A Case of Narcolepsy Type 2 and Postural Tachycardia Syndrome Secondary to Lesions of the Thalamus and Amygdala.

ABSTRACT: Although there are reports of narcolepsy type 1 caused by lesions of the central nervous system, there are far fewer reports of narcolepsy type 2 (NT2) caused by discrete brain lesions. We report a case of a patient in whom NT2 was diagnosed after a viral illness, and inflammatory lesions in the right thalamus and amygdala were found. In addition, symptoms of autonomic impairment developed and postural tachycardia syndrome was subsequently diagnosed in this patient. To our knowledge this is the first reported case of NT2 resulting from central nervous system lesions in these discrete locations, as well as the first reported case of postural tachycardia syndrome associated with narcolepsy.

Polysomnographic findings in craniopharyngioma patients.

PURPOSE: The purpose of this study is to evaluate whether damage to the hypothalamus due to craniopharyngioma or consequent surgery may involve the sleep-wake regulatory system, resulting in sleep disturbances and sleepiness. METHODS: Seven craniopharyngioma patients and 10 healthy controls were evaluated with sleep questionnaires including the Epworth Sleepiness Scale, polysomnography, and a multiple sleep latency test (MSLT). Five patients and eight controls had lumbar puncture performed to determine hypocretin-1 levels. RESULTS: Patients tended to feel sleepier than control individuals of the same age (p = 0.09). No subjects had symptoms of hypnagogic hallucinations, sleep paralyses, or cataplexies. Four patients and one control had periodic leg movements (PLMs). One patient had fragmented sleep pattern, rapid eye movement (REM) sleep without atonia, and PLMs. One patient had short sleep periods during the daytime. Four patients had fragmented sleep pattern. With the MSLT, four patients and two controls had mean sleep latency of < 8 min. One patient and three controls had sudden onset of REM sleep in 2/5 and 3/5 sleep periods, respectively. All subjects showed normal hypocretin-1 levels. Four patients had electrophysiological findings indicative of central hypersomnia including one patient meeting the criteria of narcolepsy. CONCLUSION: The sleep-wake regulatory system may be involved in craniopharyngioma patients.

Hypocretin Deficiency Associated with Narcolepsy Type 1 and Central Hypoventilation Syndrome in Neurosarcoidosis of the Hypothalamus.

We report a case of a 53-year-old man presenting with depressed alertness and severe excessive sleepiness in the setting of neurosarcoidosis. Neuroimaging demonstrated hypothalamic destruction due to sarcoidosis with a CSF hypocretin level of 0 pg/mL. The patient also experienced respiratory depression that presumably resulted from hypocretin-mediated hypothalamic dysfunction as a result of extensive diencephalic injury. This is a novel case, demonstrating both hypocretin deficiency syndrome, as well as respiratory dysfunction from destruction of hypocretin neurons and extensive destruction of key diencephalic structures secondary to the underlying neurosarcoidosis.

Manejo del vértigo posicional paroxístico benigno en atención primaria / Management of benign paroxysmal positional vertigo in first care centers

El vértigo posicional paroxístico benigno es la entidad más frecuente dentro de los vértigos de origen periférico. Se caracteriza por crisis de vértigo desencadenadas por cambios posicionales de la cabeza y de corta duración. Suele presentarse en los mayores de 40-50 años, y hasta el 50% de los casos no se deben a una causa conocida, por lo que se habla de vértigo posicional paroxístico benigno idiopático. Debido a la alta incidencia del vértigo posicional paroxístico benigno, consideramos de especial trascendencia poseer los conocimientos necesarios para poder diagnosticar y tratar con eficacia esta afección en el ámbito de la medicina de atención primaria, ya que en la mayoría de los casos se obtienen excelentes resultados a través de unas maniobras específicas y fáciles de realizar (AU)

The benign paroxysmal positional vertigo is the most common disease in the group of peripheral vertigo. It's characterized by vertiginous sensation triggered by the positional changes of the head and usually lasts less than one minute. It is most frequently seen in middle-aged patients (40-50 years old) and in up 50% of cases we do not know the cause, so we refer to them as idiopathic benign paroxysmal positional vertigo. Because of the high incidence of benign paroxysmal positional vertigo in general population, it is of utmost importance to be aware of the differential diagnosis and to be able to treat this pathology with efficacy, because in most cases we can achieve excellent results performing specific and simple maneuvers (AU)

Hypothalamic immunopathology in anti-Ma-associated diencephalitis with narcolepsy-cataplexy.

