Pyrroline-5-carboxylate reductase 2 (PYCR2) deficiency causes hereditary spastic paraplaegia in late childhood.

OBJECTIVES: PYCR2 gene variants are extremely rare condition which is associated with hypomyelinating leukodystrophy type 10 with microcephaly (HLD10). The aim of the present study is to report the clinical findings of patients having novel PYCR2 gene variant that manifest Hereditary Spastic Paraplegia (HSP) is the only symptom without hypomyelinating leukodystrophy. This is the first study that report the PYCR2 gene variants as a cause of HSP in late childhood. We believe it can contribute to expanding the spectrum of the phenotypes associated with PYCR2. METHODS: It is a retrospective study. Of the patients with similar clinical features from two related families, "patient 1" was designated as the index case, and was analyzed using Whole Exome Squence analysis (WES). The detected variation was investigated in the index case's parents, relatives, and sibling with a similar phenotype. Clinical, brain magnetic resonance (MR) images and MR spectroscopic findings of the patients were reported. RESULTS: A novel homozygous missense (NM_013328: c.383T > C, p.V128A) variant in the PYCR2 gene is detected in 5 patient from 2 related families. All the patients were male, their ages ranges from 6 to 26 years (15.58 ± 8,33 yrs). Developmantal milestones were normal without dysmorphic features. 4 (%80) patients exhibit mild intention tremor started at the age of approximately 6 years of age. 4 (%80) patients had gait difficulty and progressive lower limb spasticity started at the age of 8-12 years. White matter myelination was normal in all patients. Glycine peakes were detected on the MR spectroscopy in all patients. CONCLUSION: Some variants of PYCR2 gene are responsible for causing clinical features of HSP without hypomyelinating leukodystrophy in the pediatric patients.

Evaluation of long-term neurocognitive functions in patients with epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS)/epileptic encephalopathy with spike-and-wave activation in sleep (EE-SWAS).

OBJECTIVES: Epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS) or the newly named Epileptic encephalopathy with spike-and-wave activation in sleep (EE-SWAS) is a syndrome in which epileptiform abnormalities are associated with the progressive impairment of cognitive functions. This study aimed to evaluate the neurocognitive executive functions of patients at later ages and determine the long-term prognosis of the condition, as well as the factors affecting this. METHODS: This is a hospital-based cross-sectional study of 17 patients with a diagnosis of CSWS, and a minimum age of 7.5 years. The Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) was used for neurocognitive assessment. The use of immunotherapy (intravenous immunoglobulin and/or steroid for at least 6 months) at the time of initial diagnosis, baseline activity and spike wave index (SWI) of the last wake and sleep EEG, cranial MRI findings, active epileptic seizures since the last examination, and WISC-IV parameters were statistically compared. The results of patients with genetic etiology determined by the whole exome sequencing (WES) method are also reported. RESULTS: A total of 17 patients were included in the study, with a mean age of 10.30 ± 3.15 years (range from 7.9 to 15.8 years). The mean full scale IQ score of the subjects was 61.41 ± 17.81 (range 39-91), classified as follows: 5.9% (n = 1), average; 23.5% (n = 4), low average; 5.9% (n = 1), very low; 35.3% (n = 6), extremely low (upper range); 29.4% (n = 5), extremely low (lower range) intelligence. Among the four domains of WISC-IV, the most affected index was the Working Memory Index (WMI). EEG parameters, cranial MRI findings and treatment with immunotherapy did not have a significant effect on neurocognitive outcomes. Thirteen patients (76%) were evaluated with WES for a genetic etiology. Pathogenic variants in 5 different genes (GRIN2A, SLC12A5, SCN1A, SCN8A, ADGRV1) associated with epilepsy were detected in 5/13 patients (38%). CONCLUSION: These results indicated that neurocognition is highly affected in the long term in CSWS.

Novel, homozygous RAB3GAP1 c.2606 + 1G>A, p.Glu830ValfsTer9 variant and chromosome 3q29 duplication in a Turkish individual with Warburg micro syndrome.

