Histopathological examination of characteristic brain MRI findings in acute hyperammonemic encephalopathy: A case report and review of the literature.

INTRODUCTION: Acute hyperammonemic encephalopathy is associated with distinct brain MRI findings, namely, hyperintensity in T2-weighted sequences as well as restricted diffusion in diffusion-weighted imaging with accentuation in the insular cortex and cingulate gyrus. The pathophysiology and the histopathological correlates of these characteristic MRI findings are largely unknown. CASE REPORT: We present a 57-year-old male with a history of chronic alcohol abuse, liver cirrhosis and portal hypertension, and a clinical syndrome (variceal bleeding, depression of consciousness, seizures), elevated plasma ammonia levels, and characteristic brain MRI abnormalities suggestive of acute hyperammonemic encephalopathy. A postmortem histopathological examination revealed extensive hypoxic ischemic encephalopathy without evidence for metabolic encephalopathy. No episodes of prolonged cerebral hypoxemia were documented throughout the course of the disease. We conducted a review of the literature, which exhibited no reports of hyperammonemic encephalopathy in association with characteristic brain MRI findings and a consecutive histopathological examination. CONCLUSION: This is the first report of a patient with acute hyperammonemic encephalopathy together with characteristic brain MRI findings and a histopathological correlation. Although characteristic MRI findings of acute hyperammonemic encephalopathy were present, a histopathological examination revealed only hypoxic pathology without signs of metabolic encephalopathy.

[CXCL-13 as a biomarker in the diagnostics of neuroborreliosis]. / CXCL-13 als Biomarker in der Diagnostik der Neuroborreliose.

BACKGROUND: The chemokine CXCL-13 is a potential intrathecal biomarker for neuroborreliosis (NB). According to the literature the sensitivity of CXCL-13 in the diagnostics of NB varies between 88% and 100% and the specificity between 63% and 99.7%. The objective of this study was to analyze the sensitivity and specificity of CXCL-13 in the diagnosis of NB in an endemic area of Borrelia burgdorferi. MATERIAL AND METHODS: In a retrospective analysis of data from August 2014 to August 2016, 63 patients with clinically suspected NB were identified. The diagnosis of NB was based on the guidelines of the German Society of Neurology (DGN). RESULTS: In 10 patients a definitive diagnosis of NB could be established (CXCL-13 min. 254 pg/ml /max. >900 pg/ml). The criteria for a probable NB were fulfilled by 2 patients (CXCL-13 concentration 8 pg/ml and 69 pg/ml, respectively), 9 patients had a chronic inflammatory demyelinating disease (CXCL-13 min. 10 pg/ml/max. 649 pg/ml) and 42 patients had other neurological diagnoses. Out of these, elevated intrathecal CXCL-13 concentrations were detected in 8 patients (e. g. tuberculosis, syphilis and anti-RI antibody positive paraneoplastic syndrome). CONCLUSION: By increasing the CXCL-13 cut-off level from 20 pg/ml to 200 pg/ml, the diagnostic sensitivity for NB remains 100% and consequently the specificity increases from 69.8% to 92.4%. Moreover, a CXCL-13 cut-off set at 200 pg/ml would exclude NB in the 2 patients with probable NB. We conclude from these results that CXCL-13 represents a valuable biomarker for the exclusion of untreated NB, although with limited specificity.

Endovascular stroke therapy in Austria: a nationwide 1-year experience.

