Epilepsy and neuropsychologic deficit in a child with cerebellar astrocytoma

We report the case of a 32-month-old female patient presenting with cerebellar pilocytic astrocytoma with epileptic seizures, psychomotor delay, and severe language delay. Usually, the typical onset of cerebellar tumor is characterized by raised intracranial pressure and cerebellar incoordination. A review of the few cases reported in the literature evidencing epileptic seizures symptomatic of a focal, nondegenerative mass limited to the cerebellum is included. Moreover, a discussion about the cerebellar contribution to nonmotor functions in children is presented, in particular following tumor resection.     

Epilepsy, parkinsonism, and neuroleptic malignant syndrome in a child

A 9-year-old girl with akinetic-rigid parkinsonism with tremor is described. She was hospitalized with neuroleptic malignant syndrome that started 3 days after anticonvulsant drug treatment owing to epileptic seizures. Cranial magnetic resonance imaging (MRI) was normal, and during the follow-up, magnetic resonance spectroscopy revealed a decrement on N-acetylaspartate in the basal ganglia, suggesting neuronal dysfunction. The basal ganglia and dopamine are involved in the pathophysiology of parkinsonism and neuroleptic malignant syndrome and have been recognized in seizure propagation and seizure threshold. Parkinsonism in children is considered an acquired, secondary, and reversible disorder with a dramatic improvement to treatment. However, our patient still has parkinsonism 2 years after diagnosis. This case represents the unusual presentation of epilepsy, parkinsonism, and neuroleptic malignant syndrome, which might have a common pathophysiologic pathway (dopaminergic dysfunction) involving the basal ganglia and the hypothalamus.     

Prevalence of narcolepsy-cataplexy in Korean adolescents

Background –  Narcolepsy typically begins between adolescence and early adulthood causing severe neuropsychiatric impairments, but few prevalence studies are available on adolescent narcoleptics. In the present study, we investigated the prevalence of narcolepsy-cataplexy in adolescents.
Methods –  In total 20,407 students, aged 14–19 years, participated in this study. Ullanlinna Narcolepsy Scale (UNS) was applied to all subjects and those with a UNS score of ≥14 were contacted by phone for semi-structured interview. Subjects then suspected of having narcolepsy participated in a laboratory investigation, which included polysomnography and HLA typing, or were interviewed in detail by telephone.
Results –  Three subjects were finally diagnosed as narcolepsy with cataplexy and seven subjects might be diagnosed as narcolepsy without cataplexy. Among three narcoleptics with cataplexy, two subjects were HLA-DQB1*0602 and DRB1*1501 positive, but one subject had no test of HLA typing. The prevalence of narcolepsy with cataplexy in Korean adolescence was thus determined to be 0.015% (95% confidence interval = 0.0–0.0313%).
Conclusion –  This epidemiologic study is the first of its type on adolescent narcolepsy to use the International Classification of Sleep Disorders, 2nd edition (ICSD-2) diagnostic criteria. Considering those cases with an onset after adolescence were not included, the prevalence of narcolepsy with cataplexy determined in the present study is comparable with that of other studies in adults.     

REM-dreams recall in patients with narcolepsy-cataplexy

An abundant recall of dreams has been observed in clinical studies on patients with narcolepsy-cataplexy (NC), a neurological disorder characterized by an altered sleep architecture. Laboratory studies have shown that dream experiences developed during 1st-rapid eye movement (REM) sleep by NC patients are longer and more complex than those of healthy subjects. To establish whether these features indicate an earlier optimal functioning of the cognitive processes involved in dream generation rather than a more accurate dream recall, we compared the indicators of length and structural organization in reports of REM-dreams collected from 14 NC patients and their matched controls. During an experimental night two awakenings were provoked after 8 min in 1st- and 3rd-REM sleep; participants were asked to report their dream experience (spontaneous report) and then, if possible, further remembered parts of this experience (prompted report). All reports were analyzed using story-grammar rules, which allow us to identify units larger than single contents and describe their story-like organization. While dream recall (about 90%) was comparable in NC patients and controls, 1st-REM spontaneous reports were longer and more complex in NC patients, half of whom also provided prompted reports. After 3rd-REM awakening more than one third of NC patients and controls gave prompted reports, which were fairly comparable in length and complexity with the spontaneous reports. These findings confirm that the cognitive processes underlying dream generation reach their optimal functioning earlier in the night in NC patients than in normal subjects, and raises the question of whether the dream-stories described in spontaneous and prompted reports are part of the same or distinct REM-dreams.     

