olivopontocerebellar atrophies

Summary

Summary: A group of inherited and sporadic disorders which share progressive ataxia in combination with atrophy of the CEREBELLUM; PONS; and inferior olivary nuclei. Additional clinical features may include MUSCLE RIGIDITY; NYSTAGMUS, PATHOLOGIC; RETINAL DEGENERATION; MUSCLE SPASTICITY; DEMENTIA; URINARY INCONTINENCE; and OPHTHALMOPLEGIA. The familial form has an earlier onset (second decade) and may feature spinal cord atrophy. The sporadic form tends to present in the fifth or sixth decade, and is considered a clinical subtype of MULTIPLE SYSTEM ATROPHY. (From Adams et al., Principles of Neurology, 6th ed, p1085)

Top Publications

  1. Kasher P, Namavar Y, van Tijn P, Fluiter K, Sizarov A, Kamermans M, et al. Impairment of the tRNA-splicing endonuclease subunit 54 (tsen54) gene causes neurological abnormalities and larval death in zebrafish models of pontocerebellar hypoplasia. Hum Mol Genet. 2011;20:1574-84 pubmed publisher
    ..Also we suggest that a common disease pathway may exist between TSEN54- and RARS2-related PCH, which may involve a tRNA processing-related mechanism...
  2. Jacob F, Hasal S, Goez H. Pontocerebellar hypoplasia type 3 with severe vitamin A deficiency. Pediatr Neurol. 2011;44:147-9 pubmed publisher
    ..This case emphasizes the significance of vitamin A in the proper formation of the hindbrain. The authors conclude that vitamin A screening should be considered in maternal and newborn metabolic screening...
  3. Namavar Y, Barth P, Kasher P, van Ruissen F, Brockmann K, Bernert G, et al. Clinical, neuroradiological and genetic findings in pontocerebellar hypoplasia. Brain. 2011;134:143-56 pubmed publisher
    ..In addition, we present ten new mutations in TSEN54, TSEN2 and RARS2. Furthermore, we show that pontocerebellar hypoplasia type 1 together with elevated cerebrospinal fluid lactate may be caused by RARS2 mutations...
  4. Grosso S, Mostadini R, Cioni M, Galluzzi P, Morgese G, Balestri P. Pontocerebellar hypoplasia type 2: further clinical characterization and evidence of positive response of dyskinesia to levodopa. J Neurol. 2002;249:596-600 pubmed
    ..Finally, we report a dramatic positive response of the patient with dyskinesia/dystonia to levodopa treatment, and discuss the associated physiopathological implications...
  5. Barth P, Aronica E, de Vries L, Nikkels P, Scheper W, Hoozemans J, et al. Pontocerebellar hypoplasia type 2: a neuropathological update. Acta Neuropathol. 2007;114:373-86 pubmed
    ..Immunohistochemical evaluation of the endoplasmic reticulum stress response is negative. We conclude that the neuropathological findings in PCH-2 are sufficiently specific to enable an unequivocal diagnosis based on neuropathology...
  6. Anderson C, Davies J, Lamont L, Foulds N. Early pontocerebellar hypoplasia with vanishing testes: A new syndrome?. Am J Med Genet A. 2011;155A:667-72 pubmed publisher
    ..We propose that this condition constitutes a new form of severe PCH/atrophy with testicular regression that has onset in the fetal period...
  7. Patel M, Becker L, Toi A, Armstrong D, Chitayat D. Severe, fetal-onset form of olivopontocerebellar hypoplasia in three sibs: PCH type 5?. Am J Med Genet A. 2006;140:594-603 pubmed
    ..These patients represent the earliest reported with OPCH and provide unique information regarding the developmental neuropathology of this condition...
  8. Namavar Y, Chitayat D, Barth P, van Ruissen F, de Wissel M, Poll The B, et al. TSEN54 mutations cause pontocerebellar hypoplasia type 5. Eur J Hum Genet. 2011;19:724-6 pubmed publisher
    ..Thus, PCH5, PCH4 and PCH2 represent a spectrum of clinical manifestations caused by different mutations in the TSEN genes. We, therefore, propose to classify PCH2, PCH4 and PCH5 as TSEN mutation spectrum disorders...
