Electroencephalography Findings in Older Adults Undergoing Geriatric Treatment: A Surrogate for the Outcome?

Background: Comprehensive geriatric care (CGC) is a multidisciplinary approach developed to meet the needs of older patients. Electroencephalography (EEG) provides valuable information for monitoring the cerebral function. As a surrogate, EEG findings may help to estimate the course of diseases as well as the treatment outcomes. Objectives: Therefore, the aim of the present study is to investigate EEG findings in older patients receiving CGC. Methods: Patients with an initial EEG in a geriatric unit between May 2019 and April 2020 and treated using the CGC approach were analyzed. EEG abnormalities were defined as generalized (diffuse) background slowing and/or intermittent/persistent focal slowing and/or epileptiform discharges. Assessment results for the Barthel index (BI), Tinetti Balance and Gait test (TBGT), and Timed Up and Go test (TUG) were analyzed in relation to the presence of EEG abnormalities. Results: The study included 398 patients (mean age: 83.0 ± 6.57 years, 69.3% were female). Abnormal EEG patterns were found in 94 (23.6%) patients. Patients with EEG abnormalities had a mean age of 83.4 years versus a mean of 82.8 years in those without (p = 0.451). Based on all calculated scores, the majority of the patients improved after CGC, with a tendency to higher-grade improvements in those without EEG abnormalities (BI: 86.2% vs. 75.5%, p = 0.024; TUG: 53.3% vs. 31.9%, p < 0.001); for TBGT, only a gradual difference was detected (TBGT: 79.9% vs. 71.3%, p = 0.088). The presence of EEG abnormalities was associated with the parameters dementia (36.2% vs. 22.4%, p = 0.010), known epilepsy/seizure (19.1% vs. 5.9%, p < 0.001), structural brain lesion (47.9% vs. 19.7%, p < 0.001), and delirium (9.6% vs. 3.6%, p = 0.030) during hospitalization. Conclusions: We found EEG abnormalities in almost a quarter of the patients treated in the geriatric unit. In older patients, the presence of EEG abnormalities is associated with lower improvements after CGC.

Improved Balance and Gait Ability and Basic Activities of Daily Living after Comprehensive Geriatric Care in Frail Older Patients with Fractures.

(1) Purpose: Comprehensive geriatric care (CGC) is a multidisciplinary treatment approach for elderly patients. We aimed to investigate outcomes in fracture patients who had been treated using this approach in a large geriatric unit. (2) Methods: This observational cohort study assessed the gait function (using the Tinetti Balance and Gait Test (TBGT)) and basic activities of daily living (ADL) (using the Barthel index (BI)) before and after CGC and compared the results. Baseline data, walking ability assessments (Timed Up and Go, TUG), and cognitive status (mini mental status examination, MMSE) were also analyzed in the subgroup of patients with versus without fractures. (3) Results: Out of 1263 hospitalized patients, 1099 received CGC (median age: 83.1 years (IQR: 79.0-87.8 years); 64.1% were female). TBGT improvement was observed in 90.7% and BI increased in 82.7% of fracture patients. A TBGT improvement of >5 was noted in 47.3% and was associated with female sex, a lower BI at admission (median: 40 versus 45; p = 0.010), and poorer mobility on admission (TUG: median 5 versus 4; p = 0.001). An improvement in BI of ≥15 was observed in 63.0% of the cases, and was associated with a better cognitive status (MMSE: median 25 versus 18; p = 0.001) and inversely associated with diabetes mellitus and a previous stroke. (4) Conclusion: CGC in specialized geriatric units improves the balance and gait and the basic ADL in geriatric patients. After fracture, female patients are more likely to experience improvements in gait and balance, while patients with better cognitive condition are more likely to experience improvements in ADL.

Positive Effect of Steroids in Posterior Reversible Encephalopathy Syndrome.

