Undiagnosed and comorbid disorders in patients with presumed chronic fatigue syndrome

Objective

To assess undiagnosed and comorbid disorders in patients referred to a tertiary care center with a presumed diagnosis of chronic fatigue syndrome (CFS).

Methods

Patients referred for chronic unexplained fatigue entered an integrated diagnostic pathway, including internal medicine assessment, psychodiagnostic screening, physiotherapeutic assessment and polysomnography + multiple sleep latency testing. Final diagnosis resulted from a multidisciplinary team discussion. Fukuda criteria were used for the diagnosis of CFS, DSM-IV-TR criteria for psychiatric disorders, ICSD-2 criteria for sleep disorders.

Results

Out of 377 patients referred, 279 (74.0%) were included in the study [84.9% female; mean age 38.8 years (SD 10.3)].A diagnosis of unequivocal CFS was made in 23.3%. In 21.1%, CFS was associated with a sleep disorder and/or psychiatric disorder, not invalidating the diagnosis of CFS. A predominant sleep disorder was found in 9.7%, 19.0% had a psychiatric disorder and 20.8% a combination of both. Only 2.2% was diagnosed with a classical internal disease.In the total sample, a sleep disorder was found in 49.8%, especially obstructive sleep apnea syndrome, followed by psychophysiologic insomnia and periodic limb movement disorder. A psychiatric disorder was diagnosed in 45.2%; mostly mood and anxiety disorder.

Conclusions

A multidisciplinary approach to presumed CFS yields unequivocal CFS in only a minority of patients, and reveals a broad spectrum of exclusionary or comorbid conditions within the domains of sleep medicine and psychiatry. These findings favor a systematic diagnostic approach to CFS, suitable to identify a wide range of diagnostic categories that may be subject to dedicated care.     

Neurodegenerative lesions: Seeding and spreading

Accumulation of specific proteins has replaced loss of specific populations of neurons in the definition of most neurodegenerative diseases. In some cases, the amino-acid sequence of the protein that accumulates is altered by a mutation in the gene that codes for it but most generally, the primary structure is normal. Much evidence from human neuropathology has been collected over the years indicating that the progression of the lesions in such neurodegenerative diseases as Alzheimer's disease, Parkinson's disease and progressive supranuclear palsy follow the neuroanatomical connections. More recently, injection of aggregates of the specific proteins in the brain of experimental animals has been attempted in various experimental settings. Brain homogenates containing Aβ aggregates induce the early development of Aβ deposits in APP transgenic mice. Brain homogenates from various human tauopathies induce tau aggregates in transgenic mice expressing normal human tau. Finally, synthetic preformed fibrils of alpha-synuclein initiate the development of alpha-synuclein accumulation resembling Parkinson's disease in wild-type mice. Experiments in cell cultures suggest that the protein has to be in some specific state of oligomerization or fibrillation to be endocytosed and transported by the neuron. These data suggest that the protein that accumulates in a specific disease is initially misfolded and that this misfolding contaminates normal protein in a prion-like manner – in some cases through the neuronal connections.     

Multisensory integration across exteroceptive and interoceptive domains modulates self-experience in the rubber-hand illusion

Identifying with a body is central to being a conscious self. The now classic “rubber hand illusion” demonstrates that the experience of body-ownership can be modulated by manipulating the timing of exteroceptive (visual and tactile) body-related feedback. Moreover, the strength of this modulation is related to individual differences in sensitivity to internal bodily signals (interoception). However the interaction of exteroceptive and interoceptive signals in determining the experience of body-ownership within an individual remains poorly understood. Here, we demonstrate that this depends on the online integration of exteroceptive and interoceptive signals by implementing an innovative “cardiac rubber hand illusion” that combined computer-generated augmented-reality with feedback of interoceptive (cardiac) information. We show that both subjective and objective measures of virtual-hand ownership are enhanced by cardio-visual feedback in-time with the actual heartbeat, as compared to asynchronous feedback. We further show that these measures correlate with individual differences in interoceptive sensitivity, and are also modulated by the integration of proprioceptive signals instantiated using real-time visual remapping of finger movements to the virtual hand. Our results demonstrate that interoceptive signals directly influence the experience of body ownership via multisensory integration, and they lend support to models of conscious selfhood based on interoceptive predictive coding.     

Dissociations between the horizontal and dorsoventral axes in body‐size perception

Body size can vary throughout a person's lifetime, inducing plasticity of the internal body representation. Changes in horizontal width accompany those in dorsal‐to‐ventral thickness. To examine differences in the perception of different body axes, neural correlates of own‐body‐size perception in the horizontal and dorsoventral directions were compared using functional magnetic resonance imaging. Original and distorted (?30, ?10, +10 and +30%) images of the neck‐down region of their own body were presented to healthy female participants, who were then asked whether the images were of their own body or not based explicitly on body size. Participants perceived body images distorted by ?10% as their own, whereas those distorted by +30% as belonging to others. Horizontal width images yielded slightly more subjective own‐body perceptions than dorsoventral thickness images did. Subjective perception of own‐body size was associated with bilateral inferior parietal activity. In contrast, other‐body judgments showed pre‐supplementary motor and superior parietal activity. Expansion in the dorsoventral direction was associated with the left fusiform gyrus and the right inferior parietal lobule, whereas horizontal expansions were associated with activity in the bilateral somatosensory area. These results suggest neural dissociations between the two body axes: dorsoventral images of thickness may require visual processing, whereas bodily sensations are involved in horizontal body‐size perception. Somatosensory rather than visual processes can be critical for the assessment of frontal own‐body appearance. Visual body thickness and somatosensory body width may be integrated to construct a whole‐body representation.     

