Fernando Morgadinho Santos Coelho

Dravet syndrome: seizure control and gait in adults with different SCN1A mutations.

Purpose:  Dravet syndrome (DS) is an aggressive epileptic encephalopathy. Pharmacoresistant seizures of several types plague most patients with DS throughout their lives. Gait difficulties are a common, but inconsistent finding. The majority of cases are caused by mutations in the SCN1A gene, but little information is available about how particular mutations influence the adult phenotype. The purpose of this study is to correlate different types of SCN1A mutations and (1) seizure control, (2) occurrence of convulsive status epilepticus (cSE), and (3) the presence of crouch gait in adult patients.

Testing sleepiness and vigilance in the sleep laboratory

Purpose of review Excessive daytime sleepiness (EDS) is common and a potentially devastating public health challenge. EDS has been implicated as a contributing factor to workplace injury, motor vehicle accidents, cardiovascular disease, and impaired quality of life. Subjective self-report measures have failed to sufficiently quantify EDS. The use of objective tools found in sleep laboratories is therefore fundamental in the management of patients with EDS. The purpose of this review is to provide an overview of the current methods used to quantify sleepiness, and to highlight recent advances. Recent findings The Multiple Sleep Latency Test (MSLT), normally used for the diagnosis of narcolepsy, can be a useful tool in recognizing other forms of sleepiness. The Maintenance of Wakefulness Test (MWT) has also been confirmed as an important test to identify EDS, as well as to provide an indicator of future risk of accidents. Modifications and newer tests have been discussed with potential applications for the future. Summary Objective tests such as the MSLT and MWT are useful in the diagnosis and management of patients with EDS. However, the relatively high cost can restrict their overall usefulness in clinical medicine. Newer simple tests are under development.

Benefit of repeat multiple sleep latency testing in confirming a possible narcolepsy diagnosis.

Purpose The clinical diagnosis of narcolepsy is usually uncomplicated in the presence of cataplexy. Objective testing is more important in ambiguous disease. The gold-standard objective test in these cases is the multiple sleep latency test (MSLT). Repeat testing can be burdensome but is reasonable when faced with a diagnostic dilemma. However, there is limited evidence to support this approach. In this study, we assessed the diagnostic utility of a repeat MSLT in patients suspected of narcolepsy whose first MSLT result was nonconfirmatory. Methods Of 125 patients who underwent an MSLT between 2004 and 2009, we identified 10 (9.6%) who had undergone repeat studies. We analyzed changes in MSLT parameters while taking account of other relevant differences between testing. Results Two patients (20%) met narcolepsy criteria during the second MSLT. Nine patients (90%) met sleepiness criteria (mean sleep latency <8 minutes) during the second MSLT while only 5 did during the first (P = 0.05). Conclusions We demonstrate that a repeat MSLT confirmed the diagnosis of narcolepsy in 20% of patients whose results had been nonconfirmatory on a first MSLT. This study provides support for a repeat MSLT in cases where clinical suspicion for narcolepsy is high despite an ambiguous first test.

Traditional biomarkers in narcolepsy: Experience of a brazilian sleep centre

UNLABELLED This study was thought to characterized clinical and laboratory findings of a narcoleptic patients in an out patients unit at São Paulo, Brazil. METHOD 28 patients underwent polysomnographic recordings (PSG) and Multiple Sleep Latency Test (MSLT) were analyzed according to standard criteria. The analysis of HLADQB1*0602 allele was performed by PCR. The Hypocretin-1 in cerebral spinal fluid (CSF) was measured using radioimmunoassay. Patients were divided in two groups according Hypocretin-1 level: Normal (N) - Hypocretin-1 higher than 110 pg/ml and Lower (L) Hypocretin-1 lower than 110 pg/ml. RESULTS Only 4 patients of the N group had cataplexy when compared with 14 members of the L group (p = 0.0002). DISCUSSION This results were comparable with other authors, confirming the utility of using specific biomarkers (HLA-DQB1*0602 allele and Hypocretin-1 CSF level) in narcolepsy with cataplexy. However, the HLADQB1*0602 allele and Hypocretin-1 level are insufficient to diagnose of narcolepsy without cataplexy.

Frequencies and Associations of Narcolepsy-Related Symptoms: A Cross-Sectional Study.

