BRIEF REPORTS Decades of Delayed Diagnosis We report 4 patients with young-onset parkinson- ism, each of whom was misdiagnosed with a motor in 4 Levodopa-Responsive conversion disorder for at least a decade after their Young-Onset Monogenetic first specialist referral. Parkinsonism Patients Case reports Patient 1 Helen Ling, BScMed, BMBS, MSc,1,2 Mark Braschinsky, A British woman developed gait freezing at age 31 3 3 3 MD, PhD, Pille Taba, MD, Siiri-Merike Lu¨ u¨ s, MD, Karen during her first pregnancy. She then became unsteady Doherty, MB, BCh, BAO, MRCP,1,2 Anna Hotter, MD,4 4 1,2 and clumsy and complained of jerky tremulous hands Werner Poewe, MD, and Andrew J. Lees, MD FRCP * and curling of the toes. She also complained of pro- found fatigue and slowness of thinking. At age 37, she 1Reta Lila Weston Institute of Neurological Studies, Institute of Neurology, University College London, London, United Kingdom; started to have urinary urgency and to fall over. Over 2Queen Square Brain Bank for Neurological Disorders and Institute 14 years, she was seen by 6 neurologists and had of Neurology, University College London, London, United Kingdom; received diagnoses of motor conversion disorder 3Department of Neurology, University of Tartu, Tartu, Estonia; (MCD), chronic fatigue syndrome (CFS), and depres- 4 Department of Neurology, University Hospital of Innsbruck, Austria sion. Her movements were described as distractible, variable, and deliberately slow. Her spontaneous move- ments were considered as strikingly normal in contrast with those found on formal neurological examination. At age 45, she was reviewed at the National Hospital for Neurology and Neurosurgery in Queen Square, ABSTRACT London, where Parkinson’s disease was suspected. Background: We report 4 patients with young-onset In 2001, her brother committed suicide, which coin- monogenetic parkinsonism, each of whom was misdiag- cided with a marked deterioration in her physical symp- nosed with either a psychogenic movement disorder or chronic fatigue syndrome for 10 to 23 years after the toms at age 37. Three of her other 5 siblings had received onset of their first symptoms. psychiatric treatment for depression. Her mother had a Results: Once the diagnosis was eventually made, they longstanding history of severe depression. all had a rapid and excellent response to levodopa, albeit On examination, she walked with 2 sticks and a nar- with the early appearance of interdose dyskinesias in 3. row-based gait with stooped posture and postural insta- Conclusions: We discuss possible reasons for the bility (Video 1a). She had a melancholic, slightly anxious missed diagnosis despite the relentless progression facial expression, an asymmetrical fast resting tremor of their motor handicap. DAT scanning supported the that was also present on posture and action, and a fast revised clinical diagnosis of parkinsonism. VC 2011 Movement Disorder Society synchronous rest tremor in both legs. Her movements were very slow. Finger tapping revealed progressive Key Words: parkin; monogenetic parkinsonism; psy- reduction in amplitude without motor arrests or fatigue. chogenic movement disorders; conversion disorder; Tone was increased, which improved on distraction. chronic fatigue syndrome DAT-SPECT showed reduced tracer uptake in the basal ganglia (Fig. 1a). She was found to have heterozygous de- ------------------------------------------------------------ letion of parkin exon 5 and a duplication of parkin exons Additional Supporting Information may be found in the online version of 2, 3, and 4. After 3 weeks of L-dopa treatment of 300 mg/ this article. day, her motor UPDRS score improved from 56 to 7. She *Correspondence to: Professor Andrew J. Lees, Reta Lila Weston developed limb and trunk chorea within 7 weeks of start- Institute of Neurological Studies, Institute of Neurology, UCL, 1 Wakefield ing treatment (Video 1b). Street, London, WC1N 1PJ, United Kingdom; [email protected]. Relevant conflicts of interest/financial disclosures: Nothing to report. Patient 2 This work was supported by the Reta Lila Weston Trust. Full financial disclosures and author roles may be found in the online This Irish woman presented at age 19 with symptoms version of this article. of fatigue, poor balance, difficulty walking, and quiet Received: 12 September 2010; Revised: 1 November 2010; Accepted: speech. She was reviewed by an immunologist and psy- 8 November 2010 Published online 29 March 2011 in Wiley Online Library chiatrist and was informed she had CFS and depression. (wileyonlinelibrary.com). DOI: 10.1002/mds.23563 Her symptoms gradually deteriorated and became Movement Disorders, Vol. 26, No. 7, 2011 1337 LING ET AL. FIG. 1. (a)[123I]FP-CIT DAT images of patient 1 show absent tracer activity in both putamen nuclei and asymmetrical markedly reduced uptake in both caudate nuclei. (b)[123I]FP-CIT DAT images of patient 2 show markedly reduced uptake in the putamen and asymmetrical reduced uptake in the caudate nuclei. (c)[123I]FP-CIT DAT image of patient 3 shows asymmetrical markedly reduced uptake in the putamen and caudate nuclei. (d) [123I]FP-CIT DAT image of patient 4 shows bilateral reduced tracer uptake in the putamen and caudate nuclei. