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Screening for dopa-responsive dystonia in patients with scans without evidence of dopaminergic deficiency (SWEDD)

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Abstract

The clinical diagnosis of Parkinson’s Disease (PD) is not supported by Single Photon Emission Computed Tomography (SPECT) using dopamine transporter radioligand in 4–15 % of patients. It has been hypothesized that this phenomenon, named “Scans Without Evidence of Dopaminergic Deficiency” (SWEDD), may be an adult-onset dystonia. We investigated the hypothesis that these patients might be affected by Dopa-Responsive Dystonia (DRD). We enrolled eleven unrelated patients (8 F and 3 M) with clinical parkinsonism and normal [123I]FP-CIT SPECT. The GTP-cyclohydrolase1 (GCH1) gene was sequenced in all patients; urine biopterin and neopterin analysis was carried out in nine and oral phenylalanine (Phe) loading in seven. Neurological examination showed bradykinesia and resting/postural tremor in all patients, and rigidity in ten, suggesting a clinical diagnosis of PD. We detected mild dystonic signs in eight cases. In particular, five of them presented cranial dyskinesias. No mutation of the GCH1 gene was found. The results of the urine biopterin and neopterin analysis and the oral Phe loading did not reveal biochemical abnormalities suggestive of reduced GCH1 activity. We confirm that some clinical features, namely the presence of focal or segmental dystonia, suggest an adult-onset dystonia in SWEDD cases. However, we exclude DRD caused by GCH1 gene mutations in the present series.

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References

  1. Parkinson Study Group (2002) Dopamine transporter brain imaging to assess the effects of pramipexole vs levodopa on Parkinson disease progression. JAMA 287:1653–1661

    Article  Google Scholar 

  2. Whone AL, Watts RL, Stoessl AJ, Davis M, Reske S, Nahmias C, Lang AE, Rascol O, Ribeiro MJ, Remy P, Poewe WH, Hauser RA, Brooks DJ, REAL-PET Study Group (2003) Slower progression of Parkinson’s disease with ropinirole versus levodopa: the REAL-PET study. Ann Neurol 54:93–101

    Article  CAS  PubMed  Google Scholar 

  3. Fahn S, Oakes D, Shoulson I, Kieburtz K, Rudolph A, Lang A, Olanow CW, Tanner C, Marek K, Parkinson Study Group (2004) Levodopa and the progression of Parkinson’s disease. N Engl J Med 351:2498–2508

    Article  CAS  PubMed  Google Scholar 

  4. Marshall VL, Patterson J, Hadley DM, Grosset KA, Grosset DG (2006) Two-year follow-up in 150 consecutive cases with normal dopamine transporter imaging. Nucl Med Commun 27:933–937

    Article  PubMed  Google Scholar 

  5. Hughes AJ, Daniel SE, Ben-Shlomo Y, Lees AJ (2002) The accuracy of diagnosis of parkinsonian syndromes in a specialist movement disorder service. Brain 125:861–870

    Article  PubMed  Google Scholar 

  6. Silveira-Moriyama L, Schwingenschuh P, O’Donnell A, Schneider SA, Mir P, Carrillo F, Terranova C, Petrie A, Grosset DG, Quinn NP, Bhatia KP, Lees AJ (2009) Olfaction in patients with suspected Parkinsonism and scans without evidence of dopaminergic deficit (SWEDDs). J Neurol Neurosurg Psychiatry 80:744–748

    Article  CAS  PubMed  Google Scholar 

  7. Schneider SA, Edwards MJ, Mir P, Cordivari C, Hooker J, Dickson J, Quinn N, Bhatia KP (2007) Patients with adult-onset dystonic tremor resembling parkinsonian tremor have scans without evidence of dopaminergic deficit (SWEDDs). Mov Disord 22:2210–2215

    Article  PubMed  Google Scholar 

  8. Schwingenschuh P, Ruge D, Edwards MJ, Terranova C, Katshnig P, Carrillo F, Laura Silveira-Moriyama L, Schneider SA, Kägi G, Dickson J, Lees AJ, Quinn N, Mir P, Rothwell JC, Bhatia KP (2010) Adult onset asymmetric upper limb tremor misdiagnosed as Parkinson’s disease: a clinical and electrophysiological study. Mov Disord 25:560–569

    Article  PubMed Central  PubMed  Google Scholar 

  9. Segawa M (2003) Autosomal dominant GTP cyclohydrolase I (AD GCH 1) deficiency (Segawa disease, dystonia 5; DYT 5). Chang Gung Med J 32:1–11

