[Diagnosis of vegetative state as a basis for medical treatment on the borderline between life and death]. / Diagnostiek van vegetatieve toestand als basis voor medisch handelen op de grens van leven en dood.

The term 'vegetative state' is most appropriate for the state which develops when patients open their eyes after a comatose phase, without regaining consciousness. The definition and the diagnostic criteria from the Multi Society Task Force on Persistent Vegetative State are usable for the clinical practice in the Netherlands. The vegetative state must be differentiated from coma, locked-in syndrome and minimally conscious state. A systematic, multidisciplinary approach under the direction of a physician is key to diagnosing vegetative state. To this end, a clinical assessment is recommended with reassessment and verification of the diagnosis at appropriate moments. Careful observation remains the fundamental to the diagnosis.

Acute behavioural disturbances related to imaging studies and outcome in mild-to-moderate head injury.

The frequency of behavioural disturbances early after injury in relation to outcome was prospectively investigated in a series of 67 patients with mild-to-moderate head injury (as defined by GCS on admission). In more than half of the patients, behavioural disturbances were observed. Restlessness occurred in 40% of patients, whereas agitation was seen in 19% of patients. In all patients, restlessness and agitation disappeared before resolution of PTA. In multiple regression analysis, restlessness and PTA were found to be separate factors in predicting outcome. On imaging studies, twice as many lesions were seen in patients with restlessness and agitation (81% compared to 39%), mainly localized in the frontotemporal region. In two thirds of patients with early behavioural disturbances, residual emotional and cognitive impairments were seen 1 year after injury. This study suggests that behavioural disturbances in the early phase after injury are related to frontotemporal lesions and lends support for the view of the existence of a separate profile of patient behaviour in mild-to-moderate head injury.

Computed tomography and magnetic resonance imaging in mild to moderate head injury: early and late imaging related to outcome.

Serial magnetic resonance imaging (MRI) and computed tomographic (CT) studies were performed in mild to moderate head injury to evaluate whether early and late imaging have additional value in predicting outcome in this category of patients. During 1-year follow-up of a series of 67 patients, a CT scan on admission was performed together with MRI studies within 1 to 3 months and 6 to 12 months after injury. With CT, intracranial lesions were seen in 62% of patients compared with 44% with early and 19% with late MRI, located predominantly in the frontal and temporal regions. More than half of the lesions revealed with CT resulted in focal atrophy on MRI. Outcome was found to be worse in patients with edema and lesions on CT. Likewise, abnormalities detected with MRI were associated with poor outcome scores. In multiple regression analysis, only lesions in the frontal regions detected with early MRI were found to be predictive of outcome. With late MRI, only focal atrophy in the frontotemporal regions was found to be predictive of outcome. The findings in this study suggests that MRI studies may be valuable for predicting long-term outcome in patients with mild to moderate HI.

One year outcome in mild to moderate head injury: the predictive value of acute injury characteristics related to complaints and return to work.

OBJECTIVES: To determine the prognostic value of characteristics of acute injury and duration of post-traumatic amnesia (PTA) for long term outcome in patients with mild to moderate head injury in terms of complaints and return to work. METHODS: Patients with a Glasgow coma score (GCS) on admission of 9-14 were included. Post-traumatic amnesia was assessed prospectively. Follow up was performed at 1, 3, 6, and 12 months after injury. Outcome was determined by the Glasgow outcome scale (GOS) 1 year after injury and compared with a more detailed outcome scale (DOS) comprising cognitive and neurobehavioural aspects. RESULTS: Sixty seven patients were included, mean age 33.2 (SD 14.7) years and mean PTA 7.8 (SD 7.3) days. One year after injury, 73% of patients had resumed previous work although most (84%) still reported complaints. The most frequent complaints were headache (32%), irritability (34%), forgetfulness and poor concentration (42%), and fatigue (45%). According to the GOS good recovery (82%) or moderate disability (18%) was seen. Application of the DOS showed more cognitive (40%) and behavioural problems (48%), interfering with return to work. Correlation between the GOS and DOS was high (r=0.87, p<0.01). Outcome correlated with duration of PTA (r=-0.46) but not significantly with GCS on admission (r=0.19). In multiple regression analysis, PTA and the number of complaints 3 months after injury explained 49% of variance on outcome as assessed with the GOS, and 60% with the DOS. CONCLUSIONS: In mild to moderate head injury outcome is determined by duration of PTA and not by GCS on admission. Most patients return to work despite having complaints. The application of a more detailed outcome scale will increase accuracy in predicting outcome in this category of patients with head injury.

Lightning stroke and neuropsychological impairment: cases and questions.

