Limbic encephalitis due to GABAB and AMPA receptor antibodies: a case series.

BACKGROUND: Two novel antibodies (abs) directed to γ-aminobutyric acid B receptor (GABA(B)R) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) in patients with limbic encephalitis (LE) were first described by the Philadelphia/Barcelona groups and confirmed by the Mayo group. We present a novel series for further clinical and paraclinical refinement. METHODS: Serum and cerebrospinal fluid samples from a diagnostic laboratory were selected if found to be positive for GABA(B)R or AMPAR abs within a broad antineuronal ab panel. Data were retrospectively compiled. RESULTS: In 10 patients, we detected abs to GABA(B)R. Median age was 70 years. Five of them were diagnosed with small cell lung cancer (SCLC). Intrathecal GABA(B)R ab synthesis was found in all six patients with sufficient data available (median ab-index: 76.8). On MRI, we found bilateral mediotemporal and in two cases cortical abnormalities. EEG revealed encephalopathy, partly with epileptiform discharges. Five patients received immunotherapy, two patients tumour treatment and three both therapies. Three patients died, in five patients cognitive functions declined, one patient improved slightly and one patient fully recovered. AMPAR abs were detected in three patients with mnestic disturbances. Median age was 60.7 years. The only female patient was diagnosed with ovarian cancer. None of the patients had intrathecal ab synthesis. MRI findings showed bilateral mediotemporal abnormalities. EEG was normal in all patients. Two of the three immunologically treated patients improved, one patient stabilised on a low level. DISCUSSION: GABA(B)R and AMPAR abs are well associated with LE. GABA(B)R abs lead to severe clinical, neuroradiological and EEG abnormalities with poorer outcome.

Post-coronavirus disease 2019 polyneuropathy with significant response to immunoglobulin therapy: a case report.

BACKGROUND: The symptoms of coronavirus disease 2019, caused by the novel severe acute respiratory syndrome coronavirus 2, were originally assumed to be mainly respiratory. With increasing knowledge, however, it turned out that the spectrum of complaints varies broadly with age and concomitant diseases. While many neurological symptoms were reported in the context of the disease, ranging from permanent fatigue to recurrent headaches and concentration disturbance, treatment approaches are still in development. This case discusses a possible treatment approach with immunoglobulin therapy and its outcomes. CASE PRESENTATION: We present the case of a 56-year-old Caucasian female patient who, following coronavirus disease 2019, developed peripheral sensory and autonomic disturbances that fell within subacute demyelinating neuropathy. Because a significant improvement in symptoms as well as in the results of clinical and electrophysiological examination was reported after immunoglobulin therapy, long-term therapy does not appear to be necessary. CONCLUSION: Given the significant subjective and objective improvement reported, this case provides additional evidence that immunoglobulin therapy can be considered in post-coronavirus disease 2019 syndrome.

[Monoaminergic transmitters in the cerebrospinal fluid of patients with acute, chronic, and intermittent pain. Interface between pain and depression?]. / Monoaminerge Transmitter in der Zerebrospinalflüssigkeit von Patienten mit akuten, chronischen und episodischen Schmerzen. Schnittstelle zu depressiven Symptomen?

BACKGROUND AND STUDY PURPOSE: Pain and depression share similar neurobiological characteristics, and it is a common clinical observation that pain and depression may coincide in the same patient. They also appear to influence each other in the process of chronification. Furthermore, there is a complex coupling of pain and depression by monoaminergic transmitter system. PATIENTS AND METHODS: On the basis of these findings, norepinephrine (NE), epinephrine (E), dopamine (DOP), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and vanillylmandelic acid (VMA) concentrations were determined in the cerebrospinal fluid (CSF) in patients with acute (20), chronic (27), and episodic pain syndrome (44) in a prospective study. The biochemical parameters were correlated to self-assessment pain and depression scores. The control group consisted of 13 pain-free patients with diseases affecting the muscular system. RESULTS: Patients with chronic and episodic pain syndromes had significantly more depressive and psychovegetative symptoms compared to patients with acute pain. In patients with acute pain, DOP was significantly higher than in controls and chronic and episodic pain patients. In addition DOP was positively correlated to self-assessment pain score (p*<0.05). In patients with chronic and episodic pain, NE and 5-HIAA were positively correlated to the duration of disease and were significantly lower than in the control group. In neither of these two groups could significant correlations be established between these parameters and pain or depression self-assessment scores. In all groups, positive correlations were seen between the neurotransmitter and their metabolites. CONCLUSION: The pathological decrease of NE and 5-HIAA in the CSF points to the crucial role of noradrenergic and serotonergic transmitter systems in the generation, modulation, and perpetuation of chronic and episodic pain syndromes. It indicates that antidepressants are effective drugs in these diseases. However, a discriminative neurochemical pattern between pain and depression could not be established. The demonstration of polyvalent correlations between different neurotransmitters is indicative of complex neurobiological coupling between cortical, limbic, and hypothalamic neuronal networks on the one hand and the nociceptive descending system on the other hand in the genesis of pain and depression.

