[A 19-year-old woman with fever and high blood pressure]. / Eine 19-jährige Frau mit Fieber und Bluthochdruck.

A 19-year-old female patient was admitted to hospital for further diagnostics and treatment of a febrile infection. The cause was found to be a bronchopulmonary infection due to methicillin-sensitive Staphylococcus aureus (MSSA), which led to an infective endocarditis with mitral valve infestation and two splenic abscesses. Under treatment according to the antibiogram and laparoscopic excision of the splenic abscesses, the infection-related complications could be successfully resolved. Even during the physical examination there was a suspicion of Cushing's syndrome, which was confirmed by laboratory and radiological investigations and is associated with a general immune deficiency. Remarkable was that the initially difficult to adjust high blood pressure became normalized after transsphenoidal resection of the pituitary adenoma.

Utilization of sunglasses: A pilot study to examine a simple test for cognitive dysfunction.

OBJECTIVE: Utilization is an executive function disorder and implies an inappropriate response to external stimuli. The sunglasses test is a simple test to examine utilization by offering a pair of sunglasses to a patient without any instruction. PATIENTS AND METHODS: We performed a pilot study to examine the sunglasses test in 100 patients, of which 50 had cognitive symptoms and 50 did not have cognitive symptoms. When the patient put on the sunglasses, the test was considered positive. Cognitive dysfunction was based on the results of the MMSE, results of the clock test and neuropsychological examination (blinded). The final diagnosis was based on all results of the work-up (including MRI). RESULTS: Of the 50 patients with cognitive symptoms 30 had a positive test and 28 of them had cognitive dysfunction. Final diagnosis in most patients was Dementia due to probable Alzheimers disease, followed by Frontotemporal dementia. Seven of the 20 patients with a negative test also had cognitive dysfunction. None of the 50 patients without cognitive symptoms put on the sunglasses. Sensitivity of the sunglasses test to detect cognitive dysfunction was 80% and specificity was 97%, with a positive predictive value of 93%. CONCLUSION: Offering sunglasses is a simple test to screen for utilization. Putting on sunglasses without instruction to do so can be indicative for cognitive dysfunction and further cognitive evaluation should be considered. Future studies are needed in a larger group of patients and to determine the role of this test in different diseases with cognitive decline.

From VGKC to LGI1 and Caspr2 encephalitis: The evolution of a disease entity over time.

A wide variety of clinical syndromes has been associated with antibodies to voltage-gated potassium channels (VGKCs). Six years ago, it was discovered that patients do not truly have antibodies to potassium channels, but to associated proteins. This enabled the distinction of three VGKC-positive subgroups: anti-LGI1 patients, anti-Caspr2 patients and VGKC-positive patients lacking both antibodies. Patients with LGI1-antibodies have a limbic encephalitis, often with hyponatremia, and about half of the patients have typical faciobrachial dystonic seizures. Caspr2-antibodies cause a more variable syndrome of peripheral or central nervous system symptoms, almost exclusively affecting older males. Immunotherapy seems to be beneficial in patients with antibodies to LGI1 or Caspr2, stressing the need for early diagnosis. Half of the VGKC-positive patients lack antibodies to both LGI1 and Caspr2. This is a heterogeneous group of patients with a wide variety of clinical syndromes, raising the question whether VGKC-positivity is truly a marker of disease in these patients. Data regarding this issue are limited, but a recent study did not show any clinical relevance of VGKC-positivity in the absence of antibodies to LGI1 and Caspr2. The three VGKC-positive subgroups are essentially different, therefore, the lumping term 'VGKC-complex antibodies' should be abolished.

Olfactory dysfunction in behavioral variant frontotemporal dementia.

