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Complex Regional Pain Syndromes (CRPS) are characterized by a triad of sensory, motor and autonomic dysfunctions of still unknown origin. Pain and mechanical hyperalgesia are hallmarks of CRPS. There are several lines of evidence that central nervous system (CNS) changes are crucial for the development and maintenance of mechanical hyperalgesia. However, little is known about the cortical structures associated with the processing of hyperalgesia in pain patients. This study describes the use of functional magnetic resonance imaging (fMRI) to delineate brain activations during pin-prick hyperalgesia in CRPS. Twelve patients, in whom previous quantitative sensory testing revealed the presence of hyperalgesia to punctuate mechanical stimuli (i.e. pin-prick hyperalgesia), were included in the study. Pin-prick-hyperalgesia was elicited by von-Frey filaments at the affected limb. For control, the identical stimulation was performed on the unaffected limb. fMRI was used to explore the corresponding cortical activations. Mechanical stimulation at the unaffected limb was non-painful and mainly led to an activation of the contralateral primary somatosensory cortex (S1), insula and bilateral secondary somatosensory cortices (S2). The stimulation of the affected limb was painful (mechanical hyperalgesia) and led to a significantly increased activation of the S1 cortex (contralateral), S2 (bilateral), insula (bilateral), associative-somatosensory cortices (contralateral), frontal cortices and parts of the anterior cingulate cortex. The results of our study indicate a complex cortical network activated during pin-prick hyperalgesia in CRPS. The underlying neuronal matrix comprises areas not only involved in nociceptive, but also in cognitive and motor processing.

Computed tomography (CT) is the standard method of brain imaging in acute stroke. To an experienced examiner, nonenhanced CT will exclude hemorrhage and may indicate early ischemic signs. Reliable description of an ischemic area and the underlying vascular disease is not possible in the acute phase but is possible, particularly within the first hours, when therapeutic decisions on matters such as systemic thrombolysis are to be made. For such rapid decision-making, imaging must provide more information. Novel, contrast-enhanced CT techniques can provide this information. Perfusion CT (CTP) can show brain perfusion, allowing one to distinguish between reversible and irreversible damage in an ischemic area. Also, CT angiography (CTA) can detect occlusion or stenosis in the relevant vasculature. Using a modern, multislice CT scanner, it is now possible to combine these modalities of imaging. In a fast protocol for emergency evaluation, all three methods can be performed and evaluated to provide the crucial information within 15 min. In the first 102 patients examined within 6 h of symptom onset using this protocol, multimodal CT contributed substantially to therapeutic decisions, even though there are some limitations in these methods.

Gravity places considerable stress on the cardiovascular system but cerebral autoregulation usually protects the cerebral blood vessels from fluctuations in blood pressure. However, in conditions such as those encountered on board a high-performance aircraft, the gravitational stress is constantly changing and might compromise cerebral autoregulation. In this study we assessed the effect of oscillating orthostatic stress on cerebral autoregulation. Sixteen (eight male) healthy subjects [aged 27 (1) years] were exposed to steady-state lower body negative pressure (LBNP) at -15 and -40 mmHg and then to oscillating LBNP at the same pressures. The oscillatory LBNP was applied at 0.1 and 0.2 Hz. We made continuous recordings of RR-interval, blood pressure, cerebral blood flow velocity (CBFV), respiratory frequency and end-tidal CO(2). Oscillations in mean arterial pressure (MAP) and CBFV were assessed by autoregressive spectral analysis. Respiration was paced at 0.25 Hz to avoid interference from breathing. Steady-state LBNP at -40 mmHg significantly increased low-frequency (LF, 0.03-0.14 Hz) powers of MAP ( P<0.01) but not of CBFV. Oscillatory 0.1 Hz LBNP (0 to -40 mmHg) significantly increased the LF power of MAP to a similar level as steady-state LBNP but also resulted in a significant increase in the LF power of CBFV ( P<0.01). Oscillatory LBNP at 0.2 Hz induced oscillations in MAP and CBFV at 0.2 Hz. Cross-spectral analysis showed that the transfer of LBNP-induced oscillations in MAP onto the CBFV was significantly greater at 0.2 Hz than at 0.1 Hz ( P<0.01). These results show that the ability of the cerebral vessels to modulate fluctuations in blood pressure is compromised during oscillatory compared with constant gravitational stress. Furthermore, this effect seems to be more pronounced at higher frequencies of oscillatory stress.

