Functional neuroimaging of the vegetative state

A number of recent studies have demonstrated a role for state-of-the-art neuroimaging methods in the assessment of patients in the vegetative state and other so-called 'disorders of consciousness'. In several cases, functional MRI has been used to show that aspects of speech perception, emotional processing, language comprehension and even conscious awareness might be retained in some patients who behaviourally meet all of the criteria that define the vegetative state. This work has profound implications for clinical care, diagnosis, prognosis and medical-legal decision making (relating to the prolongation, or otherwise, of life after severe brain injury), as well as for more basic scientific questions about the nature of consciousness and the neural representation of our own thoughts and intentions.     

Recovery of patients after four months or more in the persistent vegetative state.

A retrospective review was made of the case notes of 43 consecutive patients admitted to a unit specialising in the rehabilitation of people in the persistent vegetative state. Eleven of these patients regained awareness four months or more after suffering brain damage. The time to the first reported incidence of eye tracking was between four months and three years, and the time to the first response to command was between four and 12 months. Only one patient was eventually unable to communicate, six could use non-verbal methods of indicating at least a yes or no response, and four were able to speak. Six patients remained totally dependent while two became independent in daily activities. Four patients became independent in feeding, three required help, and four remained on gastrostomy feeding. Thus some patients can regain awareness after more than four months in a vegetative state, and, although few reach full independence, most can achieve an improved quality of life within the limitations of their disabilities. The recovery period is prolonged and may continue for several years. Even patients with profound brain damage should be offered the opportunity of a specialist rehabilitation programme.     

Health-related quality of life in patients with pulmonary arterial hypertension

Background

Improved outcomes with expanding treatment options for patients with pulmonary arterial hypertension present the opportunity to consider additional end-points in approaching therapy, including factors that influence health-related quality of life. However, comparatively little is known about health-related quality of life and its determinants in patients with pulmonary arterial hypertension.

Methods

Health-related quality of life was evaluated in a cross sectional study of 155 outpatients with pulmonary arterial hypertension using generic and respiratory-disease specific measurement tools. Most patients had either World Health Organization functional Class II or III symptoms. Demographic, hemodynamic and treatment variables were assessed for association with health-related quality of life scores.

Results

Patients with pulmonary arterial hypertension suffered severe impairments in both physical and emotional domains of health-related quality of life. Patients with idiopathic ("primary") pulmonary arterial hypertension had the best, and those with systemic sclerosis the worst health-related quality of life. Greater six-minute walk distance correlated with better health-related quality of life scores, as did functional Class II versus Class III symptoms. Hemodynamic measurements, however, did not correlate with health-related quality of life scores. No differences in health-related quality of life were found between patients who were being treated with calcium channel antagonists, bosentan or continuously infused epoprostenol at the time of quality of life assessment.

Conclusion

Health-related quality of life is severely impaired in patients with pulmonary arterial hypertension and is associated with measures of functional status. Specific associations with impaired health-related quality of life suggest potential areas for targeted intervention.     

Neuroimaging technique: a diagnostic tool to detect altered states of consciousness

Vegetative and minimally conscious states diagnosis remained a major clinical challenge. New paradigms such as measurement of the global cerebral metabolism, the structural and functional integrity of fronto-parietal network, or the spontaneous activity in resting state have been shown to be helpful to disentangle vegetative from minimally conscious patients. Active neuroimagery paradigms also allow detecting voluntary and conscious activity in non-communicative patients. The implementation of these methods in clinical routine could permit to reduce the current high rate of misdiagnosis (40%).     

Symptoms and Quality of Life in Late Stage Parkinson Syndromes: A Longitudinal Community Study of Predictive Factors

Background

Palliative care is increasingly offered earlier in the cancer trajectory but rarely in Idiopathic Parkinson''s Disease(IPD), Progressive Supranuclear Palsy(PSP) or Multiple System Atrophy(MSA). There is little longitudinal data of people with late stage disease to understand levels of need. We aimed to determine how symptoms and quality of life of these patients change over time; and what demographic and clinical factors predicted changes.

Methods

We recruited 82 patients into a longitudinal study, consenting patients with a diagnosis of IPD, MSA or PSP, stages 3–5 Hoehn and Yahr(H&Y). At baseline and then on up to 3 occasions over one year, we collected self-reported demographic, clinical, symptom, palliative and quality of life data, using Parkinson''s specific and generic validated scales, including the Palliative care Outcome Scale (POS). We tested for predictors using multivariable analysis, adjusting for confounders.

