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.

Aim: Cognitive impairments have been established as part of the non‐motor phenomenology of adult dystonia. In childhood dystonia, the extent of cognitive impairments is less clear. This systematic review aims to present an overview of the existing literature to elucidate the cognitive profile of primary and secondary childhood dystonia.Method: Studies focusing on cognition in childhood dystonia were searched in MEDLINE and PsychInfo up to October 2017. We included studies on idiopathic and genetic forms of dystonia as well as dystonia secondary to cerebral palsy and inborn errors of metabolism.Results: Thirty‐four studies of the initial 527 were included. Studies for primary dystonia showed intact cognition and IQ, but mild working memory and processing speed deficits. Studies on secondary dystonia showed more pronounced cognitive deficits and lower IQ scores with frequent intellectual disability. Data are missing for attention, language, and executive functioning.Interpretation: This systematic review shows possible cognitive impairments in childhood dystonia. The severity of cognitive impairment seems to intensify with increasing neurological abnormalities. However, the available data on cognition in childhood dystonia are very limited and not all domains have been investigated yet. This underlines the need for future research using standardized neuropsychological procedures in this group.What this paper adds: There is limited data on cognition in childhood dystonia. Primary dystonia showed intact cognition and IQ, but mild working memory and processing speed deficits. Secondary dystonia showed more pronounced deficits and lower IQ, with frequent intellectual disability. There is a strong need for case‐control studies assessing cognition using standardized neuropsychological tests.

Objective:Cervical dystonia (CD) is a movement disorder characterized by involuntary muscle contractions causing sustained twisting movements and abnormal postures of the neck and head. Assumed affected neuronal regions are the cortico-striatal-thalamo-cortical circuits, which are also involved in cognitive functioning. Indeed, impairments in different cognitive domains have been found in CD patients. However, to date studies have only investigated a limited range of cognitive functions within the same sample. In particular, social cognition (SC) is often missing from study designs. Hence, we aimed to evaluate a broad range of cognitive functions including SC in CD patients.Method:In the present study 20 idiopathic CD patients and 40 age-, gender-, and IQ-matched healthy controls (HCs) were assessed with tests for non-SC (verbal memory, psychomotor speed, and executive functions) as well as for SC (emotion recognition, Theory of Mind (ToM), and empathy).Results:CD patients scored on average significantly lower than HC on tests for non-SC, but did not show impairments on any of the tests for SC.Conclusions:The current study showed impairments in non-SC in CD, but intact social cognitive functions. These results underline the importance of recognizing non-motor symptoms in idiopathic CD patients, but emphasize a focus on identifying strengths and weaknesses in cognitive functioning as these influence daily life activities.

Deep brain stimulation (DBS) of the internal globus pallidus (GPi) is a recognized treatment for medication‐refractory dystonia. Problems in executive functions and social cognition can be part of dystonia phenotypes. The impact of pallidal DBS on cognition appears limited, but not all cognitive domains have been investigated yet. In the present study, we compare cognition before and after GPi DBS. Seventeen patients with dystonia of various aetiology completed pre‐ and post‐DBS assessment (mean age 51 years; range 20–70 years). Neuropsychological assessment covered intelligence, verbal memory, attention and processing speed, executive functioning, social cognition, language and a depression questionnaire. Pre‐DBS scores were compared with a healthy control group matched for age, gender and education, or with normative data. Patients were of average intelligence but performed significantly poorer than healthy peers on tests for planning and for information processing speed. Otherwise, they were cognitively unimpaired, including social cognition. DBS did not change the baseline neuropsychological scores. We confirmed previous reports of executive dysfunctions in adult dystonia patients with no significant influence of DBS on cognitive functioning in these patients. Pre‐DBS neuropsychological assessments appear useful as they support clinicians in counselling their patients. Decisions about post‐DBS neuropsychological evaluations should be made on a case‐by‐case basis.

Early Onset Dystonia (EOD) is thought to result from basal ganglia dysfunction, structures also involved in non-motor functions, like regulation of behavior, mood and anxiety. Problems in these domains have been found in proxy-reports but not yet in self-reports of EOD patients. The main questions are whether proxy-reports differ from those of patients and how problems relate to everyday social functioning. Subjective complaints about executive problems (BRIEF) and symptoms of depression and anxiety (CBCL) were obtained through a cross-sectional questionnaire study conducted on 45 EOD patients. Scores were in the normal range in patients and proxies. Proxy-rated behavior regulation was correlated with the estimated number of friends and quality of relations. Proxy-reported scores of depression correlated with the quality of relations and were higher than self-reports of adolescent/young adult patients. EOD patients and proxies do not seem to experience problematic regulation of behavior, mood and anxiety. Still, our study revealed two important aspects: (1) all measures were related to the estimated quality of relations with others, relating questionnaires to everyday social functioning; (2) proxies reported more symptoms of depression than patients. This may indicate overestimation by proxies or higher sensitivity of proxies to these symptoms, implying underestimation of problems by patients.