Painful ophthalmoplegia--Tolosa-Hunt syndrome

Tolosa Hunt syndrome is a rare disorder caused by nonspecific inflammation in the cavernous sinus/superior orbital fissure and/or orbital apex. It is clinically characterized by alternating remissions and exacerbations, and manifested as diplopia associated with unilateral periorbital hemicranial headache. The symptoms include blepharoptosis, which is usually mild if present, bulbomotor paresis involving the pupil, and loss of sensation in the area supplied by the first division of the trigeminal nerve. Therapy for Tolosa-Hunt syndrome are systemic steroids. The course of disease in a 25-year-old man hospitalized for painful ophthalmoplegia and diplopia is presented. The history included severe pain on rightward eye movement and parabulbarly on the right, considerable defect in the area supplied by the first division of the trigeminal nerve, right hemicrania, and diplopia on looking to the left, right, upward and downward that developed after four days. A month before, the patient was observed at neurology department for severe right hemicrania. Current status included severe pain parabulbarly on the right, discrete proptosis with mild ptosis on the right eye, restricted right eye bulbar motoricity on looking nasally, nasally upward and downward, and loss of sensation in the area supplied by the first division of the trigeminal nerve. Pupilar motoricity was normal. Upon admission, neuroradiologic examination (orbit CT) and brain MR were performed, and therapy with systemic corticosteroids was initiated ex iuvantibus, in consultation with a neurologist. At 24 hours of corticosteroid therapy, the pain subsided, whereas diplopia disappeared almost completely after 5 days, now being only occasionally recorded on looking to the left and upward.     

Transverse myelitis associated with restless legs syndrome and periodic movements of sleep responsive to an oral dopaminergic agent but not to intrathecal baclofen

Periodic limb movement disorder (PLMD) and restless legs syndrome (RLS) are related sleep disorders that occur with increased frequency in spinal cord disease. Effective treatment may be obtained with dopaminergic or opioid drugs, while anticonvulsants, benzodiazepines, and possibly baclofen may be helpful. This report describes a patient who developed RLS and PLMD after acute transverse myelitis associated with infectious mononucleosis, and failed to respond to intrathecal baclofen. All symptoms of RLS/PLMD resolved after treatment with pergolide.     

The restless legs syndrome

The restless legs syndrome (RLS) is one of the commonest neurological sensorimotor disorders at least in the Western countries and is often associated with periodic limb movements (PLM) during sleep leading to severe insomnia. However, it remains largely underdiagnosed and its underlying pathogenesis is presently unknown. Women are more affected than men and early-onset disease is associated with familial cases. A genetic origin has been suggested but the mode of inheritance is unknown. Secondary causes of RLS may share a common underlying pathophysiology implicating iron deficiency or misuse. The excellent response to dopaminegic drugs points to a central role of dopamine in the pathophysiology of RLS. Iron may also represent a primary factor in the development of RLS, as suggested by recent pathological and brain imaging studies. However, the way dopamine and iron, and probably other compounds, interact to generate the circadian pattern in the occurrence of RLS and PLM symptoms remains unknown. The same is also the case for the level of interaction of the two compounds within the central nervous system (CNS). Recent electrophysiological and animals studies suggest that complex spinal mechanisms are involved in the generation of RLS and PLM symptomatology. Dopamine modulation of spinal reflexes through dopamine D3 receptors was recently highlighted in animal models. The present review suggests that RLS is a complex disorder that may result from a complex dysfunction of interacting neuronal networks at one or several levels of the CNS and involving numerous neurotransmitter systems.     

