Lori McGee-Minnich

Washington School of Psychiatry, Washington, Washington, D.C., United States

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Publications (14)58.03 Total impact

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    ABSTRACT: Background / Purpose: Selected parts of the putamen are differentially affected depending on the body part manifesting dystonia. We hypothesized that the spatial location of [ 18 F] spiperone binding within the putamen would differ in patients with dystonia limited to the hand versus the face, and we tested that hypothesis using positron emission tomography and magnetic resonance imaging. To minimize statistical and methodological concerns, we chose a straightforward but robust image analysis method, namely, an automated algorithm located the peak [ 18 F] spiperone binding within the striatum, relative to a brain atlas. Main conclusion: The location of peak [ 18 F] spiperone binding within the striatum differed significantly between groups, with the peak more inferior in patients with hand dystonia than in patients with cranial dystonia (cranial dystonia z less than hand dystonia z, p = 0.016). We conclude that in primary focal dystonia, dopamine D 2 -like receptors are distributed differentially in the putamen depending on the body part manifesting dystonia. To the best of our knowledge, this represented the first demonstration of differential receptor distribution within the putamen that corresponded to any localized behavioral sign.
    28th Annual Meeting of the Society for Neuroscience 1998; 03/2013
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    ABSTRACT: Two small case series of platelet mitochondrial complex I activity assays in Huntington's Disease (HD) report discrepant results. We measured platelet complex I and complex I/III activity in 21 subjects with early gene-positive HD and 14 age-matched controls. The 21 participants with HD that we studied are greater than the total of 16 in the two previously published of platelet ETS activity in HD. Reductions > 10% were excluded with 80% confidence. A systemic defect in complex I activity is not present in early HD when striatal neuronal degeneration is already present.
    Neurobiology of Disease 08/2007; 27(1):99-101. · 5.62 Impact Factor
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    ABSTRACT: Activity of complexes II, III, and IV of the mitochondrial electron transport system (ETS) is reduced in postmortem Huntington's disease (HD) striatum, suggesting that reduced cerebral oxidative phosphorylation may be important in the pathogenesis of neuronal death. We investigated mitochondrial oxidative metabolism in vivo in the striatum of 20 participants with early, genetically proven HD and 15 age-matched normal controls by direct measurements of the molar ratio of cerebral oxygen metabolism to cerebral glucose metabolism (CMRO(2)/CMRglc) with positron emission tomography. There was a significant increase in striatal CMRO(2)/CMRglc in HD rather than the decrease characteristic of defects in mitochondrial oxidative metabolism (6.0 +/- 1.6 vs. 5.1 +/- 0.9, P = 0.04). CMRO(2) was not different from controls (126 +/- 37 vs. 134 +/- 31 micromol 100 g(-1) min(-1), P = 0.49), whereas CMRglc was decreased (21.6 +/- 6.1 vs. 26.4 +/- 4.6 micromol 100 g(-1) min(-1), P = 0.01). Striatal volume was decreased as well (13.9 +/- 3.5 vs. 17.6 +/- 2.0 ml, P = 0.001). Increased striatal CMRO(2)/CMRglc with unchanged CMRO(2) is inconsistent with a defect in mitochondrial oxidative phosphorylation due to reduced activity of the mitochondrial ETS. Because HD pathology was already manifest by striatal atrophy, deficient energy production due to a reduced activity of the mitochondrial ETS is not important in the mechanism of neuronal death in early HD. Because glycolytic metabolism is predominantly astrocytic, the selective reduction in striatal CMRglc raises the possibility that astrocyte dysfunction may be involved in the pathogenesis of HD.
    Proceedings of the National Academy of Sciences 03/2007; 104(8):2945-9. · 9.81 Impact Factor
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    ABSTRACT: Parkinson disease (PD) is a late onset disorder with age-dependent penetrance that may confound genetic studies, since affected individuals may not demonstrate clinical manifestations at the time of evaluation. The use of endophenotypes, biologic surrogates for clinical disease diagnoses, may permit more accurate classification of at-risk subjects. Positron emission tomography (PET) measurements of 6-[18F]fluorodopa ([18F]FDOPA) uptake indicate nigrostriatal neuronal integrity and may provide a useful endophenotype for PD linkage studies. We performed [18F]FDOPA PET in 11 members of a large, multi-incident Amish family with PD, 24 normals and 48 people with clinically definite idiopathic PD (PD controls). Clinical diagnoses in the Amish were clinically definite PD in four, clinically probable in one, clinically possible in five, and normal in one. Abnormal [18F]FDOPA posterior putamen uptake was defined as less than 3 standard deviations below the normal mean. The criteria were applied to the Amish sample to determine a PET endophenotype for each. We performed genetic simulations using SLINK to model the effect phenoconversion with the PET endophenotype had on logarithm of odds (LOD) scores. PET endophenotype confirmed the status of two clinically definite subjects. Two clinically definite Amish PD subjects had normal PETs. Two possible PD were converted to "PET definite PD." The remainder had normal PETs. The average maximum LOD score with the pre-PET was 6.14 +/- 0.84. Simulating phenoconversion of subjects with unknown phenotypes increased the LOD score to 7.36 +/- 1.23. The [18F]FDOPA PET endophenotype permits phenoconversion in multi-incident PD families and may increase LOD score accuracy and power of an informative pedigree.
