Insights into phenotypic variability caused by GARS1 pathogenic variants.

BACKGROUND AND PURPOSE: Pathogenic variants of the glycyl-tRNA synthetase 1 (GARS1) gene have been described as a cause of Charcot-Marie-Tooth disease type 2D, motor axonal neuropathy with upper limb predominance (distal hereditary motor neuropathy [dHMN] type V), and infantile spinal muscular atrophy. METHODS: This cross-sectional, retrospective, observational study was carried out on 12 patients harboring the c.794C>T (p.Ser265Phe) missense pathogenic variant in GARS1. The patients' clinical data, nerve conduction studies, magnetic resonance imaging (MRI), and intraepidermal nerve fiber density in skin biopsies were reviewed. RESULTS: The mean age at onset was 9.5 years; the intrinsic hand muscles were affected before or at the same time as the distal leg musculature. The clinical examination revealed greater weakness of the distal muscles, with a more pronounced involvement of the thenar complex and the first dorsal interosseous in upper limbs. Electrophysiological studies were concordant with an exclusively motor axonal neuropathy. A pathologic split hand index was found in six patients. Muscle MRI showed predominant fatty infiltration and atrophy of the anterolateral and superficial posterior compartment of the legs. Most patients reported distal pinprick sensory loss. A reduced intraepidermal nerve fiber density was evident in skin biopsies from proximal and distal sites in nine patients. CONCLUSIONS: GARS1 variants may produce a dHMN phenotype with "split hand" and sensory disturbances, even when sensory nerve conduction studies are normal. This could be explained by a dysfunction of sensory neurons in the dorsal ganglion that is reflected as a reduction of dermal nerve endings in skin biopsies without a distal gradient.

Forefoot Morphotypes in Cavovarus Feet: A Novel Assessment of Deformity.

BACKGROUND: The cavovarus foot is a complex 3-dimensional deformity. Although a multitude of techniques are described for its surgical management, few of these are evidence based or guided by classification systems. Surgical management involves realignment of the hindfoot and soft tissue balancing, followed by forefoot balancing. Our aim was to analyze the pattern of residual forefoot deformities once the hindfoot is corrected, to guide forefoot correction. METHODS: We included 20 cavovarus feet from 16 adult patients with Charcot-Marie-Tooth who underwent weightbearing CT (mean age 43.4 years, range: 22-78 years, 14 males). Patients included had flexible deformities, with no previous surgery. Using specialized software (Bonelogic 2.1, Disior) a 3-dimensional, virtual model was created. Using morphologic data captured from normal feet in patients without pathology as a guide, the talonavicular joint of the cavovarus foot was digitally reduced to a "normal" position to simulate the correction that would be achieved during surgical correction. Models of the corrected position were exported and geometrically analyzed using Blender 3.64 to identify anatomical trends. RESULTS: We identified 4 types of cavovarus forefoot morphotypes. Type 0 was defined as a balanced forefoot (2 cases, 10%). Type 1 was defined as a forefoot where the first metatarsal was relatively plantarflexed to the rest of the foot, with no significant residual adduction after talonavicular joint correction (12 cases, 60%). Type 2 was defined as a forefoot where the second and first metatarsals were progressively plantarflexed, with no significant adduction (4 cases, 20%). Type 3 was defined as a forefoot where the metatarsals were adducted after talonavicular derotation (2 cases, 10%). CONCLUSION: In this relatively small cohort, we identified 4 forefoot morphotypes in cavovarus feet that might help surgeons to recognize and anticipate the residual forefoot deformities after hindfoot correction. Different treatment strategies may be required for different morphotypes to achieve balanced correction. LEVEL OF EVIDENCE: Level IV, retrospective case series.

3D Analysis of Joint-Sparing Charcot-Marie-Tooth Surgery Effect on Initial Standing Foot Alignment.