Isoelectric electroencephalogram in conformance with clinical findings is strongly suggestive of brain death. In clinical practice, isoelectric electroencephalogram in not-brain-dead patients is rarely seen. We report on a 53-year-old patient who suffered ischaemic encephalopathy after cardiopulmonary arrest. He had residual brainstem function with sufficient spontaneous breathing and evidence of cerebral blood flow on single photon emission computed tomography scan, but his electroencephalogram was isoelectric. He survived this condition for more than 7 weeks. This case demonstrates that isoelectric electroencephalogram can not be equated with brain death, and that in prognostic assessment both clinical findings and supportive technical methods are mandatory.

Study Design: A consecutive and controlled cohort study., Objectives: To assess the value of motor conduction time (MCT) between cortex and symptomatic leg muscles after transcranial magnetic brain stimulation as an indicator of reversible root ischemia in patients with neurogenic claudication in spinal stenosis., Summary of Background Data: Neurogenic claudication in spinal stenosis is thought to result from transient ischemia of active nerve root fibers. Subgroups of these patients have slowing of sensory or motor nerve root conduction during spinal claudication., Material and Methods: Forty-two patients with spinal claudication and radiologically confirmed signs of spinal stenosis were consecutively recruited. Motor conduction time was measured before and repetitively after challenge of walking on a treadmill (four stimuli per minute) until disappearance of the symptoms. Data of 30 patients (65 +/- 10 years) with a defined onset of motor-evoked potentials were compared with those of 12 control subjects (62 +/- 12 years)., Results: One minute after treadmill challenge, MCT increased in all 13 patients with signs of an exercise-dependent neurologic deficit by at least 1 msec (mean increase, 1.6 +/- 0.6 msec; < 0.001). Test-retest comparisons in six of these patients revealed good reproducibility of the MCT increase (coefficient of repeatability, 1.24 msec). In contrast, MCTs were unchanged or decreased in all 17 patients without exercise-dependent neurologic deficit ( < 0.01) and in the control subjects ( < 0.05)., Conclusions: Measurements of MCT before and after treadmill challenge can demonstrate reversible root ischemia in patients with spinal claudication and exercise-dependent deficit of thickly myelinated nerve root fibers.

This study describes the distribution and identity of annexin-1 positive cells in the central nervous system in patients with multiple sclerosis (MS). Glucocorticoid-inducible, anti-inflammatory properties have been ascribed to annexin-1, a member of a family of calcium-binding proteins that are referred to collectively as annexins. We have found annexin-1 to be spatially associated with active MS lesions and demonstrated a stage-dependent expression of annexin-1 in MS plaques. All of the most important pathogenetically involved cells of MS lesions showed a strong annexin-1 reactivity. Both correlation analysis and double staining procedures suggested annexin-1 expression in macrophages and perivascular lymphocytes, where a cytoplasmic reactivity was displayed, whereas in activated, gemistocytic astrocytes it was also concentrated close to the plasma membrane. Although the exact roles of annexin-1 in this setting are still to be determined, a possible contribution to anti-inflammatory processes might be suggested.

In amyotrophic lateral sclerosis (ALS) patients, hyperintense signals at the subcortical precentral gyrus in brain fluid attenuated inversion recovery (FLAIR) MR images have been found more frequently than in controls. Quantitative analysis has revealed a significant increase of the FLAIR-magnetic resonance imaging (MRI) signal at the subcortical precentral gyrus of ALS patients compared to healthy controls. In addition, hypointense signals at the rim of the precentral gyrus in FLAIR and T2-weighted images have been shown in ALS patients. In 17 ALS patients, we evaluated hyperintense signals in T2-, T1-, proton density-weighted and FLAIR MR images, and hypointense signals in T2-weighted and FLAIR images 15.7+/-3.0 months after the initial examination by visual scoring. In FLAIR images, a quantitative analysis was added. The visual scores of hyperintense signals along the corticospinal tract did not change significantly in all sequences. However, the quantitative evaluation of FLAIR images revealed a significant increase of the signal intensity at the subcortical precentral gyrus (p<0.005). In addition, the frequency of the visually evaluated hypointense signals at the precentral gyrus increased significantly (p<0.05). The change of MR results did not correlate with the change of clinical parameters. In ALS patients, the increase of the quantified MRI signal at the subcortical precentral gyrus in FLAIR images and the increase of hypointense signals at the rim of the precentral gyrus corroborate the hypothesis that these signals are related to the upper motor neuron degeneration in ALS. Their specificity and clinical relevance have to be clarified further.

