The HLA-DRB1 and HLA-DQB1 alleles are associated with multiple sclerosis disability progression in Slovak population

Objective: The aim of our present study was to analyse the association of HLA-DRB1 and -DQB1 alleles and genotypes with Multiple Sclerosis (MS) disability progression in a cohort of Central European Slovak population.

Methods: The allele and genotype variants were analyzed in 282 non-related MS patients. Rate of disease disability progression was evaluated using EDSS score in the 5^th, 7^th, 10^th, and 15^th year of disease duration, time to reach EDSS score 3 and 5, and MSSS score. Genotyping was performed by polymerase chain reaction with sequence-specific primers.

Results: We found that carriers of homozygous genotype for alleles DRB1*15 and DQB1*03 reached EDSS score 3 significantly earlier than non-carriers of these alleles (p = 0.0172; p = 0.00183, respectively). Genotype DQB1*03/03 carriage was also associated with significantly reduced time to reach EDSS score 5 (p = 0.00316). Lower EDSS score in the 5^th year of disease duration was found in carriers of DRB1*07 allele (p _cor = 0.028). When MSSS score was used, genotype DRB1*15/15 was found to be less frequent in slow progressing MS patients, when compared to MS patients with mid-rate and rapid disease disability progression (p _cor = 0.0305).

Discussion: We showed for the first time that HLA-DRB1 and -DQB1 genotypes are genetic markers associated with disability progression in Slovak MS patients. Genotypes DRB1*15/15 and DQB1*03/*03 were identified as short-term clinical negative prognostic factors, while allele DRB1*07 carriage appeared to be a positive prognostic marker of better MS outcome.     

The treatment of Kleine-Levin syndrome with lithium

A case of Kleine-Levin Syndrome without megaphagia is described in an adolescent male who responded well to lithium treatment. Seventy-two hours of sleep monitoring during a typical attack revealed decreased stages three and four but no sleep-onset REM period. Recent reports, including the present one, strongly suggest that Lithium Carbonate may be the treatment of choice for the Kleine-Levin Syndrome.     

The association of HLA-DRB1 and HLA-DQB1 alleles with genetic susceptibility to multiple sclerosis in the Slovak population

Objective: The aim of the present study was to assess the association between HLA-DRB1 and -DQB1 allele groups with the genetic predisposition to multiple sclerosis (MS) in the Caucasian Central European Slovak population.

Methods: A total of 282 unrelated patients with sporadic MS were enrolled in this case-control study. HLA-DRB1 and HLA-DQB1 allele groups were genotyped using a polymerase chain reaction with sequence-specific primers. The DRB1 and DQB1 allele carrier frequencies, genotypes and haplotype frequencies were compared between MS cases and healthy controls.

Results: Positive association with MS was found for alleles HLA-DRB1*15 (OR = 3.64; Pcor = 6.9x10–11), DRB1*03 (after elimination of carriers of DRB1*15, OR = 2.8; Pcor = 0.0029), DQB1*06 (OR = 1.99; Pcor = 7.0x10–4), genotypes HLA-DRB1*15/*15 (OR = 7.6; Pcor = 0.001) and DQB1*06/*06 (OR = 3.81; Pcor = 4.0x10–4) and for haplotype DRB1*15-DQB1*06 (OR = 3.03; Pcor = 0.001). Carriage of alleles DRB1*07 (OR = 0.53; Pcor = 0.04), DRB1*13 (OR = 0.39; Pcor = 4.0x10–4), DQB1*03 (OR = 0.46; Pcor = 1.0x10–4), genotypes HLA-DRB1*13/*11 (OR = 0.12; Pcor = 0.004), DQB1*05/*03 (OR = 0.39; Pcor = 0.035), DQB1*03/*03 (OR = 0.38; Pcor = 0.029) and haplotypes DRB1*13-DQB1*06 (OR = 0.47; Pcor = 0.0128) and DRB1*11-DQB1*03 (OR = 0.58; Pcor = 0.0352) was found to be protective against MS development.

Discussion: This is the first study performed to analyse the association of HLA-DRB1/DQB1 with susceptibility to MS in Slovakia. The results of our study confirm that HLA class II alleles, genotypes and haplotypes are associated with MS risk.     

Short-term memory dysfunction in Kleine-Levin syndrome

BACKGROUND : A previous investigation at our department of a young man with typical Kleine-Levin syndrome revealed short-term memory dysfunction as well as hypoperfusion of the temporal lobes on single photon emission tomography (SPECT) (CERETEC) examination, 6 and 7 years after recovery, suggesting long lasting or even permanent cerebral dysfunction. PATIENTS AND METHODS : We investigated four cases with classical adolescent Kleine-Levin syndrome characterized by hypersomnia and typical associated symptoms. We used neuropsychological testing and SPECT (CERETEC) of the brain. The results from the previous report related to above is included. RESULTS : Examination with SPECT (CERETEC) during remission revealed hypoperfusion of the temporal lobes and fronto-temporal region in two of four cases. There were normal findings in two. Neuropsychological testing performed during remission showed reduction in the short-term memory capacity in all four cases. CONCLUSION : It is striking that all the cases investigated showed short-term memory dysfunction. One patient who had recovered from paroxysmal symptoms (hypersomnia attacks and bulimia) 6 years earlier showed progress in the short-term memory dysfunction. A pathologic condition in the temporal lobes may be suspected in Kleine-Levin syndrome.     

