Daniel Waldvogel

Pulsatile tinnitus —a review of 84 patients

Pulsatile tinnitus can be annoying for a patient and can also be the only clue to a potentially devastating and life-threatening disease. In order to understand its clinical spectrum and management better we analysed the files of 84 patients seen at our institution over a 10-year period. Noninvasive techniques (ultrasound, computed tomography, magnetic resonance imaging) and angiography were employed as investigations tailored to the individual patient. A vascular disorder [i.e. arteriovenous fistula, dissection of the internal carotid artery (ICA), fibromuscular dysplasia, aneurysm of the ICA and sinus thrombosis] was found in 36 patients (42%), most commonly a durai arteriovenous fistula or a carotid-cavernous sinus fistula. In 26 patients with a vascular abnormality, pulsatile tinnitus was the presenting symptom. In 12 patients (14%), nonvascular disorders such as glomus tumour or intracranial hypertension with a variety of causes explained the tinnitus. We conclude that patients with pulsatile tinnitus should be investigated with noninvasive techniques. If these are negative or to clarify abnormal findings of noninvasive techniques selective angiography is needed for diagnosis and to guide treatment

Parkinsonism with excessive daytime sleepiness--a narcolepsy-like disorder?

BackgroundParkinsonian patients with excessive daytime sleepiness (EDS), hallucinations, REM sleep behavior disorder (RBD), short mean sleep latencies, and sleep-onset REM periods (SOREMP) on multiple sleep latency tests (MSLT) have been reported. In these patients a narcolepsy-like pathophysiology of sleep-wake disturbances has been suggested.Patients and methodsWe studied 14 consecutive patients with Parkinsonism and EDS. Standard studies included assessment of duration and severity of Parkinsonism (Hoehn & Yahr score), Epworth sleepiness score (ESS), history of “REM-symptoms” (RBD/hallucinations/sleep paralysis/cataplexy-like episodes), polysomnography (PSG),MSLT, and measurement of cerebrospinal fluid (CSF) levels of hypocretin-1 (orexin A).ResultsThere were 12 men and 2 women (mean age 69 years; range 54–82). The mean duration and the Hoehn & Yahr score were 6.3 years and 2.2, respectively. Diagnoses included idiopathic Parkinson’s disease (IPD, n=10), dementia with diffuse Lewy bodies (n=3), and multisystem atrophy (n=1). The ESS was ≥10 in all patients (mean 12; range 10–18). “REM-symptoms” were reported by all but two patients (hallucinations: n=9; RBD: n=9).None of the patients reported cataplexy-like symptoms or sleep paralysis. On PSG sleep apnea (apnea hypopnea index > 10/h, n=7), periodic limb movements during sleep (PLMS-index > 10/h, n=6), and features of RBD (n=5) were found. On MSLT mean sleep latency was < 5 minutes in 10 patients, and SOREMP were found in two patients. When compared with controls (n=20, mean 497 pg/ml; range 350–603), CSF hypocretin-1 levels were normal in 8 patients and low in 2 patients (221 and 307 pg/ml, respectively).ConclusionThese findings do not support the hypothesis of a “final common pathway” in the pathophysiology of narcolepsy and Parkinsonism with EDS. Sleep apnea and PLMS may play a so-far underestimated role in the pathogenesis of EDS in Parkinsonian patients.

Morphological differences in Parkinson’s disease with and without rest tremor

BackgroundRest tremor is a hallmark of Parkinson’s disease (PD), but its pathogenesis remains incompletely understood. Nigro-striatal dopamine deficiency correlates best with bradykinesia, but not with tremor. Oscillating neurons in one or multiple localizations within the basal gangliathalamo-cortical loop may cause rest tremor, and an active contribution of the cerebellum and the cerebello-thalamo-cortical projections has been postulated.ObjectiveTo compare the pattern of grey matter volume in PD patients with and without tremor to identify structural correlates of rest tremor.MethodsVoxel-based morphometry (VBM) of a high-resolution 3 Tesla, T1-weighted MR images, pre-processed according to an optimized protocol using SPM2, was performed in 24 patients with mild to moderate PD comparing local grey matter volume in patients with (n = 14) and without rest tremor (n = 10).ResultsGrey matter volume is decreased in the right quadrangular lobe and declive of the cerebellum in PD with tremor compared to those without (PFDR < 0.05).ConclusionsThese results demonstrate for the first time morphological changes in the cerebellum in PD patients with rest tremor and highlight the involvement of the cerebellum and cerebello- thalamo-cortical circuit in the pathogenesis of parkinsonian rest tremor.

