Transdermal Rotigotine Improves Sleep Fragmentation in Parkinson's Disease: Results of the Multicenter, Prospective SLEEP-FRAM Study.

Sleep disturbances occur frequently in patients with Parkinson's disease (PD). The aim of this study was to investigate the effects of rotigotine on sleep fluctuations in a sample of PD patients with self-reported complaints of nocturnal awakenings. This prospective, open-label, observational, and multicenter study enrolled consecutive outpatients with PD and administered rotigotine (mean dose 8.9 mg/day) for 3 months. The primary endpoint was the change from baseline in sleep fragmentation, assessed using the sleep maintenance subscale score of the Parkinson's Disease Sleep Scale (PDSS). The newly designed Parkinson's Disease Sleep Fragmentation Questionnaire (PD-SFQ) was used to measure other sleep parameters. A total of 62 patients were enrolled (mean age 70.2 years; 66% male). At 3 months, rotigotine significantly improved sleep fragmentation from baseline on the PDSS-2 sleep maintenance subscale (from 3.4 ± 0.9 to 1.9 ± 1.4; P < 0.0001). Rotigotine also significantly improved nocturnal motor symptoms (P < 0.0001), restless legs-like symptoms (P < 0.005), and nocturia (P = 0.004). Rotigotine significantly improved self-reported complaints of sleep fragmentation in PD patients and could be a useful treatment to improve this specific sleep problem in PD. However, these results are based on a small and clinically heterogeneous sample so they must be taken cautiously.

Rate of dementia diagnoses according to the degree of aging of the population.

BACKGROUND: There is a lack of information regarding geographical differences in the incidence and prevalence of dementia diagnosis according to the degree of aging of the population. The objectives of this study were to analyze the rate of dementia diagnoses, and to compare the dementia subtypes and the clinical characteristics of the patients depending on the degree of aging of their municipalities. METHODS: We used data from the Registry of Dementias of Girona (ReDeGi), containing the cases of dementia diagnosed in the memory clinics of the Health Region of Girona, in Catalonia (Spain), during 2007-2012. The municipalities were classified by a cluster analysis as aged or young municipalities according to their proportion of older people using population ageing indicators. The incidence rates of dementia diagnosis in each type of municipality were compared. RESULTS: The ReDeGi registered 4,314 cases in the municipalities under surveillance. The clinical incidence of dementia was lower in aged municipalities (4.5 vs. 6.1 cases per 1,000 person-years aged 65 and over). Patients from young municipalities had an increased frequency of behavioral and psychological symptoms of dementia. CONCLUSIONS: The environment may influence the clinical manifestations of dementia that predispose people to visit health specialists and obtain a diagnosis.

Psychotropic drugs in patients with Alzheimer's Disease: a longitudinal study by the Registry of Dementias of Girona (ReDeGi) in Catalonia, Spain.

OBJECTIVES: Psychotropic drugs are usually prescribed to deal with behavioral and psychological symptoms of dementia, especially when nonpharmacologic approaches are not available or have limited efficacy. Poor outcomes and serious adverse events of the drugs used must be addressed, and risk-benefit ratios need to be considered. The aim of this longitudinal study was to describe the evolution of dispensation of psychotropic drugs in patients with Alzheimer's disease (AD) and to identify the associated demographic and clinical variables. METHODS: Longitudinal study using 698 cases with AD included in the Registry of Dementias of Girona in 2007 and 2008 and followed up during 3 years. Drugs were categorized according to the Anatomical Therapeutic Chemical classification. Binary logistic regression analyses were used to detect the variables associated with the use of antipsychotics, selective serotonin reuptake inhibitors (SSRIs), anxiolytics, and hypnotics. RESULTS: Of the patients, 51.2% consumed antipsychotics at least once during the three years of the study, whereas 73.3% and 58.2% consumed SSRIs and anxiolytics, respectively; 32.8% used hypnotics. Antipsychotic use was associated with a diagnosis of AD with delusions) [odds ratio (OR) = 5.7] and with increased behavior disorders (OR = 1.2). Patients with AD with depressed mood were more likely to be treated with SSRIs (OR = 3.1), while being a woman was associated with increased dispensation of anxiolytics (OR = 1.9) and SSRIs (OR = 2.2). CONCLUSIONS: Consumption of psychotropic drugs by the patients with AD registered in the Registry of Dementias of Girona is very high. Despite all the described adverse effects and recommendations of caution in their use, antipsychotics still are extensively used.

Psychogenic paroxysmal movement disorders--clinical features and diagnostic clues.

