Misdiagnosis of the vegetative state: retrospective study in a rehabilitation unit.

OBJECTIVE--To identify the number of patients who were misdiagnosed as being in the vegetative state and their characteristics. DESIGN--Retrospective study of the clinical records of the medical, occupational therapy, and clinical psychology departments. SETTING--20 bed unit specialising in the rehabilitation of patients with profound brain damage, including the vegetative state. SUBJECTS--40 patients admitted between 1992 and 1995 with a referral diagnosis of vegetative state. OUTCOME MEASURES--Patients who showed an ability to communicate consistently using eye pointing or a touch sensitive single switch buzzer. RESULTS--Of the 40 patients referred as being in the vegetative state, 17 (43%) were considered as having been misdiagnosed; seven of these had been presumed to be vegetative for longer than one year, including three for over four years. Most of the misdiagnosed patients were blind or severely visually impaired. All patients remained severely physically disabled, but nearly all were able to communicate their preference in quality of life issues-some to a high level. CONCLUSIONS--The vegetative state needs considerable skill to diagnose, requiring assessment over a period of time; diagnosis cannot be made, even by the most experienced clinician, from a bedside assessment. Accurate diagnosis is possible but requires the skills of a multidisciplinary team experienced in the management of people with complex disabilities. Recognition of awareness is essential if an optimal quality of life is to be achieved and to avoid inappropriate approaches to the courts for a declaration for withdrawal of tube feeding.     

The vegetative state as a manifestation of a stable pathological state

The results of comprehensive monitoring of the state of 25 patients in the vegetative state (prolonged coma) before and after compensating for the factors of secondary brain damage were analyzed and followed up for no less than six months. The primary results showed that the best recovery of consciousness and cognitive functions was observed if, according to the positron emission tomography data, a diffuse decrease in the glucose metabolism rate (GMR_glu), significantly exceeding the extent of the zones of morphological/anatomical lesions, was present in the brain before treatment, while the minimal improvement was observed if the GMR_glu was sufficiently intact. These and other paradoxical results can be explained if the vegetative state is regarded as a stable pathological state of the brain, which offers new approaches to the treatment of this group of patients.     

睡眠纺锤波在植物状态病人预后判别中的价值研究

目的:探讨脑电图睡眠纺锤波在植物状态病人预后判别中的价值。方法:在长程脑电监测下观察植物状态病人的睡眠纺锤波,与其意识恢复进行相关性分析,并预测患者意识恢复的敏感性、特异性及准确性。结果:28例患者中,12例有纺锤波,其中9例意识恢复;16例无纺锤波患者中,14例未恢复意识。纺锤波的有无与患者意识恢复有相关性,P值<0.01。脑电图睡眠纺锤波对植物状态患者意识恢复判断的敏感性(83.25%)、特异性(81.82%)、准确性(82.14%)。结论:脑电图睡眠纺锤波可较准确预测植物状态患者的意识恢复能力,可作为临床评估植物状态患者意识恢复能力的辅助方法。     

Functional brain imaging in the clinical assessment of consciousness

Recent findings suggest that functional brain imaging might be used to identify consciousness in patients diagnosed with persistent vegetative state and minimally conscious state. Michael Rafii and James Brewer discuss the potential for fMRI's wider implementation in clinical practice, and associated caveats.     

The possibilities for partial rehabilitation of the integrative activity of the brain in patients in a vegetative state

An integrated neuroreconstructive approach to stimulating the pathogenetic mechanisms of a vegetative state developed due to a severe traumatic brain injury (TBI) is suggested. It has been shown that a faster and more pronounced therapeutic effect, compared with conventional therapies, could be achieved through the application of transtimpanal chemical vestibular dereception and transcranial micropolarization. The results of neurophysiological in-depth examination in dynamics have shown that over time interregional cortical interactions become more intense, “rigid,” and “tight” in patients with a vegetative state, while the temporal-parietal-occipital areas begin to dominate in the organization of these interactions in the cortex of both hemispheres. It is assumed that the vestibulothalamic tract, owing to its anatomical location, appears to be the least vulnerable under the conditions of brain stem dislocation due to a severe TBI. As a result, vestibular afferentation appears to become a predominant kind of afferentation for generating interregional cortical interactions. A pathological functional system develops on the basis of this afferentation, blocking other functional systems in the damaged brain. The suggested therapies significantly reduce the amount of vestibular afferent inputs and open a possibility for restoring more effective afferent interactions. This significantly facilitates the functioning of the brain as a multimodal analyzer.     

