The Relationship between Lumbar Puncture Opening Pressure and Retinal Nerve Fiber Layer Thickness in the Diagnosis of Idiopathic Intracranial Hypertension: Is a Lumbar Puncture Always Necessary?

OBJECTIVES: Idiopathic intracranial hypertension (IIH), is characterized by elevated intracranial pressure (ICP) without an identified cause. Today, lumbar puncture (LP) is the most common method used for diagnosis by measuring cerebrospinal fluid (CSF) pressure to reflect intracranial pressure. This invasive examination has significant disadvantages, such as complications and negative experiences for patients. Therefore, noninvasive methods for ICP measurement are desired. Optical coherence tomography (OCT) is widely used for the diagnosis and follow-up of IIH patients as it reflects papilledema. The aim of this study is to investigate the relationship between CSF pressure and OCT parameters and the ability of OCT in the diagnostic approach. METHODS: In our study, patients who were followed up with a diagnosis of IIH with complete neuro-ophthalmological examinations, including visual acuity (VA), visual field, and OCT imaging within 24 hours before lumbar puncture, were retrospectively evaluated. CSF pressure, visual acuity LogMAR, mean deviation of visual fields, retinal nerve fiber layer (RNFL) thickness measured by OCT, and treatment protocols were obtained from our hospital data system. RESULTS: A total of 42 eyes of 21 patients were enrolled in the study. A statistically significant positive and moderate correlation was found between CSF pressure values and average RNFL thickness ( r =0.507; P =0.001). The same relationship was demonstrated in all 4 quadrants: inferior, superior, nasal, and temporal. CONCLUSIONS: Increased peripapillary RNFL thickness in optic nerve head OCT may be correlated with increased ICP in IIH patients. A larger number of patients are needed to better understand the correlation between OCT parameters and CSF pressure in patients with IIH.

Mild Encephalitis/Encephalopathy with a Reversible Lesion in The Splenium.

Mild encephalitis/encephalopathy with a reversible lesion in the splenium (MERS) is a clinico-radiological syndrome with mild central nervous system symptoms and a reversible lesion in the splenium of the corpus callosum. It is mainly associated with a number of viral and bacterial infections, including Coronavirus disease 2019 (COVID-19). In this paper, we report four MERS patients. One had a mumps infection, the second had aseptic meningitis, the third had Marchiafava-Bignami disease, and the fourth had atypical pneumonia associated with COVID-19 infection.

Autoimmune encephalitis and paraneoplastic syndromes in Turkey: a multi-centre study.

BACKGROUND: Autoimmune encephalitis (AIE) and paraneoplastic syndromes (PNS) are both rare groups of neurological diseases that are difficult to diagnose. AIM: We aimed to determine the common and distinct aspects of these two aetiologies of encephalitis as well as the characteristics of our patient group. METHODS: We respectively analysed the records of the patients including symptoms, demographic features, neurological examination, cranial-magnetic-resonance-imaging (MRI), electroencephalography (EEG) findings, cerebrospinal fluid results (CSF) findings. Autoimmune/paraneoplastic autoantibodies in blood and/or CSF were all documented. RESULTS: Forty-six patients fulfilled the diagnostic criteria. Thirty-eight of them were diagnosed with AIE, and 8 of them were diagnosed with PNS. The PNS group had higher nonconvulsive status epilepticus than the AIE (2/8 vs 0/38; p=0.027). PNS patients were diagnosed with a malignancy in their follow-ups more than those in the AIE group [4/38 vs 8/8] (p<0.001). When the symptoms of antibody-positive and negative patients were compared in the AIE group, the rates of consciousness/memory problems (13/15 vs 11/23; p=0.020) and speech impairment (8/15 vs 2/23; p=0.004) were significantly higher in patients without antibodies (n: 15) than in antibody-positive patients (n: 23). In antibody-negative groups, the rates of memory problems in neurological examination (13/15 vs 12/23 p=0.028) and temporal findings on electroencephalography were more prominent than antibody-positive groups (1/23 vs 5/15; p=0.027). The number of patients with cerebellar signs was higher in antibody-positive patients (6/23 vs 0/15; p=0.038). CONCLUSION: Although the positivity of autoantibodies is critical in the diagnosis of AIE and PNS, even minor differences in clinical and laboratory findings of patients are helpful in the diagnosis, especially in the autoantibody-negative patients. Comparing the data with other population studies has shown that several inherited and environmental factors may contribute to the pathophysiology of AIE and PNS, as well as clinical and laboratory differences.