This study was designed to study the influence of gender and lateral hemispheric asymmetry on heart rate modulation during temporal lobe seizures. Heart rate was recorded during complex partial seizures in 10 female and 11 male patients (12 with a right temporal lobe focus, nine with a left focus), with simultaneous video monitoring and bilateral subdural electrode placement. Heart rate changes were analysed during the seizure, at a time when the epileptic activity was restricted to one hemisphere. In this analysed interval, the heart rate of patients with a right temporal lobe focus showed a significant increase, from 73.5 to 91.0 beats/min (F = 10.7, df = 2.3/27, p < 0.001), while the heart rate of patients with a left sided focus only increased slightly, from 77.0 to 82.5 beats/min (NS). An effect of sex was demonstrated, in that the influence of focus laterality could only be shown in male patients (F = 14.24, df = 2.58/27, p < 0.001). These results confirm the right hemispheric lateralisation of sympathetic cardiac control in male patients.

Cerebrovascular autoregulation assures constancy of cerebral perfusion despite blood pressure changes, as long as mean blood pressure remains in a range between 50-170 mmHg. Static and dynamic myogenic mechanisms dampen sudden blood pressure changes. Neurogenic influences of sympathetic, noradrenergic fibers modulate primarily proximal, large diameter segments of cerebral arteries, but also small 15-20 microns diameter vessels. Parasympathetic, vasodilating impulses are of less influence. Monoaminergic brainstem centers such as the dorsal raphe nucleus, locus coeruleus or nucleus reticularis pontis oralis also influence vessel tone. Metabolic, local parenchymal and endothelial substances have major impact on cerebral vessel tone. Particularly important are nitric oxide, calcitonin gene related peptide, substance P, endothelin, potassium channels and autocoids such as histamine, bradykinin, arachidonic acid, prostanoids, leucotrienes, free radicals or serotonin. The clinical examination of autoregulation is mostly based on brief blood pressure changes induced by drugs such as angiotensin, phenylephrine or sodium nitroprusside, or by challenge maneuvers. Frequently, blood pressure is challenged by a tilt-table maneuver, the "leg-cuff"-method according to Aaslid, or a Valsalva maneuver. The analysis of coherence and phase relation between spontaneous or metronomic breathing modulation of blood pressure and brain perfusion also assesses autoregulatory function. Cerebral blood flow is determined by means of transcranial Doppler sonography, mostly of the proximal segment of the mid-cerebral artery. There is some controversy whether a decrease of cerebral blood flow velocity measured at this segment indicates vasodilatation at the insonated segment or reflects blood flow reduction due to decreased perfusion of down-stream vessel segments. Various clinical and animal studies are presented demonstrating diameter constancy of the insonated mid-cerebral artery segment and thus indicating that slowing of mid cerebral artery blood flow velocity as assessed by transcranial Doppler sonography is due to a decrease of down-stream perfusion. Direct, intraoperative measurements of vessel diameter confirm this conclusion.

Epileptic activity can modulate reactions of the autonomic nervous system. Although there is some evidence of a differential left/right hemispheric influence on the cardiovascular system, diverse investigations have shown controversial results. In our study, complex partial seizures of patients with temporal lobe epilepsy were recorded using subdural electrodes, thus providing reliable information on the focus side. We analyzed the preictal and ictal heart rates of 27 patients, 16 revealing right and 11 revealing left temporal foci. During the seizures, both groups showed a significant increase in heart rate. Preictal tachycardia was only significant in the right focus group, whereas no significant change in heart rates could be detected in the left focus group. Our results confirm a right hemispheric lateralization of sympathetic cardiac control.

In recent years, the frequency of primary cerebral lymphoma (PCNSL) has increased, even among immunocompetent patients. In order to treat the disease optimally, early diagnosis is important. We present three patients with atypical courses of this disease and stress the importance of PCNSL in the differential diagnosis for optimal treatment. In a 75-year-old man, a space-occupying, radiopaque, enhancing CNS lesion disappeared completely after biopsy and short steroid therapy. One year later, the tumor recurred on the other side and again regressed after steroid therapy. The first biopsy showed signs of a papillary tumor, so a choroid plexus papilloma was suspected initially. A 57-year-old woman developed progressive bilateral hearing dysfunction. Lymphocytic pleocytosis led to a primary diagnosis of chronic lymphocytic meningitis. During the further course of disease, the patient developed multiple space-occupying cerebral lesions. Stereotactic biopsy revealed PCNSL. Despite combined chemo- and radiotherapy, a relapse occurred. A 49-year-old woman rapidly developed memory and concentration disturbances. Computed tomography revealed diffuse edema in both hemispheres and MRI detected severe, diffuse, white matter lesions. The CSF revealed lymphocytic pleocytosis including plasma cells. Herpes encephalitis and, after lack of clinical improvement and progression of the MRI changes, acute disseminated encephalomyelitis (ADEM) were suspected. Corticosteroid treatment was initiated. After enormous clinical improvement, a clinical relapse occurred and MRI detected bitemporal and singular space-occupying lesions in the corpus callosum and hypothalamus. Finally, open biopsy showed PCNSL. However, on examination of the treatment history of patient 1, the initial diagnosis must be revised; a PCNSL seems most probable. The phenomenon of tumor remission under steroid administration is rare. In patients 2 and 3, atypical clinical signs and symptoms delayed diagnosis of PCNSL. This tumor can mimic diverse neurological diseases and remit following corticosteroid treatment alone. In unclear cerebral disease, biopsy should be performed early for exact diagnosis and optimal treatment.

