Trunk Recovery Scale: a new tool to measure posture control in patients with severe acquired brain injury. A study of the psychometric properties.

BACKGROUND: Posture control appears deeply impaired in patients with severe Acquired Brain Injury (ABI). One of the main goals of neurorehabilitation specialists is to try to assess this neural function in a standardized manner. However, the tests available to evaluate posture control recovery after brain damage were developed for patients with focal neurological signs. We therefore developed a new test, the Trunk Recovery Scale (TRS). AIM: To evaluate the inter-rater reliability, internal consistency, external validity, and sensitivity of TRS in patients with ABI. DESIGN: Validation study. SETTING: We examined 59 patients hospitalized after a brain injury in the Intensive and the Extensive Rehabilitation Units of our hospital. POPULATION: Patients with diagnosis of severe ABI with the capacity to respond to simple verbal orders and with a Level of Cognitive Functioning Scale (LCF scale) ≥ 4. METHODS: Three raters independently assessed 20 subjects. One of the raters also assessed 39 additional subjects using TRS, Trunk Control Test (TCT), and Functional Independence Measure (FIM), and repeated the evaluation after 30 days. RESULTS: The Inter-rater reliability was generally high (ICC=0,97 and 0,92 for total score and different subscales). Weighted Kappa values indicated "substantial agreement" except for items 2, 7, and 12. Internal consistency was good: Cronbach's coefficients were 0.900 and 0.910 for different subscales, and the elimination of one item at a time did not substantially improve the internal consistency. External validity was excellent (Spearman rank correlations =0.943 and 0.849 for TCT and FIM). Sensitivity was good. CONCLUSIONS: Our data confirm that TRS reliably assesses posture control in patients with severe ABI. However, as the sample size of internal consistency and validity was limited, the results may be overestimated. We therefore propose that this study be considered the first in a series of similar studies. This series should include a Rasch Analysis, which would further evaluate the suitability of keeping or removing items with less consistency and would define the mathematical properties of different subscales and the total score. CLINICAL REHABILITATION IMPACT: Our data confirm that TRS detects subtle but potentially meaningful motor changes in patients and can therefore allow clinicians to document treatment effectiveness and define treatment objectives.

Prevalence of sleep disturbances in mild cognitive impairment and dementing disorders: a multicenter Italian clinical cross-sectional study on 431 patients.

BACKGROUND/AIMS: Sleep disturbances are common in the elderly and in persons with cognitive decline. The aim of this study was to describe frequency and characteristics of insomnia, excessive daytime sleepiness, sleep-disordered breathing, REM behavior disorder and restless legs syndrome in a large cohort of persons with mild cognitive impairment or dementia. METHODS: 431 consecutive patients were enrolled in 10 Italian neurological centers: 204 had Alzheimer's disease, 138 mild cognitive impairment, 43 vascular dementia, 25 frontotemporal dementia and 21 Lewy body dementia or Parkinson's disease dementia. Sleep disorders were investigated with a battery of standardized questions and questionnaires. RESULTS: Over 60% of persons had one or more sleep disturbances almost invariably associated one to another without any evident and specific pattern of co-occurrence. Persons with Alzheimer's disease and those with mild cognitive impairment had the same frequency of any sleep disorder. Sleep-disordered breathing was more frequent in vascular dementia. REM behavior disorder was more represented in Lewy body or Parkinson's disease dementia. CONCLUSION: A careful clinical evaluation of sleep disorders should be performed routinely in the clinical setting of persons with cognitive decline. Instrumental supports should be used only in selected patients.

Cognitive impairment in degenerative parkinsonisms: role of radionuclide brain imaging.

Cognitive impairment in Parkinson's disease (PD) and atypical parkinsonian syndromes is gaining increased clinical significance. The neurochemical and neuropathological basis in the various parkinsonian forms and even in an individual patient are not fully elucidated yet and could be heterogeneous. Loss of dopaminergic, cholinergic and noradrenergic innervation has been suggested to be the underlying neurochemical deficits for cognitive impairment and dementia in PD, but the onset of cognitive impairment and the progression to dementia may not share the same underlying neurochemical basis. Similarly, pathological evidence is also heterogeneous, ranging from subcortical pathology, limbic or cortical Lewy body type degeneration, and Alzheimer's type pathology that can be found even in the same patient with PD dementia (PDD). Typically, the prototype of early cognitive deficit in PD is a dysexecutive syndrome, but other cognitive domains are more involved when dementia develops, mainly including visuospatial, language and memory dysfunction. Functional radionuclide neuroimaging, by means of single-photon emission computed tomography and positron emission tomography, are contributing to characterize the topographic cortical pattern of cognitive impairment, as well as to define the underlying neurochemical deficit. Lastly, the advent of amyloid PET may help clarifying the meaning of amyloid load in diffuse Lewy body disease and PDD. Knowing the neurochemical and pathophysiological substrate of cognitive deficit in patients with PD or other degenerative Parkinsonisms may help the clinician in understanding the clinical condition of an individual patient in order to plan pharmacological and non-pharmacological intervention. The introduction of acetylcholinesterase inhibitors for therapy of PDD is an example of information integration between clinical-neuropsychological and pathophysiological-neurochemical aspects obtained also with the key contribution of functional neuroimaging.

