New onset status epilepticus in older patients: Clinical characteristics and outcome.

PURPOSE: We here evaluated (1) the differential characteristics of status epilepticus (SE) in older (≥60 years) compared to younger adults (18-59 years). In particular, we were interested in (2) the proportion and characteristics of new onset SE in patients with no history of epilepsy (NOSE) in older compared to younger adults, and (3) predictive parameters for clinical outcome in older subjects with NOSE. METHODS: We performed a monocentric retrospective analysis of all adult patients (≥18years) admitted with SE to our tertiary care centre over a period of 10 years (2006-2015) to evaluate clinical characteristics and short-time outcome at discharge. RESULTS: One-hundred-thirty-five patients with SE were included in the study. Mean age at onset was 64 years (range 21-90), eighty-seven of the patients (64%) were older than 60 years. In 76 patients (56%), SE occurred as NOSE, sixty-seven percent of them were aged ≥60 years. There was no age-dependent predominance for NOSE. NOSE was not a relevant outcome predictor, especially regarding age-related subgroups. Older patients with NOSE had less frequently general tonic clonic SE (GTCSE; p=0.001) and were more often female (p=0.01). Regarding outcome parameters and risk factors in older patients with NOSE, unfavourable outcome was associated with infections during in-hospital treatment (0.04), extended stay in ICU (p=0.001), and generally in hospital (p<0.001). CONCLUSION: In our cohort, older patients represented the predominant subgroup in patients with SE. Older patients suffered more often from non-convulsive semiology and had a less favourable short-time outcome. NOSE was not a predictive outcome parameter in older patients. Data suggest that avoiding infections should have a priority because higher infection rates were associated with unfavourable outcome.

[The Therapeutic Dilemma in Treatment of Intracranial Infectious Aneurysm in Patients with Infective Endocarditis: Proposal for a Patient-Centered, Interdisciplinary Treatment Concept]. / Das infektiöse Pseudoaneurysma - eine seltene Komplikation bei Patienten mit septischem Krankheitsbild: aktuelle Datenlage und Vorschlag eines diagnostischen und therapeutischen Algorithmus.

Intracranial infectious aneurysms are rare but hazardous complications of an infective endocarditis. To date, there are no evidence-based recommendations for the treatment of patients with this condition. Therefore, it remains an interdisciplinary challenge to decide which treatment steps are required and in which order they should be carried out. To illustrate the interdisciplinary dilemma in the treatment of these patients, we here present a case of a 23-year-old, drug-addicted woman with infectious endocarditis. While antibiotic treatment of the streptococcus-mitis-induced endocarditis stabilized the overall status of the patient, rupture of a basilar artery aneurysm caused her sudden death. We discuss the decision-making processes of the treatment, potential difficulties and dilemmas when dealing with patients suffering from infectious endocarditis and infectious intracranial aneurysm. Based upon case reports, studies and reviews, we present the options and risks of conservative, neurosurgical, endovascular, and cardiosurgical treatment of intracranial infectious aneurysms, and propose a patient-centered, interdisciplinary treatment concept.

Age-stratified cut-off points for the nocturnal penile tumescence measurement using Nocturnal Electrobioimpedance Volumetric Assessment (NEVA(®) ) in sexually active healthy men.

The current nocturnal penile tumescence (NPT) measurement is based on standard cut-off levels defined regardless of age. This study was conducted to provide age-stratified cut-off points for NPT measurement. Forty sexually active healthy men between 20 and 60 years old were enrolled and divided equally into four groups defined by age (20-29, 30-39, 40-49 and 50-60 years.). None of the candidates had sexual dysfunction or sleep disturbance or used supportive medication to enhance sexual function. Erectile function was evaluated by using the 5-item version of the international index of erectile function (IIEF-5). NPT was observed using the nocturnal electrobioimpedance volumetric assessment (NEVA(®) ). The NPT values of healthy men aged 20-60 years varied from 268.7% to 202.3%. The NPT differed significantly between age groups (P < 0.0009); however, no significant differences between men aged 30-39 and 40-49 (P = 0.593) were observed. Age was weakly associated with IIEF-5 scores (P = 0.004), whereas a strong and negative correlation between age and NPT (P < 0.0001) was found. IEF-5 scores were not significantly associated with NPT (P = 0.95). Therefore, the standard values for NPT testing should be considered in the evaluation of the nocturnal penile activity of men of all ages.

