Reversible Lesion Research Articles

Is There Blinding Onchocerciasis in Northern Uganda?

Background: Onchocerciasis is a filarial nematode Onchocerca volvulus transmitted by female black flies which breeds in fast flowing rivers. Clinical manifestations is ocular or skin lesions. The long-term armed conflict in northern Uganda deprived research on onchocerciasis and no attempts have been made to establish the clinical manifestation of the disease in the region. Objective: To establish whether Simulium damnosum transmitted onchocerciasis in this region was blinding. Participants: Persons from thirteen endemic parishes in Pader district in northern Uganda were examined for clinical, parasitological and ocular manifestations of onchocerciasis. Results: A total of 675 persons were examined and microfilaria prevalence in skin snips was 28%, while nodules and onchodermatitis were 30% and 29% respectively. The commonest skin lesion was Chronic Papular Onchodermatitis (17.5%). However, the prevalence of both microfilaria in the anterior chamber of the eye and reversible ocular lesions was 4%. The reversible ocular lesions of onchocerciasis observed were punctate keratitis stage B (0.1%), punctate keratitis stage D (0.1%) and punctate keratitis stage E (3.7%). While 16.1% of the respondents had irreversible ocular lesions attributed mainly to Optic atrophy (6.4%) and sclerosing keratitis (5.2%). There was significant association between irreversible onchocerciasis lesions and visual loss (p< 0.0001). Conclusion: This study confirmed the occurrence of blinding onchocerciasis in Pader district, the first ever reported in indigenous populations in Uganda.

Involvement of HLA class I molecules in the immune escape of urologic tumors

To analyze the influence of different alterations in human leukocyte antigen class I molecules (HLA I) in renal cell carcinoma, as well as in bladder and prostate cancer. We also study the correlation between HLA I expression and the progression of the disease and the response after immunotherapy protocols.It has been shown, experimentally, that the immune system can recognize and kill neoplastic cells. By analyzing the expression of HLA I molecules on the surface of cancer cells, we were able to study the tumor escape mechanisms against the immune system.Alteration or irreversible damage in HLA I molecules is used by the neoplastic cells to escape the immune system. The function of these molecules is to recognize endogenous peptides and present them to T cells of the immune system. There is a clear relationship between HLA I reversible alterations and success of therapy. Irreversible lesions also imply a lack of response to treatment. The immune system activation can reverse HLA I molecules expression in tumors with reversible lesions, whereas tumors with irreversible ones do not respond to such activation. Determine the type of altered HLA I molecules in tumors is of paramount importance when choosing the type of treatment to keep looking for therapeutic success. Those tumors with reversible lesions can be treated with traditional immunotherapy; however, tumour with irreversible alterations should follow alternative protocols, such as the use of viral vectors carrying the HLA genes to achieve damaged re-expression of the protein.From studies in urologic tumors, we can conclude that the HLA I molecules play a key role in these tumors escape to the immune system.

Reversible splenial lesion in auto-immune thyroid disease: a case report

Reversible lesions of the splenium of the corpus callosum constitute a clinicoradiological syndrome that has been associated to various medical conditions. We report the case of a 47-year-old man who presented with encephalopathy associated to auto-immune thyroid disease in which a reversible splenial lesion was isolated. Although encephalopathy associated to auto-immune thyroid disease is characterized by variable radiological findings, it has only been once associated with a reversible splenial lesion.