Warburg micro syndrome (WARBM) is a rare, autosomal recessive, neurodevelopmental disorder characterized by microcephaly, cortical dysplasia, corpus callosum hypoplasia, congenital hypotonia leading to subsequent spastic quadriplegia, severe developmental delay and hypogenitalism. Ophthalmologic findings that may affect any ocular segment including characteristic, small, atonic pupils. WARBM is known to be caused by biallelic, pathogenic variants in at least five genes although additional genetic loci may exist. The RAB3GAP1 c.748 + 1G>A, p.Asp250CysfsTer24 founder variant has been described in families of Turkish ancestry. We report the clinical and molecular findings in three, unrelated, Turkish families with WARBM. A novel c.974-2A>G variant causing WARBM in three siblings of Turkish descent was found. Functional studies of the novel, c.2606 + 1G>A variant in patients' mRNA revealed skipping of exon 22 which results in a premature stop codon in exon 23. However, the clinical consequences of this variant are blended given that the individual also had a maternally inherited chromosome 3q29 microduplication.

The course of sleep habits in newly diagnosed epilepsy in children: A prospective study.

BACKGROUND: Epilepsy and sleep have a close, complex, and reciprocal relationship. Sleep may also be adversely affected by epilepsy and anti-seizure medication (ASM). This study sought to determine sleep-related problems before and after six months of treatment with ASMs follow-up in children with epilepsy, to reveal changes in sleep habits, and to determine the effect of ASMs on sleep in different types of epilepsy. METHODS: This is a prospective study that included 61 children, aged 4-18 years with newly diagnosed epilepsy, who regularly had follow-up checks and used ASM for six months, and completed the Children's Sleep Habits Questionnaire (CSHQ). Children's Sleep Habits Questionnaire was completed before and after six months of ASM, allowing for assessments based on treatment group and type of epilepsy. RESULTS: The mean ages of 61 children were 10.6 ± 3.9 years. The participants' post-treatment total scores on the CSHQ decreased by 2.9 ± 7.8 units on average compared to their pretreatment scores (p = 0.008; p < 0.01). In the levetiracetam group, post-treatment CSHQ subscale scores showed a mean decrease for bedtime resistance (p = 0.001), sleep duration (p = 0.005), sleep anxiety (p = 0.030), and total scores (p = 0.012) (p < 0.05). In the valproic acid group, post-treatment CSHQ subscale scores showed a mean decrease in sleep duration (p = 0.007) and a mean increase in daytime sleepiness (p = 0.03) (p < 0.05). CONCLUSION: Our study found that children diagnosed with epilepsy had significantly higher rates of pretreatment sleep problems, which significantly decreased in patients who regularly attended follow-up examinations and received treatment. Except for the daytime sleepiness factor, our study found that sleep-related problems improved with treatment. It was observed that the initiation of epilepsy treatment had a positive effect on the patient's sleep, regardless of the type of treatment or epilepsy.

Chromosomal microarray and exome sequencing in unexplained early infantile epileptic encephalopathies in a highly consanguineous population.

AIM: To identify genetic causes for early infantile epileptic encephalopathies (EIEE) in Turkish children with mostly consanguineous parents. METHODS: In a selected EIEE group (N = 59) based on results of nongenetic and initial genetic testing with unexplained etiology, 49 patients underwent array-based comparative genomic hybridization (aCGH) and 49 patients underwent whole exome sequencing (WES) including 39 with negative aCGH results and 10 with WES-only. RESULTS: Diagnostic yield of aCGH and WES for pathogenic or likely pathogenic variants was 14.3% and 38.8%, respectively. Including de novo variants of uncertain significance linked to compatible phenotypes, increased the diagnostic yield of WES to 61.2%. Out of 38 positive variants, 18 (47.4%) were novel and 16 (42.1%) were de novo. Twenty-one (56.8%) patients had recessive variants inherited from mostly consanguineous healthy parents (85.7%). Fourteen (37.8%) of patients with diagnostic results had positive variants in established EIEE genes. Seizures started during neonatal period in 32.4% patients. Posture or movement disorders were comorbid with EIEE in 40.5% of diagnosed patients. We identified treatable metabolic disorders in 8.1% of patients and pathogenic variants in genes which support using targeted medicine in 19% of patients. CONCLUSIONS: Detailed electro-clinical phenotyping led to expansion of some of the known phenotypes with non-neurological and neurological findings in addition to seizures, as well as suggestion of candidate genes (SEC24B, SLC16A2 and PRICKLE2) and a copy number variant (microduplication of Xp21.1p11.4). The high ratio of recessive inheritance could be important for family counseling.

