We recently reported a novel neurological syndrome characterized by a unique NREM and REM parasomnia with sleep apnea and stridor, accompanied by bulbar dysfunction and specific association with antibodies against the neuronal cell-adhesion protein IgLON5. All patients had the HLA-DRB1*1001 and HLA-DQB1*0501 alleles. Neuropathological findings in two patients revealed a novel tauopathy restricted to neurons and predominantly involving the hypothalamus and tegmentum of the brainstem. The aim of the current study is to describe the neuropathological features of the anti-IgLON5 syndrome and to provide diagnostic levels of certainty based on the presence of associated clinical and immunological data. The brains of six patients were examined and the features required for the neuropathological diagnosis were established by consensus. Additional clinical and immunological criteria were used to define "definite", "probable" and "possible" diagnostic categories. The brains of all patients showed remarkably similar features consistent with a neurodegenerative disease with neuronal loss and gliosis and absence of inflammatory infiltrates. The most relevant finding was the neuronal accumulation of hyperphosphorylated tau composed of both three-repeat (3R) and four-repeat (4R) tau isoforms, preferentially involving the hypothalamus, and more severely the tegmental nuclei of the brainstem with a cranio-caudal gradient of severity until the upper cervical cord. A "definite" diagnosis of anti-IgLON5-related tauopathy is established when these neuropathological features are present along with the detection of serum or CSF IgLON5 antibodies. When the antibody status is unknown, a "probable" diagnosis requires neuropathological findings along with a compatible clinical history or confirmation of possession of HLA-DRB1*1001 and HLA-DQB1*0501 alleles. A "possible" diagnosis should be considered in cases with compatible neuropathology but without information about a relevant clinical presentation and immunological status. These criteria should help to identify undiagnosed cases among archival tissue, and will assist future clinicopathological studies of this novel disorder.

Tauopathy

10.1007/s00401-016-1591-8

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RLS, PLM, and their differential diagnosis—A video guide

Movement Disorders (2007)

Birgit Högl Marco Zucconi Federica Provini

This video guide has been designed as an introduction to the full spectrum of nocturnal presentations of restless legs syndrome (RLS) and periodic limb movements (PLM), and to their differential diagnoses. The DVD consists of four sections: In the first part, clinical presentations of RLS are covered (videos 1-3). In the second part, the variety of typical and less frequent presentations of PLM are demonstrated (videos 4-14). The third part shows the clinical presentation of augmentation (videos 15-19). The last section is dedicated to the differential diagnosis of RLS and PLM and demonstrates nocturnal manifestations of other motor disorders during sleep, which must be distinguished: Epilepsy, parasomnias, and other movement disorders (of sleep) (videos 20-33). After viewing this DVD, the reader should be able to: (1) appreciate the spectrum of voluntary and unvoluntary movements seen in patients with RLS during wakefulness; (2) recognize typical PLM during sleep in subjects with RLS, and appreciate the enormous variability of clinical presentations of PLM; (3) describe specific and distinct aspects of motor activity in augmentation in patients with RLS; and (4) be aware of the most important differential diagnosis of RLS/PLM from a video or nocturnal motor activity point of view, namely, nocturnal epilepsy, parasomnias, and others.

Restless Legs Syndrome

Movement Disorders

10.1002/mds.21591

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Effects of cabergoline on sleep and morning motor performance in patients with Parkinson′s disease.

European Journal of Neurology (1999)

Birgit Högl A. Rothdach Thomas C. Wetter Claudia Trenkwalder

Cabergoline

Sleep

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The need to promote sleep health in public health agendas across the globe

The Lancet Public Health (2023)

Diane C Lim Arezu Najafi Lamia Afifi Claudio L. Bassetti Daniel J. Buysse

Healthy sleep is essential for physical and mental health, and social wellbeing; however, across the globe, and particularly in developing countries, national public health agendas rarely consider sleep health. Sleep should be promoted as an essential pillar of health, equivalent to nutrition and physical activity. To improve sleep health across the globe, a focus on education and awareness, research, and targeted public health policies are needed. We recommend developing sleep health educational programmes and awareness campaigns; increasing, standardising, and centralising data on sleep quantity and quality in every country across the globe; and developing and implementing sleep health policies across sectors of society. Efforts are needed to ensure equity and inclusivity for all people, particularly those who are most socially and economically vulnerable, and historically excluded.

Globe

Global Health

Sleep

10.1016/s2468-2667(23)00182-2

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Citations (97)

Speech Biomarkers in Rapid Eye Movement Sleep Behavior Disorder and Parkinson Disease

Annals of Neurology (2021)

