Acute disseminated encephalomyelitis following Tdap vaccination and bacterial meningoencephalitis.

INTRODUCTION: Association of Acute Disseminated Encephalomyelitis (ADEM) with both recent vaccination and viral infections is well described in current literature. However, the coincidence of ADEM and bacterial infections has been rarely documented. In this report, we present a case of ADEM which occurred after bacterial meningoencephalitis and prior vaccination against tetanus, diphtheria, and pertussis (Tdap). CASE PRESENTATION: A 62-year old woman was hospitalized with an upper respiratory tract infection three weeks after Tdap triple vaccination. A few days after admission, she became somnolent and developed meningism. Cerebrospinal fluid (CSF) analysis revealed pleocytosis and increased protein/lactate levels compatible with bacterial meningoencephalitis. The patient was treated with intravenous antibacterial triple therapy in combination with dexamethasone leading to a significant improvement of clinical symptoms and improvement of CSF parameters. Five days later, the patient's condition worsened again, and she developed aphasia and right-sided hemiparesis. A magnetic resonance imaging (MRI) scan revealed distinct fluid-attenuated inversion recovery sequence (FLAIR)-hyperintense lesions in both hemispheres. Following brain biopsy, the diagnosis of ADEM was made and methylprednisolone pulse therapy was initiated for five days leading to a nearly complete remission of symptoms. CONCLUSION: ADEM is a neurological syndrome which may be associated with bacterial infection of the central nervous system (CNS). We hypothesize that the preceding Tdap triple vaccination may have contributed to the development of ADEM.

[The Geriatric Patient with Parkinson's Disease - a Neurological Challenge]. / Der geriatrische Parkinson-Patient - eine neurologische Herausforderung.

Geriatric patients with Parkinson's disease (PD) represent a particular challenge in terms of diagnostics and treatment. This overview article addresses age-related characteristics of this patient group and discusses particularities in PD symptoms in this age group, frequent comorbidities and the resulting polypharmacy. Questions regarding the availability of specialist and therapist care as well as end-of-life aspects are discussed. While comprehensive care structures are not always available, this patient group requires a multidisciplinary treatment team supervised by neurologists with ample experience in PD treatment.

ROCK2 is a major regulator of axonal degeneration, neuronal death and axonal regeneration in the CNS.

The Rho/ROCK/LIMK pathway is central for the mediation of repulsive environmental signals in the central nervous system. Several studies using pharmacological Rho-associated protein kinase (ROCK) inhibitors have shown positive effects on neurite regeneration and suggest additional pro-survival effects in neurons. However, as none of these drugs is completely target specific, it remains unclear how these effects are mediated and whether ROCK is really the most relevant target of the pathway. To answer these questions, we generated adeno-associated viral vectors to specifically downregulate ROCK2 and LIM domain kinase (LIMK)-1 in rat retinal ganglion cells (RGCs) in vitro and in vivo. We show here that specific knockdown of ROCK2 and LIMK1 equally enhanced neurite outgrowth of RGCs on inhibitory substrates and both induced substantial neuronal regeneration over distances of more than 5 mm after rat optic nerve crush (ONC) in vivo. However, only knockdown of ROCK2 but not LIMK1 increased survival of RGCs after optic nerve axotomy. Moreover, knockdown of ROCK2 attenuated axonal degeneration of the proximal axon after ONC assessed by in vivo live imaging. Mechanistically, we demonstrate here that knockdown of ROCK2 resulted in decreased intraneuronal activity of calpain and caspase 3, whereas levels of pAkt and collapsin response mediator protein 2 and autophagic flux were increased. Taken together, our data characterize ROCK2 as a specific therapeutic target in neurodegenerative diseases and demonstrate new downstream effects of ROCK2 including axonal degeneration, apoptosis and autophagy.

Differential transgene expression in brain cells in vivo and in vitro from AAV-2 vectors with small transcriptional control units.

Adeno-associated- (AAV) based vectors are promising tools for gene therapy applications in several organs, including the brain, but are limited by their small genome size. Two short promoters, the human synapsin 1 gene promoter (hSYN) and the murine cytomegalovirus immediate early promoter (mCMV), were evaluated in bicistronic AAV-2 vectors for their expression profiles in cultured primary brain cells and in the rat brain. Whereas transgene expression from the hSYN promoter was exclusively neuronal, the murine CMV promoter targeted expression mainly to astrocytes in vitro and showed weak transgene expression in vivo in retinal and cortical neurons, but strong expression in thalamic neurons. We propose that neuron specific transgene expression in combination with enhanced transgene capacity will further substantially improve AAV based vector technology.

GDNF and NT-4 protect midbrain dopaminergic neurons from toxic damage by iron and nitric oxide.

Free radical formation is considered to be a major cause of dopaminergic (DAergic) cell death in the substantia nigra leading to Parkinson's disease (PD). In this study we employed several radical donors including iron and sodium nitroprusside to induce toxic effects on DAergic neurons cultured from the embryonic rat midbrain floor. Overall cell survival was assessed by assaying LDH, and DAergic neuron survival was monitored by counting tyrosine hydroxylase-positive cells. Our data suggest that the DAergic neuron population is about fourfold more susceptible to free-radical-mediated damage than the total population of midbrain neurons. Application of the neurotrophic factors GDNF and NT-4, for which DAergic neurons have specific receptors, prior to toxin administration protected these neurons from toxin-mediated death, which, fully or in part, occurs under the signs of apoptosis. These findings underscore the importance of GDNF and NT-4 in designing future therapeutical concepts for PD.