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1/37. Impaired effective cortical connectivity in vegetative state: preliminary investigation using PET.

    Vegetative state (VS) is a condition of abolished awareness with persistence of arousal. awareness is part of consciousness, which itself is thought to represent an emergent property of cerebral neural networks. Our hypothesis was that part of the neural correlate underlying VS is an altered connectivity, especially between the associative cortices. We assessed regional cerebral glucose metabolism (rCMRGlu) and effective cortical connectivity in four patients in VS by means of statistical parametric mapping and [18F]fluorodeoxyglucose-positron emission tomography. Our data showed a common pattern of impaired rCMRGlu in the prefrontal, premotor, and parietotemporal association areas and posterior cingulate cortex/precuneus in VS. In a next step, we demonstrated that in VS patients various prefrontal and premotor areas have in common that they are less tightly connected with the posterior cingulate cortex than in normal controls. These results provide a strong argument for an alteration of cortical connectivity in VS patients.
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2/37. Cerebral arteriovenous malformation in pregnancy: presentation and neurologic, obstetric, and ethical significance.

    Cerebral arteriovenous malformations infrequently complicate pregnancy. We sought to determine the neurologic, obstetric, and ethical significance of such malformations. We present the clinical course of 2 pregnant women with arteriovenous malformations who experienced cerebral hemorrhage and a loss of capacity for decision making. We also review the neurologic and obstetric significance of arteriovenous malformations in pregnancy. Various treatment options with concern for pregnancy and the prognosis for arteriovenous malformations are outlined. The ethical issues involved for pregnant patients whose decisional capacity is compromised as a result of cerebral injury are explored. A review of persistent vegetative state and brain death (death by neurologic criteria) occurring in pregnancy allows us to explore many issues that are applicable to decisionally incapacitated but physiologically functioning pregnant women. We outline a document, the purpose of which is to obtain advance directives from pregnant women regarding end-of-life decisions and to appoint a surrogate decision maker. We believe that evaluation and treatment of the arteriovenous malformation may be undertaken without regard for the pregnancy and that the pregnancy should progress without concern for the arteriovenous malformation.
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3/37. Assessment of minimally responsive patients: clinical difficulties of single-case design.

    Improved management of very severely central nervous system (CNS) injured individuals has given rise to an increasing number of patients in a minimally responsive state. There is a growing literature stressing the importance of accurately determining these patients' level of cognitive functioning and its role in appropriate rehabilitation and long term management. The single case design model appears to be the intervention of choice, with its great flexibility and tailored approach to each individual case. The recent literature has focused on the technical aspects of the assessment, offering clear procedural guidelines. Unfortunately, there is a dearth of information about clinical factors such as clinical setting and family involvement, which may interfere with or prevent a planned intervention. The case of MT is presented, who was the subject of a single case intervention 9 months following an extremely severe traumatic brain injury. The planned intervention was to examine the effects of a psychostimulant on MT's level of arousal, in order to improve his participation in the rehabilitation programme. Beyond the results (which were equivocal), the clinical difficulties in conducting single case study designs in rehabilitation are discussed. Ways to minimize these difficulties are proposed.
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4/37. Words without mind.

    A woman (LR), unconscious for 20 years, spontaneously produces infrequent, isolated words unrelated to any environmental context. Fluorodeoxy-glucose-positron emission tomography (FDG-PET) imaging coregistered with magnetic resonance imaging (MRI) revealed a mean brain metabolism equivalent to deep anesthesia. Nevertheless, PET imaging demonstrated islands of modestly higher metabolism that included Broca's and Wernicke's areas. Functional brain imaging with magnetoencephalographic (MEG) imaging, a technique providing a temporal resolution of better than 1 msec, identified preserved dynamic patterns of spontaneous and evoked brain activity in response to sensory stimulation. Specifically, we examined spontaneous gamma-band activity (near 40 Hz) and its reset or modification during early auditory processing, a measure that correlated with human perception of sensory stimuli (Joliot, Ribary, & Llinas, 1994). Evidence of abnormal and incomplete gamma-band responses appeared in the left hemisphere only in response to auditory or somatosensory stimulation. MEG single-dipole reconstructions localized to the auditory cortex in the left hemisphere and overlapped with metabolically active regions identified by FDG-PET. The observation demonstrates that isolated neuronal groups may express well-defined fragments of activity in a severely damaged, unconscious brain. The motor fixed-action pattern character of her expressed words supports the notion of brain modularity in word generation.
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5/37. Fatal fat embolism syndrome: a case report.

    Fat embolism syndrome is a dire complication of long bone trauma. It is usually associated with neurological, hematological and respiratory involvement, the latter being the major cause of death. We present a case of severe fat embolism syndrome occurring 3 hours after a long bone injury, leading to permanent vegetative state and death without any respiratory signs. The diagnosis was confirmed by cytology of the bronchoalveolar lavage fluid. Clinical presentation of the puzzling fat embolism syndrome and diagnostic tests in suspected fat embolism syndrome are reviewed.
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6/37. Subacute central nervous system degeneration in a child: an unusual manifestation of ifosfamide intoxication.

    A 5-year-old child with desmoplastic small round-cell tumor was treated with a protocol of very-high-dose, short-term chemotherapy, containing HD-CAV (cyclophosphamide, doxorubicin, vincristine, and mesna), ifosfamide, and etoposide. Two days after the initiation of ifosfamide, he exhibited new-onset lethal encephalopathy manifested by subacutely progressive cerebellar and then temporal and frontocortical degeneration leading to a vegetative state and eventually to death. A full work-up, including brain biopsy, was negative, excluding infections and metabolic or vascular causes. ifosfamide is known to be capable of causing acute encephalopathy that can be severe but is generally reversible. This child showed a very atypical progressive, lethal course of ifosfamide toxicity. The possibility of this complication should be considered when high-dose ifosfamide treatment is planned for children.
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7/37. Residual cerebral activity and behavioural fragments can remain in the persistently vegetative brain.