BACKGROUND AND PURPOSE: Based on a tight network of stroke units (SUs) and interventional centres, endovascular treatment of acute major intracranial vessel occlusion has been widely implemented in Austria. Documentation of all patients in the nationwide SU registry has thereby become mandatory. METHODS: Demographic, clinical and interventional characteristics of patients who underwent endovascular treatment for acute ischaemic stroke in 11 Austrian interventional centres between 1 October 2013 and 30 September 2014 were analysed. RESULTS: In total, 301 patients (50.5% women; median age 70.5 years; median National Institutes of Health Stroke Scale score 17) were identified.193 patients (64.1%) additionally received intravenous thrombolysis. The most frequent vessel occlusion sites were the M1 segment of the middle cerebral artery (n = 161, 53.5%), the intracranial internal carotid artery (n = 60, 19.9%) and the basilar artery (n = 40, 13.3%). Stent retrievers were used in 235 patients (78.1%) and adequate reperfusion (modified Thrombolysis in Cerebral Infarction scores 2b and 3, median onset to reperfusion time 254 min) was achieved in 242 patients (81.4%). Symptomatic intracranial haemorrhage occurred in 7%. 43.8% of patients (n = 132) had good functional outcome (modified Rankin Scale score 0-2) and the mortality rate was 20.9% (n = 63) after 3 months. Compared to the anterior circulation, vertebrobasilar stroke patients had higher mortality. Patients with secondary hospital transportation had better outcomes after 3 months than in-house treated patients. CONCLUSION: Our results document nationwide favourable outcome and safety rates of endovascular stroke treatment comparable to recent randomized trials. The ability to provide such data and the need to further optimize such an approach also underscore the contribution of respective registries.

End of life care in high-grade glioma patients in three European countries: a comparative study.

Exploring cross-national differences is useful to evaluate whether different patterns of end of life (EOL) care meet patient's specific needs. This study aimed to (1) compare EOL care processes for high-grade glioma (HGG) patients in three European countries, (2) explore differences in perceived quality of care (QOC), and (3) identify aspects of good QOC in the EOL phase. We analyzed 207 questionnaires from relatives of deceased HGG patients, using a similar retrospective study design in three countries [The Netherlands (n = 83), Austria (n = 72) and the UK (n = 52)], and examined four subthemes: (1) organization of EOL care, (2) treatment preferences, (3) experiences with EOL care, (4) perceived QOC. Three months before death 75 % of patients were at home. In all countries, on average, 50 % were transferred to a hospital at least once and received effective symptom treatment during the last 3 months. In The Netherlands, Austria and UK, respectively, patients most often died at home (60 %), in a hospital (41 %) or hospice (41 %) (p < 0.001). Advance directives were present in 46 % of Dutch, 36 % of British and 6 % of Austrian patients (p < 0.001). Fifty-three percent of patients experienced good QOC, irrespective of country. Dying at the preferred place, satisfaction with information provided and effective symptom treatment were independently associated with good QOC. There are various cross-national differences in organization and experiences with EOL care for HGG, but patient's perceived QOC is similar in the three countries. As symptom treatment was considered effective in only half of HGG patients, and independently predicted good QOC, this particularly needs further improvement in all countries.

Relative survival of patients with non-malignant central nervous system tumours: a descriptive study by the Austrian Brain Tumour Registry.

BACKGROUND: Unlike malignant primary central nervous system (CNS) tumours outcome data on non-malignant CNS tumours are scarce. For patients diagnosed from 1996 to 2002 5-year relative survival of only 85.0% has been reported. We investigated this rate in a contemporary patient cohort to update information on survival. METHODS: We followed a cohort of 3983 cases within the Austrian Brain Tumour Registry. All patients were newly diagnosed from 2005 to 2010 with a histologically confirmed non-malignant CNS tumour. Vital status, cause of death, and population life tables were obtained by 31 December 2011 to calculate relative survival. RESULTS: Overall 5-year relative survival was 96.1% (95% CI 95.1-97.1%), being significantly lower in tumours of borderline (90.2%, 87.2-92.7%) than benign behaviour (97.4%, 96.3-98.3%). Benign tumour survival ranged from 86.8 for neurofibroma to 99.7% for Schwannoma; for borderline tumours survival rates varied from 83.2 for haemangiopericytoma to 98.4% for myxopapillary ependymoma. Cause of death was directly attributed to the CNS tumour in 39.6%, followed by other cancer (20.4%) and cardiovascular disease (15.8%). CONCLUSION: The overall excess mortality in patients with non-malignant CNS tumours is 5.5%, indicating a significant improvement in survival over the last decade. Still, the remaining adverse impact on survival underpins the importance of systematic registration of these tumours.

[Stroke in cancer patients. A paraneoplastic neurological syndrome?]. / Schlaganfall bei Tumorpatienten. Ein paraneoplastisches neurologisches Syndrom?

