Elisabeth Brandauer

Transcranial ultrasound shows nigral hypoechogenicity in restless legs syndrome

In patients with Parkinsons disease, hyperechogenicity of the substantia nigra using transcranial ultrasound has been related to increased tissue concentrations of iron. Recently, deficient iron transport mechanisms in substantia nigra neurons have been described in postmortem tissue of patients with restless legs syndrome (RLS). This study was performed to study substantia nigra echogenicity in RLS patients compared with normal control subjects and Parkinsons disease patients. RLS patients had significantly reduced midbrain areas of hyperechogenicity compared with control subjects, and even more markedly reduced hyperechogenicity compared with Parkinsons disease patients. These findings lend further support to nigral iron deficiency as a pathogenetic factor in RLS. Ann Neurol 2005

Video analysis of motor events in REM sleep behavior disorder.

In REM sleep behavior disorder (RBD), several studies focused on electromyographic characterization of motor activity, whereas video analysis has remained more general. The aim of this study was to undertake a detailed and systematic video analysis. Nine polysomnographic records from 5 Parkinson patients with RBD were analyzed and compared with sex‐ and age‐matched controls. Each motor event in the video during REM sleep was classified according to duration, type of movement, and topographical distribution. In RBD, a mean of 54 ± 23.2 events/10 minutes of REM sleep (total 1392) were identified and visually analyzed. Seventy‐five percent of all motor events lasted <2 seconds. Of these events, 1,155 (83.0%) were classified as elementary, 188 (13.5%) as complex behaviors, 50 (3.6%) as violent, and 146 (10.5%) as vocalizations. In the control group, 3.6 ± 2.3 events/10 minutes (total 264) of predominantly elementary simple character (n = 240, 90.9%) were identified. Number and types of motor events differed significantly between patients and controls (P < 0.05). This study shows a very high number and great variety of motor events during REM sleep in symptomatic RBD. However, most motor events are minor, and violent episodes represent only a small fraction.

The severity range of restless legs syndrome (RLS) and augmentation in a prospective patient cohort: Association with ferritin levels

OBJECTIVES The aim of the study was to prospectively examine all patients with a diagnosis of RLS consulting a sleep disorders clinic and to assess RLS severity and augmentation and their associations, including ferritin levels. METHODS Patients were stratified into patients with RLS as ancillary diagnosis, RLS sufferers without current augmentation and RLS sufferers with current augmentation. Work-up included RLS severity scales and blood biochemical variables including indices of iron metabolism. RESULTS In an 18-month period, 302 patients with RLS (183 women, 119 men; mean age, 59.1+/-13.7 years) were recruited. RLS was considered idiopathic in 291 patients (96.4%). Most patients (240, 79.5%) were RLS sufferers, whereas the remaining 62 (20.5%) had RLS as ancillary diagnosis. Nineteen out of 162 patients treated with dopaminergic agents (11.7%) had current augmentation. Almost one-third of all patients (31.1%) had ferritin levels <50microg/l. Patients with an ancillary diagnosis of RLS had higher ferritin levels than RLS sufferers without current augmentation. The lowest ferritin levels were present in RLS sufferers with current augmentation 132.8+/-98.0microg/l vs. 100.6+/-84.5microg/l vs. 55.8+/-43.6microg/l; p=0.002). Patients with augmentation did not differ from non-augmented patients regarding age, gender, RLS etiology, presence of previous augmentation, or any other documented comorbidity (p>0.05). CONCLUSION The severity spectrum of RLS in this clinical cohort ranged from the ancillary diagnosis of RLS to augmented RLS. There was an inverse correlation between RLS severity and ferritin levels. Patients with current augmentation had the lowest ferritin levels. Our data further strengthen a putative role of low iron stores as a potential aggravator of idiopathic RLS. Moreover, low ferritin might represent a potential biomarker of RLS augmentation under dopaminergic therapy.

