Partial Cataplexy Research Articles

Long-term use of pitolisant to treat patients with narcolepsy: Harmony III Study.

Study ObjectivesTo asses the long-term safety and efficacy of pitolisant, an histamine H3-receptor antagonist, on narcolepsy.MethodsThis open-label, single-arm, pragmatic study, recruited adult patients with narcolepsy and Epworth Sleepiness Scale (ESS) score ≥12. After a titration period, patients were treated for up to 1 year with oral pitolisant once-a-day at up to 40 mg. Concomitant stimulants and anti-cataplectic agents were allowed. The primary endpoint was safety; secondary endpoints included ESS, cataplexy, and other diary parameters.ResultsPatients (n = 102, 75 with cataplexy) received pitolisant, for the first time in 73 of them. Sixty-eight patients (51 with cataplexy) completed the 12-month treatment. Common treatment-emergent adverse events were headache (11.8% of patients), insomnia (8.8%), weight gain (7.8%), anxiety (6.9%), depressive symptoms (4.9%), and nausea (4.9%). Seven patients had a serious adverse effect, unrelated to pitolisant except for a possibly related miscarriage. One-third of patients stopped pitolisant, mostly (19.6%) for insufficient benefit. ESS score decreased by 4.6 ± 0.6. Two-thirds of patients completing the treatment were responders (ESS ≤ 10 or ESS decrease ≥ 3), and one third had normalized ESS (≤10). Complete and partial cataplexy, hallucinations, sleep paralysis, and sleep attacks were reduced by 76%, 65%, 54%, 63%, and 27%, respectively. Pitolisant as monotherapy (43% of patients) was better tolerated and more efficacious on ESS than on add-on, but efficacy was maintained in this last case.ConclusionsLong-term safety and efficacy of pitolisant on daytime sleepiness, cataplexy, hallucinations, and sleep paralysis is confirmed.

The clinical characteristics of cataplectic attack in narcolepsy type 1

ObjectiveCataplexy is a pathognomonic symptom of narcolepsy type 1. This study was conducted to clarify the clinical characteristics of cataplexy by staging, and to further analyse the correlations of clinical features and cataplectic stages in patients with narcolepsy type 1 (NT1). MethodsWe experimentally triggered patients with NT1 into cataplexy while under video-polysomnography (v-PSG) monitoring in the sleep lab. The most serious cataplectic attack from each patient was analysed. Each cataplectic episode was segmented into four stages according to the v-PSG. Correlations were analysed between cataplectic stages in pairs, and between cataplectic stages and other clinical features. ResultsWe observed 81 cataplectic episodes in 21 patients with diverse triggers, including humorous or exciting videos, tickling, recalling horrible memories and exercising. Nine patients (43%) went through complete cataplectic attacks while the others experienced partial attacks. Four cataplectic stages (ie, triggering, resisting, atonic, and recovering) were identified according to clinical and electromyograms characteristics. Resisting stage is predominant (56.4%) in cataplexy, while atonic stage is most related with the total duration of cataplexy. The Epworth Sleepiness Scale score (ESS) has a positive correlation with the total duration of cataplexy. Both duration of cataplexy and ESS score are negatively correlated with disease course. However, medication history seems have no influence on either cataplexy duration or ESS score. ConclusionFour-stage segmentation shows the dynamic process of the cataplectic attack, which is different from the traditional classification of complete or partial cataplexy. Resisting stage is necessary for every cataplexy and might reflect the compensation mechanism, while atonic stage may be omitted in some patients. The severity of narcolepsy reduces with the extension of natural course regardless of medication history.

Persistence of deep-tendon reflexes during partial cataplexy

ObjectiveDeep-tendon reflexes are abolished during generalized cataplexy, but whether this is the case in partial cataplexy currently remains unknown. Partial cataplexy may mimic other neurologic/psychiatric phenomena, and knowledge of the reflexes status may provide information for differential diagnosis. We assessed whether deep-tendon reflexes are persistent during partial cataplexy. MethodsFive drug-free patients with typical diagnoses of narcolepsy and clear-cut partial cataplexy were diagnosed in Reference Narcolepsy Centers in France and Italy. Biceps and patellar reflexes were elicited by physicians in charge and video-documented during cataplexy. Reflexes were assessed several times for each patient in different conditions and for various localizations of cataplexy. ResultsThe absence of tendon reflexes and complete loss of muscle tone during generalized cataplexy was confirmed, but the persistence of those reflexes during several partial cataplectic attacks at different ages, gender, localization of cataplexy (upper limbs, face) and reflexes (biceps, patellar) in drug-naive or withdrawal conditions was documented. ConclusionThe persistence of tendon reflexes during several partial cataplexy episodes contrasts with their absence during generalized cataplexy. This discovery has clinical implications: the persistence of tendon reflexes does not rule out cataplexy diagnosis for partial attacks, whereas their transient abolishment or persistence during generalized attacks indicates cataplexy or pseudocataplexy, respectively.

