Marianna Stamou1, Pamela J Lein2

11Department of Molecular Biosciences, School of Veterinary Medicine, 1089 Veterinary Medicine Drive, University of California, Davis, CA 95616

22ETH Zurich, Department of Health Sciences and Technology, Institute of Molecular Systems Biology, 8093 Zürich, Switzerland

DOI: 10.29245/2572.942X/2019/1.1243 View / Download Pdf

Monica Ines1, Joao Costa1,2,3*

1Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028, Lisboa, Portugal

2Laboratório de Farmacologia Clínica e Terapêutica, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028, Lisboa, Portugal

3Centro de Estudos de Medicina Baseada na Evidência, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028, Lisboa, Portugal

Transthyretin-associated familial amyloid polyneuropathy (TTR-FAP) is a neurological disease that affects severely patients and their families and caregivers over generations. It is a rare, progressive, and if untreated fatal autosomal dominant hereditary disorder. The disease may affect multiple organ systems and if untreated progress rapidly to death. TTR-FAP affects nearly 10,000 people worldwide, with known endemic regions in Portugal, Sweden, and Japan. Until recently only liver transplantation and tafamidis were treatment options across several world regions. Despite the worldwide use of these disease-modifying treatments to delay disease progression, challenges in clinical assessment and management remain because of disease heterogeneity, phenotypic diversity, small patient populations, incomplete natural history and uncertainty of treatment effect in survival. The two new treatment options (inotersen and patisiran) appear to provide important benefits for patients, based on clinical trials short-term evidence. In this review, we discuss the disease natural survival course and currently available treatments impact on survival. We also discuss the importance of treatment choice (and or sequence of treatments) to maximize survival, while preserving the patient’s health-related quality of life.

DOI: 10.29245/2572.942X/2019/1.1242 View / Download Pdf

Tehila Beiser, Rami Yaka*

Institute for Drug Research (IDR), School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, 91120, Israel

Cocaine is a powerfully addictive psychostimulant that elevates dopamine (DA) levels in the mesolimbic system and causes a feeling of wellbeing. At the same time, cocaine leads to toxic effects in many essential organs, including the brain. The harmful effects of cocaine on the brain are the basis for the development of compulsive and irrational behaviors, an integral part of cocaine addiction. Over the last two decades, it has been suggested that the damage and reinforcing properties of cocaine are associated with increased reactive oxygen species (ROS) production. This increase impairs the endogenous defense antioxidant system, either directly by cocaine metabolites, or indirectly via increased DA metabolites, resulting in oxidative stress (OS). It was thus plausible to seek an exogenous, stable and non-toxic antioxidant, which can penetrate the blood brain barrier and counteract the oxidative damage in the brain caused by drugs of abuse such as cocaine. In this mini-review we describe studies that explore the role of antioxidants in reducing the OS state in the brain reward system and consequently reversing negative behavioral outcomes induced by cocaine.

DOI: 10.29245/2572.942X/2019/1.1239 View / Download Pdf

John Grizzanti1, Rachel Corrigan1, Spencer Servizi1, Gemma Casadesus1,2*

1School of Biomedical Sciences, Kent State University, Ohio, USA

2Department of Biological Sciences, Kent State University, Ohio, USA

Growing evidence highlights the intimate relationship between type II diabetes (T2D) and Alzheimer’s disease (AD). Importantly, these two diseases share a number of pathological similarities, including amyloid accumulation, oxidative stress, inflammation, and cell death. To date, drug therapies for AD and T2D are lacking and there is a crucial need for the discovery and development of novel therapeutics for these diseases. A number of human and rodent studies have given evidence that metabolic hormone supplementation is highly valuable for improving cognitive function and overall metabolic health in both T2D and AD. The pancreatic hormone amylin has arisen as a crucial component of the disease etiology of both T2D and AD, though the exact role that amylin plays in these diseases is not yet well understood. Here, we critically review the current literature that utilizes human amylin or its synthetic analogue, pramlintide, as well as amylin receptor antagonists for the treatment of AD.