  9. Namavar Y, Barth P, Poll The B, Baas F. Classification, diagnosis and potential mechanisms in pontocerebellar hypoplasia. Orphanet J Rare Dis. 2011;6:50 pubmed publisher

More Information

Publications62

  1. Barth P, Ryan M, Webster R, Aronica E, Kan A, Ramkema M, et al. Rhabdomyolysis in pontocerebellar hypoplasia type 2 (PCH-2). Neuromuscul Disord. 2008;18:52-8 pubmed
    ..Random serum creatine kinase values in six other PCH-2 patients without clinical signs of neuromuscular involvement were increased in four. Collected data provide preliminary evidence of a subclinical myopathy associated with PCH-2...
  2. Okanishi T, Mori Y, Shirai K, Kobayashi S, Nakashima H, Kibe T, et al. Delayed gyration with pontocerebellar hypoplasia type 1. Brain Dev. 2010;32:258-62 pubmed publisher
    ..To the best of our knowledge, this is the first report of delayed gyration in PCH-1...
  3. Kolb L, Arlier Z, Yalcinkaya C, Ozturk A, Moliterno J, Erturk O, et al. Novel VLDLR microdeletion identified in two Turkish siblings with pachygyria and pontocerebellar atrophy. Neurogenetics. 2010;11:319-25 pubmed publisher
    ..Discovery of disease causing homozygous deletions in the present Turkish family capable of maintaining bipedal movement exemplifies the phenotypic heterogeneity of VLDLR-associated cerebellar hypoplasia and ataxia...
  4. Sanefuji M, Kira R, Matsumoto K, Gondo K, Torisu H, Kawakami H, et al. Autopsy case of later-onset pontocerebellar hypoplasia type 1: pontine atrophy and pyramidal tract involvement. J Child Neurol. 2010;25:1429-34 pubmed publisher
    ..Further reports of later-onset cases with histopathological examination are required to elucidate the nosology and etiology of the disorder...
  5. Graham J, Spencer A, Grinberg I, Niesen C, Platt L, Maya M, et al. Molecular and neuroimaging findings in pontocerebellar hypoplasia type 2 (PCH2): is prenatal diagnosis possible?. Am J Med Genet A. 2010;152A:2268-76 pubmed publisher
    ..We found no evidence of cerebellar dysgenesis on prenatal ultrasounds, but MRI tractography showed absence of pontine crossing fibers, a unique feature that might be useful for prenatal diagnosis of this condition...
  6. Rudnik Schoneborn S, Sztriha L, Aithala G, Houge G, Laegreid L, Seeger J, et al. Extended phenotype of pontocerebellar hypoplasia with infantile spinal muscular atrophy. Am J Med Genet A. 2003;117A:10-7 pubmed
    ..The genetic basis of PCH-1 remains to be determined. The gene locus for infantile SMA on chromosome 5q could be excluded by linkage studies. Parental consanguinity and affected siblings make autosomal recessive inheritance most likely...
  7. Korelusová I, Cendelin J, Vozez F. Motor and visuospatial abilities in a model of olivocerebellar and retinal degeneration--Lurcher mutant mice of C3H strain. Prague Med Rep. 2007;108:37-48 pubmed
    ..Motor tests were influenced by retinal degeneration only in the wild type mice. Wild type mice showed some ability of idiothetic navigation, which was not found in Lurchers...
  8. Konagaya M, Konagaya Y, Honda H, Iida M. [A clinico-MRI study of extrapyramidal symptoms in multiple system atrophy--linear hyperintensity in the outer margin of the putamen]. No To Shinkei. 1993;45:509-13 pubmed
    ..This characteristic MRI finding is useful to distinguish MSA with extrapyramidal symptoms from Parkinson's disease...
