Nonmotor disturbances in Parkinson's disease

Nonmotor disturbances (NMDs) affect most patients with Parkinson's disease (PD) and often have a profound impact on their quality of life. NMDs such as depression, anxiety, fatigue, REM sleep behavior disorder, constipation, delayed gastric emptying, altered olfaction and pain can precede the onset of motor symptoms. Other NMDs, including hallucinations, dementia, excessive daytime sleepiness, insomnia, orthostatic hypotension and bladder disturbances, typically appear later in the course of PD. For most NMDs of PD, nondopaminergic and non-nigrostriatal mechanisms (e.g. neurodegeneration of other transmitter systems in the cortex and brainstem, side effects of medications, genetic and psychosocial factors) are considered more relevant than the 'classical' dopaminergic-nigrostriatal dysfunction. The recognition of NMDs requires a high degree of clinical suspicion, the use of specific questionnaires and ancillary tests. Pharmacological and nonpharmacological approaches can be effective, but for most forms of treatment of NMDs, the scientific evidence is limited.

Orexin receptor antagonism, a new sleep-enabling paradigm: a proof-of-concept clinical trial

The orexin system is a key regulator of sleep and wakefulness. In a multicenter, double-blind, randomized, placebo-controlled, two-way crossover study, 161 primary insomnia patients received either the dual orexin receptor antagonist almorexant, at 400, 200, 100, or 50 mg in consecutive stages, or placebo on treatment nights at 1-week intervals. The primary end point was sleep efficiency (SE) measured by polysomnography; secondary end points were objective latency to persistent sleep (LPS), wake after sleep onset (WASO), safety, and tolerability. Dose-dependent almorexant effects were observed on SE , LPS , and WASO . SE improved significantly after almorexant 400 mg vs. placebo (mean treatment effect 14.4%; P < 0.001). LPS (–18 min (P = 0.02)) and WASO (–54 min (P < 0.001)) decreased significantly at 400 mg vs. placebo. Adverse-event incidence was dose-related. Almorexant consistently and dose-dependently improved sleep variables. The orexin system may offer a new treatment approach for primary insomnia.

Sleep and wakefulness disturbances in Swiss pharmacy customers

BACKGROUND AND OBJECTIVE: Sleep disturbances are prevalent but often overlooked or underestimated. We suspected that sleep disorders might be particularly common among pharmacy customers, and that they could benefit from counselling. Therefore, we described the prevalence and severity of symptoms associated with sleep and wakefulness disorders among Swiss pharmacy customers, and estimated the need for counselling and treatment. METHODS: In 804 Swiss pharmacies (49% of all community pharmacies) clients were invited to complete the Stanford Sleep Disorders Questionnaire (SDQ), and the Epworth Sleepiness Scale (EPW). The SDQ was designed to classify symptoms of sleep and wakefulness into the four most prevalent disorders: sleep apnoea syndrome (SAS), insomnia in psychiatric disorders (PSY), periodic leg movement disorders/restless legs (RLS) and narcolepsy (NAR). Data were entered into an internet-linked database for analysis by an expert system as a basis for immediate counselling by the pharmacist. RESULTS: Of 4901 participants, 3238 (66.1%) were female, and 1663 (33.9%) were male. The mean age (SD) of females and males was 52.4 (18.05), and 55.1 (17.10) years, respectively. The percentages of female and male individuals above cut-off of SDQ subscales were 11.4% and 19.8% for sleep apnoea, 40.9% and 38.7% for psychiatric sleep disorders, 59.3% and 46.8% for restless legs, and 10.4% and 9.4% for narcolepsy respectively. The prevalence of an Epworth Sleepiness Scale score >11 was 16.5% in females, and 23.9% in males. Reliability assessed by Cronbach's alpha was 0.65 to 0.78 for SDQ subscales, and for the Epworth score. CONCLUSIONS: Symptoms of sleep and wakefulness disorders among Swiss pharmacy customers were highly prevalent. The SDQ and the Epworth Sleepiness Scale score had a satisfactory reliability to be useful for identification of pharmacy customers who might benefit from information and counselling while visiting pharmacies. The internet-based system proved to be a helpful tool for the pharmacist when counselling his customers in terms of diagnostic classification and severity of symptoms associated with the sleeping and waking state.

Sleep-wake disturbances in sporadic Creutzfeldt-Jakob disease

BACKGROUND: The prevalence and characteristics of sleep-wake disturbances in sporadic Creutzfeldt-Jakob disease (sCJD) are poorly understood. METHODS: Seven consecutive patients with definite sCJD underwent a systematic assessment of sleep-wake disturbances, including clinical history, video-polysomnography, and actigraphy. Extent and distribution of neurodegeneration was estimated by brain autopsy in six patients. Western blot analyses enabling classification and quantification of the protease-resistant isoform of the prion protein, PrPSc, in thalamus and occipital cortex was available in four patients. RESULTS: Sleep-wake symptoms were observed in all patients, and were prominent in four of them. All patients had severe sleep EEG abnormalities with loss of sleep spindles, very low sleep efficiency, and virtual absence of REM sleep. The correlation between different methods to assess sleep-wake functions (history, polysomnography, actigraphy, videography) was generally poor. Brain autopsy revealed prominent changes in cortical areas, but only mild changes in the thalamus. No mutation of the PRNP gene was found. CONCLUSIONS: This study demonstrates in sporadic Creutzfeldt-Jakob disease, first, the existence of sleep-wake disturbances similar to those reported in fatal familial insomnia in the absence of prominent and isolated thalamic neuronal loss, and second, the need of a multimodal approach for the unambiguous assessment of sleep-wake functions in these patients.