BACKGROUND: The complex deformities in cavovarus feet of Charcot-Marie-Tooth (CMT) disease are difficult to evaluate. The aim of this study was to quantify the initial standing alignment correction achieved after joint-sparing CMT cavovarus reconstruction using pre- and postoperative weightbearing computed tomography (WBCT). METHODS: Twenty-nine CMT cavovarus reconstructions were retrospectively analyzed. Three-dimensional measurements were performed using semiautomated software (Bonelogic 2.1) to investigate changes in sagittal, axial, and coronal parameters. Pre- and postoperative data were compared, along with normative data. Correlation among the preoperative measurements and the amount of correction in sagittal, axial, and coronal parameters were analyzed. RESULTS: The sagittal, axial, and coronal malalignment of the hindfoot, and the sagittal and axial malalignment of the forefoot, was significantly improved after corrective surgery (P < .05). Sagittal Meary angle (from 14.8 to 0.1 degrees), axial talonavicular angle (TNA, from 3.6 to 19.2 degrees), and coronal hindfoot alignment (from 11.0 to -11.1 degrees) showed significant changes postoperatively (P < .001). Hindfoot, forefoot sagittal, and forefoot axial parameters reached comparable outcomes compared with normative value (P > .05). Regarding amount of correction, Spearman correlation demonstrated that axial Meary angle and TNA were most strongly related to improvement in sagittal Meary angle and coronal hindfoot alignment. CONCLUSION: Preoperative and postoperative WBCT measurements demonstrated that joint sparing CMT cavovarus reconstruction significantly improved sagittal, axial, and coronal deformities of CMT, and sagittal Meary angle was restored toward normative values. Apparent axial plane correction, the majority of which occurred at the talonavicular joint, had the strongest correlation with deformity correction in multiple planes. This suggests that soft tissue releases and correction of the talonavicular joint may be a key component of a cavovarus foot correction.

Assessing the coronal plane deformity in Charcot Marie Tooth Cavovarus feet using automated 3D measurements.

BACKGROUND: This study assesses the coronal-plane deformities in cavovarus feet secondary to Charcot-Marie-Tooth disease (CMT) using Weightbearing-CT (WBCT) and semi-automated 3D-segmentation software. METHODS: WBCTs from 30 CMT-cavovarus feet were matched to 30 controls and analysed using semi-automatic 3D-segmentation (Bonelogic, DISIOR). The software used automated cross-section sampling with subsequent straight-line representation of weighted centre points to calculate 3D axes of bones in the hindfoot, midfoot and forefoot. Coronal relationships of these axes were analysed. Supination/pronation of the bones in relation to the ground and within each joint were measured and reported. RESULTS: The most significant deformity in CMT-cavovarus feet occurred at the talonavicular joint (TNJ) with 23 degrees more supination than normal feet (6.4 ± 14.5 versus 29.4 ± 7.0 degrees, p < 0.001). This was countered by relative pronation at the naviculo-cuneiform joints (NCJ) of 7.0 degrees (-36.0 ± 6.6 versus -43.0 ± 5.3 degrees, p < 0.001). Combined hindfoot varus and TNJ supination resulted in an additive supination effect not compensated by NCJ pronation. The cuneiforms in CMT-cavovarus feet were therefore supinated by 19.8 degrees to the ground relative to normal feet (36.0 ± 12.1 versus 16.2 ± 6.8 degrees, p < 0.001). The forefoot-arch and 1st metatarsal-ground angles demonstrated similar supination to the cuneiforms suggesting no further significant rotation occurred distally. CONCLUSION: Our results demonstrate coronal plane deformity occurs at multiple levels in CMT-cavovarus feet. Majority of the supination arises at the TNJ, and this is partially countered by pronation distally, mainly at the NCJ. An understanding of the location of coronal deformities may help when planning surgical correction. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Reliability and sensitivity of radiographic measures of hip dysplasia in childhood Charcot-Marie-Tooth disease.

