Serological testing for syphilis in the differential diagnosis of cognitive decline and polyneuropathy in geriatric patients.

BACKGROUND: In the 19th century, neurosyphilis was the most frequent cause of dementia in Western Europe. Now dementia caused by syphilis has become rare in Germany. We studied whether routine testing of patients with cognitive abnormalities or neuropathy for antibodies against Treponema pallidum has therapeutic consequences in geriatric patients. METHODS: A Treponema pallidum electrochemiluminescence immunoassay (TP-ECLIA) is routinely performed in all in-patients treated at our institution with cognitve decline or neuropathy and no or insufficient previous diagnostic workup. Patients with a positive TP-ECLIA treated from October 2015 to January 2022 (76 months) were retrospectively evaluated. In cases of positive TP-ECLIA, further specific laboratory investigations were performed to assess whether antibiotic therapy was indicated. RESULTS: In 42 of 4116 patients (1.0%), TP-ECLIA detected antibodies directed against Treponema in serum. Specifity of these antibodies was ensured by immunoblot in 22 patients (11 × positiv, 11 × borderline values). Treponema-specific IgM was detectable in the serum of one patient, in 3 patients the Rapid Plasma Reagin (RPR) test, a modified Venereal Disease Research Laboratory test (VDRL), in serum was positiv. CSF analysis was performed in 10 patients. One patient had CSF pleocytosis. In 2 other patients, the Treponema-specific IgG antibody index was elevated. 5 patients received antibiotic therapy (4 × ceftriaxone 2 g/d i.v., 1 × doxycycline 300 mg/d p.o.). CONCLUSION: In approx. 1‰ of patients with previously undiagnosed or not sufficiently diagnosed cognitive decline or neuropathy, the diagnostic workup for active syphilis resulted in a course of antibiotic treatment.

[Congenital malformations of the brain misinterpreted as sequelae of poliomyelitis]. / Angeborene Fehlbildungen des Gehirns als Folgezustände der Poliomyelitis verkannt.

BACKGROUND: Poliomyelitis is an infectious disease of the peripheral motor neurons, which predominantly affects children and causes residual palsies. Because of the oral poliomyelitis vaccination started in Germany in 1960 and 1962 and the following rapid decline of the incidence of this infection, the postpolio syndrome in Germany is a disease of older people. METHODS: Since 2008, we have offered a poliomyelitis outpatient consultation at the Center of Geriatrics, Protestant Hospital Göttingen-Weende and have treated 33 patients. RESULTS: The spectrum of persistent deficits after poliomyelitis ranges from palsy of single extremities to severe disability with (temporary) ventilator dependence. Many patients suffer from scoliosis or shortening of limbs of different degrees, which promotes degenerative diseases of the spinal cord and joints with secondary myelopathy, injury of spinal nerve roots or peripheral nerves or respiratory failure. The postpolio syndrome is characterized by an increase of the functional deficits after decades of compensation. The palsies of 2 of the 33 patients were not caused by poliomyelitis but by myelomeningocele and schizencephaly, respectively. CONCLUSION: The motor deficits acquired in childhood enable the majority of the patients to successfully master their lives. Because of the limited compensatory capacities of postpolio patients, even small increases in the severity of the palsy can cause a severe decline of the functional status and an impairment of the ability to live an independent life. In a substantial proportion of patients with the diagnosis poliomyelitis the symptoms are caused by other diseases.

Spatial and temporal variation of routine parameters: pitfalls in the cerebrospinal fluid analysis in central nervous system infections.

The cerebrospinal fluid (CSF) space is convoluted. CSF flow oscillates with a net flow from the ventricles towards the cerebral and spinal subarachnoid space. This flow is influenced by heartbeats, breath, head or body movements as well as the activity of the ciliated epithelium of the plexus and ventricular ependyma. The shape of the CSF space and the CSF flow preclude rapid equilibration of cells, proteins and smaller compounds between the different parts of the compartment. In this review including reinterpretation of previously published data we illustrate, how anatomical and (patho)physiological conditions can influence routine CSF analysis. Equilibration of the components of the CSF depends on the size of the molecule or particle, e.g., lactate is distributed in the CSF more homogeneously than proteins or cells. The concentrations of blood-derived compounds usually increase from the ventricles to the lumbar CSF space, whereas the concentrations of brain-derived compounds usually decrease. Under special conditions, in particular when distribution is impaired, the rostro-caudal gradient of blood-derived compounds can be reversed. In the last century, several researchers attempted to define typical CSF findings for the diagnosis of several inflammatory diseases based on routine parameters. Because of the high spatial and temporal variations, findings considered typical of certain CNS diseases often are absent in parts of or even in the entire CSF compartment. In CNS infections, identification of the pathogen by culture, antigen detection or molecular methods is essential for diagnosis.

