Gait disorders in fatal familial insomnia.

BACKGROUND: Fatal familial insomnia (FFI) is a hereditary autosomal-dominant prion disease linked to a mutation of the prion protein gene and characterized by sleep and autonomic abnormalities at onset followed by motor disturbances. We describe gait abnormalities in 13 FFI cases with different disease durations. METHODS: Clinical records and corresponding videos of 13 FFI cases were regularly monitored from disease onset to death. RESULTS: Gait disturbances appeared in all FFI subjects 5 ± 2 months after disease onset following a distinct progression for the 2 genetic FFI variants. Homozygous patients developed only a cautious gait with some difficulties in turning and in tandem gait; heterozygous patients showed a clear progressive worsening of equilibrium with latero/retropulsion ultimately preventing standing and walking unaided. CONCLUSIONS: The severity and features of gait dysfunction in FFI are related to the duration of the disease, which in turn is a result of the genotype. The evolving gait dysfunction in the disease course may mirror the spread of neuronal degeneration from the thalamus to other brain areas involved in the control of gait or may be the functional effect of a disturbed neuronal network in which the thalamus is a crucial relay.

The distinct movement disorder in anti-NMDA receptor encephalitis may be related to Status Dissociatus: a hypothesis.

The majority of patients with anti-N-methyl-D-aspartate-receptor encephalitis (NMDAE) present a characteristic movement disorder, which consists of complex bilateral stereotyped movements of the arms, with perioral and eye movements, and less frequently involvement of the legs. We have observed striking similarities in the characteristics of the abnormal movements observed in NMDAE and those described in Status Dissociatus, which is characterized by a complete breakdown of state-determining boundaries (wakefulness, REM and NREM sleep) and can result from pathophysiologically diverse disorders (e.g. fatal familial insomnia, delirium tremens, Morvan's syndrome). Here, we suggest that the state of paradoxical responsiveness in which NMDAE patients present these stereotyped movements may be that of Status Dissociatus and discuss the clinical similarities and pathophysiological explanations that support such a suggestion. This hypothesis explains why patients that seem to be unconscious have a movement disorder that is not epileptic and may have management implications, since many patients with NMDAE-related movement disorder are treated with anticonvulsants that may not be indicated.

Parasomnias and nocturnal frontal lobe epilepsy (NFLE): lights and shadows--controversial points in the differential diagnosis.

Nocturnal frontal lobe epilepsy (NFLE) is characterized by seizures with complex, often bizarre, violent behaviour arising only or mainly during sleep. These unusual seizures and their occurrence during sleep are often accompanied by normal EEG tracings and neuroradiological findings, making it difficult to distinguish NFLE seizures from other non-epileptic nocturnal paroxysmal events, namely parasomnias. NFLE was described for the first time in 1981, but, as its epileptic origin was controversial, the condition was called nocturnal paroxysmal dystonia. Even though many aspects of parasomnias and NFLE have been clarified in the last two decades, the problem of differential diagnosis remains a challenge for clinicians. This paper discusses some controversial points still under debate. The difficulties in distinguishing nocturnal epileptic seizures from parasomnias reflect just one aspect of the intriguing issue of the pathophysiological relationships between all types of paroxysmal motor behaviours during sleep.

Arousal disorders.

Arousal Disorders (AD) are motor behaviours arising from NREM sleep. They comprise a spectrum of manifestations of increasing complexity from confusional arousal to sleep terror to sleepwalking. AD usually appear in childhood with a low frequency of episodes and spontaneously disappear before adolescence. The advent of video-polysomnography disclosed the existence of other phenomena alongside AD, in particular nocturnal frontal lobe seizures, requiring a differential diagnosis from AD. History-taking is usually sufficient to establish a correct diagnosis of AD even though viewing the episodes is essential for the clinician to distinguish the different motor events. Videopolysomnographic recording in a sleep laboratory is not always necessary and homemade video-recordings are useful to capture events closest to real life episodes.

Agrypnia excitata.