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.] much worse during pregnancy at age 38. She then devel- GLN100X). She had an excellent response to pramipex- oped right-hand tremor, limb dystonia, gait difficulty, ole. Three years later, L-dopa was started, and peak and frequent falls. Over the next 5 years, she was fol- dose dyskinesia developed within a few months. lowed up in a neurology clinic, but no organic cause was identified. Limb rigidity and brisk reflexes were noted but were considered inconsistent. She was Patient 3 described as being anxious and agitated during consul- At age 33, this Estonian nurse developed low mood, tations. At age 42, she was admitted to the Royal Victo- slowing of movements, and intermittent hand tremor ria Hospital in Belfast, where parkinsonism was a year after a minor car accident. She was diagnosed suspected. During examination, she was very immobile with posttraumatic stress disorder and considered to with gait freezing and postural instability and had have an obsessional, rigid personality with severe asymmetrical cogwheel rigidity, bradykinesia, right- depression by psychiatrists. She developed impairment foot dystonia, and stooped posture (Video 2). DAT- of gait and speech 2 years later and began to require SPECT revealed reduced uptake in both basal ganglia assistance to walk. She remained on antidepressants (Fig. 1b). She was later confirmed to be a compound despite the relentless progression of her motor symp- heterozygote with parkin mutations (ARG275TRP, toms. She was twice admitted to the care of 1338 Movement Disorders, Vol. 26, No. 7, 2011 DELAYED DIAGNOSIS IN MONOGENETIC PARKINSONISM Table 1. Overview of clinical characteristics of patients 1–4 Clinical characteristic Patient 1 Patient 2 Patient 3 Patient 4 Age at onset (y) 31, female 19, female 33, female 28, female Delay in correct diagnosis (y) 14 23 10 12 Presenting complaint Gait freezing Asymmetrical Low mood and slowing Neuroleptic induced bradykinetic rigidity of movements acute dystonic reaction with subsequent development of left leg tremor Predominant motor features Tremulous parkinsonism, Akinetic rigidity, hand Akinetic rigidity, festinant Tremulous parkinsonism, foot dystonia dystonia, gait freezing gait, dysphagia, anarthria postural instability Nonmotor features Fatigue, bradyphrenia, Fatigue, anxiety Low mood Low mood urinary symptoms Functional disability Walked with assistance Severe postural Bedbound, contractures, Walked independently with of 2 sticks instability requiring dysphagia with severe marked postural instability assistance with walking weight loss Genetic findings Compound heterozygote Compound heterozygote PARK1/4 duplication Compound heterozygote parkin mutation parkin mutation carrier of parkin and DJ-1 Features mistakenly identified as supportive of a conversion disorder Distractibility and inconsistency Yes Yes Yes Yes Extreme slowness/florid symptoms Yes No Yes No Paradoxical kinesis Yes No Yes No Health care worker No No Yes Yes Family history of psychiatric illness Yes No No No Variable frequency and amplitude Yes Not performed Yes Not performed on EMG tremor analysis neurologists, at ages 37 and 40. Examination showed she developed gait difficulty and a stooped posture. generalized limb rigidity and slowness of movement, Over 12 years, she was reviewed by 2 neurological with examples of paradoxical kinesis such as normal teams and psychiatrists, all of whom agreed she had reactions in catching a ball. Her gait was described as MCD. At age 40, she was referred to the Department festinant but ‘‘atypical,’’ with knees flexed and short of Neurology at Innsbruck Medical University, Austria, stride length, and she had never fallen. Her speech was where parkinsonism was suspected for the first time. slow and spoken in short sentences. The neurologists on Examination revealed pill-rolling rest tremor in the left both occasions diagnosed an MCD. At age 43, she hand, asymmetrical rigidity, and bradykinesia. She became bedbound and developed dysphagia, resulting in walked independently with small steps and had marked severe weight loss. She was admitted to the University postural instability. A dose of 300 mg/day of L-dopa Hospital of Tartu in Estonia, where an organic cause of led to complete