BACKGROUND: The diagnosis of psychogenic paroxysmal movement disorders (PPMD) can be challenging, in particular their distinction from the primary paroxysmal dyskinesias (PxD) remains difficult. METHODS: Here we present a large series of 26 PPMD cases, describe their characteristics, contrast them with primary PxD and focus on their distinguishing diagnostic features. RESULTS: Mean age at onset was 38.6 years, i.e. much later than primary PxD. Women were predominantly affected (73%). Most subjects (88.4%) had long attacks, and unlike primary PxD there was a very high within-subject variability for attack phenomenology, duration and frequency. Dystonia was the most common single movement disorder presentation, but 69.2% of the patients had mixed or complex PxD. In 50% of PPMD cases attack triggers could be identified but these were unusual for primary PxD. 42.3% of patients employed unusual strategies to alleviate or stop the attacks. Response to typical medication used for primary PxD was poor. Precipitation of the disorder due to physical or emotional life events and stressors were documented in 57.6% and 65.3% of the cases respectively. Additional interictal psychogenic signs were documented in 34.6% and further medically unexplained somatic symptoms were present in 50% of the cases. 19.2% of patients had a comorbid organic movement disorder and 26.9% had pre-existing psychiatric comorbidities. CONCLUSION: Although the phenotypic presentation of PPMD can be highly diverse, certain clinical characteristics help in distinguishing this condition from the primary forms of PxD. Recognition is important as multidisciplinary treatment approaches led to significant improvement in most cases.

Cerebellar learning distinguishes inflammatory neuropathy with and without tremor.

OBJECTIVES: This study aims to investigate if patients with inflammatory neuropathies and tremor have evidence of dysfunction in the cerebellum and interactions in sensorimotor cortex compared to nontremulous patients and healthy controls. METHODS: A prospective data collection study investigating patients with inflammatory neuropathy and tremor, patients with inflammatory neuropathy without tremor, and healthy controls on a test of cerebellar associative learning (eyeblink classical conditioning), a test of sensorimotor integration (short afferent inhibition), and a test of associative plasticity (paired associative stimulation). We also recorded tremor in the arms using accelerometry and surface EMG. RESULTS: We found impaired responses to eyeblink classical conditioning and paired associative stimulation in patients with neuropathy and tremor compared with neuropathy patients without tremor and healthy controls. Short afferent inhibition was normal in all groups. CONCLUSIONS: Our data strongly suggest impairment of cerebellar function is linked to the production of tremor in patients with inflammatory neuropathy.

Patients with rest-tremor and scans with ipsilateral dopaminergic deficit.

Dopamine transporter imaging is typically abnormal in Parkinson's disease and shows reduced striatal uptake, which is typically greater contralateral to the clinically more affected side. However, tremor-dominant Parkinson's disease patients may have significantly lower uptake in the striatum ipsilateral to the rest-tremor compared to akinetic-rigid PD patients, implying a possible role of an ipsilateral deficit in the generation of rest-tremor.We report here three patients with rest-tremor and the unexpected finding of an ipsilateral presynaptic dopaminergic deficit with normal uptake contralateral to the rest-tremor in dopamine transporter imaging. We divided them in two groups, with and without a corresponding structural lesion in brain imaging. These data may suggest a role of ipsilateral dopaminergic deficit in the generation of rest-tremor. An explanation of these findings could be damage of crossed dopaminergic fibres from the substantia nigra to thalamus, which can cause motor impairment ipsilateral to dopamine depletion experimentally. This is speculative but there is no doubt that these cases exist and we encourage others to report similar cases, as this may assist in the better understanding of the yet unknown pathophysiology of rest-tremor.

Central nervous system drug consumption depending on the time between symptom onset and the diagnosis of Alzheimer's disease: an analysis by the Registry of Dementias of Girona.

AIMS: To describe central nervous system (CNS) drug consumption patterns depending on the time to diagnosis of Alzheimer's disease (AD), and to check whether the cases diagnosed later are associated with greater severity and consuming more CNS drugs. METHODS: Cross-sectional study using 952 cases of the Registry of Dementias of Girona. A binary logistic regression was used to detect variables associated with the use of CNS drugs depending on the time to diagnosis. RESULTS: CNS drugs were consumed by 95.8% of the AD patients. Only antipsychotics presented a statistically significant increase in the frequency of prescription to patients with longer time elapsed from symptom onset to AD diagnosis. CONCLUSION: Longer time elapsed from the onset of symptoms to the diagnosis resulted in increased probability of antipsychotic consumption.

Moving toward "laboratory-supported" criteria for psychogenic tremor.