The coincidence of stroke and cancer is frequently encountered. From recent epidemiological data, the stroke risk in cancer patients seems to be equally distributed as compared to the non-cancer population. However, there are several clinical conditions in cancer patients which increase the risk for stroke: Trousseau's syndrome, non-bacterial thrombotic endocarditis and disseminated intravascular coagulation. Also some tumour-specific conditions such as coagulopathies, changes of viscosity and cellular mechanisms such as leukocytosis or thrombocytopathies must be considered. In several types of tumour treatment, such as various anticancer drugs, an increased occurrence of stroke has been reported. Presently there is no indication that stroke and cancer are related to the immune-mediated "classic" paraneoplastic syndromes. However, there are several cancer-specific types and causes of stroke which need to be considered in each patient, as they can be of significance in the treatment.

Peritumoral edema on MRI at initial diagnosis: an independent prognostic factor for glioblastoma?

BACKGROUND: Peritumoral brain edema in glioblastoma patients is a frequently encountered phenomenon that strongly contributes to neurological signs and symptoms. The role of peritumoral edema as a prognostic factor is controversial. MATERIALS AND METHODS: This multi-centre clinical retrospective study included 110 patients with histologically proven glioblastoma. The prognostic impact on overall survival of pre-treatment peritumoral edema detected on MRI-scans was evaluated. All patients had preoperative MRI, surgery, histology, and received standard treatment regimens. Edema on MRI-scans was classified as minor (<1 cm), and major (>1 cm). RESULTS: Our results confirm that peritumoral edema on preoperative MRI is an independent prognostic factor in addition to postoperative Karnofsky performance score (KPS), age, and type of tumor resection. Patients with major edema had significant shorter overall survival compared to patients with minor edema. CONCLUSION: This easily applicable early radiological characterization may contribute to a more subgroup oriented treatment in glioblastoma patients for future trials, as well as in clinical routine.

Stroke and cancer: a review.

Stroke is a disabling disease and can add to the burden of patients already suffering from cancer. Several major mechanisms of stroke exist in cancer patients, which can be directly tumour related, because of coagulation disorders, infections, and therapy related. Stroke can also occur as the first sign of cancer, or lead to its detection. The classical literature suggests that stroke occurs more frequently in cancer patients than in the average population. More recent studies report a very similar incidence between cancer and non-cancer patients. However, there are several cancer-specific types and causes of stroke in cancer patients, which need to be considered in each patient. This review classifies stroke into ischaemic, haemorrhagic, cerebral venous thrombosis and other rarer types of cerebrovascular disease. Its aim is to identify the types of stroke most frequently associated with cancer, and give a practical view on the most common and most specific types of stroke. The diagnosis of the cause of stroke in cancer patients is crucial for treatment and prevention. Management of different stroke types will be briefly discussed.

Concomitant radiochemotherapy in a patient with multiple sclerosis and glioblastoma.

The coincidence of multiple sclerosis (MS) and glioblastoma has been reported in several anecdotal reports. Little is known concerning the effects of radio- and/or chemotherapy on demyelinating brain lesions in MS patients. Moreover, there are no data concerning the effect of concomitant radiochemotherapy according to the STUPP protocol on the course ofMS in patients with coexisting glioblastoma. A 43-year-old male patient was diagnosed for relapsing-remitting MS in 1997. He received interferon and glatiramer acetate for immunomodulatory treatment and was stable until 2006 (EDSS < 1.5), when neurological deterioration occurred. He developed a left-sided hemiparesis, and an MRI showed right temporal contrast-enhancing mass lesion. A subsequent tumor resection was performed and histology revealed a glioblastoma. At the beginning of radiochemotherapy, treatment for multiple sclerosis (glatiramer acetate) was stopped. The tumor responded well to treatment and was clinically as well as radiologically stable until 9 months after diagnosis of glioblastoma. The typical radiological MS lesions remained unchanged. The patient died 12 months after diagnosis of glioblastoma due to tumor progression. This report demonstrates that concomitant radiochemotherapy according to the STUPP protocol, was safe in our patient with respect to the radiological as well as the clinical course of multiple sclerosis.

Familial hemiplegic migraine: follow-up findings of diffusion-weighted magnetic resonance imaging (MRI), perfusion-MRI and [99mTc] HMPAO-SPECT in a patient with prolonged hemiplegic aura.