Increased daytime sleepiness in Parkinson's disease: A questionnaire survey

We evaluated the frequency and severity of excessive daytime sleepiness in an outpatient population with Parkinsons disease in comparison to age‐matched controls and examined its relationship with antiparkinsonian drug therapy and sleep history. Increased daytime sleepiness and involuntary sleep episodes have been described in Parkinsons disease, but the etiology is not completely understood. The Epworth Sleepiness Scale (ESS), a validated questionnaire for daytime sleepiness, was prospectively administered to 99 consecutive outpatients with Parkinsons disease and 44 age‐matched controls. In addition, a short sleep‐screening questionnaire was used. The ESS revealed significantly increased daytime sleepiness in PD patients compared to controls (7.5 ± 4.6 vs. 5.8 ± 3.0, P = 0.013). The ESS score was abnormally high (10 or more) in 33 % of PD patients and 11.4% of controls (P = 0.001). ESS was not different between PD patients on levodopa monotherapy and those on levodopa and dopamine agonists, or between patients taking ergoline or non‐ergoline dopamine agonists. In PD patients and in controls, sleepiness was significantly associated with reported heavy snoring. Increased daytime sleepiness is more frequent in patients with PD than in elderly controls. Similar to controls, increased daytime sleepiness in PD patients is correlated with heavy snoring.

Riluzole in Huntington's disease (HD): an open label study with one year follow up.

Abstract In an open label study, we administered riluzole (50 mg twice a day) to nine patients with genetically confirmed Huntingtons disease (HD) (clinical stages 1–3; mean age 46.4 (SD 9.3) years; mean disease duration 8 (SD 3.3) years). The study was designed to evaluate (1) safety and tolerability of riluzole and (2) effects of riluzole on motor impairment, functional disability, cognitive impairment, and behavioral abnormalities using the Unified HD Rating Scale. Patients were evaluated at baseline and after three and twelve months of riluzole therapy. Laboratory tests (hematology and liver enzymes) were repeated monthly. All adverse experiences, reported spontaneously or observed directly by the investigator, were recorded. Riluzole was well tolerated. No increase of serum liver enzymes was seen throughout the study in all but one patient showing a mild elevation. At three months, mean total motor scale (TMS), mean TMS chorea subscore, and mean total functional capacity scale were significantly improved compared with baseline. At twelve months, however, this beneficial effect on motor status and overall function was not sustained. In contrast, severity and frequency of behavioral dysfunction as well as psychomotor speed assessed by the symbol digit modalities test were improved compared with baseline. Our data suggest that there are transient antichoreatic effects and more sustained effects of riluzole on psychomotor speed and behavior in patients with HD. A double-blind, placebo-controlled trial appears highly warranted to establish definitely the symptomatic versus neuroprotective actions of riluzole in HD.

REM sleep behavior disorder in 703 sleep-disorder patients: the importance of eliciting a comprehensive sleep history.

OBJECTIVES The aim of our study was to evaluate the frequency of REM sleep behavior disorder (RBD) in a mixed sleep laboratory population and to assess potential associations. Moreover, we investigated referral diagnoses of patients subsequently diagnosed with RBD and assessed the frequency of incidental RBD. METHODS Charts and polysomnographic reports of 703 consecutive patients comprising the full spectrum of ICSD-2 sleep disorders [501 males, 202 females; mean age, 51.0+/-14.1 years (range: 10-82 years)] were carefully reviewed. The vast majority of patients were adults (98.7%). Patients were categorized into those with and without RBD. For associations, all concomitant sleep and neurological diagnoses and medications were evaluated. RESULTS Thirty-four patients (4.8%) were diagnosed with RBD (27 men; 7 women, mean age, 57.7+/-12.3 years). RBD was idiopathic in 11 patients (1.6%; 9 men) and symptomatic in 23 patients (3.3%; 18 men) secondary to Parkinsonian syndromes (n=11), use of antidepressants (n=7), narcolepsy with cataplexy (n=4), and pontine infarction (n=1). Six out of 34 patients were referred for suspected RBD, 20 reported RBD symptoms only on specific questioning, and 8 patients had no history of RBD but showed typical RBD behavioral manifestations in the video-polysomnography. Logistic regression analysis revealed significant associations between RBD and the presence of Parkinsonian syndromes (odds ratio [OR] 16.8, 95%CI: 6.4-44.1; P<0.001), narcolepsy with cataplexy (OR 10.7, 95%CI: 2.9-40.2; P<0.001), SSRI use (OR 3.9, 95%CI: 1.6-9.8; P=0.003), and age (OR 1.5/10-year increase, 95%CI: 1.0-2.0; P=0.039). CONCLUSION In this population of 703 consecutive sleep-disorder patients, RBD was uncommon. Its etiology was predominantly symptomatic. The majority of RBD patients reported RBD symptoms on specific questioning only, underlining the importance of eliciting a comprehensive sleep history for the diagnosis of RBD.