    This report identifies evidence of partially functional cerebral regions in catastrophically injured brains. To study five patients in a persistent vegetative state (PVS) with different behavioural features, we employed [(18)F]fluorodeoxyglucose-positron emission tomography (FDG-PET), MRI and magnetoencephalographic (MEG) responses to sensory stimulation. Each patient's brain expressed a unique metabolic pattern. In three of the five patients, co-registered PET/MRI correlate islands of relatively preserved brain metabolism with isolated fragments of behaviour. Two patients had suffered anoxic injuries and demonstrated marked decreases in overall cerebral metabolism to 30-40% of normal. Two other patients with non-anoxic, multifocal brain injuries demonstrated several isolated brain regions with relatively higher metabolic rates, that ranged up to 50-80% of normal. Nevertheless, their global metabolic rates remained <50% of normal. MEG recordings from three PVS patients provide clear evidence for the absence, abnormality or reduction of evoked responses. Despite major abnormalities, however, these data also provide evidence for localized residual activity at the cortical level. Each patient partially preserved restricted sensory representations, as evidenced by slow evoked magnetic fields and gamma band activity. In two patients, these activations correlate with isolated behavioural patterns and metabolic activity. Remaining active regions identified in the three PVS patients with behavioural fragments appear to consist of segregated corticothalamic networks that retain connectivity and partial functional integrity. A single patient who suffered severe injury to the tegmental mesencephalon and paramedian thalamus showed widely preserved cortical metabolism, and a global average metabolic rate of 65% of normal. The relatively high preservation of cortical metabolism in this patient defines the first functional correlate of clinical- pathological reports associating permanent unconsciousness with structural damage to these regions. The specific patterns of preserved metabolic activity identified in these patients do not appear to represent random survivals of a few neuronal islands; rather they reflect novel evidence of the modular nature of individual functional networks that underlie conscious brain function. The variations in cerebral metabolism in chronic PVS patients indicate that some cerebral regions can retain partial function in catastrophically injured brains.
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8/37. Detecting residual cognitive function in persistent vegetative state.

    Despite converging agreement about the definition of persistent vegetative state, recent reports have raised concerns about the accuracy of diagnosis in some patients, and the extent to which, in a selection of cases, residual cognitive functions may remain undetected. Objective assessment of residual cognitive function can be extremely difficult as motor responses may be minimal, inconsistent, and difficult to document in many patients, or may be undetectable in others because no cognitive output is possible. Here we describe strategies for using H(2)(15)O positron emission tomography activation studies to study covert cognitive processing in patients with a clinical diagnosis of persistent vegetative state. Three cases are described in detail. Of these, two exhibited clear and predicted regional cerebral blood flow responses during well-documented activation paradigms (face recognition and speech perception) which have been shown to produce specific, robust and reproducible activation patterns in normal volunteers. Some months after scanning, both patients made a significant recovery. In a third case, blood flow data were acquired during a speech perception task, although methodological difficulties precluded any systematic interpretation of the results. In spite of the multiple logistic and procedural problems involved, these results have major clinical and scientific implications and provide a strong basis for the systematic study of possible residual cognitive function in patients diagnosed as being in a persistent vegetative state.
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9/37. Emotional adjustment following cognitive recovery from 'persistent vegetative state': psychological and personal perspectives.

    Previously, the cognitive recovery of a 26 year old woman, Kate, who developed a severe encephalomyelopathy and was in a 'minimally conscious/persistent vegetative state' for 6 months was reported. After 6 months, Kate began to respond to her environment and, at 2 years post-illness, neuropsychological assessment indicated that Kate was functioning within the normal range on tests of general intellectual functioning, executive functioning and most memory functions (with the exception of visual recognition memory). Although Kate has a severe dysarthria necessitating the use of a communication board and severe physical disabilities that require her to use a wheelchair, she has demonstrated an almost complete cognitive recovery and is among a tiny percentage of minimally conscious patients to do so. This single case report describes the emotional factors central to Kate's rehabilitation. Using a newly developed model of cognitive rehabilitation as a framework, the pivotal role that emotional and psychological factors played in Kate's adjustment to the consequences of her illness and the role of psychotherapeutic intervention in facilitating this adjustment are discussed.
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10/37. Re-evaluation of short latency somatosensory evoked potentials (P13, P14 and N18) for brainstem function in children who once suffered from deep coma.

    One of the major clinical features of brain death is deep coma. Therefore, we re-evaluated retrospectively electrophysiological examinations of brainstem function in about 31 children who had once suffered from deep coma in order to reveal its pathophysiological characteristics. The patient age at coma ranged from 1 month to 10 years (mean 2 years 1 month). The electrophysiological examinations were performed, including any of short-latency somatosensory evoked potential (SSEP), brainstem auditory evoked potential (BAEP) and blink reflexes. We first compared results between the fair and poor prognostic groups, and then re-evaluated SSEP results on a few severely impaired patients with persistent vegetative state (PVS). Subsequently, SSEP clarified more specific findings for a deep coma condition than BAEP and blink reflex. A lack of P14, N18 and N20, and an amplitude reduction or vagueness of P13 in SSEP in these children strongly suggested high risk in their future neurological prognosis. In conclusion, electrophysiological examinations, especially SSEP (P13, P14 and N18), might be very useful in obtaining a long-term neurological prognosis after deep coma in children.
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