Sleep-wake habits and disorders in a series of 100 adult epilepsy patients--a prospective study

The aim of the study was to assess sleep-wake habits and disorders and excessive daytime sleepiness (EDS) in an unselected outpatient epilepsy population. Sleep-wake habits and presence of sleep disorders were assessed by means of a clinical interview and a standard questionnaire in 100 consecutive patients with epilepsy and 90 controls. The questionnaire includes three validated instruments: the Epworth Sleepiness Scale (ESS) for EDS, SA-SDQ for sleep apnea (SA), and the Ullanlinna Narcolepsy Scale (UNS) for narcolepsy. Sleep complaints were reported by 30% of epilepsy patients compared to 10% of controls (p=0.001). The average total sleep time was similar in both groups. Insufficient sleep times were suspected in 24% of patients and 33% of controls. Sleep maintenance insomnia was more frequent in epilepsy patients (52% vs. 38%, p=0.06), whereas nightmares (6% vs. 16%, p=0.04) and bruxism (10% vs. 19%, p=0.07) were more frequent in controls. Sleep onset insomnia (34% vs. 28%), EDS (ESS >or=10, 19% vs. 14%), SA (9% vs. 3%), restless legs symptoms (RL-symptoms, 18% vs. 12%) and most parasomnias were similarly frequent in both groups. In a stepwise logistic regression model loud snoring and RL-symptoms were found to be the only independent predictors of EDS in epilepsy patients. In conclusion, sleep-wake habits and the frequency of most sleep disorders are similar in non-selected epilepsy patients as compared to controls. In epilepsy patients, EDS was predicted by a history of loud snoring and RL-symptoms but not by SA or epilepsy-related variables (including type of epilepsy, frequency of seizures, and number of antiepileptic drugs).

Evolution of sleep and sleep EEG after hemispheric stroke

The evolution of subjective sleep and sleep electroencephalogram (EEG) after hemispheric stroke have been rarely studied and the relationship of sleep variables to stroke outcome is essentially unknown. We studied 27 patients with first hemispheric ischaemic stroke and no sleep apnoea in the acute (1-8 days), subacute (9-35 days), and chronic phase (5-24 months) after stroke. Clinical assessment included estimated sleep time per 24 h (EST) and Epworth sleepiness score (ESS) before stroke, as well as EST, ESS and clinical outcome after stroke. Sleep EEG data from stroke patients were compared with data from 11 hospitalized controls and published norms. Changes in EST (>2 h, 38% of patients) and ESS (>3 points, 26%) were frequent but correlated poorly with sleep EEG changes. In the chronic phase no significant differences in sleep EEG between controls and patients were found. High sleep efficiency and low wakefulness after sleep onset in the acute phase were associated with a good long-term outcome. These two sleep EEG variables improved significantly from the acute to the subacute and chronic phase. In conclusion, hemispheric strokes can cause insomnia, hypersomnia or changes in sleep needs but only rarely persisting sleep EEG abnormalities. High sleep EEG continuity in the acute phase of stroke heralds a good clinical outcome.

Prescriptions of Chinese medicinal herbs in Switzerland: the example of suan zao ren (Ziziphi Spinosae Semen)

Introduction According to the Swiss Health Survey 2007, 1.7% of the adult population use traditional Chinese medicine (including Chinese herbal medicine, but excluding acupuncture). In contrast to conventional drugs, that contain single chemically defined substances, prescriptions of Chinese herbs are mixtures of up to 40 ingredients (parts of plants, fungi, animal substances and minerals). Originally they were taken in the form of decoctions, but nowadays granules are more popular. Medium daily dosages of granules range between 8 to 12g. In a recent work we identified the most commonly used Chinese herbs (all ingredients are referred to as herbs for reasons of simplicity) and classical formulas (mixtures). Here we present a short overview and the example of suan zao ren (Ziziphi Spinosae Semen), which is used in the treatment of insomnia and anxiety and contains saponins that have been shown to increase sleep in animal studies. Material and Methods A random sample of 1,053 prescriptions was drawn from the database of Lian Chinaherb AG, Switzerland, and analysed according to the most frequently used individual herbs and classical formulas. Cluster analysis (Jaccard similarity coefficient, complete linkage method) was applied to identify common combinations of herbs. Results The most frequently used herbs were dang gui (Angelicae Sinensis Radix), fu ling (Poria), bai shao (Paeoniae Radix Alba), and gan cao (Glycyrrhizae Radix et Rhizoma); the most frequently used classical formulas were gui pi tang (Restore the Spleen Decoction) and xiao yao san (Rambling Powder). The average number of herbs per prescription was 12.0, and the average daily dosage of granules was 8.7g. 74.3% of the prescriptions were for female, 24.8% for male patients. Suan zao ren was present in 14.2% of all prescriptions. These prescriptions contained on average 13.7 herbs, and the daily dosage of granules was 8.9g. Suan zao ren was more frequently prescribed by practitioners of non-Asian than of Asian origin but equally often for female and male patients. Cluster analysis grouped suan zao ren with yuan zhi (Polygalae Radix), bai zi ren (Platycladi Semen), sheng di huang (Rehmanniae Radix) and dan shen (Salviae Miltiorrhizae Radix et Rhizoma). Discussion Prescriptions including suan zao ren contained on average slightly more herbs than other prescriptions. This might be due to the fact that two of the three most popular classical formulas with suan zao ren are composed of 13 and 12 herbs with the possibility of adding more ingredients when necessary. Cluster analysis resulted in the clustering of suan zao ren with other herbs of the classical formula tian wang bu xin dan (Emperor of Heaven’s Special Pill to Tonify the Heart), indicating the use of suan zao ren for the treatment of insomnia and irritability. Unfortunately, the diagnoses of the patients were unavailable and thus correlations between use of suan zao ren and diseases could not be analysed.