Single photon emission computerized tomography (SPECT) in detecting neurodegeneration in Huntington's disease.

Single photon emission computerized tomography (SPECT) studies were performed on 34 manifest Huntington's disease (HD) patients at various stages of clinical pathology ranging from early chorea to late dystonia with or without signs of dementia and 12 pre-symptomatic patients with abnormal terminal CAG expansions. Thirty HD patients with obvious clinical signs and seven pre-symptomatic patients without signs or symptoms of HD displayed selective caudate hypoperfusion by direct visual inspection. Such qualitative, selective striatal hypoperfusion patterns can be indicative of early and persistent metabolic changes in striatal neuropathology. SPECT studies can be useful in documenting early pre-clinical changes in patients with abnormal terminal CAG expansions and in confirming the presence of caudate pathology in patients with clinical signs of HD.

Too many treatments for Parkinson's disease: how should they be used?

Surgical ablation for Parkinson's disease was abandoned in the 1970s after successful clinical trials of L-DOPA and L-DOPA/decarboxylase inhibitor combinations and early dopamine receptor agonists were added to prolong a viable therapeutic window beyond 5 years. The development of newer agonists with variations in receptor subtype specificity and new enzyme inhibitors with combinations of central and peripheral effects have continued to attract attention as therapeutic alternatives. Treatment options are now coming full circle with a rebirth of stereotactic neurosurgical alternatives to a wide variety of pharmacologic paradigms. The authors propose a rationale for selecting differing treatment options within historical perspective and modern treatment goals using both medical and surgical alternatives.

Extracellular perfusion of rat brain nuclei using microdialysis: a method for studying differential neurotransmitter release in response to neurotoxins.

Microdialysis probes, stereotactically placed in rat brain nuclei, allow detailed kinetic comparisons of neurotransmitter release from in situ chemical lesioning over a continuum from acute early changes (minutes) to chronic late changes (days). This technique insures a localized mechanism of action independent of systemic effects apparent with other routes of administration and independent of mechanical damage patterns encountered in conventional chemical lesioning. The example provided compares changes in extracellular gamma-aminobutyric acid (GABA) concentrations in the striatum in response to quinolinic acid (QA, 0.24 M) and 3-nitropropionic acid (3-NPA, 0.25 M). These examples of chemical lesioning represent two theoretical mechanisms of neurodeterioration in Huntington's disease, QA representing the excitotoxic component, and 3-NPA representing the impaired mitochondrial energy component [M.F. Beal, N.W. Kowall, D.W. Ellison, M.F. Mazurek, K.J. Swartz, J.M. Martin, Replication of the neurochemical characteristics of Huntington's disease by quinolinic acid, Nature 321 (1986) 168-171; M.F. Beal, E. Brouillet, B.G. Jenkins, R.J. Ferrante, N.W. Kowall, J.M. Miller, E. Storey, R. Srivastava, B.R. Rosen, B.T. Hyman, Neurochemical and histologic characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3-nitropropionic acid. J. Neurosci. 13 (1993) 4181-4192; N.C. Reynolds, W. Lin, C.M. Cameron, D.L. Roerig, Differential responses of extracellular GABA to intrastriatal perfusions of 3-nitropropionic acid and quinolinic acid in the rat, Brain Res. 778 (1997) 140-149]. An auxillary microdialysis probe implanted in the ipsilateral nucleus accumbens is used to define the physiologic extent of the cytotoxic lesion. Pre-column derivatization of perfusate fractions with o-phthalaldehyde/t-butylthiol (OPA) provides electroactivity to the OPA-GABA conjugate and facilitates electrochemical detection following high performance liquid chromatography [J.M. Peinado, K.T. McManus, R.B. Myers, Rapid method for microanalysis of endogenous amino acid neurotransmitters in brain perfusates in the rat by isocratic HPLC-EC, J. Neurosci. Methods 18 (1986) 269-276].

Analysis of gait abnormalities in Huntington disease.

