Visual evoked potentials as a method for the prospective assessment of tacrolimus neurotoxicity in patients after kidney transplantation.

INTRODUCTION: Neurotoxicity, including optic nerve injury, is one of the most common adverse effects of tacrolimus, the principal calcineurin inhibitor used after kidney transplantation (KTx). The electrophysiologic measurements of both pattern visual evoked potentials (PVEP) and flash visual evoked potentials (FVEP) are valuable when drug-induced optic neuropathy is suspected. OBJECTIVES: To determine whether VEP measurement is a sensitive and repeatable method for monitoring tacrolimus neurotoxicity. MATERIAL AND METHODS: This prospective study focused on 35 patients (20 M, 15F, 69 eyes, mean age 43 ± 11 years) who were at a median of 3.0 (IQR, 2.2-3.7) months after KTx at the time of the initial VEP evaluation and were treated with tacrolimus since KTx. The follow-up VEP examination was done after a median of 24 (22-27) months (both VEP measurements followed the ISCEV standards). The P100 wave latency and amplitude for the 1° and 15' PVEP simulations, and the P2 wave latency and amplitude for the FVEP were analyzed. RESULTS: For the 1° checks, the P100 wave latency and amplitude values were significantly worse in the follow-up examination compared to the early post-transplant time-point. Independent associations between FVEP parameters and the tacrolimus blood trough level were observed in the follow-up examination but not at the early post-transplant period. The P2 wave latency correlated with the tacrolimus trough level only in patients treated with the twice-daily, but not the once-daily, tacrolimus formulation. The brain derived neurotrophic factor (BDNF) level correlated with the P100 (15') latency (R = 0.499; p = 0.005) and the P2 latency (R = 0.409; p = 0.025) only in patients treated with the once-daily, but not the twice-daily, tacrolimus formulation. CONCLUSION: The observations in this study may support the rationale for the use of VEP measurements as non-invasive monitoring of subclinical tacrolimus neurotoxicity.

Flash visual evoked potentials (FVEP) in various stimulation conditions.

AIM: To compare flash visual evoked potentials (FVEP) elicited using a Ganzfeld bowl (G), Mini Ganzfeld (MG) and Flash Goggles (GG) with eyes open and closed. PATIENTS AND METHOD: The study group comprised 17 volunteers with mean age of 30 years; all of them were examined with the Roland Consult electrophysiological diagnostic system. Active electrodes were placed at O1 and O2. With the G and MG stimulators, the flash generated by white-light-emitting diodes (LEDs) presented standard flash of 3 cd s m-2. The GG used red LED flash of 3 cd s m-2. Stimulus frequency of 1.0 Hz, low-pass filter of 1.0 Hz and high-pass filters of 100 Hz (G); 50 Hz (MG); 30 Hz (GG) were used. P2 amplitude and latency were compared by the means of the Wilcoxon matched-pairs signed-rank test. RESULTS: After right eye stimulation (from O1; n = 17), the mean amplitudes of P2, elicited with the G, MG and GG, were 13, 7 and 10 µV, respectively. The respective latencies were 129, 114 and 110 ms. Hence, the difference between the results obtained with these stimulators was statistically significant (p < 0.05). The mean P2 amplitudes, acquired by the means of the G, MG and GG, were 13 µV, 7 µV and 10 µV for open eyes, and 11 µV, 8 µV and 8 µV for closed eyes. The respective latencies were 129, 114 and 110 ms for eyes open, and 127, 125 and 121 ms for eyes closed. These results of the MG (latency only) and GG (latency and amplitude) stimulation differed significantly (p < 0.05). CONCLUSION: The amplitudes and latencies of the FVEP P2 elicited with different stimulators are not suitable for comparison. Closing the eye during the examination had a significant effect on the components of FVEP waveform elicited with the Flash Goggle and on the latency of P2 elicited with the MG.

Visual evoked potentials in diagnostics of optic neuropathy associated with renal failure.

Chronic renal failure is associated with many neurological complications. Due to accumulation of uremic neurotoxins axonal degeneration with its secondary demyelination occurs, which results in development of polineuropathy in 60­100% of patients with chronic renal failure. One of the most severe peripheral neuropathy is optic neuropathy. It is associated with visual deterioration and reduction in quality of life. Symptoms of the optic neuropathy may appear either before or after dialysis therapy. They often worsen after renal transplant, probably due to immunosuppressive regimen. Early diagnostics of the optic neuropathy became possible by using visual evoked potentials (VEP). This reliable, sensitive and noninvasive technique provides a direct measure of subclinical impairment of visual pathways. Among hemodialysed or immunosupressed patients one can observe abnormal VEP parameters - especially prolonged latency of the P100 component, less often fluctuation of its amplitude. These alterations are pronounced even if clinical examination reveals no abnormalities. This review presents a summary of current use of visual evoked potentials in monitoring of patients with chronic renal failure.

Isolated retinal astrocytic hamartoma with 7-year follow-up: A case report.

