Abstract: Background and Aim: Hepatic encephalopathy is a frequent complication of cirrhosis. The present retrospective investigation was conducted to characterize metabolic alterations in cirrhotic patients with and without hepatic encephalopathy. We tested the hypothesis that reduced nutritional status or the degree of tissue catabolism are associated with the presence of hepatic encephalopathy. Methods: We investigated 223 patients with histologically confirmed nonalcoholic cirrhosis without hepatic encephalopathy and with hepatic encephalopathy (grades 1-3). To assess liver function, nutritional status, and energy metabolism, a variety of biochemical and clinical tests were performed including anthropometric measurements, bioelectrical impedance analysis, and indirect calorimetry. Results: Nutritional status and tissue catabolism were not significantly different between patients with and without hepatic encephalopathy. Conclusions: Our data do not support the hypothesis that malnutrition or tissue catabolism are independent risk factors for the presence of hepatic encephalopathy in patients with nonalcoholic cirrhosis.

Abstract: BACKGROUND: Focal lesions of the frontal, parietal and temporal lobe may interfere with tactile working memory and attention. To characterise the neural correlates of intact vibrotactile working memory and attention, functional MRI was conducted in 12 healthy young adults. Participants performed a forced-choice vibrotactile frequency discrimination task, comparing a cue stimulus of fixed frequency to their right thumb with a probe stimulus of identical or higher frequency. To investigate working memory, the time interval between the 2 stimuli was pseudo-randomized (either 2 or 8 s). To investigate selective attention, a distractor stimulus was occasionally presented contralaterally, simultaneous to the probe. RESULTS: Delayed vibrotactile frequency discrimination, following a probe presented 8 s after the cue in contrast to a probe presented 2 s after the cue, was associated with activation in the bilateral anterior insula and the right inferior parietal cortex. Frequency discrimination under distraction was correlated with activation in the right anterior insula, in the bilateral posterior parietal cortex, and in the right middle temporal gyrus. CONCLUSION: These results support the notion that working memory and attention are organised in partly overlapping neural circuits. In contrast to previous reports in the visual or auditory domain, this study emphasises the involvement of the anterior insula in vibrotactile working memory and selective attention.

Abstract: BACKGROUND: Alterations in brain metabolism as well as in brain function in different brain areas can be observed in severely depressed patients. METHODS: The present study combined proton magnetic resonance spectroscopy (1H MRS, n=16; healthy controls n=27) and magnetoencephalography (MEG, n=17, controls n=18) of the left auditory cortex in severely depressed inpatients pre- and post successful antidepressive therapy. For MEG recordings, patients were stimulated with trains of 4 successive vowels or 4 sine tones, respectively. For each of the 4 stimuli, the amplitude and latency of the N1m was calculated. As a measure of habituation the decrease of the individual amplitudes of the second, third and fourth N1m compared to the first N1m was calculated. RESULTS: Prior to therapy, a subset of patients presented clearly disturbed auditory processing to stimuli (missing of distinct N1m1 and subsequent habituation; 5 of 17 patients (vowels) and 9/17 (tones, respectively)). After treatment, compared to controls, a normalized habituation pattern was observed in all patients for vowels, but not for tones. In contrast, MRS revealed no significant differences between the metabolite concentrations of patients and healthy controls in both measurements. CONCLUSION: Depression may be accompanied by impaired auditory processing, which seems to improve with reduction in depressive symptoms. Auditory cortical dysfunction probably reflects only a part from more widespread aberrations of brain function occurring with severe mood disorder.

Abstract: To investigate the neural network of overt speech production, event-related fMRI was performed in 9 young healthy adult volunteers. A clustered image acquisition technique was chosen to minimize speech-related movement artifacts. Functional images were acquired during the production of oral movements and of speech of increasing complexity (isolated vowel as well as monosyllabic and trisyllabic utterances). This imaging technique and behavioral task enabled depiction of the articulo-phonologic network of speech production from the supplementary motor area at the cranial end to the red nucleus at the caudal end. Speaking a single vowel and performing simple oral movements involved very similar activation of the cortical and subcortical motor systems. More complex, polysyllabic utterances were associated with additional activation in the bilateral cerebellum, reflecting increased demand on speech motor control, and additional activation in the bilateral temporal cortex, reflecting the stronger involvement of phonologic processing.