Molecular characterization of Turkish patients with demyelinating Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth (CMT) disease represents a distinct subgroup of inherited peripheral neuropathies with a significant prevalence throughout the world and manifests both phenotypic and genetic heterogeneity. Electrophysiological studies subclassify CMT mainly as demyelinating or axonal types. In this study, we investigated the molecular characteristics of a Turkish cohort of 23 probands out of 34 symptomatic demyelinating CMT individuals from January 2019 to December 2021. In order to identify the underlying genetic cause, we applied a rational algorithm: PMP22 gene was initially analyzed for duplication, if PMP22-duplication testing was negative, other most causative genes (GJB1, MPZ) and PMP22 were then sequenced and if no variant was detected at aforementioned tests, whole exome sequencing (WES) test was finally performed. A total of 17 patients (≅ 74%; n = 23) were found to harbor a disease-causing variant in demyelinating CMT-related genes and among the variants, PMP22-duplication was the most frequent (≅ 41%). CMT1, CMTX, and CMT4 subtypes were manifested in ten, five, and two individuals respectively. GJB1 and SBF2 genes were the only detected genes associated with the CMTs other than CMT1. We also reported totally five novel variants: c.379A > C (p.Ile127Leu) and c.548G > T (p.Arg183Leu) variants in GJB1, c.988G > T (p.Glu330Ter) variant in NEFL, c.765_770delCCCTAT (p.Pro256_Ile257del) and c.2552A > C (p.His851Pro) variants in SBF2. As the understanding of pathophysiology and molecular mechanisms of CMT continues to evolve rapidly, many therapeutic strategy options including promising small-molecular compounds, gene replacement therapy, or disease-modifying therapies will soon be implemented in the clinical setting.

Auditory phoneme discrimination, articulation, and language disorders in patients with genetic epilepsy with febrile seizures plus: A case-control study.

INTRODUCTION: Genetic epilepsy with febrile seizures plus (GEFS+) is an epilepsy syndrome with clinical heterogeneity that was first described in 1997. Central auditory processing (CAP) is defined as the neurophysiological process in decoding sound waves from the outer ear to the auditory cortex. The present study aimed to analyze CAP and phonological disorders in preschool-age children with GEFS+. MATERIAL AND METHOD: This is a prospective case-control study. Twenty-seven patients diagnosed with GEFS+ aged between 4 years and 6 years and 6 months and 31 healthy controls in the same age range were included in the study. Phonological sensitivity test (SAT) and auditory discrimination test (IAT) were applied to both groups, and the results of both groups were statistically compared. RESULTS: The SAT and IAT raw and Z scores of the subjects in the study group were found to be significantly higher than those of the control group (p = 0.001; p < 0.01). Electroencephalography (EEG) status of the patients or the duration of antiseizure medication use did not have a statistically significant effect on the outcome. CONCLUSION: Patients with GEFS+ have a significantly high impairment in both articulation and auditory discrimination of phonemes compared with the healthy population. Early diagnosis and early treatment of this condition can prevent potential literacy problems and the development of dyslexia in the future.

HACE1, GLRX5, and ELP2 gene variant cause spastic paraplegies.

Hereditary spastic paraplegias (HSPs) are a clinically and genetically heterogeneous group of conditions that are characterized by lower limb spasticity and weakness. Considering the clinical overlap between metabolic causes, genetic diseases, and autosomal recessive HSP, differentiation between these types can be difficult based solely on their clinical characteristics. This study aimed to investigate the genetic etiology of patients with clinically suspected HSP. The study group was composed of seven Turkish families who each had two affected children and three families who each had a single affected child (17 total patients). The 17 probands (14 males, 3 females) underwent whole exome sequencing. Five typical HSP genes (FA2H, AP4M1, AP4E1, CYP7B1, and MAG) and three genes not previously related to HSP (HACE1, GLRX5, ad ELP2) were identified in 14 probands. Eight novel variants were identified in seven families: c.653 T > C (p.Leu218Pro) in the FA2H gene, c.347G > A (p.Gly116Asp) in the GLRX5 gene, c.2581G > C (p.Ala861Pro) in the HACE1 gene, c.1580G > A (p.Arg527Gln) and c.1189-1G > A in the ELP2 gene, c.10C > T (p.Gln4*) and c.1025 + 1G > A in the AP4M1 gene, c.1291delG (p.Gly431Alafs*3) and c.3250delA (p.Ile1084*) in the AP4E1 gene, and c.475 T > G (p.Cys159Gly) in the MAG gene. The growing use of next-generation sequencing improved diagnosis but also led to the continual identification of new causal genes for neurogenetic diseases associated with lower limb spasticity. The increasing number of HSP genes identified thus far highlights the extreme genetic heterogeneity of these disorders and their clinical and functional overlap with other neurological conditions. Our findings suggest that the HACE1, GLRX5, and ELP2 genes are genetic causes of HSP.

