X-linked olivopontocerebellar atrophy

We present a kindred with a relatively pure cerebellar degeneration that demonstrates X-linked recessive inheritance. The unique clinical picture of affected patients in our kindred is characterized by an infantile onset of ataxia; very slow rate of progression; normal strength, reflexes, and sensation; and cerebellar degeneration with involvement of the olive and pons demonstrated by neuroimaging techniques. The distinction between this and other reported olivopontocerebellar degenerations is made on the basis of the clinical features and mode of inheritance. It is not clear if the distinct clinical pattern in this kindred represents variable expression of a previously reported condition, allelic variance of previously reported kindreds, or a separate clinical entity. Molecular analysis, currently underway, may help settle the issue.     

Motor learning processes in a movement-scaling task in olivopontocerebellar atrophy and Parkinson's disease

Nine Parkinson's disease (PD), seven olivopontocerebellar atrophy (OPCA) patients and two age-matched control groups learned a linear arm movement-scaling task over 2 days, requiring movements proportional in length to visually presented target-bars. Scaling was acquired through knowledge of results (KR concerning the direction and magnitude of errors) following every second acquisition trial. Initial acquisition of both groups was significantly worse than their respective controls (poorer movement scaling), but rapidly improved to nearly identical levels. Retention for the PD group's movement scaling was as good as controls initially, but markedly poorer after 24 h. The OPCA group did not show this deficit. Both patient groups extrapolated accurately to longer, previously unpracticed target distances (no KR provided), suggesting an unimpaired capacity to generate and use an internal representation of the movement scaling. They also rapidly learned a new scaling relationship when the gain was changed. Overall, the learning of this movement-scaling task was not adversely affected in OPCA, and the impairment was restricted primarily to longer-term retention in PD. The study suggests that: (1) the ability to acquire movement scaling in a task that requires conscious use of error feedback and no new coordination may depend little on the cerebellum, and (2) the basal ganglia may participate in longer-term storage of scaling information.     

Glycerophosphoethanolamine concentration is elevated in brain of patients with dominantly inherited olivopontocerebellar atrophy

We measured the concentration of glycerophosphoethanolamine (GPEA), a membrane breakdown product, in autopsied brain of 10 patients with dominantly inherited olivopontocerebellar atrophy (OPCA), a cerebellar ataxia disorder. As compared with the controls, mean GPEA levels were significantly elevated by 37–69% in 11 of the 15 brain areas examined, including extracerebellar brain regions in which no neuronal cell loss could be detected by semiquantitative estimation. Our data suggest the possibility of altered membrane phospholipid metabolism in OPCA which could be a contributing factor in the neuronal cell death.     

橄榄桥脑小脑萎缩一家系的临床和遗传学研究

Objective To make clinical and genetic diagnosis of members within a family with an autosomal dominant olivopontocerebellar atrophy, and to analyze the relationship between clinical features and genotype. Methods Pedigree analysis, the neurological examination, accessory test like brain MRI, and the molecular genetic analysis of the coding region of SCA1(spinocerebellar ataxia type 1)、SCA3 、SCA7 、SCA12 and DRPLA(dentatorubral and palliodoluysian atrophy). Results The family manifested an autosomal dominant inheritance. In the two typical patients, brain MRI showed remarkable atrophy on cerebellum、brain stem and pons varolii. The CAG lengths of SCA3 、SCA7、SCA12 and DRPLA were normal in all family members. CAG repeat sizes of SCA1 ranged from 29 to 37 repeats in 10 healthy controls and 4 unaffected family members, whereas in the two patients, Ⅳ3 and Ⅳ7, the mutated allele were 53 and 67 respectively. The daughter of Ⅳ3 was diagnosed as presymptomatic SCA1 patient, due to the fact that she carries the mutated allele 57. Conclusion This family was genetically and clinically diagnosed to be autosomal dominant SCA1. The clinical features of SCA1 are heterogeneous, so genetic diagnosis is very important.     