RATIONALE: Retinal astrocytic hamartoma (RAH) is a rare benign tumor originating from astrocytic cells located in the neural cell layer of the retina. It is commonly seen in patients with phakomatoses such as tuberous sclerosis complex or neurofibromatosis, rarely as an isolated retinal mass. This lesion is usually asymptomatic; however, these located in the area of the optic nerve, macula, or exhibiting the features of exudation, neovascularization may present visual disturbances and decreased visual acuity. PATIENT CONCERNS: We present a rare case of a 15-year-old boy, with no significant past medical history, whose cause of visual disturbances turned out to be isolated RAH. DIAGNOSES: Based on the results of color images of the fundus, fluorescein angiography as well as the analysis of magnetic resonance imaging, the patient was diagnosed with RAH. INTERVENTIONS: Additionally an B-scan ultrasonography, static and kinetic perimetry were performed. OUTCOMES: Fundoscopic examination showed a unilateral yellowish, well-circumscribed, mulberry-like lesion with a wide base, located in inferosnasal quadrant, in the vinicity of the optic nerve. The patient underwent neurological, pediatric, and genetic evaluations that excluded other pathological findings or underlying systemic disease. LESSONS: The prognosis for RAH is generally good, however, the lesion requires regular ophthalmologic follow-up to rule out the progression of the tumor mass. The patient 7-year follow-up history is without evidence of tumor growth, local or general deterioration of the condition.

Ocular features in Aicardi syndrome: A case report.

RATIONALE: Aicardi syndrome is a genetic malformation syndrome with a triad of dysgenesis or agenesis of the corpus callosum, distinctive chorioretinal lacunae and infantile spasms. It is a rare developmental disorder first described in 1965. The disease affects 1 in 100,000 live births. PATIENT CONCERNS: We describe a 34-month-old girl diagnosed with Aicardi Syndrome. DIAGNOSIS: Based on the results of color images of the fundus, medical history as well as the analysis of karyotype and DNA microarrays, the patient was diagnosed with Aicardi's syndrome. INTERVENTIONS: Additionally an B-scan ultrasonography and an electrophysiological test was performed. OUTCOME: Fundoscopic examination revealed optic disc colobomas in both eyes, extensive chorioretinal lacunae at the posterior pole with retinal pigment epithelium regrouping and atrophy. Flash visual evoked potentials (FVEP) P2 amplitude was lower than normal range. B-scan ultrasonography revealed an optic disc lesion consistent with optic disk coloboma. LESSONS: Children with congenital central nervous system malformations should undergo regular ophthalmic checkups to facilitate diagnosis and determine prognosis of visual function development.

The Effect of Maintenance Treatment with Twice-Daily or Prolonged Once-Daily Tacrolimus Formulation on Visual Evoked Potentials in Stable Kidney Transplant Recipients.

In kidney transplant recipients (KTRs), uraemia-induced central nervous system damage partly subsides, while the long-lasting exposure to tacrolimus may cause pathologic visual evoked potentials (VEP) findings, which have not been investigated yet. Thus, the aim of the present study was to assess the effect of tacrolimus maintenance treatment on bioelectrical function of optic nerves in stable KTRs. Sixty-five stable KTRs were enrolled, including 30 patients treated with twice-daily (Prograf) and 35 patients treated with prolonged once-daily (Advagraf) tacrolimus formulation. In all patients, pattern and flash VEP measurements were performed. Tacrolimus dosing and exposure were also analyzed. Overall, 129 eyes were analyzed. In pattern VEP, both (1°) and (15') latencies of P100 waves were significantly longer, whereas (1°) and (15') amplitudes were lower in the Advagraf group as compared with the Prograf group. Multivariate regression analyses revealed that the use of Advagraf (vs. Prograf) was independently associated with longer (1°) and (15') P100 latencies and lower corresponding amplitudes, whereas log tacrolimus daily dose was only related to amplitudes in a whole study group. In flash VEP, log tacrolimus trough level was associated with negative changes in P2 wave amplitude irrespective of tacrolimus formulation, whereas its association with P2 latency was observed only in the Prograf group. Both the type of tacrolimus formulation and drug exposure influenced the VEP parameters in stable KTRs.

The age of developing diabetes and FTO polymorphisms (rs9939609, rs1421085, and rs9930506).

INTRODUCTION: Type 2 diabetes (T2DM) is a common complex metabolic disorder that has a strong genetic predisposition. Fat mass and obesity-associated protein (FTO) is one of the genes of interest to us. Hypomethylation of a CpG site in the FTO gene was significantly associated with the risk of T2DM. The aim of the study was to find the answer to the question of whether the polymorphism changes of the FTO gene in the pathogenesis of type 2 diabetes are comparable in young, middle aged, and elderly people. MATERIAL AND METHODS: The study involved 282 consecutive patients with type 2 diabetes, who attended a primary healthcare clinic in Southern Poland. The study subjects were divided into three groups according to the age at which type 2 diabetes mellitus was diagnosed (> 40 years old, 40-60 years old, and > 60 years old). The genotyping of rs9939609, rs1421085, and rs9930506 FTO polymorphisms was conducted using TaqManPre-designed SNP Genotyping Assay. RESULTS: No statistically significant difference was shown between the examined FTO polymorphism (rs9939609, rs1421085, and rs9930506) distribution between the subjects diagnosed with diabetes < 40 years , 40-60 years, and > 60 years old. CONCLUSIONS: There were no statistically significant relationships between the different analysed anthropometric and other parameters and distribution of examined FTO polymorphisms (rs9939609 , rs1421085, and rs9930506). The age of diabetes was not affect by the tested FTO polymorphisms (rs9939609 , rs1421085, and rs9930506).