OBJECTIVE: To objectify neuropsychological impairments in survivors of lightning stroke with lasting complaints about poor concentration and inability to divide their attention. DESIGN: A series of six cases of lightning stroke were studied. All patients had lost consciousness and reported amnesia of varying length. Assessment took place between one and four years after injury, ensuring that their neurological state had stabilised. They were tested with a neuropsychological battery with an emphasis on attention and memory. Personality and emotional reaction to the accident were assessed with questionnaires and a lightning fear scale. Complaints were recorded by means of a trauma complaints list including 10 questions on symptoms of the post-traumatic stress disorder. RESULTS: Patients reported fatigue and lack of energy as their main complaints. In addition, poor concentration, irritability, and emotional lability were mentioned often. Neuropsychological tests disclosed mild impairments in memory, attention, and visual reaction times. Two patients could be classified as depressed, and one of these also showed convincing signs of the post-traumatic stress disorder. CONCLUSION: As the lasting complaints and impairments could not be explained, for all six cases, as resulting from head injury concomitant with lightning stroke, cerebral hypoxia or a post-traumatic stress syndrome, it is concluded that lightning stroke can result in subtle cognitive impairments. It is speculated that most complaints of these survivors are caused by a vegetative dysregulation, a disorder that has often been noted in the literature on the effects of electrical injury to the nervous system. Such a dysregulation might cause both the main complaint of fatigue and the mild cognitive impairments identified with the present test battery.

Co-registration of PET and MRI in different courses of MS using Cobalt-55 as a Calcium-tracer.

Multiple Sclerosis (MS) is an auto-immune central nervous system (CNS) inflammation. At this moment, MRI is the most accurate paraclinical test in MS to monitor disease activity, although poorly correlated with clinical impairment. PET using Co-55 as a Ca-tracer may visualize Co-transport across the neuronal membrane, Ca-mediated inflammatory processes and passive leakage through a breach in the blood-brain barrier. Co-registration of MRI and Co-PET may actually allow identification of clinically active lesions. MRI and Co-PET were performed as described elsewhere. Based on a statistic parametric mapping (SPM-96)-software package, MRI and Co-PET were superimposed. A semi-automated technique was used to count the MS-lesions. We included four groups of eight MS-patients with relapsing-remitting (RR), primary progressive (PP), progressive relapsing (PR) and secondary progressive (SP) courses and eight healthy volunteers. MS was assessed in terms of impairment using Kurtzke's Expanded Disability Status Scale (EDSS) and Scripps Neurological Rating Scale (NRS). Co-PET displayed focal uptake throughout the MS brain, both in the grey and white matter. All four patients groups (as compared to controls) demonstrated a more inhomogeneous distribution of Co-spots with a tendency to show clustering, most evident in RR-MS. SPM-analysis revealed an essentially different distribution pattern of MS spots on MRI and Co-PET. (Merging of) Co-PET and MRI may eventually form complementary tools for identifying clinically relevant lesions, thus providing a more reliable secondary outcome measure in MS.

Positron emission tomography in primary brain tumours using cobalt-55.

Primary brain tumours are usually assessed by computed tomography (CT) and magnetic resonance imaging (MRI), sometimes in conjunction with positron emission tomography (PET). We used cobalt-55 (55Co) as a calcium (Ca) tracer to visualize decaying tumour tissue, based on the fact that Ca-influx is essential in both cell death and leukocyte activation. Net 55Co uptake may be the result of cell decay, leukocyte infiltration, (re)perfusion and the pharmacological profile of 55Co. Three patients with primary malignant brain tumours (first presentation) were studied with CT, MRI and Co-PET after the intravenous administration of 0.5 mCi 55Co. Histopathological diagnosis was obtained by biopsy or resection. Co-PET demonstrated each of the brain tumours and showed good topographical agreement with CT and MRI. Co-PET provided additional detail as to the site and size of the necrotic core and the perinecrotic rim of decaying tumour. The 55Co uptake indices varied between 2.6 and 5.3. 55Co demonstrated uptake in decaying tissue, irrespective of the integrity of the blood-brain barrier. Neither necrotic nor viable tumour tissue showed affinity for 55Co. Since 55Co is readily applicable to both PET and single photon emission tomography (SPET), differences in the uptake mechanism and functional significance of the 55Co tracer are discussed in relation to 201Tl SPET. We present a (limited) pilot series of three patients to forward the claim of this new functional technique in nuclear neurology.

Cobalt-55 positron emission tomography in ischemic stroke.

After acute cerebral stroke, the (peri-) infarct tissue is characterized by calcium (Ca)-mediated neuronal damage and inflammatory processes. Monitoring Ca-mediated damage using the isotope cobalt-55 (Co) as a Ca-tracer may enable PET-imaging of this tissue. Since the fate of (peri-) infarct tissue determines clinical outcome, Co-PET may have prognostic value in stroke. Six stroke patients were examined with Co-PET, MRI and a middle cerebral artery (mca) stroke scale (Orgogozo). In every patient, specific Co-accumulation in the appropriate brain region was seen, irrespective of the integrity of the blood-brain barrier. This pilot study suggests Co-PET as a diagnostic tool in stroke, which may provide additional information on the clinical outcome. Validation of method in larger patient series is necessary.