[Neurocysticercosis]. / Neurozystizerkose.

Neurocysticercosis is a leading cause of acquired epilepsy worldwide and endemic in underdeveloped and developing regions. As a result of increased migration and traveling, cases of neurocysticercosis reach Europe more frequently. Neurological symptoms are multifarious and often nonspecific, so that neurocysticercosis poses a diagnostic challenge. We report a case of a patient in whom the diagnosis of neurocysticercosis was achieved quickly via the patient's history, neuroimaging and serology.

Intravenous levetiracetam in clinical practice--Results from an independent registry.

PURPOSE: Most common clinical studies with antiepileptic drugs do not reflect medical everyday practice due to their strict in- and exclusion criteria and specifications of treatment regimens. Here we present a large non-interventional registry with the intention to evaluate the spectrum of applications in daily use and the efficacy and tolerability of intravenously given levetiracetam (LEV-iv). METHODS: In a prospective approach of 17 neurological and neuropediatric centres in Germany LEV-iv treated patients of all ages were included over a period of 10 months. The observational period was 10 days with daily documentation of LEV-iv administration, type and frequency of seizures, currently used drugs and doses, and adverse events (AEs). In addition, treatment efficacy and tolerability were assessed by patients and physicians at study end as well as practicability of LEV-iv using a five-step scale. RESULTS: In 95 patients LEV-iv was administered, 93 were included into the analysis. The median LEV-iv dose was 1500 mg (range 110-6000 mg) per day. Median age was 66 years (range 0.7-90.3 years). The majority of patients (n=70, 75%) suffered from status epilepticus (SE, n=55, 59%) and acute seizure clusters (n=15, 16%). Of those with SE, 41 patients (75%) had SE for the first time. Acute seizure clusters and SE terminated in 83% after LEV-iv administration. A total of 29 adverse events were reported in 17 of the 95 patients from the safety set. Ten of these were at least possibly related to LEV-iv treatment. Slight decrease of blood pressure during the infusion (3 patients each) was captured most frequently. No serious side effect was observed. Physicians rated the efficacy and tolerability of LEV-iv treatment as good or very good in 78% and 82% of the cases, respectively. CONCLUSION: In this large observational study of everyday practise the use of LEV-iv exhibited a remarkable good response and tolerability in patients with acute onset seizures (mostly SE). Further randomized controlled studies, like the established status epilepticus trial (ESET) are needed to confirm these findings.

[Pathogenesis of narcolepsy: from HLA association to hypocretin deficiency]. / Zur Pathogenese der Narkolepsie: Vom HLA-Typus als Risikoprofil zum Hypocretinmangel als Ursache.

Narcolepsy is a rare and chronic sleep disorder, characterised by excessive daytime sleepiness. Frequently associated signs are cataplexy, sleep paralysis and hypnagogic or hypnopompic hallucinations. Advances in understanding the pathogenesis of the disease have essentially been elucidated during the last fifteen years. The most significant finding has been the discovery of hypocretin-1 and -2 in 1998. Hypocretin-containing cells have widespread projections throughout the entire CNS and play a crucial role in the regulation of the sleep-wake cycle. They also contribute to olefaction and to the regulation of food intake. Animal models and human studies concordantly show that the disturbed hypocretin system is the probable cause of narcolepsy. However, it remains unclear why there is neuronal death of hypocretin-producing cells in the lateral hypothalamus. As the HLA-allele DQB1*0602 is associated with narcolepsy and hypocretin deficiency, an autoimmune reaction against hypocretin-producing neurons has been vigorously discussed. Newly discovered gene polymorphisms as well as previously unknown pathogenetic mechanisms, linking the sleep-wake cycle with the immune system, may also contribute to the pathogenetic cascade. Worthy of mention in this context is, e.g., the "insulin-like growth factor"-binding protein 3 (IGFBP3), whose overexpression causes a down-regulation of the hypocretin production. Substitution of the deficient neuropeptides by hypocretin agonists may become the causal treatment strategy of the future, if an adequate administration route can be found. Presently, animal trials, including genetic therapy, cell transplantations or the administration of hypocretin receptor agonists, are underway.

[Acute neuropathy with tetraparesis and respiratory insufficiency in cases of acute intermittent porphyria]. / Akute Neuropathie mit Tetraparese und Ateminsuffizienz bei akuter intermittierender Porphyrie.