OBJECTIVES Narcolepsy is a disabling disease with a delayed diagnosis. At least 3 years before the disorder identification, several comorbidities can be observed in patients with narcolepsy. The early recognition of narcolepsy symptoms may improve long-term prognosis of the patients. Thus, we aimed to investigate the prevalence of the symptoms associated with narcolepsy and its social and psychological association in a sample of Sao Paulo city inhabitants. METHODS We performed a cross-sectional evaluation with 1,008 individuals from the Sao Paulo Epidemiologic Sleep Study (EPISONO). Excessive daytime sleepiness (EDS) was assessed by the Epworth Sleepiness Scale. Volunteers were also asked about the occurrence of cataplectic-like, hypnagogic or hypnopompic hallucinations, and sleep paralysis symptoms. The participants underwent a full-night polysomnography and completed questionnaires about psychological, demographic, and quality of life parameters. RESULTS We observed a prevalence of 39.2% of EDS, 15.0% of cataplectic-like symptom, 9.2% of hypnagogic or hypnopompic hallucinations, and 14.9% of sleep paralysis in Sao Paulo city inhabitants. A frequency of 6.9% was observed when EDS and cataplectic-like symptoms were grouped. The other associations were EDS + hallucinations (4.7%) and EDS + sleep paralysis (7.5%). Symptomatic participants were predominantly women and younger compared with patients without any narcolepsy symptom (n = 451). Narcolepsy symptomatology was also associated with a poor quality of life and symptoms of depression, anxiety, and fatigue. CONCLUSIONS Narcolepsy-related symptoms are associated with poor quality of life and worse psychological parameters.

Parathyroidectomy Improves Restless Leg Syndrome in Patients on Hemodialysis.

Background Restless leg syndrome (RLS) is a sleep disorder with high prevalence among patients on hemodialysis. It has been postulated that high phosphate and high parathyroid hormone may be implicated in its pathogenesis. Standard international criteria and face-to-face interview are not always applied. Methods this was an interventional prospective study in which 19 patients (6 men, aged 48±11 years) with severe hyperparathyroidism were evaluated. RLS diagnosis and rating scale were accessed based on the International RLS Study Group pre- and post-parathyroidectomy. Patients also underwent standard polysomnography. Results At baseline, RLS was present in 10 patients (52.6%), and pain was the most reported symptom associated with the diagnosis. Patients with RLS had higher serum phosphate (p = 0.008) that remained independently associated with RLS in a logistic regression model, adjusted for hemoglobin, age and gender (HR = 7.28;CI = 1.14–46.3, p = 0.035). After parathyroidectomy, there was a reduction of serum parathyroid hormone, phosphate, calcium and alkaline phosphatase, and an increase of 25(OH)-vitamin D, and Fetuin-A. Parathyroidectomy alleviated RLS (from 52% to 21%; p = 0.04), which was accompanied by a decrease in severity scale, in association with relief of pain and pruritus. Polysomnography in these patients showed an improvement of sleep parameters as measured by sleep efficiency, sleep latency and percentage of REM sleep. Conclusion RLS is associated with high levels of phosphate in patients with severe secondary hyperparathyroidism on hemodialysis. Pain is most reported complain in these patients. Parathyroidectomy provided an opportunity to relief RLS. Whether the reduction of serum phosphorus or parathyroid hormone contributed to this improvement merits further investigation.

Prevalence of HLA DQB1*0602 allele in patients with migraine

BACKGROUND Studies have shown a high prevalence of migraine among narcoleptic patients. HLA-DQB1*0602 and HLA DRB1 alleles are closely associated with narcolepsy. An increase in the HLA-DRB1 allele frequency in patients with visual aura has raised greater awareness of the genetic background in migraine. PURPOSE Since the regions DR and DQ of the HLA are in tightly linkage desiquilibrium we hypothesize that HLA-DQB1*0602 might be associated to the pathophysiology of migraine. METHOD We analyzed the presence of HLA DQB1*0602 allele in 50 healthy subjects with no history of migraine, 53 patients with migraine without aura and 52 patients with migraine with aura. RESULTS There was no difference in the frequency of HLA DQB1*0602 allele when control subjects and all patients were compared. We failed to note any difference in frequencies when comparing migraine patients with and without aura. CONCLUSION Further studies with different patient populations, with other hypothalamic markers (melatonin, hypocretin) in migraine patients may shed light on to its pathophysiology.