The concept of Agrypnia excitata (AE) was originally proposed as a concept deriving from the clinical and anatomo-pathological observations obtained in three different diseases, Fatal familial insomnia (FFI), Delirium tremens (DT), and Morvan syndrome (MS). Agrypnia refers to a condition of severely reduced or absent sleep due to organic disorders. Excitata refers to the association of agrypnia with generalized motor and autonomic hyperactivation. AE is a syndrome that has been claimed to relate to a dysfunction in the thalamo-limbic circuits that govern sleep-wake cycles and autonomic activities.

Nocturnal frontal lobe epilepsy: new pathophysiological interpretations.

Since the first descriptions of Nocturnal Frontal Lobe Epilepsy (NFLE) many theories have been proposed to explain its pathophysiological mechanisms. The aim of this paper is to formulate a tentative hypothesis designed to unify the clinical, anatomo-physiological, and genetic aspects underlying this condition. According to this hypothesis, NFLE is due to a disorder in the thalamocortical circuit involved in the arousal mechanism. Other cortical-networks involving the limbic system may explain, for instance, primitive behaviors. The role of the cholinergic system and related pathways in the pathogenesis of nocturnal seizures and parasomnias is also discussed.

Motor events during REM sleep in patients with narcolepsy-cataplexy: a video-polysomnographic pilot study.

OBJECTIVE: We carried out a systematic video-polysomnographic analysis of the number and type of motor events during REM sleep in narcolepsy-cataplexy patients with REM sleep behavior disorder (NC + RBD) but not clinical RBD (NC-RBD). METHODS: Twelve NC + RBD and 10 NC-RBD male patients underwent video-polysomnography (video-PSG). Motor events of different type and complexity (i.e., elementary and complex movements and vocalizations) occurring during REM sleep were visually assessed, and indices of their frequency per hour of REM sleep were calculated. Subsequently, the index values were compared in NC + RBD versus NC-RBD patients. RESULTS: Typical RBD behaviors observed in five NC + RBD patients were not included in any type of motor events. No objective conventional sleep parameter, including visual analysis of chin electromyographic (EMG) activity, significantly differed between the two groups of NC patients. NC + RBD patients showed higher occurrence of elementary movements (p = 0.034) during REM sleep compared with NC-RBD patients, but the occurrence of complex movements did not differ significantly. CONCLUSIONS: Video-analysis of motor events during REM sleep may improve the diagnosis of RBD in NC. RBD in NC patients is mainly characterized by elementary rather than complex movements, consistent with the view that RBD with NC patients displays a distinct phenotype with respect to other RBD patients.

Oneiric stupor: the peculiar behaviour of agrypnia excitata.

Agrypnia excitata (AE) is a syndrome characterized by the inability to sleep associated with a generalized motor and autonomic over-activation. AE is caused by a thalamo-limbic system dysfunction and comprises three different conditions: Fatal Familial Insomnia (FFI), Delirium Tremens (DT), and Morvan Syndrome (MS). Oneiric Stupor episodes (OS) are the peculiar motor behaviour of AE. During OS patients perform simple automatic gestures mimicking daily-life activities. This paper is the first description of the different characteristics of OS in two patients with MS and another with FFI, emphasizing the specific clinical features that reliably differentiate OS from REM sleep behaviour disorders.

Morvan chorea and agrypnia excitata: when video-polysomnographic recording guides the diagnosis.

INTRODUCTION: Morvan chorea is an antibody-mediated limbic encephalopathy characterized by severe insomnia, mental confusion, hallucinations, enacted dreams, hyperhidrosis, and neuromyotonia. CASE DESCRIPTION: In a 78 years old man presenting with progressive insomnia apathy and depression, a video-polysomnogram documented enacted dreams mimicking daily life activity (oneiric stupor). This finding led us to perform a search for serum antibodies to voltage-gated K+ channels, which was positive. A diagnosis of Morvan chorea was done. The patient underwent plasma exchange with complete resolution of the clinical picture. CONCLUSIONS: Oneiric stupor may represent a useful precocious diagnostic marker in Morvan chorea.

Surgery vs ventilation in adult severe obstructive sleep apnea syndrome.

