Ingmar Rosén

Models for studying long-term recovery following forebrain ischemia in the rat. 2. A 2-vessel occlusion model

ABSTRACT— A model is described in which transient ischemia is induced in rats anaesthetized with N2O:O2 (70:30) by bilateral carotid artery clamping combined with a lowering of mean arterial blood pressure to 50 mm Hg, the latter being achieved by bleeding, or by bleeding supplemented with administration of trimetaphan or phentolamine. By the use of intubation, muscle paralysis with suxamethonium chloride, and insertion of tail arterial and venous catheters, it was possible to induce reversible ischemia for long‐term recovery studies.

Brain Lactic Acidosis and Ischemic Cell Damage: 1. Biochemistry and Neurophysiology

This study explores the influence of severe lactic acidosis in the ischemic rat brain on postischemic recovery of the tissue energy state and neurophysiological parameters. Severe incomplete brain ischemia (cerebral blood flow below 5% of normal) was induced by bilateral carotid artery clamping combined with hypovolemic hypotension. We varied the production of lactate in the tissue by manipulating the blood glucose concentrations. A 30-min period of incomplete ischemia induced in food-deprived animals caused lactate to accumulate to 15–16 μmol g−1 in cortical tissue. Upon recirculation these animals showed: (1) a considerable recovery of the cortical energy state as evaluated from the tissue concentrations of phosphocreatine, ATP, ADP, and AMP; and (2) return of spontaneous electrocortical activity as well as of somatosensory evoked response (SER). In contrast, administration of glucose to food-deprived animals prior to ischemia caused an increase in tissue lactate concentration to about 35 μmol g−1. These animals did not recover energy balance in the tissue and neurophysiological functions did not return. In other experiments the production of lactate during 30 min of complete compression ischemia was increased from about 12 μmol g−1 (normoglycemic animals) to 20–30 μmol g−1 by preischemic hyperglycemia and. in separate animals, combined hypercapnia. The recovery of the cortical energy state upon recirculation was significantly poorer in hyperglycemic animals. It is concluded that a high degree of tissue lactic acidosis during brain ischemia impairs postischemic recovery and that different degrees of tissue lactic acidosis may explain why severe incomplete ischemia, in certain experimental models, is more deleterious than complete brain ischemia.

Predictive value of early continuous amplitude integrated EEG recordings on outcome after severe birth asphyxia in full term infants.

The background pattern in single channel amplitude integrated EEG recordings (aEEG) was recorded in 47 infants within the first six hours after birth to see if this could predict outcome after birth asphyxia. The aEEG background pattern during the first six hours of life was continuous and of normal voltage in 26 infants. All these infants survived; 25 were healthy, one had delayed psychomotor development. A continuous but extremely low voltage pattern was present in two infants, both of whom survived with severe handicap. Five infants had flat (mainly isoelectric) tracings during the first six hours of life; four died in the neonatal period, and one survived with severe neurological handicap. Burst-suppression pattern was identified in 14 infants, of whom five died, six survived with severe handicap, and three were healthy at follow up. The type of background pattern recorded within the first six postnatal hours in the aEEG tracings predicted outcome correctly in 43 of 47 (91.5%) infants. Use of aEEG monitoring can predict outcome, with a high degree of accuracy, after birth asphyxia, within the first six hours after birth. The predictive value of a suppression-burst pattern was, however, somewhat lower than the other background patterns. The aEEG seems to be a feasible technique for identifying infants at high risk of subsequent brain damage who might benefit from interventionist treatment after asphyxia.

Tubular repair of the median or ulnar nerve in the human forearm: a 5-year follow-up

The long-term outcome from silicone tube nerve repair was compared with the outcome from routine microsurgical repair in a clinical randomized prospective study, comprising 30 patients with median or ulnar nerve injuries in the distal forearm. Postoperatively, the patients underwent neurophysiological and clinical assessments of sensory and motor function regularly over a 5-year period. After 5 years there was no significant difference in outcome between the two techniques except that cold intolerance was significantly less severe with the tubular technique. In the total group there was ongoing improvement of functional sensibility throughout the 5 years after repair. It is concluded that tubular repair of the median and ulnar nerves is at least as good as routine microsurgical repair, and results in less cold intolerance.