Polyfunctionality of neurons: The blocking of extreme pathological afferentation leads to an improvement of the higher functions of the brain

In this paper, a possible mechanism for improving the functional state of the brain regions maintaining locomotor, visual, auditory, and higher functions of the brain during the correction of the generalized spastic syndrome (botulinotherapy with Xeomin) in patients in the vegetative state (VS) is discussed. If the vegetative state is considered as a stable pathological condition (SPC) of the brain, then, in terms of the theory of the structural-functional organization of brain systems with rigid and flexible elements (N.P. Bechtereva), the therapy led to an unbalance of SPC, functional liberation of neurons, redistribution of their functions to ensure other activities, and the formation of new interneuronal connections. Taking into account the functional variability of neurons (S.V. Medvedev), the blocking of the neuromuscular transmission in spastic muscles reduces the abnormal afferent and efferent hyperactivity of motor and sensory neuronal circuits, which liberates the brain for other activities. Clinically, this allows considering botulinotherapy of drug-resistant muscle spasticity in patients in VS and minimal consciousness not only as a symptomatic treatment but also as indirect neuroprotection.     

Floral activity in solutions of deoxyribonucleic Acid extracted from tobacco stems

For Nicotiana tabacum cv. Wis. 38 plants, the capabilities of solutions containing DNA, extracted from either homogenates of stems in a floral state or nuclei of stems in a vegetative state, to effect flowering of vegetative plants have been studied. Previous work indicates that the DNA from homogenates of stems in a floral state is mainly nuclear. If DNA solutions are supplied to axillary buds of vegetative plants and if the axillary buds are defoliated every 4th day for 12 days, the buds supplied a solution of DNA from stems in a floral state initiate flowers under noninductive conditions, and the buds supplied a solution of DNA from stems in a vegetative state remain vegetative. Heating and rapidly cooling a solution of DNA from stems in a floral state enhances its floral activity. Heating and cooling a DNA solution also results in novel flowers showing up in many treated plants. Novel flowers are more striking in the offspring than in the parents. The capabilities of heated-cooled DNA solution to initiate flowers in noninductive conditions and to cause novel flowers are eliminated completely by treating (before heating and cooling) the DNA solution with deoxyribonuclease. Heated-cooled solutions of DNA extracted from nuclei of either vegetative stems or vegetative leaves contain no floral activity.     

Detecting number processing and mental calculation in patients with disorders of consciousness using a hybrid brain-computer interface system

Background

For patients with disorders of consciousness such as coma, a vegetative state or a minimally conscious state, one challenge is to detect and assess the residual cognitive functions in their brains. Number processing and mental calculation are important brain functions but are difficult to detect in patients with disorders of consciousness using motor response-based clinical assessment scales such as the Coma Recovery Scale-Revised due to the patients’ motor impairments and inability to provide sufficient motor responses for number- and calculation-based communication.

Methods

In this study, we presented a hybrid brain-computer interface that combines P300 and steady state visual evoked potentials to detect number processing and mental calculation in Han Chinese patients with disorders of consciousness. Eleven patients with disorders of consciousness who were in a vegetative state (n?=?6) or in a minimally conscious state (n?=?3) or who emerged from a minimally conscious state (n?=?2) participated in the brain-computer interface-based experiment. During the experiment, the patients with disorders of consciousness were instructed to perform three tasks, i.e., number recognition, number comparison, and mental calculation, including addition and subtraction. In each experimental trial, an arithmetic problem was first presented. Next, two number buttons, only one of which was the correct answer to the problem, flickered at different frequencies to evoke steady state visual evoked potentials, while the frames of the two buttons flashed in a random order to evoke P300 potentials. The patients needed to focus on the target number button (the correct answer). Finally, the brain-computer interface system detected P300 and steady state visual evoked potentials to determine the button to which the patients attended, further presenting the results as feedback.