Molecular forms of somatostatin-like immunoreactivity in the cerebrospinal fluid of patients with senile dementia of the Alzheimer type.

In the cerebrospinal fluid (CSF) of 53 patients with senile dementia of the Alzheimer type (SDAT) and 12 elderly controls, we measured somatostatin (SLI) and its molecular forms: high-molecular weight form (HMV-SST), somatostatin-14 (SST-14), somatostatin-25/28 (SST-28/25), and des-ala-somatostatin (des-ala-SST) using high pressure liquid chromatography (HPLC) and a radioimmunoassay. In SDAT, SLI was significantly decreased (p < 0.05) and correlated with dementia scores (r = -0.65, p < 0.05). HPLC separation showed a marked heterogeneity of SLI in the CSF with a preponderance of SST-14 and SST-25/28. The significant loss of SST-14 (p < 0.05) in SDAT was found to be correlated with dementia scores (r = 0.65). Moreover, qualitative and quantitative changes in the molecular pattern of SLI in SDAT indicated dysregulated synthesis and/or processing of somatostatin relating to the severity of dementia. The long-term administration of neuroleptics in severe cases of SDAT caused a significant increase of SLI (p < 0.05) and influenced the ratio of HMV-SST/SST-14 and SST25/28/SST-14.

Thunderclap headache caused by Erve virus?

Systematic studies of a possible human neuropathogenicity of the Erve virus have not yet been carried out. In a randomized, blind study 166 patients with viral encephalitis, 46 patients with cerebral hemorrhage, 72 patients with "thunderclap" headache, and 205 healthy blood donors were examined by indirect immunofluorescence for Erve virus antibodies. None of the patients with encephalitis, two patients with cerebral hemorrhage (4.3%), 10 patients with thunderclap headache (13.9%; p < 0.0001), and two blood donors (1.0%) exhibited antibodies against the Erve virus. These results suggest a human pathogenicity of the Erve virus for the first time.

Femoral injection of echo contrast medium may increase the sensitivity of testing for a patent foramen ovale.

OBJECTIVE: The diagnosis of a patent foramen ovale (PFO) as a cause of stroke is of increasing interest especially in young (<45 years) patients. METHODS: We studied potential right-to-left shunting using transesophageal echocardiography (TEE) and bilateral transcranial Doppler sonography (TCD) of the middle cerebral artery (MCA) simultaneously in 44 patients. All patients were younger than age 45 years and suffered from an acute ischemic stroke or transient ischemic attack. Other possible etiologies were excluded. Echo contrast medium was injected in an alternating mode via antecubital or femoral veins. Tests were performed with and without the Valsalva maneuver. The criteria for a PFO were that the contrast pass from the right to the left atrium (TEE) and early detection (<10 seconds) of more than 10 micro air bubbles in at least one MCA by TCD. RESULTS: A PFO was diagnosed in 22 patients (50%). The detection rate with TEE/TCD was 11.4%/4.5% via antecubital injection, 18%/13.6% via antecubital injection plus the Valsalva maneuver, 38.6%/36% via femoral injection alone, and 50%/50% via femoral injection plus the Valsalva maneuver. The difference between femoral and antecubital injections was significant with and without the Valsalva maneuver (p < 0.01, chi2 test). There were no differences between TEE and TCD after femoral injection with the Valsalva maneuver. The brain transit time was 4.6 +/- 2.1 seconds for femoral injection and 6.3 +/- 4.1 seconds for antecubital injection. CONCLUSIONS: The sensitivity in detecting a PFO was markedly increased by femoral injection. This may be caused by different inflow patterns to the right atrium: inferior vena caval flow is directed to the right atrial septum, whereas superior vena caval flow is directed to the tricuspid valve. Thus, femoral injection may help to improve the detection of PFO and may explain the differences between TEE and TCD findings in previous studies.