“I feel my arm shaking”: partial cataplexy mistaken for drug-resistant focal epilepsy

“I feel my arm shaking”: partial cataplexy mistaken for drug-resistant focal epilepsy

A Case Report of Narcolepsy with Partial Cataplexy Misdiagnosed as Epilepsy

A Case Report of Narcolepsy with Partial Cataplexy Misdiagnosed as Epilepsy

Hypocretin-1 Deficiency in a Girl With ROHHAD Syndrome

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) is a rare and complex pediatric syndrome, essentially caused by dysfunction of 3 vital systems regulating endocrine, respiratory, and autonomic nervous system functioning. The clinical spectrum of ROHHAD is broad, but sleep/wake disorders have received relatively little attention so far, although the central hypothalamic dysfunction would make the occurrence of sleep symptoms likely. In this case report, we expand the phenotype of ROHHAD with a number of striking sleep symptoms that together can be classified as a secondary form of narcolepsy. We present a 7-year-old girl with ROHHAD who displayed the classic features of narcolepsy with cataplexy: excessive daytime sleepiness with daytime naps, visual hallucinations, and partial cataplexy reflected in intermittent loss of facial muscle tone. Nocturnal polysomnography revealed sleep fragmentation and a sleep-onset REM period characteristic for narcolepsy. The diagnosis was confirmed by showing an absence of hypocretin-1 in the cerebrospinal fluid. We discuss potential pathophysiological implications as well as symptomatic treatment options.

Effect of clomipramine in a dog with cataplexy

Abstract : A 5-year-old, castrated male, Maltese was presented with history of acute flaccid paralysis. The dog waspresented with sudden loss of muscle tone and involuntary movements of hind limbs. Neurologic examination revealedreduced postural reaction in the bilateral hind limbs. MRI of brain showed moderate hydrocephalus, but otherexamination results were normal. Based on the characteristic episodes and examination results, canine cataplexy wassuspected. Treatment was initiated with clomipramine as cataplexy control. Clinical signs resolved with 3-monthmedication. This case demonstrates therapeutic diagnosis of cataplexy. To the author’s knowledge, this is the first reportof cataplexy treating with clomipramine.Keywords : cataplexy, clomipramine, narcolepsy Cataplexy in dogs is relatively rare disease and manifestsitself as sudden weakness of muscle tone, often triggered bypositive emotional stimuli [5]. In genetically narcolepticDoberman puppies, the mean age of onset of cataplexy isabout 9 weeks, and female has more severe cataplexy thanmales [9]. Most of narcolepsy, which is sleep disorder, dogs experi-ence clinical signs of cataplexy [2]. Two different pathophys-iology mechanisms are involved in cataplexy and narcolepsy.Mutation in the hypocretin-receptor-2 gene causes the famil-ial type [7, 8, 10]. This type is inherited autosomal recessivetransmission and onset is young age (≤ 6 months) [10]. Theother is sporadic type caused by loss of the hypocretinligand, which is an excitatory peptide neurotransmitter madein the hypothalamus [4]. Onset of age is wide range as com-pared with familial type [10]. In human medicine, generalized cataplexy causes com-plete collapse of patients, whereas partial cataplexy affectsonly the face, voice or arms. In severe cases, respiratory andextraocular muscles could be attacked [6]. In veterinary med-icine, cataplexy attack may be affect all muscles or restrictedto head, trunk or certain limbs [4]. According to the previousreports [4], most cataplexy attacks initiated in the hind legsand affected bilateral.This report describes therapeutic diagnosis and successfuluse of clomipramine in the treatment of dog with cataplexy.A 5-year-old, castrated male, Maltese dog was presented tohistory of flaccid paralysis 1 to 2 times a week. The dog fellto the ground completely atonic, and bilateral hind limbsmoved involuntary. There was no loss of consciousness. Thisneurological signs observed 2 months prior to the presenta-tion, and episode lasted a few seconds to 2 min. A severeepisode also occurred with loss of consciousness, elicited byexcitement. Previous administration of nonsteroidal antin-flammatory drug (Firocoxib, Previcox; Merial, France) bythe referring veterinarian for pain control didn’t improve theclinical signs. Physical examination revealed intermittenthind limbs weakness when physical manipulation of bothpatellar (grade I/IV medial patellar luxation), but no otherabnormalities were found. The hemogram showed stress leu-kogram (21,030/µL, reference range, 6,000~17,000/µL), andserum chemistry profiles were within normal limits. Therewere no remarkable abnormalities in the thoracic, abdominaland accurately positioned hind limb radiographs. Electrocar-diography was also examined for exclusion of possibility ofcardiogenic episode, and result had no remarkable findings.To rule out myasthenia gravis and neurologic sign inducedby canine distemper virus infection, laboratory examinationswere performed, and acetylcholine receptor antibody concen-tration was within reference range (0.02 nmol/L, referencerange 0.0~0.6 nmol/L), and canine distemper polymerase chainreaction (PCR) of cerebrospinal fluid (CSF) sample result wasnegative. Result of food-elicited cataplexy test (FECT) foridentifying cataplexy was not revealed unusual outcome. Onneurologic examination, the dog presented reduced posturalreaction in the bilateral hind limbs, and this result could besuspected lesion of 4th lumbar vertebra to 3rd sacral verte-bra. However, lumbosacral region was normal at magnetic

