Robert Pichler

Instant tough bonding of hydrogels for soft machines and electronics

A strategy for bonding water-rich hydrogels to diverse materials for electronic skins, energy storage, and soft optics is reported. Introducing methods for instant tough bonding between hydrogels and antagonistic materials—from soft to hard—allows us to demonstrate elastic yet tough biomimetic devices and machines with a high level of complexity. Tough hydrogels strongly attach, within seconds, to plastics, elastomers, leather, bone, and metals, reaching unprecedented interfacial toughness exceeding 2000 J/m2. Healing of severed ionic hydrogel conductors becomes feasible and restores function instantly. Soft, transparent multilayered hybrids of elastomers and ionic hydrogels endure biaxial strain with more than 2000% increase in area, facilitating soft transducers, generators, and adaptive lenses. We demonstrate soft electronic devices, from stretchable batteries, self-powered compliant circuits, and autonomous electronic skin for triggered drug delivery. Our approach is applicable in rapid prototyping and in delicate environments inaccessible for extended curing and cross-linking.

Sarcoidois and Radiation-Induced Astrogliosis Causes Pitfalls in Neuro-Oncologic Positron Emission Tomography Imaging by O-(2-[18F]Fluoroethyl)-l-Tyrosine

Positron emission tomography (PET) imaging has become popular in staging and restaging of cancer because of the possibility that the radiopharmaceutical [F]fluorodeoxyglucose (FDG) could show increased glucose metabolism. Because of the high background activity in normal cortical brain tissue and low FDG avidity in some gliomas, Cand F-labeled amino acids usually replace FDG in brain tumor imaging. There is less information about false-positive pitfalls in amino acid PET imaging compared with FDG. L-[C]methionine (C-MET) can be accumulated by inflammatory processes whereas O-(2-[F]fluoroethyl)-L-tyrosine (F-FET) should not accumulate. We observed false-positive FET-PET imaging in lesions with reactive astrogliosis, which was revealed later on by histology. In the first case report, a 38-year-old man was referred to our neurologic hospital because of seizures in August 2009. A lesion 1 cm in diameter located at the mesial right temporal lobe suggestive of tumor was observed by magnetic resonance imaging. FET-PET revealed faint but clearly visible tracer accumulation in the lesion, indicating low-grade brain glioma (Figs 1A and 1B). Small, soft, whitishpink tissue fragments were histopathologically examined. Many sharply delineated granulomas were found in the gray matter. In the center of each granuloma, epithelioid cells and multinucleated giant cells were visible. In the adjacent gray matter, distinct reactive astrogliosis was clearly detectable on hematoxylin and eosin staining (Fig 2) and immunhistochemically with an antibody against glial fibrillary acidic protein (Fig 3). A brain tumor was not evident. The lesion was diagnosed as cerebral sarcoidosis. Restaging by FDG-PET computed tomography revealed active thoracic lymph nodes, so corticoids were added to anticonvulsive treatment. At last follow-up in April 2010, no residual disease was observed. In the second case report, a 79-year-old man underwent magnetic resonance brain imaging for evaluation of slow progressive cognitive deficit. A lesion of unknown significance was observed in the left polar temporal lobe in July 2009. FET-PET proved the lesion to be markedly FET avid (Figs 4A and 4B) and was suggestive of a brain tumor; the lesion was extirpated by neurosurgery. In histologic sections, massive reactive astrogliosis and hypercellularity were noted in the white matter (Fig 5). Blood vessels with