Neuropsychiatric comorbidities in genetic/idiopathic generalized epilepsies and their effects on psychosocial outcomes.

INTRODUCTION: Idiopathic/genetic generalized epilepsy (GGE) accounts for 15-20% of all epilepsy cases. Neuropsychiatric comorbidities and disorders, such as attention-deficit hyperactivity disorder (ADHD), academic failure, and poor social competence, are present at a higher rate in patients with epilepsy compared with the general population. In this study, we aimed to determine the frequency of neuropsychiatric comorbidities in GGE subgroups, and to reveal the risk factors in the patient group with neuropsychiatric comorbidities. MATERIAL AND METHOD: This hospital-based, cross-sectional study follows the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. Patients with seizure-controlled GGE were invited to a semi-structured interview at the hospital. Variables [photosensitivity, valproic acid (VPA) resistance, timing of the neuropsychiatric comorbidities Attention deficit and hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and low academic performance), seizure control, and timing of the antiepileptic treatment] were statistically analyzed and evaluated in terms of their association with GGE subgroups [Generalized tonic-clonic seizures alone (EGTGS), juvenile myoclonic epilepsy (JME), and juvenile absence epilepsy (JAE)], RESULTS: Total 101 patients with GGE were included in the study and the mean age was 13.94 ±â€¯1.66 years. A total of 12.9% (n = 13) of the patients had EGTGS, 49.5% (n = 50) had JME, and 37.6% (n = 38) had JAE. VPA resistance, photosensitivity, and the presence of neuropsychiatric symptoms before the starting of epilepsy were found to be risk factors in the GGE group with neuropsychiatric comorbidities compared with the group without neuropsychiatric comorbidities (p < 0.001). The subgroups of GGE did not show any relationship with psychiatric disorders, including ADHD, ODD, and low academic performance (neuropsychiatric comorbidities) (p > 0.005). No correlation was found between seizure control and decline in neuropsychiatric symptoms (p > 0.05). CONCLUSION: In this study, the onset of psychiatric symptoms prior to the onset of epilepsy, photosensitivity, and VPA resistance were the most important factors affecting neuropsychiatric comorbidities. The JME, JAE, and EGTCS subgroups, early initiation of antiepileptic treatment, and seizure control were found to have no effect on poor psychosocial outcome and neuropsychiatric comorbidities.

Comparison of brain F-18 FDG PET/MRI with PET/CT imaging in pediatric patients.