High dose vitamin D exacerbates central nervous system autoimmunity by raising T-cell excitatory calcium.

Poor vitamin D status is associated with a higher relapse rate and earlier disability in multiple sclerosis. Based on these associations, patients with multiple sclerosis are frequently supplemented with the vitamin D precursor cholecalciferol, although it is unclear whether this regimen is of therapeutic benefit. To model consequences of this common practice, mice were fed for more than 3 months with a low, medium or high dose of cholecalciferol, representative of vitamin D deficiency, modest and disproportionally high supplementation, respectively, in patients with multiple sclerosis. Compared to vitamin D-deprived mice, its moderate supplementation reduced the severity of subsequent experimental autoimmune encephalomyelitis, which was associated with an expansion of regulatory T cells. Direct exposure of murine or human T cells to vitamin D metabolites inhibited their activation. In contrast, mice with 25-(OH) vitamin D levels above 200 nmol/l developed fulminant experimental autoimmune encephalomyelitis with massive CNS infiltration of activated myeloid cells, Th1 and Th17 cells. When dissecting this unexpected outcome, we observed that high, but not medium dose vitamin D had caused mild hypercalcaemia, which rendered T cells more prone to pro-inflammatory activation. Exposing murine or human T cells to equivalent calcium concentrations in vitro enhanced its influx, triggering activation, upregulation of pro-inflammatory gene products and enhanced transmigration across a blood-brain barrier model. These findings suggest that vitamin D at moderate levels may exert a direct regulatory effect, while continuous high dose vitamin D treatment could trigger multiple sclerosis disease activity by raising mean levels of T-cell excitatory calcium.

Training improves the handling of inhaler devices and reduces the severity of symptoms in geriatric patients suffering from chronic-obstructive pulmonary disease.

PURPOSE: Elderly patients with impaired vision, cognitive decline or motor/sensory disturbances of their fingers suffering from chronic-obstructive pulmonary disease (COPD) encounter difficulties in handling inhaler devices used as the cornerstones of treatment of pulmonary obstruction. Many elderly patients make severe mistakes which impede adequate drug delivery to the bronchioles. This multimodal training program was designed to reduce the number of handling mistakes of inhaler devices. METHODS: From October 1, 2016 to September 30, 2017, a prospective intervention study was conducted in 38 in-patients > 65 years (median age 79 years) with previously diagnosed COPD. The effect of an 8-day intervention comprising daily counselling and video demonstration according to the recommendations of the German Airway League on the frequency of mistakes during handling of inhaler devices, the forced expiratory volume in 1 s (FEV1), the forced vital capacity (FVC) and the perception of symptoms (COPD Assessment Test, CAT) were studied. Measurements on days 1 and 8 were compared by Wilcoxon signed rank test. RESULTS: The number of handling mistakes per patient decreased as a consequence of the intervention from 3.0 (0-7) to 0.5 (0-6) [median (minimum-maximum; p < 0.0001)]. The CAT Score decreased from 19.5 (14/24) to 14.5 (10.75/21) [median (25./75. percentile; p < 0.0001) indicating a substantial reduction of clinical symptoms. Conversely, FEV1 and FVC only slightly increased (difference statistically not significant). At study entry, the number of handling mistakes was inversely correlated with the Mini Mental Status Test (MMST) score (p = 0.01). The reduction of the number of handling mistakes during the intervention was not correlated with the MMST. CONCLUSION: In COPD, intensive training for 8 days improved the handling of inhalers and reduced clinical symptoms in geriatric patients. Patients with cognitive abnormalities also benefitted from this intervention. TRIAL REGISTRATION: German Clinical Trials Registry DRKS00023196 , date of registration September 29, 2020 (retrospectively registered).

