Quality of life in stiff-person syndrome.

Stiff person syndrome (SPS) is a rare, chronic disorder characterized by painful spasm and stiffness. We investigated the quality of life (QoL) in SPS patients, and identified factors associated with impairment in patients' QoL. Twenty-four SPS patients (10 men, 14 women; mean age +/- S.D., 52.6 +/- 9.5 years) completed the medical outcomes study Short Form health survey (SF-36), the Beck Depression Inventory (BDI), and a questionnaire asking for sociodemographic and clinical details. Extent of the disease was assessed using a distribution of stiffness score. SPS patients showed markedly reduced mean scores for all dimensions of the SF-36 when compared to norms from the general population of the United Kingdom. QoL scores showed a strong correlation with the extent of the disease. Depression was a common finding; 14 of 24 patients had depressive symptoms as evidenced by the BDI. There was a significant and strong correlation between the BDI score and several SF-36 subscores. This is the first study to address QoL in patients with SPS. We have shown that SPS has a significant impact on patients' reported QoL. The association between depression and QoL highlights the importance of recognizing and treating depression in SPS.     

Acute ataxia, Graves' disease, and stiff person syndrome.

Stiff person syndrome (SPS) has been associated with autoimmune diseases, such as Type 1 diabetes mellitus and autoimmune thyroid disease (Hashimoto's thyroiditis), among others. The association of SPS with hyperthyroidism is extremely rare. We describe a patient with uncontrolled Graves' disease and undiagnosed SPS, who presented initially with acute ataxia simulating a cerebrovascular accident. Initiation of immunosuppressive therapy dramatically improved the patient's Graves' disease within 2 weeks but the neurological symptoms were not alleviated after a follow-up period of 3 years.     

Brain gamma-aminobutyric acid changes in stiff-person syndrome

BACKGROUND: Patients with stiff-person syndrome (SPS) have circulating antibodies against glutamic acid decarboxylase, the rate-limiting enzyme responsible for the synthesis of gamma-aminobutyric acid (GABA). Although the patients' symptoms of stiffness and unexpected spasms can be explained on the basis of reduced or impaired inhibitory neurotransmitters, such as GABA, it is unclear whether the level of GABA in the brains of these patients is reduced and, if so, whether the reduction is due to anti-glutamic acid decarboxylase antibodies. OBJECTIVE: To measure GABA levels in the brains of patients with SPS. DESIGN: Prospective case-control study. SETTING: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Md. PATIENTS: Eight patients with SPS with high titers of circulating anti-glutamic acid decarboxylase antibodies and typical clinical symptoms of SPS and 16 control subjects. MAIN OUTCOME MEASURES: Results of brain magnetic resonance imaging and magnetic resonance spectroscopy, which measures GABA levels in specific brain regions. RESULTS: No abnormalities were noted on brain magnetic resonance images. A prominent and significant decrease in GABA level was, however, observed in the sensorimotor cortex and a smaller decrease in the posterior occipital cortex but not in the cingulate cortex or pons. CONCLUSIONS: The reduction of brain GABA in patients with SPS supports the clinical symptoms and indicates that the inhibitory GABAergic pathways are involved in the disease. Regardless of the responsible autoantigens, in SPS autoantibodies block the function of GABAergic neurons and interfere with the synthesis of GABA but do not cause structural changes in the brain.     

Stiff person syndrome: avoiding misdiagnosis

Abstract Stiff person syndrome (SPS) is a rare neurological disorder characterised by muscular rigidity and superimposed spasms of the trunk and limbs that may be precipitated by voluntary movements and unexpected tactile, auditory or emotional stimulation. The high prevalence of autoantibodies against glutamic acid decarboxylase (antiGAD) in both serum and cerebrospinal fluid, as well as the frequent association of SPS with other autoimmune disorders, suggest an autoimmune pathogenesis. SPS is frequently misdiagnosed as axial dystonia or psychogenic movement disorder. We report a patient with SPS in order to emphasise the reasons for this common misdiagnosis.     