Parry-Romberg syndrome: is it a "relapsing-remitting" disease?

Parry-Romberg syndrome, also known as progressive hemifacial atrophy, is a rare, slowly progressive disorder characterized by unilateral, painless atrophy of the skin and subcutaneous tissue of the face. Neurological manifestations such as epilepsy, migraine and trigeminal neuralgia are relatively common and accompany in 15-20% of cases. Various etiologies such as infection, trauma, embryonic developmental dysfunction, sympathetic dysfunction and autoimmune disorders have been suggested as possible causes. Here we describe a 37-year-old woman whose disease manifested with dynamic contrast enhanced white matter changes over a period of two years, suggesting a "relapsing-remitting" course. Besides the inflammatory activity, positive serum-autoantibodies, inflammatory findings in cerebrospinal fluid, and an overlapping systemic autoimmune disorder may further support the hypothesis of autoimmune-inflammatory mediated pathogenesis.

A variant of Guillain-Barre syndrome after SARS-CoV-2 vaccination: AMSAN.

Introduction - Coronavirus disease 2019 (COVID-19) is a respiratory infection that has rapidly become a global pandemic and vaccines against SARS-CoV-2 have been developed with great success. In this article, we would like to present a patient who developed Guillain-Barré syndrome (GBS), which is a serious complication after receiving the inactive SARS-CoV-2 vaccine (CoronaVac). Case report - A 76-year-old male patient presented to the emergency department with nine days of progressive limb weakness. Two weeks prior to admission, he received the second dose of CoronaVac vaccine. Motor examination revealed decreased extremity strength with 3/5 in the lower extremities versus 4/5 in the upper extremities. Deep tendon reflexes were absent in all four extremities. Nerve conduction studies showed predominantly reduced amplitude in both motor and sensory nerves, consistent with AMSAN (acute motor and sensory axonal neuropathy). Conclusion - Clinicians should be aware of the neuro-logical complications or other side effects associated with COVID-19 vaccination so that early treatment can be an option.

Prognostic Significance of Fragmented QRS in Patients with Acute Ischemic Stroke.

OBJECTIVES: There are studies in the literature showing the clinical importance of fragmented QRS (fQRS) in many systemic diseases. In this study, we aimed to investigate the frequency and prognostic value of fQRS on electrocardiogram (ECG) in patients with acute ischemic stroke. MATERIALS AND METHODS: We prospectively enrolled 241 patients with acute ischemic stroke between January 2018 and January 2020. ST depression and elevation, QRS duration, PR interval, RR interval, QTc interval, QTc dispersion (QTcd), T negativity, Q wave, and fQRS were evaluated on ECG. Brain computed tomography (CT) and diffusion magnetic resonance imaging (MRI) images were obtained in the acute period and the National Institute of Health Stroke Scale (NIHSS) score was calculated for each patient. Patients were followed up for a period of two years. RESULTS: The 241 patients comprised 121 (50.2%) men and 120 (49.8%) women with a mean age of 67.52 ± 13.00 years. In Cox regression analysis, age, NIHSS, QTcd, and fQRS were found to be independent predictors of mortality (age, hazard ratio [HR]: 1.063, p < 0.001; NIHSS, HR: 1.116, p = 0.006; QTcd, HR: 1.029, p = 0.042; fQRS, HR: 2.048, p = 0.037). Two-year mortality was higher in patients with fQRS than in patients without fQRS (31% vs. 9%, p = 0.001). CONCLUSIONS: The fQRS is associated with poor prognosis in patients with acute ischemic stroke.

Sars-Cov-2 infection related inflammatory and demyelinating disease; a brief case series.

BACKGROUND: Since March 2020, during the Coronavirus disease 2019 (COVID-19) pandemic, it has been observed that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has neurological involvement with various clinical tables. METHODS: We present 3 new cases admitted to our clinic with various neurological findings which were affected by SARS-CoV-2. RESULTS: Imaging studies have shown that inflammatory/demyelinizing lesions appeared in different areas of the central nervous system which were accepted as an atypical demyelinating spectrum associated with Covid 19. CONCLUSIONS: With increasing experience, it has been suggested that SARS-CoV-2 may also have a neurotrophic effect. The spectrum of neurological involvement is also expanding as the pandemic continues. These 3 cases suggest that the virus plays a role in the clinical onset of the inflammatory/demyelinating disease.

