CURRENT SCIENCE REVIEWS By Joe Bruman October 1997 p. 1 of 4 Krauss J et al; Arch Neur 1997;54:1026-1029; In a patient whose levodopa-resistant symptoms presumably arose=20 from peripheral trauma rather than idiopathic PD, unilateral microelectrode-guided pallidotomy induced marked and lasting=20 improvement. Samuel M et al; Brain 1997;120:1301-1313: Studying the effect of pallidotomy on selective impairment of=20 voluntary movement, they did PET scans on 6 off-medication PD=20 patients performing standardized motor tasks, before the=20 surgery and 3-4 months afterward. Improvements in UPDRS score=20 and response time were associated with increased activity in the supplementary motor area and the dorsal prefrontal cortex. Eidelberg D et al; Brain 1997;120:1315-1324: They used PET to study glucose metabolism of the pallidum and=20 thalamus in 42 awake and unmedicated PD patients, before and during pallidotomy, to assess the effect of PD on the pathway relation between the two areas. Soliveri P et al; Brain 1997;120:1325-1337: Learning new motor (tracking) skills is impaired by PD. By testing PD patients both on and off medication, they found that PD affects internal (kinesthetic) guidance more than visual guidance. Cunnington R et al; Brain 1997;120:1339-1353: To clarify whether PD impairment of voluntary movement occurs mainly in preparation or in execution, they recorded movement- related EEG potential in 14 PD patients and 10 healthy controls,=20 while they either performed or imagined standard motor tasks.=20 Later-stage PD patients were impaired more in the preparation or=20 tne termination phase, rather than in the execution phase. Wascher E et al; Brain 1997;120:1355-1375: To distinguish cognitive defects from those of activation in the motor impairment of PD, they measured response force and EEG potentials in 15 PD patients and 15 healthy controls, while performing tests of either timing or recognition. In both cases the PD patients were slower. Krauss J et al; J Neurosurg 1997 Sep,87(3):358-367: They report good and lasting results of microelectrode-guided pallidotomy in 34 out of 36 advanced PD patients, besides some history and details of technique. Optimal location for the lesion (region to be destroyed) is still being refined. The initial=20 lesion size in this series averaged 18 cubic mm (less than a small grape seed). Various methods for creating the lesion: cutting,=20 freezing, radioactive implants, electrical resistance heating,=20 balloons, or injected poison such as alcohol, are now more or less superseded by radiofrequency heating, which permits the best precision and control. Followup MRIs confirmed the value of=20 microelectrode recording to ensure accuracy of lesion placment. Ansorge O et al; Neur 1997 Aug,49(2):610-613: Problems of water excretion and blood pressure adaptation in PD suggest impaired function of the hypothalamus. So they studied (postmortem) neural tissue of the supraoptic nucleus (SON) of the hypothalamus, in PD patients and controls. The expected loss of neurons was associated with enlargement of the remaining ones. CURRENT SCIENCE REVIEWS By Joe Bruman October 1997 p. 2 of 4 Ellis C et al; Neur 1997 Aug,49(2):438-444: By proton magnetic resonance spectroscopy they studied the effect of levodopa on the ratio of n-acetylaspartate to choline in the=20 putamen of 9 levodopa-na=EFve PD patients, 7 advanced PD patients under levodopa treatment, and 11 healthy controls. Compared with controls, the ratio was reduced in the drug-naive group but not=20 in those getting levodopa, suggesting use of the measurement as a reversible marker of striatal dysfunction. Wermuth I et al; Neur 1997 Aug,49(2):426-432: In a statistical survey of 43,709 Faroe Islands residents,=20 they found 82 (0.2%) with confirmed PD, an incidence about 60% higher than a similar group on the mainland. They believe the=20 anomaly may be due to earlier diagnosis but not to earlier onset or longer duration. Grondin R et al; Neur 1997 Aug,49(2):421-426: In tests on induced-PD monkeys they are studying therapeutic potential of the D1 agonist A-86929 and other DA agonists. Adler C et al; Neur 1997 Aug,49(2):393-399: A prospective, randomized, placebo-controlled, double-blind, parallel-group, 6-month study of the nonergoline D2-dopamine=20 agonist ropinirole as monotherapy in 241 early-PD patients=20 showed it to be effective, safe, and well-tolerated. Isacson O, Breakfield X; Nature Medicine 1997 Sep;3(9):964-969: Comprehensive review of benefits/risks in animal-tissue CNS grafts. Detailed analysis of 2 examples: replacement of dopamin- ergic neurons lost in PD, and apoptosis-gene transfer for suppression of brain tumors. Fetal transplants for PD, either human or animal, risk transmitting infection. An impediment to use of human tissue is the need to pre-screen the prospective mother's blood. Pig fetal cells may carry retroviruses (agents that subvert host nucleic DNA) dangerous to humans. The safest prospect is cells cultured and well-screened in the laboratory. Holtzman D, Deshmukh M; Nature Medicine 1997 Sep;3(9):954-955: The role of apoptosis (programmed cell death) in neurodegenerative diseases such as PD is uncertain. But workers find that PCD is mediated by enzymes called caspases. In mice with artifical ALS, a caspase inhibitor slowed progress of the disease. Agid Y et al; Lancet, 6 Sep 97:712: They did an 8-week, open-label, multicenter study on 146 PD=20 patients who were at the stage