  9. Konagaya M, Konagaya Y, Iida M. Clinical and magnetic resonance imaging study of extrapyramidal symptoms in multiple system atrophy. J Neurol Neurosurg Psychiatry. 1994;57:1528-31 pubmed
    ..Putaminal slit-hyperintensity is a useful MRI feature in the differential diagnosis between Parkinson's disease and multiple system atrophy predominantly affecting the extrapyramidal system...
  10. Sanchez Cruz G, Velázquez Perez L, Gómez Peña L, Martínez Góngora E, Castellano Sánchez G, Santos Falcón N. [Dysautonomic features in patients with Cuban type 2 spinocerebellar ataxia]. Rev Neurol. 2001;33:428-34 pubmed
    ..Dysautonomic features are the clinical signs and symptoms derived from anomalous functioning of the sympathetic or parasympathetic nervous systems in either the peripheral or central parts...
  11. Phadke S, Puri R, Phadke R. Severe form of congenital cerebral and cerebellar atrophy: a neurodegenerative disorder of fetal onset. J Clin Ultrasound. 2007;35:347-50 pubmed
  12. Cervinkova M, Mandakova P, Sima P. Changes in proliferation activity and relative distributions of lymphoid cell subpopulations in congenitally athymic nu/nu mice and Lurcher mice with spontaneous olivopontocerebellar degeneration. Folia Microbiol (Praha). 2006;51:497-505 pubmed
  13. Akizu N, Cantagrel V, Schroth J, Cai N, Vaux K, McCloskey D, et al. AMPD2 regulates GTP synthesis and is mutated in a potentially treatable neurodegenerative brainstem disorder. Cell. 2013;154:505-17 pubmed publisher
    ..These data suggest AMPD2-related PCH as a potentially treatable early-onset neurodegenerative disease. ..
  14. Minnerop M, Specht K, Ruhlmann J, Schimke N, Abele M, Weyer A, et al. Voxel-based morphometry and voxel-based relaxometry in multiple system atrophy-a comparison between clinical subtypes and correlations with clinical parameters. Neuroimage. 2007;36:1086-95 pubmed
    ..In MSA-C, there was a stronger reduction of gray matter in the basal parts of the cerebellum, of white matter in the brainstem and of the relaxation rate R2 in the cerebellum and brainstem...
  15. Landers M, Adams M, Acosta K, Fox A. Challenge-oriented gait and balance training in sporadic olivopontocerebellar atrophy: a case study. J Neurol Phys Ther. 2009;33:160-8 pubmed publisher
    ..Therefore, the purpose of this study was to investigate the use of challenge-oriented gait and balance training to improve gait and balance in OPCA...
  16. Biancalana V, Toft M, Le Ber I, Tison F, Scherrer E, Thibodeau S, et al. FMR1 premutations associated with fragile X-associated tremor/ataxia syndrome in multiple system atrophy. Arch Neurol. 2005;62:962-6 pubmed
    ..It has been proposed that FXTAS might be a common neurodegenerative disorder...
  17. Duggal H. Cognitive affective psychosis syndrome in a patient with sporadic olivopontocerebellar atrophy. J Neuropsychiatry Clin Neurosci. 2005;17:260-2 pubmed
  18. Kato S, Nakamura H. Cytoplasmic argyrophilic inclusions in neurons of pontine nuclei in patients with olivopontocerebellar atrophy: immunohistochemical and ultrastructural studies. Acta Neuropathol. 1990;79:584-94 pubmed
    ..In elucidating the pathogenesis of OPCA, it was considered to be an important neuropathological finding that some of the remaining pontine neurons affected by OPCA developed characteristic cytoplasmic argyrophilic inclusions...
  19. Nakazato Y, Yamazaki H, Hirato J, Ishida Y, Yamaguchi H. Oligodendroglial microtubular tangles in olivopontocerebellar atrophy. J Neuropathol Exp Neurol. 1990;49:521-30 pubmed
    ..The fibrillary elements were between 20 and 30 nm in diameter. It is suggested that OMT are primarily composed of altered microtubules, and are related to the neurodegenerative process of OPCA...
