title: Ataxia, dystonia and myoclonus in adult patients with Niemann-Pick type C.
abstract: Niemann-Pick type C (NP-C) is a rare autosomal recessive progressive neurodegenerative disorder caused by mutations in the NP-C 1 or 2 gene. Besides visceral symptoms, presentation in adolescent and adult onset variants is often with neurological symptoms. The most frequently reported presenting symptoms of NP-C in adulthood are psychiatric symptoms (38 %), cognitive decline (23 %) and ataxia (20 %). Myoclonus can be present, but its value in early diagnosis and the evolving clinical phenotype in NP-C is unclear. In this paper we present eight Dutch cases of NP-C of whom five with myoclonus.
  
  
  
  Eight patients with genetically confirmed NP-C were recruited from two Dutch University Medical Centers. A structured interview and neuropsychological tests (for working and verbal memory, attention and emotion recognition) were performed. Movement disorders were assessed using a standardized video protocol. Quality of life was evaluated by questionnaires (Rand-36, SIP-68, HAQ). In four of the five patients with myoclonic jerks simultaneous EEG with EMG was performed.
  
  
  
  A movement disorder was the initial neurological symptom in six patients: three with myoclonus and three with ataxia. Two others presented with psychosis. Four experienced cognitive deficits early in the course of the disease. Patients showed cognitive deficits in all investigated domains. Five patients showed myoclonic jerks, including negative myoclonus. In all registered patients EEG-EMG coherence analysis and/or back-averaging proved a cortical origin of myoclonus. Patients with more severe movement disorders experienced significantly more physical disabilities.
  
  
  
  Presenting neurological symptoms of NP-C include movement disorders, psychosis and cognitive deficits. At current neurological examination movement disorders were seen in all patients. The incidence of myoclonus in our cohort was considerably higher (63 %) than in previous publications and it was the presenting symptom in 38 %. A cortical origin of myoclonus was demonstrated. Our data suggest that myoclonus may be overlooked in patients with NP-C. All patients scored significantly lower on physical domains of HRQoL. Symptomatic treatment of movement disorders may improve physical functioning and subsequently HRQoL.
authors: Department of Neurology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands.
authors: L H
authors: LH
authors: Koens
authors: Department of Neurology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands.
authors: A
authors: A
authors: Kuiper
authors: Department of Clinical Neuropsychology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands.
authors: M A
authors: MA
authors: Coenen
authors: Department of Neurology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands.
authors: J W J
authors: JW
authors: Elting
authors: Department of Neurology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands.
authors: J J
authors: JJ
authors: de Vries
authors: Department of Neurology, University of Amsterdam, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
authors: M
authors: M
authors: Engelen
authors: Department of Neurology, University of Amsterdam, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
authors: J H T M
authors: JH
authors: Koelman
authors: Division of Metabolic Diseases, University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Hanzeplein 1, 9700 RB, Groningen, The Netherlands.
authors: F J
authors: FJ
authors: van Spronsen
authors: Department of Clinical Neuropsychology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands.|Department of Clinical and Developmental Neuropsychology, University of Groningen, Faculty of Behavioral and Social Sciences, Grote Kruisstraat 2/1, 9712 TS, Groningen, The Netherlands.
authors: J M
authors: JM
authors: Spikman
authors: Division of Metabolic Diseases, University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Hanzeplein 1, 9700 RB, Groningen, The Netherlands.|Department of Genetics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands.
authors: T J
authors: TJ
authors: de Koning
authors: Department of Neurology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands. m.a.j.de.koning-tijssen@umcg.nl.
authors: M A J
authors: MA
authors: Tijssen
mesh_terms: D000293:Adolescent; D000328:Adult; D001259:Ataxia / Q000473:pathology / Q000503:physiopathology; D002648:Child; D004421:Dystonia / Q000473:pathology / Q000503:physiopathology; D004569:Electroencephalography; D004576:Electromyography; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009207:Myoclonus / Q000473:pathology / Q000503:physiopathology; D052556:Niemann-Pick Disease, Type C / Q000473:pathology* / Q000503:physiopathology*; D011788:Quality of Life; D055815:Young Adult
keywords: Ataxia; Cognitive deficits; Cortical myoclonus; EEG-EMG coherence; Niemann-Pick type C