Microsurgical sequestectomy at 36 weeks of pregnancy: A case report.

About 30% of pregnant women experience lower back pain. The cause is usually increased mechanical stress combined with the ligament laxity induced by relaxin. Rarely, lower back pain is related to disc herniation. We report such a case, where microsurgical sequestectomy was performed at 36 weeks and three days of gestation because of severe extensor paresis of the left foot and big toe. The case shows that microsurgical treatment during pregnancy is safe. After treatment the patient regained full motor function and her pain regressed. She had a spontaneous vaginal delivery at 38 weeks.

A family with pheochromocytoma-paraganglioma inherited tumour syndrome. Serial 18F-DOPA PET/CT investigations.

AIM: Hereditary pheochromocytoma-paraganglioma syndromes are characterized by multiple pheochromocytomas (PCC) and paragangliomas (PGLs), inherited in an autosomal dominant manner. Early detection and removal of tumours may prevent or minimize complications related to mass effects and malignant transformation. Having confirmed the diagnosis, it is important to localize the tumours and reveal their extent preoperatively. This study aimed to introduce 18F-DOPA PET/CT as a highly sensitive non-invasive diagnostic tool for early detection of mass lesions in patients with pheochromocytoma-paraganglioma inherited tumour syndrome and to report about its impact on patient management. PATIENTS, METHODS: We are currently supervising one of the largest documented families in Germany with genetically determined SDHD gene mutation. We performed 18F-DOPA PET/CT in order to detect tumours in asymptomatic gene carriers and enable subsequent surgical therapy. RESULTS: In seven patients undergoing 12 18F-DOPA PET/CT scans 17 lesions have been detected. Three of these lesions, located in the head and neck region, have had no morphologic correlate in CT and one had also no morphologic correlate in MRI. Of the six histologically analyzed lesions five have been tumors (PGL or PCC) and one has been a nodular hyperplasia. This means the 18F-DOPA PET/CT scan in our study group had a sensitivity of 83%. 18F-DOPA PET/CT investigations lead to change in the management in 5/7 studied patients (70%). CONCLUSION: The benefits of PET/CT in detection of pheochromocytoma and paraganglioma are well documented, but we are the first to use this technique for screening of a rare hereditary disease (estimated prevalence 0.3/100 000).

Influences of pCO2 and bicarbonate concentration on bioelectric phenomena in ischemic hippocampal ex vivo tissue.

While the vasomotor effects of pCO(2) modulation are well documented, the influence of the carbon dioxide-bicarbonate system on the ischemia tolerance of brain tissue itself is controversial. Guinea-pig hippocampal tissue was subjected to ischemia simulation in an interface environment and examined electrophysiologically. Characteristics of anoxic depolarization as well as the postischemic recovery of evoked potentials were registered. During ischemia simulation, pH was changed and afterwards restored to 7.4. pH of 7.6 (n=6), and 7.8 (n=6) were adjusted by increasing bicarbonate concentration without changing pCO(2), while pH 8.2 was reached either with normal pCO(2) (n=8) or with zero CO(2) (n=9). pH 7.1 was created by doubling pCO(2) (n=22) or reducing bicarbonate (n=21), while acid pH of 6.9 (high pCO(2) and low bicarbonate) led to erratic measurements in the interface setup. Alkalotic conditions did not improve electrophysiological stability of the tissue, and pH 8.2 impeded the recovery of evoked potentials. Hypercarbic pH 7.1 led to significantly longer latency of depolarization while the same pH with lowered bicarbonate did not. Evoked potentials, however, recovered only partially after ischemia at hypercarbic pH 7.1. Once the tissue had recovered from anoxic depolarization at control pH, hypercarbic acidosis did not have any further protective effect when ischemia simulation was repeated (n=12). These results do not strengthen the concept of hyperventilation in intensive care, while they suggest a potential of hypercarbia within broader strategies delaying the onset of secondary brain damage.

Increased chromosomal imbalances in recurrent pituitary adenomas.