Validation of the Innsbruck REM sleep behavior disorder inventory

A diagnosis of definite REM sleep behavior disorder requires both a positive history for REM sleep behavior disorder and polysomnographic demonstration of REM sleep without atonia. To improve and facilitate screening for REM sleep behavior disorder, there is a need for simple clinical tools with sufficient sensitivity and specificity for the identification of subjects with probable REM sleep behavior disorder. We developed a short REM sleep behavior disorder screening questionnaire with 7 REM sleep behavior disorder– and 2 non‐REM sleep behavior disorder–specific control items and performed a validation study in 70 REM sleep behavior disorder subjects and 140 sleep disorder controls. Response patterns to all 7 REM sleep behavior disorder–specific items differed between REM sleep behavior disorder and non‐REM sleep behavior disorder patients (all P < 0.05), whereas the 2 non‐REM sleep behavior disorder–specific control items did not differentiate between REM sleep behavior disorder and non‐REM sleep behavior disorder (all P > .05). In 5 of the 7 REM sleep behavior disorder–specific items, AUC was greater than 0.700. These 5 items were included in the Innsbruck REM sleep behavior disorder inventory. In this questionnaire, a cutoff of 0.25 (number of positive symptoms divided by number of answered questions) had a sensitivity of 0.914 and a specificity of 0.857 for both idiopathic and Parkinsons‐related REM sleep behavior disorder (AUC, 0.886). The Innsbruck REM sleep behavior disorder inventory is a promising, easy‐to‐use, short screening tool for REM sleep behavior disorder with excellent sensitivity and specificity for both idiopathic and Parkinsons‐related REM sleep behavior disorder.

Disturbance of rapid eye movement sleep in spinocerebellar ataxia type 2

Five genetically confirmed spinocerebellar ataxia type 2 (SCA2) patients were admitted to our sleep laboratory for two all‐night video‐polysomnographies. A standard montage was used, including electroencephalography, vertical and horizontal electrooculography, electromyography of mental, submental, and tibialis anterior muscles, and respiratory monitoring. Four of five SCA2 patients had insufficient muscle atonia during rapid eye movement (REM) sleep. All patients exhibited myoclonic jerks during REM sleep, while elaborated behavior was not observed in the video. Abnormal motor control during sleep with periodic leg movements and REM sleep without atonia occurs frequently in SCA2. This finding may reflect a dysfunction of dopaminergic and/or brainstem and cerebellar outflow pathways.

