Cataplexy: A Laughing Matter?
April 1, 2008 3 minutes read
Cataplexy: A Laughing Matter?
Abstract & Commentary
By Charles Pollak, MD Professor, Clinical Neurology, Director, Center for Sleep Medicine, Weill-Cornell Medical College Dr. Pollak reports no financial relationship relevant to this field of study.
Synopsis: Functional MRI imaging in patients with narcolepsy supports the hypothesis of decreased hypothalamic activity with reduced orexin production.
Source: Schwartz S, et al. Abnormal activity in hypothalamus and amygdala during humour processing in human narcolepsy with cataplexy. Brain 2008;131(Pt 2):514-522.
Narcolepsy with cataplexy (NC) is a specific, though uncommon, sleep-wake disorder that usually starts in the late teens and persists throughout one's lifetime. Cataplexy manifests itself as skeletal muscle weakness ranging in severity from a slight loss of tone in the face to head bobbing, knee buckling, or total collapse to the ground. Along with muscle weakness, there is atonia and areflexia. Episodes are of sudden onset and usually last no longer than a few seconds to a few minutes. There is no disturbance of consciousness, and there is full recovery of motor function. Episodes often are triggered by laughter or another emotion (anger, surprise, embarrassment). Cataplexy is a pathognomonic symptom of narcolepsy: even when the emotion-triggered weakness is subtle and fleeting, its occurrence unequivocally confirms the diagnosis.
It has recently been discovered that NC is associated with a reduction or absence of orexin (hypocretin), a lateral hypothalamic neuropeptide associated with sleep, feeding behaviors, and motor functions. The vast majority of people with NC have low or undetectable levels of orexin (hypocretin) in the cerebrospinal fluid, most likely reflecting specific loss of the hypothalamic orexin-producing neurons. This constitutes a key lesion in NC, as central administration of orexin-A to mice acutely suppresses both cataplectic behavioral arrests and increases wakefulness.
It has long been thought that cataplexy is dependent upon descending inhibitory pathways terminating at the spinal level at the alpha motoneuron. The same pathways are utilized during normal REM sleep, which also is associated with hypotonia and hyporeflexia. Indeed, cataplexy has been described as an abnormal displacement of REM sleep into wakefulness. However, the rostral mechanisms that account for the sudden motor disability in response to emotion remain obscure.
Schwartz and colleagues exposed 12 NC patients and 12 controls to humorous pictures while they were being imaged with event-related functional-MRI (fMRI) to quantify brain activity. All of the NC patients reported that joking and laughing were a main trigger of cataplectic attacks. This was a novel paradigm, since fMRI had never been performed on cataplectic patients. By comparing regions of interest between NC patients and controls, the investigators found that in all of the patients with NC, humorous pictures elicited reduced activity in the hypothalamus and enhanced activity in the amygdala, which is consistent with the orexin hypothesis.
Commentary
It is well accepted that connections from the amygdala to the hypothalamus can modulate reflex responses to emotional stimuli. The recent findings suggest that the hypothalamus might modulate amygdaloid activity during positive emotions via projections from hypothalamic orexin neurons to the amygdala. The authors speculate that the reduced hypothalamic activation and increased amygdala response to humor that they observed with fMRI could both be explained by loss of hypothalamic orexin neurons. The key role of orexin neuron loss, perhaps secondary to selective autoimmune degeneration, in the pathophysiology of NC is, therefore, consistent with these unique fMRI findings. The narcolepsy story keeps getting more interesting!
Functional MRI imaging in patients with narcolepsy supports the hypothesis of decreased hypothalamic activity with reduced orexin production.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content