BACKGROUND: Standardized uptake values (SUVs) are important indexes for evaluating the accuracy of disease diagnoses achieved via fluoro-18 deoxyglucose (F-18 FDG) positron emission tomography/computed tomography (PET/CT) and positron emission tomography/magnetic resonance imaging (PET/MRI). The purpose of this study is to describe normal cerebral FDG uptake in the pediatric population and compare SUVmax/mean results for brain images obtained from PET/CT and PET/MRI in neurologically healthy pediatric examinees. METHODS: This study included 20 patients who were < 18 years of age and were without intracranial malignancy and/or brain disorders. Patients underwent either PET/CT imaging (n = 10) or PET/MRI imaging (n = 10) after 70-80 min of F-18 FDG injection. The SUVmax and SUVmean for various brain regions were calculated and compared between sides and imaging modalities using with appropriate statistical tests. RESULTS: The median SUVmax/SUVmean values of the right-sided frontal, parietal, temporal, and occipital lobes were 8.63/ 6.18, 8.85 / 6.97, 6.88 / 4.99, and 11.06 / 7.02 in PET/CT, respectively, and 11.45 / 8.59, 10.16 / 8.47, 8.82 / 6.6, and 11.71 / 8.25 in PET/MRI, respectively. The median SUVmax/SUVmean values of the left-sided frontal, parietal, temporal, and occipital lobes were 9.05 / 6.86, 8.03 / 6.62, 6.49 / 4.77, and 10.6 / 7.73 in PET/CT, respectively, and 10.7 / 8.16, 11.06 / 7.88, 8.13 / 6.09, and 10.96 / 9.22 in PET/MRI, respectively. CONCLUSIONS: These results showed that there was no statistically significant difference in SUVs values between the two brain imaging modalities except from SUVmax value of left-sided parietal lobe and no asymmetric radiopharmaceutical uptake between the left and right brain regions or cerebellums in each modality, suggested that in brain imaging, PET/MRI can be used reliably instead of PET/CT.

Active Giant Cell Vasculitis Diagnosis with 68Ga PSMA PET/CT Imaging.

Vasculitis is a multisystem disease characterized by inflammation with infiltration of leukocytes into the blood vessels. Giant cell arteritis (GCA) is the most common form of vasculitis that mostly affects medium- and large-sized arteries. 18Fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) is increasingly used to diagnose inflammation of large arteries in GCA. Galium-68 prostate-specific membrane antigen (PSMA) PET/CT has a vital role in the assessment of patients with prostate cancer for recurrence and metastasis of the disease. Various benign and non-prostate malignant conditions may give rise to increased PSMA uptake. Herein, we demonstrate that PSMA uptake can be seen in GCA.

Acute flaccid myelitis outbreak through 2016-2018: A multicenter experience from Turkey.

AIM: We aim to describe the demographic characteristics, etiology, neurophysiology, imaging findings, treatment, prognosis, and prognostic factors of acute flaccid myelitis. METHODS: The clinical data, laboratory test and, magnetic resonance imaging (MRI) results of pediatric patients diagnosed with acute flaccid myelitis according to the Centers for Disease Control criteria between August 1, 2016, and December 31, 2018, from 13 centers in Turkey were reviewed. RESULTS: Of the 34 cases identified, 31 were confirmed (91.2%). Eighteen patients (55.9%) were boys. The median patient age was 4 years (interquartile range 2.5-6.9 years). Most of the patients were admitted in 2018 (n = 27). A preceding history of a febrile illness was reported in all patients, with a median of 4 days (interquartile range 3-7 days) before symptom onset. Thirty-one patients had T2 hyperintensity on spinal MRI, and 18 patients had cerebrospinal fluid pleocytosis. The most common infectious agents were entero/rhinoviruses (n = 5) in respiratory specimens. All patients except one received immunotherapy either alone or in combination. Among 27 patients with follow-up data 24 had persistent weakness. Involvement of four limbs together with an abnormal brain MRI at onset were associated with a poor prognosis. CONCLUSION: The number of patients with acute flaccid myelitis increased since 2012, spiking with every 2-year interval, largely in the pediatric population. The median age decreases with every outbreak. Clinicians should be aware of the clinical picture for early collection of specimens and early start of rehabilitation programs. Further studies are needed to better characterize the etiology, pathogenesis, risk factors, and treatment of this rare condition.

A Novel ELP2 Compound Heterozygous Mutation in a Boy with Severe Intellectual Disability, Spastic Diplegia, Stereotypic Behavior and Review of the Current Literature.

The elongator complex consists of 6 highly conserved subunit proteins and is indispensable for various cellular functions, such as transcription elongation, histone acetylation, and tRNA modification. The elongator complex contains 2 subunits, each of which consists of 3 different proteins (encoded by the ELP1-3 and ELP4-6 genes). According to the OMIM database, ELP2 gene variations have been reported to be associated with autosomal recessive mental retardation type 58. Here, we report a male patient with severe intellectual disability, spastic diplegia, and stereotypic behavior; in addition, we also provide a review of the current literature. Using whole-exome sequencing analysis, we detected a novel compound heterozygous variation in the ELP2 gene. We present this case report to clarify the clinical findings of a very rare neurodevelopmental phenotype and to contribute new information to the current literature on genotype-phenotype correlations.