OBJECTIVE: To evaluate patterns of successful gait strategy in Huntington disease (HD) at various stages of illness to improve fall avoidance and maintenance of independence. DESIGN: Repeated measurements of gait kinematic parameters and joint performance during gait cycles of six HD patients compared to 30 age-matched controls. SETTING: A standard gait laboratory. SUBJECTS: Six HD patients, rank-ordered for disease severity from minimal chorea to generalized dystonia, selected because they were ambulatory despite 3 to 17 years' disease duration. One patient was from a nursing home (walked with assistance) and five were living independently, either alone or with a working spouse who was the caregiver. MAIN OUTCOME MEASURES: Standardized gait evaluations (retroreflective markers on standard bony landmarks) from five video angles, fed into digitizer to computer-generate joint angles and standard gait kinematic parameters. RESULTS: Wide variability in gait kinematic parameters and joint interaction plots (phase plane and angle-angle plots) was observed between individuals and successive trials of the same limb, tending to increase with disease severity. Joint interaction plots show that random, highly variable distractions from planned trajectories are more apparent distally. CONCLUSIONS: Chorea in HD does not appreciably affect the center of gravity during ambulation, and the consistency of gait profiles at heel strike shows that the ultimate target is achieved in each step despite random and frequent variability during the gait cycle.

Complications of fluid overload in heat casualty prevention during field training.

Several troops evacuated from field training sites as heat casualties were determined to be fluid overload casualties. Common features of this paradoxical syndrome were dilute primary electrolytes with physical exhaustion and muscle weakness after rapid free water intake. A pattern of skipping meals, working in a hot and humid environment, and consuming large volumes of water as "protection against becoming a heat casualty" predisposed these troops to the physical impairment that they intended to avoid. The mechanisms leading to both appropriate and inappropriate physiological responses to free water replacement are discussed as a basis for avoiding this specific heat casualty situation.

Differential responses of extracellular GABA to intrastriatal perfusions of 3-nitropropionic acid and quinolinic acid in the rat.

Although both quinolinic acid and 3-nitropropionic acid destroy medium sized, GABAergic, spiny projection neurons after direct perfusion of neurotoxin into the rat striatum, changes in extracellular GABA concentration in the striatum within the first 90 min reflect different toxic mechanisms in these two animal models for Huntington's disease. Since quinolinic acid acts as a potent excitotoxin, the early depolarizing response in GABAergic neurons results in an early increase in extracellular GABA activity (peak at 40 min) whereas the more indirect action of 3-nitropropionic acid on mitochondrial energy metabolism results in a delayed increase in extracellular GABA activity (peak at 60 min) with a pattern of gradual increase and decline. The localized delivery of cytotoxin provides an opportunity for kinetic comparisons of direct and indirect cytotoxic mechanisms that can be useful in developing neuroprotective treatment strategies in Huntington's disease.

DNA testing and genetic counseling: truth or consequences.

Advances in medical genetics are providing a major clinical challenge to practitioners seeing patients concerned about their risk of developing either inherited disease or susceptibility to acquired disease. Popular information can easily exceed our professional ability to provide services to well-read patients who want answers with scientific certainty. The challenge also involves ethical questions regarding confidentiality and the way that results are disclosed. More often than not, the test itself becomes the focus of psychosocial expectations for the future and lifestyle of the patient and family. The behavioral consequences of disclosure of test results need to be anticipated by the caregiver to avoid adverse psychological outcomes.

Compliance, reliability, and validity of self-monitoring for physical disturbances of Parkinson's disease. The Parkinson's Symptom Diary.

Previous clinical research in Parkinson's disease has recognized the value of self-monitoring procedures in which patients observe and record the frequency and severity of their own symptoms as these occur within the patient's social and work environment. We discuss issues of methodology and report a study of compliance, test-retest reliability, and validity with a new self-monitoring instrument, the Parkinson's Symptom Diary. Two recordings of frequency (loss of balance, hesitation-freezing) and two ratings of severity (tremor, difficulty walking) were made four times daily for one week by patients (N = 73) who were without apparent loss of cognitive or memory functions. A total of 91% of the diaries received (97% of requested) met strict compliance criteria so that independent sampling over days could be assumed. Test-retest stability over one month was demonstrated for each score (all Spearman rho greater than .85) in a representative subsample of 28 patients. Criterion validity was demonstrated for each score by an expected pattern of correlations with independently obtained observer ratings of the same or related indices of disease, and by comparison with Hoehn and Yahr disability stages. By its simplicity, this self-assessment device can be an invaluable complement to traditional methods of clinical and laboratory assessment in the care and evaluation of Parkinson patients.