BACKGROUND: Hip dysplasia is a lack of femoral head coverage and disruption of hip and acetabular alignment and congruency, with severity ranging from mild subluxation in nascent at-risk hips to complete dislocation. Presentation of hip dysplasia in neuromuscular conditions can be sub-clinical or associated with a limp with or without hip pain, abductor and flexor weakness and reduced hip range of motion. Untreated hip dysplasia leads to early onset osteoarthritis requiring hip arthroplasty in early adulthood. Hip dysplasia occurs in 6-20% of children with Charcot-Marie-Tooth disease, however little is known about the reliability and sensitivity of detection on plain film pelvic radiographs. METHODS: 14 common measures of hip dysplasia on anteroposterior pelvis radiographs were independently assessed by 2 orthopaedic specialists in 30 ambulant children with Charcot-Marie-Tooth disease. Hip health was also categorised based on clinical impression to assess the sensitivity of radiographic measures to identify hip dysplasia status. RESULTS: 8 measures (acetabular index, head width, lateral centre-edge angle, lateral uncoverage, medial joint width, migration percentage, neck shaft angle, triradiate status) exhibited 'excellent' reliability between clinical evaluators. 5 of the 30 patients (17%) were identified as having nascent hip dysplasia. Reliable radiographic measures that significantly distinguished between nascent hip dysplasia and healthy hips were acetabular index, lateral centre edge angle, medial joint width and migration percentage. CONCLUSIONS: We have identified a subset of reliable and sensitive radiographic hip measures in children with Charcot-Marie-Tooth disease to prioritise during hip screening to mitigate the deleterious effects of hip dysplasia, pain and disability in adulthood.

Cavovarus With a Twist: Midfoot Coronal and Axial Plane Rotational Deformity in Charcot-Marie-Tooth Disease.

BACKGROUND: The cavovarus deformity of Charcot-Marie-Tooth (CMT) disease is often characterized by a paradoxical relationship of hindfoot varus and forefoot valgus. The configuration of the midfoot, which links these deformities, is poorly understood. Accurate assessment of 3-dimensional alignment under physiologic loadbearing conditions is possible using weightbearing computed tomography (WBCT). This is the first study to examine the rotational deformity in the midfoot of CMT patients and, thus, provide key insights to successful correction of CMT cavovarus foot. METHODS: A total of 27 WBCT scans from 21 CMT patients were compared to control WBCTs from 20 healthy unmatched adults. CMT patients with a history of bony surgery, severe degenerative joint disease, or open physes in the foot were excluded. Scans were analyzed using 3-dimensional software. Anatomic alignment of the tarsal bones was calculated relative to the anterior-posterior axis of the tibial plafond in the axial plane, and weightbearing surface in the coronal plane. RESULTS: Maximal rotational deformity in CMT patients occurred at the transverse tarsal joints, averaging 61 degrees of external rotation (supination), compared to 34 degrees among controls (P < .01). The talonavicular joint was also the site of peak adduction deformity in the midfoot, with an average talonavicular coverage angle measuring 12 degrees compared with -11 degrees in controls (P < .01). CONCLUSION: This 3-dimensional WBCT analysis is the first to isolate and quantify the multiplanar rotational deformity in the midfoot of CMT patients. Compared with healthy unmatched control cases, CMT patients demonstrated increased axial plane adduction and coronal plane rotation at the talonavicular (TN) joint. These findings support performing soft tissue release at the TN joint to abduct and derotate the midfoot as a first step for targeted deformity correction. LEVEL OF EVIDENCE: Level III, retrospective case-control study.

New Keys to Early Diagnosis: Muscle Echogenicity, Nerve Ultrasound Patterns, Electrodiagnostic, and Clinical Parameters in 150 Patients with Hereditary Polyneuropathies.

Hereditary neuropathies are of variable genotype and phenotype. With upcoming therapies, there is urgent need for early disease recognition and outcome measures. High-resolution nerve and muscle ultrasound is a dynamic, non-invasive, well-established tool in the field of inflammatory and traumatic neuropathies. In this study, we defined nerve and muscle ultrasound parameters as recognition and progression markers in 150 patients with genetically confirmed hereditary neuropathies, including Charcot-Marie-Tooth (CMT) disease (CMT1A, n = 55; other CMT1/4, n = 28; axonal CMT, n = 15; CMTX, n = 15), hereditary neuropathy with liability to pressure palsies (HNPP, n = 16), hereditary transthyretin-amyloidosis (ATTRv, n = 14), and Fabry's disease (n = 7). The CMT1A, followed by the CMT1/4 group, had the most homogeneous enlargement of the nerve cross-sectional areas (CSA) in the ultrasound pattern sum (UPSS) and homogeneity score. Entrapment scores were highest in HNPP, ATTRv amyloidosis, and Fabry's disease patients. In demyelinating neuropathies, the CSA correlated inversely with nerve conduction studies. The muscle echo intensity was significantly highest in the clinically most affected muscles, which was independent from the underlying disease cause and correlated with muscle strength and disease duration. Further correlations were seen with combined clinical (CMTES-2) and electrophysiological (CMTNS-2) scores of disease severity. We conclude that nerve ultrasound is a helpful tool to distinguish different types of hereditary neuropathies by pattern recognition, whereas muscle ultrasound is an objective parameter for disease severity. The implementation of neuromuscular ultrasound might enrich diagnostic procedures both in clinical routines and research.