DOI: 10.29245/2572.942X/2019/1.1212 View / Download Pdf

Genki Tohnai1, Ryoichi Nakamura1, Masahiro Nakatochi2, Naoki Atsuta1, Masahisa Katsuno1, Gen Sobue1,3*

1Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan

2Statistical Analysis Section, Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan

3Research Division of Dementia and Neurodegenerative Disease, Nagoya University Graduate School of Medicine, Nagoya, Japan

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease, and the etiology of sporadic ALS is unknown. The TANK-binding kinase 1 (TBK1) gene identified as an ALS gene, contributes towards a predisposition for ALS. In this review, we analyzed variants of TBK1 found in ALS cohort studies belonging to various regions and ethnic populations. TBK1 variants tend to be enriched in patients with ALS compared to patients without ALS. The frequency of TBK1 variants is more in the familial Caucasian than that in the Asian population. However, loss of function (LoF) variant associated with sporadic ALS is almost similar among the Asian group, including Japanese population. LoF variants were frequently reported to be associated with the TBK1 biology. These findings indicate that TBK1- LoF variants are pathogenic for ALS, regardless of race or region.

DOI: 10.29245/2572.942X/2019/1.1236 View / Download Pdf

Renata M. Lataro1, Helio C. Salgado2*

1Department of Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil

2Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil

There is a consensus in the literature that the autonomic dysfunction in arterial hypertension involves the increase of sympathetic activity and, also, reduction of vagal tone. In the last years, the role played by inflammation in the development of hypertension and target organs injuries, such as heart and blood vessels, has been emphasized. Although the clinical importance of sympathetic hyperactivity and its treatment of arterial hypertension is recognized, the therapeutic benefit of increasing parasympathetic activity in hypertensive patients still requires an in-depth investigation. The increased vagal activity may produce beneficial effects on cardiovascular modulation and inflammation, preventing target organ damage. Parasympathetic neurotransmission can be improved by the inhibition of acetylcholinesterase action. Anticholinesterase agents prevent the hydrolysis of acetylcholine by acetylcholinesterase, prolonging its availability within the cholinergic cleft. This article will highlight the key concepts of the cardiac autonomic imbalance and the increase of acetylcholine availability under inflammation and control of arterial hypertension. In conclusion, significant evidence exists associating the reduction of parasympathetic activity and the occurrence of inflammation involving the pathophysiology of hypertension; suggesting that the improvement of vagal activity by the increased availability of acetylcholine has a remarkable potential for the therapeutic intervention on arterial hypertension.

DOI: 10.29245/2572.942X/2018/6.1226 View / Download Pdf

Lisa M. James1,2,3, Apostolos P. Georgopoulos1,2,3,4*

1Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN, 55417, USA

2Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN 55455, USA

3Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN 55455, USA

4Department of Neurology, University of Minnesota Medical School, Minneapolis, MN 55455, USA

DOI: 10.29245/2572.942X/2018/6.1235 View / Download Pdf

George Stoica1*, Heidi Martini-Stoica2

1Texas A&M University, College Station, TX,USA

2Baylor College of Medicine, Houston, TX, USA

DOI: 10.29245/2572.942X/2018/6.1231 View / Download Pdf

Hildegard M. Schuller

Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville TN, USA

DOI: 10.29245/2572.942X/2018/6.1230 View / Download Pdf

Toshiyuki Mizui1, 2*, Masami Kojima1,2,3#

Biomedical Research Inst. (BMD), National Institute of Advanced Industrial Science and Technology (AIST), 1-8-31 Midorioka, Ikeda, Osaka, 563-8577 Japan

Core Research for Evolutional Science and Technology (CREST), Science and Technology Agency (JST), Kawaguchi, 332-0012, Japan