Neurogeriatrics-a vision for improved care and research for geriatric patients with predominating neurological disabilities.

Geriatric medicine is a rapidly evolving field that addresses diagnostic, therapeutic and care aspects of older adults. Some disabilities and disorders affecting cognition (e.g. dementia), motor function (e.g. stroke, Parkinson's disease, neuropathies), mood (e.g. depression), behavior (e.g. delirium) and chronic pain disorders are particularly frequent in old subjects. As knowledge about these age-associated conditions and disabilities is steadily increasing, the integral implementation of neurogeriatric knowledge in geriatric medicine and specific neurogeriatric research is essential to develop the field. This article discusses how neurological know-how could be integrated in academic geriatric medicine to improve care of neurogeriatric patients, to foster neurogeriatric research and training concepts and to provide innovative care concepts for geriatric patients with predominant neurological conditions and disabilities.

Pharmacokinetics and pharmacodynamics of antibiotics in central nervous system infections.

PURPOSE OF REVIEW: The barriers surrounding the central nervous system (CNS) together with the emergence of multiresistant pathogens pose a therapeutic challenge for the effective treatment of CNS infections. RECENT FINDINGS: In addition to vancomycin, colistin and aminoglycosides, classically used for intrathecal injection, drug concentrations in cerebrospinal fluid after intrathecal injection of daptomycin and tigecyclin were recently studied. SUMMARY: The entry of antiinfectives into the CNS compartments is determined by the physicochemical properties of the drug and by conditions in the host. The most important drug properties are lipophilicity at a neutral pH, molecular mass and drug binding to serum proteins. In clinical practice, active transport is of importance only for some drugs. In recent years, intrathecal injection of antiinfectives in addition to systemic therapy has regained attention as a means to achieve high cerebrospinal fluid concentrations. The classification of antibacterials and antifungals into time-dependent and concentration-dependent compounds is also valid for the CNS compartments.

[Geriatrics - an interdisciplinary challenge]. / Geriatrie - eine interdisziplinäre Herausforderung.

The care of elderly patients will continue to challenge the healthcare system over the next decades. As a rule geriatric patients suffer from multimorbidities with complex disease patterns, and the ability to cope with everyday life is severely reduced. Treatment is provided by a multiprofessional geriatric team, and the primary goal is improvement of functional status, quality of life in the social environment and autonomy by employing a holistic approach. In Germany geriatric care is provided by physicians from various medical specialties (e.g. general practitioners, internists, neurologists and psychiatrists). In the training for the subspecialty clinical geriatrics, these specialties enjoy equal rights. Recent efforts to establish a qualification as physician for internal medicine and geriatrics have initiated a discussion to make the suitability for qualification as a geriatrician dependent on the medical specialty. Geriatric patients benefit from multidisciplinary cooperation. Neurologists possess great expertise in the treatment of patients with dementia, depression, delirium, consequences of degenerative spinal cord diseases and vertebral bone fractures, stroke, Parkinson's syndrome, epileptic seizures, vertigo and dizziness, neuropathies, lesions of peripheral nerves and in the multimodal therapy of pain. To function in a position of responsibility in a geriatric department, neurologists need skills in general internal medicine. These are acquired either on a geriatric ward or during specialization as a neurologist by full time secondment to large neurological or interdisciplinary intensive care units.

Vitamin D deficiency decreases survival of bacterial meningoencephalitis in mice.

BACKGROUND: Meningoencephalitis caused by Escherichia coli is associated with high rates of mortality and risk of neurological sequelae in newborns and infants and in older or immunocompromised adults. A high prevalence of neurological disorders has been observed in geriatric populations at risk of hypovitaminosis D. METHODS: In vivo, we studied the effects of vitamin D3 on survival and the host's immune response in experimental bacterial meningoencephalitis in mice after intracerebral E. coli infection. To produce different systemic vitamin D3 concentrations, mice received a low, standard, or high dietary vitamin D3 supplementation. Bacterial titers in blood, spleen, and brain homogenates were determined. Leukocyte infiltration was assessed by histological scores, and tissue cytokine or chemokine concentrations were measured. RESULTS: Mice fed a diet with low vitamin D3 concentration died earlier than control animals after intracerebral infection. Vitamin D deficiency did not inhibit leukocyte recruitment into the subarachnoid space and did not lead to an increased density of bacteria in blood, spleen, or brain homogenates. The release of proinflammatory interleukin (IL)-6 was decreased and the release of anti-inflammatory IL-10 was increased in mice fed a diet with high vitamin D3 supplementation. CONCLUSION: Our observations suggest a detrimental role of vitamin D deficiency in bacterial central nervous system infections. Vitamin D may exert immune regulatory functions.