Periodic limb movements both in non-REM and REM sleep: relationships between cerebral and autonomic activities.

OBJECTIVE: To investigate the temporal relationship between cerebral and autonomic activities before and during periodic limb movements in NREM and REM sleep (PLMS). METHODS: Patterns of EEG, cardiac and muscle activities associated with PLMS were drawn from polysomnographic recordings of 14 outpatients selected for the presence of PLMS both in NREM and REM sleep. PLMS were scored during all sleep stages from tibial EMG. Data from a bipolar EEG channel were analyzed by wavelet transform. Heart rate (HR) was evaluated from the electrocardiogram. EEG, HR and EMG activations were detected as transient increase of signal parameters and examined by analysis of variance and correlation analysis independently in NREM and REM sleep. Homologous parameters in REM and NREM sleep were compared by paired t-test. RESULTS: The autonomic component, expressed by HR increase, took place before the motor phenomenon both in REM and NREM sleep, but it was significantly earlier during NREM. In NREM sleep, PLM onset was heralded by a significant activation of delta-EEG, followed by a progressive increase of all the other bands. No significant activations of delta EEG were found in REM sleep. HR and EEG activations positively correlated with high frequency EEG activations and negatively (in NREM) with slow frequency ones. CONCLUSIONS: Our findings suggested a heralding role for delta band only in NREM sleep and for HR during both NREM and REM sleep. Differences in EEG and HR activation between REM and NREM sleep and correlative data suggested a different modulation of the global arousal response. SIGNIFICANCE: In this study, time-frequency analysis and advanced statistical methods enabled an accurate comparison between brain and autonomic changes associated to PLM in NREM and REM sleep providing indications about interaction between autonomic and slow and fast EEG components of arousal response.

A time course study on the "in vitro" effects of T3 and testosterone on androgen and estrogen receptors in peripuberal primary rat Sertoli cells.

The effect of Tri-iodothyronine (T3) administration leading to the precocius differentiation of Sertoli cell in prepuberal rats has been previously shown. The functional maturation of Sertoli cells is associated with changes in androgen metabolism. We have recently demonstrated that T3 influences androgen metabolism in Sertoli cells by inhibiting aromatase activity and reduces drastically the ER contents in peripubertal hypothyroid rats. To better understand the role of T3 in modulating steroid action on Sertoli cells, we performed a time course study evaluating the in vitro effects of T3 and testosterone (T) on androgen (ARs) and estrogen (ERs) receptor content in Sertoli cells isolated from two weeks old Wistar rats. ARs and ERs basal levels did not change during the time course study indicating that the exposure to culture medium per se did not affect either receptor type. After 24 hrs of incubation with either T3 or T, a decrease of ERs in both nucleus and cytosol was observed. Such a decrease was augmented by the simultaneous administration of both hormones. ARs displayed a different temporal pattern in the two cellular compartments and exhibited an earlier rise in the cytosol induced by either T3 or T. At 36 hrs, ARs were significantly enhanced in both compartments in response to either T or T3 exposure while combined hormonal treatment caused an additive increase compared with the single treatment group. As a consequence of the opposite behaviour pattern displayed by ARs and ERs, the ratio between total ARs and ERs contents was increased after 24 hrs of exposure to hormonal treatment. To evaluate if treatments performed induced a functional maturation of Sertoli cells, transferrin levels in culture medium were measured. The increase of this protein paralleled that of ARs content as well as that of ARs/ERs ratio. This study demonstrates that thyroid hormone induces a progressive increase of (AR)/(ER) ratio in the differentiating Sertoli cells bringing them to a prevalent androgen dependency along their functional maturation.

Effect of triiodothyronine administration on estrogen receptor contents in peripuberal Sertoli cells.