橄榄桥脑小脑萎缩一家系的临床和遗传学研究

目的 对一个常染色体显性遗传橄榄桥脑小脑萎缩(olivopontocerebellar atrophy,OPCA)家系进行临床诊断,探讨其临床特点并明确其基因诊断.方法 完成家系调查,对包括先证者在内的家系成员进行神经科体检,行头部核磁共振(magnetic resonance imaging,MRI)等辅助检查,并进行基因诊断.结果 该家系呈常染色体显性遗传,其中两例成员有明显异常临床表现,家族史调查显示另有9例有相似临床表现的成员已去世,头部MRI示小脑、脑干以及桥脑萎缩明显.结合家族史、临床表现以及MRI检查结果,其诊断符合橄榄桥脑小脑萎缩.对所有家系成员进行致病基因分析发现,脊髓小脑共济失调2型(spinocerebellar ataxia type 2,SCA2)、3型(SCA3)、7型(SCA7)、12型(SCA12)以及齿状核红核苍白球丘脑下部核萎缩(dentatorubral-pallidoluy-sian atrophy,DRPLA)致病基因检测均正常.10例健康对照SCA1目的片段CAG重复数为29～37,而2例患者异常等位基因CAG重复数分别为53和67,5例无症状家系成员中,1例CAG重复数为57,确诊为症状前患者,另外4例CAG重复数在29～37之间,排除患病可能.结论 该家系为CAG动态突变引起的橄榄桥脑小脑萎缩,临床特征存在异质性,基因诊断符合SCA1.     

Normal serotonin but elevated 5-hydroxyindoleacetic acid concentration in cerebellar cortex of patients with dominantly-inherited olivopontocerebellar atrophy.

Beas-Zarate and coworkers (Eur. J. Pharmacol., 198 (1991) 7-14) recently reported markedly reduced concentration of presynaptic serotonin neurotransmitter markers in cerebellum of rodents which had suffered destruction of the inferior olivary-cerebellar (climbing fibre) projections by the neurotoxin 3-acetylpyridine; these experimental animal data suggested that serotonin might be one of the neurotransmitters released by climbing fibres. We measured the concentration of serotonin and its major metabolite 5-hydroxyindoleacetic acid (5-HIAA) in autopsied cerebellar cortex of 14 patients with dominantly-inherited olivopontocerebellar atrophy (OPCA) who all had near-total degeneration of the inferior olivary climbing fibres. As compared with the controls, mean concentration of serotonin in cerebellar cortex of the OPCA patients was normal whereas 5-HIAA levels (+79%, P less than 0.02) and 'turnover' ratio 5-HIAA/serotonin (+148%, P less than 0.05), on average, were significantly elevated. These data do not support the notion that serotonin is a predominant neurotransmitter of the human climbing fibre. However, the markedly elevated serotonin turnover ratio suggests the possibility of increased serotonergic neuronal activity, which might alter, and perhaps improve, the functioning of the preserved cerebellar cortical neurones in OPCA.     

Nocturnal asthma

Nocturnal symptoms and overnight decrements in lung function are a common part of the asthma clinical syndrome. As many as 75% of asthmatic subjects are awakened by asthma symptoms at least once per week, with approximately 40% experiencing nocturnal symptoms on a nightly basis. An extensive body of research has demonstrated that nocturnal symptoms of cough and dyspnea are accompanied by circadian variations in airway inflammation and physiologic variables, including airflow limitation and airways hyperresponsiveness. Alterations in beta2-adrenergic and glucocorticoid receptors and hypothalamic-pituitary-adrenal axis function might play a role in modulating the nocturnal asthma phenotype, and recent studies have suggested that melatonin, a neurohormonal controller of circadian rhythms, might be important as well. Treatment strategies in nocturnal asthma are similar to those used in persistent asthma, although dosing of medications to target optimum effect during periods of nocturnal worsening is beneficial.     

Nocturnal Panic

This article reviews the phenomenon of nocturnal panic, or waking from sleep in a state of panic. The review covers the presenting features of nocturnal panic and the evidence for cognitive and physiological mediating variables. A psychobiological conceptualization that parallels conceptualilatlons for daytime panic attacks is offered. Obstacles for future research in this area include ambiguities in the definition of nocturnal panic, and its distinctiveness from other sleep disorders, as well as measurement issues. Implications from a psychobiological conceptualization include the appropriateness of cognitive-behavioral treatment for nocturnal panic.     