BACKGROUND AND PURPOSE: Management of severe obstructive sleep apnea-hypopnea syndrome (OSAHS) is challenging and needs multidisciplinary cooperation. Ventilation is considered the gold standard of treatment in severe OSAHS. The aim of the study was to compare the therapeutical efficacy of a type of surgery (maxillomandibular advancement [MMA]) vs a ventilatory treatment modality (autotitrating positive airway pressure [APAP]). MATERIALS AND METHODS: At the ENT Department of Forlì Hospital (University of Pavia), in strict cooperation with the Sleep Lab of the University of Bologna, a prospective randomized controlled trial was designed and performed. After fully informing them, 50 consecutive patients who have severe OSAHS were enrolled and randomized into a conservative (APAP) or surgical (MMA) section. Demographic, biometric, polysomnogram (PSG) and Epworth Sleepiness Scale profiles of the 2 groups were statistically not significantly different. RESULTS: One year after surgery or continuous APAP treatment, both groups showed a remarkable improvement of mean Apnea-Hypopnea Index (AHI) and Epworth Sleepiness Scale levels; the degree of improvement was not statistically different. CONCLUSIONS: Given the relatively small sample of subjects studied and the relatively brief follow-up, MMA proved to be a valuable alternative therapeutical tool in our adult and severe OSAHS patient group, with a success rate not inferior to APAP.

Daytime sleepiness and neural cardiac modulation in sleep-related breathing disorders.

Sleep-related breathing disorders are common causes of excessive daytime sleepiness, a socially and clinically relevant problem. Mechanisms responsible for daytime sleepiness are still largely unknown. We investigated whether specific alterations in autonomic cardiac modulation during sleep, commonly associated with sleep-related breathing disorders, are related to excessive daytime sleepiness. Fifty-three patients with sleep-related breathing disorders underwent nocturnal polysomnography. Excessive daytime sleepiness was diagnosed as a Multiple Sleep Latency Test response less than or equal to 600 s. We explored the relation of excessive daytime sleepiness, objectively determined, with indices of autonomic cardiac regulation, such as baroreflex sensitivity and heart rate variability, with polysomnographic indices of the severity of sleep-related breathing disorders and with quality of sleep. Patients with excessive daytime sleepiness, when compared with patients without, had significantly lower baroreflex sensitivity and significantly higher low-to-high frequency power ratio of heart rate variability during the different stages of nocturnal sleep. By contrast, no differences were found in indices quantifying the severity of sleep-related breathing disorders or sleep quality. We demonstrated that excessive daytime sleepiness is accompanied by a deranged cardiac autonomic control at night, the latter probably reflecting autonomic arousals not detectable in the EEG. As abnormal autonomic regulation is also known to be associated with increased cardiovascular risk, a possible relation between excessive daytime sleepiness and cardiovascular events in patients with sleep-related breathing disorders deserves to be investigated in future studies.

Cataplexy features in childhood narcolepsy.

Cataplexy, the hallmark of narcolepsy, has been well characterized in adults but not in children. This study systematically used structured clinical assessments and video-recordings (49 episodes in eight cases) to evaluate cataplexy in 23 patients diagnosed before the age of 18 years. Forty-three percent of patients had falls as part of their attacks. During cataplexy knees, head, and jaw were the most frequently compromised body segments; eyelids, arms, and trunk being less commonly involved. More rarely, blurred vision, slurred speech, irregular breathing, or a sudden loss of smiling mimics were reported. One-third of the sample presented with a previously unrecognized description of cataplexy that we coined "cataplectic facies," consisting of a state of semipermanent eyelid and jaw weakness, on which partial or complete cataplectic attacks were superimposed. The usual triggering emotions, such as laughter, joking, or anger, were not always present, especially when close to an abrupt onset, hampering diagnosis. Video-recordings of cataplectic attacks may be useful to document the attack, allowing a comparison with archived presentations.

Fatal familial insomnia and agrypnia excitata.

This review summarizes the pioneering steps culminating in the identification of a novel disease, fatal familial insomnia (FFI), a hereditary prion disease. Together with Morvan's chorea and delirium tremens, FFI is characterized by an inability to sleep associated with motor and autonomic overactivation. We named this pattern agrypnia excitata, a syndrome caused by a dysfunction in thalamolimbic circuits. This review highlights the strategic role of the limbic thalamus in the central autonomic network running from the limbic cortex to the lower brainstem and regulating sleep and wakefulness.