Parkinson's disease and dementia: clinical and neurochemical correlations.

In 38 old aged parkinsonian patients, two major subgroups could be established: one with predominant akinesia, rigidity, postural instability and accompanying cognitive impairment with intellectual deterioration correlated with duration of disease but not with age of onset and another with predominant tremor and relatively intact intellectual functions. The mean somatostatin-like immunoreactivity (SLI) level in the cerebrospinal fluid (CSF) was significantly lower in parkinsonian patients (21.4 +/- 8.1 fmol ml-1) compared to senile control patients (29.5 +/- 9.4 fmol ml-1). In contrast to senile dementia of Alzheimer's type SLI was not correlated with dementia scores but with motor disease progression. Homovanillic acid (HVA) significantly decreased only in patients without L-DOPA treatment. Correlations between SLI, HVA and 5-hydroxyindole acetic acid (5-HIAA) indicate a degeneration of multiple neuronal networks which includes somatostatinergic neurons.

Lateralization in autonomic dysfunction in ischemic stroke involving the insular cortex.

Autonomic nervous system dysfunction is a common complication of ischemic stroke. Clinical and experimental data indicate hemispheric lateralization in the control of autonomic activity. The insular cortex has also been shown to play a crucial role in the central autonomic network. The aim of this study was to assess cardio-autonomic dysfunction in patients with ischemic insular versus non-insular cortex infarction, and to demonstrate a possible lateralization in autonomic activity mediated by the insular cortex. Sympathetic function was prospectively assessed by determining plasma norepinephrine and epinephrine in 15 patients with left-hemisphere (LH; four insular infarction), and 14 with right-hemisphere (RH) middle cerebral artery (MCA) stroke (five insular infarction). Systolic and diastolic blood pressure and heart rate were recorded during the first 5 days after stroke. Sympathetic activity was significantly higher in insular than in non-insular infarction (p < 0.05) with concomitantly elevated cardiovascular parameters in insular stroke patients. The pathological activation of the sympathetic nervous system was most excessive in RH-stroke involving the insular cortex (p < 0.05). Our data indicate a hemispheric lateralization in autonomic activity which is mediated by the right-sided insular cortex. Patients with RH stroke involving the insular cortex are most susceptible to develop cardio-autonomic dysfunction.

Renin activation correlates with blood amount and distribution in subarachnoid haemorrhage.

Blood extent and localization visible in CCT predicts complications and prognosis in patients suffering from subarachnoid haemorrhage (SAH). Plasma renin activity (PRA) elevation is one of the hormonal parameters of autonomic disorders after SAH and its prognostic relevance could be confirmed by this study, too. But the correlation of PRA with blood amount and distribution was the main target of this study. Large amounts of blood are connected with higher PRA-levels and more PRA-rises. Even a linear correlation between the amount of blood defined by a CCT-score and PRA in ng ml h-2 could be established. A significant correlation was found between intraventricular, suprasellar blood, ventricular enlargement of the third/lateral ventricles and PRA-elevations. Disorders of hypothalamic and/or medullary centres of sympathetic control are thought to be the underlying cause and to depend on blood extent and distribution.

Altered activity of the sympathetic nervous system and changes in the balance of hypophyseal, pituitary and adrenal hormones in patients with cluster headache.

Twelve patients (age 43.4 +/- 6.3 years) with episodic cluster headache (CH) were examined during the cluster period. Plasma norepinephrine levels in patients suffering from CH were significantly decreased compared with the control group (p < 0.01). There were also statistically significant correlations between norepinephrine levels and clinical features of the pain attacks including duration (r = 0.75, p < 0.05), intensity (r = 0.64, p < 0.05) and frequency (r = 0.68, p < 0.06), thereby suggesting a pathophysiological involvement of the sympathetic nervous system in CH. Increased plasma levels of plasmacortisol and ACTH in patients with CH, especially in the morning and in the evening, suggest an alteration of the feedback circuit involving the hypothalamus, the pituitary and the adrenal gland, an imbalance in the hormones related to these structures, as well as an alteration of the circadian rhythm. In addition, CH patients demonstrated significantly decreased levels of norepinephrine (p < 0.05), HVA (p < 0.01) and 5-HIAA (p < 0.01) in the cerebrospinal fluid (CSF) consistent with a central genesis of CH. These significant relationships between neurochemical parameters and the clinical patterns suggest a complex interplay between the hypothalamus, neuroendocrinological parameters, activity of the autonomic nervous system and the pain of CH.