OBJECTIVE: Several neurodegenerative disorders show olfactory dysfunction. In patients with frontotemporal dementia (FTD), olfactory impairment is probably due to the involvement of the temporal and orbitofrontal lobes. We hypothesized that due to the disrupted areas in FTD, there would be an impairment in smell identification, differentiation and association. Moreover, we hypothesized that there would be a correlation between the severity of FTD and the severity of odor dysfunction. METHODS: In the current study, we compared odor identification, discrimination and association of nine patients with behavioral variant FTD with eleven healthy controls using the Brief Smell Identification Test and the Odor Perception and Semantics Battery. RESULTS: The results showed significant differences in the odor association test, but not in the identification or discrimination test. There was no correlation between disease severity and the performance in the odor tests. CONCLUSION: We showed impairment of odor association that is most likely due to disruption of specific associative areas involved in olfactory processing. Specifically, we propose that the impairment may well be due to disrupted areas in the temporal lobe and amygdala.

Effects of dark chocolate consumption on the prothrombotic response to acute psychosocial stress in healthy men.

Flavanoid-rich dark chocolate consumption benefits cardiovascular health, but underlying mechanisms are elusive. We investigated the acute effect of dark chocolate on the reactivity of prothrombotic measures to psychosocial stress. Healthy men aged 20-50 years (mean ± SD: 35.7 ± 8.8) were assigned to a single serving of either 50 g of flavonoid-rich dark chocolate (n=31) or 50 g of optically identical flavonoid-free placebo chocolate (n=34). Two hours after chocolate consumption, both groups underwent an acute standardised psychosocial stress task combining public speaking and mental arithmetic. We determined plasma levels of four stress-responsive prothrombotic measures (i. e., fibrinogen, clotting factor VIII activity, von Willebrand Factor antigen, fibrin D-dimer) prior to chocolate consumption, immediately before and after stress, and at 10 minutes and 20 minutes after stress cessation. We also measured the flavonoid epicatechin, and the catecholamines epinephrine and norepinephrine in plasma. The dark chocolate group showed a significantly attenuated stress reactivity of the hypercoagulability marker D-dimer (F=3.87, p=0.017) relative to the placebo chocolate group. Moreover, the blunted D-dimer stress reactivity related to higher plasma levels of the flavonoid epicatechin assessed before stress (F=3.32, p = 0.031) but not to stress-induced changes in catecholamines (p's=0.35). There were no significant group differences in the other coagulation measures (p's≥0.87). Adjustments for covariates did not alter these findings. In conclusion, our findings indicate that a single consumption of flavonoid-rich dark chocolate blunted the acute prothrombotic response to psychosocial stress, thereby perhaps mitigating the risk of acute coronary syndromes triggered by emotional stress.

Are atraumatic spinal needles as efficient as traumatic needles for lumbar puncture?

The most frequent complication of lumbar puncture is post lumbar puncture headache (PLPH). Recent studies confirmed that the use of atraumatic spinal needles significantly reduces the risk of PLPH. However, the majority of neurologists still use traumatic needles, possibly caused by misconceptions and beliefs about practical performance of atraumatic spinal needles. Therefore, we investigated the practical characteristics of atraumatic and traumatic spinal needles. An experimental setup with a fluid column was used with (1) a physiological NaCl 0.9 % solution and (2) a high protein content solution. Flow rates and duration of pressure measurements were measured using a traumatic needle and an atraumatic needle. The average flow rate differed less than 10 % between the two needle types with NaCl solution, and for the high protein solution the difference was even smaller. Time taken to perform accurate pressure measurements did not differ between the two needle types using NaCl 0.9 %, and was even slightly shorter for the atraumatic needle when using the high protein solution. Average flow rates and duration of pressure measurements are comparable between atraumatic spinal needles and traumatic needles. Therefore, these performance characteristics are no reason to favor traumatic needles over atraumatic needles.

The Lusitania Province as a center of diversification: the phylogeny of the genus Microlipophrys (Pisces: Blenniidae).