Sleep preoccupation in poor sleepers: psychometric properties of the Sleep Preoccupation Scale

OBJECTIVES: Despite daytime factors being implicated as having a key perpetuating role in many of the recent cognitive models of sleep disturbance, standardized, validated measures of sleep-related daytime processing are rare. The aim of the present studies was to develop, refine, and psychometrically evaluate the Sleep Preoccupation Scale (SPS), a self-report tool that examines levels of daytime sleep-related processing. METHODS: The SPS is constructed using a quantitative content analysis of responses from a survey of older adults (n=116). The scale is then refined using principal components analysis on a general population sample (n=456), and finally, the convergent validity is examined in a general population sample (n=722). RESULTS: The results suggest the SPS is a reliable and valid measure of sleep-related daytime processing and discriminates different sleeper groups (poor, average, and good sleepers). CONCLUSION: The findings are related to the models of poor sleep and, in particular, insomnia, and future directions are discussed.     

Electrophysiological characteristics in four patients from Brazil with stiff person syndrome

Stiff person syndrome (SPS) is a rare immune-mediated disorder of the central nervous system characterized by muscle rigidity and episodic muscle spasms. The diagnosis of SPS is based on electrophysiological studies. We analyzed the electrophysiological features in four patients from Brazil who fulfilled the clinical criteria for SPS. The most common electrophysiological abnormalities were continuous motor unit activity, co-contracting, and the presence of the cutaneomuscular reflex. Despite all patients having clinical characteristics of SPS during the disease, no patient met all the electrophysiological criteria for SPS even after repeat electrophysiological studies. This shows that a diagnosis of SPS should not be restricted to patients with all the classic electrophysiological changes but should be considered in the presence of one or some of those changes.     

A case of childhood stiff-person syndrome with striatal lesions: A possible entity distinct from the classical adult form

Parainfectious or autoimmune striatal lesions have been repeatedly described in children. We report a 7-year-old girl with painful muscle spasms, leading to the diagnosis of childhood stiff-person syndrome (SPS). Striatal lesions were demonstrated by diffusion-weighted magnetic resonance imaging (MRI) and single-photon emission computed tomography but not by conventional MRI. Autoantibodies against glutamic acid decarboxylase (GAD) were absent. Steroid pulse therapy and high-dose intravenous immunoglobulin resolved all the symptoms with slight sequelae. Childhood SPS may be characterized by absent anti-GAD antibodies and a transient benign clinical course, and it may have a pathomechanism distinct from that in adult SPS.     

Autoimmune stiff person syndrome and related myelopathies: understanding of electrophysiological and immunological processes

Stiff person syndrome (SPS) is a disabling autoimmune central nervous system disorder characterized by progressive muscle rigidity and gait impairment with superimposed painful spasms that involve axial and limb musculature, triggered by heightened sensitivity to external stimuli. Impaired synaptic GABAergic inhibition resulting from intrathecal B-cell-mediated clonal synthesis of autoantibodies against various presynaptic and synaptic proteins in the inhibitory neurons of the brain and spinal cord is believed to be an underlying pathogenic mechanism. SPS is most often idiopathic, but it can occur as a paraneoplastic condition. Despite evidence that anti-GAD and related autoantibodies impair GABA synthesis, the exact pathogenic mechanism of SPS is not fully elucidated. The strong association with several MHC-II alleles and improvement of symptoms with immune-modulating therapies support an autoimmune etiology of SPS. In this review, we discuss the clinical spectrum, neurophysiological mechanisms, and therapeutic options, including a rationale for agents that modulate B-cell function in SPS.     

Insight in schizophrenia: its relationship to measures of executive functions.

Lack of awareness of specific symptoms among persons with schizophrenia has not been adequately studied in the context of neuropsychological function. The purpose of this study is to investigate whether poor insight as measured by the Scale to Assess Unawareness of Mental Disorder is empirically related to performance measures having a known association with executive functions in a group of individuals with chronic schizophrenia. The results showed that unawareness and misattribution of negative symptoms are significantly associated with deficits in some aspects of executive functioning even after a test of general intelligence had been partialed from the analyses. We conclude that unawareness of negative symptoms is associated with executive functioning in individuals with chronic schizophrenia. Unawareness of other symptoms (i.e., positive symptoms) may reflect dysfunction in other types of neuropsychological processes, or it may reflect motivation to deceive oneself or others.     