Continuous amplitude-integrated electroencephalogram predicts outcome in hypothermia-treated cardiac arrest patients

Objective:To assess the prognostic value of continuous amplitude-integrated electroencephalogram in comatose survivors after cardiac arrest and treated with hypothermia. Design:Prospective observational study. Setting:General intensive care unit at a university hospital. Patients:Comatose patients after cardiac arrest and treated with hypothermia. Interventions:Patients were sedated and continuously monitored using an amplitude-integrated electroencephalogram. Monitoring was commenced on arrival in the intensive care unit and continued until recovery of consciousness, death, or 120 hrs after cardiac arrest. The amplitude-integrated electroencephalogram was interpreted together with the original electroencephalogram and analyzed without knowledge of the patients clinical status. The amplitude-integrated electroencephalogram patterns at start of registration and at normothermia and the transitions of the amplitude-integrated electroencephalogram patterns over time were correlated to outcome. Measurements and Main Results:A total of 111 consecutive patients were assessed; 11 patients were not included because of technical reasons and five were excluded because of death before normothermia. Ninety-five patients remained; 57 (60%) eventually regained consciousness, of whom 49 (52%) lived an independent life at 6 months. Thirty-one patients (33%) at start of registration and 62 patients (65%) at normothermia had a continuous electroencephalogram pattern, and this was strongly associated with recovery of consciousness (29/31 [90%] and 54/62 [87%]). A suppression-burst pattern was always transient and patients with suppression-burst at any time remained in coma until death. An initial flat pattern was registered in 47 patients, but this had no prognostic value. Electrographic status epilepticus was a common finding (26/95 patients [27%]) and two types of electrographic status epilepticus were identified: one developed from suppression-burst and one developed from a continuous background. Two patients from the latter group regained consciousness. Conclusions:Continuous amplitude-integrated electroencephalogram adds valuable early positive and negative prognostic information in comatose survivors after cardiac arrest. We identified two types of postanoxic electrographic status epilepticus, which is a novel finding with possible therapeutic implications.

Neuron-specific enolase correlates with other prognostic markers after cardiac arrest

Objective: Therapeutic hypothermia (TH) is a recommended treatment for survivors of cardiac arrest. Prognostication is complicated since sedation and muscle relaxation are used and established indicators of a poor prognosis are lacking. This prospective, observational study describes the pattern of commonly used prognostic markers in a hypothermia-treated cohort of cardiac arrest patients with prolonged coma. Methods: Among 111 consecutive patients, 19 died, 58 recovered, and 34 were in coma 3 days after normothermia (4.5 days after cardiac arrest), defined as prolonged coma. All patients were monitored with continuous amplitude-integrated EEG and repeated samples of neuron-specific enolase (NSE) were collected. In patients with prolonged coma, somatosensory evoked potentials (SSEP) and brain MRI were performed. A postmortem brain investigation was undertaken in patients who died. Results: Six of the 17 patients (35%) with NSE levels <33 μg/L at 48 hours regained the capacity to obey verbal commands. By contrast, all 17 patients with NSE levels >33 failed to recover consciousness. In the >33 NSE group, all 10 studied with MRI had extensive brain injury on diffusion-weighted images, 12/16 lacked cortical responses on SSEP, and all 6 who underwent autopsy had extensive severe histologic damage. NSE levels also correlated with EEG pattern, but less uniformly, since 11/17 with NSE <33 had an electrographic status epilepticus (ESE), only one of whom recovered. A continuous EEG pattern correlated to NSE <33 and awakening. Conclusions: NSE correlates well with other markers of ischemic brain injury. In patients with no other signs of brain injury, postanoxic ESE may explain a poor outcome.