The Kleine-Levin syndrome and the treatment with methylphenidate

A 17-year-old man was referred to the Med-Psych-Unit because of recurrent episodes of hypersomnia, megaphagia, hypersexual behaviour and cognitive disturbances. Over the period of three years he suffered more than 10 episodes of hypersomnia each lasting 8 to 16 days. The clinical presentation was suggestive of the Kleine-Levin syndrome. The symptoms disappeared after treatment with methylphenidate, but it was not clear whether this could be attributed to the medication or to the self-limiting character of the illness. The Kleine-Levin syndrome is often clinically not recognised due to the variation in the symptoms and the lack of objective diagnostic examination.     

Sleep patterns in Kleine-Levin syndrome.

Diurnal and nocturnal sleep records were obtained from a male and a female with Kleine-Levin syndrome, during excessive daytime sleep attacks and while they were asymptomatic. A common pattern of abnormal sleep was seen in both patients even during the asymptomatic period. The female, aflicted with a severe form of periodic hypersomnia, showed nocturnal and diurnal sleep onset REM periods. The different pattern of sleep abnormality in the female could be an expression of the severity of her symptoms or might indicate a variant of sleep abnormality present only in females with Kleine-Levin syndrome.     

Kleine-Levin syndrome in a 14-year-old girl: CSF hypocretin-1 measurements

CSF hypocretin-1 measurements were performed during a period of hypersomnia and during an asymptomatic interval in a 14-year-old girl affected with severe Kleine-Levin syndrome. A twofold decrease in hypocretin-1 was evidenced during the period of hypersomnia in comparison with the asymptomatic interval. Together with previous data, this result is in favour of recurrent dysfunction at the hypothalamic level in Kleine-Levin syndrome.     

Persistent deficits of visual recall in Kleine-Levin syndrome

Kleine-Levin syndrome (KLS) is commonly described as a self-limiting disorder exhibiting episodes of hypersomnia and psychiatric symptoms but without any enduring disabilities. Recently, some authors have reported persistent or even progressive memory deficits associated with the disorder. Nevertheless, literature about cognitive disturbances in KLS is rare. Our report describes a patient with deficits of visual and verbal recall after remission of an episode, as well as selective deficits of visual recall 6 months later. Neuropsychological testing is necessary in all patients with KLS to further characterize the profile and impact of associated cognitive deficits.     

Efficacy of lithium treatment in Kleine-Levin syndrome.

The Kleine-Levin syndrome (KLS) is characterized by periodic, sudden-onset episodes of hypersomnia, compulsive hyperphagia, and behavioral-emotional symptoms, lasting from a few days to a few weeks, with complete remission in the intercritical periods. We report on efficacy of lithium treatment in a highly recurring form of the disorder in a 17-year-old male adolescent. The decreasing severity of the disorder paralleled the progressive increase of lithium dosage, up to 0.9 mEq l(-1). Implications regarding the pharmacological treatment of this neglected disorder are discussed.     

Photosensitivity during the hypersomnic phase in a patient with Kleine-Levin syndrome

The case of an adolescent with Kleine-Levin syndrome is presented who exhibited a consistent and predictable photoparoxysmal self-limited response to intermittent photic stimulation during all relapses of his hypersomnic phase. A possible cause of this association that has not been previously reported is speculated based on observations concerning the two disorders.     

An unusual case of Kleine-Levin syndrome associated with sleep terrors

The authors describe a case of Kleine-Levin syndrome (KLS) which in the hypersomniac period presents, together with the classical symptoms, frequent arousals accompanied by sleep terrors. Polygraphic study shows the absence of any nyctohemeral cycle and very frequent parasomnias occurring during arousals from NREM sleep. On the basis of data from the literature, the authors suggest that a disturbance of maintenance of sleep might not be exceptional in KLS, even if none of the previous reports describes such frequent parasomnias.     

Multiple Sleep Latency Test findings in Kleine-Levin syndrome

Multiple Sleep Latency Test (MSLT) findings in a case of Kleine-Levin syndrome are reported for the first time. MSLT data indicate sleepiness as severe as in narcolepsy or obstructive sleep apnea and the occurrence of four sleep onset rapid eye movement (REM) periods, with a greater REM propensity at 2:00 p.m. and 4:00 p.m. than at 10:00 a.m. and 12:00 noon. The replication of such findings might suggest that Kleine-Levin syndrome could be considered a form of periodic REM sleep disinhibition. Therefore, the traditional hypothesis of diencephalic dysfunction may require modification to include the role of more caudal brain stem structures specifically activated during REM sleep.