Acute intermittent porphyria is a hereditary disorder resulting from a partial deficiency of the third enzyme in the haeme biosynthetic pathway. Symptoms are due to metabolic effects on the peripheral autonomic and sensomotoric, as well as the central nervous system. We report on the case of a life-threatening acute crisis with tetraplegia and respiratory insufficiency.

[Anti-NMDA receptor encephalitis: a neurological and psychiatric emergency]. / Anti-NMDA-Rezeptor-Enzephalitis: Ein neurologisch-psychiatrischer Notfall.

Anti-NMDA receptor encephalitis is a severe autoimmune disease, first described in 2007.  Since then a number of cases have been published, suggesting that to date the disease is a considerably underdiagnosed entity. The clinical picture develops over a relatively long period of time and is initially characterised by psychiatric symptoms such as decreased levels of consciousness and hallucinations as well as paranoid behaviour. In the course of the disease neurological symptoms occur, in particular, seizures, autonomic dysfunction and dyskinesias. Due to the young age of many patients, the symptoms are often mistaken as to result from drug-induced psychosis. Anti-NMDA receptor Encephalitis was first described in young women with teratomas. In the past few years the disorder has also been reported in men and children and without any detectable neoplasia. The diagnosis is based on the characteristic clinical picture and supportive findings in MRI, EEG and the cerebrospinal fluid. Hereby, highly specific autoantibodies directed against the NR1 subunit of the NMDA-type glutamate receptors in the CSF (or serum) play an important role and should be sought specifically in any case of an "encephalitis of unknown cause". The prognosis of the disease is favourable, even when autonomic disorders entail ventilation and/or prolonged intensive care treatment is necessary. Nonetheless, the clinical outcome is highly dependent on an early diagnosis and immunotherapy without delay. In the case of a malignancy, tumour removal is also crucial. Taken together, an interdisciplinary approach including neurologists, psychiatrists, oncologists and gynaecologists is essential in order to detect and effectively treat this disorder.

[Concussive convulsions: seizure or no seizure?]. / Kommotionelle Konvulsionen: Epileptischer Anfall oder nicht?

Convulsions following traumatic brain injury (TBI) represent a diagnostic and therapeutic challenge. They can be differentiated into late (> 7 days after TBI), early (1 - 7 days after TBI), immediate (within the first 24 h after TBI), and impact seizures (within seconds after TBI). Some authors suggest that most impact seizures are non-epileptic in origin and hence coined the term "concussive convulsions" for benign impact seizures. Early and late post-traumatic seizures frequently indicate structural brain damage and transition to chronic, post-traumatic epilepsy. The data for impact seizures or concussive convulsions is less clear: only a small percentage of impact seizures is associated with structural brain damage and the development of post-traumatic epilepsy, rather the majority of cases are benign and associated with an excellent prognosis. Here, we present a case report as a starting point for pathophysiological and clinical considerations regarding convulsions that start within seconds after TBI.

[Diagnostic work-up in Whipple's disease with cerebral involvement]. / Zerebraler Morbus Whipple: Welche Diagnostik ist Sinnvoll?

The diagnostic work-up in the case of a suspected cerebral involvement of Whipple's disease involves neuroimaging and analysis of cerebrospinal fluid (CSF) including polymerase chain reaction (PCR) assays for Tropheryma whipplei. As neurological findings may be complex and unspecific, extracerebral symptoms often lead to the suspicion of Whipple's disease. We report the cases of two patients in whom the suspected diagnosis of Whipple's disease could not be proved either by endoscopy or by the analysis of CSF. Only by means of a cerebral biopsy was the diagnosis assumed and specific therapy was initiated.

[Epileptic seizures: effects on cardiac function]. / Kardiale Auswirkungen epileptischer Anfälle.

Sudden loss of consciousness can be caused by syncope or epileptic seizure, which therefore requires a diagnostic work-up including cardiological and neurological examinations. Thus, in clinical practice cooperation of these two medical specialties is common and of high relevance. Seizures may lead to cardiac arrhythmia or ictal asystole, and "sudden unexpected death in epilepsy" (SUDEP) is an important field of epilepsy research. Cardiac channelopathies such as long QT syndrome may be associated with seizures, suggesting a possible link between cardiac and cerebral channelopathy. We here review in detail cardiac effects due to epileptic seizures as well as possible pathogenetic correlations between cardiac and epileptic diseases.