Familial hemiplegic migraine (FHM) is a rare inherited autosomal dominant disorder. Migraine aura may last up to several weeks and then resolve without sequel. We report a 21-year-old male with FHM since the age of 3 years. Diffusion-weighted magnetic resonance imaging (DWI), perfusion-MR imaging (P-MRI) and [99mTc] hexamethyl-propyleneamine-oxime-single photon emission tomography (HMPAO-SPECT) were performed on day 2, when he was somnolent with right-sided hemiplegia, on day 9 when a mild hemiparesis was still present and on day 24 after recovery. The right central region showed normal findings in DWI, whereas P-MRI and SPECT revealed hyperperfusion on day 2, less marked on day 9, and normal findings on day 24. In conclusion, this case report indicates for the first time, by means of SPECT, P-MRI and DWI studies, that even extremely long-lasting migraine aura is not associated with cerebral ischaemia. Therefore, it supports the revised International Headache Society criteria where the term 'persistent' aura is proposed.

Churg Strauss syndrome during treatment of bronchial asthma with a leucotriene receptor antagonist presenting with polyneuropathy.

Bronchial asthma can be associated with Churg Strauss syndrome (CSS). A peripheral neuropathy may be the initial manifestation of CSS. There is also some evidence that leucotriene receptor antagonists (LTAs) may trigger CSS in asthmatic patients, especially when steroids are tapered previously. However, the pathogenesis is unclear and the association between CSS and LTAs remains a matter of controversy. The aim of this report is to clarify this issue. A 79-year-old male patient with bronchial asthma for twenty years was admitted due to progressing gait disorder developing within the last two weeks. Asthma had been treated with a leucotriene receptor antagonist (Montelukast) for four years, as well as low doses of inhaled steroids and beta-2-agonists. On admission, neurological examination revealed a mild ataxia on both upper limbs and multifocal sensory disturbances without motor deficits. Nerve conduction velocity studies demonstrated normal results for the upper limbs and an axonal sensorimotor neuropathy of the lower limbs. Electromyography exhibited no spontaneous activity in the right tibialis anterior and rectus femoris muscle. Nerve-muscle biopsy revealed an eosinophilic vasculitis in both nerve and muscle. Laboratory examination showed leucocytosis and marked eosinophilia. A diagnosis of CSS was made. This case demonstrates a severe neuropathy in an asthmatic patient, during long lasting treatment with a LTA and continuous low doses of inhaled steroid, as the initial clinical feature of CSS.

Presentación polineuropática de un síndrome de Churg Strauss desarrollado durante el tratamiento con un antagonista del receptor de los leucotrienos / Churg Strauss syndrome during treatment of bronchial asthma with a leucotriene receptor antagonist presenting with polyneuropathy

El asma bronquial suele estar asociada con el síndrome de Churg Strauss (SCS). El SCS puede presentarse con una semiología polineuropática: También evidencia que los antagonistas del receptor de los leucotrienos (ARL) pueden precipitar un SCS en pacientes asmáticos, especialmente tras la supresión de corticoides. La patogenia, sin embargo, es incierta y la asociación de SCS y ARL controvertida. El caso aquí descrito pretende clarificar esta cuestión. Un paciente de 79 años con asma bronquial de 20 años de evolución fue hospitalizado porque desarrolló un trastorno de la marcha de 2 semanas de evolución. El asma había sido tratada con un ARL (Montelukast) durante 4 años, así como con inhalaciones de esteroides y betabloqueantes. Al ser admitido al hospital, la exploración neurológica reveló ligera ataxia de las manos e hipoestesia parcheada sin déficit motor. El estudio electroneurográfico puso de manifiesto signos de neuropatía sensitivomotora axonal en las piernas; en la electromiografía se registraron potenciales espontáneos de denervación en los músculos tibial anterior y recto anterior del muslo. La biopsia de músculo y nervio evidenció una vasculitis eosinofilica. En los estudios hematológicos había leucocitosis con eosinofilia. Se estableció un diagnóstico de SCS. Este caso demuestra la aparición de una acusada polineuropatía en un paciente asmático durante el tratamiento con un ARL y esteroides inhalados como forma de presentación del SCS (AU)

Akinetic mutism caused by bilateral infiltration of the fornix in a patient with astrocytoma.

