The effect of CSF drain on the optic nerve in idiopathic intracranial hypertension

Background: Elevation of intracranial pressure in idiopathic intracranial hypertension induces an edema of the prelaminar section of the optic nerve (papilledema). Beside the commonly observed optic nerve sheath distention, information on a potential pathology of the retrolaminar section of the optic nerve and the short-term effect of normalization of intracranial pressure on these abnormalities remains scarce. Methods: In this exploratory study 8 patients diagnosed with idiopathic intracranial hypertension underwent a MRI scan (T2 mapping) as well as a diffusion tensor imaging analysis (fractional anisotropy and mean diffusivity). In addition, the clinical presentation of headache and its accompanying symptoms were assessed. Intracranial pressure was then normalized by lumbar puncture and the initial parameters (MRI and clinical features) were re-assessed within 26 h. Results: After normalization of CSF pressure, the morphometric MRI scans of the optic nerve and optic nerve sheath remained unchanged. In the diffusion tensor imaging, the fractional anisotropy value was reduced suggesting a tissue decompression of the optic nerve after lumbar puncture. In line with these finding, headache and most of the accompanying symptoms also improved or remitted within that short time frame. Conclusion: The findings support the hypothesis that the elevation of intracranial pressure induces a microstructural compression of the optic nerve impairing axoplasmic flow and thereby causing the prelaminar papilledema. The microstructural compression of the optic nerve as well as the clinical symptoms improve within hours of normalization of intracranial pressure

Longitudinal Testing of Olfactory and Gustatory Function in Patients with Multiple Sclerosis

Background The aim of the study was to investigate changes of the olfactory and gustatory capacity in patients with multiple sclerosis (MS). Methodology 20 MS patients were tested longitudinally for 3 years after initial testing. The Threshold Discrimination Identification test (TDI) was used for subjective olfactometry. Objective olfactometry was performed by registering olfactory evoked potentials (OEP) by EEG. The Taste Strip Test (TST) was used for gustatory testing. Results 45% of the patients showed olfactory dysfunction in the follow-up TDI test and 50% showed delayed OEP´s. 20% of the patients showed gustatory dysfunction on follow-up visit. The patients showed mild disease activity with 0,3 ± 0,5 relapses over the testing period and no significant change of their olfactory and gustatory capacity. The olfactory capacity for the discrimination of odors correlated inversely with the number of relapses (r = -0.5, p ≤ 0.05). The patients were aware of their olfactory deficit. Conclusions Olfactory and gustatory dysfunction is a symptom in MS patients and may be a useful parameter to estimate disease progression in MS patients. As the discrimination of odors is processed in higher central regions of the central nervous system (CNS), the results suggest that olfactory dysfunction could be due to CNS damage

Emotional experience in patients with clinically isolated syndrome and early multiple sclerosis

Background and purpose: Evidence suggests that there are changes in the processing of emotional information (EP) in people with multiple sclerosis (MS). It is unclear which functional domains of EP are affected, whether these changes are secondary to other MS-related neuropsychological or psychiatric symptoms and if EP changes are present in early MS. The aim of the study was to investigate EP in patients with early MS (clinically isolated syndrome and early relapsing/remitting MS) and healthy controls (HCs). Methods: A total of 29 patients without neuropsychological or psychiatric deficits and 29 matched HCs were presented with pictures from the International Affective Picture System with negative, positive or neutral content. Participants rated the induced emotion regarding valence and arousal using nine-level Likert scales. A speeded recognition test assessed memory for the emotional stimuli and for the emotional modulation of response time. A subgroup of participants was tested during a magnetic resonance imaging (MRI) session. Results: Patients in the MRI subgroup rated the experience induced by pictures with positive or negative emotional content significantly more weakly than HCs. Further, these patients were significantly less aroused when watching the pictures from the International Affective Picture System. There were no effects in the non-MRI subgroup or effects on emotional memory or response times. Conclusions: Emotional processing changes may be present in early MS in the form of flattened emotional experience on both the valence and arousal dimensions. These changes do not appear to be secondary to neuropsychological or psychiatric deficits. The fact that emotional flattening was only found in the MRI setting suggests that EP changes may be unmasked within stressful environments and points to the potential yet underestimated impact of the MRI setting on behavioral outcomes