Adie-Holmes syndrome associated with COVID-19 infection: A case report.

With increasing experience, it has been suggested that the SARS-CoV-2 virus has a neurotropic effect. Here, we present a case of a tonic pupil who developed after COVID-19 infection. A 36-year-old woman presented with progressive photophobia and blurred vision. On neurological examination, loss of deep tendon reflexes accompanying a tonic pupil was detected and brain MR imaging was normal. With this case, we aimed to describe a rare pattern of neurological involvement caused by the possible SARS-CoV-2 virus.

Comparing Colored and White-Black Visual Evoked Potentials in Multiple Sclerosis Patients.

INTRODUCTION: We compared white-black (WB), white-red (WR), and black-red (BR) checkerboard stimulated visual evoked potentials (VEPs) in multiple sclerosis (MS) patients and aimed to evaluate if redcolored VEP is more sensitive than WB VEP for the diagnosis of optic neuritis (ON). METHODS: Twenty-nine MS patients (21 females [72.4%]) and 35 healthy control subjects (24 females [68.6%]) were included in the study. Neurological and ophthalmological examinations were conducted for all subjects and VEP and optical coherence tomography (OCT) investigations were performed. RESULTS: A significant difference was found between MS patients and the control group for WB, WR, BR stimulated VEP P100 latencies and retinal nerve fiber length (RNFL) and ganglion cell complex (GCC) thicknesses, but there was no difference for WB, WR, and rb stimulated VEP amplitude values between the groups. There was no significant pathological difference between the eyes with an ON history in MS and eyes without an ON history in MS and control subjects after WB, WR, and BR stimulation (p=). CONCLUSIONS: The WB checkerboard stimulated VEP is an ample test for routine use; further studies are necessary regarding the utility of rb stimulated VEP in detecting subclinical ON.

Comparative analysis of fingolimod versus teriflunomide in relapsing-remitting multiple sclerosis.

BACKGROUND: Fingolimod and teriflunomide are commonly used in the treatment of relapsing-remitting multiple sclerosis (RRMS). These have not been compared in controlled trials, but only in observational studies, with inconclusive results. Comparison of their effect on relapse and disability in a real-world setting is therefore needed. OBJECTIVES: The objective of this study was to compare the efficacy of fingolimod and teriflunomide in reducing disease activity in RRMS. METHODS: This multicenter, retrospective observational study was carried out with prospectively collected data from 15 centers. All consecutive RRMS patients treated with teriflunomide or fingolimod were included. Data for relapses, Expanded Disability Status Scale (EDSS) scores and brain magnetic resonance imaging (MRI) scans were collected. Patients were matched using propensity scores. Annualized relapse rates (ARR), disability accumulation, percentage of patients with active MRI and treatment discontinuation over a median 2.5-year follow-up period were compared. RESULTS: Propensity score matching retained 349 out of 1388 patients in the fingolimod group and 349 out 678 in the teriflunomide group for final analyses. Mean ARR decreased markedly from baseline after 1 and 2 years of treatment in both the fingolimod (0.58-0.17 after 1 year and 0.11 after 2 years, p < 0.001) and teriflunomide (0.56-0.29 after 1 year and 0.31 after 2 years, p < 0.001) groups. Mean ARR was lower in fingolimod-treated patients than in those treated with teriflunomide at years 1 (p = 0.02) and 2 (p = 0.004). Compared to teriflunomide, the fingolimod group exhibited a higher percentage of relapse-free patients and a lower percentage of MRI-active patients after 2.5-year follow-up. Disability worsening was similar between the two groups. Patients were less likely to discontinue fingolimod than teriflunomide (p < 0.001). CONCLUSION: Fingolimod was associated with a better relapse control and lower discontinuation rate than teriflunomide. The two oral therapies exhibited similar effects on disability outcomes.

Optic neuritis as an early sign of multiple sclerosis.