Abstract: BACKGROUND: A combination of magnetoencephalography and proton magnetic resonance spectroscopy was used to correlate the electrophysiology of rapid auditory processing and the neurochemistry of the auditory cortex in 15 healthy adults. To assess rapid auditory processing in the left auditory cortex, the amplitude and decrement of the N1m peak, the major component of the late auditory evoked response, were measured during rapidly successive presentation of acoustic stimuli. We tested the hypothesis that: (i) the amplitude of the N1m response and (ii) its decrement during rapid stimulation are associated with the cortical neurochemistry as determined by proton magnetic resonance spectroscopy. RESULTS: Our results demonstrated a significant association between the concentrations of N-acetylaspartate, a marker of neuronal integrity, and the amplitudes of individual N1m responses. In addition, the concentrations of choline-containing compounds, representing the functional integrity of membranes, were significantly associated with N1m amplitudes. No significant association was found between the concentrations of the glutamate/glutamine pool and the amplitudes of the first N1m. No significant associations were seen between the decrement of the N1m (the relative amplitude of the second N1m peak) and the concentrations of N-acetylaspartate, choline-containing compounds, or the glutamate/glutamine pool. However, there was a trend for higher glutamate/glutamine concentrations in individuals with higher relative N1m amplitude. CONCLUSION: These results suggest that neuronal and membrane functions are important for rapid auditory processing. This investigation provides a first link between the electrophysiology, as recorded by magnetoencephalography, and the neurochemistry, as assessed by proton magnetic resonance spectroscopy, of the auditory cortex.

Abstract: We used magnetoencephalography to study contralesional auditory reorganization in three men with chronic unilateral ischemic lesions of the auditory cortex. Although no response was found over the lesioned hemisphere, processing in the unaffected hemisphere was indistinguishable vs healthy controls. In contrast to sensorimotor and language systems, the auditory system seems to lack contralateral reorganization, presumably because patients are typically not aware of hearing deficits and thus do not perform training.

Abstract: BACKGROUND: Cluster headache (CH) is a neurovascular, primary headache disorder. There are, however, several case reports about patients whose CH started shortly after a structural brain disease or trauma. Motivated by a patient who developed CH 3 weeks after the removal of an eye and by similar case reports, we tested the hypothesis that the removal of an eye is a risk factor for CH. METHODS: A detailed headache questionnaire was filled out by 112 patients on average 8 years after enucleation or evisceration of an eye. RESULTS: While 21 % of these patients experienced previously unknown headaches after the removal of an eye, no patient fulfilled the diagnostic criteria for CH. CONCLUSION: Our data does not suggest that the removal of an eye is a major risk factor for the development of CH.

Abstract: The esophagus plays a major role in the act of swallowing. The aim of the present investigation was to apply whole-head magnetoencephalography in order to study the cortical processing of esophageal sensation in healthy humans in whom the cortical representation of swallowing had been established previously. The proximal esophagus was stimulated in nine participants by intermittent 5 ml water infusion. Submental EMG recording was used to identify trials, which were contaminated by subsequent swallowing. Esophageal stimulation led to changes in rhythmic activity of the brain that were localized in the left lateral primary sensorimotor cortex. The pattern of cortical activation showed the same hemispheric lateralization as that of volitional swallowing, however, being localized more lateral. The close anatomical vicinity of these two functions points to an important physiological link between the cortical processing of esophageal sensation and the cortical control of swallowing.

Abstract: Conjoined lumbosacral nerve roots (CLNR) are the most common anomalies involving the lumbar nerve structures which can be one of the origins of failed back syndromes. They can cause sciatica even without the presence of a additional compressive impingement (such as disc herniation, spondylolisthesis or lateral recess stenosis), and often congenital lumbosacral spine anomalies (such as bony defects) are present at the "conjoined sheaths". This congenital anomaly has been reported in 14% of cadaver studies, but myelographic or computed tomographic studies have revealed an incidence of approximately 4% only. Diagnostic methods such as magnetic resonance imaging (MRI) are helpful for determination of the exact anatomical relations in this context. We present five typical cases of conjoined nerve roots observed during a 1 year period, equivalent to 6% of our out-patients without a history of surgical treatment on the lumbar spine. In all cases with suspicious radiological findings MRI or lumbar myelography combined with CT and multiplanar reconstructions is recommended.