Reversible bone lesions induced by tenofovir disoproxil fumarate

Metabolic bone disease is increasingly common in HIV-infected patients on antiretroviral therapy (ART) [1]. Manifestations of ART-induced bone disease include low bone mineral density, increased bone turnover, osteopenia, osteoporosis, and increased fracture risk [2–4]. To our knowledge, reversible tenofovir disoproxil fumarate (TDF)-induced bone lesions have not been described. We describe a patient who developed diffuse foci of increased bone turnover on a TDF-containing regimen and which resolved upon discontinuation of TDF. A 33-year-old Caucasian woman with HIV had multiple risk factors for metabolic bone disease including low BMI, Caucasian race, and tobacco use. A protease inhibitor-containing regimen was initiated and eventually included TDF, which continued unabated for 74 months. Severe lower-extremity pain began approximately 36 months after TDF was added, occurred with movement, and limited activities of daily living (ADL). Eventually, generalized pain extended to the wrists, upper arms, and thorax, and fluctuated in intensity for several months. At 74 months, pain was reported to be excruciating with significant overall impairment of ADL. Chemistries and serum markers for bone disease including vitamin D, parathyroid hormone, and calcium were within normal limits, with the exception of alkaline phosphatase and liver transaminases, each of which was greater than two and three times the upper limit of normal, respectively. Serum creatinine and blood urea nitrogen were normal. All antiretrovirals were discontinued due to severe bone pain. A technetium bone scan revealed multiple foci of increased activity in distal tibiae, bilateral calcaneus bones, multiple costovertebral junctions and ribs, sternum, sacroiliac joints, and right iliac and superior pubic ramus (Fig. 1). Shortly after these findings, the same protease inhibitor-containing regimen, without TDF, was resumed. The patient reported significant improvement in pain and function 3 months later, and a bone scan 11 months after stopping TDF was normal. Additionally, alkaline phosphatase declined shortly after TDF was discontinued and normalized 12 months later.Fig. 1: Technetium bone scan.In conclusion, reversible bone lesions detected by technetium bone scan present a unique finding and a likely manifestation of TDF-induced metabolic bone disease. In our patient, imaging abnormalities occurred after greater than 6 years of continued TDF use, and resolved after 11 months of TDF-sparing ART, whereas other risk factors for bone disease, including protease inhibitor use, remained constant. A bone scan may be useful for discriminating pain caused by metabolic bone disease on long-term TDF from other types of chronic pain. Acknowledgements Conflicts of interest Financial support: No financial support was received for the manuscript. Disclaimers: There are no conflicts of interest for Staci M. Lockhart or Douglas A. Drevets.

Reversible basal ganglia lesions in neuropsychiatric lupus: a report of three pediatric cases

Central nervous system involvement represents a serious and common complication of systemiclupus erythematosus (SLE). We describe the characteristics of patients with neuropsychiatric (NP) SLE complicated with reversible basal ganglia lesions. We describe the cases of three NPSLE patients. They presented with NP manifestations such as headache, cognitive dysfunction, tremors, seizures, and mood disorder. The levels of autoantibodies to NMDA (N-methyl-d-aspartate) receptor antibodies and antiribosomal-P antibodies were elevated, indicating the presence of an acute phase. Marked elevation of interleukin-6 in cerebrospinal fluid was noted when these patients showed NP symptoms. Moreover, the patients presented with high-intensity lesions in the basal ganglia on T2-weighted images, fluid-attenuated inversion recovery (FLAIR) images, diffusion-weighted images (DWI) and apparent diffusion coefficient (ADC) maps. Following immunosuppressive treatment, almost complete improvement of the lesions was noted. The reported cases indicate that reversible vasculopathies represent vasogenic edema localized in basal ganglia lesions and that activation of the autoimmune system and inflammation could lead to NP manifestations in SLE.

Reversible lesions in the brain parenchyma in Wilson's disease confirmed by magnetic resonance imaging: earlier administration of chelating therapy can reduce the damage to the brain.

The aim of this study was to evaluate the resolution of brain lesions in patients with Wilson's disease during the long-term chelating therapy using magnetic resonance imaging and a possible significance of the time latency between the initial symptoms of the disease and the introduction of this therapy. Initial magnetic resonance examination was performed in 37 patients with proven neurological form of Wilson's disease with cerebellar, parkinsonian and dystonic presentation. Magnetic resonance reexamination was done 5.7 ± 1.3 years later in 14 patients. Patients were divided into: group A, where chelating therapy was initiated < 24 months from the first symptoms and group B, where the therapy started ≥ 24 months after the initial symptoms. Symmetry of the lesions was seen in 100% of patients. There was a significant difference between groups A and B regarding complete resolution of brain stem and putaminal lesions (P = 0.005 and P = 0.024, respectively). If the correct diagnosis and adequate treatment are not established less than 24 months after onset of the symptoms, irreversible lesions in the brain parenchyma could be expected. Signal abnormalities on magnetic resonance imaging might therefore, at least in the early stages, represent reversible myelinolisis or cytotoxic edema associated with copper toxicity.

