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ARTICLES: A. Gregory, S. K. Westaway, I. E. Holm, P. T. Kotzbauer, P. Hogarth, S. Sonek, J. C. Coryell, T. M. Nguyen, N. Nardocci, G. Zorzi, D. Rodriguez, I. Desguerre, E. Bertini, A. Simonati, B. Levinson, C. Dias, C. Barbot, I. Carrilho, M. Santos, I. Malik, J. Gitschier, and S. J. Hayflick Neurodegeneration associated with genetic defects in phospholipase A2 Neurology 2008; 71: 1402-1409 [Abstract] [Full text] [PDF]

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Neurodegeneration associated with genetic defects in phospholipase A2

Menachem Sadeh   (29 January 2009)

Neurodegeneration associated with genetic defects in phospholipase A2 29 January 2009
Menachem Sadeh, Department of Neurology,Tel Aviv University Wolfson Medical Center, Holon 58100, Israel Send Correspondence to journal: Re: Neurodegeneration associated with genetic defects in phospholipase A2 mesadeh{at}post.tau.ac.il Menachem Sadeh	In their interesting article, Gregory et al. describe two main pathological features of infantile neuroaxonal dystrophy (INAD) and idiopathic neurodegeneration with brain iron accumulation (NBIA): axonal spheroids and iron deposits. [1] The authors describe these two elements as unrelated and induced by the defective phospholipase A2. However, I believe that the accumulated iron plays a role in spheroid formation. As the authors note, the association of spheroids and iron accumulation appears in another disease, pantothenate kinase-associated neurodegeneration (PKAN, formerly Hallervorden-Spatz syndrome). [2] Iron-positive macrophages were described in another rare disease, hereditary diffuse leukoencephalopathy with spheroids (HDLS). [3] Moreover, the combination of axonal spheroids and iron deposits is seen in non-metabolic disorders, such as superficial siderosis of the CNS. In this disorder, chronic or intermittent spilling of blood into the subarachnoid space, and spread of heme by the cerebrospinal fluid causes infiltration of iron and ferritin in the cortex associated with abundant axonal spheroids. [4] Spheroids were described in the vicinity of hemosiderin-laden macrophages surrounding arteriovenous malformations, and even in hemorrhagic infarctions. [5] Thus, accumulation of iron alone may induce spheroid formation. The spheroids of the hereditary diseases may differ from those of superficial siderosis of the CNS. However, the strong association of spheroids and iron in hereditary diseases and acquired disorders suggests a causative relation, and perhaps the toxic effect of iron has a role in spheroid formation. References 1. Gregory A, Westaway SK, Holm IE, et al. Neurodegeneration associated with genetic defects in phospholipase A2. Neurology 2008;71:1402-1409. 2. Hayflick SJ. Pantothenate kinase-associated neurodegeneration (formerly Hallervorden-Spatz syndrome). J Neurol Sci 2003;207:106–107. 3. Marotti JD, Tobias S, Fratkin JD, Powers JM, Rhodes CH. Adult onset leukodystrophy with neuroaxonal spheroids and pigmented glia: report of a family, historical perspective, and review of the literature. Acta Neuropathol 2004;107:481–488. 4. Koeppen AH, Barron KD. Superficial siderosis of the central nervous system. A histological, histochemical and chemical study. J Neuropathol Exp Neurol 1971;30:448-469. 5. Sadeh M, Sandbank U: Neuroaxonal dystrophy and hemosiderin in the central nervous system. Ann. Neurol 1980;7:286-287. Disclosure: The author reports no disclosures. Editor’s Note: The authors of the article were offered the opportunity to respond but declined.