Acute hepatitis E virus infection presenting as meningo-encephalitis.

BACKGROUND: Acute hepatitis E infection (HEV), with its high incidence in Europe, should be considered as a differential diagnosis of acute viral hepatitis and can in some cases manifest with pronounced neurological symptoms. CLINICAL CASE: We report on a 33-year-old female patient with severe arthralgia, myalgia, headache and psychomotor deterioration. Laboratory analyses showed elevated transaminases without signs of cholestasis. Acute hepatitis E virus infection was detected in serum. She reported fatigue and dysesthesias not responsive to analgesics. Cerebrospinal fluid (CSF) analysis revealed an inflammatory syndrome. HEV RNA was detected in the CSF. The infection remained mild, but dysesthesias persisted. Eight weeks after the first admission, the symptoms worsened again. Complete and sustained remission was achieved following intravenous corticosteroid treatment. CONCLUSION: In patients with acute neurological symptoms and liver enzyme elevation, HEV infection should be considered. Neurologic symptoms such as fatigue, arthralgia, myalgia and dysesthesia along with psychomotor retardation should prompt CSF analysis.

S1 guidelines "lumbar puncture and cerebrospinal fluid analysis" (abridged and translated version).

INTRODUCTION: Cerebrospinal fluid (CSF) analysis is important for detecting inflammation of the nervous system and the meninges, bleeding in the area of the subarachnoid space that may not be visualized by imaging, and the spread of malignant diseases to the CSF space. In the diagnosis and differential diagnosis of neurodegenerative diseases, the importance of CSF analysis is increasing. Measuring the opening pressure of CSF in idiopathic intracranial hypertension and at spinal tap in normal pressure hydrocephalus constitute diagnostic examination procedures with therapeutic benefits.Recommendations (most important 3-5 recommendations on a glimpse): The indications and contraindications must be checked before lumbar puncture (LP) is performed, and sampling CSF requires the consent of the patient.Puncture with an atraumatic needle is associated with a lower incidence of postpuncture discomfort. The frequency of postpuncture syndrome correlates inversely with age and body mass index, and it is more common in women and patients with a history of headache. The sharp needle is preferably used in older or obese patients, also in punctures expected to be difficult.In order to avoid repeating LP, a sufficient quantity of CSF (at least 10 ml) should be collected. The CSF sample and the serum sample taken at the same time should be sent to a specialized laboratory immediately so that the emergency and basic CSF analysis program can be carried out within 2 h.The indication for LP in anticoagulant therapy should always be decided on an individual basis. The risk of interrupting anticoagulant therapy must be weighed against the increased bleeding risk of LP with anticoagulant therapy.As a quality assurance measure in CSF analysis, it is recommended that all cytological, clinical-chemical, and microbiological findings are combined in an integrated summary report and evaluated by an expert in CSF analysis. CONCLUSIONS: In view of the importance and developments in CSF analysis, the S1 guideline "Lumbar puncture and cerebrospinal fluid analysis" was recently prepared by the German Society for CSF analysis and clinical neurochemistry (DGLN) and published in German in accordance with the guidelines of the AWMF (https://www.awmf.org). /uploads/tx_szleitlinien/030-141l_S1_Lumbalpunktion_und_Liquordiagnostik_2019-08.pdf). The present article is an abridged translation of the above cited guideline. The guideline has been jointly edited by the DGLN and DGN.

Anti-contactin-associated protein-2 encephalitis: relevance of antibody titres, presentation and outcome.

