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The Ravina et al. systematic review of potential neuroprotective agents for PD identified 59 potential neuroprotective compounds. Further detailed review points to 12 currently available compounds with various mechanisms of action that merit exploratory investigation for clinical use with a goal of neuroprotection early in the course of PD.
see page 1234
Neuroprotective agents for clinical trials in Parkinson’s disease
A public policy experiment Commentary by Roger L. Albin, MD
In this issue, Ravina et al. describe a process supported by the National Institute of Neurological Disorders and Stroke (NINDS) to identify candidate compounds for "neuroprotection" trials in PD. This is a particularly difficult task because our notions of pathogenesis remain vague, epidemiologic studies have failed to generate a list of potent risk factors, and preclinical models have uncertain relevance. Because of these limitations, other less scientific factors often have a greater role in the choice of potential treatments than they should. Chief among these other factors are business decisions by pharmaceutical companies that may reflect input from the marketing department more than the research department.FIGURE
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Designing trials to determine whether these agents actually have neuroprotective effects will not be easy. However, even the term "neuroprotection" has been clouded by so many arguments about pathogenesis and mechanisms of action that most clinical trialists prefer more concrete terms such as "course-modifying." Designing a study that can clearly distinguish course-modifying effects from symptomatic effects is particularly difficult. No matter how clever the trial design, clinical measures of impairment and disability may not be adequate for this purpose, raising interest in potential biomarkers to be used as secondary or even surrogate endpoints. Even the most studied of these (e.g., ß-CIT SPECT and fluorodopa PET imaging) have failed to produce unambiguous evidence of neuroprotection in recent studies. Thus, selecting promising agents to study is only the first of many daunting tasks on the road to neuroprotection in PD.
Limb-girdle muscular dystrophy type 2I
Poppe et al. report the phenotype of a common type of limb-girdle muscular dystrophy (LGMD), LGMD2I, due to mutations in the fukutin-related protein gene (FKRP). Age at presentation varies widely and rate of progression may be slow. Cardiomyopathy and respiratory failure (from intercostal and diaphragmatic muscle weakness) are frequent.
see page 1246
In the original Tunisian family assigned the LGMD2I mutation, Driss et al. identified a novel homozygous FKRP mutation and abnormal expression of 
-dystroglycan and laminin-2 in their muscles, confirming that LGMD2I is due to FKRP defects.
see page 1341
The accompanying Editorial by Wicklund and Hilton-Jones considers these two papers and the (thus far) 15 LGMDs: 5 autosomal recessive LGMDs (denoted 1A through 1E); 10 autosomal recessive LGMDs (2A through 2J). The specific gene lesions have been defined for 13 of the 15 mutated proteins and include an enzyme (calpain), membrane signaling and repair (caveolin, dysferlin), sarcolemmal integrity (sarcoglycans), and contractile proteins (e.g., titin). They note that identification of genotype is important since certain LGMDs have a predilection for cardiopulmonary failure (as is the case in the LGMD2I report) and since widely varying treatment strategies will be required for successful gene therapy.
see page 1230
The pathogenesis of tremor in essential tremor and PD
Essential tremor Pagan et al. used MRS to define differences in the cerebellum of essential tremor vs matched normals. The N-acetyl-aspartate to creatine ratio is low.
see page 1344
The accompanying editorial by Rottenberg contrasts the Pagan et al. studies of essential tremor with those published in Neurology 2003;60:601–605 by Doder et al. on Parkinson’s disease tremor. The Pagan et al. work suggests an oscillator in the cerebellum in essential tremor, whereas the studies of PD with PET imaging of 5-HT1A receptors pointed to an abnormality of serotonin-synthesizing neurons in midline raphe neurons being associated both with total and resting PD tremor.
see page 1232
Pregabalin for treatment of postherpetic neuralgia
Dworkin et al. conducted a double-blind trial of pregabalin in 173 patients with postherpetic neuralgia. Within 1 week, pregabalin treatment resulted in significant, clinically important pain relief and improved sleep compared with placebo.FIGURE
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see page 1274
Chromosomal abnormalities in ALS
Meyer et al. studied 85 ALS patients and identified five individuals each with different balanced chromosomal rearrangements. The unexpected frequency of chromosome abnormalities may represent a genomic risk for apparently sporadic ALS.
see page 1348
Outcome of trigeminal nerve section in the treatment of chronic cluster headache
Jarrar et al. followed 17 patients who underwent trigeminal root section for chronic cluster headache. Patients were symptomatic for a mean of 9 years, and, after a mean of 6.7 years follow up, 76% had complete or nearly complete relief. There was relatively little morbidity.
see page 1360
Snoring and chronic daily headache
Scher et al. found chronic daily headache (CDH) strongly associated with frequent snoring episodes. CDH is a risk factor that appears to be independent of the usual risk factors for sleep-disordered breathing.
see page 1366
Carotid dissection related to martial arts
Pary and Rodnitzky describe a patient who suffered a serious stroke due to dissection of the internal carotid artery as a result of participating in the martial art of taekwondo. FIGURE
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see page 1392
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