Findings

Over two thirds of patients had severe disability, over one third being wheelchair-bound/bedridden. Symptoms were highly prevalent in all conditions - mean (SD) of 10.6(4.0) symptoms. More than 50% of the MSA and PSP patients died over the year. Over the year, half of the patients showed either an upward (worsening, 24/60) or fluctuant (8/60) trajectory for POS and symptoms. The strongest predictors of higher levels of symptoms at the end of follow-up were initial scores on POS (AOR 1.30; 95%CI:1.05–1.60) and being male (AOR 5.18; 95% CI 1.17 to 22.92), both were more predictive than initial H&Y scores.

Interpretation

The findings point to profound and complex mix of non-motor and motor symptoms in patients with late stage IPD, MSA and PSP. Symptoms are not resolved and half of the patients deteriorate. Palliative problems are predictive of future symptoms, suggesting that an early palliative assessment might help screen for those in need of earlier intervention.     

Endometrial assessment with Isaacs cell sampler.

The value of the Isaacs endometrial cell sampler in the cytologic assessment of the endometrium was studied in 121 unanaesthetised patients aged over 40. Satisfactory aspirates for cytological diagnosis of endometrial state were obtained in 111 patients (91%) whereas endometrial specimens for histological diagnosis were obtained in only 89 patients (79%). In only four out of 83 cases were there diagnostic discrepancies between the aspirates and the curettings. It is concluded that the technique is safe, quick, comfortable, and reliable for assessing endometrial state. It should therefore prove valuable for screening, particularly in the management of menopausal women requiring oestrogen treatment.     

Patients in the persistent vegetative state: problems in their long term management.

Physicians responsible for the long term management of patients in the persistent vegetative state face several problems. These include deciding whether tube feeding is treatment or nutritional care, whether withdrawal of tube feeding is an appropriate form of management, what clinical advantage there is in active treatment; at what level of awareness can a patient be said to have a quality of life; and who should determine a patient''s right to die. These problems are determined more by social, legal, emotional, cultural, religious, and economic forces than by clinical facts.     

Psychological rehabilitation after myocardial infarction: multicentre randomised controlled trial.

OBJECTIVE: To evaluate rehabilitation after myocardial infarction. DESIGN: Randomised controlled trial of rehabilitation in unselected myocardial infarction patients in six centres, baseline data being collected on admission and by structured interview (of patients and spouses) shortly after discharge and outcome being assessed by structured interview at six months and clinical examination at 12 months. SETTING: Six district general hospitals. SUBJECTS: All 2328 eligible patients admitted over two years with confirmed myocardial infarction and discharged home within 28 days. INTERVENTIONS: Rehabilitation programmes comprising psychological therapy, counselling, relaxation training, and stress management training over seven weekly group outpatient sessions for patients and spouses. MAIN OUTCOME MEASURES: Anxiety, depression, quality of life, morbidity, use of medication, and mortality. RESULTS: At six months there were no significant differences between rehabilitation patients and controls in reported anxiety (prevalence 33%) or depression (19%). Rehabilitation patients reported a lower frequency of angina (median three versus four episodes a week), medication, and physical activity. At 12 months there were no differences in clinical complications, clinical sequelae, or mortality. CONCLUSIONS: Rehabilitation programmes based on psychological therapy, counselling, relaxation training, and stress management seem to offer little objective benefit to patients who have experienced myocardial infarction compared with previous reports of smaller trials.     

Mtp-40 and alpha antigen gene fragment amplification for the detection of Mycobacterium tuberculosis in Colombian clinical specimens

In this study, the use of Mtp-40 and alpha antigen polymerase chain reaction (PCR) amplification fragments for the precise tuberculosis (TB) diagnosis was evaluated. One hundred and ninety two different samples were obtained from 113 patients with suspected TB. Mtp-40 and alpha antigen protein genes were amplified by the PCR technique and compared to both the "gold standard" (culture) test, as well as the clinical parameters (including a clinical record and X-ray film exam in 113 patients). Thirty-eight of the 113 patients had a presumptive clinical diagnosis of TB; 74% being detected by PCR technique, 58% by culture and 44% by direct microscopic visualization. Weconclude that it is possible to use PCR as a suitable technique for the detection of any mycobacteria by means of the alpha antigen product, or the specific infection of Mycobacterium tuberculosis by means of the mtp-40 gene. This might be a good supporting tool in difficult clinical TB diagnosis and pauci-bacillary cases.     

Brain death in three neurosurgical units.