Graduate School of Frontier Bioscience, Osaka University, Suita 565-0871, Japan

Most growth factors are initially synthesized as precursors. To produce biologically active mature peptides, the pro-domain is cleaved by proteolytic processing. However, compared with mature bioactive growth factors, the biological roles of pro-domains are poorly understood. Recent new findings on brain-derived neurotrophic factor (BDNF), a growth factor in the brain that promotes neuronal survival, differentiation, and synaptic plasticity, have been reported. Interestingly, the pro-domain (pro-peptide) of BDNF is endogenously present and localized at presynaptic termini, where it surprisingly functions as a facilitator of long-term depression (LTD). Given that BDNF elicits synaptic transmission and long-term potentiation (LTP), BDNF and its pro-peptide might exert distinct roles in synaptic plasticity in the central nervous system (CNS). In addition to reports on the BDNF pro-peptide, we review recent literature on the role of BDNF in the peripheral nervous system (PNS), and in brain-body interactions following exercise. Together, these findings provide new insight into BDNF biology.

DOI: 10.29245/2572.942X/2018/6.1228 View / Download Pdf

Ido Rippin, Hagit Eldar-Finkelman*

Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Israel

DOI: 10.29245/2572.942X/2018/6.1227 View / Download Pdf

Qin Wang, Richard Grater*, Luisette Delva, Elvana Veizaj, Cheryl Black, Chris Rowbottom, Roger Rusesabagina, Ellen Rohde, Patricia Schroeder, Tonika Bohnert, Guangqing Xiao

Preclinical Pharmacokinetics and In Vitro ADME, Biogen Inc. 225 Binney St Cambridge, MA 02142, USA

Objective: The convective flow of CSF plays a crucial role for CNS to clear endogenous and xenobiotic substances. The objective of this study is to investigate the impact of modifying CSF flow with acetazolamide and arginine vasopressin (AVP) on the CNS clearance of ibuprofen and acetaminophen.

Results: Microdialysis studies indicated that acetaminophen AUC ratio (Kp,uu) between brain ISF and unbound plasma increased from 0.40 ± 0.14 in the vehicle control group to 0.60 ± 0.27 in the acetazolamide treated group (P < 0.05). Conversely, acetaminophen’s steady-state ISFC to unbound_plasmaC ratio (Kp,uu) decreased from 0.44 ± 0.08 to 0.36 ± 0.07 upon IV infusion of 0.3 µg/hr AVP (P < 0.05). Using CSF concentration as a surrogate of unbound brain drug concentration, AVP treatment reduced the CSFAUC0-5hr/unbound_plasmaAUC0-5hr ratio from 1.63 to 0.85 for acetaminophen, and the CSFC4hr / unbound_plasmaC4hr ratio decreased from 0.91 ± 0.27 to 0.54 ± 0.12 for ibuprofen (P < 0.05).

Conclusion: We have demonstrated that acetazolamide decreases the CNS clearance of acetaminophen, while AVP increases the CNS clearance of both acetaminophen and ibuprofen. Such changes are caused by altering the CSF production rates.

DOI: 10.29245/2572.942X/2018/5.1217 View / Download Pdf

Laxminarayan Bhat*, Marc Cantillon, and Robert Ings

Reviva Pharmaceuticals, Inc., Sunnyvale, CA, USA

Schizophrenia is a condition comprising of both treatment and comorbidity factors that both complicate its management and present multiple unmet needs. Brilaroxazine (RP5063), a dopamine (D)/serotonin (5-HT) modulator, possesses a broad in vitro pharmacology profile against D2/3/4 and 5-HT1A/2A/2B/6/7 receptors, nicotinic acetylcholine (α4β2) receptors, and the serotonin transporter. In Phase 1 and 2 clinical experience in healthy volunteers, patients with schizophrenia and schizoaffective disorder, brilaroxazine was well tolerated, with the repeated 100 mg oral dose as the maximum tolerated dose. Investigators observed no cardiometabolic, cardiovascular, prolactin, or neurologic complications. Adherence in Phase 2 was good with discontinuation rates generally less than placebo. In a Phase 2 evaluation of patients with acute exacerbations in schizophrenia and schizoaffective disorders, brilaroxazine met its primary endpoint of significance versus placebo for Total Positive and Negative Symptom Scale (PANSS) Score at Day 28 as compared to baseline. In Phase 1 multi-dose pharmacodynamic evaluation, brilaroxazine displayed clinical activity in patients with stable disease and a PANSS greater than 50, as early as Day 10 of treatment. Pharmacokinetic analyses demonstrated brilaroxazine to have a substantial and relatively rapid oral absorption, linear (dose proportional) increases in maximum concentration (Cmax) and area under the curve (AUC), lack of excessive accumulation, and a relatively long terminal half-life of about 60 hours. Early clinical findings with brilaroxazine in schizophrenia and schizoaffective disorders indicate that this compound appears to be effective, well tolerated, and possess a straightforward once-daily dosing pharmacokinetic profile.