The effect of gonadectomy on the clinical course of chronic experimental allergic encephalomyelitis.

Experimental allergic encephalomyelitis (EAE) is an animal model for the human neurological disease multiple sclerosis (MS). Upon immunization with guinea pig spinal cord under a low dose of Cyclosporin A, male Lewis rats develop a severe chronic (relapsing) course of EAE (CR-EAE). By contrast, female Lewis rats develop a more mitigated course of EAE: only half of the female rats develop relapses. To further analyze factors determining this sexual dimorphism in the course of EAE, in the present study male and female Lewis rats were gonadectomized before induction of CR-EAE. Now both male and female rats all developed a severe chronic course of EAE, showing extensive pathological changes in the CNS. In the female sham-gonadectomy (control) group only one third of the rats developed relapses. These female rats only showed mild pathological changes in the CNS. In the male sham-gonadectomy (control) group all rats developed relapses of EAE and showed extensive pathological changes in the CNS. From these data we conclude that the presence of the ovaries (partially) protects female rats against relapses of EAE and CNS injury. Presence or absence of the testes apparently makes no difference on the course of EAE. We propose that sex hormones produced in the ovaries protect female rats against relapses of EAE and underlying CNS injury.

The fronto-temporal component in mild and moderately severe head injury.

The history of the identification of the so-called (fronto-)temporal lobe contusion is reviewed. Treatment of minor head injuries actually starts with the right diagnosis. Injuries of the temporal lobe, characterized by a comparatively long period of post-traumatic amnesia should be distinguished from minor head injuries (cerebral concussion). Treatment of minor head injuries should include good information and explanation of the medical aspects of minor head injuries to prevent the so called post-concussional syndrome, with long lasting sequelae. Changes of neurotransmitter metabolism in various kinds of head injuries have been known for many years. Treatment with precursors of neurotransmitters (particularly physostigmine and L-DOPA) can be useful in unconsciousness and amnestic syndromes.

Cobalt-55 positron emission tomography in traumatic brain injury: a pilot study.

Traumatic brain injury is usually assessed with the Glasgow coma scale (GCS), CT, or MRI. After such injury, the injured brain tissue is characterised by calcium mediated neuronal damage and inflammation. Positron emission tomography with the isotope cobalt-55 (Co-PET) as a calcium tracer enables imaging of affected tissue in traumatic brain injury. The aim was to determine whether additional information can be gained by Co-PET in the diagnosis of moderate traumatic brain injury and to assess any prognostic value of Co-PET. Five patients with recent moderately severe traumatic brain injury were studied. CT was performed on the day of admission, EEG within one week, and MRI and Co-PET within four weeks of injury. Clinical assessment included neurological examination, GCS, neuropsychological testing, and Glasgow outcome scale (GOS) after one year. Co-PET showed focal uptake that extended beyond the morphological abnormalities shown by MRI and CT, in brain regions that were actually diagnosed with EEG. Thus Co-PET is potentially useful for diagnostic localisation of both structural and functional abnormalities in moderate traumatic brain injury.

Cobalt-55 positron emission tomography in relapsing-progressive multiple sclerosis.

Multiple sclerosis (MS) is an immune-mediated disease of the white matter in the brain that can have a progressive course. However, the progression of relapsing-remitting (RR) MS into relapsing-progressive (RP) MS might represent a more fundamental change in disease activity, i.e. decay of vulnerable neurons and oligodendrocytes. In RP-MS, this may imply that the major loss of brain tissue structure is caused by a combination of demyelination and cellular loss, both of which are likely to cause disability in MS. We used the PET isotope cobalt-55 (Co) as a calcium (Ca) tracer to visualize brain tissue damage, based on the fact that Ca influx is essential in both cell death and T-lymphocyte activation in MS. The aim of this study was to determine whether Co-PET detects any RP-MS lesions and, if so, to assess any correlation with the progression rate (PR) of the disease and with MS lesions as detected by MRI. Seven RP-MS patients (Poser) with EDSS > 4.0 (Kurtzke) and 7 healthy controls underwent MRI (Miller, Barkhof) and Co-PET. Comparison of both image modalities was made by merging. Co-PET lesion frequency was assessed and correlated with the PR of the disease. Co-PET demonstrated significantly more lesions in the MS brain than in the healthy brain, both periventricular and cortical. Every single MRI lesion could be retrieved as a Co-PET lesion. The Co-PET lesion frequency correlated significantly with PR. Our pilot study possibly suggests Co-PET as a tool in estimating disease activity in RP-MS.(ABSTRACT TRUNCATED AT 250 WORDS)

Cobalt-57 SPET in relapsing-progressive multiple sclerosis: a pilot study.