Does memory impairment exist in narcolepsy-cataplexy?

Approximately one-half of patients with the narcolepsy-cataplexy syndrome suffer from subjective memory problems, mainly involving recent events. Ten untreated narcoleptic patients (7 male, 3 female, aged 28-65 years) with such problems and 10 matched controls were given a battery of tests to study the complaint. Tests included the digit span, Knox cube, recurring figures (verbal and nonverbal), visual reproduction, paired associates learning and logical memory test, plus naming and fluency tests to control for language capabilities. No significant intergroup differences were found. It is concluded that narcoleptics do not have a true organic memory deficit, but rather experience a subjective problem due to drowsiness which they are able to suppress during short testing sessions in a laboratory environment.     

Story-like organization of REM-dreams in patients with narcolepsy-cataplexy

Narcolepsy with cataplexy (NC) is a neurological disorder characterized by excessive daytime sleepiness and an altered architecture of sleep. Previous laboratory studies have shown that frightening, bizarre and visually vivid contents are more frequent in dream experiences developed during the first period of REM sleep by NC patients than healthy subjects. As the structural organization of dream experiences of NC patients has not been yet examined, we compared its indicators in dream reports collected from a sample of NC patients and their matched controls. During an experimental night two awakenings were provoked after 8min of REM sleep in the first and third sleep cycle. Dream reports were analyzed using the rules of story grammars, capable of identifying units larger than single contents and describing their story-like organization. While dream recall (about 85%) was comparable in NC patients and controls, 1st-REM dream reports were longer in NC patients. Statistical analyses on the 12 NC patients and their matched controls who reported dreams after both REM periods showed that dream experiences occurring in 1st-REM reports of NC patients were longer and had a more complex organization than those of controls. These findings suggest that the cognitive processes underlying dream generation reach their optimal functioning earlier in the night in NC patients than in normal subjects.     

Central alpha 1 adrenoceptor subtypes in narcolepsy-cataplexy: a disorder of REM sleep

The present study suggests the specific involvement within the central nervous system of an alpha 1 adrenoceptor subtype in a behavior, the control of cataplexy, a pathological analogue of rapid eye movement (REM) sleep atonia. Experiments have shown that prazosin, an alpha 1 antagonist, dramatically aggravates canine narcolepsy-cataplexy through a central mechanism, and that [3H]prazosin binding sites are increased in the amygdala of narcoleptic dogs. However, the corresponding Scatchard plots were curvilinear and best fit was obtained with a two-site model, suggesting the existence of two [3H]prazosin binding sites. These two sites (high and low affinity [3H]prazosin binding sites) met the criteria for authentic receptors and were respectively very similar to the alpha 1a and alpha 1b (high and low affinity for WB4101, respectively) subtypes recently described in the rat and rabbit. Our results of in vivo pharmacology and in vitro [3H]prazosin binding in canine narcolepsy now clearly implicate the low affinity [3H]prazosin binding site (alpha 1b) in canine narcolepsy: (1) Prazosin, an alpha 1 antagonist with similar affinity for both subtypes, was much more potent in increasing cataplexy than WB4101, a compound with more affinity for the alpha 1a receptor. (2) Chlorethylclonidine and phenoxybenzamine, two irreversible blockers of the alpha 1 receptors with more affinity for the alpha 1b receptors, aggravate cataplexy for up to two weeks. (3) The alpha 1 receptor upregulation previously reported by our group in the amygdala of narcoleptic dogs was due to a selective increase in the low affinity [3H]prazosin binding sites. A role for noradrenaline in REM sleep regulation has been suspected for many years, but has never been clearly elucidated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sodium oxybate in the treatment of childhood narcolepsy-cataplexy: a retrospective study