BACKGROUND AND PURPOSE: To clarify the relevance of titres of IgG antibodies against contactin-associated protein-2 (CASPR2) in diagnosing anti-CASPR2 encephalitis and to describe features and outcomes. METHODS: This was a retrospective analysis of 64 patients with CASPR2 antibodies, categorized independently as 'autoimmune encephalitis' or 'other disease'. Logistic regression methods were performed to identify potential predictors of 'autoimmune encephalitis' in addition to CASPR2 antibodies. RESULTS: An upfront CASPR2 antibody serum titre cut-off at ≥1:200 had a diagnostic sensitivity of 85% and a specificity of 81%. Logistic regression analyses indicated that, in addition to titre, encephalitic magnetic resonance imaging (MRI) was a significant predictor of 'autoimmune encephalitis' (Nagelkerke's R2 = 0.81, P < 0.001) with high sensitivity (84%) and very high specificity (100%). Patients with CASPR2 antibodies and an estimated probability of >70% of having anti-CASPR2 encephalitis (n = 22) had limbic encephalitis (n = 18, one patient plus ataxia), Morvan syndrome (n = 2) or a hyperkinetic movement disorder (n = 2). Median modified Rankin score (mRS) at diagnosis was 3 (range 1-4). Twenty patients were male; median age was 64 (range 54-75) years; 5/15 patients with cerebrospinal fluid data had intrathecal CASPR2 antibody synthesis, and 12/19 with follow-ups >3 months (median 12 months, range 4-43 months) improved by ≥1 mRS point resulting in a median mRS of 2 (range 0-6; one death; all but one having received immunotherapy); and 2/15 patients with follow-up MRI developed hippocampal atrophy. CONCLUSIONS: Only higher CASPR2 serum antibody titres indicate anti-CASPR2 encephalitis, and diagnostic accuracy increases if MRI findings are considered. Anti-CASPR2 encephalitis has characteristic features and a favourable outcome with immunotherapy.

[Cytology of cerebrospinal fluid : Standards, importance and modern methods]. / Liquorzytologie : Standards, Stellenwert und moderne Methoden.

Cytology is an integral part of cerebrospinal fluid (CSF) analysis. It is relevant for the diagnostics and differential diagnosis of inflammatory, hemorrhagic and neoplastic central nervous system (CNS) processes. This article summarizes the recommended procedures and typical clinical patterns. In addition, modern immunocytochemical and flow cytometry methods for CSF cytology are presented. In particular, the diagnostic contribution and clinical relevance in several CNS conditions are discussed.

[Delirium: Concepts, Etiology, and Clinical Management]. / Delir: Konzepte, Ätiologie und klinisches Management.

Delirium is a common condition: up to 35 percent of non-ICU- and 80 percent of ICU-patients experience delirium - particularly the elderly suffering from cerebral dysfunction accompanied by acute infection, surgery, or change of medication. Medical staff should be alert for decrease (within hours) of concentration, memory, orientation, and consciousness - especially when agitation appears and symptoms are fluctuating. Vegetative lapses and seizures may complicate the course, in particular in delirium in withdrawal (of alcohol or drugs). Treatment comprises neuroleptic and sedative medication (be careful with benzodiazepines because of their delirogenic potential) as well as alpha-2-agonists for vegetative derangements and anti-epileptics in case of seizures. As usual: start with low doses, and keep the medical treatment as short as possible. Additionally, take care in the · search and solution of delir-causes,. · termination of unnecessary medication (in particular, anticholinergic agents),. · comfort, intimacy and orientation,. · cognitive training and mobilization.. Avoiding a delirium is the best medicine. For that reason, identification of patients at risk, early detection of signs of delirium and prevention are most important. Beside factors 2 to 4, personalized treatment has been proved to be very helpful.

[Nationwide evaluation of German university teaching methods in neurology]. / Deutschlandweite Evaluation der universitären Lehre im Fach Neurologie.

BACKGROUND: Germany is confronted with a lack of medical doctors and an increasing need for neurologists in particular. In order to recruit future doctors in neurology it is essential to attract young students when still at university. OBJECTIVES: This article presents the first German national survey of medical students' acceptance of teaching methods in neurology. The participants evaluated teaching methods and examination formats and were asked about their preferences. MATERIAL AND METHODS: The survey was based on a questionnaire distributed to 22 German medical schools and 1245 participating students. RESULTS: Interactive teaching methods, especially courses in practical examinations, clinical internships and bedside teaching were highly rated among the students. In contrast, multiple choice tests, as one of the most widespread examination methods, were poorly rated compared to practical and oral examinations. For most of the students it was not decisive, in which semester teaching of neurology took place, while the majority asked for additional and more intensive neurological education. CONCLUSION: The data give an overview of teaching of neurology in Germany and students' assessment of various approaches. The results should be utilized towards reorientation of future curricula that should aim at innovative and even more practically oriented teaching.

Non-dipping nocturnal blood pressure and psychosis parameters in Parkinson disease.