The Lusitania Province has been considered a transition zone between the Atlantic northern cold waters and Tropical warm waters. Tropical species have expanded their ranges during warm periods and either retreated during cold periods or survived in local refuges. Successive waves of dispersion into this Province could have favored diversification through geographic isolation. Taxa that remained in this large Province may also have diversified in loco. We analyzed molecular markers of the genus Microlipophrys (family Blenniidae) that confirm the validity of this genus and of the seven recognized species. Microlipophrys and its sister clade apparently originated within Lusitania and dispersed into the tropics at a later stage.

Efficacy of 3,4-diaminopyridine and pyridostigmine in the treatment of Lambert-Eaton myasthenic syndrome: a randomized, double-blind, placebo-controlled, crossover study.

3,4-Diaminopyridine and pyridostigmine are widely used to treat Lambert-Eaton myasthenic syndrome (LEMS), either alone or in combination. 3,4-Diaminopyridine enhances the release of acetylcholine at the neuromuscular synapse, and pyridostigmine inhibits the degradation of this neurotransmitter. Although this could lead to a synergistic effect on neuromuscular transmission, no studies have compared the effects of these drugs in patients with LEMS. Therefore, we performed a placebo-controlled, double-dummy, double-blind, randomized, crossover study in nine patients with LEMS.

The Lambert-Eaton myasthenic syndrome 1988-2008: a clinical picture in 97 patients.

BACKGROUND: Neuromuscular symptoms in patients with Lambert-Eaton myasthenic syndrome (LEMS) and a small cell lung cancer (SCLC) develop more rapidly than in LEMS patients without a SCLC. We studied how this clinical information, which is readily available at the first consultation, can be used to predict the presence of SCLC. PATIENTS AND METHODS: In our study we included 52 LEMS patients with SCLC and 45 non-tumor patients (NT-LEMS). We interviewed patients using a structured checklist and reviewed their clinical records. We compared frequency and onset of symptoms during the course of LEMS. RESULTS: In the first six months, over half the SCLC-LEMS patients had developed seven separate symptoms, while NT-LEMS patients developed only two symptoms. Proximal leg weakness and dry mouth were early symptoms in both groups. Rapid involvement of proximal arm muscles (p=0.0001), distal arm muscles (p=0.0037), distal leg muscles (p=0.0002), dysartria (p=0.0091) and the presence of erectile dysfunction (p=0.007) were found significantly more often in SCLC-LEMS patients in both cohorts. Cerebellar symptoms, although present in 9% of LEMS patients, were almost exclusively related to SCLC-LEMS. CONCLUSION: A rapidly progressive course of disease from onset in LEMS patients should raise a high suspicion of SCLC. Special attention should be paid to involvement of upper extremities, involvement of distal arm and distal leg muscles, to erectile dysfunction and probably ataxia in order to discriminate between SCLC-LEMS and NT-LEMS.

Clinical fluctuations in MuSK myasthenia gravis are related to antigen-specific IgG4 instead of IgG1.

We studied the longitudinal relation between disease severity and titers of antigen-specific IgG subclasses in sera of patients with myasthenia gravis and antibodies to Muscle Specific Kinase (MuSK MG). Six patients were included of whom 55 samples had been collected during 2.5-13.4 years. Anti-MuSK antibodies were determined by ELISA and with a cell-based immunofluorescence assay. Disease severity was scored on a semi continuous scale. Only antigen-specific IgG4, and not IgG1, titers were significantly associated with disease severity in a linear mixed effect model (p = 0.036). Levels of IgG4 antibodies were above IgG1 in all samples except in one patient who went into clinical remission while switching from IgG4 to IgG1. The results support an important role for IgG4 in the pathogenesis of MuSK MG, in contrast to MG with anti-acetylcholine receptor antibodies.

Monocyte proinflammatory cytokine release is higher and glucocorticoid sensitivity is lower in middle aged men than in women independent of cardiovascular risk factors.