Optic neuritis (ON) is an acute inflammatory demyelinating disorder of the optic nerve. The general characteristics of isolated ON include unilateral, subacute, and painful visual loss without systemic or other neurological symptoms. The etiology for ON varies including demyelinating disorders or infections, inflammation, toxic reasons, and genetic disorders. In most cases the responsible etiology may not be known for ON and in this case, it is termed idiopathic ON. When a patient presents with an initial episode of ON, patients should undergo further tests. Assessing the patient with routine blood work, magnetic resonance imaging, cerebrospinal fluid tests, and visual evoked potentials provide further insight. In this review, we aimed to provide a review of ON as an initial symptom of multiple sclerosis and present clinical characteristics, therapy options, and recent literature.

Clinical and pathological insights into the dynamic nature of the white matter multiple sclerosis plaque.

OBJECTIVE: An extensive analysis of white matter plaques in a large sample of multiple sclerosis (MS) autopsies provides insights into the dynamic nature of MS pathology. METHODS: One hundred twenty MS cases (1,220 tissue blocks) were included. Plaque types were classified according to demyelinating activity based on stringent criteria. Early active, late active, smoldering, inactive, and shadow plaques were distinguished. A total of 2,476 MS white matter plaques were identified. Plaque type distribution was analyzed in relation to clinical data. RESULTS: Active plaques were most often found in early disease, whereas at later stages, smoldering, inactive, and shadow plaques predominated. The presence of early active plaques rapidly declined with disease duration. Plaque type distribution differed significantly by clinical course. The majority of plaques in acute monophasic and relapsing-remitting MS (RRMS) were active. Among secondary progressive MS (SPMS) cases with attacks, all plaque types could be distinguished including active plaques, in contrast to SPMS without attacks, in which inactive plaques predominated. Smoldering plaques were frequently and almost exclusively found in progressive MS. At 47 years of age, an equilibrium was observed between active and inactive plaques, whereas smoldering plaques began to peak. Men displayed a higher proportion of smoldering plaques. INTERPRETATION: Disease duration, clinical course, age, and gender contribute to the dynamic nature of white matter MS pathology. Active MS plaques predominate in acute and early RRMS and are the likely substrate of clinical attacks. Progressive MS transitions to an accumulation of smoldering plaques characterized by microglial activation and slow expansion of pre-existing plaques. Whether current MS therapeutics impact this pathological driver of disease progression remains uncertain.

Poor early relapse recovery affects onset of progressive disease course in multiple sclerosis.

OBJECTIVE: To evaluate the relationship between early relapse recovery and onset of progressive multiple sclerosis (MS). METHODS: We studied a population-based cohort (105 patients with relapsing-remitting MS, 86 with bout-onset progressive MS) and a clinic-based cohort (415 patients with bout-onset progressive MS), excluding patients with primary progressive MS. Bout-onset progressive MS includes patients with single-attack progressive and secondary progressive MS. "Good recovery" (as opposed to "poor recovery") was assigned if the peak deficit of the relapse improved completely or almost completely (patient-reported and examination-confirmed outcome measured ≥6 months post relapse). Impact of initial relapse recovery and first 5-year average relapse recovery on cumulative incidence of progressive MS was studied accounting for patients yet to develop progressive MS in the population-based cohort (Kaplan-Meier analyses). Impact of initial relapse recovery on time to progressive MS onset was also studied in the clinic-based cohort with already-established progressive MS (t test). RESULTS: In the population-based cohort, 153 patients (80.1%) had on average good recovery from first 5-year relapses, whereas 30 patients (15.7%) had on average poor recovery. Half of the good recoverers developed progressive MS by 30.2 years after MS onset, whereas half of the poor recoverers developed progressive MS by 8.3 years after MS onset (p = 0.001). In the clinic-based cohort, good recovery from the first relapse alone was also associated with a delay in progressive disease onset (p < 0.001). A brainstem, cerebellar, or spinal cord syndrome (p = 0.001) or a fulminant relapse (p < 0.0001) was associated with a poor recovery from the initial relapse. CONCLUSIONS: Patients with MS with poor recovery from early relapses will develop progressive disease course earlier than those with good recovery.

Relapses and disability accumulation in progressive multiple sclerosis.