Jan Rusz Jan Hlavnička Michal Novotný Tereza Tykalová Amélie Pelletier

This multilanguage study used simple speech recording and high-end pattern analysis to provide sensitive and reliable noninvasive biomarkers of prodromal versus manifest α-synucleinopathy in patients with idiopathic rapid eye movement sleep behavior disorder (iRBD) and early-stage Parkinson disease (PD).We performed a multicenter study across the Czech, English, German, French, and Italian languages at 7 centers in Europe and North America. A total of 448 participants (337 males), including 150 with iRBD (mean duration of iRBD across language groups 0.5-3.4 years), 149 with PD (mean duration of disease across language groups 1.7-2.5 years), and 149 healthy controls were recorded; 350 of the participants completed the 12-month follow-up. We developed a fully automated acoustic quantitative assessment approach for the 7 distinctive patterns of hypokinetic dysarthria.No differences in language that impacted clinical parkinsonian phenotypes were found. Compared with the controls, we found significant abnormalities of an overall acoustic speech severity measure via composite dysarthria index for both iRBD (p = 0.002) and PD (p < 0.001). However, only PD (p < 0.001) was perceptually distinct in a blinded subjective analysis. We found significant group differences between PD and controls for monopitch (p < 0.001), prolonged pauses (p < 0.001), and imprecise consonants (p = 0.03); only monopitch was able to differentiate iRBD patients from controls (p = 0.004). At the 12-month follow-up, a slight progression of overall acoustic speech impairment was noted for the iRBD (p = 0.04) and PD (p = 0.03) groups.Automated speech analysis might provide a useful additional biomarker of parkinsonism for the assessment of disease progression and therapeutic interventions. ANN NEUROL 2021;90:62-75.

Sleep

10.1002/ana.26085

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Auditory Startle Reaction is disinhibited in idiopathic Restless Legs Syndrome

SLEEP (2007)

Birgit Frauscher Wolfgang N. Löscher Birgit Högl Werner Poewe Markus Kofler

Because the auditory startle reaction is abnormal in disorders with substantia nigra pathology, we hypothesized that auditory startle responses (ASRs) might also be altered in restless legs syndrome (RLS).Neurophysiologic study of the auditory startle reaction.Neurology departments of a university hospital and an affiliated local hospital.Fifteen patients with idiopathic RLS (6 de novo, 9 untreated after a 7-day wash-out period of levodopa, mean duration of RLS [corrected] symptoms 21.2 +/- 17.9 years, mean IRLS [corrected] severity score 23.5 +/- 6.7) and 15 sex- and age-matched healthy controls were investigated.Not applicable.ASRs were elicited by 8 high-intensity auditory stimuli differing randomly in tonal frequency and intensity. Reflex electromyographic activity was simultaneously recorded with surface electrodes from 8 facial, neck, arm, and leg muscles. In RLS patients, ASRs were significantly more frequent (541 of 960 possible responses; controls, 430 of 960), and ASR area under the curve was significantly larger (3812 +/- 450 microVms; controls, 1756 +/- 226 microVms). Analysis per body region revealed that ASRs were significantly more frequent in RLS patients than in controls in leg muscles (138/360 vs 55/360); ASR latencies to leg muscles were significantly shorter in RLS patients (129 +/- 6 ms vs 160 +/- 11 ms); ASR area under the curve was significantly larger in RLS patients in facial (7547 +/- 1326 mmicroVms vs 2982 +/- 448 microVms) and leg muscles (1373 +/- 308 microVms vs 541 +/- 193 microVms).Our data demonstrate disinhibition of reticulospinal pathways in RLS patients as compared to normal controls, likely originating from dysfunction rostral to the lower brainstem.

Restless Legs Syndrome

10.1093/sleep/30.4.489

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Citations (28)

Optimizing odor identification testing as quick and accurate diagnostic tool for Parkinson's disease

Movement Disorders (2016)

Philipp Mahlknecht Raimund Pechlaner Sanne Boesveldt D. Volc Bernardette Pinter

The aim of this study was to evaluate odor identification testing as a quick, cheap, and reliable tool to identify PD.Odor identification with the 16-item Sniffin' Sticks test (SS-16) was assessed in a total of 646 PD patients and 606 controls from three European centers (A, B, and C), as well as 75 patients with atypical parkinsonism or essential tremor and in a prospective cohort of 24 patients with idiopathic rapid eye movement sleep behavior disorder (center A). Reduced odor sets most discriminative for PD were determined in a discovery cohort derived from a random split of PD patients and controls from center A using L1-regularized logistic regression. Diagnostic accuracy was assessed in the rest of the patients/controls as validation cohorts.Olfactory performance was lower in PD patients compared with controls and non-PD patients in all cohorts (each P < 0.001). Both the full SS-16 and a subscore of the top eight discriminating odors (SS-8) were associated with an excellent discrimination of PD from controls (areas under the curve ≥0.90; sensitivities ≥83.3%; specificities ≥82.0%) and from non-PD patients (areas under the curve ≥0.91; sensitivities ≥84.1%; specificities ≥84.0%) in all cohorts. This remained unchanged when patients with >3 years of disease duration were excluded from analysis. All 8 incident PD cases among patients with idiopathic rapid eye movement sleep behavior disorder were predicted with the SS-16 and the SS-8 (sensitivity, 100%; positive predictive value, 61.5%).Odor identification testing provides excellent diagnostic accuracy in the distinction of PD patients from controls and diagnostic mimics. A reduced set of eight odors could be used as a quick tool in the workup of patients presenting with parkinsonism and for PD risk indication. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Identification

10.1002/mds.26637

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Citations (60)

[Cardiopulmonary stress test in variable frequency stimulation: a comparison of Activitrax and Nova-MR pacemakers in VVI/AAI stimulation].

PubMed (1988)

Alt E R Völker Birgit Högl Dean MacCarter

Treadmill

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Citations (2)