Intravenous immunoglobulins in the therapy of paraneoplastic neurological disorders.

The treatment of paraneoplastic neurological syndromes (e.g., tumor therapy, immunosuppressive therapy, plasmapheresis) rarely leads to an improvement in the neurological symptoms. We treated four patients suffering from paraneoplastic neurological syndromes with intravenous immunoglobulins. All four had high titers of antineuronal antibodies in serum and CSF. Two of the patients, one suffering from paraneoplastic cerebellar degeneration and the other from paraneoplastic brain stem encephalitis and polyneuropathy, received intravenous immunoglobulin treatment within 3 weeks of the onset of neurological symptoms. Both patients showed clinical improvement within 2 weeks after the initiation of therapy. They also showed a decline in the intrathecal antibody synthesis of the antineuronal antibody. Two other patients, who had suffered from paraneoplastic neuropathy for 3 and 6 months showed no improvement with the intravenous immunoglobulin therapy. In these cases there was no effect on intrathecal antibody synthesis. When started early, intravenous immunoglobulins may be of therapeutical value in treating paraneoplastic neurological syndromes. Specific intrathecal antibody synthesis may be a better measure of clinical course that autoantibody serum titers.

CSF substance P somatostatin and monoaminergic transmitter metabolites in patients with narcolepsy.

We have measured the concentrations of substance P, somatostatin, homovanillic acid (HVA), vanillyl mandelic acid (VMA) and 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) of six patients suffering from narcolepsy and 12 age- and gender-matched controls using high pressure liquid chromatography (HPLC) and radioimmunoassay (RIA). Substance P and somatostatin were significantly decreased in our patients compared to controls (36.9 +/- 9.1 fmol/ml versus 52.5 +/- 9.9 fmol/ml, P < 0.05 and 30.3 +/- 7.8 fmol/ml versus 43.9 +/- 9.8 fmol/ml, P < 0.05, respectively). 5-HIAA (P < 0.05) and VMA (P < 0.05) were also significantly decreased. HVA was significantly increased (P < 0.01). The CSF concentrations of substance P and somatostatin correlated with the clinical parameters duration of disease (r = -0.68, P < 0.05 and r = -0.72, P < 0.05, respectively) and severity of cataplectic symptoms (r = -0.71, P < 0.05 and r = -0.78, P < 0.01). In addition, substance P correlated with the intensity of sleepiness and the frequency of day-sleep attacks (r = -0.69, P < 0.05 and r = -0.68, P < 0.05, respectively). Substance P affects the amount of dopamine release in the nigra-striatal region, and decreased amounts could contribute to the pathogenesis of narcolepsy. Reduced levels of substance P, which affects serotonin release, may be responsible for diminished release of serotonin which in turn could affect sleep cycles. Because somatostatin affects motor behavior through dopaminergic mechanisms and since the levels of somatostatin correlate with the intensity of cataplectic symptoms, we speculate that an interaction between somatostatin and dopaminergic neurons plays a role in the pathogenesis of narcolepsy.

Antineuronal antibody-associated paraneoplastic neuropathy in Hodgkin's disease.

Paraneoplastic neurological syndromes in patients with Hodgkin's disease are rare findings. Subacute, paraneoplastic cerebellar degeneration or autonomic dysfunctions were described before. In some of these cases, autoantibodies against central or peripheral nervous system structures were found in serum and CSF. We present a 30-year-old white male who developed a progredient, clinical and electrophysiological distal sensomotoric neuropathy. Six months after the beginning of the neurological disturbances, Hodgkin's disease (Stadium III BE) was diagnosed. Other reasons for neuropathy, such as direct impairment of the peripheral nervous system by tumor masses or drug-induced neuropathy, were excluded. Cerebrospinal fluid (CSF) analysis showed a mild pleocytosis, elevated total protein (9.8 g/l) and identical oligoclonal bands in serum and CSF. Blood-CSF barrier damage was detected by Reiber formula. Indirect immunofluorescence and western blot analysis demonstrated an autoantibody against peripheral and central nervous system structures in serum and CSF. Although the autoantibody responded to a 38-40 kDa-protein in western blot and showed nuclear staining of myenteric plexus and Purkinje cell nuclei in the immunofluorescence test, this antibody was shown to be not identical to anti-Hu. An intrathecal synthesis of the antineuronal antibody was detected by antibody specificity index. Tumor therapy, plasmapheresis and treatment with intravenous immunoglobulins did not improve the neuropathy. According to our knowledge this is the first case of antineuronal antibody-associated sensomotoric neuropathy in Hodgkin's disease.