Abstract: Activation of the auditory cortex habituates with repeated stimulation. While behaviorally adaptive in most circumstances, decreasing auditory responsiveness could interfere with speech perception. We therefore tested whether auditory habituation differs for speech and non-speech stimuli and for left and right auditory cortex. We examined seven right-handed subjects in whom we had determined left-hemispheric language dominance by event-related blood flow assessment. We recorded magnetoencephalographic-evoked responses to trains of four sine tones or vowels and measured the decrement from the first to the last stimulus of the response component about 100 ms after stimulus onset (N1). For the sine tones there was a decrement in both hemispheres. Conversely, for vowels there was significant attenuation of the auditory decrement in the left compared with the right hemisphere (p=0.017). This left-hemisphere persistence in auditory responsiveness to vowels demonstrates that the human brain processes speech stimuli differently than non-speech stimuli and that the left-hemisphere plays a dominant role in this speech-specific auditory processing.

Abstract: The aim of this study was to measure and quantify habituation effects to auditory stimulation within the auditory cortex of 11 depressed patients with major depressive disorder compared to 11 healthy subjects. Habituation was visualized by functional magnetic resonance imaging (fMRI) employing a block design (repeated stimulation with sine tones). A subgroup of patients (n = 5) presented the following abnormal habituation fMRI pattern: significantly lower activation after the first stimulation block (p = 0.05), missing characteristic signal decay to repeated acoustic stimulation and a marked undershoot after each stimulation block. This abnormal pattern may indicate functional deficits in auditory processing occurring with depression, but our results need be confirmed in a larger, more homogeneous patient group. This paradigm may be a useful tool for assessing cortical dysfunction in mood disorders.

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Abstract: Previous magnetoencephalography (MEG) studies of sleep spindles have identified a complex and widespread distribution in parietal and frontal cortices by fitting a dipolar model to the data. In this study, we used a whole-head 151-channel MEG system with simultaneous electroencephalography (EEG) recording in eight normal subjects. All subjects fell asleep during stage 2 and 3; EEG spindles have been observed in all cases. The current source density distribution of sleep spindles in the 10-15 Hz frequency band was localized by means of synthetic aperture magnetometry, and statistically tested using a permutation analysis. Source locations of the sleep spindles were found primarily in the frontal cortex, including dorsolateral and medial prefrontal areas, as well as the parietal cortex, including the vicinity of the primary sensorimotor areas. These results suggest that sleep spindles are similar in frequency content and spatial location to mu rhythm, and that these two oscillatory activities might also have a common neural basis and physiological meaning.

Abstract: Recently, a new method for placing nasogastric tubes (NGT) in dysphagic patients was proposed, which uses the swallowing reflex and was therefore called ’reflex placement.’ The authors describe the use of this method in a patient with a large left sided striatocapsular hemorrhage, in whom decompressive craniotomy had been performed previously. Whereas the conventional approach of placing NGT led to a massive increase of intracranial pressure (ICP) and to a decline in cerebral perfusion pressure (CPP), the new method allowed a swift placement with only minor changes of ICP and CPP. The strict avoidance of intermittent peaks of ICP constitutes a basic principle of care in patients with space occupying brain lesions. We therefore suggest that, despite the admittedly larger effort, the reflex placement of NGTs should be used in such circumstances.

Abstract: This study presents data on the clinical characteristics and possible mechanisms of the phantom eye syndrome in 112 patients after removal of one eye. The prevalence of phantom eye pain was 26%, nonpainful phantom sensations 29%, and visual hallucinations 31%. Headaches and preoperative eye pain were associated with the presence of phantom experiences. These results suggest that pain is an important cofactor for the development of phantom eye phenomena.

Abstract: This study employed whole head magnetoencephalography and synthetic aperture magnetometry to investigate the cortical topography of the preparation and the execution of volitional and reflexive water swallowing and of a simple tongue movement. Concerning movement execution, activation of the mid-lateral primary sensorimotor cortex was strongly lateralized to the left during volitional water swallowing, less strongly lateralized to the left during reflexive water swallowing, and not lateralized at all during tongue movement. In contrast, the preparation for both volitional water swallowing and tongue movement showed a bilateral activation of the primary sensorimotor cortex. No activation was seen prior to reflexive water swallowing. Activation of the left insula and frontal operculum was observed only during both the preparation and the execution of volitional water swallowing. These new findings suggest a left hemispheric dominance for the cortical control of swallowing in humans.