Reversible Splenial Lesion in the Corpus Callosum on MRI after Ingestion of a Herbicide Containing Glufosinate Ammonium: A Case Report

Glufosinate ammonium (GLA) is a broad-spectrum herbicide used worldwide. As the use of GLA-containing herbicides has increased, poisoning from incidental and deliberate ingestion has also increased, and has been mostly reported from Japan. Most of glufosinate poisoning events were associated with suicide attempts using BASTA® (Bayer, Leverkusen, Germany). BASTA®, a herbicide containing glufosinate ammonium (18.5%) and the anionic surfactant, polyoxyethylene alkylether sulfate (30%), has been widely used in many countries since 1984 (1). Glufosinate poisoning has been reported to induce central nervous system (CNS) symptoms, such as drowsiness, memory impairment, and seizures. Also, the included anionic surfactant, which increases blood vessel permeability, may cause symptoms such as reduced circulatory blood volume, altered cardiac function, and systemic peripheral vessel resistance (1). Periventricular white matter ischemias, hippocampal lesions, and both hippocampal and striatal lesions have been reported following GLA intoxication, together with radiological findings (2, 3). We describe a patient who developed a reversible callosal lesion by ingesting a GLA-containing herbicide in an attempted suicide.

Acute Toxicity by Water Containing Hexavalent or Trivalent Chromium in Native Brazilian Fish, Piaractus mesopotamicus: Anatomopathological Alterations and Mortality

This study evaluated the toxicity of hexavalent and trivalent compounds of chromium to the pacu, Piaractus mesopotamicus, in acute exposures of 96 h through mortality and histopathological responses. Hexavalent potassium dichromate was more toxic than trivalent compounds of chromium chloride, chromium oxide and chromium carbochelate. Sufficient mortalities occurred only with potassium dichromate to yield an LC50 value at 124.2 mg L(-1). Hexavalent chromium caused reversible and irreversible lesions, which may affect organ functionality. Histopathological evaluation showed that trivalent chromium caused lesions of lower severity. Pacu subjected to different concentrations of chromium carbochelate showed no histopathological changes in the kidneys, liver, skin and gills, being similar to those of the control fish. Among the three sources of Cr(3+), only chromium chloride at 200 mg L(-1) resulted in mortality, which reached 100 % within the first 18 h. These findings confirm that trivalent chromium, when administered within recommended levels, may be used safely in aquaculture.

Mild encephalopathy with reversible lesion of the splenium caused by infectious endocarditis

Mild encephalopathy with reversible lesion of the splenium of corpus callosum is a rare disease revealing mild neurological symptoms, such as disturbance, ataxia, vertigo and in some cases headache. Magnetic resonance signal alterations in the splenium of the corpus callosum can be found in patients suffering from different diseases, mostly viral infections, but also seizures, antiepileptic drug therapy, bacterial infections, hypoglycaemia, Wernicke encephalopathy, Marchiafava Bignami disease, hemolytic uremic syndrome, acute urinary retention, and acute axonal trauma. We report a 32-year old man admitted to our hospital with fever and vomiting. In the neurological examination he presented with mild dizziness and confusion. Until that time no cardiac symptoms had been reported. Due to the neurological symptoms an MR scan of the brain was performed visualizing an area of restricted diffusion with a diameter of 7 mm located in the central portion of the splenium of the corpus callosum being hyperintense on Fluid Attenuated Inversion Recovery (FLAIR) and T2-weighted turbo spin-echo images. Furthermore, multiple punctate lesions with similar appearance on diffusion weighted imaging were found in both hemispheres suspicious of embolic ischemic etiology. Consecutive transesophageal echocardiography revealed endocarditis of the mitral valve. Transient lesions of the splenium recovering within a month are not specific and there is a wide range of differential diagnoses. They may indicate severe disease despite of initially mild neurological symptoms. Pathophysiology of these lesions is not clearly understood yet, even if there exist some – however not proven – theories, such as rapidly resolving intramyelinic edema or influx of inflammatory cells associated with cytotoxic edema.