["Thunder clap headache": an independent form of headache?]. / Der "Thunderclap Headache": eine eigenständige Kopfschmerzform?

Acute severe headache indicative of subarachnoid haemorrhage (SAH), but without the requisite proof, is defined as thunderclap. A special pathophysiological mechanism for the development of this headache is not known as yet. This retrospective study comprised 84 patients. All had the typical clinical signs of a SAH, but cranial computer tomography and lumbar puncture excluded this diagnosis. In 82% of these patients the headache was classified according to aetiologically defined symptomatic groups. One patient with headache of vascular aetiology had an angiographically proven, but not ruptured aneurysm. No definite cause for the headache was found in 18% of cases. None of the patients followed up over a period of between 12 months and 6 years developed SAH or any other severe neurological disorder. 9% reported repeat of the headache event. Thunderclap headache seems to be only a descriptive term for patients with symptoms typical of a SAH without signs of bleeding. Thunderclap headache has no diagnostic or prognostic specificity and therefore we recommend use of this term only as a description of the headache characteristic. Thunderclap headache is not a predictor of a future SAH. Cerebral angiography should be restricted to cases with neurological deficits.

Stress and strain of blue and white collar workers during work and leisure time: results of psychophysiological and behavioral monitoring.

This study of 29 blue and 57 white collar workers (mean age 50 and 51 yr) investigated behavior and the level of subjective stress and objective strain during work and leisure time. Physiological and psychological parameters as well as behavioral activities were assessed simultaneously using a special ambulatory monitoring device capable of storing 23 h records. Total strain was operationalized by heart rate (HR), physical strain by physical activity, emotional strain by non-metabolic HR, and mental strain by HR variability. Analysis of the physiological parameters for the working hours from 8 to 16 h revealed differences between the hours for physical activity, HR, and non-metabolic HR but not for HR variability. Between 12 and 13 h, physical activity was somewhat lower and non-metabolic HR higher, presumedly caused by the lunch break. Physical activity and HR were higher for blue than white collar workers due to the different tasks of the workers. Self-reports of excitement and enjoyment during the working hours showed no main effects in the MANOVA. Comparison between total working time and leisure time revealed lower physical activity and HR but higher non-metabolic HR for leisure time. In the self-reports, however, leisure time was rated less exciting and more pleasant than working time. There was no indication of higher emotional strain for one or the other group, but mental strain at work was somewhat higher for the blue collar workers. In a questionnaire, white collar workers reported having significantly more stress at work and outside work than blue collar workers. Analysis of the behavior during leisure time (physical activity, activity, social contacts) showed only minor differences between the groups.

Recurrent monofocal demyelinating disease.

We describe a patient with recurrent brainstem symptoms and migraine-like headache. Magnetic resonance imaging (MRI) showed a symptomatic hyperintense T2-weighted lesion in the middle cerebellar peduncle and the trigeminal nuclei and an asymptomatic periventricular lesion of Dawson finger shape. The findings were suspicious for a first demyelinating event, possibly representing the first manifestation of multiple sclerosis (MS). Nevertheless, this case report also illustrates several pitfalls in the differential diagnosis of MS.

[The role of S100B-protein in neonatology, pediatric intensive care, and pediatrics]. / Neuromonitoring mittels S100B-Protein: Stellenwert für die Neonatologie, pädiatrische Intensivmedizin und Pädiatrie.

During the last years neuromonitoring with various biochemical markers such as S100B protein has been introduced into the clinical settings of neonatal and pediatric intensive care. Several investigations have been undertaken to correlate S100B protein concentrations to the diagnosis and prognosis of neonates and children with severe cerebral disorders. This articles gives a review on the current knowledge, indications and limitations on the use of S100B protein after non-traumatic and traumatic brain injury in neonates and children.

