Hans-Georg Imhof

Interleukin-6 released in human cerebrospinal fluid following traumatic brain injury may trigger nerve growth factor production in astrocytes

Cytokines are involved in nerve regeneration by modulating the synthesis of neurotrophic factors. The role played by interleukin-6 (IL-6) in promoting nerve growth factor (NGF) after brain injury was investigated by monitoring the release of IL-6 and NGF in ventricular cerebrospinal fluid (CSF) of 22 patients with severe traumatic brain injuries. IL-6 was found in the CSF of all individuals and remained elevated for the whole study period. NGF appeared in the CSF if IL-6 levels reached high concentrations and was often detected simultaneously with or following an IL-6 peak. The amounts of NGF correlated with the severity of the injury, as indicated by the clinical outcome of the patients. The functional relationship of IL-6 and NGF was investigated utilizing cultured mouse astrocytes. The CSF of 8 patients containing IL-6 induced NGF production in astrocytes, whereas control CSF without IL-6 had no effect. The induction of NGF was inhibited up to 100% by adding anti-IL-6 antibodies. These results were corroborated when astrocytes were exposed to recombinant IL-6 at different concentrations resulting in NGF production. Thus, the production of IL-6 within the injured brain may likely contribute to the release of neurotrophic factors by astrocytes.

Are unilateral right posterior cerebral lesions sufficient to cause prosopagnosia? Clinical and radiological findings in six additional patients

Controversy has arisen regarding the neuropathological basis of prosopagnosia. Some investigators suggest that bilateral lesions are needed to cause the deficit, whereas others felt that a unilateral right posterior lesion is sufficient. Six patients with prosopagnosia with clinical and radiological evidence of unilateral right posterior lesions are presented. Our observations together with evidence from similar cases described in the literature suggest that an appropriately placed right hemispheric lesion may be sufficient to produce prosopagnosia.

Moyamoya disease in Europe, past and present status

A questionnaire was distributed in early 1996 to 160 leading European neurological, neuro-pediatric and neurosurgical centers to assess the present status of Moyamoya disease in Europe. The response rate was 43%. Information was obtained on a total of 168 patients, of whom 110 had presented before 1992, and 58 from 1993 onward. 82% of the patients were Caucasian. In all other respects, the clinical findings were similar to those observed in Japan. The present study yields an incidence of 0.3 patients per center per year, which is approximately one-tenth of the incidence in Japan. Alongside these results, the history of the recognition and treatment of this disease in Europe is briefly discussed.

Experimental Axonal Injury Triggers Interleukin-6 mRNA, Protein Synthesis and Release into Cerebrospinal Fluid:

Diffuse axonal injury is a frequent pathologic sequel of head trauma, which, despite its devastating consequences for the patients, remains to be fully elucidated. Here we studied the release of interleukin-6 (IL-6) into CSF and serum, as well as the expression of IL-6 messenger ribonucleic acid (mRNA) and protein in a weight drop model of axonal injury in the rat. The IL-6 activity was elevated in CSF within 1 hour and peaked between 2 and 4 hours, reaching maximal values of 82,108 pg/mL, and returned to control values after 24 hours. In serum, the levels of IL-6 remained below increased CSF levels and did not exceed 393 pg/mL. In situ hybridization demonstrated augmented IL-6 mRNA expression in several regions including cortical pyramidal cells, neurons in thalamic nuclei, and macrophages in the basal subarachnoid spaces. A weak constitutive expression of IL-6 protein was shown by immunohistochemical study in control brain. After injury, IL-6 increased at 1 hour and remained elevated through the first 24 hours, returning to normal afterward. Most cells producing IL-6 were cortical, thalamic, and hippocampal neurons as confirmed by staining for the neuronal marker NeuN. These results extend our previous studies showing IL-6 production in the cerebrospinal fluid of patients with severe head trauma and demonstrate that neurons are the main source of IL-6 after experimental axonal injury.