The frequency of late-onset Pompe disease in pediatric patients with limb-girdle muscle weakness and nonspecific hyperCKemia: A multicenter study.

The aim of this multicenter study was to screen for late-onset Pompe disease in high-risk children with limb-girdle muscle weakness and nonspecific hyperCKemia using the dried blood spot (DBS) test. Seventy-two children from four pediatric neurology departments in Turkey were enrolled in the study: 37 with limb-girdle muscle weakness and 35 with nonspecific hyperCKemia. Acid α-glucosidase (GAA) activity was measured on DBS by tandem mass spectrometry. Six patients tested positively for Pompe disease. In three patients, one with the limb-girdle muscle weakness and two with nonspecific hyperCKemia, this was confirmed by genetic analysis. The overall frequency of late-onset Pompe disease in the study population was 4.2%. The c.1784C>T mutation found in one patient is a new mutation whereas the c.1655T>C mutation detected in the other two patients is not novel. In conclusion, Pompe disease should be suspected in patients with limb-girdle muscle weakness and nonspecific hyperCKemia. The DBS test is a safe and reliable method of diagnosis but must be confirmed by genetic analysis. In patients with a positive DBS test and negative genetic analysis, tissue assay of GAA should be considered.

Clinical value of technetium-99m-labeled octreotide scintigraphy in local recurrent or metastatic medullary thyroid cancers: a comparison of lesions with 18F-FDG-PET and MIBI images.

AIM: Various studies have been conducted for determining the most optimal method for the early diagnosis of local recurrent or distant metastatic thyroid cancers. The aim of this study was to evaluate the clinical utility of technetium-99m (Tc-99m)-labeled octreotide derivatives in the detection of recurrence or distant metastases in medullary thyroid cancer patients and to compare the lesions with those detected using 18F-fluorodeoxyglucose (18F-FDG)-PET and Tc-99m MIBI studies in the same patient group. PATIENTS AND METHODS: Sixteen medullary thyroid cancer patients [two male and 14 female; mean age 52.0 ± 14.1 years (range 13-72 years)] were included in this study. All patients underwent a whole-body scan 1 and 4 h after injection with octreotide derivatives and single photon emission computed tomography images were taken of the sites suspicious for metastasis. The lesions seen in Tc-99m HYNIC octreotide studies were compared with those seen in 18F-FDG-PET and Tc-99m MIBI studies. RESULTS: Among the Tc-99m-labeled octreotide scintigraphy studies, nine were evaluated as true positive (56.2%) and one was evaluated as false positive (6.2%); six were false negative (37.5%). In 16 patients, the total number of lesions seen on octreotide scintigraphy was 21. Thirteen of the 16 patients underwent 18F-FDG-PET imaging. Of the 13 patients studied, 10 showed true-positive (76.9%) and three showed false-negative (23.1%) results. The total number of lesions seen on 18F-FDG-PET was 23. The Tc-99m MIBI study yielded positive results in seven of 16 patients (43.7%) and negative results in nine patients (56.3%). The total number of lesions on Tc-99m MIBI was 12. CONCLUSION: The Tc-99m-labeled somatostatin receptor scintigraphy analogs HYNIC-tyrosine octreotide and HYNIC-TATE are useful imaging alternatives in somatostatin receptor-expressing thyroid cancers. Radiolabeling using these analogs is easy and they are readily available for routine use.

Tc 99m bone scan and fluorodeoxyglucose positron emission tomography in evaluation of disseminated langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder in which pathological langerhans cells accumulate in a variety of organs. Manifestations may include lung infiltrates, lymph node involvements, bone lesions, hepatic, hematopoietic and endocrine dysfunctions. In this case report we present fluorine-18 positron emission tomography (F-18 PET/CT) and bone scintigraphy findings of a 18-year-old male patient with disseminated LCH, mimicking multiple hypermetabolic metastatic lesions. Clinicians should be aware that LCH infiltrations can be seen as intense uptake and to differentiate infiltrations from other metastatic intense uptake with fluorodeoxyglucose PET/CT and bone scintigraphy, clinical and laboratory findings should be kept in mind.