BACKGROUND: Non-motor symptoms are increasingly recognized in Parkinson disease (PD) and include physical as well as psychological symptoms. A psychological condition that has been well studied in PD is psychosis. Cardiovascular autonomic dysfunction in PD can include a reversed or loss of blood pressure (BP) circadian rhythm, referred to as nocturnal non-dipping. The aim of this study was to determine the relationship between 24 h ambulatory blood pressure measurements (ABPM), i.e., absence or presence of nocturnal dipping, and psychosis scores in PD. METHODS: Twenty-one patiens with PD underwent 24 h ABPM using an autonomic protocol. A decrease in nocturnal mean arterial blood pressure of less than 10% was defined as non-dipping. Patients were interviewed (including the brief psychiatric rating scale; BPRS) for the assessment of psychosis. RESULTS: Eleven patients were dippers and 10 were non-dippers. BPRS scores were higher in non-dippers, who, on average, met the criteria for psychosis (mean non-dipper BPRS: 34.3 ± 7.3 vs mean dipper BPRS: 27.5 ± 5.3; cutoff for "mildly ill" 31). There was a correlation between BPRS scores and non-dipping, indicating that those patients who had a blunted nocturnal fall in BP were more prone to psychotic symptoms (Pearson's Correlation = 0.554, p = 0.009). CONCLUSION: These results suggest that, among PD patients, a non-dipping circadian rhythm is associated with more severe symptoms of psychosis than is a dipping circadian rhythm. This association warrants further investigation.

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.

[University teaching in clinical neurology: present situation and future requirements]. / Universitäre Lehre in der Neurologie : Aktuelle Situation und zukünftiger Bedarf.

BACKGROUND: In German Hospitals there is a lack of medical personnel and doctors in particular. Clinical specialities and hospitals are in competition for students and young doctors and these, in turn, have clear cut demands regarding working conditions and professional training. To date there is considerable heterogeneity regarding clinical teaching in neurology between different German universities. There are no data available for systematic comparison. MATERIAL AND METHODS: This article presents for the first time data from a survey on academic teaching in neurology in German university hospitals. RESULTS AND CONCLUSION: The data show that many faculties are dedicated to modern and practical teaching methods and have employed state of the art examinations and progress tests. Further and ongoing efforts will be needed in order to inspire medical students and young doctors for this interesting clinical speciality. Connecting individual formats and networking between universities, teaching hospitals, including novel developments together with the young neurologists will help to structure our efforts and increase sustained attractiveness of clinical neurology for the following generations of young doctors.

[Anxiety in patients with postural tachycardia syndrome (POTS)]. / Ängstlichkeit bei Patienten mit posturalem Tachykardiesyndrom (POTS).

BACKGROUND: The postural tachycardia syndrome (POTS) is a condition of the autonomic nervous system with symptoms of orthostatic intolerance. In POTS patients, orthostatic stress leads to an overshoot of heart rate increase without a fall in blood pressure. The purpose of this study is to distinguish between anxiety disorders and anxiety as a concomitant phenomenon of orthostatic stress. METHODS: 50 patients fulfilling the diagnostic criteria (orthostatic symptoms, heart rate increase of > 30 bpm or up to > 120 bpm by testing with tilt-table) were included. The study design included a thorough medical history as well as standardised questionnaires about anxiety. RESULTS: The average heart rate increase was 36 bpm after ten minutes of standing and 42 bpm after maximal standing time (max. 45 minutes). POTS patients scored significantly higher than a comparison group in a range of anxiety disorders by using anxiety questionnaires like "Beck Angst-Inventar" (BAI) and trait test of "State-Traits-Angstinventar" which include autonomic items. When questionnaires were used that exclude autonomic items (anxiety sensitivity index: ASI; Interaktions-Angst-Fragebogen: IAF) there was no difference. CONCLUSION: POTS patients do not exhibit signals of anxiety disorders more often than control groups, provided that questionnaires without autonomic items are used.

Bortezomib-induced severe autonomic neuropathy.

Peripheral neuropathy is a known side effect of bortezomib therapy. Acute autonomic neuropathy may also follow treatment with this cytotoxic agent used for treatment of multiple myeloma. Here, we report clinical characteristics and patterns of autonomic involvement in a 75-year-old patient who presented with recurring syncopes.

Gastroparesis in myotonic dystrophy 1.

