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.

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.

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.

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.

[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.

[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.

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.

Location-dependent patterns in cardio-autonomic dysfunction in ischaemic stroke.

BACKGROUND AND STUDY PURPOSE: Autonomic nervous system dysfunction is a common complication of acute cerebrovascular disorders. The aim of this study was to investigate a possible location-dependent difference in cardio-autonomic function in patients with ischaemic stroke. PATIENTS AND METHODS: Sympathetic function was prospectively assessed by determining plasma norepinephrine and epinephrine in 19 patients with left-hemisphere (LH), 14 with right-hemisphere (RH) and 6 with brainstem/cerebellar (BS) stroke. Blood pressure, heart rate, cardiac output and transcranial flow velocity in the middle cerebral artery were recorded during the first 5 days after stroke. RESULTS: Stroke caused an initial increase in sympathetic function in all 3 groups with a spontaneous decrease in norepinephrine in LH (p < 0.01) and BS stroke (p < 0.05) only. Norepinephrine was significantly higher in RH than in BS stroke (p < 0.05). The alterations in autonomic function were paralleled by a sustained elevation in cardiovascular parameters mainly in RH stroke. CONCLUSIONS: Plasma catecholamines are feasible in monitoring location-dependent autonomic dysfunction in ischaemic stroke. Hemispheric lateralization in autonomic control should be taken into account in the management of stroke because of an increased susceptibility to cardio-autonomic dysfunction in patients with RH stroke.

Disturbance in the serum IgG subclass distribution in patients with anti-Hu positive paraneoplastic neurological syndromes.

Autoantibodies in patients with paraneoplastic neurological syndromes (PNS) have been reported to be predominantly IgG1 and IgG3 isotypes. However, no data are available about the IgG subclass distribution of the total serum IgG in these patients. Therefore, we investigated the IgG subclass distribution (given as percentage of total IgG) in 15 anti-Hu positive PNS patients, 15 patients with small cell lung cancer (SCLC) without PNS and 23 healthy controls using a commercial enzyme-linked immunosorbant assay test. Although IgG1 (and to a lower extent IgG3) are the predominant subclasses of the anti-Hu antibodies, PNS and SCLC showed a significant decrease in IgG1 and a concomitant increase in IgG2 compared with healthy controls (P < 0.05, respectively). In contrast, only SCLC patients, but not PNS patients, had higher IgG3 and IgG4 values compared with controls (P < 0.05, respectively). There was no correlation between IgG subclass levels and the titre or the predominant isotype of the antineuronal antibodies. PNS patients with autonomic disturbances had lower IgG4 levels than PNS patients without autonomic disturbances (P < 0.05). Our study demonstrates a disturbance in the IgG subclass distribution in PNS patients which is partly different from SCLC patients. The isotype regulation of the anti-Hu antibody seems to be independent from this phenomenon.

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.

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.

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.

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.

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.

[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.

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.

Cerebrospinal fluid neuropeptides and monoaminergic transmitters in patients with trigeminal neuralgia.

The pathogenesis of trigeminal neuralgia remains largely unknown. "Peripheral" as well as "central" causes have been suggested. To investigate the role of serotonergic, noradrenergic, dopaminergic, and peptidergic systems, we determined the concentrations of epinephrine, norepinephrine, and their breakdown product, vanillylmandelic acid, in the cerebrospinal fluid of 16 patients (55.3 +/- 8.3 years) with trigeminal neuralgia. As a marker for the dopaminergic system, we determined cerebrospinal fluid concentrations of dopamine and its metabolite, homovanillic acid. As a marker for the serotonergic system, we measured cerebrospinal fluid levels of the serotonin metabolite, 5-hydroxyindoleacetic acid. In addition, levels of the neuropeptides, substance P and somatostatin, were determined. The concentration of norepinephrine (P < 0.01) and its metabolite, vanillylmandelic acid, (P < 0.05) were significantly decreased in our patients. The level of the dopamine metabolite, homovanillic acid, was also significantly reduced (P < 0.01). Also significantly decreased was 5-hydroxyindoleacetic acid (P < 0.01). Substance P was significantly elevated (P < 0.05). Somatostatin was significantly decreased (P < 0.05). We hypothesize that the sum of complex neurochemical changes plays a role in the pathogenesis of trigeminal neuralgia. The elevated substance P could support the concept of a neurogenic inflammation in the trigeminovascular system, whereas changes in the monoaminergic transmitters and their metabolites seem to reflect a more central dysfunction possibly due to a longer duration of the disease and an accompanying depression.

Neurochemical differences in the CSF between Binswanger's and Alzheimer's disease.

In 21 patients suffering from Binswanger's disease (BD) and in 53 patients suffering from Alzheimer's disease, we measured cerebrospinal fluid (CSF) concentrations of somatostatin-like immunoreactivity (SLI), high molecular weight form somatostatin (HMV-SST), somatostatin-25/28 (SST-25/28), somatostatin-14 (SST-14), Des-ala-somatostatin (Des-ala-SST), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA). The patients were classified into three stages of intellectual deterioration according to the global deterioration scale (GDS). Levels of SLI were significantly decreased in BD in general and in SDAT patients with severe dementia (GDS 7), compared to a control group (BD overall 19.7 +/- 11.6 fmol/ml, SDAT 18.6 +/- 7.9 vs. 30.5 +/- 8.6 fmol/ml in controls, p < 0.01 for both). In SDAT patients, SLI levels correlated with dementia scores (r = -0.65, p < 0.05), but not in BD. HVA levels were decreased significantly in SDAT and BD patients with severe dementia (SDAT 273.5 +/- 138.7, BD 224.3 +/- 69.9 vs. 364.9 +/- 103.8 nmol/ml, p < 0.01 in controls, p < 0.05 for both). In BD patients with light dementia (GDS 2-4), HVA levels were significantly elevated (p < 0.05). In BD, HVA levels correlated with dementia (r = -0.59, p < 0.01). 5-HIAA was significantly elevated in BD patients with light dementia (p < 0.05). Qualitative and quantitative changes in the molecular forms of SLI are compatible with a dysregulated posttranslational processing SDAT and BD. We also observed significant correlations between SLI, 5-HIAA and HVA in BD indicating a neurochemical heterogeneous and generalized process affecting several transmitter systems and functions. In summary, our study shows that despite their quite different neuropathology, SDAT and BD do not differ fundamentally in their neurochemical profile.

Case report: anti-Coa in a Co-(a+)-typed patient with chronic renal insufficiency.

The recently identified molecular structure of the Colton blood group system is characterized by an amino acid substitution at position 45 (Colton a: alanine, Colton b: valine) of the archetypical water channel protein Aquaporin-1 (AQP1), which regulates water homeostasis in the erythrocyte membrane and in the proximal tubule of the nephron. We identified a patient with the unique constellation of an antibody with the specificity anti-Coa and the Co (a+) phenotype. The serological antigen typing was confirmed by molecular typing with PCR-RFLP. The antibody has to be interpreted as an antibody against a partial Colton a antigen or as an autoantibody despite a negative direct antiglobulin test (DAT). The patient is suffering from chronic renal insufficiency of unknown origin, rising speculation about a pathophysiological relationship between the serological constellation and the clinical disease under the aspect of localization of the Colton antigens on AQP1.