OBJECTIVE: We examined the effect of relapses-before and after progression onset-on the rate of postprogression disability accrual in a progressive multiple sclerosis (MS) cohort. METHODS: We studied patients with primary progressive MS (n = 322) and bout-onset progressive MS (BOPMS) including single-attack progressive MS (n = 112) and secondary progressive MS (n = 421). The effect of relapses on time to Expanded Disability Status Scale (EDSS) score of 6 was studied using multivariate Cox regression analysis (sex, age at progression, and immunomodulation modeled as covariates). Kaplan-Meier analysis was performed using EDSS 6 as endpoint. RESULTS: Preprogression relapses (hazard ratio [HR]: 1.63; 95% confidence interval [CI]: 1.34-1.98), postprogression relapses (HR: 1.37; 95% CI: 1.11-1.70), female sex (HR: 1.19; 95% CI: 1.00-1.43), and progression onset after age 50 years (HR: 1.47; 95% CI: 1.21-1.78) were associated with shorter time to EDSS 6. Postprogression relapses occurred in 29.5% of secondary progressive MS, 10.7% of single-attack progressive MS, and 3.1% of primary progressive MS. Most occurred within 5 years (91.6%) after progressive disease onset and/or before age 55 (95.2%). Immunomodulation after onset of progressive disease course (HR: 0.64; 95% CI: 0.52-0.78) seemingly lengthened time to EDSS 6 (for BOPMS with ongoing relapses) when analyzed as a dichotomous variable, but not as a time-dependent variable. CONCLUSIONS: Pre- and postprogression relapses accelerate time to severe disability in progressive MS. Continuing immunomodulation for 5 years after the onset of progressive disease or until 55 years of age may be reasonable to consider in patients with BOPMS who have ongoing relapses.

Assessment of structural and functional visual outcomes in relapsing remitting multiple sclerosis with visual evoked potentials and optical coherence tomography.

The purpose of this study is to consider the clinical utility of optical coherence tomography (OCT) and find a correlation with VEP. Effects of different disease modifying treatments (DMT) were further evaluated by measuring OCT parameters and whether a correlation exists between the RNFL thickness, disease duration and expanded disability status scale (EDSS) were also assessed. 13 patients were on interferon beta-1a (IFN), 14 patients were receiving glatiramer acetate (GA), 19 patients were not being treated with any DMT and 21 healthy controls were included the study. During OCT examination, retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness was found to be lower in all MS groups but macular volume (MV) was lower only in GA group than controls. Although, P100 latencies were longer than controls in all MS groups, there was no statistically significant difference between IFN and w/o DMT groups. Patients with ON history, P100 latencies were found significantly longer than those without ON. VEP amplitudes were found lower with ON history patients than those without ON, however this was not statistically significant. EDSS strongly correlated with P100 latency, RNLF, GCC but no correlation was observed with VEP amplitude and MV. Our results show that RNFL, GCC and MV were all decreased in MS patients with or without DMT comparing to controls and it is more prominent in eyes with ON. Further follow-up studies are warranted to understand the pathophysiology of CNS axonal degeneration and involvement of optic nerves.

Onset of progressive phase is an age-dependent clinical milestone in multiple sclerosis.

BACKGROUND: It is unclear if all patients with relapsing-remitting multiple sclerosis (RRMS) ultimately develop progressive MS. Onset of progressive disease course seems to be age- rather than disease duration-dependent. Some forms of progressive MS (e.g. primary progressive MS (PPMS)) are uncommon in population-based studies. Ascertainment of patients with PPMS from clinic-based populations can facilitate a powerful comparison of age at progression onset between secondary progressive MS (SPMS) and PPMS but may introduce unclear biases. OBJECTIVE: Our aim is to confirm that onset of progressive disease course is more relevant to the patient's age than the presence or duration of a pre-progression relapsing disease course in MS. METHODS: We studied a population-based MS cohort (n=210, RRMS n=109, progressive MS n=101) and a clinic-based progressive MS cohort (n=754). Progressive course was classified as primary (PPMS; n=322), single attack (SAPMS; n=112) and secondary progressive (SPMS; n=421). We studied demographics (chi(2) or t-test), age-of-progression-onset (t-test) and time to Expanded Disability Status Scale of 6 (EDSS6) (Kaplan-Meier analyses). RESULTS: Sex ratio (p=0.58), age at progression onset (p=0.37) and time to EDSS6 (p=0.16) did not differ between the cohorts. Progression had developed before age 75 in 99% of patients with known progressive disease course; 38% with RRMS did not develop progression by age 75. Age at progression onset did not differ between SPMS (44.9±9.6), SAPMS (45.5±9.6) and PPMS (45.7±10.8). In either cohort, only 2% of patients had reached EDSS6 before onset of progression. CONCLUSIONS: Patients with RRMS do not inevitably develop a progressive disease course. Onset of progression is more dependent on age than the presence or duration of a pre-progression symptomatic disease course. Moderate disability is sustained predominantly after the onset of a progressive disease course in MS.

