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ALBIN RL, YOUNG AB, PENNEY JB: The functional anatomy of basal ganglia disorders Trends Neurosci 12:366, 1989 ALEXANDER GE, CRUTCHER MD: Functional architecture of basal ganglia circuits: Neural substrates of parallel processing Trends Neurosci 13: 266, 1990 BHATIA KP, MARSDEN CD: The behavioral and motor consequence of focal lesions of the basal ganglia in man Brain 117:859, 1994 BREEDVELD GJ, PERCY AK, MACDONALD ME, et al: Clinical and genetic heterogeniety in benign hereditary chorea Neurology 59:579, 2002 BROOKS VB: The Neural Basis of Motor Control New York, Oxford University Press, 1986 CARPENTER MB: Brainstem and infratentorial neuraxis in experimental dyskinesia Arch Neurol 5:504, 1961 CARPENTER MB: Anatomy of the corpus striatum and brainstem integrating systems, in Brooks VB (ed): Handbook of Physiology Sec 1: The Nervous System Vol 2: Motor Control, part 2 Bethesda, MD, American Physiological Society, 1981, pp 947 995 CARPENTER MB, WHITTIER JR, METTLER FA: Analysis of choreoid hyperkinesia in the rhesus monkey: Surgical and pharmacological analysis of hyperkinesia resulting from lesions of the subthalamic nucleus of Luys J Comp Neurol 92:293, 1950 CHUANG C, FAHN, SRUCHT SJ: The natural history and treatment of acquired hemidystonia: report of 33 cases and review of the literature J Neurol Neurosurg Psychiatry 72:59, 2002 CHURCH AJ, CARDOSO F, DALE RC, et al: Anti-basal ganglia antibodies in acute and persistent Sydenham chorea Neurology 59:227, 2002 COOPER IS: Involuntary Movement Disorders New York, Hoeber-Harper, 1969 DELONG MR: Primate models of movement disorders of basal ganglia origin Trends Neurosci 13:281, 1990 DEMIRKIRIAN M, JANKOVIC J: Paroxysmal dyskinesias: Clinical features and classi cation Ann Neurol 38:571, 1995 DENNY-BROWN D, YANAGISAWA N: The role of the basal ganglia in the initiation of movement, in Yahr MD (ed): The Basal Ganglia New York, Raven Press, 1976, pp 115 148 DOBYNS WB, OZELIUS LJ, KRAMER PL, et al: Rapid-onset dystoniaparkinsonism Neurology 43:2596, 1993 DOOLING EC, ADAMS RD: The pathological anatomy of post-hemiplegic athetosis Brain 98:29, 1975 EMERY SE, VIECO PT: Sydenham chorea: Magnetic resonance imaging reveals permanent basal ganglia injury Neurology 48:531, 1997 FAHN S: High-dosage anticholinergic therapy in dystonia Neurology 33: 1255, 1985 GOMBART L, SOARES J, ALEXANDER GE: Functional anatomy of the basal ganglia and motor systems, in Watts RL, Koller WC (eds): Movement Disorders, 2nd ed New York, McGraw-Hill, 2004, pp 87 100 GREENGARD P: The neurobiology of slow synaptic transmission Science 294:1024, 2001 HALLETT M: Clinical neurophysiology of akinesia Rev Neurol 146:585, 1990 HALLETT M, KHOSHBIN S: A physiological mechanism of bradykinesia Brain 103:301, 1980 HUDGINS RL, CORBIN KB: An uncommon seizure disorder: Familial paroxysmal choreoathetosis Brain 91:199, 1968 JANKOVIC J, TOLOSA ES (eds): Parkinson s Disease and Movement Disorders, 3rd ed Baltimore, Lippincott, Williams & Wilkins, 1998 JENNER P: Pharmacology of dopamine agonists in the treatment of Parkinson s disease Neurology 58:S1-S8, 2002 KRAUSS JK, MUNDINGER F: Functional stereotactic surgery for hemiballism J Neurosurg 58:278, 1996 KURLAN R, SHOULSON I: Familial paroxysmal dystonic choreoathetosis and response to alternate-day oxazepam therapy Ann Neurol 13:456, 1983 LANCE JW: Familial paroxysmal dystonic choreoathetosis and its differentiation from related syndromes Ann Neurol 2:285, 1977 LANG EA, LOZANO AM: Parkinson s disease: Second of two parts N Engl J Med 339:1130, 1998 MARSDEN CD, OBESO JA: The functions of the basal ganglia and the paradox of stereotaxic surgery in Parkinson s disease Brain 117:877, 1994 MARSDEN CD, LANG AE, QUINN NP, et al: Familial dystonia and visual failure with striatal CT lucencies J Neurol Neurosurg Psychiatry 49: 500, 1986 MARTIN JP: Papers on Hemiballismus and the Basal Ganglia London, National Hospital Centenary, 1960 MARTIN JP: The Basal Ganglia and Posture Philadelphia, Lippincott, 1967 MITCHELL IJ, BOYCE S, SAMBROOK MA, et al: A 2-deoxyglucose study of the effects of dopamine agonists on the parkinsonian primate brain Brain 115:809, 1992 MOUNT LA, REBACK S: Familial paroxysmal choreoathetosis: Preliminary report on a hitherto undescribed clinical syndrome Arch Neurol Psychiatry 44:841, 1940 NOVOTNY EJ JR, DORFMAN LN, LOUIS A, et