Pes cavovarus in Charcot-Marie-Tooth compared to the idiopathic cavovarus foot: A preliminary weightbearing CT analysis.

BACKGROUND: Pes cavovarus is a foot deformity that can be idiopathic (I-PC) or acquired secondary to other pathology. Charcot-Marie-Tooth disease (CMT) is the most common adult cause for acquired pes cavovarus deformity (CMT-PC). The foot morphology of these distinct patient groups has not been previously investigated. The aim of this study was to assess if morphological differences exist between CMT-PC, I-PC and normal feet (controls) using weightbearing computed tomography (WBCT). METHODS: A retrospective analysis of WBCT scans performed between May 2013 and June 2017 was undertaken. WBCT scans from 17 CMT-PC, 17 I-PC and 17 healthy normally-aligned control feet (age-, side-, sex- and body mass index-matched) identified from a prospectively collected database, were analysed. Eight 2-dimensional (2D) and three 3-dimensional (3D) measurements were undertaken for each foot and mean values in the three groups were compared using one-way ANOVA with the Bonferroni correction. RESULTS: Significant differences were observed between CMT-PC or I-PC and controls (p<0.05). Two-dimensional measurements were similar in CMT-PC and I-PC, except for forefoot arch angle (p=0.04). 3D measurements (foot and ankle offset, calcaneal offset and hindfoot alignment angle) demonstrated that CMT-PC exhibited more severe hindfoot varus malalignment than I-PC (p=0.03, 0.04 and 0.02 respectively). CONCLUSIONS: CMT-related cavovarus and idiopathic cavovarus feet are morphologically different from healthy feet, and CMT feet exhibit increased forefoot supination and hindfoot malalignment compared to idiopathic forms. The use of novel three-dimensional analysis may help highlight subtle structural differences in patients with similar foot morphology but aetiologically different pathology. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Closed arthrodesis in infected neuropathic ankles using Ilizarov ring fixation.

AIMS: Infected and deformed neuropathic feet and ankles are serious challenges for surgical management. In this study we present our experience in performing ankle arthrodesis in a closed manner, without surgical preparation of the joint surfaces by cartilaginous debridement, but instead using an Ilizarov ring fixator (IRF) for deformity correction and facilitating fusion, in arthritic neuropathic ankles with associated osteomyelitis. METHODS: We retrospectively reviewed all the patients who underwent closed ankle arthrodesis (CAA) in Ilizarov Scientific Centre from 2013 to 2018 (Group A) and compared them with a similar group of patients (Group B) who underwent open ankle arthrodesis (OAA). We then divided the neuropathic patients into three arthritic subgroups: Charcot joint, Charcot-Maire-Tooth disease, and post-traumatic arthritis. All arthrodeses were performed by using an Ilizarov ring fixator. All patients were followed up clinically and radiologically for a minimum of 12 months to assess union and function. RESULTS: The union rate for Group A was 81% (17/21) while it was 84.6% (33/39) for Group B. All the nonunions in Group A underwent revision with an open technique and achieved 100% union. Mean duration of IRF was 71.5 days (59 to 82) in Group A and 69 days (64.8 to 77.7) in Group B. The American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot score was similar in both groups. The postoperative hospital stay was shorter in Group A (21 days (SD 8)) than Group B (28 days (SD 9)). In the latter Group there were more problems with wound healing and greater requirement for antibiotic treatment. The mean operating time was 40 minutes (SD 9) in Group A compared to 80 minutes (SD 13) in Group B. Recurrence of infection occurred in 19% (4/21) and 15.5% (6/39) for Group A and Group B respectively. CONCLUSION: We found CAA using an IRF to be an effective method for ankle arthrodesis in infected neuropathic foot and ankle cases and afforded comparable results to open methods. Due to its great advantages, Ilizarov method of CAA should always be considered for neuropathic ankles in suitable patients. Cite this article: Bone Joint J 2020;102-B(4):470-477.