IMPORTANCE: Idiopathic narcolepsy with cataplexy is thought to be an autoimmune disorder targeting hypothalamic hypocretin neurons. Symptomatic narcolepsy with low hypocretin level has been described in Ma antibody­associated encephalitis; however, the mechanisms underlying such an association remain unknown. OBSERVATIONS: We described a 63-year-old man with clinical criteria for diencephalic encephalitis with sleepiness, cataplexy, hypocretin deficiency, and central hypothyroidism, together with brainstem encephalitis reflected by supranuclear ophtalmoparesis and rapid eye movement sleep behavior disorder with underlying abnormalities on brain magnetic resonance imaging. An autoimmune process was demonstrated by the detection of antibodies against Ma protein. Death occurred 4 months after disease onset without any tumor detected. Neuropathology, immunohistochemistry, and immunoreactivity results were compared with those obtained in idiopathic narcolepsy-cataplexy and with normal control brains. The principal findings revealed almost exclusive inflammation and tissue injury in the hypothalamus. The type of inflammatory reaction suggests cytotoxic CD8+ T lymphocytes being responsible for the induction of tissue injury. Inflammation was associated with complete loss of hypocretinergic neurons. Autoantibodies of the patient predominantly stained neurons in the hypothalamus and could be absorbed with Ma2. CONCLUSIONS AND RELEVANCE: The encephalitic process, responsible for narcolepsy-cataplexy and hypocretin deficiency, reflects a CD8+ inflammatory-mediated response against hypocretin neurons.

[Diagnostic and therapeutic update in narcolepsy]. / Actualizacion diagnostica y terapeutica en narcolepsia.

Narcolepsy is an emblematic, unique disease within sleep disorders that is characterised by excessive daytime sleepiness, cataplexy and other abnormal manifestations of REM sleep. In the last 14 years truly spectacular progress has been made in our knowledge of this disease, since the discovery of its cause, i.e. a loss of the hypothalamic neurons that synthesise hypocretin, a previously unknown neurotransmitter, and its probable aetiopathogenic mechanisms, i.e. an autoimmune process in a patient with very precise immunological characteristics - a specific type of HLA and a specific type of T-cell receptor. The cause of this autoimmune process remains unknown. The definitive treatment - the administration of hypocretin, which is the substance missing in the organism - is still unavailable, but there are powerful drugs for treating its main symptoms, the sleepiness and the cataplexy. Some of these are classic compounds (methylphenidate, clomipramine), while others are more recent (modafinil, venlafaxine, sodium oxybate), but together they allow many patients to experience significant improvements. Lack of knowledge about the disease, both on the part of patients and their relatives as well as physicians, is the reason for the great delay in its diagnosis, with even more dramatic consequences when the disease begins in infancy.

Melanin concentrating hormone in central hypersomnia.

BACKGROUND: Narcolepsy with cataplexy (NC) is a disabling disorder characterized by excessive daytime sleepiness and abnormal rapid eye movement (REM) sleep manifestations, due to a deficient hypocretin/orexin neurotransmission. Melanin concentrating hormone (MCH) neurons involved in the homeostatic regulation of REM sleep are intact. We hypothesized that an increased release of MCH in NC would be partly responsible for the abnormal REM sleep manifestations. METHODS: Twenty-two untreated patients affected with central hypersomnia were included: 14 NC, six idiopathic hypersomnia with long sleep time, and two post-traumatic hypersomnia. Fourteen neurological patients without any sleep disorders were included as controls. Using radioimmunoassays, we measured hypocretin-1 and MCH levels in cerebrospinal fluid (CSF). RESULTS: The MCH level was slightly but significantly lower in patients with hypersomnia (98 ± 32 pg/ml) compared to controls (118 ± 20 pg/ml). After exclusion of patients affected with post-traumatic hypersomnia the difference became non-significant. We also failed to find any association between MCH level and hypocretin level, the severity of daytime sleepiness, the number of SOREMPs, the frequency of cataplexy, and the presence of hypnagogic hallucinations or sleep paralysis. CONCLUSION: This study reports the first measurement of MCH in CSF using radioimmunoassay technology. It appears to be a non-informative tool to differentiate etiologies of central hypersomnia with or without REM sleep dysregulation.

Narcolepsy in Parkinson's disease.

Non-motor symptoms in Parkinson's disease (PD), such as excessive daytime sleepiness, 'sleep attacks', insomnia, restless legs syndrome and rapid eye movement sleep behavior disorder, are common and provide a challenge to treatment. These sleep symptoms are also described in patients suffering from the sleep/wake disorder, narcolepsy. The International Classification of Sleep Disorders (ICSD-2) narcolepsy criteria uses a number of markers for diagnosis, of which lack or deficiency of cerebrospinal fluid (CSF) hypocretin-1 levels is a key marker. Hypocretin neurons prominently located in the lateral hypothalamus and perifornical nucleus have been proposed to interact with mechanisms involving sleep and arousal. Low hypocretin-1 levels in the CSF have been shown to correlate with hypothalamic hypocretin cell loss in narcolepsy and other forms of hypersomnia; therefore, it has been proposed that degenerative damage to hypocretin neurons (such as in PD) may be detected by low CSF hypocretin-1 concentrations, and may also explain the sleep symptoms experienced by some PD patients. To date, there is mixed conflicting data describing hypocretin-1 levels in the CSF of patients with parkinsonism associated with sleep symptoms, with most studies showing no significant decrease when compared with controls. However, hypocretin-1 CSF deficiency has been shown in some studies to be more prominent in PD patients with sleep symptoms versus those without. Notably, the hypocretin system has been shown not to be selectively disrupted, with one study showing melanin concentrating hormone cell loss in the same patients with hypocretin loss. It is likely that hypocretin deficiency in PD patients occurs secondary to collateral damage caused by the neurodegenerative process involving the hypothalamus. Awareness of narcoleptic events in PD is important for driving related advice, in addition to the possible use of dopamine D3 receptor active agonists.