The clinical features of cataplexy: A questionnaire study in narcolepsy patients with and without hypocretin-1 deficiency

BackgroundNarcolepsy is often not recognized or accurately diagnosed. This may be due to the fact that cataplexy, a core symptom which is virtually 100% specific, can—in practice—only be diagnosed based on the patient’s history. However, the current definition of cataplexy is not very precise and the common distinction between “typical” and “atypical” cataplexy is not well codified. MethodsWe aimed to provide a detailed description of the phenotypic variability of cataplexy. We included 109 patients with a definite history of cataplexy and a proven hypocretin-1 deficiency. The questionnaire contained 37 items to broadly cover the clinical aspects of cataplexy, including triggers, pattern and duration of muscle weakness, associated aspects such as sensory phenomena, and limitations in daily life due to cataplexy. Results“Laughing” only listed in place 11th of most frequent triggers. “Laughing excitedly” was much more potent, showing that a certain intensity of the emotion is important for a “cataplectogenic” effect. Anger was the highest ranking “non-humorous” trigger, followed by “unexpectedly meeting someone well known.” About 60% of patients also had spontaneous cataplectic attacks. Forty-five percent of patients experienced both partial and complete attacks and 30% only partial cataplexy. Fifteen percent of complete attacks were reported to last longer than 2min. An abrupt return of muscle function was an important feature. The jaw and the face were most often involved in partial attacks, even more than the knee or the leg. ConclusionsCataplexy presents with a large phenotypical diversity, so the current “typical” versus “atypical” distinction may be difficult to hold. We propose that grading cataplexy with different levels of diagnostic confidence may be more useful.

Normalization of hypocretin-1 in narcolepsy after intravenous immunoglobulin treatment

In May 2006, a 28-year-old woman abruptly experienced excessive daytime sleepiness (EDS) and 2 to 3 short, refreshing but irresistible naps per day. She also reported increased nighttime sleep duration of more than 3 hours. Her Epworth Sleepiness Scale score was 22, indicating severe sleepiness. She also developed clear-cut generalized and partial cataplexy provoked by laughter but also by stress with a frequency of more than 1 attack per day. A rapid but large weight gain was noted up to 6 kg within 2 weeks, without a clear change in appetite. She never experienced sleep paralysis, hypnagogic hallucinations, or mood disorders. She had no personal or familial history of a particular disease, and no treatment. She was seen by us 15 days after the first cataplexy episode to confirm the diagnosis of narcolepsy with cataplexy.1 Nighttime polysomnography results were unremarkable; a multiple sleep latency test (PSG-MSLT) indicated a mean sleep latency of 5 minutes and 2 sleep-onset REM periods. She was positive for HLA DRB1*1501 and DQB1*0602. Brain …

Treatment with Venlafaxine in Six Cases of Children with Narcolepsy and with Cataplexy and Hypnagogic Hallucinations

Narcolepsy with cataplexy is a chronic neuropsychiatric disorder associated with inappropriate control of rapid eye movement (REM) sleep. The main symptoms are excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and disturbed nocturnal sleep. Cataplexy is marked by episodes of muscular weakness and may cause the patient to collapse to the ground. So far, pharmacotherapy of cataplexy and hypnagogic hallucinations has been predominantly based on tricyclic antidepressants. Recently, new drugs that block the reuptake of norepineprine and serotonin (e.g., venlafaxine) have been suggested as first-line treatment. These drugs have become our choice in treating children with cataplexy and nightmares as a symptom in narcolepsy. We describe clinical case reports of venlafaxine treatment in 6 children aged 7-12 years old when diagnosed with narcolepsy-cataplexy. In 2 cases with up to 50 daily cataplectic attacks, an initial effect of 37.5 mg of venlafaxine was initially observed. However, during the first year, the dose had to be increased to 112.5 mg daily to avoid cataplexy. A third patient with partial cataplexy was treated with 75 mg of venlafaxine daily. In 2 cases, hypnagogic hallucinations, described by the patients as nightmares, were the most troubling symptom and were successfully treated with only 37.5 mg of venlafaxine daily. Side effects included an increase of disturbed nocturnal sleep when venlafaxine was taken after 2:00 p.m. No major aggressive or suicidal thoughts and no raised blood pressure were recorded. Venlafaxine has proven to be an effective treatment of cataplexy and hypnagogic hallucinations in 6 children with narcolepsy. No severe side effects were observed.

Conception, Pregnancy, Delivery, and Breastfeeding in a Narcoleptic Patient with Cataplexy

Conception, Pregnancy, Delivery, and Breastfeeding in a Narcoleptic Patient with Cataplexy