  20. Sadaoka T, Kakitsuba N, Fujiwara Y, Kanai R, Takahashi H. Sleep-related breathing disorders in patients with multiple system atrophy and vocal fold palsy. Sleep. 1996;19:479-84 pubmed
    ..We recommend treatment of respiratory disorders when loud laryngeal snoring occurs in patients with MSA, even if they do not complain of dyspnea while awake...
  21. Kish S, Du F, Parks D, Robitaille Y, Ball M, Schut L, et al. Quinolinic acid catabolism is increased in cerebellum of patients with dominantly inherited olivopontocerebellar atrophy. Ann Neurol. 1991;29:100-4 pubmed
    ..Increased quinolinic acid phosphoribosyltransferase activity may represent a mechanism, in the degenerating cerebellum, to protect quinolinic acid-sensitive granule cells in patients with olivopontocerebellar atrophy...
  22. Moretti R, Torre P, Antonello R, Carraro N, Zambito Marsala S, Ukmar M, et al. Peculiar aspects of reading and writing performances in patients with olivopontocerebellar atrophy. Percept Mot Skills. 2002;94:677-94 pubmed
  23. Wakabayashi K, Mori F, Nishie M, Oyama Y, Kurihara A, Yoshimoto M, et al. An autopsy case of early ("minimal change") olivopontocerebellar atrophy (multiple system atrophy-cerebellar). Acta Neuropathol. 2005;110:185-90 pubmed
    ..Moreover, alpha-synuclein accumulation was more severe in the neurites than in the cytoplasm or nucleus. This case demonstrates the early pattern of brain pathology in MSA-cerebellar (olivopontocerebellar atrophy)...
  24. Heo J, Lee S, Chu K, Kim M. The efficacy of combined estrogen and buspirone treatment in olivopontocerebellar atrophy. J Neurol Sci. 2008;271:87-90 pubmed publisher
    ..We conducted an open-labeled pilot trial to assess the efficacy of estrogen with buspirone treatment...
  25. Hevner R. Progress on pontocerebellar hypoplasia. Acta Neuropathol. 2007;114:401-2 pubmed
  26. Lee S, Mori S, Kim D, Kim S, Kim S, Chu M, et al. Diffusion tensor MRI and fiber tractography of cerebellar atrophy in phenytoin users. Epilepsia. 2003;44:1536-40 pubmed
    ..The purpose of this study was to investigate the afferent fiber system to the cerebellum in patients with phenytoin (PHT)-induced cerebellar atrophy in comparison with cerebellar atrophy of other etiologies by using DT-MRI...
  27. Barcal J, Korelusová I, Cendelin J, Vozeh F. The time-dependent block of NMDA glutamate receptor influences hippocampal LTP in inborn cerebellar degeneration mouse model. Prague Med Rep. 2007;108:29-36 pubmed
    ..Our results suggest a similar effect of blockade either after single or chronic MK-801 administration; both of them practically disrupted LTP generation with differences between healthy and neurodegenerative animals...
  28. Hamaguchi H, Kanda F, Hosaka K, Fujii M, Chihara K. [Comparison between MRI and 3D-SSP in olivopontocerebellar atrophy and cortical cerebellar atrophy]. Rinsho Shinkeigaku. 2004;44:263-7 pubmed
    ..Simultaneous examination both MRI and 3D-SSP might be useful for differential diagnosis of spinocerebellar degenerations...
  29. Vozeh F, Voller J, Cendelin J. Neural functional and morphological consequences of retinal degeneration in C3H Lurcher mutant and wild type mice. Prague Med Rep. 2006;107:95-102 pubmed
    ..The neurohistological examination of the brain visual projections of animals affected with the retinal defect showed most detectable changes in dendritic spines of the V1 cortex (lower density in general and less immature types)...
  30. Berent S, Giordani B, Gilman S, Trask C, Little R, Johanns J, et al. Patterns of neuropsychological performance in multiple system atrophy compared to sporadic and hereditary olivopontocerebellar atrophy. Brain Cogn. 2002;50:194-206 pubmed
    ..Patients with MSA had greater neuropsychological dysfunction, particularly in memory and other "higher order" cognitive processes, than patients with either sOPCA or dOPCA...