Eight pituitary adenomas (four gonadotroph cell adenomas, three prolactin cell adenomas, one null cell adenoma) and their respective recurrences in the same patients were studied by comparative genomic hybridization. Chromosomal imbalances were found in seven of eight patients affecting two of eight primary and seven of eight recurrent tumors. Overall, pituitary adenomas showed an average of 1.6 chromosomal imbalances per primary and 3.4 per recurrent tumor (P < 0.01). Prolactin cell adenomas showed an average of 4.3 chromosomal changes per primary and 6.3 per recurrent tumor, which were significantly more common than in gonadotroph cell adenomas (0 vs 1.7 changes; P < 0.05) and the null cell adenoma (0 vs 1.0 changes; P < 0.05). The most common changes were gains of 4q (in three of eight recurrences), 5q, and 13q (in two of eight recurrences each) as well as losses of chromosome 2 (in both primary and recurring tumors of two patients), 1p, 8q, 10, and 12q (in two of eight recurrences). Minimal common regions associated with recurrent adenomas were gains of 4q31.2-34 (three recurrences), 5q14-23 and 13q21-31 and losses of 12q24.3-qter (two recurrences each). The average MIB-1 proliferation indices were 1.2% for primary and 1.9% for recurrent adenomas (P < 0.005). Our findings suggest that acquisition of certain chromosomal imbalances is related to and may underlie adenoma recurrence.

Acute protective effect of nimodipine and dimethyl sulfoxide against hypoxic and ischemic damage in brain slices.

Nimodipine and dimethyl sulfoxide (DMSO) were tested (alone and in combination) regarding their ability to increase hypoxic tolerance of brain slices under 'hypoxic' (deprivation of oxygen) or 'ischemic' (hypoxia+withdrawal of glucose) conditions. Direct current (DC) and evoked potentials were recorded in the CA1 region of hippocampal slices of adult guinea pigs. After induction of hypoxia or ischemia, the latency of anoxic terminal negativity (ATN) of the DC potential was determined during superfusion with artificial cerebrospinal fluid alone (aCSF), and during superfusion with aCSF containing DMSO [0.1% (14.1 mmol/l) and 0.4% (56.3 mmol/l)] with the addition of nimodipine (40 micromol/l). Latencies of ATN with first hypoxia were 6.7+/-3.7 min in the control group, 9. 3+/-4.2 min in the 0.4% DMSO group and 12.3+/-5.5 min (P=0.007) in the nimodipine/0.4% DMSO group. Latencies of ATN with first ischemia were 2.9+/-2 min in the control group, 4.1+/-1.6 min in the 0.1% DMSO group, 7.1+/-3.9 min in the 0.4% DMSO group (P=0.006), 5.3+/-1. 5 min in the nimodipine/0.1% DMSO group and 7.6+/-3 min (P<0.001) in the nimodipine/0.4% DMSO group. DMSO (0.4%), either alone or in combination with nimodipine, increase the latency of the ATN after acute onset of hypoxia and ischemia.

Neuroprotection by 21-aminosteroids: insights from latencies of anoxic terminal negativity in hippocampus slices of guinea pig.

The protection of neuronal function by 21-aminosteroids against a hypoxic challenge was tested in guinea pig hippocampal slices. 21-aminosteroids, which apart from a protective mechanism against membrane lipid peroxidation, provide direct membrane stabilizing effects, are reported. We tested whether the 21-aminosteroid U-74389G delays the anoxic terminal negativity (ATN) of the DC-potential during hypoxia. Hippocampal slices were placed at the interface of artificial cerebrospinal fluid (aCSF) and gaseous phase (normoxic: 95% O2, 5% CO2; hypoxic: 95% N2, 5% CO2). Population spikes obtained by stimulation of Schaffer-collaterals as well as the DC-Potential were recorded in the CA1 region. The latency of appearance of ATN after oxygen deprivation was determined. In control experiments, the latency of ATN was 12.6 +/- 3.1 min (n = 6, mean +/- SEM). With application of U-74389G, the ATN-latency was 8.8 +/- 3.2 min (n = 6). We conclude that the cerebroprotective effect of the 21-aminosteroid is not mediated via direct membrane stabilization.

Dimethyl sulfoxide increases latency of anoxic terminal negativity in hippocampal slices of guinea pig in vitro.