Structural Olfactory Nerve Changes in Patients Suffering from Idiopathic Intracranial Hypertension

BACKGROUND: Complications of idiopathic intracranial hypertension (IIH) are usually caused by elevated intracranial pressure (ICP). In a similar way as in the optic nerve, elevated ICP could also compromise the olfactory nerve system. On the other side, there is growing evidence that an extensive lymphatic network system around the olfactory nerves could be disturbed in cerebrospinal fluid disorders like IIH. The hypothesis that patients with IIH suffer from hyposmia has been suggested in the past. However, this has not been proven in clinical studies yet. This pilot study investigates whether structural changes of the olfactory nerve system can be detected in patients with IIH. METHODOLOGY/PRINCIPAL FINDINGS: Twenty-three patients with IIH and 23 matched controls were included. Olfactory bulb volume (OBV) and sulcus olfactorius (OS) depth were calculated by magnetic resonance techniques. While mean values of total OBV (128.7±38.4 vs. 130.0±32.6 mm(3), p=0.90) and mean OS depth (8.5±1.2 vs. 8.6±1.1 mm, p=0.91) were similar in both groups, Pearson correlation showed that patients with a shorter medical history IIH revealed a smaller OBV (r=0.53, p<0.01). In untreated symptomatic patients (n=7), the effect was greater (r=0.76, p<0.05). Patients who suffered from IIH for less than one year (n=8), total OBV was significantly smaller than in matched controls (116.6±24.3 vs. 149.3±22.2 mm(3), p=0.01). IIH patients with visual disturbances (n=21) revealed a lower OS depth than patients without (8.3±0.9 vs. 10.8±1.0 mm, p<0.01). CONCLUSIONS/SIGNIFICANCE: The results suggest that morphological changes of the olfactory nerve system could be present in IIH patients at an early stage of disease

Optic Nerve Head Quantification in Idiopathic Intracranial Hypertension by Spectral Domain OCT

Objective: To evaluate 3D spectral domain optical coherence tomography (SDOCT) volume scans as a tool for quantification of optic nerve head (ONH) volume as a potential marker for treatment effectiveness and disease progression in idiopathic intracranial hypertension (IIH). Design and Patients: Cross-sectional pilot trial comparing 19 IIH patients and controls matched for gender, age and body mass index. Each participant underwent SDOCT. A custom segmentation algorithm was developed to quantify ONH volume (ONHV) and height (ONHH) in 3D volume scans. Results:Whereas peripapillary retinal nerve fiber layer thickness did not show differences between controls and IIH patients, the newly developed 3D parameters ONHV and ONHH were able to discriminate between controls, treated and untreated patients. Both ONHV and ONHH measures were related to levels of intracranial pressure (ICP). Conclusion: Our findings suggest 3D ONH measures as assessed by SDOCT as potential diagnostic and progression markers in IIH and other disorders with increased ICP. SDOCT may promise a fast and easy diagnostic alternative to repeated lumba