Objective: The relationship between acute monosymptomatic optic neuritis (AON) and subsequent multiple sclerosis (MS) is still doubtful. We investigated the risk of developing MS in patients from North Bavaria, who were suffering from AON., Patients/methods: Twenty-nine patients with clinical evidence of AON were included in the study. Initial evaluation included brain resonance imaging (MRI) and a clinical neurological examination. Follow-up examinations were performed after 72-108 months (mean: 96 months) in 26 patients (three patients were lost to follow-up) and consisted of a second complete neurological examination. Diagnosis of MS was established according to the criteria of Poser CM, Paty DW, Scheinberg L. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 1983:13:227-231., Results: At follow-up, 14 of 26 patients (54%) had converted to clinically definite MS. Nine patients (64%) had developed MS within 2 years after the onset of AON., Conclusion: We observed the development of MS in 54% of the 26 investigated AON patients. The exceptional feature of the present study was the relatively long follow-up period of 8 years.

Objectives: After electrical stimulation of the esophagus cerebral responses are recordable, their cortical source is under discussion. Brain mapping using electroencephalography recordings demonstrated partially controversial results. Sources of evoked responses can be localized more easily using magnetoencephalography than electroencephalography., Methods: We examined 22 volunteers by recording electrical somatosensory potentials after electrical stimulation of the esophagus. In 9 of these 22 subjects additional recording of magnetic fields was performed and the sources of the evoked magnetic fields were computed., Results: The evoked potentials after electrical stimulation of the esophagus had a similar latency as the previously published data. The source localization done by magnetoencephalography suggest that first a region of the postcentral gyrus is activated which is temporo-lateral to the primary somatosensory cortex of the pharynx. This region is suggested to be the primary somatosensory region of the esophagus. This source was followed by a source in the parietal operculum thought being part of the secondary somatosensory cortex. Simultaneously the insular cortex was activated pointing to a parallel neuronal pathway to the central autonomic nervous system., Conclusion: After electrical stimulation of the esophagus somatosensory cortical areas of the temporal postcentral gyrus and the operculum are activated. In parallel activation of the insular cortex as part of the central autonomic network was found.

Background and Purpose: Transcranial Doppler sonography (TCD) studies may help to elucidate the nature and role of vascular abnormalities in migraine. Our aim in this study was to evaluate cerebrovascular autoregulative response in migraine patients with and without aura to blood pressure increase using stress TCD., Patients and Methods: Using transcranial Doppler ultrasound at rest and during ergometer stress (stress TCD), we studied the changes in mean flow velocities and resistance index (RI) in relation to physical stress in the middle cerebral artery. Fifteen migraine patients without aura, 15 migraine patients with aura, and 15 healthy control subjects were examined. Patients suffered from predominantly unilateral headache and were studied during an attack-free period. The Pourcelot's RI as a measure of cerebrovascular reactivity was calculated by dividing the difference between systolic and diastolic velocity by the systolic velocity., Results: None of the subgroups showed any difference during ergometer exercise with regard to blood pressure, endtidal CO2, heart rate, or mean flow velocity. In all subgroups, sufficient physical stress was achieved. With respect to RI change, migraine patients without aura and healthy controls did not differ (p > 0.05). However, the RI change of migraine patients with aura was significantly lower than the RI change of migraine patients without aura or healthy subjects (p > 0.05). The discrimination analysis showed in addition that RI change (absolute and as a percentage) and mean flow velocity change (as a percentage) could be used as diagnostic variables to detect patients with aura symptoms., Conclusion: Differences exist in cerebrovascular reactivity in migraine patients with aura that may contribute to the neurologic disturbances in these patients during attack. We propose that there is disorder of myogenic cerebrovascular autoregulation in migraine patients with aura during headache-free intervals.