The validity of clinical criteria for diagnosing brain death has been investigated in three ways. A total of 447 published cases were reviewed. In three neurosurgical units (Cambridge, Glasgow, and Swansea) 609 patients diagnosed clinically as brain dead were studied; 326 had final cardiac asystole while still being ventilated, and ventilation was discontinued in the remainder. No patient recovered. The median time in hospital before the heart finally stopped was 3 1/2-4 1/2 days, with 30-40 hours on the ventilator. Analysis of prospective data from three countries on patients with severe head injuries showed that not one of 1003 survivors would ever have been suspected of being brain dead even in their worst state soon after injury. Recovery after supposed brain death has been alleged in patients who were thought to be brain dead but in fact were not and in cases where reflex movements in the limbs were mistaken for signs of life. The safeguards in diagnosing brain death include establishing irreversible structural brain damage, excluding the effects of drugs, and allowing enough time to elapse to establish the diagnosis beyond doubt. The studies reported here show that the clinical criteria used in the United Kingdom are reliable. There is no need for confirmatory tests such as an electroencephalogram provided that all the conditions for clinical diagnosis have been fulfilled and all the tests carried out.     

Diagnostic and economic evaluation of new biomarkersfor Alzheimer¿s disease: the research protocol of a prospective cohort study

ABSTRACT: BACKGROUND: New research criteria for the diagnosis of Alzheimer's disease (AD) have recently been developed to enable an early diagnosis of AD pathophysiologyby relying on emerging biomarkers. To enable efficient allocation of health care resources, evidence is needed to support decision makers on the adoption of emerging biomarkers in clinical practice. The research goals are to 1) assess the diagnostic test accuracy of current clinical diagnostic work-up and emerging biomarkers in MRI, PET and CSF, 2) perform a cost-consequence analysis and 3) assess long-term cost-effectiveness by an economic model.Methods/designIn a cohort design 223 consecutive patients suspected of having a primary neurodegenerative disease are approached in four academic memory clinics and followed for two years. Clinical data and data on quality of life, costs and emerging biomarkers are gathered.Diagnostic test accuracy is determined by relating the clinical practice and new research criteria diagnoses to the reference diagnosis. The clinical practice diagnosis at baseline is reflected by a consensus procedure among experts using clinical information only (no biomarkers). The diagnosis based on the new research criteria is reflected by decision rules that combine clinical and biomarker information. The reference diagnosis is determined by a consensus procedure among experts based on clinical information on the course of symptoms over a two-year time period.A decision analytic model is built combining available evidence from different resources among which (accuracy) results from the study, literature and expert opinion to assess long-term cost-effectiveness of the emerging biomarkers. DISCUSSION: Several other multi-centre trials study the relative value of new biomarkers for early evaluation of AD and related disorders. The uniqueness of this study is the assessment of resource utilization and quality of life to enable an economic evaluation. The study results are generalizable to a population of patients who are referred to a memory clinic due to their memory problems.Trial registrationNCT01450891.     

Fine Needle Aspiration Cytodiagnosis As A Pre-Requisite For Primary Medical Treatment of Breast Cancer

The accurate non-surgical diagnosis of breast lumps allows assessment of breast cancer patients for conservation or neoadjuvant primary treatment before surgical intervention. We have analysed the accuracy of clinical assessment, fine needle aspiration cytology (FNAC), and mammography in over 868 women seen in a symptomatic breast clinic. Clinical examination by an experienced breast physician, together with FNAC, detected over 99% of the cancers with a 12% false positive rate. A cytological diagnosis of definite carcinoma was obtained in 69% of women with breast cancer with no false positive result from the women with benign conditions producing a 100% positive predictive value. These results indicate that it would be acceptable to give pre-surgical systemic endocrine or chemotherapy to women with positive cytology which is therefore a prerequisite for a neoadjuvant therapy programme.     

Patient-Reported Outcomes for Quality of Life Assessment in Atrial Fibrillation: A Systematic Review of Measurement Properties

BackgroundAtrial fibrillation is a large and growing burden across all types of healthcare. Both incidence and prevalence are expected to double in the next 20 years, with huge impact on hospital admissions, costs and patient quality of life. Patient wellbeing determines the management strategy for atrial fibrillation, including the use of rhythm control therapy and the clinical success of heart rate control. Hence, evaluation of quality of life is an emerging and important part of the assessment of patients with atrial fibrillation. Although a number of questionnaires to assess quality of life in atrial fibrillation are available, a comprehensive overview of their measurement properties is lacking.InterpretationGiven the low ratings for many measurement properties, no single questionnaire can be recommended, although AFEQT performed strongest. Further studies to robustly assess reliability, validity and responsiveness of AF-specific quality of life questionnaires are required. This review consolidates the current evidence for quality of life assessment in patients with atrial fibrillation and identifies priority areas for future research.     