    Google Scholar 

  10. Ichinose H, Ohye T, Takahashi E, Seki N, Hori T, Segawa M, Nomura Y, Endo K, Tanaka H, Tsuji S, Fujita K, Nagatsu T (1994) Hereditary progressive dystonia with marked diurnal fluctuation caused by mutations in the GTP cyclohydrolase I gene. Nat Genet 8:236–242

    Article  CAS  PubMed  Google Scholar 

  11. Nygaard TG, Trugman JM, de Yebenes JG, Fahn S (1990) Dopa-responsive dystonia: the spectrum of clinical manifestations in a large North American family. Neurology 40:66–69

    Article  CAS  PubMed  Google Scholar 

  12. Trender-Gerhard I, Sweeney MG, Schwingenschuh P, Mir P, Edwards MJ, Gerhard A, Polke JM, Hanna MG, Davis MB, Wood NW, Bhatia KP (2009) Autosomal-dominant GTPCH1-deficient DRD: clinical characteristics and long-term outcome of 34 patients. J Neurol Neurosurg Psychiatry 80:839–845

    Article  CAS  PubMed  Google Scholar 

  13. Jeon BS, Jeong JM, Park SS, Kim JM, Chang YS, Song HC, Kim KM, Yoon KY, Lee MC, Lee SB (1998) Dopamine transporter density measured by [123I]beta-CIT single-photon emission computed tomography is normal in dopa-responsive dystonia. Ann Neurol 43:792–800

    Article  CAS  PubMed  Google Scholar 

  14. Furukawa Y, Nishi K, Kondo T, Mizuno Y, Narabayashi H (1993) CSF biopterin levels and clinical features of patients with juvenile parkinsonism. Adv Neurol 60:562–567

    CAS  PubMed  Google Scholar 

  15. Bandmann O, Goertz M, Zschocke J, Deuschl G, Jost W, Hefter H, Müller U, Zöfel P, Hoffmann G, Oertel W (2003) The phenylalanine loading test in the differential diagnosis of dystonia. Neurology 60:700–702

    Article  CAS  PubMed  Google Scholar 

  16. Erro R, Picillo M, Vitale C, Amboni M, Moccia M, Longo K, Cozzolino A, Giordano F, De Rosa A, De Michele G, Pellecchia MT, Barone P (2013) Non-motor symptoms in early Parkinson’s disease: a 2-year follow-up study on previously untreated patients. J Neurol Neurosurg Psychiatry 84:14–17

    Article  PubMed  Google Scholar 

  17. Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55:181–184

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Segawa M, Nomura Y, Nishiyama N (2003) Autosomal dominant guanosine triphosphate cyclohydrolase I deficiency (Segawa disease). Ann Neurol 54:S32–S45

    Article  CAS  PubMed  Google Scholar 

  19. Antonozzi I, Carducci C, Vestri L, Pontecorvi A, Moretti F (1988) Rapid and sensitive method for high-performance liquid chromatographic analysis of pterins in biological fluids. J Chromatogr 459:319–324

    Article  CAS  PubMed  Google Scholar 

  20. Hyland K, Fryburg JS, Wilson WG, Bebin EM, Arnold LA, Gunasekera RS, Jacobson RD, Rost-Ruffner E, Trugman JM (1997) Oral phenylalanine loading in dopa-responsive dystonia: a possible diagnostic test. Neurology 48:1290–1297

    Article  CAS  PubMed  Google Scholar 

  21. Chace DH, Millington DS, Terada N, Kahler SG, Roe CR, Hofman LF (1993) Rapid diagnosis of phenylketonuria by quantitative analysis for phenylalanine and tyrosine in neonatal blood spots by tandem mass spectrometry. Clin Chem 39:66–71

    CAS  PubMed  Google Scholar 

  22. Saunders-Pullmana R, Blau N, Hyland K, Zschocke J, Nygaard T, Raymond D, Shanker V, Mohrmann K, Arnold L, Tabbal S, deLeon D, Ford B, Brin M, Chouinard S, Ozelius L, Klein C, Bressman SB (2004) Phenylalanine loading as a diagnostic test for DRD: interpreting the utility of the test. Mol Genet Metabol 83:207–212