Abstract: BACKGROUND: Phantom pain is a well known and extensively documented complication after limb amputation. Nearly all surgical disciplines have to deal with phantom symptoms related to different anatomical regions and organs but limited data is available about phantom eye pain (PEP) after enucleation. Only one pilot study is present in literature. It was the aim of this study to analyze a group of patients with a standardized surgical procedure of enucleation concerning the incidence of PEP and its relation to further preoperative and postoperative data. PATIENTS AND METHODS: A standardized questionnaire was sent to all enucleation patients with primary orbital implant performed between 1/1/1986 and 12/31/1995 at Munster University. Data of 94 patients could be analyzed with regard to PEP, perioperative pain symptoms and further ophthalmological and surgical data. RESULTS: 24 of 94 patients reported PEP after enucleation. The frequency of PEP was less than once per month in the majority of patients (71%). 2 of 24 patients suffered from PEP on more than 4 days/month. Perioperative pain symptoms (ocular pain [OP], preoperative and postoperative headache) were reported with a higher proportion (each p<0.0025) in patients with PEP compared to those not affected by PEP. All patients with a preoperative history of OP longer than 5 years and 75% of patients with OP longer than 12 months of pre-enucleation OP were affected by PEP. CONCLUSIONS: Phantom eye pain is present in nearly 1/4 of patients after enucleation and is significantly related to other perioperative pain symptoms.

Abstract: Neuropsychological studies have demonstrated that the production of nouns and verbs can be dissociated in aphasia. These reports have been taken as evidence for separate representations of nouns and verbs in the human brain. We used whole-head magnetoencephalography to record cortical dynamics of action and object naming in 10 healthy adults and in 1 anomic patient with superior naming of verbs compared with nouns due to a left posterior parietal lesion. A single set of 100 line drawings was used for both action and object naming. In normal subjects, the activation sequences in action and object naming were essentially identical, advancing from the occipital to posterior temporoparietal and further to the left frontal cortex, without consistent involvement of the classical left inferior frontal (Broca) and temporal (Wernicke) language areas. In the anomic patient, pronounced differences between action and object naming emerged in the left hemisphere. The activation sequence was disrupted at the level of the damaged parietal cortex and did not reach the left frontal cortex even in the relatively easier action naming. The more severely impaired object naming was associated with exceptionally strong and early activation of the left inferior frontal cortex (Broca) and subsequent pronounced activation of the left middle temporal cortex, silent in action naming. Verb and noun retrieval thus utilized a spatiotemporally similar neuronal network in healthy individuals. A clear dissociation in cortical correlates of verb and noun retrieval only became evident in our anomic patient, in whom damage to the language network has resulted in disproportionately worse performance in object than action naming.

Abstract: The somatosensory system is capable of functional reorganization following peripheral denervation or training. Studies on human amputees with phantom limb pain provided evidence that these reorganizational changes are modulated through nociceptive input. In the present study we used magnetoencephalographic recordings of six healthy volunteers to assess whether acute pain by itself causes a reorganization of the primary somatosensory cortex. After the induction of an intense experimental pain at the thenar of the left hand by intradermal injection of capsaicin, the extent of the cortical hand representation and the distance between the hand representation and the localization of the lip decreased. A likely mechanism for this acute reorganization is that pain induced hyperresponsiveness of the left thenar to tactile input from neighboring body sites.

Abstract: Chronic hypoxaemia in chronic obstructive pulmonary disease is a well known risk factor for polyneuropathy but the impact of intermittent hypoxaemia on peripheral nerve function has not been established so far. A case-control study was performed to evaluate the prevalence of polyneuropathy in obstructive sleep apnoea (OSA). Out of 24 patients with OSA, 17 (71%) had clinical signs of polyneuropathy versus seven (33%) out of 21 matched controls. The mean amplitude of the sural sensory nerve action potential was smaller in the OSA group than in the control group, indicating axonal nerve damage. The differences were significant and could not be attributed to other known risk factors for polyneuropathy. The severity of axonal damage in patients with OSA correlated with the percentage of the night time with an O(2) saturation below 90%. It is assumed that recurrent intermittent hypoxaemia in OSA is an independent risk factor for axonal damage of peripheral nerves.