A novel neurodevelopmental syndrome responsive to 5-hydroxytryptophan and carbidopa

Tryptophan hydroxylase (TPH; EC 1.14.16.4) catalyzes the first rate-limiting step of serotonin biosynthesis by converting l-tryptophan to 5-hydroxytryptophan. Serotonin controls multiple vegetative functions and modulates sensory and alpha-motor neurons at the spinal level. We report on five boys with floppiness in infancy followed by motor delay, development of a hypotonic-ataxic syndrome, learning disability, and short attention span. Cerebrospinal fluid (CSF) analysis showed a 51 to 65% reduction of the serotonin end-metabolite 5-hydroxyindoleacetic acid (5HIAA) compared to age-matched median values. In one out of five patients a low CSF 5-methyltetrahydrofolate (MTHF) was present probably due to the common C677T heterozygous mutation of the methylenetetrahydrofolate reductase (MTHFR) gene. Baseline 24-h urinary excretion showed diminished 5HIAA values, not changing after a single oral load with l-tryptophan (50-70 mg/kg), but normalizing after 5-hydroxytryptophan administration (1 mg/kg). Treatment with 5-hydroxytryptophan (4-6 mg/kg) and carbidopa (0.5-1.0 mg/kg) resulted in clinical amelioration and normalization of 5HIAA levels in CSF and urine. In the patient with additional MTHFR heterozygosity, a heterozygous missense mutation within exon 6 (G529A) of the TPH gene caused an exchange of valine by isoleucine at codon 177 (V177I). This has been interpreted as a rare DNA variant because the pedigree analysis did not provide any genotype-phenotype correlation. In the other four patients the TPH gene analysis was normal. In conclusion, this new neurodevelopmental syndrome responsive to treatment with 5-hydroxytryptophan and carbidopa might result from an overall reduced capacity of serotonin production due to a TPH gene regulatory defect, unknown factors inactivating the TPH enzyme, or selective loss of serotonergic neurons.     

Association between migraine and restless legs syndrome

Migraine and restless legs syndrome (RLS) are common medical disorders that often co-occur. Various hypotheses have suggested that the co-occurrence of these distinct disorders could be related to shared genetic, neurobiological, or environmental factors. In this article, we review the available evidence regarding hypotheses concerning the possible causal roots of the frequently observed RLS/migraine association. We found only one study that implicated genetic mechanisms as potential causal factors. In addition, the dopamine theory appears to be overly simplistic. However, the roles of sleep disturbance and obesity have not been systematically investigated. Thus, it is suggested that these two factors be investigated further for a better understanding of their possible role in the pathophysiology of migraine and RLS. Elucidation of these issues would make an important contribution to methods of therapy and could potentially reduce the burden imposed by these disorders.     

Periodic leg movements and restless legs syndrome

Study objectives

Periodic leg movements (PLM) are a common phenomenon in several somatic and psychiatric disorders, often related to sleep disorders. We examined the prevalence of PLM, periodic leg movement disorder (PLMD), and restless legs syndrome (RLS) in psychiatric inpatients suffering from severe sleep disturbances and tried to find possible influences of the prescribed medication.

Design, setting and patients

In a retrospective data analysis, we explored the patient’s records in 117 psychiatric inpatients, suffering from comorbidity with severe sleep disturbances.

Measurements and results

We found PLM was positive in 61.5% of our sample, while diagnosing PLMD in 25.6% and RLS in 19.7%. A total of 74% of our RLS patients suffered from PLM. Adding dopaminergic medication or reducing neuroleptic agents improved subjective sleep quality and lowered PLM indices in patients with persistent sleep disturbances. Age-related results showed high PLM scores in patients below 40 years.

Conclusions

PLM occurred in more than 60% of the study group and a PLMD was found in about 25% of our patients. We found PLM indices in our younger patients relatively high in comparison with healthy adults. However, we found no statistically significant influence of the initially prescribed medication – maybe due to polypharmacy. Goal-directed addition of dopaminergic agents or the reduction of neuroleptic drugs results in lower PLM indices and improved subjective sleep quality.     

Anophthalmos-syndactyly (Waardenburg) syndrome without oligodactyly of toes

We report on 2 brothers from a consanguineous family from a small city of southeast Turkey. Both have bilateral anophthalmia, soft tissue syndactyly of the feet, bilateral partial synostosis of metatarsals IV and V, and basal synostosis of the fourth and fifth toes on the right in the older sib only, thus differing from all previously reported cases of anophthalmos-syndactyly syndrome. © 1995 Wiley-Liss, Inc.     