Narcolepsy presenting as REM sleep behaviour disorder.

REM sleep behaviour disorder (RBD) is a neurological condition well known to be associated with the synucleinopathies in middle-aged patients. However, there is much less data concerning its development, evolution, and association with other disorders in younger patients. We report two patients aged less than 33 years who presented with clinical and polysomnographical features of RBD, both of whom proved to have previously undiagnosed narcolepsy. Whilst the association of narcolepsy with RBD has been previously recognised, this is the first report of narcoleptic patients presenting with RBD. Narcolepsy should be included in the differential diagnosis of young patients presenting with abnormal behaviour during sleep compatible with RBD.

Glutaric aciduria type II and narcolepsy in pregnancy.

BACKGROUND: Glutaric aciduria type II is a rare disorder affecting the metabolism of fatty acid oxidation and several mitochondrial dehydrogenase enzymes. Narcolepsy and cataplexy is a disorder affecting sleep cycles and rapid eye movement activity. There is little information on outcome or management for either disorder in pregnancy. CASE: This is a case of a 16-year-old with glutaric aciduria type II and narcolepsy with cataplexy, treated with L-carnitine, riboflavin, fluoxetine, and modafinil during pregnancy. Intrapartum management included intravenous carnitine administration, and the patient underwent cesarean delivery at term without complication. CONCLUSION: This inborn error of metabolism and sleep disorder can be effectively treated during pregnancy with nutritional supplementation and stimulants. Because of the risk of cataplexy during labor, cesarean delivery is recommended to minimize the patient's risk.

Narcolepsy-cataplexy associated with precocious puberty.

In children, narcolepsy may be the symptom of a brain lesion or genetic disease. The authors report two cases with severe narcolepsy-cataplexy emerging in childhood in close temporal association with obesity and precocious puberty.

The number of hypothalamic hypocretin (orexin) neurons is not affected in Prader-Willi syndrome.

CONTEXT: Narcoleptic patients with cataplexy have a general loss of hypocretin (orexin) in the lateral hypothalamus, possibly due to an autoimmune-mediated degeneration of the hypocretin neurons. In addition to excessive daytime sleepiness, Prader-Willi syndrome (PWS) patients may show narcolepsy-like symptoms, such as sleep-onset rapid eye movement sleep and cataplexy, independent of obesity-related sleep disturbances, which suggests a disorder of the hypocretin neurons. OBJECTIVE: We hypothesized that the narcolepsy-like symptoms in PWS are caused by a decline in the number of hypocretin neurons. DESIGN: We estimated the number of hypocretin neurons in postmortem hypothalami using immunocytochemistry and an image analysis system. SETTING: This study was conducted at the Netherlands Institute for Brain Research. PATIENTS: Eight PWS adults, three PWS infants, and 11 controls were studied. MAIN OUTCOME MEASURE: The total number of hypocretin neurons in the lateral hypothalamus was measured. RESULTS: There was no significant difference in the total number of hypocretin-containing neurons among the seven PWS patients (in whom sufficient hypothalamic material was available to quantify total cell number) and seven age-matched controls, either in adults or in infants. A significant decline with age was found in adult PWS patients (r = -0.9; P = 0.037). CONCLUSIONS: We conclude that a decrease in the number of hypocretin neurons does not play a major role in the occurrence of narcolepsy-like symptoms in PWS.

Central administration of vitamin B12 aggravates cataplexy in canine narcolepsy.

Experimental evidence in canine narcolepsy suggests that central cholinergic systems are critically involved in the regulation of cataplexy, an abnormal manifestation of REM sleep atonia. In the current study, we found that intracerebroventricular perfusion of methyl-B12, (10(-5)-10(-2) M), significantly aggravated cataplexy and enhanced REM sleep in narcoleptic dogs. Choline, a direct precursor of acetylcholine, was also found to aggravate cataplexy, while cyano-B12, a vitamin B12 analog without methyl donating abilities, had no effect on cataplexy. Since both methyl-B12 and choline are reported to enhance acetylcholine synthesis, enhancement of the biosynthesis of acetylcholine may be involved in the effects observed in canine narcolepsy. Our results suggest that central administration of methyl-B12 has the potential to modulate both normal and pathological REM sleep.