1/51. A video-polygraphic analysis of the cataplectic attack. OBJECTIVES AND methods: To perform a video-polygraphic analysis of 11 cataplectic attacks in a 39-year-old narcoleptic patient, correlating clinical manifestations with polygraphic findings. Polygraphic recordings monitored EEG, EMG activity from several cranial, trunk, upper and lower limbs muscles, eye movements, EKG, thoracic respiration. RESULTS: Eleven attacks were recorded, all of them lasting less than 1 min and ending with the fall of the patient to the ground. We identified, based on the video-polygraphic analysis of the episodes, 3 phases: initial phase, characterized essentially by arrest of eye movements and phasic, massive, inhibitory muscular events; falling phase, characterized by a rhythmic pattern of suppressions and enhancements of muscular activity, leading to the fall; atonic phase, characterized by complete muscle atonia. Six episodes out of 11 were associated with bradycardia, that was maximal during the atonic phase. CONCLUSIONS: Analysis of the muscular phenomena that characterize cataplectic attacks in a standing patient suggests that the cataplectic fall occurs with a pattern that might result from the interaction between neuronal networks mediating muscular atonia of REM sleep and neural structures subserving postural control. ( info) |
2/51. Hypersomnolence and narcolepsy; a pragmatic diagnostic neurophysiological approach. Out of a group of 250 consecutive patients who were examined for various disorders of sleep and waking at Ghent University Hospital within a period of 24 months, 30 patients with hypersomnolence associated with a suspected underlying neurological etiology were selected. The population consisted of 15 males and 15 females with mean age of 36 years (range: 16-60 years). Twenty-one patients had had hypersomnolence for more than 2 years. All patients underwent a single night polysomnography (PSG) and a 4-nap multiple sleep latency test (MSLT). PSG was normal in 23 patients. Sleep onset REM period (SOREMP) was defined as the occurrence of REM sleep within 15 min. after initiation of sleep. PSG demonstrated SOREMP's in only 1 patient and showed evidence of obstructive sleep apnea in 4 patients. Two patients had a low sleep efficiency. MSLT demonstrated hypersomnolence in 17 patients of whom 6 showed SOREMP. Significant hypersomnolence was defined as a mean sleep latency < or = 5 min. 4 patients fulfilled the classical clinical and polygraphic criteria (> or = 2 SOREMP) of narcolepsy. In 8 patients the tentative diagnosis of idiopathic CNS hypersomnolence was made. 13 patients did not sleep during MSLT. These results emphasize the relative importance of MSLT. Our limited 4-nap MSLT protocol proved useful in distinguishing narcolepsy from idiopathic CNS hypersomnolence. ( info) |
| coffin-lowry syndrome (CLS) is an X-linked semidominant condition, caused by mutations in the gene encoding the ribosomal protein s6 kinase-2 (RSK-2), a growth factor regulating protein kinase, which is mapped to Xp 22.2. The syndrome is mainly seen in males. It is manifested by moderate to severe mental retardation and characteristic facial, hand and skeletal malformations. We present a female patient with fully manifested CLS, confirmed by molecular analysis, who experienced daily drop episodes, diagnosed as "cataplexy". The episodes were precipitated by emotional or auditory stimuli and were significantly reduced, by selective serotonine re-uptake inhibitors. ( info) |
| OBJECTIVE: coffin-lowry syndrome (CLS) is a rare disorder characterized by moderate to severe mental retardation, facial dysmorphism, tapering digits, and skeletal deformity. Paroxysmal drop attacks occur in patients with CLS, characterized by sudden loss of muscle tone induced by unexpected tactile or auditory stimuli. Our objective is to characterize these attacks better using neurophysiologic studies. methods: We report 2 teenage boys with CLS and stimulus-induced drop episodes (SIDEs). Simultaneous surface electromyogram (EMG) and video electroencephalogram were performed during SIDEs on our 2 patients. RESULTS: Both patients had SIDEs stimulated by a loud noise, unexpected light touch stimulation, or visual threat that were characterized by abrupt episodes of complete or partial loss of lower extremity tone. These events were not associated with impairment of consciousness, and immediate recovery was noted. Simultaneous surface EMG and video electroencephalogram revealed no epileptiform discharges in either patient. In the first patient, after unexpected tactile or auditory stimulation, tonic EMG activity in paraspinal muscles was lost briefly, similar to that seen in cataplexy. In the second patient, at 6 years of age, sudden nonepileptic drop episodes were induced by an unexpected tactile, auditory, or visual stimulation. At 11 years of age, his episodes had changed to brief myoclonic jerk and tonic spasm that were triggered by unexpected tactile and auditory stimuli. An increase in tonic EMG activity occurred during the attacks, consistent with hyperekplexia. CONCLUSIONS: Our data suggest that SIDEs in CLS are a heterogeneous group of nonepileptic events that may manifest features of both cataplexy and hyperekplexia, even in the same patient. ( info) |
| narcolepsy is a disorder of impaired expression of wakefulness and rapid-eye-movement (REM) sleep. This manifests as excessive daytime sleepiness and expression of individual physiological correlates of REM sleep that include cataplexy and sleep paralysis (REM sleep atonia intruding into wakefulness), impaired maintenance of REM sleep atonia (e.g. REM sleep behaviour disorder [RBD]), and dream imagery intruding into wakefulness (e.g. hypnagogic and hypnopompic hallucinations). Excessive sleepiness typically begins in the second or third decade followed by expression of auxiliary symptoms. Only cataplexy exhibits a high specificity for diagnosis of narcolepsy. While the natural history is poorly defined, narcolepsy appears to be lifelong but not progressive. Mild disease severity, misdiagnoses or long delays in cataplexy expression often cause long intervals between symptom onset, presentation and diagnosis. Only 15-30% of narcoleptic individuals are ever diagnosed or treated, and nearly half first present for