[Altered function of the hypothalamic-pituitary-adrenal axis in patients with acute, chronic and episodic pain]. / Funktionsstörung der hypothalamisch-hyphophysär-adrenalen Achse bei Patienten mit akuten, chronischen und intervallartigen Schmerzsyndromen.

INTRODUCTION: Complex disorders of the hypothalamic-pituitary-adrenal axis constitute phenomena whose etiopathogenetic significance is the subject of controversy. The frequent coincidence with depressive symptoms further complicates interpretation. PATIENTS AND METHODS: Daily variations in cortisol levels were measured in 20 patients with acute pain, 27 with chronic pain in the lumbar musculoskeletal system, and 44 with episodic forms of headache to determine the daily average and then correlated with differentiated algesimetric data. RESULTS: Patients with chronic and episodic pain had significantly higher scores on the McGill Pain Questionnaire and more affective items as an expression of depressive symptoms than patients with acute pain. The three groups did not however exhibit significant differences for the depression scale and list of "psychovegetative" disorders. In comparison to an age-matched pain-free control population (n=17), the average daily levels of cortisol were significantly higher in all three groups besides singularly elevated daily levels, but no correlations between the cortisol values and overall algesimetric data could be established. Chronic pain patients with high depression scores had significantly higher cortisol levels irrespective of pain intensity. DISCUSSION: Pain experiences cause increased plasma cortisol levels with significant elevation of the daily average. Whereas in cases of acute pain, a direct but unspecific stress reaction not connected with the pain seems to be likely, the underlying cause in cases of chronic and episodic pain appears to be a complex and enduring activation of the hypothalamic-pituitary-adrenal axis, likewise independent from pain, probably associated with concomitant depressive symptoms and disruption of the circadian rhythm of release controlled by the hypothalamus.

Antinuclear antibodies define a subgroup of paraneoplastic neuropathies: clinical and immunological data.

OBJECTIVE: Paraneoplastic neuropathy is a clinical and immunological heterogeneous disorder and attempts have been made to classify subgroups of this disease. Only 30-50% of the clinical defined cases have antineuronal antibodies. METHODS: The clinical and immunological features of 36 patients with paraneoplastic neuropathy from the authors' database were analysed including the type and course of the neuropathy, associated tumours, and the presence of antineuronal and other autoantibodies. RESULTS: Antineuronal antibodies were detected in 17/36 patients (47%) and anti-Hu was the most frequent antineuronal antibody. Nine patients had high titre antinuclear antibodies (ANA, median titre 1/1000) without antineuronal antibodies. ANA reactivities were different in most patients. Comparison of the ANA positive and ANA negative patients revealed that ANA positive paraneoplastic neuropathy is more frequently associated with breast cancer but is not associated with lung cancer (p<0.05). The main clinical type in these patients was sensorimotor neuropathy. No ANA positive patient had central nervous system involvement. Although the Rankin score at the time of diagnosis was not different, the functional outcome in ANA positive patients was better than in ANA negative patients (p<0.05). CONCLUSIONS: Paraneoplastic neuropathy is a heterogeneous disorder. ANA may define a subgroup of paraneoplastic neuropathy with different clinical and immunological features and may be related to better prognosis of the neuropathic symptoms.

[Autonomic dysfunction in migraine und tension-type headache--pilot study]. / Autonome Regulationsstörung bei Migräne und Spannungskopfschmerz. Pilotstudie.

UNLABELLED: Autonomic nervous system (ANS) dysfunction in migraine has been hypothesized during the last years. However, the pathophysiological relevance of this dysfunction on the etiology and the maintenance of the headaches remains unclear. The aim of this study was to investigate connections between the ANS dysfunction and the clinical appearances of the pain and its processing in migraine and tension-type headache (TTH). METHODS: Ten migraine-patients (31,4+/-10,6 years) and ten TTH-patients (49,3+/-14,6 years) underwent a cardiovascular reflex testing during headache-free intervals. A questionnaire was obtained to determine the patients' clinical pain-symptoms. RESULTS: The ANS function testings showed sympathetic hypofunction in both groups of patients. In the migraine-group, there was a significant correlation between the pain-intensity and the extent of the autonomic dysfunction (r=0,82) In the TTH-group, we found a correlation between the results of the orthostatic test and the v. Zerssen-depression-scale (r=0.69). CONCLUSIONS: These results suggest a sympathetic dysfunction in both headache-syndromes and suggest that the ANS plays an important role on the pathophysiology and the maintenance of the headaches.