A rare saccade velocity profile in Stiff-Person Syndrome with cerebellar degeneration

Stiff-Person Syndrome (SPS) is an immune-mediated disorder of the central nervous system characterized by muscle rigidity, episodic muscle spasms, and high titers of antibodies against glutamic acid decarboxylase (GAD). The presence of cerebellar ataxia in SPS is extremely rare, but occurs. Clinical observations of ocular motor abnormalities have been noted in a few SPS patients. The purpose of this study is to provide a detailed quantitative documentation of ocular motor abnormalities in a patient with SPS and progressive cerebellar signs. Detailed clinical assessment of a woman with SPS and precise eye movement recordings using the magnetic search coil technique was performed. In addition to other ocular motor abnormalities that included longer latencies for saccades, downbeat nystagmus, and loss of downward smooth pursuit, a rare saccade velocity profile consisting of multi-component saccades was observed. We postulate that these ocular motor findings are related to impairment of GABAergic neurotransmission because antibodies to glutamic acid decarboxylase (GAD-Abs) have been implicated in the pathogenesis of both SPS and some cases of cerebellar ataxia. In addition, this unusual saccadic velocity profile may have important implications for modeling the saccadic system and furthering a complete understanding of saccade generation.     

Stiff-person syndrome: an autoimmune disease

Stiff-person syndrome (SPS) is characterized by progressive, usually symmetric rigidity of the axial muscles with superimposed painful spasms precipitated by tactile stimuli, passive stretch, volitional movement of affected or unaffected muscles, startling noises, and emotional stimuli. Electromyography demonstrates continuous normal motor unit potentials in the affected muscles. Both the rigidity and the spasms are relieved by sleep, general anesthesia, myoneural blockade, peripheral nerve blockade, and partially by diazepam. Evidence for an autoimmune etiology of SPS includes its association with other autoimmune diseases and autoantibodies and the presence of antibodies against glutamic acid decarboxylase (GAD) in the cerebrospinal fluid (CSF) of many affected patients. We describe two patients with this syndrome who had GAD antibodies in both CSF and serum. Partial relief of the symptoms in these patients by corticosteroid therapy provides additional evidence of an autoimmune etiology of SPS and of the role of immunotherapy in its treatment.     

Inner body and outward appearance: the relationships between appearance orientation, eating disorder symptoms, and internal body awareness

This study investigated the associations of appearance orientation and eating disorder symptoms with internal body awareness in an eating-disordered group of women and a general sample of women. In the eating-disordered group, appearance orientation was positively associated with internal body awareness. Eating disorders symptoms were negatively related to the awareness of bodily signals. No significant associations were found in the general sample of women. The results indicate that in eating-disordered individuals preoccupation with the body and eating-disordered behaviors are not only negatively associated with hunger, but with awareness of other bodily signals as well.     

Inner Body and Outward Appearance: The Relationships Between Appearance Orientation,Eating Disorder Symptoms,and Internal Body Awareness

This study investigated the associations of appearance orientation and eating disorder symptoms with internal body awareness in an eating-disordered group of women and a general sample of women. In the eating-disordered group, appearance orientation was positively associated with internal body awareness. Eating disorders symptoms were negatively related to the awareness of bodily signals. No significant associations were found in the general sample of women. The results indicate that in eating-disordered individuals preoccupation with the body and eating-disordered behaviors are not only negatively associated with hunger, but with awareness of other bodily signals as well.     

Sleep preoccupation in poor sleepers: Psychometric properties of the sleep Preoccupation Scale

ObjectivesDespite daytime factors being implicated as having a key perpetuating role in many of the recent cognitive models of sleep disturbance, standardized, validated measures of sleep-related daytime processing are rare. The aim of the present studies was to develop, refine, and psychometrically evaluate the Sleep Preoccupation Scale (SPS), a self-report tool that examines levels of daytime sleep-related processing.MethodsThe SPS is constructed using a quantitative content analysis of responses from a survey of older adults (n=116). The scale is then refined using principal components analysis on a general population sample (n=456), and finally, the convergent validity is examined in a general population sample (n=722).ResultsThe results suggest the SPS is a reliable and valid measure of sleep-related daytime processing and discriminates different sleeper groups (poor, average, and good sleepers).ConclusionThe findings are related to the models of poor sleep and, in particular, insomnia, and future directions are discussed.     

Awareness of warning symptoms and risk factors of stroke in the general population and in survivors stroke.