Hypocalcemic choreoathetosis and tetany after bisphosphonate treatment

On the basis of several randomized controlled trials, zoledronic acid, a highly potent and long-acting bisphosphonate, is emerging as the new standard of care for managing skeletal morbidity in patients with advanced cancers involving bone.1 Symptomatic hypocalcemia after treatment with bisphosphonates has been described before.2,3 To our knowledge, this is the first report on a patient with hypocalcemic choreoathetosis after bisphophonate therapy. An 85-year-old man received an infusion of 4 mg zoledronic acid because of prostate cancer with extensive bone metastases. The day after the infusion, he developed perioral paresthesia and numbness and tingling in his extremities. He complained of new-onset debilitating fatigue and diffuse pain and stiffness in both legs. He was unable to stand or walk without the help of two people, while prior to bisphosphonate treatment he had been able to walk approximately 1,000 meters before claudication due to lumbar spine stenosis limited further walking. On admission, he appeared fidgety and gave the impression of general restlessness. He had increased tone, decreased distal sensation, and diminished reflexes in both legs. Plantar responses were flexor. Muscle power was normal, and there were no signs of disturbance of vigilance or mental function. His speech was slightly slurred. From time to time, he had selflimited painful tetanic spasms in both legs. The most striking neurological disturbances were brief paroxysms of unilateral or bilateral choreoathetoid arm movements. These episodes lasted up to a minute and occasionally appeared precipitated by movements such as reaching out. His past medical history was unremarkable for movement disorders and medication interfering with extrapyramidal motor systems or with psychotropic effects. Lesions in the basal ganglia and spinal cord compression were ruled out by magnetic resonance imaging. Laboratory tests revealed extreme hypocalcemia (0.7 mmol/L; normal: 2.15–2.6 mmol/L), while all other electrolytes were in the normal range. Calcium concentration corrected for albumin was identical to the measured calcium level. Creatine phosphokinase (CK) was highly elevated (2858 U/L; normal: 24–171 U/L), indicating rhabdomyolysis, while the myocardial-specific isoenzyme of CK was in the normal range ( 10% of CK). Parathyroid hormone (PTH) was significantly elevated (195 pg/mL; normal: 15–65 pg/mL). Electrocardiography (ECG) showed normofrequent sinus rhythm (70 bpm) with marked QT interval prolongation (496 ms). After initiation of treatment with calcium and vitamin D, the spells of choreoathetosis and tetany in his legs resolved within a few days and ECG showed normalization of QT time. Electrophysiological studies were compatible with mild to moderate distal symmetric axonal and demyelinating polyneuropathy. The patient declined further evaluation of the polyneuropathy because of lack of symptoms and was discharged from hospital with mild residual hypocalcemia after complete resolution of the presenting neurological symptoms. Neurological complications of hypocalcemia seem to be the consequence of loss of inhibition, primary neuronal hyperexcitability, or changes in permeability of muscle membranes. Clinically evident hypocalcemia, regardless of its cause, generally presents in milder forms and is usually the result of a chronic disease state.4 In patients with prostate cancer, increased calcium utilization by extensive osteoblastic metastases is hypothesized to be the primary phenomenon inducing hypocalcemia and compensatory hyperparathyroidism. In these patients, bisphosphonates may further reduce serum calcium and increase PTH levels, which could limit therapeutic effectiveness of bisphosphonates unless calcium supplementation were given in doses sufficient to maintain PTH in the normal range.5 We suppose that in our patient, preexisting asymptomatic chronic hypocalcemia worsened and was unmasked after bisphosphonate therapy. Rhabdomyolysis may have further reduced the level of metabolically active calcium by elevation of phosphates (from CK), lactate, and other anions that chelate calcium.4 Our case report illustrates that zoledronic acid may trigger severe symptomatic hypocalcemia with neuromuscular complications and new-onset movement disorders. To minimize adverse events, assessment and correction of calcium homeostasis before initiating zoledronate therapy are recommended.3

10-year-outcomes after rituximab for myasthenia gravis: Efficacy, safety, costs of inhospital care, and impact on childbearing potential

Rituximab (RTX) has emerged as an attractive off-label treatment option for patients with myasthenia gravis (MG) refractory to other immune therapies. However, data on long-term outcome after RTX for MG are still scarce. Here we present the 10-year outcomes [median (range) 10.1 (6.7-11.2) years] with respect to efficacy, safety, costs of inhospital care, and impact on childbearing potential in all four MG patients treated by one of the authors with RTX. In all patients, RTX led to sustained clinical improvement and eventual tapering of other immune therapies. RTX was well tolerated, and complications were not observed. After the start of RTX, annual costs for hospital admissions were markedly reduced compared to costs in the year preceding RTX. Under close clinical observation, two patients had uncomplicated pregnancies giving birth to a healthy child. With regard to its efficacy, excellent tolerance, lack of complications, low frequency of repeat infusions and pending patent expiry in many countries, RTX appears to compare favourably with other immune therapies used for MG. Multicentre trials and registries are urgently needed to further address long-term safety issues and clarify the efficacy and role of RTX in managing MG.