A confident clinical diagnosis of psychogenic tremor is often possible, but, in some cases, a "laboratory-supported" level of certainty would aid in early positive diagnosis. Various electrophysiological tests have been suggested to identify patients with psychogenic tremor, but their diagnostic reliability has never been assessed "head to head" nor compared to forms of organic tremor other than essential tremor or PD. We compared baseline tremor characteristics (e.g., frequency and amplitude) as well as electrophysiological tests previously reported to distinguish psychogenic and organic tremor in a cohort of 13 patients with psychogenic tremor and 25 patients with organic tremor, the latter including PD, essential-, dystonic-, and neuropathic tremors. We assessed between-group differences and calculated sensitivity and specificity for each test. A number of tests, including entrainment or frequency changes with tapping, pause of tremor during contralateral ballistic movements, increase in tremor amplitude with loading, presence of coherence, and tonic coactivation at tremor onset, revealed significant differences on a group level, but there was no single test with adequate sensitivity and specificity for separating the groups (33%-77% and 84%-100%, respectively). However, a combination of electrophysiological tests was able to distinguish psychogenic and organic tremor with excellent sensitivity and specificity. A laboratory-supported level of diagnostic certainty in psychogenic tremor is likely to require a battery of electrophysiological tests to provide sufficient specificity and sensitivity. Our data suggest such a battery that, if supported in a prospective study, may form the basis of laboratory-supported criteria for the diagnosis of psychogenic tremor.

A longitudinal functional MRI study of non-arteritic anterior ischaemic optic neuropathy patients.

BACKGROUND: Non-arteritic anterior ischaemic optic neuropathy (NA-AION) can cause disabling visual loss and traditionally, visual prognosis has been considered poor, although recent studies have demonstrated improvements in visual acuity in about 30% of patients over time. The aim of the study was to determine whether there was significant cortical reorganisation with functional MRI (fMRI) after acute NA-AION by comparing affected individuals with healthy controls. METHODS: 9 patients with NA-AION were studied acutely and then after 1, 2, 3 and 6 months. 23 healthy volunteers underwent scanning at least twice. At each time point, patients were assessed clinically and with fMRI. For the fMRI experiments, subjects underwent monocular visual stimulation (wearing goggles with flashing LED displays). RESULTS: When stimulating the affected eye, occipital activation was reduced in patients compared with controls. Also, within the NA-AION group, activation in the right Brodmann areas (BA) 44 and 45 was seen during the early phase of the condition. The same areas were activated within the NA-AION group several months later for fellow eye stimulation. When the NA-AION and healthy control groups were formally compared however, these areas (BA 44/45) were not significantly different. NA-AION subjects did show greater activation in visual related areas compared with controls when stimulating the fellow eye. Visual acuity was correlated with more occipital cortex activation when stimulating the affected eye. CONCLUSIONS: There is cortical re-organisation of the fMRI response in extra-visual areas, seen when both affected and fellow eyes are stimulated after NA-AION.

Mental rotation of body parts and sensory temporal discrimination in fixed dystonia.

Fixed dystonia is an uncommon but severely disabling condition typically affecting young women following a minor peripheral injury. There is no evidence of any structural lesions of the central nervous system nor any clear peripheral nerve or root damage. Electrophysiological techniques such as short intracortical inhibition, cortical silent period and a plasticity inducing protocol have revealed similarities but also differences compared to classical mobile dystonia. To further explore the pathophysiology of fixed dystonia we compared mental rotation of body parts and sensory temporal discrimination in 11 patients with fixed dystonia, 11 patients with classical mobile dystonia and 10 healthy controls. In the mental rotation task subjects were presented with realistic photos of left or right hands, feet and the head of a young women with a black patch covering the left or the right eye in six different orientations. Subjects had to verbally report the laterality of the presented stimuli. To assess sensory temporal discrimination subjects were asked to discriminate whether pairs of visual, tactile (electrical), or visuo-tactile stimuli were simultaneous or sequential (temporal discrimination threshold) and in the latter case which stimulus preceded the other (temporal order judgement). In accordance with previous studies patients with mobile dystonia were abnormal in mental rotation and temporal discrimination, whereas patients with fixed dystonia were only impaired in mental rotation. Possible explanations for this deficit may include the influence of the abnormal body posture itself, a shared predisposing pathophysiology for mobile and fixed dystonia, or a body image disturbance. These findings add information to the developing pathophysiological picture of fixed dystonia.

Efficacy of botulinum toxin in severe Tourette syndrome with dystonic tics involving the neck.

Severe dystonic tics involving the neck may lead to the development of serious spine disease. The pharmacological treatment of tics offers symptomatic relief, but clinically relevant improvement of severe tics is not frequently achieved and serious adverse events may result. Botulinum toxin (BnT) appears to be a safe and effective treatment for tics, but some concern exists about which group of patients may benefit from treatment. We report a patient affected by Tourette syndrome with tetraparesis and cervical myelopathy secondary to violent dystonic tics involving the neck, in which a more aggressive course of treatment with BnT in addition to neuroleptic medication resulted in complete resolution of cervical tics after 12 months of follow-up.