Multiple sclerosis (MS) is predominantly a progressive immune-mediated disease of the white matter in the brain. We used single photon emission tomography (SPET) and cobalt-57 (57Co) as a calcium (Ca) analogue to visualize brain tissue damage, based on the fact that Ca influx occurs in both cell death and T-lymphocyte activation in MS. The aim of this study was to determine if 57Co-SPET detects MS lesions and, if so, to compare this with clinical data on the patient. Five MS patients underwent neurological examination including Expanded Disability Status Scale (EDSS) assessment and 57Co-SPET, using a single-headed camera. All available data were compared. The lesions were recognized as areas of increased signal intensity, although the poor count rate did not allow any statistical quantification. A relationship between one 57Co-SPET parameter (cobalt plaque load) and EDSS was demonstrated. In conclusion, this pilot study suggests that 57Co-SPET using a single-headed camera is not an appropriate imaging modality in MS. To obtain a more favourable signal-to-noise ratio, the use of a multi-headed camera, the administration of a higher activity of 57Co and a longer acquisition time are recommended. Validation of this method among a larger group of patients and a comparison with healthy volunteers is needed.

A study of multiple sclerosis patients with magnetic resonance spectroscopic imaging.

Eleven patients with clinically definite MS and three healthy controls were investigated by magnetic resonance spectroscopic imaging. The data sets were analysed for all voxels containing white matter only. We classify these voxels in healthy controls as normal white matter (NWM), and in MS patients as normal-appearing white matter unaffected by MS lesions (NAWM) or white matter affected by MS lesions. The spectra belonging to the voxels were analysed for content of cholines, creatines and N-acetylaspartate (NAA), and compared as a group. It was found that lesions differ from white matter in chemical composition and, moreover, that normal-appearing white matter differs from healthy white matter. Specifically, levels of NAA are lower in patients. There seems to be a linear relation between the composition of white matter and the expanded disability status scale value for the patient. The presence of lactate could not be established, and no unambiguous differences were found between patients with relapsing-remitting and relapsing-progressive disease.

Correlation between magnetic resonance imaging and clinical parameters in multiple sclerosis.

In this study, the course of 60 consecutive multiple sclerosis patients (relapsing-remitting (RR), relapsing-progressive (RP), primary-progressive (PP)) was compared with the number and mean size of the lesions as well as the total load of the lesions as shown on magnetic resonance imaging (MRI). Significant differences were found between RR and RP patients in total load and number of lesions. Between RR and PP patients statistical significant differences were found in total load, number and size of the lesions when correlated with EDSS. Between RP and PP patients statistical differences were found in total load and size of the lesions on MRI. Patients with a relapsing course of the MS (RR or RP) had a higher total load and size of the lesions than PP patients. The total load, number and size of the lesions corrected for EDSS were also lower compared to relapsing patients. Factor analysis showed a correlation between clinical progression rate and progression rate of MRI abnormalities. No correlation between EDSS and total load of MRI lesions could be found. In conclusion, this study confirms the results of previous studies of differences between MRI scans of patients with a different course of MS.

On the pathogenesis of multiple sclerosis. A revised model of the cause(s) of multiple sclerosis, especially based on epidemiological data.

Data from an epidemiological study are used to analyse the course of multiple sclerosis. It could be proved that the course of MS is not as haphazard as was often supposed. In general the course is described as being a chronic progressive one, in the majority of patients preceded by a relapsing-remitting period. In contrast to the relapsing-remitting phase the chronic progressive phase of the course does not show marks of being an autoimmune process. From recent data obtained by MRI and NMR spectroscopy it can be concluded that the chronic progression of handicaps in multiple sclerosis is related to neuronal and axonal damage. The relation between these different pathogenetic processes should be the aim of further research.

[MRI and MRS diagnosis. Application in multiple sclerosis patients and research animals with experimental allergic encephalomyelitis]. / MRI- en MRS-onderzoek. Toepassing bij patiënten met multipele sclerose en proefdieren met experimentele allergische encephalomyelitis.

MR imaging and spectroscopy offer a noninvasive way to observe lesions and biochemical changes, respectively, that may provide new insights into demyelinating diseases such as MS. Although the role and importance of some of the metabolites, such as choline and N-acetyl aspartate in brain function and disease are not fully understood, the specificity of these changes may provide information about the stage and reversibility of the brain lesions. Animal studies are particularly insightful when MR spectroscopic signals are correlated with histologic and biochemical techniques. Clinical application of spectroscopic imaging could arise from the capability to differentiate between early lesions that might respond to therapy and older irreversible lesions. Although more data need to be obtained, MR spectroscopy shows promise for monitoring progression of MS and evaluating therapy.