Behavioral and Psychological Factors in the Assessment and Treatment of Obesity Surgery Patients

Objective: To provide evidence‐based guidelines on the psychological and behavioral screening of weight loss surgery (WLS) candidates and the impact of psychosocial factors on behavior change after gastric bypass surgery. Research Methods and Procedures: The members of the Behavioral and Psychological subgroup of the Multidisciplinary Care Task Group conducted searches of MEDLINE and PubMed for articles related to WLS, behavior changes, and mental health, including quality of life (QOL) and behavior modification. Pertinent abstracts and literature were reviewed for references. A total of 198 abstracts were identified; 17 papers were reviewed in detail. Search periods were from 1980 to 2004. Results: We found a high incidence of depression, negative body image, eating disorders, and low QOL in severely obese patients. Our task subgroup recommended that all WLS candidates be evaluated by a licensed mental health care provider (i.e., psychiatrist, psychologist, or social worker), experienced in the treatment of severely obese patients and working within the context of a multidisciplinary care team. We also recommended development of pre‐ and postsurgical treatment plans that address psychosocial contraindications for WLS and potential barriers to postoperative success. Discussion: The psychological consequences of obesity can range from lowered self‐esteem to clinical depression. Rates of anxiety and depression are three to four times higher among obese individuals than among their leaner peers. A comprehensive multidisciplinary program that incorporates psychological and behavior change services can be of critical benefit in enhancing compliance, outcome, and QOL in WLS patients.     

Salt sensitivity of the vegetative and reproductive stages in chickpea (Cicer arietinum L.): Podding is a particularly sensitive stage

Soil salinity is an increasing problem, including in regions of the world where chickpea is cultivated. Salt sensitivity of chickpea was evaluated at both the vegetative and reproductive phase. Root-zone salinity treatments of 0, 20, 40 and 60 mM NaCl in aerated nutrient solution were applied to seedlings or to older plants at the time of flower bud initiation. Even the reputedly tolerant cultivar JG11 was sensitive to salinity. Plants exposed to 60 mM NaCl since seedlings, died by 52 d without producing any pods; at 40 mM NaCl plants died by 75 d with few pods formed; and at 20 mM NaCl plants had 78-82% dry mass of controls, with slightly higher flower numbers but 33% less pods. Shoot Cl exceeded shoot Na by 2-5 times in both the vegetative and reproductive phase, and these ions also entered the flowers. Conversion of flowers into pods was sensitive to NaCl. Pollen from salinized plants was viable, but addition of 40 mM NaCl to an in vitro medium severely reduced pollen germination and tube growth. Plants recovered when NaCl was removed at flower bud initiation, adding new vegetative growth and forming flowers, pods and seeds. Our results demonstrate that chickpea is sensitive to salinity at both the vegetative and reproductive phase, with pod formation being particularly sensitive. Thus, future evaluations of salt tolerance in chickpea need to be conducted at both the vegetative and reproductive stages.     

Salvage of ischemic digits using a lateral arm fascial flap

Four patients underwent microvascular transfer of a lateral arm fascial flap to salvage severely ischemic digits by means of induction of neovascularization. The cause of the digital ischemia was direct trauma (crush injury) in one patient and chronic embolic phenomena (proximal arterial occlusion) in three patients. None of the patients had responded to traditional therapy, including treatment with one or more of the following: anticoagulation, lytic therapy, oral vasodilators, digital sympathectomy, and vein bypass grafting. Each patient underwent noninvasive (Doppler ultrasound, digital pressures, digital temperatures, vascular refill) and invasive (angiogram) vascular assessment preoperatively. After microvascular transfer of the lateral arm fascial flap, all patients reported symptomatic relief, and objective improvements were documented by both noninvasive and invasive assessment criteria. One patient developed a seroma at the donor site; another experienced a late complication of thrombosis of the flap after his wound dehisced. A 6-month follow-up evaluation demonstrated neovascular collateralization and stable improvement without regression in the remaining patients. The authors present their clinical experience and propose a treatment algorithm for patients with chronic digital ischemia.     

The community hospital: a three-year study.

In a three-year period a community hospital of 40 beds discharged 2086 patients, their mean length of stay being 14.8 days. Some 68% of the patients treated were over 65, and 8.9% died in hospital. While the most common diagnosis on admission was disease of the respiratory tract, this does not indicate the actual cause of admission. For 142 patients from one practice this was acute illness in 44% of the cases, assessment in 20%, and a need for nursing care in 36%. If the community hospital had not been available about half these patients would have been admitted to the general hospital.     