The prevalence of restless legs syndrome among pregnant women in Japan and the relationship between restless legs syndrome and sleep problems

STUDY OBJECTIVES: To clarify the prevalence of restless legs syndrome (RLS) in pregnant women living in Japan and to analyze the relationship between sleep problems and RLS, in order to discuss ways for pregnant women to obtain comfortable sleep and to improve the health of both the mother and child. DESIGN: A cross-sectional questionnaire survey. SETTING: 500 clinical institutions with maternity services were randomly sampled from a list of organizations identified in a survey by the Japan Association of Obstetricians and Gynecologists. Of these 500 institutions, 260 participated in the survey. PARTICIPANTS: 16,528 pregnant women living in Japan. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: In this survey of pregnant women, the prevalence of RLS was found to be 19.9%. An analysis was conducted on the relationship between RLS and other factors such as subjective evaluation of sleep, difficulty initiating sleep, difficulty maintaining sleep, early morning awaking, and excessive daytime sleepiness. The result of this analysis suggested that women with these sleep-related problems were more likely to have RLS than those without. In addition, RLS was more prevalent in the later stages of pregnancy. CONCLUSION: In the pregnant women in our survey, the prevalence of RLS was found to be 19.9%, which is higher than the prevalence of RLS that has been found in the general public in a previous study. This suggests that RLS-related sleep problems may be an important public health issue among pregnant women in Japan. This finding may have implications for attempts to improve sleep hygiene in this group.     

Association between irritable bowel syndrome and restless legs syndrome in the general population

This study aimed to explore the association between restless legs syndrome and irritable bowel syndrome in an epidemiological cohort. We included 3365 adults, of whom 1602 were female (age 52.5 ± 7.5 years), who had participated in the Korean Genome and Epidemiology Study (2005–2006). The diagnosis of restless legs syndrome was based on the criteria proposed by the International Restless Legs Syndrome Study Group, and irritable bowel syndrome was defined according to the Rome II criteria. The prevalence of each condition was determined and their association was tested by logistic regression analysis. Age, sex, haemoglobin concentration, renal insufficiency, use of medications and depressive mood were all adjusted for. The prevalence of restless legs syndrome and irritable bowel syndrome was 4.5 and 11.1%, respectively. Irritable bowel syndrome was more prevalent in the group with restless legs syndrome (24.0 versus 10.5%, P < 0.001). Subjects with restless legs syndrome were older (54.2 ± 8.4 versus 52.4 ± 7.4, P = 0.006) and more depressive (26.7 versus 12.5%, P < 0.001), and were predominantly female (57.3 versus 47.2%, P = 0.015), had more frequent insomnia symptoms (44.0 versus 28.2%, P < 0.001), had lower haemoglobin concentration (13.7 ± 1.5 versus 14.1 ± 1.6 g dL^?1P = 0.004) and higher highly sensitive C‐reactive protein (1.8 ± 5.1 versus 1.4 ± 2.9 mg dL^?1, P = 0.08). The adjusted odds ratio of restless legs syndrome in relation to irritable bowel syndrome was 2.59 (1.74–3.85, P < 0.001). Irritable bowel syndrome appeared to be associated with restless legs syndrome independently from other major risk factors for restless legs syndrome. Searching for the mechanisms underlying this association is indicated.     

