Comment

www.thelancet.com/neurology Vol 12 May 2013 423

and some of less immediate importance, but that are potentially relevant (eg, synuclein-positive neurites in non-dopaminergic areas of the brain or in the periphery).

The cores of the three tiers are quite clearly defi ned, but towards the edge of each tier, the picture becomes more blurred. Thus, there is little reason to suspect that α-synuclein expression in muscle fi bers in inclusion body myositis5 is directly relevant to Parkinson’s disease, although one could argue that the presence of α-synuclein, phosphorylated tau, and amyloid in inclusion body myositis suggests a neuromuscular degeneration spectrum disorder. However fanciful, this point shows one of the shortcomings of the proposed tiers: they do not include degeneration of nigral dopamine neurons and decreased striatal dopamine concentrations, with presenting motor defi cits. Without the core dopamine defi cit, it is not possible to ascertain whether one is facing a forme fruste of Parkinson’s disease, a spectrum disorder, or simply an unrelated disorder that shares one feature. The addition of longitudinal (prospective) studies to the formulation off ered by Berg and colleagues would substantially enhance its usefulness.

One concern with any attempt to chart the path for research on diagnosis of Parkinson’s disease is how to avoid, false-positive (type I) errors, particularly in the present climate of obtaining ever increasing data. Surprisingly, the tiers do not include epidemiological data for environmental factors. As shown by Berg and colleagues, some of the conundrums in defi ning some genetic forms of parkinsonism arise because patients can present with typical Parkinson’s disease symptoms, but Lewy bodies are not found at autopsy. However, numbers of familial cases are often too scarce to assess genetic forms of parkinsonism with certainty; this drawback is particularly true for post-mortem assessments and clinicopathological correlations in these rare forms of parkinsonism.

The proposed pathway towards new research criteria would aims at diagnostic assessment by use of fi ndings in one of the three tiers, independent of assessments in the other two tiers, but does not articulate clearly a way to link data across the tiers.

Research in Alzheimer’s disease has progressed by emphasising concurrent assessments in various domains along the disease process. We now have the technological capability to seamlessly integrate information from various sources for any given patient, and use this

information for clinical management or research purposes. For example, some institutions now routinely bank DNA samples and genotype all patients. These data can then either be placed in the patient’s electronic chart with other laboratory, neuroimaging, and clinical data to guide diagnosis and treatment,6 or can be accumulated as de-identifi ed data for research purposes. These processes can be accomplished within a hospital or shared across institutions for large-scale research endeavors (such as the US National Human Genome Research Institute Electronic Medical Records and Genetics [eMERGE] Network).7 This simultaneous mining of data from the diff erent tiers could greatly improve our ability to recognise informative patterns and defi ne the illness; a task at which James Parkinson was remarkably talented.

Ariel Y DeutchVa nderbilt University Medical Center, Nashville, TN 37232-2050, USAariel.deutch@vanderbilt.edu

I serve on an Eli Lilly advisory board on schizophrenia.

1 Berg D, Lang AE, Postuma RB, et al. Changing the research criteria for the diagnosis of Parkinson’s disease: obstacles and opportunities. Lancet Neurol 2013; published online April 11. http://dx.doi.org/10.1016/S1474-4422(13)70047-4.

2 Stern MB, Lang A, Poewe W. Toward a redefi nition of Parkinson’s disease. Mov Disord 2012; 27: 54–60.

3 Bhidayaisri R and Reichmann H. Diff erent diagnostic criteria for Parkinson’s disease: what are the pitfalls? J Neur Transm 2013; 120: 619–25.

4 Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 1992; 55: 181–84.

5 Askanas V, Engel WK, Alvarez RB, et al. Novel immunolocalization of alpha-synuclein in human muscle of inclusion-body myositis, regenerating and necrotic muscle fi bers, and at neuromuscular junctions. J Neuropathol Exp Neurol 2000; 59: 592–98.

6 Roden DM, Pulley JM, Basford MA, et al. Development of a large-scale de-identifi ed DNA biobank to enable personalized medicine. Clin Pharmacol Ther 2008; 84: 362–69.

7 Manolio TA, Chisholm RL, Ozenberger B, et al. Implementing genomic medicine in the clinic: the future is here. Genet Med 2013; published online Jan 10. DOI:10.1038/gim.2012.157.

CorrectionsMiller TM, Pestronk A, David W, et al. An antisense oligonucleotide against SOD1 delivered intrathecally for patients with SOD1 familial amyotrophic lateral sclerosis: a phase 1, randomised, fi rst-in-man study. Lancet Neurol 2013; published online March 29. http://dx.doi.org/10.1016/S1474-4422(13)70061-9—In this Article a confl ict of interest should have been added: “DS does extensive consulting for pharmaceutical companies including Aptiv Solutions, Agenix, Asubio Pharmaceuticals, Alexion Pharmaceuticals, Cytokinetics, Edison Pharmaceuticals, GlaxoSmith Kline, Merck, NeuroNova, and Pfi zer”. This correction has been made to the online version as of April 17, 2013, and the printed Article is correct.

Moreno-De-Luca A, Myers SM, Challman TD, Moreno-De-Luca D, Evans DW, Ledbetter DH. Developmental brain dysfunction: revival and expansion of old concepts based on new genetic evidence. Lancet Neurol 2013; 12: 406–14—In fi gure 1A of this Personal View, the key should have read 22q11.2. Additionally, in the fi rst sentence of the third paragraph in the “Historical perspetive” section, Arnold Gesell should not have been listed. These corrections have been made to the online version as of April 17, 2013.