We present a case of posterior reversible encephalopathy syndrome with severe clinical manifestation. Apart from initial aphasia, hemiparesis, and a generalized seizure, the patient had a prolonged loss of consciousness. Although blood pressure was normalized, the clinical status deteriorated continuously. After adding steroids to the therapy, the patient recovered rapidly, suggesting that this could have been a useful therapeutic approach. Even the vasogenic edema in the cerebral magnetic resonance imaging disappeared shortly within 6 days.

Diagnosing moyamoya syndrome using ultrasound - a case report.

BACKGROUND: Moyamoya syndrome is a vasculopathy characterised by progressive occlusion of the cerebral arteries resulting in the development of abnormal collateral circulation. To diagnose this syndrome, imaging of the cerebral arteries is required including CT- or MR-angiography and conventional angiography. We present a case of moyamoya disease with typical findings detected in the sonography. The diagnosis was suspected after reviewing the initial ultrasound images of the cerebral arteries with evidence for obliterated intracranial arteries and the detection of an existing collateral circulation network. CASE PRESENTATION: A 62 years old male patient presented in the hospital's emergency department with symptoms indicating a subacute cerebrovascular event. Immediate sonographic studies showed a right-sided pulsatile Doppler-signal in the common and internal carotid arteries, suggestive of distal stenoses. In addition, the transcranial examination indicated obliteration of both middle cerebral arteries. Numerous arterial vessels suggestive of leptomeningeal collateral arteries revealed a strong arterial leptomeningeal flow. At this stage of the diagnostic work-up, the collateral circulation network, characteristic of moyamoya disease, was indicated by sonography. Moyamoya syndrome was verified by conventional angiography. The aetiological work remained empty, so the diagnosis of moyamoya disease was established. CONCLUSION: Our case report indicates that sonography can be a useful tool for detecting the vaculopathy in moyamoya syndrome. In case routine procedures, such as the CT- or MR-angiography, with evidence for obliterated intracerebral arteries, ultrasound studies might provide important information regarding an existing collateral network in the scope of a moyamoya syndrome.

A putative role for cell cycle-related proteins in microtubule-based neuroplasticity.

Cyclins and cyclin-dependent kinases (Cdks) are the main components that control the orderly progression through cell cycle. In the mature nervous system, terminally differentiated neurons are permanently withdrawn from cell cycle, as mitotic quiescence is essential for the functional stability of the complexly wired neuronal system. Recently, we characterized the expression and colocalization of cyclins and Cdks in terminally differentiated pyramidal neurons. The functional impact of the expression of cell cycle-related proteins in differentiated neurons, however, has not been elucidated yet. In the present study, we show by immunoelectron microscopy and immunobiochemical methods an association of cyclins and Cdks with the microtubule network. Cyclins D, E, A and B as well as Cdks 1, 2 and 4 were also found to be associated with the microtubule-associated protein tau. Cyclin/Cdk complexes, in addition, exhibit kinase activity towards tau. In vitro, downregulation of cyclins and Cdks by a siRNA approach and by pharmacological inhibition promotes neurite extension. Taken together, these results indicate that the expression of cell cycle-related proteins in terminal differentiated neurons is associated with physiological functions beyond cell cycle control that might be involved in microtubule-based mechanisms of neuroplasticity.

Constitutive expression of functionally active cyclin-dependent kinases and their binding partners suggests noncanonical functions of cell cycle regulators in differentiated neurons.