of motor fluctuations, to compare the COMT inhibitor tolcapone against bromocriptine as adjunctives to levodopa therapy. Tolcapone was better at increasing "on" time, reducing "off" time, and reducing levodopa requirement. More of the bromocriptine subjects required domperidone to manage peripheral dopaminergic adverse effects. Beric A et al; J Neur N'surg Psych 1997;63:159-162: During pallidotomy surgery on 73 PD patients, they measured the stimulus required at an electrode in the globus pallidus to excite limb muscle contraction. The threshold was lower when applied on the dominant side (i.e. left side in right-handed=20 patient). CURRENT SCIENCE REVIEWS by Joe Bruman October 1997 p. 3 of 4 Churchyard A et al; J Neur N'surg Psych 1997;63:228-234 The team that reported signs of shorter lifespan among selegiline recipients has found a new worry about the drug. In 9 of 16 such recipients, tilting the head up to an angle of 45 deg caused severe hypotension, to the point where 2 of them fainted. Reuneveld J et al; J Neur N'surg Psych 1997;63:258: After a third tetanus shot, an otherwise healthy worker developed severe parkinsonism. The syndrome abated dramatically with levodopa therapy, but they don't say if continued maintenance was required. SPECT imaging revealed a pattern similar to that of progressive supranuclear palsy or multiple system atophy. Goto S et al; Neur 1997;49:707-710: After surgery involving general anesthesia, a patient suffered an ischemic/hypoxic stroke, and in the 6 months following recovery developed severe parkinsonism symptoms, which were markedly alleviated by staged bilateral posteroventral pallidotomy. Metman L et al; Neur 1997;49:711-713: A dosage-range trial of levodopa on 25 cases of advanced PD showed similar threshold for relief of parkinson symptoms and onset of dyskinesia, i.e. the therapeutic window was zero. Rather than=20 smaller and more frequent doses, in such cases they suggest that the fuller response and longer duration of bigger doses may be of benefit. Logroscino G et al; Neur 1997;49:714-717: Concentration of iron in the substantia nigra of PD patients has been suspected to produce free radicals and neuron death. But surprisingly, serum concentration of iron and iron-related=20 compounds in 104 patients was lower than in the controls, implying=20 a systemic defect in iron metabolism related to PD. Turjanski N et al; Neur 1997;49:717-723: Suspecting the source of peak-dose levodopa-induced dyskinesia in advanced PD to be in supersensitized striatal D1 and D2 receptors, they did comparative PET studies on treated vs untreated patients, finding no significant difference in receptor binding. Shannon K et al; Neur 1997;49:724-728: Although other dopamine agonists usually require levodopa as an adjunct, a double-blind test of pramipexole alone on 335 early-PD patients for 31 weeks showed it to be safe and effective therapy. Limousin P et al; Ann Neur 1997;42:283-291: By PET mapping of cerebral blood flow during performance of=20 assigned movement tasks, they compared the value of the internal pallidum with that of the sub-thalamic nucleus as sites (6 PD=20 patients each) for deep-brain stimulation, finding the STN to be=20 the more effective. Koller W et al; Ann Neur 1997;42:292-299: Assessing up to a year of unilateral deep-brain stimulation at=20 the ventral intermediate nucleus (VIM) of the thalamus in 29=20 essential tremor patients and 24 PD patients, they found it highly effective for reducing tremor in both groups. (Note: The term "high-frequency" in the title is misleading, it means 120 to 180 Hz, compared with the effective minimum of about 50 Hz.)=20 CURRENT SCIENCE REVIEWS By Joe Bruman October 1997 p. 4 of 4 Durso R et al; Ann Neur 1997;42:300-304: Using tagged samples to measure central metabolism of levodopa in 8 PD patients of varying status, they found no significant correlation of levodopa-related benefit with duration of the=20 disease or with prior levodopa experience. Nutt J et al; Ann Neur 1997;42:349-355: Using tapping speed ability in 18 previously untreated PD patients=20 as an index of long-duration (baseline) response or short-duration (after infusion) response to levodopa, they conclude that both LDR and SDR continue to improve during the first year. They also found a pattern of poorer response in late afternoon or evening.=20 Buee-Scherer V et al; Ann Neur 1997;42:356-359: Three patients who contracted encephalitis during the epidemic of the 1920s at age 8 to 10 developed parkinsonism at age 20 to 30, which responded to levodopa when it became available in the 1970s=20 but persisted until their deaths 60 or so years later. Postmortem analysis of neurofibrillary tangles in all three showed a chemical distinction from those of progressive supranuclear palsy or corticobasal degenerstion. Ghika J, Bogousslavsky J; Arch Neur 1997;54:1104-1108: Survey of 893 patients with parkinsonism of various causes showed that presymptomatic hypertension is a major feature in diagnosis of progressive supranuclear palsy. Jenner P; Arch Neur 1997;54(8)Aug (ad): Attempt to sort out the relative benefits of D1 vs D2 receptor=20 agonists in PD, and the various available examples. They=20 represent two different pathways and components of the motor system. D1 stimulation in some respects is better than D2, but a combination of both (as in pergolide) may be better yet.=20 --=20 J. R. Bruman (818) 789-3694 3527 Cody Road Sherman Oaks, CA 91403-5013