18F-fluorodeoxyglucose and 18F-flumazenil positron emission tomography in patients with refractory epilepsy

Abstract Background Epilepsy is a neurological disorder characterized by epileptic seizures as a result of excessive neuronal activity in the brain. Approximately 65 million people worldwide suffer from epilepsy; 20–40% of them are refractory to medication therapy. Early detection of disease is crucial in the management of patients with epilepsy. Correct localization of the ictal onset zone is associated with a better surgical outcome. The modern non-invasive techniques used for structural-functional localization of the seizure focus includes electroencephalography (EEG) monitoring, magnetic resonance imaging (MRI), single photon emission tomography/computed tomography (SPECT/CT) and positron emission tomography/computed tomography (PET/CT). PET/CT can predict surgical outcome in patients with refractory epilepsy. The aim of the article is to review the current role of routinely used tracer 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) as well as non routinely used 18F-Flumazenil (18F-FMZ) tracers PET/CT in patients with refractory epilepsy. Conclusions Functional information delivered by PET and the morphologic information delivered by CT or MRI are essential in presurgical evaluation of epilepsy. Nowadays 18F-FDG PET/CT is a routinely performed imaging modality in localization of the ictal onset zone in patients with refractory epilepsy who are unresponsive to medication therapy. Unfortunately, 18F-FDG is not an ideal PET tracer regarding the management of patients with epilepsy: areas of glucose hypometabolism do not correlate precisely with the proven degree of change within hippocampal sclerosis, as observed by histopathology or MRI. Benzodiazepine-receptor imaging is a promising alternative in nuclear medicine imaging of epileptogenic focus. The use of 11C-FMZ in clinical practice has been limited by its short half-life and necessitating an on-site cyclotron for production. Therefore, 18F-FMZ might be established as one of the tracers of choice for patients with refractory epilepsy because of better sensitivity and anatomical resolution.

[A case of affective disorder with psychotic symptoms as late manifestation of Huntington's Chorea].

We report about a woman of 60 years who received psychiatric inpatient treatment for an affective disorder with psychotic symptoms on several occasions. As time elapsed symptoms of dementia became more and more obvious. Despite a comprehensive workup with neuroimaging methods (SPECT, PET) the correct diagnosis of Huntingtons Chorea was not attained until the characteristic movements appeared. Up till then pathologic movements had hardly occurred and there were no known cases of Huntingtons Chorea in the family. This case is remarkable as the patient was not only treated with different antidepressants and antipsychotics but with a course of ECT too. Beyond this it shows the enormous stress this illness imposes on patients and their caregivers.

Hereditary neuropathy with liability to pressure palsies presenting with sciatic neuropathy

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal-dominant disorder associated with recurrent mononeuropathies following compression or trivial trauma. Reports on sciatic neuropathy as the presenting manifestation of HNPP are very scarce. We report on a 21-year-old previously healthy man who was admitted with sensorimotor deficits in his left leg. He had no history of preceding transient episodes of weakness or sensory loss. Clinical and electrophysiological examinations were consistent with sciatic neuropathy. Cerebrospinal fluid investigation and MRI of the nerve roots, plexus, and sciatic nerve did not indicate the underlying aetiology. When extended electrophysiological tests revealed multiple subclinical compression neuropathies in the upper limbs, HNPP was contemplated and eventually confirmed by genetic testing.

Bioptically Confirmed Creutzfeldt-Jakob Disease: Clinical Findings and MRI Characteristics of the Heidenhain Variant