A rare differential diagnosis of excessive daytime sleepiness - Artery of Percheron territory infarct

Stroke is an example of neurological diseases that can commonly drives Excessive Daytime Sleepiness (EDS). Extensive strokes with brain edema can leave a brain herniation and coma. Other causes of EDS after stroke are strategic lesions at Thalamus and brainstein. A 56-year-old man, right handed, with hypertension and hypercholesterolemia was admitted at Emergency Room due to 5 days onset of EDS, memory impairment, and left-sided weakness. A brain magnetic resonance imaging showed paramedian thalamic hyperintensity with rostral midbrain hyperintensity extending along the pial surface of the interpeduncular fossa. The artery of Percheron (AP) is an unusual anatomical variation that originates from the posterior cerebral artery and irrigates the paramedian regions of the thalamus and part of the midbrain. It is important the clinical suspicions with detailed drowsy patients history. Awareness of the clinical and neuroimaging features of this stroke syndrome is essential for timely diagnosis and appropriate management.

Human hypocretin-deficient narcolepsy - aberrant food choice due to impaired taste?

Authors demonstrate that patients with narcolepsy type 1 (N1) have more tendency of eat salty snacks after satiety than health volunteers. A few mechanisms to explain the weight gain have been discussed in narcolepsy. The hypocretin-1 deficiency can influence the olfactory system. The olfactory system should be modulated through hypocretin-1 via connections from the hypothalamic to other brain regions. Likewise, hypocretin-1 can be synthesized locally in our olfactory mucosa with possible private role modulating the olfactory. In experimental studies, different kinds of smell influence the preference for type of diet. Olfactory and taste sensations help control of appetite and regulate the quantity and quality of foods that will be chosen. N1 patients have lower levels of hypocretin-1 and consequent inferior olfactory threshold, less olfactory discrimination, and these findings improved after nasal hypocretin-1 administration. It is possible that the hyposmia influenced the quality and quantity of food by narcoleptic patients. We suggest that a complementary analysis of olfactory function should be done concomitant with food preferences to compare narcoleptic patients with and without hypocretin-1 deficiency.

Evaluating the underestimated risk factors associated with carotid artery stenosis.

Stroke is the third leading cause of premature deaths and one of the most prevalent causes of disability-adjusted lifeyears [1]. Risk factors and their motor and cognitive impairment induced mechanisms have been frequently investigated. Ischaemic strokes can be a result of cardiovascular emboli or local artery stenosis. Carotid artery diseases are responsible for 10% to 20% of strokes [2]. The study performed by Everts et al. [3] is very interesting. The authors performed a prospective exploratory study with symptomatic patients aged between 51.3 and 85.3 years with extracranial carotid artery stenosis of ≥70%. The main finding of the present study was the correlation between the carotid artery stenosis and impairments in various cognitive and emotional domains, including verbal fluency and anxiety. These results suggest that carotid artery stenosis may induce neuropsychological impairments even in patients without a previous stroke history. Thus, controlling the risk factors of atherosclerotic lesions seems to be essential to prevent prior cerebrovascular impairments. Several studies have demonstrated the association between sleep-disordered breathing, such as obstructive sleep apnoea, and cardiovascular outcomes [4, 5]. However, primary snoring is still an underestimated respiratory condition. Recently, a study discussed the possible relationship between primary snoring and carotid artery intima-media thickness [6]. The results of this study showed that the intima-media thickness of patients who snored was greater, when considering eight different points of the carotid artery, compared with those of nonsnorers. Therefore, primary snoring could be a possible mechanism for the aggravation of the carotid stenosis, leading to greater hypoperfusion and embolisation, eventually resulting in a cognitive and executive function deficit. In general, studies show that prevention is still the best and most cost-effective way to avoid cardiovascular events. Primary snoring is underestimated and understudied among sleep disorders, but it seems to be related to stroke. Therefore, we emphasise that primary snoring and cardiovascular outcomes must be studied. A higher prevalence of snoring and cultural tolerance of this symptom is a problem. It is important to study more extensively the outcomes, causes and comorbidities of primary snoring, such as neurovascular diseases that are the major causes of health expenditures and disabling sequelae.