In a 59-year-old female patient, a World Health Organization (WHO) grade II astrocytoma had been diagnosed 16 years ago, which finally progressed into WHO grade III. Several right frontal neurosurgical resections, local radiation and a local radioimplant had been applied. Despite this long record, she was reported alert with a Karnofsky index of 90% until admission. Within a few weeks she rapidly developed akinetic mutism. Upon admission, computed tomography (CT) scan showed a large cystic right frontal defect and a suggested small tumor recurrence. White matter of the frontal lobe appeared to be translucent and compatible with previous radiation. The severe mental changes were initially attributed to a delayed radiation encephalopathy. Neuropathologically, the white matter of the frontal lobe showed mild elevated cell density consistent with gliosis; however, a tumor recurrence invading the tip of the corpus callosum and invading the entire length both fornices appeared. From the neuropathological findings of massive local tumor recurrence in both fornices, together with the acute clinical onset, it seems unlikely that the sequel of radiotherapy caused akinetic mutism, but the symmetric and severe involvement of the limbic system. We conclude that the rapid progression from a state of alertness to a full clinical picture of akinetic mutism was because of infiltration of both fornices.

Acquired neuromyotonia and peripheral neuropathy in a patient with Hodgkin's disease.

Acquired neuromyotonia is characterized by hyperexcitability of motor nerves resulting in continuous muscle fiber activity. It occurs most often as a paraneoplastic syndrome in patients with cancers of the immune system. Antibodies against voltage-gated potassium channels (VGKCs) have been detected in some patients. Peripheral neuropathy is sometimes present. We report on a patient with Hodgkin's lymphoma in complete remission who developed paresthesias followed by neuromyotonia with bulbar involvement. Peripheral sensorimotor neuropathy was diagnosed electrophysiologically and evidence of axonal degeneration and demyelination was detected by sural nerve biopsy. The patient's complaints, including dysarthria, improved after carbamazepine treatment.

Effects of selective serotonin reuptake inhibitors on objective and subjective sleep quality.

The purpose of this paper is to review the effects of selective serotonin (5-HT) reuptake inhibitors on objective and subjective sleep and awakening quality measures. Polysomnography (PSG) demonstrated in both healthy volunteers and depressed patients a decrease in sleep efficiency and total sleep time, a lengthening of sleep latency and a deterioration in sleep continuity, including an increase in the number of awakenings and wake time during the total sleep period. Sleep architecture mostly showed an increase in S1 and S2 and a decrease in S3, S4 and REM sleep as well as a lengthening of REM latency. Objective awakening quality, if measured at all by psychometry, generally showed no decrements. Concerning subjective sleep and awakening quality, normals demonstrated either no changes or a tendency towards a deterioration, while in patients some improvement was observed. Reasons for this discrepancy will be discussed. Novel 5-HT reuptake inhibitors with additional modes of action such as 5-HT2 antagonism (e.g. trazodone, nefazodone) are more likely to improve objective and subjective sleep quality, although some shortcomings may be inherent in regard to comorbidity (e.g. sleep-related breathing disorders). Thus, PSG seems to be a necessity for diagnosis and treatment of complex sleep disorders.

Theophylline in snoring and sleep-related breathing disorders: sleep laboratory investigations on subjective and objective sleep and awakening quality.

The aim of the present investigation was to comparatively examine the effect of theophylline on various sleep-related breathing disorders of different severity. In a single-blind, placebo-controlled crossover study, 30 patients were polysomnographically diagnosed as suffering from primary snoring (n = 7), obstructive snoring (n = 12) or moderate sleep apnea (n = 11). Subsequent polysomnographic investigations included one baseline, one placebo and one theophylline (Respicur retard 400 mg, Byk Gulden, Konstanz, Germany) night. Subjective sleep and awakening quality was evaluated by means of a test battery completed in the morning. Concerning respiratory variables, theophylline was most effective in patients with moderate sleep apnea. Obstructive snorers only showed a tendency towards improvement and primary snorers remained unchanged. Sleep architecture generally remained unchanged in all three patient groups. Objective awakening quality was partly improved in primary snorers, obstructive snorers, as well as in moderate sleep apnea patients as compared with baseline, but not as compared with placebo. Regarding subjective sleep and awakening quality, only primary snorers and obstructive snorers showed an improvement, as compared with baseline while moderate sleep apnea patients remained unchanged. Based on intergroup comparison, we conclude that patients with moderate sleep apnea showed the most pronounced improvement in regard to respiratory events. Concerning sleep initiation and maintenance, sleep architecture and subjective sleep and awakening quality, no significant intergroup differences were found. Regarding objective awakening quality, attention showed a significantly greater improvement in primary than in obstructive snorers and sleep apnea patients, while motor performance was most improved in obstructive snorers.