DOI: 10.29245/2572.942X/2018/5.1225 View / Download Pdf

Kristin A Richardson1, Robert J Wessells1*

1Department of Physiology, Wayne State School of Medicine, Detroit, MI 48201, USA

DOI: 10.29245/2572.942X/2018/5.1224 View / Download Pdf

Effie-Photini C. Tsilibary1,2, Eric P. Souto1, Lisa M. James1,2, Brian E. Engdahl1,2, Apostolos P. Georgopoulos1,2*

1Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, Minnesota, USA

2Department of Neuroscience, University of Minnesota Medical School, Minneapolis, Minnesota, USA

Gulf War Illness (GWI) is a chronic debilitating disease of unknown etiology that affects the brain and has afflicted many veterans of the 1990-91 Gulf War (GW). We showed recently1 that blood serum from patients suffering from GWI exerts detrimental effects on neural cultures, including reduced growth, increased apoptosis, and disruption of neural network function. Remarkably, these adverse effects were prevented by the concomitant addition to the culture of serum from healthy Gulf War (GW) era veterans. We interpreted those findings1 in the context of our hypothesis that GWI is, at least partly, due to circulating pathogenic persistent antigens2, probably coming from vaccines administered to GW veterans who lacked crucial Human Leukocyte Antigen (HLA) class 2 alleles3 and, therefore, could not make antibodies against those antigens; by contrast, healthy GW veterans who received the same vaccines and possessed HLA protection3 made antibodies that neutralized the various antigens. Thus, we hypothesized that the beneficial effect of the healthy serum on preventing the adverse GWI serum effects was due to the presence of antibodies against the persistent antigens. Here we tested this hypothesis by assessing the effect of pooled human immunoglobulin G (IgG) on ameliorating the GWI adverse effects on neural growth and apoptosis in neuroblastoma N2A cultures. We tested this effect in 14 GWI patients and found that IgG exerted a potent ameliorating effect by inhibiting the reduction in growth and increased apoptosis of GWI serum. These results lend support to our persistent antigen hypothesis1,2 and suggest an immunotherapy approach for treating GWI. This approach is further strengthened by our finding that the severity of GWI neurocognitive/mood (NCM) symptoms was positively correlated with the degree of apoptosis caused by GWI serum on the neural culture, thus validating the relevance of the apoptotic effect to NCM symptomatology. Finally, we used this relation to predict NCM scores based on the reduced apoptosis effected by IgG addition and found a predicted reduction in NCM symptom severity by ~60%. Altogether, these findings point to the possible beneficial use of IgG in treating GWI.

DOI: 10.29245/2572.942X/2018/5.1219 View / Download Pdf

Nobuko Inoue1, 2, Hitoshi Sakano2*

1Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan

2Department of Brain Function, University of Fukui School of Medicine, 23-3 Shimo-aizuki, Matsuoka, Fukui 910-1193, Japan

Odorant molecules are detected by olfactory sensory neurons (OSNs) in the olfactory epithelium. Odor information is then transmitted to the olfactory cortex through synapses with mitral/tufted (M/T) cells. We recently analyzed a pair of signaling molecules, Semaphorin (Sema) 7A expressed in OSN axons and its receptor Plexin (Plxn) C1 localized to M/T-cell dendrites. In the knockout mice for Sema7A or PlxnC1, initiation of synapse formation is perturbed. Rescue and reconstitution experiments demonstrated that interactions of Sema7A and PlxnC1 are essential to induce the post-synaptic assembly. Pharmacological blocking of NMDA receptors indicated that synaptic transmission induces primary-dendrite selection after the synapses are formed. We conclude that Sema7A/PlxnC1 signaling is key for initiating synapse formation followed by dendrite selection in M/T cells. Since other Sema molecules are known to regulate targeting of OSN axons without involving neuronal activities, Sema7A is a unique example of Sema family proteins that regulates synapse formation and dendrite selection in an activity-dependent manner. Possible roles of Sema7A/PlxnC1 signaling will be discussed in the context of olfactory circuit formation in neonates.