Alcohol use among college students: responses to raising the purchase age.

On December 1, 1985, New York State raised its alcohol purchase age from 19 to 21. We used a quasi-experimental research design to explore the changes in alcohol use behaviors and attitudes of undergraduates at a large central New York university before and after this legislation was enacted. The overwhelming majority of this undergraduate population is under 21 years old and is thus affected by the new legislation. A comparison of data from the two survey times revealed that 90% of the undergraduates sampled continued to drink at least occasionally. Our analysis of drinking quantity showed a slight moderation in alcohol consumption overall, with the greatest changes occurring for the heaviest drinkers--men and members of Greek organizations. Even with apparent moderation in student drinking, reported negative consequences such as physical injuries were more common. A change in drinking location to less-controlled environments, such as private rooms and unmonitored parties, is offered as one possible explanation.

Serum free levels and evaluation anticonvulsant drug interactions.

In clinical practice, serum level monitoring of anticonvulsant drugs is usually adequate. When there is an alteration in the binding of the anticonvulsant drug to the plasma proteins, however, the relationship between the serum concentration and therapeutic efficacy or toxicity becomes difficult to interpret. This can occur with combinations such as non-steroidal anti-inflammatory drugs (NSAIDs), phenytoin (Dilantin), carbamazepine (Tegretol), and valproic acid (Depakene) or when the albumin level is low. A failure to rely on serum free levels of the anti-convulsant under these circumstances can easily result in poor clinical decisions. The technique of serum free level measurement and illustrative examples of specific cases are provided to document the usefulness of this invaluable laboratory test.

Simultaneous analysis of methionine- and leucine-enkephalin from rat brain: quantification by liquid chromatography-electrochemistry.

This study focuses on the application of liquid chromatography with electrochemical detection (LC-ED) for the analysis of methionine-enkephalin (ME) and leucine-enkephalin (LE) extracted from rat brain regions. The high applied potentials necessary for enkephalin detection required the development of an efficient sample processing protocol. Brain extracts were processed using chromatographic mode sequencing (CMS). The decrease in electroactive interfering substances by CMS improved the chromatographic resolution of ME and LE and the electrode performance. Other qualitative and analytical methods were used to evaluate the enkephalin data obtained by LC-ED for rat brain regions. This study demonstrates that LC-ED provides both the sensitivity and specificity necessary for the analysis of enkephalins from rat brain regions.

Subjective oscillopsia ("jiggling" vision) presumably due to aminoglycoside ototoxicity. A report of two cases.

Following aminoglycoside antibiotic therapy, two patients developed self-limited subjective oscillopsia in the absence of a detectable ocular motility disturbance (nystagmus or opsoclonus). Oscillopsia represents a rare, but highly distressing symptom resulting from disruption of the vestibulo-ocular reflex, producing profound illusory movement of the visual environment. Although the differential diagnosis includes vascular, inflammatory, and structural disorders impacting on either the central or peripheral projections of this brainstem reflex, iatrogenic aminoglycoside ototoxicity was the likely explanation in the two patients presented. Ways of minimizing the risk of aminoglycoside toxicity are briefly reviewed.

Factor analysis of Parkinson's impairment. An evaluation of the final common pathway.

The question of how pathophysiologic mechanisms may combine to yield significant performance impairment in Parkinson's disease was studied by factor analysis of the covariation among behavioral deficits observed during simulated daily living activities. Eighty-four patients with idiopathic Parkinson's disease were videotape-recorded while performing a sequence of nine common tasks of daily living in a standardized format. Acceptable observer reliability was achieved for ten clinical signs that were factor-analyzed to suggest three dimensions of motor performance: ambulation, tremor, and animation. The findings are discussed with respect to traditional concepts of Parkinson's disease and the possible interplay between primary disease mechanisms.