Sleep laboratory studies in restless legs syndrome patients as compared with normals and acute effects of ropinirole. 2. Findings on periodic leg movements, arousals and respiratory variables.

The restless legs syndrome (RLS) is a common sensorimotor disorder which leads to severe sleep disturbances and showed a prevalence of 7.9% in our sleep laboratory. The aim of this study was to investigate periodic leg movements (PLM), arousal and respiratory variables in 12 untreated RLS patients and to measure the acute effects of 0.5 mg ropinirole, a nonergoline dopamine agonist, as compared with placebo. In the target variable PLM/h of total sleep time (PLM/h TST), RLS patients showed an increased value of 40/h (normal 0-5/h). Further, we found an increased number of PLM (368), PLM/h of time in bed (49/h), PLM/h of REM sleep (11), PLM/h of non-REM sleep (46) and PLM/h awake (61). The arousal index was also increased (32/h; normal 0-25/h), as were arousals due to PLM. In the confirmatory part of our descriptive data analysis, ropinirole 0.5 mg significantly improved, as compared with placebo, the index PLM/h TST by 75%. In the descriptive part, all the other PLM variables were improved as well. Arousals due to PLM decreased, while spontaneous arousals increased. Respiratory variables, which had a priori been in the normal range, showed a slight but significant improvement after the dopamine agonist. Thus, 0.5 mg ropinirole significantly improved the target variable PLM/h TST, along with objective and subjective sleep quality and morning noopsychic performance, as described in the preceding paper. Our data encourage further sleep studies including all above-mentioned variables in a larger group of RLS/PLM during sleep patients as well as long-term efficacy trials.

[Daytime tiredness correlated with nocturnal respiratory and arousal variables in patients with sleep apnea: polysomnographic and EEG mapping studies]. / Tagesmüdigkeit korreliert mit nächtlichen Atmungs- und Arousal-Variablen bei Schlafapnoepatienten: Polysomnographische und EEG-Mapping-Untersuchungen.

There is evidence that daytime tiredness is caused by apnea/hypopnea with oxygen desaturation and/or by sleep fragmentation due to arousals. The aim of this study was to investigate objective and subjective sleep and awakening quality and daytime vigilance--objectified by midmorning mapping of vigilance-controlled EEG (V-EEG)--in sleep apnea patients (N: 18), as compared with age- and sex-matched normal controls (N: 18) as well as to correlate nocturnal respiratory distress and arousals to daytime brain function. Statistical analyses demonstrated a deterioration in subjective and objective sleep and awakening quality in apnea patients. Midmorning V-EEG mapping in apnea patients exhibited less total power, more delta and theta, less alpha and beta activity, as well as a slower dominant frequency and centroid of the total activity compared to controls, which suggests a vigilance decrement. The Spearman rank correlation between 6 polysomnographically registered respiratory variables and 36 diurnal quantitative EEG measures demonstrated the following: the higher the apnea, apnea-hypopnea, snoring and desaturation indices and the lower the minimum and average low oxygen saturation, the more pronounced was diurnal tiredness. Eleven arousal measures based on ASDA criteria showed the following significant correlations: the higher the nocturnal arousal index and the more arousals due to hypopneas, the greater was daytime tiredness. On the other hand, the greater the average frequency change during arousals and the more spontaneous arousals, the better was daytime vigilance. Our findings show that, in contrast to the lengthy Multiple Sleep Latency (MSLT) and Maintenance of Wakefulness (MWT) tests which evaluate sleep pressure under resting conditions conducive to sleep, V-EEG mapping provides a brief objective measure of a sleep apnea patient's daytime tiredness under conditions of wakefulness more appropriate to reflect the patient's everyday life.