  31. Chou H, Ogawa N, Asanuma M, Hirata H, Mori A. Dopamine deficiency in the weaver mutant mouse: an animal model of olivopontocerebellar atrophy. Res Commun Chem Pathol Pharmacol. 1991;74:117-20 pubmed
    ..Noradrenaline levels did not differ from controls. This study shows that weaver mice have specific deficiencies in the dopamine system...
  32. Leroy J, Lyon G, Fallet C, Amiel J, De Praeter C, Van den Broecke C, et al. Congenital pontocerebellar atrophy and telencephalic defects in three siblings: a new subtype. Acta Neuropathol. 2007;114:387-99 pubmed
  33. Barcal J, Cendelin J, Korelusová I, Vozeh F. Does transplantation of cerebellar embryonic tissue influence hippocampal LTP in adult Lurcher mutant mice?. Prague Med Rep. 2006;107:81-8 pubmed
    ..Also interstrain differences were described. Our results support ideas about tight cooperation among brain structures which are involved in mechanisms of learning and memory...
  34. Vianello M, Manara R, Betterle C, Tavolato B, Mariniello B, Giometto B. X-linked adrenoleukodystrophy with olivopontocerebellar atrophy. Eur J Neurol. 2005;12:912-4 pubmed
    ..Consequently, cerebellar symptoms should be considered as a clinical presentation of X-ALD. Early recognition of this rare disorder would be useful for genetic counselling and therapy...
  35. Barone R, Pavone L, Fiumara A, Bianchini R, Jaeken J. Developmental patterns and neuropsychological assessment in patients with carbohydrate-deficient glycoconjugate syndrome type IA (phosphomannomutase deficiency). Brain Dev. 1999;21:260-3 pubmed
    ..This study expands our understanding on the clinical spectrum of CDGIA syndrome and may be helpful for planning rehabilitation and education...
  36. Wang P, Liu R, Yang B, Soong B. Topographic brain mapping of the international cooperative ataxia rating scale. A positron emission tomography study. J Neurol. 2007;254:722-8 pubmed
    ..The results suggested that the clinical severity of SCA patients correlated with the functional impairment in the frontal regions, the targets of cerebellar efferent projections...
  37. Ozawa T, Paviour D, Quinn N, Josephs K, Sangha H, Kilford L, et al. The spectrum of pathological involvement of the striatonigral and olivopontocerebellar systems in multiple system atrophy: clinicopathological correlations. Brain. 2004;127:2657-71 pubmed
  38. Nakamura K, Nishiyama K, Kodera H, Nakashima M, Tsurusaki Y, Miyake N, et al. A de novo CASK mutation in pontocerebellar hypoplasia type 3 with early myoclonic epilepsy and tetralogy of Fallot. Brain Dev. 2014;36:272-3 pubmed publisher
  39. Parvizi J, Joseph J, Press D, Schmahmann J. Pathological laughter and crying in patients with multiple system atrophy-cerebellar type. Mov Disord. 2007;22:798-803 pubmed
    ..Our findings are consistent with the view that the cerebellum and its interconnected structures may be involved in the regulation of emotional expression...
  40. Barcal J, Cendelin J, Korelusová I, Tuma J, Vozeh F. Glutamate receptor block in Lurcher mutant mice during ontogeny and its effect on hippocampal long-term potentiation. Prague Med Rep. 2010;111:127-34 pubmed
    ..It can be concluded that the results support the ideas of close functional cooperation between the brain structures which are involved in mechanisms of learning and memory...
  41. Tian Z, Chen T, Zhong N, Li Z, Yin F, Liu S. Clinical study of transplantation of neural stem cells in therapy of inherited cerebellar atrophy. Beijing Da Xue Xue Bao Yi Xue Ban. 2009;41:456-8 pubmed
    ..To study the clinical effect of neural stem cell transplantation in the treatment of inherited cerebellar atrophy (CA)...