Moyamoya disease and Moyamoya syndrome: experience in Europe; choice of revascularisation procedures

Objectives. To present our clinical experience in terms of disease presentation and choice of revascularisation procedure in our first group of 23 European Moyamoya angiopathy (disease and syndrome) patients. Method and patient selection. Twenty three patients were diagnosed and treated from 1997–2001 in our neurosurgical department. All patients underwent preoperative angiography, colour Doppler examination, cranial MRI and/or CT scans, HMPAO-SPECT or H215O PET (baseline and Diamox challenge) scans.Nineteen patients presented with child-juvenile Moyamoya angiopathy with an average age at presentation of 8 years (range 1–17 years), in 4 patients adult Moyamoya was diagnosed with a mean age at presentation of 34 years (range 23–40 years). Results. In all but one patient bilateral affection was present at the time of diagnosis. All patients underwent direct and/or additional indirect revascularisation procedures. Twenty-one patients underwent bilateral revascularisation procedures. In two patients a unilateral procedure was performed.A direct STA-MCA bypass (superficial temporal artery branch – middle cerebral artery branch anastomosis) was performed in all patients. Additional direct STA-ACA bypass (STA – anterior cerebral artery branch anastomosis) was performed in 10 patients. Indirect arteriosynangiosis using the occipital artery was performed in the posterior cerebral artery (PCA) territory in 3 patients. The frontal branch of the STA was used for arteriosynangiosis in the frontal region in another 2 patients. Indirect frontal durasynangiosis was performed in 14 patients. The number and location of multiple revascularisation procedures was determined according to the angiographic findings as well as the site of decreased perfusion reserves seen on H215O PET. A one stage revascularisation procedure was performed in 7 patients. Fourteen patients underwent two stage procedures. Following operation no complications were encountered in all but one adult patient who died postoperatively due to a massive middle cerebral artery infarct on the nonoperated side. Conclusions. As territorial hemodynamic disorder seems to be a characteristic in Moyamoya disease and/or syndrome, judging from our experience with European patients in our series, and several reports hitherto, treatment with multiple revascularisation procedures is considered to be justified.

EEG reactivity in the prognosis of severe head injury

Article abstract—We compared reactivity of EEG to external stimuli—an easily and quickly available measure—with the central conduction time (CCT) of the somatosensory evoked potentials, currently the most-used electrophysio-logic method to predict outcome in severe head injury (SHI), and with the initial Glasgow Coma Scale (GCS) score. In 50 patients, comatose subsequent to SHI, we measured EEG reactivity and CCT within 48 to 72 hours and compared them with the outcome after 1.5 years. Using discriminant analysis, EEG reactivity correctly classified 92%, CCT classified 82%, and both measures together classified 98% of the patients into globally good or bad outcome groups. GCS allowed a correct classification in only 72% and, combined with either of the two electrophysiologic measures, did not further increase predictability. EEG reactivity is an excellent long-term global outcome predictor in SHI, superioi- to CCT and GCS. When the two electrophysiologic measures are combined, a prognostic accuracy is achieved that is better than that of any other reported method.

Long-term hypothermia in patients with severe brain edema after poor-grade subarachnoid hemorrhage: feasibility and intensive care complications.

&NA; The purpose was to evaluate the feasibility and intensive care complications of long‐term hypothermia (>72 hours) in the treatment of severe brain edema after poor‐grade subarachnoid hemorrhage (SAH) Hunt and Hess grade 4 to 5. Among 156 patients with SAH, 21 patients were treated with mild hypothermia (33.0 to 34.0°C) combined with barbiturate coma because of severe brain edema and elevated intracranial pressure (>15 mm Hg) after early aneurysm clipping. Hypothermia was sustained for at least 24 hours after maintaining an intracranial pressure of <15 mm Hg. Nine patients were treated for <72 hours (group 1: mean 42.2 hours, range 8–66 hours) and 12 for >72 hours (group 2: mean 153.9 hours, range 78–400 hours). Three patients (14%) died during the hypothermia treatment. Good functional outcome after 3 months (Glasgow Outcome Score 4–5) was achieved in 10 patients (48%). The outcome did not differ between the two groups. All patients developed severe infections. In group 2 the mean value of minimal leukocyte counts during hypothermia was significantly lower (6.9 vs. 11.8 × 109/L; P = 0.001), and thrombocytopenia (<150 × 109/L) occurred significantly more often (48 vs. 33%; P = 0.032). In 48% of patients with poor‐grade SAH, good functional outcome was achieved with combined mild hypothermia and barbiturate coma after early aneurysm surgery. This may be a feasible treatment even for longer than 72 hours. All patients developed severe infections as potentially hazardous side effects. To determine whether mild hypothermia alone is effective in the treatment of severe SAH patients, controlled studies to compare the effects of barbiturate coma alone, mild hypothermia alone, and combined barbiturate coma with hypothermia are needed.