Implicación de las moléculas HLA de clase I en el escape inmunitario de tumores urológicos

Context and objectiveTo analyze the influence of different alterations in human leukocyte antigen class I molecules (HLA I) in renal cell carcinoma, as well as in bladder and prostate cancer. We also study the correlation between HLA I expression and the progression of the disease and the response after immunotherapy protocols. Evidences acquisitionIt has been shown, experimentally, that the immune system can recognize and kill neoplastic cells. By analyzing the expression of HLA I molecules on the surface of cancer cells, we were able to study the tumor escape mechanisms against the immune system. Evidences synthesisAlteration or irreversible damage in HLA I molecules is used by the neoplastic cells to escape the immune system. The function of these molecules is to recognize endogenous peptides and present them to T cells of the immune system. There is a clear relationship between HLA I reversible alterations and success of therapy. Irreversible lesions also imply a lack of response to treatment. The immune system activation can reverse HLA I molecules expression in tumors with reversible lesions, whereas tumors with irreversible ones do not respond to such activation. Determine the type of altered HLA I molecules in tumors is of paramount importance when choosing the type of treatment to keep looking for therapeutic success. Those tumors with reversible lesions can be treated with traditional immunotherapy; however, tumour with irreversible alterations should follow alternative protocols, such as the use of viral vectors carrying the HLA genes to achieve damaged re-expression of the protein. ConclusionFrom studies in urologic tumors, we can conclude that the HLA I molecules play a key role in these tumors escape to the immune system.

Epigenetic Regulation of TNFA Expression in Periodontal Disease

Tumor necrosis factor-α (TNF-α) plays a central role in the molecular pathogenesis of periodontal disease. However, the epigenetic regulation attributable to microbial and inflammatory signals at the biofilm-gingival interface are poorly understood. In this study, the DNA methylation alteration within the TNFA promoter in human gingival biopsies from different stages of periodontal disease is investigated and the regulatory mechanism of TNFA transcription by DNA methylation is explored. Gingival biopsies were obtained from 17 patients with chronic periodontitis (CP) and 18 periodontally healthy individuals. Another 11 individuals participated in an experimentally induced gingivitis study, and gingival biopsies were collected at the baseline, induction, and resolution phase. To confirm that TNFA promoter methylation modulated TNFA transcription, THP.1 cells were treated with a DNA methyltransferase inhibitor, 5-Aza-2-deoxycytidine (5-Aza-2dC), and an RAW294.7 cell line transfected with a TNFA promoter-specific luciferase reporter system with or without methylation was used. In gingival biopsies from individuals with severe CP, two individual cytosine-guanine dinucleotides (CpG sites) within the TNFA promoter (at -163 and -161 bp) displayed increased methylation in CP samples compared to those with gingival health (16.1% ± 5.1% versus 11.0% ± 4.6%, P = 0.02 and 19.8% ± 4.1% versus 15.4% ± 3.6%, P = 0.04, respectively). The methylation level at -163 bp was inversely associated with the transcription level of TNFA (P = 0.018). However, no significant difference in the TNFA promoter methylation pattern was observed in samples biopsied during the induction or resolution phase of experimentally induced gingivitis, which represented a reversible periodontal lesion. THP.1 cells treated with 5-Aza-2dC demonstrated a time-dependent increase in TNFA messenger level. It was also found that the luciferase activity decreased 2.6-fold in a construct containing an in vitro methylated TNFA promoter when compared to the unmethylated insert (P = 0.03). Although the biopsy samples represented a mixed cell population, the change in promoter methylation status in chronic periodontal disease suggested that DNA methylation may be an important regulatory mechanism in controlling TNFA transcriptional expression in periodontal disease.

Reversible lesions of cerebellar dentate nuclei associated with metronidazole therapy

Reversible lesions of cerebellar dentate nuclei associated with metronidazole therapy

Oxygénothérapie hyperbare et gaz inertes dans l’ischémie cérébrale et le traumatisme crânien

Cerebral ischemia is a common thread of acute cerebral lesions, whether vascular or traumatic origin. Hyperbaric oxygen (HBO) improves tissue oxygenation and may prevent impairment of reversible lesions. In experimental models of cerebral ischemia or traumatic brain injury, HBO has neuroprotective effects which are related to various mechanisms such as modulation of oxidative stress, neuro-inflammation or cerebral and mitochondrial metabolism. However, results of clinical trials failed to prove any neuroprotective effects for cerebral ischemia and remained to be confirmed for traumatic brain injury despite preliminary encouraging results. The addition of inert gases to HBO sessions, especially argon or xenon which show neuroprotective experimental effects, may provide an additional improvement of cerebral lesions. Further multicentric studies with a strict methodology and a better targeted definition are required before drawing definitive conclusions about the efficiency of combined therapy with HBO and inert gases in acute cerebral lesions.