Vegetative versus Minimally Conscious States: A Study Using TMS-EEG,Sensory and Event-Related Potentials

Differential diagnoses between vegetative and minimally conscious states (VS and MCS, respectively) are frequently incorrect. Hence, further research is necessary to improve the diagnostic accuracy at the bedside. The main neuropathological feature of VS is the diffuse damage of cortical and subcortical connections. Starting with this premise, we used electroencephalography (EEG) recordings to evaluate the cortical reactivity and effective connectivity during transcranial magnetic stimulation (TMS) in chronic VS or MCS patients. Moreover, the TMS-EEG data were compared with the results from standard somatosensory-evoked potentials (SEPs) and event-related potentials (ERPs). Thirteen patients with chronic consciousness disorders were examined at their bedsides. A group of healthy volunteers served as the control group. The amplitudes (reactivity) and scalp distributions (connectivity) of the cortical potentials evoked by TMS (TEPs) of the primary motor cortex were measured. Short-latency median nerve SEPs and auditory ERPs were also recorded. Reproducible TEPs were present in all control subjects in both the ipsilateral and the contralateral hemispheres relative to the site of the TMS. The amplitudes of the ipsilateral and contralateral TEPs were reduced in four of the five MCS patients, and the TEPs were bilaterally absent in one MCS patient. Among the VS patients, five did not manifest ipsilateral or contralateral TEPs, and three of the patients exhibited only ipsilateral TEPs with reduced amplitudes. The SEPs were altered in five VS and two MCS patients but did not correlate with the clinical diagnosis. The ERPs were impaired in all patients and did not correlate with the clinical diagnosis. These TEP results suggest that cortical reactivity and connectivity are severely impaired in all VS patients, whereas in most MCS patients, the TEPs are preserved but with abnormal features. Therefore, TEPs may add valuable information to the current clinical and neurophysiological assessment of chronic consciousness disorders.     

The Clinical Utility of fMRI for Identifying Covert Awareness in the Vegetative State: A Comparison of Sensitivity between 3T and 1.5T

In the last few years, mental imagery fMRI paradigms have been used successfully to identify covert command-following and awareness in some patients who are thought to be entirely vegetative. However, to date there is only evidence supporting their use at magnetic fields of 3T, which limits their applicability in clinical settings where lower field strengths are typically used. Here, we test the ‘gold standard’ fMRI paradigm for detecting residual awareness in non-responsive patients by comparing its sensitivity at 1.5T and 3T in the same group of healthy volunteers. We were able to successfully detect brain activity showing command-following in most participants at both 3T and 1.5T, with similar reliability. These results demonstrate that fMRI assessment of covert awareness is clinically viable and therefore justify a broader use of these methods in standard assessments in severely brain injured patients.     

Changes in the Pulmonary Function Test after Radioactive Iodine Treatment in Patients with Pulmonary Metastases of Differentiated Thyroid Cancer

ObjectivePulmonary function test (PFT) is a useful tool for an objective assessment of respiratory function. Impaired pulmonary function is critical for the survival and quality of life in patients with pulmonary metastases of solid cancers including thyroid cancer. This study aimed to evaluate clinical factors associated with severely impaired pulmonary function by serial assessment with PFT in patients with pulmonary metastasis of differentiated thyroid cancer (DTC) who received radioactive iodine treatment (RAIT).PatientsThis retrospective study enrolled 31 patients who underwent serial PFTs before and after RAIT for pulmonary metastasis of DTC. We evaluated the risk factors for severe impairment of pulmonary function.ResultsThe median age of the patients was 44.1 years and 18 of them were female patients. Severe impairment of pulmonary function was observed in five patients (16%) after a median of three RAITs (cumulative I-131 activity = 20.4 GBq). These patients were older and more frequently had mild impairment of baseline pulmonary function, respiratory symptoms, or progressive disease compared with patients with stable pulmonary function. Neither cumulative dose nor number of RAIT was associated with decreased pulmonary function. Coexisting pulmonary diseases, presence of respiratory symptoms, and metastatic disease progression were significantly associated with severe decrease in forced vital capacity during follow-up (p =.047, p =.011, and p =.021, respectively).ConclusionsPulmonary function was severely impaired during follow-up in some patients with pulmonary metastasis of DTC after a high-dose RAITs. Neither the number of RAIT nor the cumulative I-131 activity was associated with decreased pulmonary function. Serial PFT might be considered for some high-risk patients during follow-up.