Awareness among the general population of the risk factors and warning symptoms of stroke is essential for preventative purposes and for immediate effective treatment. The aim of the present study was to assess the awareness, among the general population and stroke survivors, of the risk factors and warning symptoms of stroke, to develop an educational strategy for its prevention and immediate effective treatment. Six hundred and sixty stroke patients (370 male, 290 female) and 4000 people from the general population who accompanied the patients (2800 male, 1200 female) were interviewed, using three sets of questionnaires, on the risk factors and warning symptoms of stroke. Poor knowledge or awareness of the risk factors and warning symptoms of stroke was found in both groups. Both groups suggested educational programs for stroke using printed information, audiovisual programs and community survey programs using simple and understandable information for the prevention and immediate effective treatment of stroke. Poor awareness of stroke contributes to a delay in the arrival of patients in hospital emergency departments for immediate effective treatment. Multifaceted programs regarding stroke, including printed information, audiovisual programs and stroke service programs, are advocated by both patients and the general population to improve stoke treatment and prevention.     

Antiamphiphysin-positive stiff-person syndrome associated with small cell lung cancer.

The paraneoplastic amphiphysin(+) stiff-person syndrome (SPS) has so far only been described in women with breast adenocarcinoma. Here, we describe the rare case of a female patient with antiamphiphysin(+) SPS due to small cell cancer of the lung.     

Focal stiff-person syndrome

Stiff-person syndrome (SPS) is a disorder of motor function characterized by rigidity of axial musculature and fluctuating painful spasms, which are often induced by startle or emotional stimuli. Neurophysiological studies have demonstrated the presence of continuous motor unit activity in muscle at rest, with abnormally enhanced extereoceptive reflexes. Although criteria for the diagnosis of SPS were proposed, several variants of this syndrome have been described before. In this communication, we report the case of a patient with a focal form of SPS. A 39-year-old woman developed progressive instability in her gait, spasms and stiffness restricted to both legs. The electromyographic examination showed continuous motor unit activity of the affected muscles at rest. Moreover, high anti-GAD antibodies titers were found in CSF and serum. Clinical symptoms, electrophysiological and immunological profiles suggest a focal form of SPS. Clinical and immunological findings indicate that SPS is a heterogeneous disease, suggesting the need to redefine its diagnostic criteria. Definition of the range of clinical expression and immunological profiles could be important for the clinical management of these patients.     

A neuropsychological assessment of phobias in patients with stiff person syndrome

A neuropsychological assessment was performed in 10 patients with stiff person syndrome (SPS) to determine whether their anxiety and phobic symptoms precede stiffness and spasms or represent a reaction to disability. No neurocognitive dysfunction was noted. Patients perceived fears and anxiety as realistic and caused by SPS rather than due to an inherent phobic neurosis.     

The effects of orexin-A and orexin receptors on anxiety- and depression-related behaviors in a male rat model of post-traumatic stress disorder

Orexin neurons play an important role in stress-related mental disorders including post-traumatic stress disorder (PTSD). Anxiety- and depression-related symptoms commonly occur in combination with PTSD. However, the role of the orexin system in mediating alterations in these affective symptoms remains unclear. The medial prefrontal cortex (mPFC) is implicated in both cognitive and emotional processing. In the present study, we investigated anxiety- and depression-related behavioral changes using the elevated plus maze, the sucrose preference test, and the open field test in male rats with single prolonged stress (SPS) induced-PTSD. The expression of orexin-A in the hypothalamus and orexin receptors (OX1R and OX2R) in the mPFC was detected and quantified by immunohistochemistry, western blotting, and real-time polymerase chain reaction. We found that the SPS rats exhibited enhanced levels of anxiety, reduced exploratory activities, and anhedonia. Furthermore, SPS resulted in reductions in the expression of orexin-A in the hypothalamus and the increased the expression of OX1R in the mPFC. The intracerebroventricular administration of orexin-A alleviated behavioral changes in SPS rats and partly restored the increased levels of OX1R in the mPFC. These results suggest that the orexin system plays a role in the anxiety- and depression-related symptoms observed in PTSD.     

Time passes slowly for patients with depressive state

Twenty-three depressive inpatients and the same number of matched non-psychiatric controls were examined on three occasions - following admission, 14 days after, and 28 days after the admission - by administering a self-rating questionnaire of time awareness and Hamilton's Rating Scale for Depression (HRS). The patients were found to feel time passing slowly. This was correlated with the severity of depression expressed as the total HRS score. No significant differences emerged between diagnostic groups, namely endogenous depression, neurotic depression, and schizophrenia or paranoid state with depressive symptoms. Correlations of the time awareness with symptoms listed in the HRS also denied a specific relationship of time awareness to specific diagnoses. The subjective feeling of slow time flow reflects, therefore, the depth of depressive state in general, which is nevertheless not specific to any diagnostic subcategory.