[Acute headache: limitations of cerebral computed tomography and analysis of cerebrospinal fluid in the diagnosis of subarachnoid haemorrhage]. / Plötzliche und stärkste Kopfschmerzen: Wie sicher ist der kombinierte Einsatz von Computertomografie und Lumbalpunktion zum Ausschluss einer Subarachnoidalblutung?

Subarachnoid haemorrhage constitutes a neurological emergency. In most cases the diagnosis is easy to establish by cerebral computed tomography or cerebrospinal fluid tap. However, in rare cases verification of the diagnosis is more difficult and a residual uncertainty remains. We describe three patients supposed to have a subarachnoid haemorrhage without pathological findings in both cerebral computed tomography and cerebrospinal fluid. In these cases vasospasm or cerebral aneurysm were detected by means of transcranial Doppler sonography and/or conventional angiography. We comment on the special features of this rare presentation of a severe acute neurological emergency, and we discuss diagnostic work-up and differential diagnoses.

Do negative CCT and CSF findings exclude a subarachnoid haemorrhage? A retrospective analysis of 220 patients with subarachnoid haemorrhage.

OBJECTIVE: Subarachnoid haemorrhage (SAH) constitutes a neurological emergency. In most cases, the diagnosis is easy to establish; however, in rare cases, verification of the diagnosis is difficult. In this retrospective analysis, we report the clinical characteristics of patients with SAH who were admitted to our neurological intensive care unit. We focus on the additional diagnostic approaches in patients with a high suspicion of SAH but failure of the 'classic' diagnostic tools. METHODS: A retrospective chart review was performed for all patients in whom SAH was diagnosed between 1996 and 2008. Two hundred and twenty patients were analysed for presenting symptoms, radiological and laboratory findings, hospital course and outcome. RESULTS: A total of 220 patients were identified (mean age 50.5 years, 127 women). In 217 patients, the diagnosis was based upon cerebral computed tomography (CCT) or lumbar puncture. In three patients, the diagnostic work-up was continued because of distinct clinical signs even though CCT and cerebrospinal fluid (CSF) were negative for SAH. In these patients, vasospasm was detected by transcranial doppler sonography (TCD) and/or diagnosis of aneurysm was confirmed by conventional angiography. CONCLUSION: Subarachnoid haemorrhage with negative CCT and CSF is a rare presentation of a severe acute neurological emergency. Further diagnostic as TCD/computed tomography (CT)-A or MR-A should be considered in all patients with typical clinical presentation for SAH but unremarkable CCT and CSF as an additional diagnostic tool. Ultimately, a conventional angiography should be performed if distinct clinical signs of SAH are presented.

[Mistaking a long QT syndrome for epilepsy: does every seizure call for an ECG?]. / Fehldiagnose Epilepsie beim Long-QT-Syndrom: Sollte bei jedem Anfall ein EKG abgeleitet werden?

Syncope is a common and difficult differential diagnosis for epilepsy. One possible cause for a cardiac syncope is a long QT syndrome (LQTS). LQTS with torsade de pointes tachycardia can lead to lethal ventricular fibrillation and cardiac arrest. Patients with LQTS when first diagnosed as suffering from epileptic fits often experience a particularly long diagnostic delay which may even take years. In some cases, the diagnosis of LQTS is not made until the patient needs resuscitation due to a cardiac arrest. Therefore, ECG recording should be performed for every patient presenting with a seizure considered to be of epileptic origin not only at the beginning of the disease but also when fits occur in spite of antiepileptic treatment in order to prevent an incorrect diagnosis and delay in making the correct diagnosis.

[Thrombolytic therapy in conversion disorder with sensorimotor hemisyndrome]. / Lysetherapie bei Konversionsstörung mit sensomotorischem Hemisyndrom.

We here report on a 43-year-old man who was repeatedly admitted to our stroke unit with acute onset of sensorimotor hemisyndrome of acute onset. In most cases symptoms ceased shortly after admission, but twice when symptoms persisted thrombolytic therapy was applied. This case demonstrates that in emergency situations a rare differential diagnosis like conversion disorder with sensorimotor deficits may be hard to establish even if the patient presents to the same emergency unit.

[Detection of aneurysm by 3 Tesla MRA in third cranial nerve palsy]. / Aneurysma-Detektion mit 3 Tesla-MR-Angiografie bei einseitiger Okulomotorius-Parese.