Sarcopenic obesity: molecular clues to a better understanding of its pathogenesis?

An age-dependent decline in skeletal muscle mass, strength, and endurance during the aging process is a physiological development, but several factors may exacerbate this process, leading to the threatening state of sarcopenia, frailty, and eventually higher mortality rates. Obesity appears to be such a promoting factor and has been linked in several studies to sarcopenia. The reason for this causal association remains poorly understood. Notwithstanding the fact that a higher body mass might simply lead to diminished physical activity and therefore contribute to a decline in skeletal muscle, several molecular mechanisms have been hypothesized. There could be an obesity derived intracellular lipotoxicity (i.e., elevated intramuscular levels of lipids and their derivatives), which induces apoptosis by means of an elevated oxidative stress. Paracrine mechanisms and inflammatory cytokines, such as CRP and IL-6 could be confounders of the actual underlying pathological mechanism. Due to a cross-talk of the hypothalamo-pituitary axis with nutritional status, obese subjects are more in a catabolic state of metabolism, with a higher susceptibility to muscle wasting under energy restriction. Obesity induces insulin resistance in the skeletal muscle, which consequently leads to perturbed metabolism, and misrouted signaling in the muscle cells. In obesity, muscle progenitor cells could differentiate to an adipocyte-like phenotype as a result of paracrine signals from (adipo)cytokines leading to a reduced muscular renewal capacity. The present review outlines current knowledge concerning possible pathways, which might be involved in the molecular pathogenesis of sarcopenic obesity.

Neurocognitive functions and brain atrophy after proven neuroborreliosis: a case-control study.

BACKGROUND: Patients often report neurocognitive difficulties after neuroborreliosis (NB). The frequency and extent of cognitive problems in European patients have been studied incompletely. METHODS: Sixty patients received a neurological and neuropsychological work-up 6 months or longer after treatment for proven NB. Quality of life, psychiatric symptom load, and brain atrophy were measured. All results were compared with a group of 30 healthy control persons adapted for age, gender and education being serologically negative for Borrelia burgdorferi senso latu. A cognitive sum score and a global sum score including cognitive, psychological results and quality of life data was calculated for both groups. RESULTS: Patients after NB showed a lower (i.e. more impaired) score on the Scripps Neurological rating scale (SNRS), but the observed neurological deficits were generally mild (mean ± SD: 97.1 ± 4.7 vs. 99.1 ± 2.4, p = 0.02). The mean neuropsychological domain results of the NB group were all within the normal range. However, a lower performance was found for the frontal executive function z-values (mean ± SD -0.29 ± 0.60 vs. 0.09 ± 0.60; p = 0.0059) of NB patients. Comparing the global sum score (mean ± SD 11.3 ± 4.2 NB vs. 14.3 ± 2.9 control , p = 0.001) and the cognitive sum score of the NB group with those of the control group (mean ± SD -0.15 ± 0.42 NB vs. 0.08 ± 0.31 control , p = 0.0079), both differences were statistically different. The frequencies of impaired global sum scores and those of the pathological cognitive sum scores (p = 0.07) did not differ statistically. No significant differences were found for health-related quality of life (hrQoL), sleep, psychiatric symptom load, or brain atrophy. CONCLUSION: The mean cognitive functions of patients after proven NB were in the normal range. However, we were able to demonstrate a lower performance for the domain of frontal executive functions, for the mean cognitive sum score and the global sum score as a sign of subtle but measurable sequelae of neuroborreliosis. Brain atrophy is not a common consequence of neuroborreliosis.