Results

Two of the six patients who were in a vegetative state, one of the three patients who were in a minimally conscious state, and the two patients that emerged from a minimally conscious state achieved accuracies significantly greater than the chance level. Furthermore, P300 potentials and steady state visual evoked potentials were observed in the electroencephalography signals from the five patients.

Conclusions

Number processing and arithmetic abilities as well as command following were demonstrated in the five patients. Furthermore, our results suggested that through brain-computer interface systems, many cognitive experiments may be conducted in patients with disorders of consciousness, although they cannot provide sufficient behavioral responses.

     

220例植物状态患者早期电生理与预后的相关性

目的：观察植物状态患者早期电生理检查脑干听觉诱发电位、体感诱发电位反应与后期意识是否恢复和预后的相关性。方法：对入院220例的植物状态患者分别在患病三个月内进行早期的脑干听觉诱发电位和体感诱发电位检查,每项电生理检查结果进行量化分级评分,并采用Glasgow结局量表（GOS）分别评价植物状态在一年时的意识状态和转归情况,出院的患者进行随访问卷调查,了解其预后情况。结果：植物状态患者早期脑干听觉诱发电位和体感诱发电位的不同表现与预后存在显著差异（P〈0．05）,表现越好,其预后就越好。脑干听觉诱发电位和体感诱发电位与植物状态患者意识恢复存在明显相关性（P〈0．05）。结论：脑干听觉诱发电位和体感诱发电位可作为早期评价植物状态患者意识转归和预后的重要工具。     

Evolutionary history of vegetative reproduction in Porpidia s.L. (Lichen-forming ascomycota)

The evolutionary history of gains and losses of vegetative reproductive propagules (soredia) in Porpidia s.l., a group of lichen-forming ascomycetes, was clarified using Bayesian Markov chain Monte Carlo (MCMC) approaches to monophyly tests and a combined MCMC and maximum likelihood approach to ancestral character state reconstructions. The MCMC framework provided confidence estimates for the reconstructions of relationships and ancestral character states, which formed the basis for tests of evolutionary hypotheses. Monophyly tests rejected all hypotheses that predicted any clustering of reproductive modes in extant taxa. In addition, a nearest-neighbor statistic could not reject the hypothesis that the vegetative reproductive mode is randomly distributed throughout the group. These results show that transitions between presence and absence of the vegetative reproductive mode within Porpidia s.l. occurred several times and independently of each other. Likelihood reconstructions of ancestral character states at selected nodes suggest that--contrary to previous thought--the ancestor to Porpidia s.l. already possessed the vegetative reproductive mode. Furthermore, transition rates are reconstructed asymmetrically with the vegetative reproductive mode being gained at a much lower rate than it is lost. A cautious note has to be added, because a simulation study showed that the ancestral character state reconstructions were highly dependent on taxon sampling. However, our central conclusions, particularly the higher rate of change from vegetative reproductive mode present to absent than vice versa within Porpidia s.l., were found to be broadly independent of taxon sampling.     

Visual fixation in the vegetative state: an observational case series PET study

Background

Assessment of visual fixation is commonly used in the clinical examination of patients with disorders of consciousness. However, different international guidelines seem to disagree whether fixation is compatible with the diagnosis of the vegetative state (i.e., represents "automatic" subcortical processing) or is a sufficient sign of consciousness and higher order cortical processing.

Methods

We here studied cerebral metabolism in ten patients with chronic post-anoxic encephalopathy and 39 age-matched healthy controls. Five patients were in a vegetative state (without fixation) and five presented visual fixation but otherwise showed all criteria typical of the vegetative state. Patients were matched for age, etiology and time since insult and were followed by repeated Coma Recovery Scale-Revised (CRS-R) assessments for at least 1 year. Sustained visual fixation was considered as present when the eyes refixated a moving target for more than 2 seconds as defined by CRS-R criteria.

Results

Patients without fixation showed metabolic dysfunction in a widespread fronto-parietal cortical network (with only sparing of the brainstem and cerebellum) which was not different from the brain function seen in patients with visual fixation. Cortico-cortical functional connectivity with visual cortex showed no difference between both patient groups. Recovery rates did not differ between patients without or with fixation (none of the patients showed good outcome).