Clinicians should consider impaired gastric emptying when evaluating patients with myotonic dystrophy type 1 and severe symptoms of upper gut dysmotility. Gastric emptying time measurement by radionuclide study, although informative, is rarely done in clinical practice.

An Empirical Analysis of the Current Need for Teleneuromedical Care in German Hospitals without Neurology Departments.

Indroduction. At present, modern telemedicine methods are being introduced, that may contribute to reducing lack of qualified stroke patient care, particularly in less populated regions. With the help of video conferencing systems, a so-called neuromedical teleconsultation is carried out. Methods. The study included a multicentered, completely standardized survey of physicians in hospitals by means of a computerized on-line questionnaire. Descriptive statistical methods were used for data analysis. Results. 119 acute hospitals without neurology departments were included in the study. The most important reasons for participating in a teleneuromedical network is seen as the improvement in the quality of treatment (82%), the ability to avoid unnecessary patient transport (76%), easier and faster access to stroke expertise (72%) as well as better competitiveness among medical services (67%). The most significant problem areas are the financing system of teleneuromedicine with regard to the acquisition costs of the technical equipment (43%) and the compensation for the stroke-unit center with the specialists' consultation service (31%) as well as legal aspects of teleneuromedicine (27%). Conclusions. This investigation showed that there is a high acceptance for teleneuromedicine among co-operating hospitals. However these facilities have goals in addition to improved quality in stroke treatment. Therefore the use of teleneuromedicine must be also associated with long term incentives for the overall health care system, particularly since the implementation of a teleneuromedicine network system is time consuming and associated with high implementation costs.

Recurrent orbital myositis mimicking sixth nerve palsy: diagnosis with MR imaging.

We present a case with recurrent orbital myositis sequentially affecting both lateral rectus muscles separately. In the first episode, the absence of the required symptoms for the diagnosis of orbital myositis led to the erroneous diagnosis of sixth nerve palsy. Eventually, the correct diagnosis was established with cerebral MR imaging. Orbital myositis should be included in the differential diagnosis of what appears clinically to be abducens palsy, and MR imaging with a focus on the orbita is mandatory in such patients.

Cardiac denervation occurs independent of orthostatic hypotension and impaired heart rate variability in Parkinson's disease.

Patients with idiopathic Parkinson's disease (PD) have impaired sympathetically mediated neurocirculatory innervation. Here we analyzed the correlation between cardiac (123)I-metaiodobenzylguanidine (MIBG) uptake, orthostatic hypotension and heart rate variability in treated patients with PD. Orthostatic hypotension (OH) as a hallmark of sympathetic neurocirculatory failure was found with a high prevalence in PD. PD is known to affect cardiac innervation, resulting in a suppressed heart rate variability and a postganglionic noradrenergic lesion. We measured continuous arterial blood pressure in rest and 70 degrees head-up tilt for at least 20 min, heart rate variability in the supine position, standing, deep respiration and Valsalva manoeuvre in 58 patients with PD (27 male, 31 female; mean age 71 years, mean PD duration 5.1 years, Hoehn and Yahr 3.1+/-0.8). Sympathovagal balance was estimated by the low-frequency (LF: 0.04-0.15Hz) and high-frequency bands (HF: 0.15-0.4Hz) ratio in the analysis of heart rate variability in each condition. Myocardial adrenergic function was analyzed by imaging MIBG using the single-photon emission computed tomography technique. MIBG uptake expressed as heart-to-mediastinum ratio was reduced in all PD patients (H/M-ratio: 1.14+/-0.16). We found no correlation between myocardial MIBG uptake and sympathovagal balance, blood pressure or other autonomic findings. The LF/HF ratio in tilt-table testing was significantly more reduced in PD with OH than without OH (2.18 vs. 1.49, p=0.022). MIBG uptake did not differ. It is concluded that scintigraphy with MIBG appears to be a highly sensitive and useful tool to demonstrate sympathetic postganglionic cardiac nerve disturbances. Loss of sympathetic innervation of the heart seems to occur early and independent of orthostatic hypotension, baroreflex failure and impaired heart rate variability in PD.

[Early evaluation of neurological prognosis and therapy after cardiopulmonary resuscitation: current opportunities and clinical implications]. / Neurologische Prognose und Therapie nach kardiopulmonaler Reanimation: Aktuelle Möglichkeiten und klinische Implikationen.