Extracranial localization of intracranial interictal epileptiform activity using LORETA (low resolution electromagnetic tomography)

Besides the standard clinical methods of EEG waveshape analysis, mathematical models for reconstruction of dipolar sources from the digitized surface EEG have been introduced in epilepsy research. Although useful for localizing focal sources, these methods are inadequate for analyzing widespread epileptiform activity. A recently introduced alternative method called LORETA (low resolution electromagnetic tomography, Pascual-Marqui et al., 1994), directly computes the current distribution throughout the full brain volume, assuming that neighboring neuronal populations are simultaneously and synchronously activated. In mathematical terms the method selects the smoothest of all possible 3-dimensional current distributions, inherently introducing a certain amount of dispersion. In 7 patients, undergoing simultaneous EEG recording from 10 intracranial (subdural) and 22 extracranial electrodes, 111 subdural discharges (61 subtemporal and 50 lateral temporal) were identified. The exact time point of maximal intracranial activity was automatically identified, and the LORETA solution at that timepoint was computed from the surface EEG. Statistical comparison revealed significantly higher LORETA current density in the area corresponding to the subdurally recorded spike compared to other areas, and a more anterior and more medial LORETA location for subtemporal compared to lateral temporal spikes. This study indicates that the LORETA technique may become a useful method to localize electrical activity in the brain.

Silent seizures in sick infants in early life. Diagnosis by continuous cerebral function monitoring

ABSTRACT. Cerebral electric activity was surveilled with a Cerebral Function Monitor (CFM) technique in 87 newborn infants under neonatal intensive care. A total of 26 infants had electrographical signs of repeated seizure activity. Among these infants 14 had periods of one hour or more of silent seizures, i.e. typical pattern of ictal epileptic activity on CFM without clinical symptoms or signs of convulsions. The occurrence of silent seizures and their pattern in relation to the clinical condition and management was unpredictable in most cases. Besides general limpness or flaccidity in an outward quiet baby these infants showed no clinical fits or clonic convulsions. The findings indicate that anticonvulsive therapy in small infants may be insufficient and need re‐evaluation, since the long‐term effect of silent seizures on cerebral function and activity is still uncertain.

Postural Hypotension and EEG Variables Predict Cognitive Decline: Results from a 5-Year Follow-Up of Healthy Elderly Women

Quantified electroencephalographic activity (EEG) has been used to study normal ageing and dementia. Few studies have described longitudinal changes in the very old. A cognitive decline has been described in subjects with white-matter lesions and hypertension but the association with hypotension is unclear. Our aim was to study the predictive value of quantified EEG for the development of cognitive decline and associations with postural hypotension. Participants. Thirty-three healthy women aged 75-95 years, with no signs of cerebrovascular disease, dementia or acute illness at baseline examination took part in a longitudinal 5-year follow-up study. The women were recruited from a random selection using the Municipal Registry. Quantified EEG was assessed twice and recorded on a Siemens-Elema connected to a Biological Banker. The medical and neuropsychological examination was conducted twice. Dementia was classified according to DSM criteria. The assessment included Mini-Mental Scale Examination (MMSE), spatial and vocabulary tests. Blood pressure was measured in supine position and an orthostatic test was performed with continuous ECG recording. Seven women (cases) developed cognitive decline at the 5-year follow-up, defined as newly developed MMSE < 27 and dementia symptoms. Low beta activity at baseline predicted development of cognitive decline. The women who remained healthy at follow-up showed an increase of alpha and theta activity. The cases had a higher orthostatic blood pressure fall during tilting at baseline (16 mm Hg) than the controls (1 mm Hg, p < 0.01). The orthostatic reaction was correlated with increased levels of theta and alpha activity at follow-up (r = -0.47 to -0.52; p < 0.01). Low beta activity predicts for cognitive decline in the elderly and an orthostatic blood pressure reaction is a risk factor for cognitive decline.

An Atlas of Amplitude-integrated EEGs in the newborn

1. Methodology. 2. The Electrocortical Background, Its Normal Maturation, Classification, and Effects of Medication. 3. Pitfalls and Caveats. 4. Seizures. 5. Hypoxia-ischemia. 6. Focal Hemorrhagic and Ischemic Lesions in the Full-term Infant 7. Hemorrhagic and Ischemic Lesions in the Preterm Infant. 8. Metabolic Diseases, Brain Malformations, and Central Nervous System Infections.