The diagnostic work-up of patients with third cranial nerve palsy includes neuroimaging because the lesion of the oculomotor nerve may result from compression due to an aneurysm. The advantages and disadvantages of different neuroimaging techniques, i. e. magnetic resonance angiography (MRA), computed tomography angiography (CTA) and intra-arterial digital subtraction angiography (DSA), are still under debate. In this context, the present case report demonstrates that the application of 3 Tesla-MRA may help to detect an aneurysm of the internal carotid artery which had remained undetected by non-invasive standard methods applied before. Therefore 3 Tesla-MRA may help to fill a gap in diagnostic approaches between non-invasive (MRA, CTA) and invasive (DSA) neuroimaging techniques.

High resolution positron emission tomography demonstrates basal ganglia dysfunction in early Parkinson's disease.

High resolution positron emission tomography (PET) with the newly developed HRRT scanner (Siemens/CTI) permits the reliable quantification of 18-Fluorodeoxyglucose (FDG) uptake as a marker of neuronal activity in small subcortical nuclei which are involved in the pathophysiology of Parkinson's disease (PD). We investigated the normalized cerebral metabolic rates of glucose (nCMRGlc) with HRRT PET in basal ganglia (BG) nuclei of 10 early-stage PD patients and in 9 healthy volunteers. PET data were co-registered to magnetic resonance images and analyzed in a three-dimensional volume-of-interest (VOI) approach. After normalization for global brain activity, PD patients showed a significantly higher nCMRGlc than controls bilaterally in the BG output nuclei (pallidum, substantia nigra) and unilateral in the caudate and putamen. The metabolic activity of the nucleus accumbens, the subthalamic nucleus, the corpus amygdaloideum and the red nucleus was normal. These first HRRT PET data in living parkinsonian humans extend previous brain imaging findings of abnormal network activity in the BG and confirm output nuclei and striatal overactivation also in early stage PD patients.

[Cerebrotendinous xanthomatosis]. / Zerebrotendinöse Xanthomatose.

HISTORY AND CLINICAL FINDINGS: A 43-year-old woman had since childhood suffered from progressive dementia. Gait ataxia and mild polyneuropathy were noted in the neurological examination. She also had painful xanthomas of the achilles tendons. A bilateral cataract operation had been performed during adolescence. INVESTIGATIONS: An elevated concentration of cholestanol and a normal cholesterol level were found in the blood samples. The cerebral computed tomography revealed slight cerebral atrophy, predominantly affecting the cerebellum. Neurophysiological tests detected a sensory polyneuropathy in the legs. In addition the electroencephalogram showed a generalized slowing of electrical activity. DIAGNOSIS, TREATMENT AND COURSE: Clinical findings and laboratory values indicated the diagnosis of a cerebrotendinous xanthomatosis. After initiation of a drug therapy, based on a combination of an HMG-CoA-reductase inhibitor (simvastatin 20 mg/day) and a bile acid, chenodeoxycholic acid (15 mg/kg/day), further progression of the disease was prevented. CONCLUSION: The diagnosis of cerebrotendinous xanthomatosis is easily made in patients presenting all clinical symptoms expected in the disease. However, up to 30% of the patients do not show severe xanthomas. Especially in early stages of the disease the diagnosis may be difficult. Treatment can be efficacious and should be started as early as possible to prevent irreversible damage, particularly in the nervous system.

Autologous blood stem cell transplantation in refractory systemic lupus erythematodes with recurrent longitudinal myelitis and cerebral infarction.

Autologous hematopoietic stem cell transplantation (ASCT) has the potential to eliminate autoreactive lymphocytes and may represent a therapeutic option for patients with refractory autoimmune diseases. We describe a 19-year old woman with neuropsychiatric systemic lupus erythematodes (NPSLE) presenting with acute longitudinal myelitis and aseptic meningitis. Despite therapy with methylprednisolone and cyclophosphamide (CYC), recurrence of longitudinal myelitis and a disabling stroke-like relapse occurred. Hematopoietic stem cells were mobilized by CYC at 2 g/m2 and G-CSF. The patient was conditioned by CYC at 200 mg/kg and anti-thymocyte globulin and 3.6 x 10(6) CD34+ cells/kg were infused. Hematopoietic regeneration was observed on day 12 after ASCT. Currently, 18 months after ASCT, the patient is in clinical remission with no evidence for residual serological or neuroradiological activity of SLE. Although a longer follow-up will be needed to reliably assess the efficacy of ASCT in this patient, the present case demonstrates that ASCT may represent a therapeutic option for patients with severe NPSLE.