    Article  Google Scholar 

  23. Benamer TS, Patterson J, Grosset DG, Booij J, de Bruin K, van Royen E, Speelman JD, Horstink MH, Sips HJ, Dierckx RA, Versijpt J, Decoo D, Van Der Linden C, Hadley DM, Doder M, Lees AJ, Costa DC, Gacinovic S, Oertel WH, Pogarell O, Hoeffken H, Joseph K, Tatsch K, Schwarz J, Ries V (2000) Accurate differentiation of parkinsonism and essential tremor using visual assessment of [123I]-FP-CIT SPECT imaging: the [123I]-FP-CIT study group. Mov Disord 15:503–510

    Article  CAS  PubMed  Google Scholar 

  24. Jennings DL, Seibyl JP, Oakes D, Eberly S, Murphy J, Marek K (2004) (23I) beta-CIT and single-photon emission computed tomographic imaging vs clinical evaluation in Parkinsonian syndrome: unmasking an early diagnosis. Arch Neurol 61:1224–1229

    Article  PubMed  Google Scholar 

  25. Utiumi MA, Felício AC, Borges CR, Braatz VL, Rezende SA, Munhoz RP, Bressan RA, Ferraz HB, Teive HA (2012) Dopamine transporter imaging in clinically unclear cases of parkinsonism and the importance of scans without evidence of dopaminergic deficit (SWEDDs). Arq Neuropsiquiatr 70:667–673

    Article  PubMed  Google Scholar 

  26. Sixel-Doring F, Liepe K, Mollenhauer B, Trautmann E, Trenkwalder C (2011) The role of 123I-FP-CIT-SPECT in the differential diagnosis of Parkinson and tremor syndromes: a critical assessment of 125 cases. J Neurol 258:2147–2154

    Article  PubMed  Google Scholar 

  27. Marek K, Seibyl J, Eberly S, Oakes D, Shoulson I, Lang AE, Hyson C, Jennings D, Parkinson Study Group PRECEPT Investigators (2014) Longitudinal follow-up of SWEDD subjects in the PRECEPT study. Neurology 82:1791–1797

    Article  PubMed Central  PubMed  Google Scholar 

  28. Leuzzi V, Carducci C, Chiarotti F, D’Agnano D, Giannini MT, Antonozzi I, Carducci C (2013) Urinary neopterin and phenylalanine loading test as tools for the biochemical diagnosis of Segawa disease. JIMD Rep 7:67–75

    Article  PubMed Central  PubMed  Google Scholar 

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Ethical standards

The study was in accord with the Helsinki Declaration of 1975. All participants were informed about the purpose of the study and gave written informed consent. Since the research involves no risk for the patients and data have been anonymized, according to Italian laws, approval of Ethics Committee is not needed.

Conflicts of interest

The authors have no conflict of interest.

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Authors and Affiliations

  1. Department of Neurosciences and Reproductive and Odontostomatological Sciences, Federico II University, Via Pansini 5, 80131, Naples, Italy

    Anna De Rosa, Silvio Peluso, Maria Lieto, Andrea Mazzella, Francesco Saccà & Vincenzo Brescia Morra

  2. Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy

    Claudia Carducci, Carla Carducci, Vincenzo Leuzzi & Giuseppe De Michele

  3. Biostructure and Bioimaging Institute CNR, Naples, Italy

    Sabina Pappatà

Authors
  1. Anna De Rosa
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  2. Claudia Carducci
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  3. Carla Carducci
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  4. Silvio Peluso
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  5. Maria Lieto
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  6. Andrea Mazzella
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  7. Francesco Saccà
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  8. Vincenzo Brescia Morra
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  9. Sabina Pappatà
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  10. Vincenzo Leuzzi
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  11. Giuseppe De Michele
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Corresponding author

Correspondence to Anna De Rosa.

Electronic supplementary material

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415_2014_7477_MOESM1_ESM.wmv

Video presents: (Patient 1) Tremor of right hand during walking (first fragment), dystonic posture of the right hand with hyperabduction of the fifth finger in Mingazzini’s position (second fragment), bilateral muscle spasm of the lower part of the face, more marked on the left side, and mild bilateral bradykinesia at finger tapping test (third fragment); (Patient 2) Left facial hemispasm; (Patient 3) Left facial hemispasm, more marked for the lower part of the face. (The patients provided informed consent to be videotaped for publication). Supplementary material 1 (WMV 8,535 kb)

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De Rosa, A., Carducci, C., Carducci, C. et al. Screening for dopa-responsive dystonia in patients with scans without evidence of dopaminergic deficiency (SWEDD). J Neurol 261, 2204–2208 (2014). https://doi.org/10.1007/s00415-014-7477-6

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  • DOI: https://doi.org/10.1007/s00415-014-7477-6

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