The developments of cardiopulmonary resuscitation and intensive care medicine have made possible survival after cardiac arrest. However, only 10-30% of patients with initially successful resuscitation later reach a state without severe neurological impairment. Ethical and socioeconomic reasons therefore make early prognosis important for certain patients. There are no reliable parameters for predictions of good clinical outcome. If clinical information is consistent with severe hypoxic brain damage, cortical somatosensory evoked potentials are absent, and neuron-specific enolase values exceed 33-65 microg/l, recovery of consciousness can be excluded. The same result can be predicted if brain imaging shows severe hypoxemic changes or if a myoclonic status occurs on the first day. In summary, the prognosis in patients with cerebral anoxy and cardiopulmonary resuscitation remains poor. Treatment with hypothermia for 24 h is recommended.

Aneurysm of the extracranial carotid artery with spontaneous echo contrast revealed by duplex sonography.

A 56-year old male patient without cerebrovascular disease or risk factors presented with a painless, pulsatile right-sided cervical swelling. Ultrasonography showed a large aneurysm of the right common and internal carotid artery with homogeneous thickening of the vessel wall as well as a parietal thrombus and a dilation of the left common and internal carotid artery with markedly reduced blood flow velocities. In the enlarged lumen of the right internal carotid artery spontaneous echo contrast was apparent with slow, ineffective but orthograde blood flow motions. Ensuing diagnostic procedures revealed multiple aneurysms involving the aorta and its branches. Despite surgical removal of the aneurysm and glucocorticoid therapy, the patient died from a ruptured aneurysm of a coronary artery a few weeks later. Post-mortem examination showed panarteritis consistent with Takayasu's disease. Spontaneous echo contrast is a frequent echocardiographic finding in patients with atrial fibrillation and mitral stenosis, indicating decreased blood flow. This is associated with an increased risk of embolism. In our patient, spontaneous echo contrast indicated severely disturbed haemodynamics due to a large aneurysm of the carotid artery. In the rare case of multiple aneurysms, differential diagnosis should include dissections, infections, and connective tissue diseases. Takayasu's arteritis, however, should also be considered, which usually presents with stenoses, but may be associated with multiple aneurysms of the aorta or its branches. If the diagnostic criteria are present, immunosuppressive treatment should be initiated.

[Selective immunoadsorption in neurologic complications of systemic lupus erythematosus]. / Selektive Immunadsorption bei neurologischen Komplikationen eines systemischen Lupus erythematodes.

Vasculitis of the nervous system is a rare cause of multifocal neurologic symptoms and may involve both the central and peripheral nervous systems. Typical symptoms include headache, encephalopathy with cognitive impairment and psychotic symptoms, epileptic seizures, and peripheral neuropathies. Here we report the case of a 71-year-old female presenting with Raynaud's syndrome and paresthesia of the feet. Several weeks later she was admitted to our hospital with a status epilepticus and complex partial seizures. On admission she had mild aphasia, distal paresis of the arms without sensory deficits, and disorientation with hallucinations. Cerebral MRI revealed small, multifocal infarctions in several arterial territories. Multiple cerebral artery stenoses were detected by ultrasound. Examination of the CSF was unremarkable. Serologic tests for autoimmune disorders detected Ro antibodies compatible with systemic lupus erythematosus or Sjögren's syndrome. A sural nerve biopsy revealed ischemic axonal neuropathy. During administration of i.v. methylprednisolone, the symptom progression stopped but dosages could not be tapered due to severe CNS symptoms (mental decline, disorientation, aphasia, hallucinations). Slow but sustained clinical improvement was achieved by immunoadsorption over 3 weeks followed by a combined high-dose immunosuppressive treatment with cyclophosphamide and prednisolone that paralleled a reduction in anti-Ro titers and normalization of cerebral blood flow velocities as detected by repeated transcranial Doppler sonography. Systemic vasculitis may present with multiple neurologic and psychiatric symptoms due to involvement of the central and peripheral nervous systems. After excluding systemic infection, immunosuppressive therapy should be started early. In our case a combination of high-dose methylprednisolone, immunoadsorption with elimination of Ro antibodies, and cyclophosphamide led to the patient's recovery.