Frequency of dementia syndromes with a potentially treatable cause in geriatric in-patients: analysis of a 1-year interval.

In addition to neurodegenerative and vascular causes of dementia, in the differential diagnosis potentially reversible conditions of dementia also must be assessed. Routine laboratory parameters and neuroimaging, which are recommended for the differential diagnosis of suspected dementia by the German S3 Guideline "Dementia", were retrospectively studied in 166 geriatric patients with suspected dementia. Delirium was diagnosed in six patients (3.6%). These six patients were excluded from the study. Of the 160 remaining patients, there were 99 (59.6%) with an already known dementia. In this subgroup of patients, we found a potentially treatable cause of dementia in 18.2%. In the remaining 61 patients (36.8%), the newly diagnosed dementia syndrome was established according to ICD-10 criteria. Potentially reversible causes of the dementia syndrome were found in 19 of these patients (31.1%). The most common cause was depressive pseudodementia in eight patients followed by vitamin B12 deficiency in six patients. A significant amount of our patients showed laboratory or imaging changes suggestive of potentially reversible causes of the dementia syndrome upon admission. The results of our study indicate the importance of careful differential diagnosis of dementia based on the recommendations of guidelines. Although therapy of these potential causes is not always accompanied by a full recovery, the identification and therapy of treatable causes of cognitive deficits are possible even for general practitioners, who often are the primary contact persons of affected individuals.

Vitamin d deficiency reduces the immune response, phagocytosis rate, and intracellular killing rate of microglial cells.

Meningitis and meningoencephalitis caused by Escherichia coli are associated with high rates of mortality and neurological sequelae. A high prevalence of neurological disorders has been observed in geriatric populations at risk of hypovitaminosis D. Vitamin D has potent effects on human immunity, including induction of antimicrobial peptides (AMPs) and suppression of T-cell proliferation, but its influence on microglial cells is unknown. The purpose of the present study was to determine the effects of vitamin D deficiency on the phagocytosis rate, intracellular killing, and immune response of murine microglial cultures after stimulation with the Toll-like receptor (TLR) agonists tripalmitoyl-S-glyceryl-cysteine (TLR1/2), poly(I·C) (TLR3), lipopolysaccharide (TLR4), and CpG oligodeoxynucleotide (TLR9). Upon stimulation with high concentrations of TLR agonists, the release of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) was decreased in vitamin D-deficient compared to that in vitamin D-sufficient microglial cultures. Phagocytosis of E. coli K1 after stimulation of microglial cells with high concentrations of TLR3, -4, and -9 agonists and intracellular killing of E. coli K1 after stimulation with high concentrations of all TLR agonists were lower in vitamin D-deficient microglial cells than in the respective control cells. Our observations suggest that vitamin D deficiency may impair the resistance of the brain against bacterial infections.

A fortunate bitten tongue-Hypothyroidism despite repeatedly normal plasma thyrotropin levels.

Key Clinical Message: Hypophyseal dysfunction may be overlooked by the currently generally accepted laboratory routine for the differential diagnosis in patients suffering from symptoms of depression or dementia. Abstract: Hypothyroidism is an important cause of depression and potentially reversible cognitive impairment. Whereas the determination of the plasma concentration of thyrotropin (TSH) is generally considered part of the laboratory screening tests for dementia, the measurement of total or free triiodothyronine (T3, FT3), thyroxine (T4, FT4) and cortisol in plasma does not belong to the routine diagnostic workup in patients with depression or suspected dementia. In an 87-year-old lady suffering from increasingly poor general health, decreased fluid and food intake, mood depression and lack of energy, three measurements of plasma TSH produced normal values. A cranial computed tomography (cCT) 2 days prior to hospital admission had been assessed as apparently normal. A second cCT performed following a loss of consciousness complicated by tongue bite showed a hypophyseal tumor. Then, low plasma levels of FT3, FT4 and cortisol were found. Following hormone replacement and transsphenoidal tumor resection, the patient recovered rapidly. The present case report illustrates the pitfalls of measuring merely the TSH level in the detection of thyroid and hypophyseal dysfunction.

Unilateral phrenic nerve lesion in Lyme neuroborreliosis.