Cerebral oxygenation and systemic trauma related factors determining neurological outcome after brain injury

We examined the relationship between clinical and radiological findings, cerebral oxygenation patterns during intensive care management, presence of systemic trauma related injuries and severity of illness in 50 patients (age: 32.3 +/- 12 years, GCS: 8 +/- 4) who were rescued from the accident scene within a 30 min period after trauma. Presence of systemic injuries was quantified using the Injury Severity Score (ISS) and severity of illness was scored using the Acute Physiology and Chronic Health Evaluation (APACHE II). Cerebral oxygenation parameters included continuous monitoring of jugular bulb oxygen saturation (SjvO(2)) for 12 840 h, and 2323 periodical blood sampling for measurement of arteriovenous differences in oxygen content (AVDO(2)), arteriovenous difference of lactate (AVDL) and lactate oxygen index (LOI). Fifteen patients (30%) presented with anisocoria or non-reacting pupils. Diffuse lesions on computed tomography (CT) were found in 34% of the patients and in 66% a mass lesion was removed. The mean ISS was 28 +/- 15.3 and 34 patients (68%) had an APACHE II score between 20 and 29 (mean 24 +/- 15). No statistically significant association between age (P = 0.45), gender (P = 0.83), initial Glasgow Coma Score (GCS) (P = 0.43), episodes of cerebral perfusion pressure (CPP) < 70 mm Hg (P = 0.8), ISS (P = 0.28), pupillary abnormalities (P = 0.57), initial CT findings (P = 0.74), APACHE II scores (P = 0. 36) and outcome could be demonstrated. The number of SjvO(2)desaturations (< 60%) was the only statistically significant factor associated with outcome (P = 0.05). The percentage of patients with poor neurological outcomes (GOS 1-3) was 38% in patients with no or one desaturation episode, and 57.6% in those with multiple desaturations. In conclusion, in patients who are resuscitated early and quickly transferred to the hospital, the number of SjvO(2)desaturations during intensive care management might be associated with outcome more strongly than other clinical and radiological features.

Lower cranial nerve palsies due to internal carotid dissection.

A 41-year-old man experienced intense headache and neck pain, bruits, and a complete unilateral cranial nerve palsy IX-XII (Collet-Sicard syndrome) after a trivial back trauma. Magnetic resonance imaging and angiography demonstrated features of bilateral internal carotid artery dissection with aneurysm formation at the base of the skull compressing the nerves at the level of the jugular foramen. Severe dysphagia persisted for 1 month but rapidly improved after occlusion of the carotid aneurysm with a detachable balloon.

Distal posterior inferior cerebellar artery aneurysms: Clinical characteristics and surgical management

SummaryBackground. Aneurysms located on the distal posterior inferior cerebellar artery (PICA) are rare, and their underlying clinical features and surgical management are poorly understood. We report our series of 16 patients with 18 distal PICA aneurysms. Method. All patients with distal PICA aneurysms were treated between March 1996 and August 2004. We excluded all PICA aneurysms that involved the vertebral artery. Patients were analysed in the light of their clinical profiles, radiological studies, intraoperative findings and outcomes. All patients underwent non-enhanced and contrast enhanced CT scans followed by 4-vessel cerebral angiography on admission. The hemorrhagic patterns on initial CT scans were assessed using the Fisher Grading Score. The outcomes were documented using the Glasgow Outcome Scale at time of discharge and at three or twelve months follow-up. Findings. The series included 6 men and 10 women. Massive intraventricular haemorrhage was found in 13 patients with proven CT subarachnoid haemorrhage, one patient revealed SAH without intraventricular components, one presented with only intraventricular blood in the occipital horns and 3 aneurysms were found incidentally without presence of blood. Fourteen aneurysms were saccular and four were fusiform. Nine cases were associated with another cerebrovascular lesion. A lateral transcondylar or a median suboccipital approach was used to secure the aneurysms in 15 patients, either by direct clipping (14 lesions) or vessel sacrifice (3 lesions). One aneurysm was treated by an endovascular approach. At long-term follow up, an excellent or good outcome was achieved in 75% of cases. One patient died due to pre-existing cardiopulmonary complications. Conclusions. Most of our cases of ruptured distal PICA aneurysms presented with haematocephalus. These were frequently associated with another vascular abnormality and 22% were fusiform or multilobulated. These specific features require special management strategies entailing an appropriate surgical approach to the aneurysm, clipping method, haematoma removal, ventricular drainage and when suitable choice of endovascular interventions.