Conclusions

Our findings suggest that sustained visual fixation in (non-traumatic) disorders of consciousness does not necessarily reflect consciousness and higher order cortical brain function.

     

The Subcellular Localization of Isoperoxidases in Capsicum annuum Leaves and their Different Expression in Vegetative and Flowered Plants

The subcellular localization of leaf peroxidases (EC 1.11.1.7)and their expression in vegetative and flowered plants has beenstudied in Capsicum annuum (var. annuum) in order to assesswhether the expression of new peroxidase isoenzymes can characterizethe floral state which determines the beginning of reproductivedevelopment. The results showed that floral development is accompaniedby a significant increase in the level of soluble (non-sedimentable)leaf peroxidase, independently of leaf position along the internodes,and therefore independently of the leaf age. An analysis ofthe leaf peroxidase isoenzyme patterns along the internodesfor vegetative and flowered plants shows that the increase inperoxidase activity is due to a general increase in the activityof all the pre-existing peroxidase isoenzymes, although isoenzymeB₂ and, especially, isoenzyme A₁ showed a distinctive and majorincrease in activity. These two isoenzymes are mainly ionically-boundto cell walls, probably in equilibrium with the same isoenzymesmoving freely in the cell-wall free spaces. The differs fromother peroxidase isoenzymes, such as isoperoxidase B₆, whichis mainly located in the covalently-bound cell-wall fractionand in mesophyll vacuoles. These results are discussed in thelight of a possible role of cell wall peroxidases as markersof the floral state in Capsicum annuum morphogenesis.Copyright1993, 1999 Academic Press Capsicum, floral state, leaf peroxidases, subcellular localization, vegetative state     

Overexpression of EVE1, a novel ubiquitin family protein, arrests inflorescence stem development in Arabidopsis

In Arabidopsis, inflorescence stem formation is a critical process in phase transition from the vegetative to the reproductive state. Although inflorescence stem development has been reported to depend on the expression of a variety of genes during floral induction and repression, little is known about the molecular mechanisms involved in the control of inflorescence stem formation. By activation T-DNA tagging mutagenesis of Arabidopsis, a dominant gain-of-function mutation, eve1-D (eternally vegetative phase1-Dominant), which has lost the ability to form an inflorescence stem, was isolated. The eve1-D mutation exhibited a dome-shaped primary shoot apical meristem (SAM) in the early vegetative stage, similar to that seen in the wild-type SAM. However, the SAM in the eve1-D mutation failed to transition into an inflorescence meristem (IM) and eventually reached senescence without ever leaving the vegetative phase. The eve1-D mutation also displayed pleiotropic phenotypes, including lobed and wavy rosette leaves, short petioles, and an increased number of rosette leaves. Genetic analysis indicated that the genomic location of the EVE1 gene in Arabidopsis thaliana corresponded to a bacterial artificial chromosome (BAC) F4C21 from chromosome IV at ～17cM which encoded a novel ubiquitin family protein (At4g03350), consisting of a single exon. The EVE1 protein is composed of 263 amino acids, contains a 52 amino acid ubiquitin domain, and has no glycine residue related to ubiquitin activity at the C-terminus. The eve1-D mutation provides a way to study the regulatory mechanisms that control phase transition from the vegetative to the reproductive state.     

Effect of the short-term exposure to negative air ions on individuals with vegetative disorders

The humans with vegetative disorder have been under the short-time exposition to negatively charged air ions, produced by Tchizhevski aeroionizer "Elion-132". The state of vegetative nervous system and some other physiological systems and organs of treated humans were estimated by acupuncture R. Voll method. It was found, that treatment by negatively charged air ions leads to the normalization of the state of mentioned above acupuncture points in the most (87%) of the tested humans with vegetative disorder. In 13% of tested persons these indicators became worse after this procedure. In the each case the changes in the state of different acupuncture points had the single-directed character. The suggestion was made, that vegetative nervous system plays the important role in the formation of organism's integrated reaction to the action of negatively charged air ions.     