Relevance of obesity to select neurological diseases

Die vorliegende kumulative Habilitationsschrift setzt sich mit der Bedeutung von Adipositas und den damit einhergehenden metabolischen Risikofaktoren auseinander. Dabei wird ein Zusammenhang zu verschiedenen neurologischen Krankheitsbildern aufgezeigt. Nach einer Einführung über die Epidemiologie von Übergewicht und Adipositas werden eigene Beiträge zur idiopathischen intrakraniellen Hypertension (IIH), zu arteriosklerotischen Stenosen der Arteria carotis interna (ICA) sowie zur Bedeutung der Blockade von SUR1-Rezeptoren in der Akutphase des ischämischen Schlaganfalls vorgestellt und diskutiert. Die IIH gehört zu den Kopfschmerzerkrankungen, deren Hauptmerkmal ein erhöhter Liquordruck ist. In der Habilitationsschrift wird die Bedeutung einer erstmals nachgewiesenen Störung des olfaktorischen Systems bei dieser Erkrankung dargestellt. Zudem wird darauf eingegangen, wodurch eine Riechstörung bei der IIH verursacht sein könnte. Es wird belegt, dass Patienten mit Stenosen der ICA meist Träger mehrerer metabolischer Risikofaktoren sind. Durch die eigenen Arbeiten wurden wichtige Destabilitätsmerkmale von ICA-Stenosen identifiziert. Im Anschluss wird dargestellt, wie durch diese Erkenntnisse innovative bildgebende Verfahren entwickelt wurden. Durch Blockade des SUR1-Rezeptors scheinen Diabetiker in der Akutphase eines ischämischen Schlaganfalls zu profitieren. Das wird durch die aufgeführten Publikationen des Verfassers belegt. Die Bedeutung der Erkenntnisse wird aufgrund der daraufhin initialisierten prospektiven randomisierten multizentrischen Phase II Studien belegt. Die bisher publizierten Ergebnisse dieser Studien stützen die Reliabilität der eingebrachten Beiträge. Sollten die vorgestellten Erkenntnisse ihre Reliabilität, Validität und klinische Anwendbarkeit weiter belegen, stellen sie einen zusätzlichen Nutzen für Patienten mit Übergewicht und metabolischen Risikofaktoren dar.The current work deals with obesity and obesity-related metabolic risk factors in the context of neurological diseases. After giving an overview on the epidemiology of obesity and the metabolic syndrome, I present and discuss my work on idiopathic intracranial hypertension (IIH), atherosclerotic stenosis of the internal carotid artery (ICA) and the sulfonylurea receptor (SUR)-1 in the acute phase of ischemic stroke. IIH is typically characterized by elevated cerebrospinal fluid pressure and by headache. The work presented here establishes that IIH also affects the olfactory system. Based on my data, potential mechanisms underlying olfactory impairments in IIH are discussed. Patients suffering from carotid stenosis frequently display metabolic risk factors. Here, my work centers on markers of plaque instability and how these were defined by innovative new imaging techniques. Finally, I present results from clinical studies in type-2 diabetics indicating that blockade of the SUR1 receptor by sulfonylureas may exert beneficial effects in ischemic stroke. Based on this clinical data, prospective trials have been launched. It will be interesting to probe further whether SUR1 receptor antagonism might provide benefits to patients suffering from acute stroke

Patients' Perceptions of Opioid Replacement Therapy: a Comparison of Diamorphine and Methadone/Levomethadone

Diamorphine was first legalized as a novel treatment option for heroin dependence in Germany in 2009. Today, specialized clinics in ten German cities provide diamorphine to heavily addicted patients. As the medical and societal context of diamorphine-assisted therapy is evolving, continued research into patients’ perceptions of opioid replacement therapy remains important. From February 2018 to June 2018, we conducted a survey study of outpatients on maintenance treatment with either diamorphine (n = 85) or methadone/levomethadone (n = 126). Patients were asked to complete a self-report questionnaire querying, besides socio-demographic information, the study participant’s satisfaction with the substitute drug, relapse with illicit drugs, patterns of craving, and alcohol consumption. Duration of opioid dependence did not differ significantly between groups. Patients on diamorphine were approximately 3 years younger than patients on methadone/levomethadone. They also had a higher frequency of daily intake of their substitute drug and had had their dosage adjusted more often during the preceding 6 months. Still, diamorphine patients reported greater satisfaction with their substitute drug in tandem with significant reductions in relapse-related behaviors and cravings. While the most common relapse reported by patients on methadone replacement was heroin relapse (68%), most instances of illicit drug use in the diamorphine group involved cocaine (48%). Although self-reported alcohol consumption did not differ significantly between groups, a higher percentage of diamorphine patients than methadone patients endorsed decreased alcohol consumption since entering therapy. Taken together, these findings point to meaningful differences between diamorphine and methadone/levomethadone in opioid replacement therapy