A Review of the 54th Annual Meeting of the American Academy of Neurology
Special Report
Editor’s Note: A number of important and interesting papers in movement disorders were presented at the 54th meeting of the American Academy of Neurology held in Denver, Colo, from April 13-20, 2002. Interested readers can access the full text of these abstracts at www.aan.com.
Medical and surgical treatments of Parkinson’s disease (PD) were a primary focus of the AAN meeting. Hubble and colleagues assessed the effect of a novel adenosine A2A receptor antagonist in patients with PD (S21.001). They demonstrated that treatment with this agent (named KW-6002) reduced the amount of time patients spent in the off state by 1.7 hours, without worsening dyskinesias. In patients with mild PD, Bianchine and colleagues assessed the tolerability of Rotigotine, a new dopamine agonist available as a transdermal patch (S21.002). They showed a dose-dependent improvement in motor performance with minimal adverse events. Two presentations that received significant media attention concerned possible evidence of a neuroprotective effect of 2 new dopamine agonists in PD. Marek (S11.004) presented data from the Parkinson Study Group consortium on the rate of nigrostriatal dopaminergic degeneration after initial treatment with pramipexole or levodopa in the CALM-PD study (recently reported in JAMA. 2000;284:1931-1938). Using serial SPECT imaging of the dopamine transporter, they demonstrated a slower rate of loss of striatal tracer uptake in patients treated with pramipexole (16% at 46-month follow-up) vs. those treated with levodopa (26% at the same time period). In a similar study, Whone and colleagues (S11.006) used fluorodopa PET scanning to measure progression of PD in early patients treated with ropinirole vs. levodopa. Patients treated with ropinirole experienced a 13% decline in fluorodopa uptake over 2 years, whereas patients treated with levodopa lost 20% over the same time. Although methodological questions remain about these 2 studies (for instance whether treatment with agonist or levodopa affects SPECT or PET scanning results), the similarity of these findings suggests the possibility that treatment with agonists in early PD may be neuroprotective.
Several other papers are worthy of mention, including Merino-Andreu (S21.005) studied 56 moderately disabled Parkinson patients with polysomnography and multiple sleep latency testing. One third of their patients were unaware of experiencing daytime sleep episodes that lasted as long as 12 minutes, suggesting that this problem is highly prevalent in Parkinson patients. Ondo and colleagues (P06.016) presented a double-blind, placebo-controlled study of modafinil as a treatment for excessive daytime sleepiness in PD, showing that this agent (recently approved for use in narcolepsy) is safe and effective. Many poster presentations confirmed earlier studies of the success of bilateral subthalamic nucleus stimulation in patients with advanced PD. The expense of the procedure has led some investigators to explore subthalamotomy as an alternative. Su presented data (P01.103) on 8 patients treated with this procedure (both unilateral and bilateral), showing sustained benefit in bradykinesia, tremor, and gait at 18-month follow-up.
Three important papers were presented in the area of transplantation for PD. Watts (S31.004) presented results of 6 patients treated with unilateral stereotaxic implantation of cultured human retinal pigment epithelial cells attached to microcarrier beads, demonstrating moderate improvement in motor performance without significant adverse events. More impressive, Gill (S31.003) presented 5 patients who were treated with continuous infusion of glial derived neurotrophic factor directly into the dorsal putamen. A dramatic improvement in motor deficits (by rating scales and videotapes) was seen, with a reduction in dyskinesias. A placebo-controlled, double-blind study of this technique is planned. Transplant studies should be viewed with caution, as demonstrated by Pillai and colleagues’ PET imaging study of Parkinson patients treated with embryonic dopamine cell transplantation (S31.005). Despite adequate engraftment of the transplant, motor improvements were only observed in patients younger than age 60. So-called "runaway dyskinesias" seen in the placebo-controlled, double-blind surgical trial of embryonic dopamine cell transplantation were also reported in a patient transplanted in another such trial, also occurring in the medication-free off state (P01.116).
Recent advances in hyperkinetic movement disorders were presented as well. Higgins (S36.001) used linkage disequilibrium to refine the location on chromosome 2p23 of a susceptibility locus for autosomal dominant early-onset essential tremor. Verbessem and colleagues reported a negative result of a double-blind, randomized, placebo-controlled trial of oral creatine in 41 patients with Huntington’s disease (S46.004), showing no change in cognitive or motor status. Thomas described the clinical heterogeneity of patients with pantothenate kinase-associated neurodegeneration (S41.001). Patients affected with this autosomal recessive disorder may present in adulthood as well as in childhood, with adults more frequently affected with parkinsonism and children more frequently presenting with dystonia. Three papers summarized recent work on inherited myoclonus-dystonia. Asmus (S07.005) identified 6 novel loss-of-function mutations in the epsilon-sarcoglycan gene, and Ozelius (P05.143) reported further mutations in other families afflicted with this condition. Grimes (S07.004) presented a family with myoclonus-dystonia in which linkage to the epsilon-sarcoglycan gene was excluded: instead linkage to chromosome 18p11 was proposed. Finally, Frucht and colleagues reported their PET scanning study of patients with posthypoxic myoclonus, or Lance-Adams syndrome (S60.001). They demonstrated a highly significant increase in glucose metabolism in cerebellar vermis and ventrolateral thalamus, implying activation of the cerebello-thalamocortical loops in these patients. —Steven Frucht, Assistant Professor of Neurology, Movement Disorders Division, Columbia-Presbyterian Medical Center, Assistant Editor, Neurology Alert.
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