Changes in volume,surface area,and frequency of nuclear pores on the vegetative nucleus of tobacco pollen in fresh,hydrated, and activated conditions

The vegetative nucleus (VN) of Nicotiana tabacum L. has been qualitatively and quantitatively studied in fresh, hydrated, and activated pollen. Techniques included the use of optical sectioning by confocal scanning laser microscopy to obtain volume and surface area measurements, and stereoscopic pairs; and freeze-etch electron microscopy to estimate the frequency of nuclear pores per m² in the vegetative nucleus. Several morphological changes were observed to occur in pollen grain nuclei during the early processes of tube growth. In freshly dehisced pollen grain, the vegetative and generative nuclei were side by side, but following hydration and activation of the grain, the elongated generative nucleus became partially surrounded by the vegetative nucleus. It was found that during hydration, the surface area of the vegetative nucleus increased and there was a decrease in the frequency of nuclear pores. The calculated total number of pores remained similar. After activation and pollen-tube growth, the vegetative nucleus retained the same surface area as in the hydrated state but the frequency of nuclear pores decreased; therefore, the calculated total number of pores was significantly lowered. When considered alongside complementary biochemical data, these morphological results indicate that RNA production in the vegetative nucleus decreases following germination.Abbreviations VN vegetative nucleus (nuclei) - GN generativenucleus - GC generative cell - CSLM confocal scanning laser microscope We acknowledge research support by the Biotechnology Action Programm of the Commission of European Communities, and CNR for the fellowship awarded to Dr. Wagner. We would also like to thank Mrs. C. Faleri for the expert technical help.     

西藏特有竹子Arundinaria macclureana的名实辨正

Arundinaria macclureana是在现代植物学中根据在西藏采集的标本描述的第一个竹子。其模式标本是1938年采集的,但只有花枝,没有地下茎、秆箨等重要特征。尽管如此,该种还成为了新属Borinda的模式种。在研究了其模式标本后,使本文第一作者联想起1991年在藏东南采集的西藏箭竹（Fargesia setosa）。西藏箭竹的模式标本采集于1977年,但只有营养体,没有花枝。在对比研究两个名称的模式后,确认二者实为同种。经与共同作者一起讨论,认为其正确学名为Fargesia macclureana,但该种所在的筱竹属群的关系还有待进一步的研究。     

The Ethics of Elective (Non-Therapeutic) Ventilation

Elective ventilation (EV) is ventilation applied, not in the interest of patients, but in order to secure transplantable organs. It carries with it a small risk that patients who would otherwise have died will survive in a persistent vegetative state. Is EV ever justifiable? We argue: (1) The only thing which can justify exposing patients to risk not taken for their benefit is their consent, and we cannot rely on implied consent or third party consent in the case of EV. Thus, absent explicit consent of patients, EV is not justifiable. (2) It is not clear that explicit consent should be sought, or where it is offered honoured, given the potential EV has for deterring organ donors and causing stress to staff and families.     

The Identity of an Endemic Tibetan Bamboo,Arundinaria macclureana ( Gramineae,Bambusoideae)

Arundinaria macclureana Bor was the first bamboo described in modern taxonomy based on Tibetan material. Since the type bears only flowering branches without critical vegetative characteristics such as rhizomes and culm- sheaths, its identity has long been doubtful. Even so, it provides the type of a newly created genus, Borinda. By checking the type specimens of A1 macclureana as well as the type of Fargesia setosa T. P. Yi, which is a species only known by its vegetative state, and by collecting in the field, a conclusion is reached that these two entities are conspecific. Fargesia macclureana, a name published in less- received literature is the correct name for this endemic Tibetan bamboo, although re- evaluation of the relationships within the Thamnocalamus group is needed.     

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.     

The role of the parasympathetic nervous system in the regulation of microsomal monooxygenase activity in the liver of rats

The effect of vegetative nervous system activation or depression (subdiaphragmatic vagotomy, atropine, proserine and acetylcholine treatments) on the hepatic microsomal enzymes activities has been studied on Wistar male rats. It is found, that hepatic denervation and atropine treatment decreased cytochrome P450 content and aniline hydroxylase activity. Proserine and acetylcholine induced an opposite effect. It is considered that these different changes in the microsomal enzyme activities with variations in the vegetative nervous system state have proved the nervous control of these processes.