A liminal stage after predictive testing for Huntington disease.

BACKGROUND: Following predictive testing for Huntington disease (HD), knowledge of one's carrier status may have consequences on disease onset. Our study aimed to address two questions. First, does knowledge of being a carrier of the pathological HD mutation trigger onset of the disease? Second, does this knowledge influence self-awareness and allow carriers to identify signs and symptoms of disease onset? METHODS: Between 2012 and 2015, 75 HD mutation carriers were examined using the Unified Huntington's Disease Rating Scale (UHDRS) motor score. Onset estimation made with the disease burden score was compared with UHDRS findings. We collected qualitative data with questionnaires and semistructured interviews. RESULTS: 38 women and 37 men, aged 43.7 years±10.5 (20-68), were interviewed after a mean delay between test and study interview of 10.5 years±4.7 (from 4 to 21 years). Estimation of age at onset was 4.5±8.5 years earlier than data-derived age at onset. Participants were categorised according to their motor score: scores <5 were premanifest (n=35), and scores >5 were manifest carriers (n=40). Self-observation was a major preoccupation for all, independent of their clinical status (82% vs 74%, p=0.57). Among manifest carriers, 56% thought they showed symptoms, but only 33% felt ill. Interestingly, this was also observed in those without motor signs (20% and 9%). Being a mutation carrier did not significantly facilitate recognition of motor signs. Interviews with premanifest carriers allowed the burden of self-observation to be illustrated despite lack of motor signs. CONCLUSIONS: Estimating age at onset based on disease burden score may not be accurate. The transition to disease was experienced as an ambiguous or liminal experience. The view of mutation carriers is not always concordant with medical onset estimation, highlighting the difficulties involved in the concept of onset and its use as an outcome in future disease-modifying trials.

Deep brain stimulation for dystonia.

The few controlled studies that have been carried out have shown that bilateral internal globus pallidum stimulation is a safe and long-term effective treatment for hyperkinetic disorders. However, most recent published data on deep brain stimulation (DBS) for dystonia, applied to different targets and patients, are still mainly from uncontrolled case reports (especially for secondary dystonia). This precludes clear determination of the efficacy of this procedure and the choice of the 'good' target for the 'good' patient. We performed a literature analysis on DBS for dystonia according to the expected outcome. We separated those with good evidence of favourable outcome from those with less predictable outcome. In the former group, we review the main results for primary dystonia (generalised/focal) and highlight recent data on myoclonus-dystonia and tardive dystonia (as they share, with primary dystonia, a marked beneficial effect from pallidal stimulation with good risk/benefit ratio). In the latter group, poor or variable results have been obtained for secondary dystonia (with a focus on heredodegenerative and metabolic disorders). From this overview, the main results and limits for each subgroup of patients that may help in the selection of dystonic patients who will benefit from DBS are discussed.

Deep brain stimulation for dystonia.

The few reported controlled studies show that bilateral stimulation of the globus pallidus interna (GPi) is a safe and effective long-term treatment for hyperkinetic disorders. However, the recently published data on deep brain stimulation (DBS) applied to different targets or patients (especially those with secondary dystonia) are mainly uncontrolled case reports, precluding a clear determination of its efficacy, and providing little guidance as to the choice of a "good" target in a "good" patient. This chapter reviews the literature on DBS in primary dystonia, paying particular attention to the risk:benefit ratio in focal and segmental dystonias (cervical dystonia, cranial dystonia) and to the predictive factors for a good outcome. The chapter also highlights recent data on the marked benefits of the technique in myoclonus dystonia (in which pallidal, as opposed to thalamic, stimulation is more effective) and in tardive dystonia-dyskinesia. Although, the decision to treat appears relatively straightforward in patients with primary dystonia, myoclonus-dystonia, and tardive dystonia who have a normal findings on magnetic resonance imaging and normal cognitive function, there are still no reliable tools to help predict the timescale of postoperative benefit. This chapter provides a comprehensive analysis of the use of the treatment in various types of secondary dystonia, with little to moderate benefit in most cases, based on single cases or small series. Beyond the reduction in the severity of dystonia, the global motor and functional outcome is difficult to determine owing to the paucity of adequate evaluation tools. Because of the large interpatient variability, different targets may be effective depending on the symptoms in each individual.

Nonmotor symptoms in Parkinson's disease in 2012: relevant clinical aspects.

Nonmotor symptoms (NMSs) of Parkinson's disease (PD) are common, but they are often underrecognized in clinical practice, because of the lack of spontaneous complaints by the patients, and partly because of the absence of systematic questioning by the consulting physician. However, valid specific instruments for identification and assessment of these symptoms are available in 2012. The administration of the self-completed screening tool, NMSQuest, associated with questioning during the consultation, improves the diagnosis of NMSs. NMSs play a large role in degradation of quality of life. More relevant NMSs are described in this review, mood disorders, impulse control disorders, cognitive deficits, hallucinations, pain, sleep disorders, and dysautonomia.