Dimethyl sulfoxide (DMSO), which is widely used as a solvent for a variety of drugs, was used in the present study to investigate its ability to increase the hypoxic tolerance of brain tissue in vitro. DC-potentials and evoked potentials (EP, Schaffer collateral stimulation) were recorded in the CA1 region of hippocampal slices from adult guinea pigs. The latencies of the negative DC-potential shift (anoxic terminal negativity, ATN) after onset of hypoxia (95% N2, 5% CO2) were determined during superfusion with artificial cerebrospinal fluid (aCSF) or DMSO 0.4% dissolved in aCSF, respectively. The latencies of ATN were increased by DMSO application from 7.5+/-0.9 min (mean +/- SEM) under control conditions (n = 38) to 11.1+/-1.3 min with DMSO (n = 22, P < 0.01). These results demonstrate a neuroprotective effect of DMSO.

Management of a ruptured cerebral aneurysm in infancy. Report of a case of a ten-month-old boy.

A ten month old unconscious boy with hemiplegia (Hunt and Hess IV) was first admitted to a district hospital without a CT scanner or a neurosurgical service (Glasgow-Coma-Score 4, no pathological pupillary signs). Therefore, he was transferred to the Pediatric Department of the University Hospital the same night. An emergency CT scan that night showed intracerebral and subarachnoid hemorrhage with enlarged ventricle (Fisher grade 5). Angiography was not available within reasonable time. Thus in the stage of progressively increasing clinical deterioration, still without pupillary signs, an external ventricular drain-age was placed. Immediately after reduction of the cerebrospinal fluid volume, arterial hypertension was noticed--the right pupil was mydriatic and fixed. Without further apparative diagnosis an emergency craniotomy was performed for decompression under the suspicion of a secondary hemorrhage due to a rerupture of a middle cerebral artery aneurysm. A bleeding aneurysm of the right middle cerebral artery was found and clipped. A mass transfusion was necessary and a pulmonary air embolism occurred. The infant died in tabula. The histological specimens revealed disruption of the internal elastic membrane of both MCA. This emphasizes a congenital nature of the aneurysm. We conclude that cerebral arterial aneurysms have to be considered in the differential diagnosis of stroke-like symptoms in infancy and early childhood, although the incidence of reported cases is less than one case per year. Since no valid screening parameter is available, diagnosis is often made only after rupture of the aneurysm. This causes problems for emergency management. Infants and children with stroke or stroke-like symptoms should immediately be transferred to a hospital with a neurosurgical unit.

Neuroprotection of mild hypothermia: differential effects.

To estimate whether mild hypothermia during repetitive hypoxia provides a neuroprotective effect on brain tissue, hippocampal slice preparations were subjected to repetitive hypoxic episodes under different temperature conditions. Slices of guinea pig hippocampus (n=40) were placed at the interface of artificial cerebrospinal fluid (aCSF) and gas (normoxia: 95% O2, 5% CO2; hypoxia: 95% N2, 5% CO2). Evoked potentials (EP) and direct current (DC) potentials were recorded from hippocampal CA1 region. Slices were subjected to two repetitive hypoxic episodes under the following temperature conditions: (A) 34 degrees C/34 degrees C, (B) 30 degrees C/30 degrees C and (C) 34 degrees C/30 degrees C. Hypoxic phases lasted until an anoxic terminal negativity (ATN) occurred. The recovery after first hypoxia lasted 30 min. Tissue function was assessed regarding the latency of ATN and the recovery of evoked potentials. The ATN latencies with protocol A (n = 25) for the first and second hypoxia were 5.9+/-1.3 min (mean+/-S.E.M., 1st hypoxia) and 2.4+/-0.9 min (2nd hypoxia), with protocol B the latencies (n = 7) were significantly longer: 25.2+/-7.1 min and 15.6+/-7.7 min. With protocol C (n=8), the latencies were 5.6+/-1.8 and 3.3+/-0.5 min. No differences were seen in the recovery of the EPs with protocols A-C. Our results suggest that a mild hypothermia is only neuroprotective if applied from an initial hypoxia onwards.

Flat and steep terminal negativity in the DC-potential after deprivation of oxygen and glucose in human neocortical slices.