In the etiopathology of tension type headache, vascular and autonomic disorders are discussed. Fifteen patients with chronic tension type headache according to the criteria of the IHS were investigated using the TCD-ergometer-test--a method used to evaluate the myogenic mechanism of cerebrovascular autoregulation--and the results were compared with the findings in fifteen healthy control subjects. The patients' Mean Flow Velocity (TAVmean) and Resistance Index (RI) at rest and after exercise were significantly decreased (p < 0.05). During exercise they normalized. The patients' endtidal pCO2 at rest and during exercise was significantly lower than the corresponding values of the control group (p < 0.05). Regarding blood pressure elevation and heart rate increase during exercise both groups did not differ significantly (p > 0.05). These findings suggest that patients with tension type headache have a diminished vascular tone in the cerebral vessels at rest which is normalised during exercise. The reduced endtidal pCO2 is considered as a physiological response to increase vascular tone via metabolic mechanism of cerebrovascular autoregulation. In conclusion it is suggested that therapeutic procedures which activate sympathetic autonomic nervous function to train cerebral vessels should be more carefully considered.

The diagnostic sensitivity of Vibrameter and tuning fork examination towards uremic and alcoholic neuropathy was tested in 75 patients. In 40 uremic and 35 alcoholic patients, we compared the sensitivity of neurological examination, nerve conduction studies (NCS) and vibration thresholds assessed at the malleoli by means of Vibrameter and scaled tuning fork. Vibrameter results were correlated with NCS. Polyneuropathy was diagnosed in 52 patients, but in 16 patients diagnosis depended upon inclusion of Vibrameter testing in the examination protocol. In uremic patients, Vibrameter (47.5%) showed abnormalities as often as NCS (45%), and more often than clinical (32.5%) or tuning fork examination (2.5%). In alcoholic patients, Vibrameter revealed abnormalities more often (60%) than NCS (34.3%) or tuning fork (14.3%). Correlations between NCS and vibratory thresholds were low (-0.52 < or = Rs < or = -0.35). Vibrameter studies are far more sensitive than tuning fork tests. The technique complements NCS and refines the diagnosis of uremic and alcoholic neuropathies.

The case of a patient is reported who suffered from disturbed concentration and memory and constructive apraxia. She had only mild neuropsychological deficits at the first examination. T2-weighted MRI presented extensive focal white matter changes. A brain biopsy showed changes typical for Alzheimer's disease (AD). The extent of the white matter lesions was surprising compared to the mild clinical signs she had. This case confirms that AD may result in prominent white matter disease caused by incomplete infarction or demyelination.

Continuous electroencephalographic recordings were taken in 25 children who had ethrane-nitrous oxide anaesthesia without a basal anaesthetic. The recordings confirmed the repeatedly reported occurrence of certain abnormal wave patterns distinctive of seizures during ethrane anaesthesia. Although these dysrhythmias were more frequent and more pronounced at higher ethrane concentrations and during hyperventilation, sharp spikes began to appear already at concentrations of 1.0/p.c. without hyperventilation and at moderate depths of anaesthesia. In no case did the usual criteria for assessing depth of anaesthesia provide an indication of over-dosage. Although in the individual case there was a close relationship between the concentration of ethrane in the inhaled mixture and the electroencephalographic changes, the differences between the cases were too great to allow any prediction as to the concentration of ethrane that would bring on the dysrhythmia. Considering that increased cerebral oxygen consumption has been observed to accompany the abnormal wave patterns ethrane is not recommended for use in epileptic children or those with a familial history of epilepsy.

A group of 30 alcoholics as identified using the MALT score were examined both within the first 36 h of alcohol withdrawal and then again at the end of a 10-day treatment in hospital. We looked for clinical signs of dehydration, water and electrolyte imbalance, and concentration of steroid metabolites in the urine. Cranial computed tomography was also performed twice, again at the beginning and end of the 10-day period. The size of cerebrospinal fluid spaces was calculated through measuring the frontal interhemisphere distance, the width of cortical sulci, the ventricle III diameter, the Cella media index and also the number of vermal sulci. All patients had a brain atrophy which did not disappear within the 10 days. The neuroradiological parameters remained completely unchanged in the control examination. However, the laboratory parameters of the internal milieu had normalized. Therefore, it is submitted that the shrinkage of the brain of alcoholics cannot be due to a reversible intra- or extracellulary dehydration. There was also no proof of a hormonal cause for the brain shrinkage. As a consequence other etiological factors gain importance, such as malnutrition or a toxic alcohol effect.