The effects of thyroid hormone on androgen metabolism in peripuberal Sertoli cells through the inhibition of estradiol production have been reported previously. It was our intention to investigate further the possible role of thyroid hormone on the interaction between testicular steroids and Sertoli cells by analyzing the effects of triiodothyronine (T3) on estrogen receptor content in 2-, 3- and 4- week-old euthyroid rats. Triiodothyronine treatment (3 micrograms/100 body wt per day) given during the last week prior to sacrifice resulted in reduced testicular growth in 2-week-old animals. Sertoli cells from all groups were cultured initially under basal conditions for the first 24 h and subsequently in the presence of testosterone and/or T3 for the additional 24 h. The in vitro addition of T3 induced a decrease of estrogen receptors (ERs) in 2- and 3-week-old animals that appeared more pronounced especially in the presence of T3 and testosterone. When T3 was tested in vivo we noticed that the decrease of ER content was even greater in all three groups under the in vitro influence of both T3 and testosterone. In 3-week-old animals a simultaneous assay of ERs in both nuclear and cytoplasmic compartments was performed. The ER concentrations in the nucleus were closely related to those of the cytoplasm. The in vivo administration of T3 was responsible for a greater decrease of ERs in the nucleus than in the cytosol. On the basis of these results, and in agreement with our previous data, we speculate that the effect of T3 in the maturational events of Sertoli cells could involve both estradiol production and ER content.

Thyroid hormone modulates androgen and oestrogen receptor content in the Sertoli cells of peripubertal rats.

A possible role of tri-iodothyronine (T3) on the interplay between testicular steroids and Sertoli cells has been investigated on the basis of previous findings demonstrating a direct inhibitory influence of T3 on aromatase activity and oestradiol production in peripuberal Sertoli cells. In this context, the present study was focused on the effects of T3 on oestrogen receptor (ER) and androgen receptor (AR) contents in the cytosol and nucleus of Sertoli cells isolated from 2-, 3- and 4-week-old euthyroid, hypothyroid and hypothyroid treated rats. Hypothyroidism was induced by the oral administration of 0.025% methimazole (MMI) from birth until the rats were killed at 2, 3 and 4 weeks of age. Half of the MMI-treated animals were injected i.p. with L-tri-iodothyronine (T3; 3 micrograms/100 g body weight) during the last week before death. Sertoli cells from all groups were initially cultured under basal conditions for the first 24 h and subsequently in the presence of testosterone with or without T3 for an additional 24 h. Hypothyroidism was associated with severe impairment of body as well as testicular growth. Euthyroid ERs showed an elevated Kd (0.76 nM) which was similar in the different age groups investigated. The in vitro addition of T3 or testosterone induced a decrease in ER content and this decrease was greater after exposure to both hormones. In 2- and 3-week-old hypothyroid rats, ER content was markedly increased and was reversed in euthyroid rats when T3 was given in vivo. When ERs were assayed in the Sertoli cell nucleus and cytoplasm of 2- and 3-week-old animals, a strong relationship in ER content in the two cellular compartments was observed. Neither of the hormones tested seemed to affect the AR content in the nucleus significantly, while the in vitro addition of testosterone or T3 or both hormones together augmented the ARs in the cytosol to a greater extent, resulting in an increase in their total (cytosolic and nuclear) content in the cells. The present data suggest that T3 down-regulates ERs and up-regulates ARs in peripuberal Sertoli cells. The additive effect of testosterone and T3 in up-regulating ARs could possibly involve a role for T3 in influencing the androgen responsiveness of the Sertoli cells during spermatogenesis.

Effect of oestradiol and insulin on the proliferative pattern and on oestrogen and progesterone receptor contents in MCF-7 cells.

In a long-term experiment MCF-7 cells showed an exponential proliferation rate in fetal calf serum while they become quiescent in growth-factor- and steroid-free serum. The mitogenic activity of this cell line was increased by oestradiol and insulin, exposure to both hormones showing a synergic effect. These mitogen-mediated effects are inhibited by genistein a phytoestrogen which, by itself at the doses used, did not affect either the basal proliferation rate or the total protein content. Immunoblotting and Scatchard analysis reveal respectively that insulin increases the oestrogen receptor (ER) content and its binding capacity. The presence of genistein decreases the ER content and completely abolishes the binding capacity of this protein. Insulin is able to increase progesterone receptor (PR) levels while, in the presence of genistein, the above-reported effect was completely abolished. On the basis of the latter data the authors suggest that insulin is able to affect the phosphorylation status of ER and PR, inducing functional changes in both proteins, although this was in the absence of their natural ligands. Indeed, the presence in the medium of a tyrosine kinase inhibitor such as genistein could substantially decrease both ER and PR levels in these cells.