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Abstract: In this longitudinal study multichannel MEG was used to localize and to quantify focal pathological spontaneous neuromagnetic activity in six patients with transient ischemic attacks (TIA) and two patients with transient global amnesia (TGA). Slow (2-6 Hz) and beta (14-30 Hz) activity were monitored up to 10 weeks. Results were compared with normative data, and changes over time were statistically analyzed. MEG detected pathological activity that persisted clinical symptoms. Focal slow activity originating from sensorimotor (TIA) and mesiotemporal (TGA) cortices exceeded normal values up to 14 times during the first hours after the attack and recovered to normal within 11 days. Focal beta activity was not useful to monitor the time course of TIA or TGA.

Abstract: Hemispheric asymmetry is known for higher brain functions like language and attention. We tested whether such an asymmetry also exists in the representation of elementary sensory functions. Magnetic source imaging was used to compare the cortical somatosensory hand representation in seven right- and five left-handed individuals. In all right-handers the representation of the dominant hand was larger than the contralateral one in the corresponding hemispheres. In contrast, only two out of five left-handers revealed a larger representation of the dominant left hand compared to the right one. In agreement with previous findings on the lateralization of language and attention, there is a strong correlation between handedness and the extent of the cortical hand representation in right-, but not in left-handers. We conclude that a profound functional hemispheric asymmetry also exists in primary sensory cortices.

Abstract: In multiple sclerosis (MS) inflammatory infiltrations cause white matter lesions. Magnetoencephalography (MEG) offers the opportunity to localize abnormal electric activity of neurons with a high spatio-temporal resolution. In this study, we investigated patients with MS in order to find if abnormal cortical activity is associated with (subcortical) MS lesions using simultaneous bilateral recording of biomagnetic activity. Eight patients suffering from definite laboratory-supported MS with mainly somatosensory deficits and multiple bihemispheric plaques revealed by MRI were included in the study. To obtain normative data, 8 healthy volunteers were investigated following the same measuring protocol. Spontaneous magnetic brain activity was recorded using a 2x37-channel biomagnetic system (BTI, USA). Offline analysis included digital filtering (to separately investigate slow and beta wave activity), a Principle Component Analysis and the Dipole Density Plot. Localization results were inserted into MR images using our contour fit procedure. The dipole distribution in the brain was quantified and compared between the groups by statistical analysis. In all MS patients, the maximum of focal abnormal activity was localized in cortical areas adjacent to the fiber lesions. In the healthy subjects, no focal abnormal brain activity could be found. However, the standardized maximum concentrations of dipoles were significantly higher in the MS patients than in the healthy control group both in the slow and in the beta wave analysis. These results let assume that subcortical lesions can occur together with abnormal cortical neuronal activity. The results are discussed in respect to their impact on the interpretation of the analysis of spontaneous magnetic brain activity.

Abstract: Prostaglandin E analogs have been shown to be effective in the treatment of refractory trigeminal neuralgia in patients with multiple sclerosis. Prostaglandin E inhibits the functions of T lymphocytes which are involved in the pathophysiology of cluster headache. Therefore, a double-blind, placebo-controlled, crossover study on the efficacy of misoprostol in chronic refractory cluster headache was performed. Eight patients were treated with 600 micrograms misoprostol and with placebo for a 2-week period. No differences in attack frequency, intensity, global impression, and side effects could be detected, suggesting that prostaglandin E analogs are not effective in the treatment of chronic cluster headache.

Abstract: Autonomic functions of different primary headache types have been investigated in several studies, most of them analyzing cardiovascular reflex mechanisms or biochemical changes. The results are contradictory; only in tension-type headache and in cluster headache has a sympathetic hypofunction been shown in a preponderance of studies. We analyzed the peripheral autonomous potentials (PAPs) in different primary headache types and in drug-induced headache and compared the results with those of healthy subjects and of patients with low back pain. Latencies of PAPs were significantly increased in all headache types but not in low back pain; amplitudes of PAPs did not show significant differences compared to healthy subjects. Patients with a long duration of drug abuse had increased PAP latencies, whereas patients with a high number of migraine attacks per year had decreased latencies. Our data suggest that sympathetic hypofunction as measured by PAP latencies is a general phenomenon in headache but not in all pain syndromes. Drug abuse leads to an increase of this hypofunction. While measuring PAPs is not an appropriate method by which to differentiate between headache disorders, it allows assessment of autonomic disturbances in primary and drug-induced headache.