DOI: 10.29245/2572.942X/2018/5.1223 View / Download Pdf

A. S. M. Ali Reza1, Mst. Samima Nasrin1, A. H. M. Khurshid Alam2*

1Department of Pharmacy, Faculty of Science and Engineering, International Islamic University, Chittagong, Bangladesh

2Department of Pharmacy, University of Rajshahi, Bangladesh

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder of the brain characterized by memory loss and, impaired judgment and language use. As AD incidence increases with age, AD has become a large socioeconomic burden that will only continue growing as populations age. Natural compounds that possess polyphenolic (phenolics and flavonoids) content and antioxidant property have the capacity to reduce the progression and symptoms of neurodegenerative diseases, including AD. In this mini-review, we emphasize the pathomechanisms of AD, including oxidative stress and modulatory roles of natural antioxidants in preventing AD. We discuss the antioxidant, phytochemical, and anticholinesterase properties of the plant Elatostema papillosum, which are relevant to the management of AD.

DOI: 10.29245/2572.942X/2018/5.1211 View / Download Pdf

Bernhard J. Mitterauer*

Volitronics-Institute for basic research and psychopathology, Salzburg, Austria

A model of imbalances in tripartite synapses responsible for the pathophysiology of mental disorders and epilepsy is reviewed. A tripartite synapse consists of the presynapse and the postsynapse as the neuronal component and the astrocyte as the glial component. Based on a formalism of system-balancing it is hypothesized that the expression of astroglial receptors determines imbalances of neurotransmission. In depression, tripartite synapses are imbalanced since neurotransmitters cannot activate the overexpressed astroglial receptors in the time leading to a prolonged neurotransmission. Inversely, in mania the imbalance of tripartite synapses is caused by a surplus of neurotransmitters overactivating underexpressed astroglial receptors causing a shortened neurotransmission. If astroglial receptors are non-functional, they cannot be activated by neurotransmitters leading to an unconstrained neurotransmission responsible for schizophrenia. In epilepsy, astroglial receptors are overexpressed, but glutamatergic synapses are hyperactivated and GABAergic synapses are hypoactivated causing an imbalance between excitatory and inhibitory tripartite synapses responsible for epileptogenesis. It is suggested that common imbalances of astroglia-synapse interactions may be responsible for mental disorders and epilepsy.

DOI: 10.29245/2572.942X/2018/5.1216 View / Download Pdf

Deborah R. Gustafson1,2*

1Department of Neurology, State University of New York, Downstate Medical Center, New York, USA

2Department of Health and Education, University of Skövde, Sweden

DOI: 10.29245/2572.942X/2018/5.1220 View / Download Pdf

Michaela T. Haindl1, Muammer Ücal2, Franz Fazekas1, Sonja Hochmeister1*

1Department of Neurology, Medical University Graz, Auenbruggerplatz 22, 8036 Graz, Austria

2Research Unit of Experimental Neurotraumatology, Department of Neurosurgery, Medical University Graz, Auenbruggerplatz 29, 8036 Graz, Austria

Success in developing new drugs for diseases often depends on laboratory research usually involving animal models. For the early disease phases of multiple sclerosis (MS) this prerequisite was given by experimental autoimmune encephalomyelitis (EAE), an animal model which reflects the pathophysiological mechanisms of the disease quite well. Only a few models resemble cellular features of the progressive disease form of MS (like cortical demyelination) and if they do observable lesions are rather sparse and short lived. The lack of suitable animal models delayed and complicated drug development. Recently a few promising animal models reassembling many characteristics of progressive MS have been described aiming at both a better understanding of cellular mechanisms of this disease phase as well as the development of new therapeutic options. The authors of new rat models postulate novel findings of cortical pathology summarized in this article. The models differ in their focus and not all distinct models are reflecting all features of progressive MS but together they allow research on different aspects of the disease and offer the opportunity to expand our knowledge and clear the way for drug development.

