Volume Articles

Cerebral Multimorbidity in Aging

Kurt A. Jellinger

The aging brain is characterized by the simultaneous presence of multiple pathologies, and the prevalence of multi-morbidity increases with age. Large clinico-pathological correlative studies have shown that in brains of both cognitively intact and impaired aged subjects, the presence of a single disease is a rare finding, while most brains show neurodegenerative, cerebrovascular and other pathologies, which frequently have been missed clinically and may even be difficult to identify at postmortem examination. Since both clinical and autopsy studies differ in selection and classification criteria and in the applied evaluation methods, irrespective of the clinical symptoms, the reported frequency of cerebral pathologies varies considerably. The frequent co-occurrence of different pathologies indicates their mutual interaction in order to promote cognitive decline and other clinical symptoms. These facts have also implications for improvement of clinical diagnosis and prognosis, for the development of specific biomarkers, preventive strategies, and therapeutic targets for cerebral multi-morbidity.

Recent advances in multiple system atrophy

Kurt A. Jellinger

Multiple system atrophy (MSA) is a fatal orphan neurodegenerative disorder that manifests with autonomic, parkinsonian, cerebellar, and pyramidal features. It is characterized by the accumulation of misfolded α-synuclein (αSyn) in oligodendroglia and neurons, affecting multiple parts of the central, autonomic and perípheral system. Both the etiology and pathogenesis of MSA are unknown, although a genetic component has been proposed. Accumulation of aberrant αSyn in oligodendrocytes, preceded by relocation of p25α protein from myelin into oligodendroglia, results in the formation of insoluble glial cytoplasmic inclusions (GCIs). These changes are associated with proteasomal, mitochondrial and lipid transport dysfunction, oxidative stress, reduced trophic transport, neuroinflammation and other noxious factors. Their interaction induces dysfunction of the oligodendroglial-myelin-axon-neuron complex, resulting in the system-specific pattern of neurodegeneration characterizing MSA as a synucleinopathy with oligodendroglio-neuronopathy. Propagation of modified toxic αSyn species from neurons to oligodendroglia by "prion-like" transfer and its spreading to associate neuronal pathways result in multi-system involvement. No reliable biomarkers are currently available for the clinical diagnosis and prognosis of MSA and neither effective neuroprotective nor disease-modifying therapies of MSA are available, although novel treatment strategies targeting αSyn are under discussion. Multidisciplinary research to elucidate the genetic and molecular background of the deleterious cycle of noxious processes to develop reliable diagnostic biomarkers and to deliver targets for effective treatment of this hitherto incurable disorder is urgently needed.

Commentary: A Systematic Review of the Risk of Intra-Cranial Haemorrhage in those Presenting Late to the ED Following Head Injury

Carl Marincowitz and Will Townend

Background: Head injury represents an extremely common presentation to Emergency Departments (ED), but not all patients present immediately after injury. There is evidence that clinical deterioration following head injury will usually occur within 24 hours. It is unclear whether this means that head injury patients that present in a delayed manner, especially after 24 hours, have a lower prevalence of significant traumatic injuries.

Methods: This is a commentary on a systematic review that we conducted with the aim of identifying all studies that assess the risk of significant injuries in delayed ED presentation head injury populations. We postulated that the risk of injury may be different in this group compared to patients that present immediately.

Results: Three studies were eligible for inclusion. They were all of poor methodological quality, and heterogeneity prevented meta-analysis. The reported prevalence of traumatic intra-cranial injury on CT was between 2.2% and 6.3%.

Conclusion: Available evidence suggests that head injury patients who present in a delayed fashion to the ED may have lower rates of intra-cranial injury compared to non-delayed head injury patients. However, the evidence is sparse and it is of too low quality to guide clinical practice. Further research is required to help the clinical risk assessment of this group.

Commentary: Are Developmental Skills Acquired Normally in Rett Syndrome?

Jeffrey L. Neul^1,2, Alan K. Percy²

Commentary on: Absence of Stimulus-driven Synchronization Effects on Sensory Perception in Autism: Evidence for Local Under-Connectivity

Mark Tommerdahl

Commentary: Severe fetal acidemia in cases of clinical chorioamnionitis in which the infant later developed cerebral palsy

Yoshio Matsuda

Comment: Relevance of sonography for botulinum toxin treatment of cervical dystonia: An expert recommendation

Wolfgang H Jost

For years we have been injecting botulinum toxin relying mainly on our clinical experience and, in some cases, on the use of electromyography. Within that time some therapists introduced sonography for guidance and emphasize the advantages of this technique. Schramm et al., for example, pointed out the relevance of sonography for botulinum toxin treatment in cervical dystonia. Within a short time the importance of sonography has been well documented in this indication. Even assuming a critical distance, the significance of this technique has become largely indisputable.

Commentary: Quantitative home-based assessment of Parkinson's symptoms: The SENSE-PARK feasibility and usability study

Godinho C^1,2,3, Domingos J^1,3, Domingos J^1,3,4*

Healthcare professionals and pharmaceutical companies invest a great amount of time and effort in continuously creating electronic health solutions. These technology system developments may represent a step forward in care as ultimately it is not possible to manage what cannot be evaluated.

Yet, the use of future generations of technology depends on their specific design, fabrication, distribution, and, most importantly, patients adopting these new technologies as life companions. Data management and the use of artificial intelligence appear as new technological challenges. The overload, sharing and handling of information give rise to new legal, social, and ethical discussions in a field where there is a lack of universal criteria for data ownership, privacy and sharing.

Future technological progress requires much cooperation between multidisciplinary teams including sufficient sharing and benchmarking within open access frameworks.