Introduction Creutzfeldt-Jakob disease (CJD) belongs to the group of transmissible human spongiform encephalopathies. It is a very rare neurodegenerative disease of the brain, which occurs in humans as genetic, transmitted or sporadic form. Mutations in the prion protein gene are the cause of the genetic form of prion disease, which shows an autosomal dominant inheritance with almost 100% penetrance. Besides the familial Creutzfeldt-Jakob disease also Gerstmann-Sträussler-Scheinker syndrome and fatal familial insomnia are counted toward this group of diseases. In contrast to its sporadic form the genetic form of the disease has a longer duration (14 months) and the affected patients are younger. Iatrogenic transmission among humans has so far only been described in cases of direct contact with infectious tissue due to dura mater or corneal grafts or due to the administration of growth hormones or gonadotropins extracted from pituitary glands of corpses [1–3]. In 1996, Will et al. described a new variant of CJD, which cumulatively occurred in Great Britain and is counted toward the group of bovine spongiform encephalopathies (BSE). Today it is assumed that the new variant of Creutzfeldt-Jakob disease (today known as vCJD) has a causal relationship with the consumption of BSE-contaminated beef [4]. Within the rest of Europe CJD shows a consistent incidence of one case per one million population per year, with sporadic CJD being the most common form of occurrence of the disease worldwide. The patients that are mostly affected are elderly persons aged between 60 and 70 who develop rapidly progressing dementia combined with myoclonia, ataxia, extrapyramidal and pyramidal disorders within only a few weeks. The clinical end-stage is usually reached after an average disease duration of 6 months and its clinical picture corresponds largely to that of akinetic mutism. A suspected clinical diagnosis of CJD can be confirmed through additional diagnostic procedures like electroencephalograms (EEG), diagnostic investigations of cerebrospinal fluid (CSF) and magnetic resonance images (MRI). The EEG shows periodic biand triphasic complexes. However, these so-called periodic “sharp-wave” complexes can disappear again during the course of the disease but occasionally, they can be provoked through certain stimuli [5, 6]. CSF samples show inconspicuous standard parameters but an abnormally high concentration of neuronal and astrocytic proteins like protein 14-3-3, tau, NSE, and S100 [7, 8]. Among these proteins protein 14-3-3 represents the most important group because with it the prion disease can be established with a specificity of 93% and a sensitivity of 94%. As regards imaging techniques to establish CJD, computed tomography has no significance due to the usually negative findings [9]. By now, MRI is the investigative method of choice with the FLAIR sequence and the diffusion-weighted sequence having the best sensitivity [10–13]. In T2-weighted pictures of the common form of CJD hyperintensities can

Uptake of 68Ga–Prostate-Specific Membrane Antigen PET in Adrenal Gland: A Potential Pitfall

A 76-year-old man with prostate cancer pT2c N0 M0 R1 GS9 (4+5) operated 2009 and radiated postoperatively underwent restaging by Ga-PSMA-PET in January 2017 because of PSA rise at 0.44 ng/ml under medication with GnRH analogues. An intense focal uptake of the diffusely enlarged left adrenal gland was observed as the only pathological finding. Further evaluation by MRI imaging revealed a plump left adrenal gland with a relatively enlarged diameter of 2 cm and excluded tumor and nodular hyperplasia as well. Without any change of the therapeutic regime the patient presented in July 2017 with a PSA level of 0.05 ng/ml and no sign of cancer progress.

A Bodybuilder With Weak Hands and Feet: Corticosteroid-Responsive Pure Motor Chronic Inflammatory Demyelinating Polyradiculoneuropathy Following Anabolic Steroid Use.

of conditions with a spectrum of clinical severity ranging from mild Bethlem myopathy (BM) to severe Ullrich muscular dystrophy. The disease is a result of heterozygous-dominant mutations in the COL6A1, COL6A2, and COL6A3 genes that encode 3 of the collagen 6 (COL6) chains, with the glycine substitution causing a kink in the tetramer and, consequently, an inability to form microfibrils. BM can be either inherited from an affected parent or occur de novo in sporadic cases especially involving glycine substitutions, although recessive inheritance has also been described. BM is a benign myopathy with onset in the first 2 decades of life. It is characterized by contractures (commonly finger flexors and ankles) and slowly progressive proximal muscle weakness. A majority of patients remain ambulatory into their fifth decade of life, although muscle weakness may occur after this time. Other atypical presentations include a limb-girdle muscular dystrophy phenotype without contractures. Immunohistochemical COL6 staining on muscle biopsies (which was not performed in this case) may reveal alterations in the amount of COL6 in the muscle or basement membrane. However, such immunostaining is often normal on muscle biopsies of patients with genetically confirmed BM, and the current “gold standard” diagnostic test for BM is molecular genetic testing. This case demonstrates a previously unreported atypical presentation of BM or COL6A-related disorders. The patient presented with facial and proximal upper limb weakness and eyelid ptosis without contractures, due to a novel mutation in the COL6A2 gene. This expands the phenotypical heterogeneity of the COL6A-related myopathies.