DOI: 10.29245/2572.942X/2018/5.1218 View / Download Pdf

Karla Cervantes Gracia1, Holger Husi2,3*

1University of Monterrey, Health Sciences Division, Monterrey, 66238, Mexico

2Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, G12 8TA, UK

3Department of Diabetes and Cardiovascular Science, University of the Highlands and Islands, Centre for Health Science, Inverness, IV2 3JH, UK

DOI: 10.29245/2572.942X/2018/5.1210 View / Download Pdf

William K. Summers1*, Roy L. Martin1, Yimeng Liu2, Bernice Peña1, Gary M. Marsh2

1Alzheimer’s Corporation,6000 Uptown Blvd, Suite 308, Albuquerque, NM 87110, USA

2Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, University of Pittsburgh, A410 Crabtree Hall, 130 DeSoto St, Pittsburgh, PA 15261, USA

DOI: 10.29245/2572.942X/2018/5.1215 View / Download Pdf

Curtis Osborne*, John Paul Taylor, Alan J. Thomas

Institute of Neuroscience, Biomedical Research Building, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, UK

DOI: 10.29245/2572.942X/2018/4.1213 View / Download Pdf

Melita Salkovic-Petrisic*

Department of Pharmacology and Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia

Incretin-based drugs originally developed for the treatment of type 2 diabetes mellitus are currently under investigation for their therapeutic potential in sporadic Alzheimer’s disease (AD). Two major incretin hormones are glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), which both additionally have neuroprotective, neurotrophic and neurogenesis-promoting effects upon the stimulation of GLP-1 and GIP receptors in the brain. This review points out another approach to the incretin-related sAD therapy based on the therapeutic potential of oral galactose in a streptozotocin-induced rat model of sporadic AD (STZ-icv model). Chronic oral galactose treatment prevents the development and ameliorates already developed cognitive deficits in the early stage of sAD-like pathology in STZ-icv rat model. The underlying mechanism(s) of these beneficial effects might be related to stimulation of endogenous GLP-1-mediated central effects and normalization of cerebral glucose hypometabolism as well as other oral galactose-induced effects along the oro-gastro-intestinal tract. The beneficial effects on cognitive impairment seem to depend on galactose exposure, presence and stage of sAD-like pathology. Further research is needed to clarify therapeutic potential and safety profile of oral galactose treatment as well as its possible advantages over or synergistic activity with the GLP-1 analogues and inhibitors of dipeptidyl peptidase-4.

DOI: 10.29245/2572.942X/2018/4.1204 View / Download Pdf

Martin Berli*, Lazaros Vlachopoulos, Sabra Leupi, Thomas Boeni, Charlotte Vlachopoulos-Baltin

Department of Orthopedicsn University Hospital Balgrist Zurich, Switzerland

A brief review of the above-mentioned article: forty patients with 43 affected feet and 60 cases of osteomyelitis were included in this study. They were split into two groups, one with osteomyelitis outside and another one with osteomyelitis within the active Charcot region. The results showed that the amputation rate did not differ between the two groups, although in group 1 – osteomyelitis outside the active Charcot region.

amputations were exclusively performed at the forefoot and in group 2 – with osteomyelitis within the active Charcot region – exclusively in the mid- and hindfoot. Amputations in group 2 were, therefore, more high level. The duration of immobilization and antibiotic treatment was significantly longer in group 2. We conclude, that patients treated for osteomyelitis in an active Charcot foot should be considered and treated as separate entities, depending on whether the osteomyelitis is located within or outside the active Charcot region. If osteomyelitis occurs outside the active Charcot region, primary amputation may be preferred to internal resection.

DOI: 10.29245/2572.942X/2018/4.1176 View / Download Pdf