Neurodegeneration in Alzheimer's disease and various experimental lesion paradigms are associated with an unscheduled upregulation of cell cycle-related proteins, indicating a link between cell cycle reactivation and neuronal death. Recent evidence, however, suggests that at least some of the canonical cell cycle regulators are constitutively expressed in differentiated neurons of the adult brain. Systematic investigations on the constitutive expression of cell cycle regulators in differentiated neurons in vivo, providing the basis for further insights into their potential role under pathological conditions, however, have not been carried out. Here, we demonstrate a constitutive neuronal expression of Cdks 1, 2, and 4; their activators cyclins D, A, B, and E; and their inhibitors p15(Ink4b), p16(Ink4a), p18(Ink4c), p19(Ink4d), p21(Waf1/Cip1), p27(Kip1), and p57(Kip2) within the neocortex of adult mice by western blot and immunocytochemistry. Expression was verified by single-cell reverse transcriptase-polymerase chain reaction applied to individual microscopically identified neurons captured with laser dissection. Immunoprecipitation and in vitro kinase assays revealed that Cdks 1, 2, and 4 are properly complexed to cyclins and exhibit kinase activity. This physiological expression of positive cell cycle regulators in adult neurons is clearly not related to neuronal proliferation. Taken together, our findings demonstrate a constitutive expression of functionally active cyclin-dependent kinases and their regulators in differentiated neurons suggesting a noncanonical role of cell cycle regulators potentially linked to neuronal plasticity and/or stability.

Expression of cell cycle-related proteins in developing and adult mouse hippocampus.

Developmental structuring of brain is the result of a strictly coordinated process that involves controlled cell division, neuronal migration and terminal differentiation. Neurogenesis occurs generally during embryonic and early postnatal stages and will be finished in the mature brain. Once differentiated, neurons are incapable of further division but retain the capability of structural and functional plasticity. However, there are distinct regions in the adult brain of mammals that generate neurons continuously throughout life. Among them, the hippocampus, which is known as a region with a high degree of neuroplasticity, is of particular interest in the context of adult neurogenesis. In general, progression through cell cycle phases is regulated by the sequential expression and activation of regulatory proteins like cyclin dependent kinases (cdk), cyclins, or cdk inhibitors (cdki). In postmitotic and terminally differentiated neurons, cell cycle activity is arrested by enrichment of cdkis. The timing of cell cycle exit and neuronal differentiation is likely to be regulated in part by cell cycle regulatory proteins. However, the expression of cell cycle markers in the postnatal or adult brain is still a matter of controversial debate. In the present study, we examined the expression of cdks, cyclins and cdkis within the mouse hippocampus at different developmental stages (embryonic days 17, 19; postnatal day 11 and adult) using immunohistochemical methods. During the prenatal development, cell cycle proteins were localized predominantly in nuclei of all presumptive neuronal populations but expression was not restricted to proliferative cells. With developmental progression, the subcellular localization of most markers was increasingly shifted from nuclear to the cytoplasmic compartment. However, even in the adult, cell cycle-related proteins were found in terminally differentiated pyramidal and granule neurons. Here, they were mainly localized in the perikaryal cytoplasm but only sporadically in neuronal nuclei. Occasionally, immunoreactivity was also found in dendrites and mossy fibers. The present results suggest that cell cycle arrest and terminal differentiation is not necessarily incompatible with the expression of cell cycle-related markers. Thus, they may have supplementary functions in differentiated neurons that might be associated with neuronal plasticity.

Amyloid deposition in APP23 mice is associated with the expression of cyclins in astrocytes but not in neurons.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the intracellular accumulation of highly phosphorylated tau protein, the extracellular formation of amyloid plaques and a significant loss of neurons. Recent evidence suggests that neuronal death in AD involves an aborted attempt of cells to re-enter the cell cycle. To study the effect of amyloid deposits on cell cycle related events in vivo, the expression of cell cycle markers was examined by immunohistochemistry in amyloid precursor protein (APP) transgenic mice (APP23 mice, Swedish double mutation). Abeta deposition in APP23 mice is associated with prominent gliosis that is characterized by an astrocytic expression of cyclins D1, E and B1 as well as the nuclear translocation of cyclin-dependent protein kinase 4. However, amyloid plaque formation is not accompanied by significant changes in the neuronal expression of cyclins or cyclin-dependent kinase inhibitors. It is concluded, therefore, that in contrast to AD, amyloid pathology in APP23 mice is not associated with changes in the expression of cell cycle markers in neurons. The results support the assumption that the neuronal re-expression of cell cycle components in AD is not a consequence of Abeta formation and deposition.