al: A neurodegenerative disorder with generalized dystonia: A new mitochondriopathy Neurology 35(suppl 1):273, 1985 NYGAARD TG, TRUGMAN JM, YEBENES JG: Dopa-responsive dystonia: The spectrum of clinical manifestations in a large North American family Neurology 40:66, 1990 PENNEY JB, YOUNG AB: Biochemical and functional organization of the basal ganglia, in Jankovic J, Tolosa ES (eds): Parkinson s Disease and Movement Disorders, 3rd ed Baltimore, Lippincott, Williams & Wilkins, 1998, pp 1 13 PICCOLO I, STERZI R, THIELLA G, et al: Sporadic choreas: Analysis of a general hospital series Eur Neurol 41:143, 1999 PLANT GT, WILLIAMS AC, EARL CJ, MARSDEN CD: Familial paroxysmal dystonia induced by exercise J Neurol Neurosurg Psychiatry 47:275, 1984 RAO J: Functional neurochemistry of the basal ganglia, in Watts RL, Koller WC: Movement Disorders, 2nd ed New York, McGraw-Hill, 2004, pp 113 130.

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ronal death is likely to be more complex than is currently envisioned However, the extent of neural tissue dysfunction is not dictated solely by the activation of these mechanisms in neurons It is now clear that highly toxic in uences are exerted on oligodendroglial cells in white matter during ischemia Moreover, the injury to both neurons and oligodendroglial cells is augmented in brain tissues by an in ammatory response to the initial injury, activating endothelial cells to express cell adhesion molecules that can attract additional in ammatory cells and upregulating levels of in ammatory proteases (eg, metalloproteases) and cytokines (eg interleukins and chemokines) These events are summarized in the review by Lo and coworkers It is evident that these events are highly complex, invoking multiple parallel molecular phenomena The salient feature of these molecular pathways is that they provide points for potential therapeutic interventions As one example, it is clear that as ATP production fails and energy gradients are depleted, there is signi cant accumulation of lactic acid in cerebral tissue, and all the biochemical changes consequent to the cellular acidosis occur These may also be of importance in determining the extent of cell damage (see reviews of Raichle and of Plum) Myers and Yamaguchi showed that monkeys infused with glucose before the induction of cardiac arrest suffered more brain damage than did either fasted or salineinfused animals They suggested that the high cerebral glucose level under anaerobic conditions led to increased glycolysis during the ischemic episode and that the accumulated lactate was neurotoxic On the basis of such observations, Plum has suggested that scrupulous control of the blood glucose might reduce the risk of cerebral infarction in diabetic and other stroke-prone patients and during conditions of potential hyperglycemia Clinical implementation of this idea is dif cult and its advantages remain to be established Regarding anoxic damage of the brain, Ames and Nesbett have studied the rabbit retina in an immersion chamber in which O2 and various substrates could be altered directly rather than through the vasculature They found that cells could withstand complete absence of O2 for 20 min After 30 min of anoxia, there was irreversible damage, re ected by an inability of the tissue to utilize glucose and to synthesize protein Hypoglycemia further reduced the tolerance to hypoxia, whereas the tolerance could be prolonged by reducing the energy requirements of cells (increasing magnesium in the medium) Ames postulated that the long period of tolerance of retinal neurons to complete anoxia in vitro, in comparison to that in vivo, is related to what he called the no-re ow phenomenon (swelling of capillary endothelial cells, which prevents the restoration of circulation), as mentioned earlier Body temperature is yet another important factor in determining the extent of infarction A reduction of even 2 to 3 C (36 to 54 F) reduces the metabolic requirements of neurons and increases their tolerance to hypoxia by 25 to 30 percent These biochemical, cellular, and CBF ndings enable one to conceptualize maneuvers for restoring blood ow within the marginally hypoperfused zone and salvaging brain tissue, particularly since under conditions of partial ischemia, cerebral tissue may survive for periods of 5 to 6 h or even longer.

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