Fatigue and excessive daytime sleepiness in idiopathic Parkinson's disease differently correlate with motor symptoms, depression and dopaminergic treatment

Background and purpose:  A comprehensive study of both fatigue and excessive daytime sleepiness (EDS) in association with Parkinson’s disease (PD)‐related symptoms and treatment has not been performed yet. To assess the frequency and severity of fatigue and EDS in patients with idiopathic PD and to study their relation to motor and non‐motor symptoms and dopaminergic treatment.

Excessive daytime sleepiness in Parkinson's disease: characteristics and determinants.

Background/Aims: Excessive daytime sleepiness (EDS) is frequent in patients with Parkinson’s disease (PD). Occasionally, EDS in PD exhibits narcolepsy-like features. We aimed to assess characteristics and determinants of EDS in consecutive patients with PD. Methods: Thirty consecutive patients with PD underwent a detailed clinical examination. EDS was assessed using the Epworth Sleepiness Scale (ESS) and Multiple Sleep Latency Test (MSLT). Sleep was assessed using video-polysomnography. Cerebrospinal fluid (CSF) hypocretin-1 levels were obtained in 3 patients. Results: ESS was >10 in 17 patients (57%). Mean sleep latency (MSL) on MSLT was <5 min in 11 patients (37%). There was a significant negative correlation between ESS and MSL. None of the 11 patients with MSL <5 min showed a sleep onset REM (SOREM) episode. Patients with EDS had higher dopamine agonists/levodopa equivalent doses, higher apnea/hypopnea index and exhibited wearing-off symptoms more often. Hypocretin-1 was normal in 3 patients tested. Conclusion: EDS, which can sometimes be severe, is common in PD patients even in the absence of SOREM and detectable CSF-hypocretin deficiency. In PD, EDS is a multifaceted phenomenon, the determinants of which include severity of PD, wearing-off symptoms, dosage of antiparkinsonian drugs and sleep-disordered breathing.

Progressive dopamine and hypocretin deficiencies in Parkinson's disease: is there an impact on sleep and wakefulness?

Sleep–wake disturbances are frequent in patients with Parkinson’s disease, but prospective controlled electrophysiological studies of sleep in those patients are surprisingly sparse, and the pathophysiology of sleep–wake disturbances in Parkinson’s disease remains largely elusive. In particular, the impact of impaired dopaminergic and hypocretin (orexin) signalling on sleep and wakefulness in Parkinson’s disease is still unknown. We performed a prospective, controlled electrophysiological study in patients with early and advanced Parkinson’s disease, e.g. in subjects with presumably different levels of dopamine and hypocretin cell loss. We compared sleep laboratory tests and cerebrospinal fluid levels with hypocretin‐deficient patients with narcolepsy with cataplexy, and with matched controls. Nocturnal sleep efficiency was most decreased in advanced Parkinson patients, and still lower in early Parkinson patients than in narcolepsy subjects. Excessive daytime sleepiness was most severe in narcolepsy patients. In Parkinson patients, objective sleepiness correlated with decrease of cerebrospinal fluid hypocretin levels, and repeated hypocretin measurements in two Parkinson patients revealed a decrease of levels over years. This suggests that dopamine and hypocretin deficiency differentially affect sleep and wakefulness in Parkinson’s disease. Poorer sleep quality is linked to dopamine deficiency and other disease‐related factors. Despite hypocretin cell loss in Parkinson’s disease being only partial, disturbed hypocretin signalling is likely to contribute to excessive daytime sleepiness in Parkinson patients.

Body side and predominant motor features at the onset of Parkinson's disease are linked to motor and nonmotor progression.