  42. Kee K, Hand P. Cerebellar ataxia and snoring. J Clin Neurosci. 2006;13:249, 307 pubmed
  43. Manquillo A, Martinez J, Paradinas F, Saez J, Quintana P, Revilla C, et al. [Behavior disorders during REM sleep. Two clinical cases]. Rev Neurol. 1999;28:1170-4 pubmed
  44. Thullier F, Lalonde R, Lestienne F. Effects of dopaminergic agents and of an NMDA receptor antagonist on motor coordination in Lurcher mutant mice. Pharmacol Biochem Behav. 1999;63:213-9 pubmed
    ..These results indicate that NMDA receptor antagonism or stimulation of some dopaminergic mechanisms partially improve genetically determined cerebellar ataxia in mice...
  45. Vig P, Desaiah D, Joshi P, Subramony S, Fratkin J, Currier R. Decreased insulin-like growth factor I-mediated protein tyrosine phosphorylation in human olivopontocerebellar atrophy and lurcher mutant mouse. J Neurol Sci. 1994;124:38-44 pubmed
    ..These results suggest that the process of cerebellar degeneration in human OPCA and lurcher mutant mouse may be associated with altered IGF-I receptor binding and protein tyrosine phosphorylation...
  46. Papp M, Lantos P. Accumulation of tubular structures in oligodendroglial and neuronal cells as the basic alteration in multiple system atrophy. J Neurol Sci. 1992;107:172-82 pubmed
  47. Suarez H, Muse P, Suarez A, Arocena M. Postural behaviour responses to visual stimulation in patients with vestibular disorders. Acta Otolaryngol. 2000;120:168-72 pubmed
    ..4 Hz in normal subjects, while the CVD and cerebellar patients showed sway frequencies in both the X and Y axes. The clinical implications of these findings are discussed...
  48. Jinnou H, Okanishi T, Enoki H, Ohki S. Pontocerebellar hypoplasia type 3 with tetralogy of Fallot. Brain Dev. 2012;34:392-5 pubmed publisher
    ..To the best of our knowledge, this represents the first report of pontocerebellar hypoplasia with congenital cardiac malformation...
  49. Gallant N, Baldwin E, Salamon N, Dipple K, Quintero Rivera F. Pontocerebellar hypoplasia in association with de novo 19p13.11p13.12 microdeletion. Am J Med Genet A. 2011;155A:2871-8 pubmed publisher
    ..2. Our findings suggest chromosomal microarray analysis may be useful in determining etiology of syndromic PCH...
  50. Wan J, Yourshaw M, Mamsa H, Rudnik Schoneborn S, Menezes M, Hong J, et al. Mutations in the RNA exosome component gene EXOSC3 cause pontocerebellar hypoplasia and spinal motor neuron degeneration. Nat Genet. 2012;44:704-8 pubmed publisher
  51. Zafeiriou D, Ververi A, Tsitlakidou A, Anastasiou A, Vargiami E. Recurrent episodes of rhabdomyolysis in pontocerebellar hypoplasia type 2. Neuromuscul Disord. 2013;23:116-9 pubmed publisher
    ..The possible mechanisms associating encephalopathy and myopathy in pontocerebellar hypoplasia type 2 are discussed...
  52. Vig P, Subramony S, Currier R, Desaiah D. Inositol 1,4,5-trisphosphate metabolism in the cerebella of Lurcher mutant mice and patients with olivopontocerebellar atrophy. J Neurol Sci. 1992;110:139-43 pubmed
    ..These data suggest that altered phosphoinositide turnover may be associated with the onset of neuronal degeneration in human OPCA...
  53. Taoka T, Kin T, Nakagawa H, Hirano M, Sakamoto M, Wada T, et al. Diffusivity and diffusion anisotropy of cerebellar peduncles in cases of spinocerebellar degenerative disease. Neuroimage. 2007;37:387-93 pubmed
    ..This study accessed the feasibility of using tractography-based analysis to evaluate the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of three cerebellar peduncles in subtypes of spinocerebellar degenerative disease...