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 05/2006; 141B(3):245-9. · 3.23 Impact Factor
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    ABSTRACT: Manganese exposure reportedly causes a clinically and pathophysiologically distinct syndrome from idiopathic Parkinson's disease (PD). We describe the clinical features and results of positron emission tomography with 6-[18F]fluorodopa ([18F]FDOPA PET) of a patient with parkinsonism occurring in the setting of elevated blood manganese. The patient developed parkinsonism associated with elevated serum manganese from hepatic dysfunction. [18F]FDOPA PET demonstrated relatively symmetric and severely reduced [18F]FDOPA levels in the posterior putamen compared to controls. The globus pallidum interna had increased signal on T1-weighted magnetic resonance imaging (MRI) images. We conclude that elevated manganese exposure may be associated with reduced striatal [18F]FDOPA uptake, and MRI may reveal selective abnormality within the internal segment of the pallidum. This case suggests that the clinical and pathophysiological features of manganese-associated parkinsonism may overlap with that of PD.
    Movement Disorders 05/2005; 20(4):492-6. · 4.56 Impact Factor
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    ABSTRACT: We sought to determine the effect of deep brain stimulation (DBS) frequency on tremor suppression in essential tremor (ET) patients with deep brain stimulators implanted in the ventral intermediate nucleus (VIM) of the thalamus. A uniaxial accelerometer was used to measure tremor in the right upper extremity of subjects with a diagnosis of ET who had DBS electrodes implanted in the left VIM. The root-mean-square acceleration was used as the index of tremor magnitude and normalized to the OFF DBS condition. There was a highly significant inverse sigmoidal relationship between stimulation frequency and normalized tremor acceleration (X(2)/DoF = 0.42, r(2) = 0.997). Tremor acceleration had a nearly linear response to stimulation frequencies between 45 and 100 Hz with little additional benefit above 100 Hz. These findings have two important implications. Clinically, frequency of thalamic stimulation is an important variable for optimal tremor control with maximal benefit achieved with 100 to 130 Hz in most patients. Second, thalamic DBS provides tremor benefit in a graded manner and is not an all-or-nothing phenomenon.
    Movement Disorders 11/2004; 19(10):1163-8. · 4.56 Impact Factor
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    ABSTRACT: To assess whether subthalamic nuclei (STN) stimulation's primary mechanism of action is to drive or inhibit output neurons. Cerebral blood flow responses to STN stimulation were measured using PET in 13 patients with Parkinson disease. Patients were scanned with stimulators off and on (six scans each condition). Clinical ratings, EMG, and videotaping of movements were obtained at each scan. Scans with observable tremor or movement were eliminated from analysis. Brain regions where STN stimulation significantly altered blood flow were identified. STN stimulation increased blood flow in midbrain (including STN), globus pallidus, and thalamus, primarily on the left side, but reduced blood flow bilaterally in frontal, parietal, and temporal cortex. These data suggest that STN stimulation increases firing of STN output neurons, which increases inhibition of thalamocortical projections, ultimately decreasing blood flow in cortical targets. STN stimulation appears to drive, rather than inhibit, STN output neurons.
    Neurology 10/2003; 61(6):816-21. · 8.30 Impact Factor
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    ABSTRACT: Degeneration of nigrostriatal neurons and subsequent striatal dopamine deficiency produce many of the symptoms of Parkinson disease (PD). Initially restoration of striatal dopamine with oral levodopa provides substantial benefit, but with long term treatment and disease progression, levodopa can elicit additional clinical symptoms, reflecting altered effects of levodopa in the brain. The authors examined whether long term treatment affects the brain's response to levodopa in the absence of these altered clinical responses to levodopa. Positron emission tomography (PET) measurements were used of brain-blood flow before and after an acute dose of levodopa in three groups: PD patients treated long term with levodopa without levodopa induced dyskinesias, levodopa naive PD patients, and controls. It was found that the PD group treated long term responded to acute levodopa differently from controls in left sensorimotor and left ventrolateral prefrontal cortex. In both regions, the treated PD group had decreased blood flow whereas the control group had increased blood flow in response to levodopa. Levodopa naive PD patients had little or no response to levodopa in these regions. Within the treated PD group, severity of parkinsonism correlated with the degree of abnormality of the sensorimotor cortex response, but not with the prefrontal response. It is concluded that long term levodopa treatment and disease severity affect the physiology of dopaminergic pathways, producing altered responses to levodopa in brain regions associated with motor function.