BACKGROUND: Among a variety of more common differential diagnoses, the aetiology of acute respiratory failure includes Lyme neuroborreliosis. CASE PRESENTATION: We report an 87-years old huntsman with unilateral phrenic nerve palsy as a consequence of Lyme neuroborreliosis. CONCLUSION: Although Lyme neuroborreliosis is a rare cause of diaphragmatic weakness, it should be considered in the differential workup because of its potentially treatable nature.

[Geriatric traumatological rounds in a primary care hospital]. / Die alterstraumatologische Visite in einem Krankenhaus der Regelversorgung.

Geriatric traumatological rounds (GTR) with representatives of several disciplines are a challenge in the setting of primary care hospitals with limited resources. The GTR were started with only an experienced traumatologist and a geriatrician in 2019. Routine quality control data showed a reduction of the frequency of cardiac failure and mortality after the start of the GTR. Therefore, even the minimum variant of GTR with the focus on the differential diagnosis of falls and adequate drug treatment appears to be beneficial for the patient. Special attention is given to the medical treatment of cardiac failure, pulmonary diseases, osteoporosis, psychiatric disorders and anemia. Vitamin B12 and folate deficiency are substituted. When anticoagulants or platelet aggregation inhibitors are indicated, they are resumed early. Potentially inadequate drugs for older patients are avoided. Doses of many drugs used in geriatric patients must be adjusted to a reduced renal function often present in old age. Frequent electrolyte abnormalities are diagnosed and adequately treated.

Ceftriaxone-induced neutropenia successfully overcome by a switch to penicillin G in Cardiobacterium hominis endocarditis.

Leukopenia, including agranulocytosis, is a severe complication of treatment with all ß-lactam antibiotics. Its incidence increases with age. Cardiobacterium hominis endocarditis after implantation of an aortic valve bio-prosthesis in a 77-year-old woman was treated with ceftriaxone 2 g/day plus gentamicin 160 mg/day intravenously. On Day 25 of treatment, blood leukocytes had decreased to 1800/µl (neutrophils 370/µl). Antibiotic therapy was switched to penicillin G 20 million international units (IU)/day. Thereafter, blood leukocytes including neutrophils normalized suggesting that penicillin G was less bone marrow-toxic than ceftriaxone. High-dose ciprofloxacin, the alternative to penicillin G, was avoided because of the risk of cognitive and behavioral side effects. The present case suggests that with close laboratory monitoring a ß-lactam with differing side chains should not be considered contraindicated after ß-lactam antibiotic-induced neutropenia.

Overton's rule helps to estimate the penetration of anti-infectives into patients' cerebrospinal fluid.

In 1900, Ernst Overton found that the entry of anilin dyes through the cell membranes of living cells depended on the lipophilicity of the dyes. The brain is surrounded by barriers consisting of lipid layers that possess several inward and outward active transport systems. In the absence of meningeal inflammation, the cerebrospinal fluid (CSF) penetration of anti-infectives in humans estimated by the ratio of the area under the concentration-time curve (AUC) in CSF (AUC(CSF)) to that in serum (AUC(CSF)/AUC(S)) correlated positively with the lipid-water partition coefficient at pH 7.0 (log D) (Spearman's rank correlation coefficient r(S) = 0.40; P = 0.01) and negatively with the molecular mass (MM) (r(S) = -0.33; P = 0.04). The ratio of AUC(CSF) to the AUC of the fraction in serum that was not bound (AUC(CSF)/AUC(S,free)) strongly correlated with log D (r(S) = 0.67; P < 0.0001). In the presence of meningeal inflammation, AUC(CSF)/AUC(S) also correlated positively with log D (r(S) = 0.46; P = 0.002) and negatively with the MM (r(S) = -0.37; P = 0.01). The correlation of AUC(CSF)/AUC(S,free) with log D (r(S) = 0.66; P < 0.0001) was as strong as in the absence of meningeal inflammation. Despite these clear correlations, Overton's rule was able to explain only part of the differences in CSF penetration of the individual compounds. The site of CSF withdrawal (lumbar versus ventricular CSF), age of the patients, underlying diseases, active transport, and alterations in the pharmacokinetics by comedications also appeared to strongly influence the CSF penetration of the drugs studied.