The so-called terminal negativity (TN) of the DC-potential is a characteristic reaction of neuronal tissue to hypoxia or ischemia. In a previous study on human neocortical slices, two types of TN with flat and steep slopes of rise (< or >10 mV/min) were found with hypoxia. The aim of the present study was to further investigate causes underlying the occurrence of flat and steep TN. Experiments were performed on 23 human neocortical slices (500 micron) resected from 13 patients (epilepsy and tumour surgery). DC-potential and evoked potentials (white matter stimulation) were recorded in layer III. The extracellular potassium concentration ([K+]o) was measured by K+-sensitive microelectrodes. In an interface type chamber, ischemic episodes were induced by oxygen and glucose deprivation. They were terminated when TN had peaked. Both flat and steep TN also existed with ischemic conditions. There was a linear correlation between the slope of rise of TN and the associated slope of rise in [K+]o, respectively, but none regarding latencies of TN or recovery of evoked potentials. Peak levels in [K+]o were 13.9+/-0.9 mmol/l. Compared to control, the slope of rise and latency of TN were clearly increased by addition of dimethyl sulfoxide (DMSO, 0.4%) to the bath solution, whereas nimodipine (40 micromol/l) in 0.4% DMSO had neither an effect on slope of rise of TN nor on latency of TN. As a whole, our observations suggest, that the actual metabolic state determines the occurrence of flat or steep TN.

Intracranial metastasis of a spinal myxopapillary ependymoma. A case report.

A 37-year-old man exhibited a suprasellar tumor which histologically proved to be a myxopapillary ependymoma. Since these gliomas are virtually restricted to the cauda equina region, magnetic resonance imaging (MRI) was performed which revealed multiple spinal tumors. The present case seems to be the first report on spontaneous intracranial seeding of a spinal myxopapillary ependymoma.

Hypothermia as cerebroprotective measure. Experimental hypoxic exposure of brain slices and clinical application in critically reduced cerebral perfusion pressure.

An in vitro human neocortical and rodent hippocampus brain slice technique was used under repeated hypoxia to investigate the cerebroprotective effect of hypothermia. As a hallmark of the neuronal hypoxic reaction anoxic terminal negativity (ATN) was registered to test whether hypothermia delays the onset of ATN. The experiments clearly confirm an assumed protective effect of hypothermia in vitro and in vivo and give for the first time evidence of the lack of the protective effect of hypothermia once hypoxia has occurred under normothermic conditions, probably by a critical depletion of cellular ATP-stores. In patients with severe traumatic brain injury and critically low cerebral perfusion pressure mild hypothermia is able to improve clinical outcome.

A case of severe cerebral trauma in a patient under chronic treatment with cyclosporine A.

A case of severe cerebral head injury in a child, chronically treated with cyclosporine A after orthotopic liver transplantation, is presented. The initial Glasgow Coma Scale score after the motor vehicle accident was 3, and computed tomography showed multiple sites of intracerebral bleeding, an epidural hematoma, and signs of perifocal edema. Although these lesions are normally associated with a poor outcome, the child recovered unexpectedly well. In brain injury, a lucid interval can be followed by secondary neurologic deterioration due to a loss of high-energy metabolites, a release of neurotransmitters, and an increase in intracellular Ca2+. These events finally led to cell damage in the penumbra of an ischemic infarction. Among other drugs, immunosuppressants such as cyclosporine A have been shown to exhibit neuroprotective properties in experimental models if given during this time interval of secondary neurologic deterioration. Although human data on these effects are still lacking, we conclude that neuroprotective actions of cyclosporine A may have been involved in the favorable outcome in this 14-year-old boy.

Analysis of a protein kinase C-alpha mutation in human pituitary tumours.

It is generally accepted that protein kinase C-alpha (PKC-alpha) is an important enzyme in the cellular regulation of growth and differentiation by phosphorylating proteins. Recent studies have described a point mutation of PKC-alpha (position 908 of the genetic sequence, codon GAC becoming GGC) in invasive human pituitary tumours which leads to an exchange of amino acids in the protein. We investigated 11 human pituitary tumours to evaluate the data obtained previously. cDNA was subcloned and up to ten individual clones were sequenced from each tumour, resulting in 85 clones analyzed in total. All of the pituitary adenomas showed a normal wild-type sequence of PKC-alpha DNA. Even if the tumour was 'invasive' (infiltration of the dura mater) no mutation at position 908 of the sequence was found. Moreover, using Western blot analyses we did not observe any differences in PKC-alpha protein expression in invasive as compared with noninvasive pituitary adenomas. Until now we have been unable to confirm the data of other investigators, suggesting that mutated PKC-alpha is an inconsistent feature of invasive pituitary tumours.