Tubulointerstitial nephritis and cancer chemotherapy: update on a neglected clinical entity

Cancer patients are particularly vulnerable to drug-induced kidney injury during their chemotherapy. Whereas the direct nephrotoxic effects of these drugs are well recognized, that of tubulointerstitial nephritis (TIN) is less well known, underdiagnosed and often reported only as a functional tubular disorder. The diagnosis of acute TIN is important because of its insidious onset with tubular dysfunction, its potential reversibility if detected early and the possibility of its response to steroid treatment. We performed a literature review (44 cases) and reviewed our institutional biopsy register (12 cases) of patients on cancer chemotherapy with documented TIN. Biopsies were considered in three groups: acute TIN, chronic TIN and acute on chronic TIN. The outcomes that were evaluated were recovery of kidney function, development of chronic kidney disease and onset of end-stage renal disease (ESRD). Ifosfamide, BCG, tyrosine kinase inhibitors and premetrexed were the most commonly implicated drugs. Ifosfamide and premetrexed were associated with worst outcomes. Recovery of kidney function was better in acute TIN (ATIN) (29%) with fewer progressing to ESRD (12.9%) than with chronic TIN (7.6% recovery, 15.3% ESRD). Steroid use appeared to favorably alter outcomes in ATIN (40% recovery) compared with conservative treatment (18.75% recovery). Peak serum creatinine, age, gender and type of malignancy did not influence outcomes. As a potentially reversible lesion that can respond to withdrawal of the suspected agent, and in some cases to a short course of steroid therapy, it is important to consider ATIN in the differential diagnosis of all cases of acute kidney injury in cancer patients on chemotherapy.

Current status of auditory aging and anti‐aging research

The development of presbycusis, or age-related hearing loss, is determined by a combination of genetic and environmental factors. The auditory periphery exhibits a progressive bilateral, symmetrical reduction of auditory sensitivity to sound from high to low frequencies. The central auditory nervous system shows symptoms of decline in age-related cognitive abilities, including difficulties in speech discrimination and reduced central auditory processing, ultimately resulting in auditory perceptual abnormalities. The pathophysiological mechanisms of presbycusis include excitotoxicity, oxidative stress, inflammation, aging and oxidative stress-induced DNA damage that results in apoptosis in the auditory pathway. However, the originating signals that trigger these mechanisms remain unclear. For instance, it is still unknown whether insulin is involved in auditory aging. Auditory aging has preclinical lesions, which manifest as asymptomatic loss of periphery auditory nerves and changes in the plasticity of the central auditory nervous system. Currently, the diagnosis of preclinical, reversible lesions depends on the detection of auditory impairment by functional imaging, and the identification of physiological and molecular biological markers. However, despite recent improvements in the application of these markers, they remain under-utilized in clinical practice. The application of antisenescent approaches to the prevention of auditory aging has produced inconsistent results. Future research will focus on the identification of markers for the diagnosis of preclinical auditory aging and the development of effective interventions.

Diabetic uremic syndrome studied with cerebral MR spectroscopy and CT perfusion

Diabetic uremic syndrome (DUS) is an increasingly reported acute neurometabolic cerebral disease with characteristic clinical and imaging features. Clinical spectrum includes a wide range of movement disorders such as acute parkinsonism. Imaging studies show reversible (with hemodialysis) bilateral lesions in the lenticular nuclei. DUS pathophysiology has not been entirely clarified yet. Our case study shows certainly that LN lesions are characterized with increased lactate peak with MR spectroscopy and decreased perfusion in computerized tomography perfusion along with increased diffusion with apparent diffusion coefficient (ADC) mapping in the subacute phase of the syndrome. Abnormalities were almost normalized quickly after metabolic control by hemodialysis. Together with reports indicating that a deficit of glucose use exacerbated with acute increase of uremic toxins in bilateral LN, observed changes (lactate peak and hypoperfusion) led us to state that a primary metabolic depression may cause this syndrome. Metabolic depression is probably due to uncompensated uremic toxin accumulation related mitochondrial supression and/or dysfunction. This definition fits well to the other elements of DUS such as ADC evolution and marked lesion regression. Our single case study is not supportive of other previously credited mechanisms such as microvascular dysfunction related focal ischemia or hypoperfusion, prolonged uremic toxin related histotoxic hypoxia, central pontine myelinolysis-like demyelination and posterior leukoencephalopathy spectrum disorder related vasogenic edema.