ObjectiveTo evaluate the efficacy and side effect profile of sodium oxybate in the treatment for narcolepsy–cataplexy in the pediatric age group.MethodsA retrospective study was conducted on 15 children and adolescents with narcolepsy–cataplexy who had been treated with sodium oxybate. The mean age at diagnosis of narcolepsy was 11 years (range 3–17 years). Subjects were followed for 3–90 months (mean 33) after starting sodium oxybate. During this period of time they were also maintained on other medications for sleepiness (n = 14) and cataplexy (n = 6). The charts were reviewed for documentation of improvement in sleepiness or cataplexy, side effects, and functioning in daily life.ResultsSubsequent to the addition of sodium oxybate, sleepiness improved in 13/15 patients. In patients who had Epworth Sleepiness Scale (ESS) assessments, the score fell from a baseline median of 18 to 12 (n = 10, p = 0.01). The number of cataplexy episodes estimated by parents decreased from a median of 38/week pre-treatment to <1/week post treatment (n = 14, p < 0.001). Cataplexy severity, measured on an arbitrary scale, fell from a median of 3 (severe) to 1 (mild) in all 15 subjects (p < 0.001).Two of the 15 patients (13%) discontinued sodium oxybate, one for insurance reasons and the other due to constipation and dissociative feelings. A third patient stopped the medication temporarily due to body aches and dizziness, but then resumed treatment without recurrence of symptoms. Side effects in four others included tremor, blurring of vision, nocturnal awakenings, and increased nightmares. Overall, side effects occurred in 6/15 (40%) individuals. Improvement in social/academic spheres was noted in 11/15 (73%) subjects after starting sodium oxybate. The median BMI before and after treatment remained unchanged at 23 (n = 14, p = 0.99). Median values of height and weight before and after treatment also did not change significantly. The mean dose of sodium oxybate was 5 ± 2 g. Dose escalation owing to development of tolerance was not encountered.ConclusionsSodium oxybate is effective in alleviating sleepiness and cataplexy in childhood onset narcolepsy–cataplexy. The therapeutic response was sustained over time, and without development of tolerance. Forty percent of the subjects experienced adverse effects.     

Deep brain stimulation of hypothalamus for narcolepsy-cataplexy in mice

BackgroundNarcolepsy type 1 (NT1, narcolepsy with cataplexy) is a disabling neurological disorder caused by loss of excitatory orexin neurons from the hypothalamus and is characterized by decreased motivation, sleep-wake fragmentation, intrusion of rapid-eye-movement sleep (REMS) during wake, and abrupt loss of muscle tone, called cataplexy, in response to sudden emotions.ObjectiveWe investigated whether subcortical stimulation, analogous to clinical deep brain stimulation (DBS), would ameliorate NT1 using a validated transgenic mouse model with postnatal orexin neuron degeneration.MethodsUsing implanted electrodes in freely behaving mice, the immediate and prolonged effects of DBS were determined upon behavior using continuous video-electroencephalogram-electromyogram (video/EEG/EMG) and locomotor activity, and neural activation in brain sections, using immunohistochemical labeling of the immediate early gene product c-Fos.ResultsBrief 10-s stimulation to the region of the lateral hypothalamus and zona incerta (LH/ZI) dose-responsively reversed established sleep and cataplexy episodes without negative sequelae. Continuous 3-h stimulation increased ambulation, improved sleep-wake consolidation, and ameliorated cataplexy. Brain c-Fos from mice sacrificed after 90 min of DBS revealed dose-responsive neural activation within wake-active nuclei of the basal forebrain, hypothalamus, thalamus, and ventral midbrain.ConclusionAcute and continuous LH/ZI DBS enhanced behavioral state control in a mouse model of NT1, supporting the feasibility of clinical DBS for NT1 and other sleep-wake disorders.     

Antibodies in narcolepsy-cataplexy patient serum bind to rat hypocretin neurons

Autoimmunity is considered the most likely cause of human narcolepsy-cataplexy, but no specific autoantibodies or antigen(s) have yet been identified. By means of indirect avidin-biotin immunohistochemical method, we searched for antibodies in serum from narcolepsy-cataplexy patients and controls that bind to rat hypocretin neurons. No staining was found in eight out of nine narcolepsy-cataplexy patients or controls. The serum from one narcolepsy-cataplexy patient, however, strongly produced staining of the membrane and superficial cytoplasm of neurons in the lateral hypothalamus. Dual staining revealed that the vast majority of the hypocretin-positive neurons were positive, but nonhypocretin neurons in the same area were binding antibodies from the patient's serum. These results show that antibodies bind to specific hypocretin- and nonhypocretin-containing neurons in the hypothalamus and indicate the presence of autoantibodies in narcolepsy patients.