OBJECTIVE: To investigate whether stimulated monocyte cytokine release and its inhibition by glucocorticoids differs between men and women. DESIGN: In vitro monocyte interleukin 6 (IL-6) and tumour necrosis factor alpha (TNFalpha) release after lipopolysaccharide stimulation were assessed with and without co-incubation with increasing doses of dexamethasone and hydrocortisone separately. Glucocorticoid sensitivity was defined as the amount of a particular glucocorticoid required to inhibit lipopolysaccharide stimulated monocyte cytokine release by 50%. The established cardiovascular risk factors of age, body mass index, number of cigarettes smoked daily, low density cholesterol to high density cholesterol ratio, systolic and diastolic blood pressure, and haemoglobin A1c were used as covariates. SETTING: Aircraft manufacturing plant in southern Germany. PATIENTS: 269 middle aged male and 36 middle aged female employees. RESULTS: Release of monocyte IL-6 and TNFalpha (each p = 0.001) was higher in samples from men than in those from women. Inhibition of lipopolysaccharide stimulated IL-6 and TNFalpha release by either glucocorticoid was less pronounced in samples from men than in those from women (IL-6: dexamethasone p = 0.033, hydrocortisone p = 0.029; TNFalpha: dexamethasone p < 0.001, hydrocortisone p = 0.089). CONCLUSIONS: The finding suggests that proinflammatory activity of circulating monocytes is higher in men than in women independent of cardiovascular risk factors, thereby providing one explanation for the relatively greater coronary risk in men.

Difference in distribution of muscle weakness between myasthenia gravis and the Lambert-Eaton myasthenic syndrome.

BACKGROUND: Myasthenia gravis and the Lambert-Eaton myasthenic syndrome (LEMS) may have a similar distribution of muscle weakness. Deciding on a diagnosis of myasthenia gravis or LEMS on clinical grounds may therefore be difficult. OBJECTIVE: To compare the localisation of initial muscle weakness and the distribution of weakness at the time of maximum severity in patients with myasthenia gravis and LEMS. SUBJECTS: 101 patients with myasthenia gravis and 38 patients with LEMS. RESULTS: In myasthenia gravis, initial weakness involved extraocular muscles in 59%, bulbar muscles in 29%, and limb muscles in 12% of the patients. In LEMS no patient had ocular weakness, 5% had bulbar weakness, and 95% had weakness of the limbs as the first symptom (p < 0.001). At the point of maximum severity, weakness in myasthenia gravis was purely ocular in 25%, oculobulbar in 5%, restricted to the limbs in 2%, and present in both oculobulbar muscles and limbs in 68%. At this point, none of the LEMS patients had weakness restricted to extraocular or bulbar muscles (p = 0.002). The legs were affected in all LEMS patients, whereas in 12 patients with generalised myasthenia gravis limb weakness was restricted to the arms (p = 0.024). CONCLUSIONS: In a patient suspected to have a myasthenic syndrome whose first symptom is ocular weakness, LEMS is virtually excluded. Limb weakness confined to the arms is only found in generalised myasthenia gravis and not in LEMS. Muscle weakness in myasthenia gravis tends to develop in a craniocaudal direction, and in the opposite direction in LEMS.

HLA class I and II in Lambert-Eaton myasthenic syndrome without associated tumor.

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder, in which antibodies against voltage-gated calcium channels located at nerve terminals cause muscle weakness and autonomic dysfunction. In approximately half of the patients the autoimmune process is initiated by a tumor. In the other half of patients no tumor is found and the etiology is unknown. The aims of this study were to investigate the strength of HLA-associations with nontumor LEMS (NT-LEMS) and to study the relation of HLA-haplotypes with age at onset of LEMS and other clinical features. Therefore, typing of HLA class I and II was performed in 19 patients with NT-LEMS, who were clinically evaluated. NT-LEMS was significantly associated with alleles of both HLA-class I (i.e. HLA-B8) as well as -class II (i.e. HLA-DR3 and -DQ2). HLA-B8+ patients had significantly younger age at onset of LEMS and tended to be female. This study shows that HLA-class I haplotype is associated with a distinct phenotype in NT-LEMS.