Cerebral vasoreactivity decreases overnight in severe obstructive sleep apnea syndrome: A study of cerebral hemodynamics

BACKGROUND OSAS has been associated with surrogate markers of atherosclerosis and is a known risk factor for stroke. However, there is limited data on the effects of recurring apneas in severe OSAS on cerebral circulation and their consequences on cerebrovascular reactivity and compliance. OBJECTIVE To evaluate cerebral blood flow velocity (CBFV) changes and vascular compliance in patients with severe obstructive sleep apnea syndrome (OSAS) using transcranial Doppler sonography (TCD) and cerebral pulse transit time (PTT). METHODS Seven patients (1 woman, 6 men, mean age 57.4 years) with severe OSAS underwent polysomnography at the sleep laboratory of the Neurology Department of Innsbruck Medical University. TCD was performed continuously during the whole night using a pulsed wave probe and was co-registered with routine polysomnography. Cerebrovascular reactivity was assessed by calculation of apnea and hypopnea-related CBFV changes. Arterial compliance was characterized by PTT derived from phase difference analysis between ECG and TCD signals. Sleep time was dichotomized into periods with high density of consecutive respiratory events (CRE) vs. periods with low density of consecutive respiratory events (non-CRE). TCD measurements of CBFV showed a regular, undulating pattern with flow minima immediately before apneas or hypopneas and maxima closely after their termination, reciprocally to peripheral O(2) saturation. CBFV reactivity was significantly diminished in CRE compared to non-CRE periods. PTT phase differences were reduced in non-CRE, and even more so in CRE periods, compared to initial wake phases. CONCLUSION We found severe disturbances of cerebrovascular reactivity in OSAS patients. Our data demonstrate loss of vasoreactivity and increase of arterial stiffness, indicated by CBF hyporeactivity and PTT reduction, especially during CRE periods. These changes are likely to impair cerebral circulation and may be detrimental to the endothelium.

Delayed diagnosis, range of severity, and multiple sleep comorbidities: a clinical and polysomnographic analysis of 100 patients of the innsbruck narcolepsy cohort.

STUDY OBJECTIVES Narcolepsy is reported to affect 26-56/100,000 in the general population. We aimed to describe clinical and polysomnographic features of a large narcolepsy cohort in order to comprehensively characterize the narcoleptic spectrum. METHODS We performed a chart- and polysomnographybased review of all narcolepsy patients of the Innsbruck narcolepsy cohort. RESULTS A total of 100 consecutive narcolepsy patients (87 with cataplexy [NC], 13 without cataplexy [N]) were included in the analysis. All subjects had either excessive daytime sleepiness or cataplexy as their initial presenting clinical feature. Age at symptom onset was 20 (6-69) years. Diagnostic delay was 6.5 (0-39) years. The complete narcolepsy tetrad was present in 36/100 patients; 28/100 patients had three cardinal symptoms; 29/100 had two; and 7/100 had only excessive daytime sleepiness. Severity varied broadly with respect to excessive daytime sleepiness (median Epworth Sleepiness Scale score: 18, range 10-24), cataplexy (8-point Likert scale: median 4.5, range 1-8), hypnagogic hallucinations (median 4.5, range 1-7), and sleep paralysis (median 3, range 1-7). Sleep comorbidity was highly prevalent and ranged from sleeprelated movement disorders (n = 55/100), parasomnias (n = 34/100), and sleeprelated breathing disorders (n = 24/100), to insomnia (n = 28/100). REM sleep without atonia or a periodic limb movement in sleep index > 5/h were present in most patients (90/100 and 75/100). A high percentage of narcoleptic patients in the present study had high frequency leg movements (35%) and excessive fragmentary myoclonus (22%). Of the narcolepsy patients with clinical features of REM sleep behavior disorder (RBD), 76.5% had EMG evidence for RBD on the multiple sleep latency test (MSLT), based on a standard cutoff of a minimum of 18% of 3-sec miniepochs. CONCLUSION This study is one of the largest monocentric polysomnographic studies to date of patients with narcolepsy and confirms the frequent comorbidity of narcolepsy with many other sleep disorders. Our study is the first to evaluate the percentage of patients with high frequency leg movements and excessive fragmentary myoclonus in narcolepsy and is the first to demonstrate EMG evidence of RBD in the MSLT. These findings add to the growing body of literature suggesting that motor instability is a key feature of narcolepsy.