    Journal of Neurology Neurosurgery & Psychiatry 08/2003; 74(7):844-51. · 4.92 Impact Factor
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    ABSTRACT: To determine whether welding-related parkinsonism differs from idiopathic PD. Welding is considered a cause of parkinsonism, but little information is available about the clinical features exhibited by patients or whether this is a distinct disorder. The authors performed a case-control study that compared the clinical features of 15 career welders, who were ascertained through an academic movement disorders center and compared to two control groups with idiopathic PD. One control group was ascertained sequentially to compare the frequency of clinical features, and the second control group was sex- and age-matched to compare the frequency of motor fluctuations. Welders were exposed to a mean of 47,144 welding hours. Welders had a younger age at onset (46 years) of PD compared with sequentially ascertained controls (63 years; p < 0.0001). There was no difference in frequency of tremor, bradykinesia, rigidity, asymmetric onset, postural instability, family history, clinical depression, dementia, or drug-induced psychosis between the welders and the two control groups. All treated welders responded to levodopa. Motor fluctuations and dyskinesias occurred at a similar frequency in welders and the two control groups. PET with 6-[18F]fluorodopa obtained in two of the welders showed findings typical of idiopathic PD, with greatest loss in posterior putamen. Parkinsonism in welders is distinguished clinically only by age at onset, suggesting welding may be a risk factor for PD. These preliminary data cannot exclude a genetic contribution to susceptibility in these exposed individuals.
    Neurology 01/2001; 56(1):8-13. · 8.30 Impact Factor
  • Advances in neurology 02/1998; 78:161-8.
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    ABSTRACT: In this study we have investigated the pathophysiology of two idiopathic focal dystonias: hand cramp with excessive cocontractions of agonist and antagonist hand or forearm muscles during specific tasks, such as writing, and facial dystonia manifested by involuntary eyelid spasms (blepharospasm) and lower facial and jaw spasms (oromandibular dystonia). We used positron emission tomography (PET) to measure the in vivo binding of the dopaminergic radioligand [18F]spiperone in putamen in 21 patients with these two focal dystonias and compared the findings with those from 13 normals. We measured regional cerebral blood flow and blood volume in each subject as well as the radiolabeled metabolites of [18F]spiperone in arterial blood. A stereotactic method of localization, independent of the appearance of the images, was used to identify the putamen in all of the PET images. We analyzed the PET and arterial blood data with a validated nonsteady-state tracer kinetic model representing the in vivo behavior of the radioligand. An index of binding called the combined forward rate constant was decreased by 29% in dystonics, as compared with normals (p < 0.05). There were no significant differences between dystonics and normals in regional blood flow, blood volume, nonspecific binding, permeability-surface area product of [18F]spiperone or the dissociation rate constant. These findings are consistent with a decrease of dopamine D2-like binding in putamen and are the first demonstration of a receptor abnormality in idiopathic dystonia. These results have important implications for the pathophysiology of dystonia as well as for function of the basal ganglia.
    Journal of Neuroscience 01/1997; 17(2):843-50. · 6.91 Impact Factor
  • Abstracts of the Society for Neuroscience. 01/1996; 22(Part 1):224.
  • Abstracts of the Society for Neuroscience. 01/1995; 21(Part 2):1429.
  • B A Racette, L McGee-Minnich, J S Perlmutter
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    ABSTRACT: We investigated the efficacy and safety of botulinum toxin A (BTX) manufactured from a new bulk strain for the treatment of cervical dystonia. This was a single-blinded retrospective comparison of length of benefit, subjective improvement, and complications of treatment in 50 patients treated with the old form of toxin designated 79-11 and the new toxin strain BCB2024. The mean duration of benefit of the 79-11 strain and the BCB2024 strain were the same. Subjective efficacy, measured on a -4 to +4 scale, demonstrated no difference between the two strains. Dysphagia occurred in 12% of patients injected with the 79-11 strain and 14% of subjects injected with the BCB2024 strain. We also used a clinician's global assessment that incorporated the duration of benefit, subjective efficacy, and complications as a secondary analysis. There was no significant difference between the two forms of botulinum toxin A according to this scale. We conclude that the 79-11 strain and the BCB2024 strain offer similar peak efficacy duration of benefit, and adverse events.
    Clinical Neuropharmacology 22(6):337-9. · 1.82 Impact Factor

Publication Stats

589 Citations
58.03 Total Impact Points

Institutions

  • 2003–2013
    • Washington School of Psychiatry
      Washington, Washington, D.C., United States
  • 2004–2007
    • Washington University in St. Louis
      • Department of Neurology
      San Luis, Missouri, United States
  • 2001–2007
    • University of Washington Seattle
      • • Department of Neurology
      • • Department of Neurological Surgery
      Seattle, WA, United States