Does habitual body avoidance and checking behavior influence the decrease of negative emotions during body exposure in eating disorders?

Abstract

The aim of the present study was to assess whether habitual body avoidance and body-checking behavior influences the decrease of negative emotions during body exposure. Twenty-one eating-disordered female participants completed the Body Image Avoidance Questionnaire and the Body Checking Questionnaire. On another day, a 40-min body exposure session was conducted under standardized conditions. Every 10 min, negative emotions were assessed. It was shown that the extent of decrease in negative emotions during the body exposure session could be predicted by a lower degree of body checking. Results indicate that habitual checking behavior seems to negatively influence the effect of body exposure. Therefore, an adaptation of body exposure to patients with a higher degree of body-checking behavior might be promising.     

Stance instability in spinocerebellar ataxia type 6

Balance impairment is a principal symptom of cerebellar disease, but is poorly understood partly because subjects with heterogenous cerebellar and extracerebellar lesions have often been studied. Spinocerebellar ataxia type 6 (SCA6) provides an opportunity to understand balance dysfunction associated with a relatively homogenous cerebellar lesion. This study investigated stance instability in SCA6 and how it is affected by varying stance width. Body sway, as well as its directional preponderance and distribution across joints, was measured three‐dimensionally in 17 SCA6 and 17 matched healthy control subjects. Subjects stood for 40 seconds on a stable surface with their eyes open and feet positioned at various stance widths (32, 16, 8, 4, and 0 cm). SCA6 subjects swayed faster than controls at every stance width. Decreasing the stance width produced a disproportionate increase in sway speed in SCA6 subjects, compared to controls. Directional preponderance of sway was dependent on stance width, but did not differ between groups. Joint instability was increased by reducing stance width in both groups, but there was greater instability of the ankle joint in the roll plane in the SCA6 group. Measures of global instability correlated strongly with disease severity measured with the Scale for the Assessment and Rating of Ataxia (r = 0.79). The sway characteristics suggest a disruption of sensorimotor processing for balance control in SCA6. The correlation with disease severity implies that balance impairment is a feature of progression of SCA6 clinical syndrome. With stance width standardized, the instability measures employed could provide sensitive, continuous outcome measures of longitudinal or therapeutic change. © 2012 Movement Disorder Society     

Effects of whole body vibration training on balance in adolescents with and without Down syndrome

The present study aimed to determine whether a whole body vibration training program (WBV) is able to improve static standing balance in adolescents with and without Down syndrome (DS). Thirty adolescents with DS aged 11–20 years (DSG) and 27 adolescent, age/sex matched, without DS (CG) joined the study. Participants of each group were divided into two comparable groups, those who performed WVB (in DSG: VDSG; in CG: VCG) and those who did not perform WVB (in DSG: nVDSG; in CG: nVCG). Static-standing-balance under four conditions (C1: openeyes/fixed-foot-support; C2: closed-eyes/fixed-foot-support; C3: openeyes/compliant-foot-support; C4: closed-eyes/compliant-foot-support) was examine, before and after a 20-week WBV training program. For balance study, Postural-Parameters (PPs), based on center of pressure (COP) oscillations (anterior/posterior and medial/lateral COP excursion and COP mean velocity), and PPs ratios among the four conditions were calculated. After WBV training, no significant differences were found in any parameter in the VCG and nVCG and neither in the nVDSG, but there was a decrease of mean values in the analyzed PPs under C4, with significant differences in medial/lateral COP excursion and COP mean velocity, and a significant decrease in the ratio C4/C1 of the mean velocity in VDSG. Therefore, WBV training had positive effects in the balance of DS adolescents although only under specific conditions, with vision and somatosensory input altered. The positive results of this study are encouraging and open a wide field of research, looking for the most efficient program for this population.     

Valosin‐containing protein immunoreactivity in tauopathies,synucleinopathies, polyglutamine diseases and intranuclear inclusion body disease

Valosin‐containing protein (VCP) is associated with multiple cellular functions, including ubiquitin‐dependent protein degradation. Mutations in VCP are known to cause inclusion body myopathy with Paget's disease and frontotemporal dementia and familial amyotrophic lateral sclerosis (fALS; ALS14), both of which are characterized by trans‐activation response DNA protein 43 (TDP‐43)‐positive neuronal cytoplasmic and nuclear inclusions. Recently, immunoreactivity for fALS‐associated proteins (TDP‐43, fused in sarcoma (FUS), optineurin and ubiquilin‐2) were reported to be present in cytoplasmic and nuclear inclusions in various neurodegenerative diseases. However, the extent and frequency of VCP‐immunoreactive structures in these neurodegenerative diseases are uncertain. We immunohistochemically examined the brains of 72 cases with neurodegenerative diseases and five control cases. VCP immunoreactivity was present in Lewy bodies in Parkinson's disease and dementia with Lewy bodies, and neuronal nuclear inclusions in five polyglutamine diseases and intranuclear inclusion body disease, as well as in Marinesco bodies in aged control subjects. However, other neuronal and glial cytoplasmic inclusions in tauopathies and TDP‐43 proteinopathies were unstained. These findings suggest that VCP may have common mechanisms in the formation or degradation of cytoplasmic and nuclear inclusions of neurons, but not of glial cells, in several neurodegenerative conditions.