Short-term lack of cerebral perfusion with good outcome. Advantages of early intracranial pressure monitoring.

A 21-year-old man was injured by a tailboard of a truck. He suffered a severe head injury with bilateral depressed skull fractures necessitating surgical decompression. On admission to the hospital the patient showed bending to pain stimuli (Glasgow Coma Score 5). Anisocoria was noticed from the beginning. Initial intracranial pressure (ICP), measured 3 hours after injury, was 30 mm Hg, and the cerebral perfusion pressure (CPP) was 70 mm Hg. During surgical elevation of the skull fracture on the right side an un-explainable rise of ICP to values of 100 mm Hg occurred, which corresponded to the mean arterial blood pressure (MAP). At the same time both pupils were dilated and fixed indicating a lack of cerebral perfusion. Due to immediate trephination of the opposite side, the ICP was lowered to values below 20 mm Hg, and sufficient cerebral perfusion (above 50 mm Hg) was regained. The patient showed a good recovery and was transferred to a rehabilitation center 5 weeks after injury. This case report emphasizes the importance of early and continuous intracranial pressure monitoring for adequate therapy in neurosurgical emergencies.

Anoxic terminal negative DC-shift in human neocortical slices in vitro.

In animal models, the hallmark of a hypoxic condition is a strong negative shift of the DC potential (anoxic terminal negativity, ATN). This DC-shift is interpreted to be primarily due to a breakdown of the membrane potential of neurons. Such massive neuronal depolarizations have not been reported for all human neocortical neurons in vitro even during prolonged hypoxic periods. This poses the question whether ATN develop also in human neocortical slices made hypoxic. ATN could be observed when human brain slice preparations (n = 15, 13 patients) were subjected to periods of hypoxia (10 to 120 min). These ATN were usually monophasic and appeared with a latency of 16 +/- 4 min (mean +/- S.E.M.). Separating the ATN according to their slopes of rise, steep (> 10 mV/min) and flat (< 10 mV/min) ATN could be distinguished. Steep and flat ATN may be regarded as two different entities of reactions since steep ATN had also greater amplitudes and slopes of decay as compared a flat ATN. With repetitive hypoxias, the latency of both the steep and flat ATN was reduced for the following hypoxic episodes. During hypoxic DC-shifts, evoked potentials were suppressed. With the 1st through 4th hypoxia, they recovered fully within 30 min after reoxygenation when hypoxia was terminated at the plateau of ATN; with extension of hypoxia, recovery was only partial. From the 5th hypoxia onwards, recovery usually did not take place or was not complete.

The effects of verapamil and flunarizine on epileptiform activity induced by bicuculline and low Mg2+ in neocortical tissue of epileptic and primary non-epileptic patients.

In human neocortical slices the specific L-type calcium channel blocker verapamil had been shown to be antiepileptic in the low Mg(2+)-model of epilepsy. The present investigation demonstrated: (1) verapamil exerted also an antiepileptic effect on epileptiform field potentials (EFP) induced by the GABAA-antagonist bicuculline. (2) The unspecific calcium channel modulator flunarizine, which in contrast to verapamil penetrates the blood-brain barrier, depressed EFP in the low Mg(2+)-model and in the bicuculline model. (3) There was no significant difference in the antiepileptic efficacy of verapamil and flunarizine in epileptic (epilepsy surgery) and primary non-epileptic (tumor surgery) neocortical slices.

Repetitive hypoxic exposure of brain slices and electrophysiological responses as an experimental model for investigation of cerebroprotective measurements.

An in vitro hippocampal (CA 1 region, guinea pig) slice technique using repeated hypoxia was employed to model electrophysiological changes (DC-potentials and evoked potentials (EP) by stimulation of Schaffer-collaterals) occurring in the hypoxic CA1 pyramidal layer. A standardized neuronal response under repeated hypoxic conditions was observed in this model, consisting of disappearance of EP and a trend towards partially reversible, but progressive synaptic failure subsequent anoxic depolarisation (AD). Slices treated with the calcium antagonist nimodipine showed a prolongation of AD latency between the first and following hypoxias. So it seems possible to simulate hypoxic lesions of the brain tissue by using this in vitro slice model.