  Parallel organization of functionally segregated circuits linking basal ganglia and cortex. , 1986, Annual review of neuroscience.

[4]  R. Hichwa,et al.  Normal caudate glucose metabolism in persons at risk for Huntington's disease. , 1987, Archives of neurology.

[5]  H. Herzog,et al.  Cortical and subcortical glucose consumption measured by PET in patients with Huntington's disease. , 1990, Brain : a journal of neurology.

[6]  R. Ferrante,et al.  Neuropathological Classification of Huntington's Disease , 1985, Journal of neuropathology and experimental neurology.

[7]  G. Dobben,et al.  Bicaudate index in computerized tomography of Huntington disease and cerebral atrophy , 1978, Neurology.

[8]  H. Herzog,et al.  Cerebral glucose consumption measured by PET in patients with and without psychiatric symptoms of Huntington's disease , 1989, Psychiatry Research.

[9]  G. Pearlson,et al.  MRI-guided region of interest placement on emission computed tomograms , 1993, Psychiatry Research: Neuroimaging.

[10]  S. Folstein,et al.  Neuropsychological and neuroradiological correlates in Huntington's disease. , 1988, Journal of neurology, neurosurgery, and psychiatry.

[11]  S. Folstein.  Huntington's disease : a disorder of families , 1989 .

[12]  J. Mazziotta,et al.  Reduced cerebral glucose metabolism in asymptomatic subjects at risk for Huntington's disease. , 1987, The New England journal of medicine.

[13]  R. Roos,et al.  Neuronal distribution in the putamen in Huntington's disease. , 1985, Journal of neurology, neurosurgery, and psychiatry.

[14]  R J Leigh,et al.  The measurement of abnormal movement: methods developed for Huntington's disease. , 1983, Neurobehavioral toxicology and teratology.

[15]  Terry L. Jernigan,et al.  Cerebral structure on MRI, part II: Specific changes in Alzheimer's and Huntington's diseases , 1991, Biological Psychiatry.

[16]  I. Shoulson,et al.  Clinical‐pathologic correlation in Huntington's disease , 1989, Neurology.

[17]  R. Reitan.  Validity of the Trail Making Test as an Indicator of Organic Brain Damage , 1958 .

[18]  K. F. Schroeder,et al.  Morphometric studies of the neuropathological changes in choreatic diseases , 1976, Journal of the Neurological Sciences.

[19]  S. Folstein,et al.  Putamen volume reduction on magnetic resonance imaging exceeds caudate changes in mild Huntington's disease , 1992, Annals of neurology.

[20]  R. Hichwa,et al.  Positron emission tomographic scan investigations of Huntington's disease: Cerebral metabolic correlates of cognitive function , 1988, Annals of neurology.

[21]  C. Markham,et al.  Cerebral metabolism and atrophy in huntington's disease determined by 18FDG and computed tomographic scan , 1982, Annals of neurology.

[22]  Arthur L. Benton,et al.  Differential behavioral effects in frontal lobe disease , 1968 .

[23]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[24]  C. Nahmias,et al.  Reduced striatal glucose consumption and prolonged reaction time are early features in Huntington's disease , 1984, Journal of the Neurological Sciences.

[25]  Godfrey D. Pearlson,et al.  User-friendly method for rapid brain and CSF volume calculation using transaxial MRI images , 1991, Psychiatry Research: Neuroimaging.

[26]  G D Pearlson,et al.  Quantitative changes in mesial temporal volume, regional cerebral blood flow, and cognition in Alzheimer's disease. , 1992, Archives of general psychiatry.

[27]  D. Stuss,et al.  The Frontal Lobes , 1986 .

[28]  M. Hayden,et al.  Positron emission tomography in the early diagnosis of Huntington's disease , 1986, Neurology.

[29]  W. Oldendorf,et al.  N-isopropyl-[123I] p-iodoamphetamine: single-pass brain uptake and washout; binding to brain synaptosomes; and localization in dog and monkey brain. , 1980, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[30]  N. Butters,et al.  Computed tomographic, neurologic, and neuropsychological correlates of Huntington's disease. , 1983, The International journal of neuroscience.

[31]  P. Sharp,et al.  Technetium-99m HMPAO imaging in patients with basal ganglia disease. , 1988, The British journal of radiology.

[32]  J. Stroop.  Studies of interference in serial verbal reactions. , 1992 .

[33]  P. Sharp,et al.  Imaging of cerebral blood flow markers in Huntington's disease using single photon emission computed tomography. , 1988, Journal of neurology, neurosurgery, and psychiatry.

[34]  A. Franks.  Function and dysfunction in the basal ganglia , 1990 .

[35]  J. Brandt,et al.  Reduced basal ganglia volume associated with the gene for Huntington's disease in asymptomatic at‐risk persons , 1994, Neurology.

[36]  W. Martin,et al.  Cortical glucose metabolism in Huntington's disease , 1992, Neurology.

[37]  S. Folstein,et al.  The diagnosis of Huntington's disease , 1986, Neurology.

[38]  G Pearlson,et al.  Bicaudate ratio as a measure of caudate volume on MR images. , 1991, AJNR. American journal of neuroradiology.

[39]  M. Hayden,et al.  The combined use of positron emission tomography and DNA polymorphisms for preclinical detection of Huntington's disease , 1987, Neurology.

[40]  G. Pearlson,et al.  Cortical circumferential profile of SPECT cerebral perfusion in Alzheimer's disease , 1991, Psychiatry Research: Neuroimaging.

[41]  O. Paulson,et al.  Reduced regional cerebral blood flow in Huntington's disease studied by SPECT. , 1992, Journal of neurology, neurosurgery, and psychiatry.

[42]  J. Morris,et al.  The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part I. Clinical and neuropsychological assesment of Alzheimer's disease , 1989, Neurology.

[43]  S. Folstein,et al.  Trial of d-α-tocopherol in Huntington's disease , 1995 .

[44]  J. Vonsattel,et al.  Morphometric Demonstration of Atrophic Changes in the Cerebral Cortex, White Matter, and Neostriatum in Huntington's Disease , 1988, Journal of neuropathology and experimental neurology.

[45]  R. Hichwa,et al.  PET scan investigations of Huntington's disease: Cerebral metabolic correlates of neurological features and functional decline , 1986, Annals of neurology.

[46]  G. V. von Schulthess,et al.  Regional quantitative noninvasive assessment of cerebral perfusion and function with N-isopropyl-[123I]p-iodoamphetamine. , 1985, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.