Lateral entorhinal modulation of piriform cortical activity and fine odor discrimination.

The lateral entorhinal cortex (LEC) receives direct input from olfactory bulb mitral cells and piriform cortical pyramidal cells and is the gateway for olfactory input to the hippocampus. However, the LEC also projects back to the piriform cortex and olfactory bulb. Activity in the LEC is shaped by input from the perirhinal cortices, hippocampus, and amygdala, and thus could provide a rich contextual modulation of cortical odor processing. The present study further explored LEC feedback to anterior piriform cortex by examining how LEC top-down input modulates anterior piriform cortex odor evoked activity in rats. Retrograde viral tracing confirmed rich LEC projections to both the olfactory bulb and piriform cortices. In anesthetized rats, reversible lesions of the ipsilateral LEC increased anterior piriform cortical single-unit spontaneous activity. In awake animals performing an odor discrimination task, unilateral LEC reversible lesions enhanced ipsilateral piriform cortical local field potential oscillations during odor sampling, with minimal impact on contralateral activity. Bilateral LEC reversible lesions impaired discrimination performance on a well learned, difficult odor discrimination task, but had no impact on a well learned simple odor discrimination task. The simple discrimination task was impaired by bilateral reversible lesions of the anterior piriform cortex. Given the known function of LEC in working memory and multisensory integration, these results suggest it may serve as a powerful top-down modulator of olfactory cortical function and odor perception. Furthermore, the results provide potential insight into how neuropathology in the entorhinal cortex could contribute to early olfactory deficits seen in Alzheimer's disease.

Ultrasonic Stimulation of the Cholinergic Anti-Inflammatory Pathway for Renal Protection

AKI encompasses a large spectrum of pathophysiological processes starting from the early reversible proximal tubular lesion to the definite loss of glomerular filtration and even death. Even discrete AKI ( i.e. , ≥0.3 mg/dl increase in serum creatinine in humans) has been reported to be associated

A Case of Nonconvulsive Status Epilepticus with a Reversible Contralateral Cerebellar Lesion: Temporal Changes in Magnetic Resonance Imaging and Single-Photon Emission Computed Tomography Finding

A 67-year-old woman was brought to our institution because of unconsciousness. Clinical and electrophysiological findings lead us to diagnose her with nonconvulsive status epilepticus. Initial magnetic resonance imaging revealed hyperintensity in the left cerebral cortex and the right cerebellum on diffusion-weighted image and fluid-attenuated inversion recovery (FLAIR). Single-photon emission computed tomography showed increased blood flow in the left frontal cerebrum but not in the right cerebellum. The hyperintensity in the left cerebrum on the follow-up FLAIR was still present. The contralateral cerebellum remained undamaged even though the blood flow was not increased in this region because the excitotoxicity there was far lesser than that in the cerebrum.

Reversible Splenic Lesion in a Patient with Febrile Infection-Related Epilepsy Syndrome (FIRES)

Febrile infection-related epilepsy syndrome (FIRES) is a severe epileptic syndrome that manifests with refractory seizures or status epilepticus in previously healthy children after banal febrile illness. The neuroimaging findings in the acute phase of FIRES are nonspecific or normal. We report the case of a 7-year-old boy with FIRES who presented with a reversible lesion in the splenium of the corpus callosum on brain magnetic resonance imaging (MRI). The patient developed clusters of clonic seizures with a deviation of the eyes after a 3-day history of fever. A reversible splenial lesion was observed on brain MRI and, therefore, the initial diagnosis was mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). However, the intractable complex partial seizures necessitated a long-term midazolam infusion, indicating that FIRES was a more likely diagnosis than MERS. All other findings of this patient met the diagnostic criteria for FIRES. With this diagnosis, a high-dose phenobarbital was administrated, and the seizures were successfully controlled. This case indicated that FIRES should be considered even in patients with a reversible splenial lesion associated with encephalitis/encephalopathy.