Patients with Parkinsons disease most often have asymmetric motor features at onset, and specific motor signs (ie, tremor versus bradykinesia and rigidity) frequently characterize the first few years of disease evolution. Some previous clinical evidence has suggested that body side and a predominance of motor manifestations at disease onset are linked to long‐term evolution and disease progression. We prospectively analyzed 206 patients with Parkinsons disease according to the most affected side and predominant motor signs at onset. Patients were divided into left‐side rigid‐akinetic (n = 71), right‐side rigid‐akinetic (n = 59), left‐side tremor (n = 41), and right‐side tremor (n = 35) subgroups. These subgroups were compared in terms of motor and cognitive functions, mean motor deterioration per year (calculated as the motor score divided by disease duration), total equivalent doses of dopaminergic drugs, and the presence of hallucinations and rapid eye movement sleep behavior disorder. Disease duration was similar in all groups. Motor fluctuations were more likely to occur in rigid‐akinetic patients. In a multiple model analysis adjusted for potential confounders, faster disease progression was associated with right‐side (P = 0.045) and rigid‐akinetic onset (P = 0.001). With respect to nonmotor symptoms, the rigid‐akinetic type was associated with increased risk of cognitive decline (P = 0.004) compared with the tremor type. A trend was noticed toward an increased risk of developing visual hallucinations in rigid‐akinetic patients and toward an increased frequency of rapid eye movement sleep behavior disorder in those who had left‐sided onset of symptoms. Our findings corroborate that body side and type of motor signs at the time of diagnosis affect the evolution of motor severity and may also have an impact on some nonmotor manifestations.

REM Sleep Behavior Disorder is not Linked to Postural Instability and Gait Dysfunction in Parkinson

To evaluate a potential association of REM‐sleep behavior disorder (RBD) with gait and postural impairment in Parkinsons disease (PD). Gait difficulties and postural impairment are frequent in PD and are a major cause of disability. Animal studies indicate a key role of the pedunculopontine nucleus (PPN) in gait, postural control, and REM sleep, and also in the pathophysiology of RBD. In humans, such an association has not been investigated. Twenty‐six patients with mild‐to‐moderate PD (13 with polysomnography confirmed and 13 with excluded RBD), and 20 age‐matched healthy controls were prospectively investigated. Gait assessment on a treadmill, and static and dynamic posturography were performed. PD patients with RBD do not differ from those without RBD in gait and postural control. Greater severity of PD or prevalence of gait and postural disturbances in the presence of RBD were not found. RBD was not associated with any particular motor phenotype. We found no association of RBD with gait disturbances and postural impairment. Human gait and postural control and RBD appear to depend upon different neuronal circuits.

Learning a high-precision locomotor task in patients with Parkinson's disease

We evaluated the acquisition and performance of a high‐precision locomotor task in patients with Parkinsons disease (PD) and healthy subjects. All subjects walked on a treadmill and had to step repetitively as low as possible over an obstacle without touching it. During blocks 1 and 2, the subjects had full vision and received additional acoustic warning and feedback signals. During block 3, vision became restricted. Changes in foot clearance and the number of obstacle hits were evaluated. Initially, PD patients performed poorer and improved foot clearance slower. After task repetition, the groups performed similarly. Restricting vision deteriorated performance in both groups. The similar performance of PD patients after task repetition might indicate that adequate training could improve adaptive locomotor behavior in PD patients.

Heart rate variability in patients with idiopathic Parkinson’s disease with and without obstructive sleep apnea syndrome

BACKGROUND Obstructive sleep apnea syndrome (OSAS) is associated with repeated apnea-induced sympathetic surges leading to specific alterations of the power spectrum of heart rate variability (HRV). Sympathetic dysfunction evolves early in idiopathic Parkinsons disease (PD), but the consequences on cardiac autonomic response to OSAS have not been studied so far in PD patients. METHODS Sixty-two patients with PD (35 without OSAS (PD-wo), 27 with OSAS (PD-OSAS)) and 62 age-matched control subjects (25 without OSAS (Co-wo), 37 with OSAS (Co-OSAS)) were included. HRV variables - including mean R-R interval, standard deviation of all normal-to-normal R-R intervals (SDNN), both low frequency (LF) and high frequency (HF) power bands, and the LF/HF ratio - were computed automatically from full-night polysomnography and calculated separately for each sleep stage. RESULTS HRV variables were similar in PD-wo and PD-OSAS. In contrast, Co-OSAS showed significantly higher LF power in NREM1 and NREM2 sleep and higher LF/HF ratio in NREM1, NREM2 and slow wave sleep than Co-wo. Similarly, correlations between HRV variables and parameters of OSAS severity were found only in controls but not in PD patients. CONCLUSION Our results suggest that the sympathetic response to OSAS is blunted in PD, giving further clinical evidence of the sympathetic denervation commonly observed in this neurodegenerative disorder.