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Abstract: Functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) were performed in six subjects during self-paced finger movement performance, tactile somatosensory stimulation and binaural auditory stimulation using identical stimulation paradigms. Both functional imaging modalities localized brain activity in adjacent areas of anatomically correct cortex. The mean distances measured between fMRI activity and the corresponding MEG dipoles were 10.1 mm (motor), 10.7 mm (somatosensory), 13.5 mm (auditory right hemisphere) and 14.3 mm (auditory left hemisphere). The distances found may reflect the correlation between electrophysiological and hemodynamic responses due to the different underlying substrates of neurophysiology measured by fMRI and MEG: BOLD contrast vs neuronal biomagnetic activity.

Abstract: Lipoprotein-X (Lp-X) is an abnormal low-density lipoprotein frequently found in liver disease. It is regarded as the most sensitive and specific biochemical parameter for the diagnosis of intra- and extrahepatic cholestasis. Moreover, Lp-X is supposed to contribute to the development of hypercholesterolemia in cholestatic liver disease, because it fails to inhibit de novo cholesterol synthesis. This investigation will focus on the relationship between the presence of Lp-X and serum lipid concentrations in cirrhosis. The significance of Lp-X in the diagnosis of cholestasis, compared with alkaline phosphatase (AP), gamma-glutamyl transferase (GGT), and bilirubin levels, will be assessed as well. The present cross-sectional study includes 212 patients with histopathologically proven cirrhosis. The detection of Lp-X and the quantification of -, beta-, and pre-beta-cholesterol was based on agar gel electrophoresis and polyanion precipitation. For the characterization of liver function, the concentrations of albumin and bilirubin, the activities of liver enzymes, and coagulation times were assessed. In a subgroup of 40 individuals, liver biopsies were re-evaluated to confirm or exclude intrahepatic cholestasis. As a result, there was no association between the appearance of Lp-X and total cholesterol concentrations. While all patients with Lp-X showed intrahepatic cholestasis (predictive value of the positive test = 1), only 16 of 28 patients with cholestasis formed Lp-X (sensitivity = 0.57). The activities of AP and of GGT, as well as the concentrations of bilirubin, were strongly elevated in most patients, with and without cholestasis. The predictive values of AP, GGT, and bilirubin were 0.77, 0.69, and 0.74 for the positive test and 0.5, 0, and 0.6 for the negative test, respectively. We conclude that Lp-X is not related to hypercholesterolemia in cirrhosis. The positive, but not the negative, Lp-X test has high predictive value for the diagnosis of cholestasis in cirrhosis. The biochemical parameters traditionally used for the assessment of extrahepatic cholestasis, AP, GGT, and bilirubin, do not support the diagnosis of intrahepatic cholestasis caused by cirrhosis.

Abstract: In human amputees with painful phantom sensations, mislocalizations of tactile stimuli to the phantom increase with the amount of cortical representational reorganization and the extent of phantom pain. A similar phenomenon was incidentally encountered in healthy subjects. For reasons unrelated to the question of mislocalization, we performed a study involving the application of experimental acute pain to the hand followed by non-noxious tactile stimulation of the ipsilateral lip. During lip stimulation, two out of six subjects spontaneously reported perceiving an additional phantom-like sensation in the hand synchronously to the non-noxious lip stimulation. Similar, although more diffuse, phantom sensations were observed in two out of seven additional subjects who were then tested specifically for this effect. The observation is compatible with a pain-induced hyperresponsiveness of the cortical hand area to somatotopically adjacent inputs from the lip. This suggests that, even in the absence of deafferentation, pain can lead to a representational reorganization.

Abstract: A 37-year-old man developed an ipsilateral headache which fulfilled the criteria for cluster headache after orbital extenteration because of a traumatic lesion of the bulb. The headache could be treated successfully by drugs usually applied in the therapy of cluster headache. Six similar cases of cluster headache after orbital exenteration could be identified in the literature suggesting that the eye itself is not necessarily part of the pathogenesis of cluster headache. We hypothesize that orbital exenteration can cause cluster headache by lesions of sympathetic structures. Possibly, these mechanisms are similar to those of sympathetic reflex dystrophy (Sudeck-Leriche syndrome) causing pain of the limbs.