Amphotericin-induced stridor: a review of stridor, amphotericin preparations, and their immunoregulatory effects.

BACKGROUND: Various adverse effects have been reported with the use of amphotericin B. The respiratory adverse effects include dyspnea, tachypnea, bronchospasm, hemoptysis, and hypoxemia. Stridor has not been previously reported with the use of amphotericin B. OBJECTIVE: To review the mechanism of action and reports of respiratory adverse effects for amphotericin B, the liposomal preparations of amphotericin B, and the differential diagnosis of stridor. DATA SOURCES: A MEDLINE search from 1966 to 2002 was performed to review the current literature for possible mechanisms and immunoregulatory effects related to the infusion of amphotericin B. RESULTS: Amphotericin B has been shown to increase tumor necrosis factor alpha (TNF-alpha) concentrations in macrophages. In addition, it induces prostaglandin E2 synthesis and increases the production of interleukin 1beta (IL-1beta) in mononuclear cells. The immunoregulatory effects of amphotericin B include increases in apoptosis, production of monocyte chemoattractant protein 1, superoxide anion, nitric oxide, and intercellular adhesion molecule 1 expression. CONCLUSIONS: Amphotericin B induces the production of TNF-alpha, interferon-gamma, and IL-1beta, which may potentiate its toxic effects. Some liposomal preparations induced lower levels of TNF-alpha and nitric oxide and may be useful in patients unable to tolerate amphotericin B deoxycholate.     

Intermittent stridor and dyspnea in an adult.

We describe an adult patient who had stridor and dyspnea as initial symptoms of a thyroglossal duct cyst. Spirometry and noninvasive imaging techniques have been useful for diagnosis of this condition.     

Munchausen's stridor: non-organic laryngeal obstruction

A patient had at least 15 hospital admissions for symptoms of acute dyspnoea accompanied by loud stridorous sounds. These episodes had been diagnosed as acute airway obstruction and she was treated on all occasions on an emergency basis. In the absence of a definitive etiology and with other clues, it was then recognized that the patient was imitating the clinical appearance of laryngeal obstruction. Following the establishment of this, psychiatric care was initiated with the goal of rehabilitation of the patient, and there have been no further episodes to the present time.     

Nocturnal temperature in affective disorder

The temperature rhythms of 9 drug-free patients with primary affective disorder were measured during depression and after recovery and compared with those of 12 normal controls. The patients had higher nocturnal temperatures and decreased 24-hour amplitudes when depressed than when they had recovered and compared to the controls. There was no evidence that the temperature minimum occurred earlier in the night in depression compared to controls. However, in 4 of 7 patients the temperature minimum occurred earlier in the night during depression compared to recovery.     

Sustained-Release Terbutaline in Nocturnal Asthma

Fifteen adult patients with nocturnal asthma entered a double blind study. They received a single evening dose of one sustained-release (SR) terbutaline tablet à 7.5 mg or an identical placebo tablet for 1 week, each in a randomised cross-over fashion in addition to their usual medication. In the 12 evaluated patients there was no change in evening PEF but a significant improvement in morning PEF (P less than 0.05) and in overnight fall of PEF (P less than 0.01) on active treatment. Symptoms were improved by both placebo and active medication. Three patients experienced tremor as a side effect. A single evening dose of SR-terbutaline can be of help in nocturnal asthma.     

Nocturnal hemodynamic patterns in dogs

Several species which have a single daily wake-sleep cycle show a progressive fall in cardiac output and rise in total peripheral resistance during sleep, a cardiovascular response which may reflect a progressive decrease in plasma volume. The present study showed that no such progressive overnight changes in cardiac output or total peripheral resistance occur in the dog, a carnivore which tends to be awake and to drink intermittently during the night. Progressive overnight bradycardia (-12.7 +/- 3.1%) and compensatory increase in stroke volume (14.8 +/- 6.0%) were observed in this species, however. These findings are consistent with the view that differences between primates and carnivores in overnight hemodynamic function are related to species differences in sleep and ingestive behavior.