Epidemiology of restless legs syndrome in Korean adults

STUDY OBJECTIVES: To investigate the prevalence of restless legs syndrome (RLS) in Korea. DESIGN: A large population-based telephone interview method using the Korean version of the Johns Hopkins telephone diagnostic interview for the RLS. SETTING: A computer aided telephone interview method. PARTICIPANTS: A total of 5,000 subjects (2,470 men and 2,530 women) were interviewed in depth. A representative sample aged 20 to 69 years was constituted according to a stratified, multistage random sampling method. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Of the respondents, 373 respondents (7.5%) of the population (pop) met the criteria for the definite or probable RLS groups: 194 (3.9% of pop) respondents fulfilled the criteria for definite RLS and 179 (3.6% of pop) respondents fulfilled the criteria for probable RLS. The prevalence of RLS was generally higher for women than men (4.4% vs. 3.3% for definite, 8.7% vs. 6.2% for definite plus probable). About 90% of RLS individuals were experiencing symptoms at the time of the interview and this was similar for both RLS groups. Seventy-four respondents (1.48%) reported symptoms were moderately or severely distressing and were therefore classified as RLS "sufferers." Of those with a diagnosis of RLS sufferer, 24.3% reported being treated for their symptoms, compared to 12.4% of RLS not designated a "sufferer." CONCLUSION: RLS is common and underdiagnosed in Korea with nearly 1% of the population reporting disturbed sleep related to their RLS. These results are comparable to other countries.     

Personality traits in patients with restless legs syndrome

Objective

In restless legs syndrome (RLS), the prevalence of depressive symptoms and anxiety has been found to be increased. However, most studies did not consider specific personality characteristics of patients although they might have a crucial influence on the mental state of the patient. The aim of this study was to compare RLS patients with healthy controls in view of personality traits, depression, and anxiety.

Methods

In all, 30 consecutive patients with idiopathic RLS (de novo) were compared to 30 age- and sex-matched healthy controls. The severity of symptoms was assessed using the RLS severity scale. Sleep disorders, depression, and anxiety disorders were exclusion criteria for the control group. Participants were asked to fill in the NEO Five-Factor Inventory (NEO-FFI) to assess personality traits, as well as the Self-Rating Depression Scale (SDS) and the Self-Rating Anxiety Scale (SAS).

Results

RLS patients scored significantly higher on the SDS (39.0?±?7.4 vs. 28.8?±?5.7, p?<?0.001) as well as the SAS (37.4?±?4.9 vs. 26.0?±?4.3, p?<?0.001) compared to the control group. In the NEO-FFI, patients exhibited significantly higher scores on the subscale “neuroticism” (52.3?±?8.4 vs. 41.6?±?9.0, p?<?0.001). In addition, they scored significantly lower on the subscales “openness to experience” (45.3?±?6.9 vs. 51.9?±?10.5, p?=?0.007) and showed a trend in “agreeableness” (48.6?±?11.5 vs. 55.5?±?9.6, p?=?0.017; ns after Bonferroni correction) compared to healthy controls.

Discussion

RLS patients seem to be more worried, nervous, and discontent. They are more easily irritable and more vulnerable to stress. They also tend to withdraw from social contacts and rather occupy themselves with their symptoms.     

Restless legs syndrome in patients with depressive disorders

Aim

Recent community-based studies have shown strong associations between restless legs syndrome (RLS) and major depressive disorder and panic disorder. The aim of the study was to investigate whether patients with a manifest depressive disorder have an increased prevalence of RLS and whether there is an association with different depressive disorders.

Methods

Three psychiatry departments in two countries (Germany and Australia) each recruited 100?consecutive patients with current depression. All patients completed a standardized questionnaire including diagnostic questions for RLS, the Center for Epidemiologic Studies Depression Scale (CES-D), and the International RLS Severity Scale (IRLS), if RLS was present. The treating doctors completed a second standardized questionnaire including RLS diagnostic questions and comorbidities.

Results

A total of 277?questionnaires could be evaluated, 184 in Germany (96 in Bremen, 88 in Freiburg) and 93 in Australia. The Australian patients were younger than the German patients (45.4?±?13.8 vs. 49.7?±?15.0?years, p?=?0.02); the gender distribution was not different (p?=?0.71). The minimal diagnosis criteria for RLS were fulfilled by 8.3% of the German and 17.0% of the Australian patients (p?=?0.02). The treating physicians rated 4.3% of the German and 12.4% of the Australian patients as RLS cases. RLS prevalence was similar across all subtypes of depression.

Conclusion

RLS is not more frequent in patients with manifest depression in Germany as compared to the general population. Possible reasons for the higher prevalence of RLS in depressive patients in Australia are discussed.