Management of optic neuritis as a clinically first event of multiple sclerosis.

PURPOSE OF REVIEW: This article aims to provide a review of demyelinating optic neuritis as a presenting symptom of multiple sclerosis, clinical features, management options, and recent literature. RECENT FINDINGS: To date, several questions remain to be unsolved relating to the presentation, treatment, and implications of optic neuritis. Although some authors recommend high-dose corticosteroids for the treatment of acute demyelinating optic neuritis, there is still no consensus relating to corticosteroids treatment including the dosage and length of treatment. Studies have shown that the risk of developing clinically definite multiple sclerosis (MS) after presenting with a clinically isolated syndrome including optic neuritis is increased in patients with an abnormal brain MRI. Better diagnostic tools are needed to precisely predict the conversion to MS and the factors influencing disease severity to determine the most appropriate therapeutic paradigm and avoid unnecessary treatment. SUMMARY: Management of optic neuritis presenting as a demyelinating first event still remains inconclusive relating to the acute management and long-term treatment. But recent literature suggests high-dose corticosteroids for acute treatment and disease-modifying treatments may be a valuable option for long-term treatment. However, decision is very individualized and is based on the clinical and imaging findings of the patient.

Diagnosis and management of giant cell arteritis: a review.

PURPOSE OF REVIEW: This article aims to provide a review of giant cell arteritis (GCA) clinical features, differential diagnosis, treatment options, and recent literature. RECENT FINDINGS: GCA, first described by Horton et al., is a systemic immune-mediated vasculitis affecting medium-sized and large-sized arteries. Characteristic findings include headache, jaw claudication, visual loss, and constitutional symptoms (malaise, fever, weight loss, loss of appetite). Localized GCA symptoms are the end-result of vascular insufficiency and tissue ischemia. Temporal artery biopsy (TAB) remains the gold standard for diagnosis. Additional diagnostic tests include blood tests (erythrocyte sedimentation rate, ESR; C-reactive protein, CRP; platelets) and imaging modalities (ultrasound of the arteries; fluorescein angiography, FA; MRI; and positron emission tomography, PET). The mainstay of management includes high-dose corticosteroids, and additional cytotoxic drugs, antitumor necrosis factor monoclonal antibody, and antiplatelet aggregation therapy may be used. The goal of treatment is to prevent ischemic damage and halt progression of visual loss in the affected eye and prevent involvement of the fellow eye. SUMMARY: Further research is warranted concerning the immunogenetics of GCA. Further treatment trials are also needed to develop more specific and sensitive diagnostic tests and new corticosteroid-sparing treatment modalities.

Correlation of cumulative corticosteroid treatment with magnetic resonance imaging assessment of avascular femoral head necrosis in patients with multiple sclerosis.

Increased risk of osteoporosis, fractures, and avascular necrosis (AVN) has been suggested in multiple sclerosis (MS). Patients with MS are often exposed to corticosteroid treatment (CST) during the disease course and conflicting reports exist regarding complications of CST. Our study aims to investigate the association between cumulative doses of CST and radiographic evaluation of AVN of the femoral head in MS. Twenty-six MS patients (mean age, 38.4±10 yr) were enrolled and prospectively evaluated for AVN by magnetic resonance imaging (MRI). The mean disease duration was 11.5±8.5 years and mean expanded disability status scale (EDSS) score was 3±2. The cumulative dosage of CST varied between 20 g and 60 g; patients were grouped into two categories: 1) CST between 20-40 g, 17 (65%) patients; 2) CST ≥40 g; 9 (35%) patients. The relationship between cumulative CST dosage and MRI diagnosis of AVN was statistically insignificant (P>0.9). Clarification of the cumulative effect of CST in the development of AVN is of great importance for future long-term steroid treatment strategies.