diagnosis after the age of 40 years. attention to periodic leg movements (PLM), sleep apnoea and RBD is particularly important in the management of the older narcoleptic patient, in whom these conditions are more likely to occur. Diagnosis requires nocturnal polysomnography (NPSG) followed by multiple sleep latency testing (MSLT). The NPSG of a narcoleptic patient may be totally normal, or demonstrate the patient has a short nocturnal REM sleep latency, exhibits unexplained arousals or PLM. The MSLT diagnostic criteria for narcolepsy include short sleep latencies (<8 minutes) and at least two naps with sleep-onset REM sleep. Treatment includes counselling as to the chronic nature of narcolepsy, the potential for developing further symptoms reflective of REM sleep dyscontrol, and the hazards associated with driving and operating machinery. Elderly narcoleptic patients, despite age-related decrements in sleep quality, are generally less sleepy and less likely to evidence REM sleep dyscontrol. Nonpharmacological management also includes maintenance of a strict wake-sleep schedule, good sleep hygiene, the benefits of afternoon naps and a programme of regular exercise. Thereafter, treatment is highly individualised, depending on the severity of daytime sleepiness, cataplexy and sleep disruption. Wake-promoting agents include the traditional psychostimulants. More recently, treatment with the 'activating' antidepressants and the novel wake-promoting agent modafinil has been advocated. cataplexy is especially responsive to antidepressants which enhance synaptic levels of noradrenaline (norepinephrine) and/or serotonin. Obstructive sleep apnoea and PLMs are more common in narcolepsy and should be suspected when previously well controlled older narcolepsy patients exhibit a worsening of symptoms. The discovery that narcolepsy/cataplexy results from the absence of neuroexcitatory properties of the hypothalamic hypocretin-peptidergic system will significantly advance understanding and treatment of the symptom complex in the future. ( info) |
6/51. Decreased cerebrospinal fluid hypocretin-1 levels near the onset of narcolepsy in 2 prepubertal children. We present 2 cases of narcolepsy with prepubertal onset. Although excessive daytime sleepiness and cataplexy had appeared early in both patients, the presence of sleep-onset rapid eye movement periods was detected several months after the onset of hypersomnia. The levels of hypocretin in the cerebrospinal fluid were reduced when measured 3 weeks (Patient 1) and 2 months (Patient 2) after the appearance of hypersomnia, before the presence of sleep-onset rapid eye movement periods was confirmed. Because the symptoms of narcolepsy in children are often obscure and easily mistaken as other diseases, and the electrophysiologic studies may not be specific in the early stage, the definite diagnosis tends to be delayed. Measurement of hypocretin-1 levels in the cerebrospinal fluid is useful for the early diagnosis of narcolepsy with prepubertal onset. ( info) |
| narcolepsy and cataplexy began one year before treatment of a left mid-temporal primary B-cells lymphoma in a HLA DR2 negative man. Treatment with radio therapy and immunosuppression induced regression of the lymphoma and disappearance of narcolepsy and cataplexy. ( info) |
8/51. HLA-DR2 negative narcolepsy in Australian Caucasians: clinical features, serology and sequence specific oligonucleotide typing. An almost invariable association with HLA-DR2 and DQw1 has previously been reported in Japanese and caucasian narcoleptics. We performed HLA typing in 18 Australian narcoleptics using serological techniques and sequence specific oligonucleotide probes. HLA-DQw1 was present in 15 patients and DR2 in 12; 3 patients with cataplectic narcolepsy were DR2-negative. The serological haplotype most strongly associated with narcolepsy was DRw15 (a subtype of DR2), DQw1. DRw15-positive patients were positive for the alleles DRB1*1501 and DQB1*0602 defined with oligonucleotide probes. We conclude that the association of narcolepsy with DR2 and DQw1 is not as strong as previously reported and the absence of DR2 or DQw1 does not preclude the diagnosis of classical narcolepsy, at least in caucasians. Secondly, DR2-positive narcoleptics possess characteristic serological subtypes and alleles defined with oligonucleotide probes that are also found in normals. Thirdly, the occurrence of DR2-negative cataplectic narcoleptics points to the existence of more than one narcolepsy susceptibility gene. ( info) |
| patients with sleep disorders present with a variety of complaints including excessive daytime sleepiness, daytime spells, inability to sleep, uncomfortable sensation in the extremities, and unusual night time behaviors. This article provides eight vignettes on patients with sleep disorders including narcolepsy, idiopathic hypersomnia, obstructive sleep apnea, restless legs syndrome, and rapid eye movement behavior disorder. The discussion provides data regarding the epidemiology, pathophysiology, and diagnostic approach for these conditions. The various treatment options for these sleep disorders are also identified. ( info) |
10/51. Diagnostic ambiguities in a case of post-traumatic narcolepsy with cataplexy. narcolepsy arising from trauma can present particular problems of differential diagnosis. In this case study presentation the patient suffered a head trauma, without unconsciousness, and began to experience unusual episodic behaviours. Symptom presentation differed from the typical clinical manifestations of idiopathic narcolepsy leading to an 8-year search for a definitive diagnosis. Key relevant aspects that led to diagnostic ambiguities were the order of symptom development, negative for the antigen HLA DR2, significance of the Multiple Sleep Latency Test (MSLT) mean sleep latency versus number of sleep onset rapid eye movement periods, the somewhat atypical features of cataplexy, the coexistence of sleep apnoea, and the mildness of the original head injury. It is argued that cases of post-traumatic narcolepsy should be considered in the context of their clinical development over time and that practitioners should be aware that this form of narcolepsy can differ from the typical clinical history of idiopathic narcolepsy. ( info) |