Homozygous splice-site mutation c.78 + 5G>A in PMP22 causes congenital hypomyelinating neuropathy.

Congenital hypomyelinating neuropathy (CHN) presents in the neonatal period and results in delayed development of sensory and motor functions due to several gene mutations including in EGR2, MPZ, CNTNAP1, and PMP22. The phenotype of homozygous splice-site mutation in the PMP22 gene has not been described in humans or animal models. Here we describe a family carrying a pathogenic splice-site c.78 + 5G>A mutation in the PMP22 gene. We evaluated the clinical, electrophysiological, histological, and genetic features of the family. The proband with homozygous mutation presented with CHN, while his consanguineous parents with heterozygous mutation were asymptomatic. The proband was a 7-year-old boy. He had motor retardation after birth and had remained unable to walk independently at the time of the study. The compound muscle action potentials and sensory nerve action potentials were not recordable in the boy. The motor and sensory nerve conduction velocities of the parents were slightly to moderately decreased, although they had no symptoms of peripheral neuropathy. The sural nerve biopsy of the boy revealed hypomyelinating neuropathy with absence of large myelinated fibers, no myelin breakdown products, and numerous basal lamina onion bulb formations. To our knowledge, this is the first report of a homozygous splice-site mutation in the PMP22 gene in humans. Our study expands the phenotype and genotype of PMP22-related neuropathy.

To Block or Not to Block: Role of Ultrasonography in Guiding an Anesthetic Plan for a Patient With Charcot-Marie-Tooth Disease.

A 31-year-old man scheduled for a fifth metatarsal head resection secondary to osteomyelitis presented to the preoperative holding area for placement of an ultrasound-guided popliteal nerve block as part of a multimodal pain management plan. During the preoperative evaluation, a medical history of CharcotMarie-Tooth disease was noted. The patient had decreased range of motion and neuropathy in both lower extremities and required an assistive device when ambulating. Before placement of the block, a pre-procedure scan of the popliteal fossa revealed abnormal sonoanatomy of the distal sciatic nerve as well as the proximal tibial and common peroneal nerve branches. The surgeon was consulted regarding the ultrasonography findings, and the proposed block was abandoned. A field block proximal to the surgical site was performed under monitored anesthesia care, with an understanding that the case would convert to general anesthesia using a laryngeal mask airway if the procedure was not tolerated. The surgery was performed as planned without any difficulties, and the patient was transferred to the postanesthesia care unit. The postoperative course was uneventful, and the patient was discharged home.

BAG3 mutation in a patient with atypical phenotypes of myofibrillar myopathy and Charcot-Marie-Tooth disease.

Bcl2-associated athanogene 3 (BAG3) mutations have been reported to cause the myofibrillar myopathy (MFM) which shows progressive limb muscle weakness, respiratory failure, and cardiomyopathy. Myopathy patients with BAG3 mutation are very rare. We described a patient showing atypical phenotypes. We aimed to find the genetic cause of Korean patients with sensory motor polyneuropathy, myopathy and rigid spine. We performed whole exome sequencing (WES) with 423 patients with sensory motor polyneuropathy. We found BAG3 mutation in one patient with neuropathy, myopathy and rigid spine syndrome, and performed electrophysiological study, whole body MRI and muscle biopsy on the patient. A de novo heterozygous p.Pro209Leu (c.626C>T) mutation in BAG3 was identified in a female myopathy. She first noticed a gait disturbance and spinal rigidity at the age of 11, and serum creatine kinase levels were elevated ninefolds than normal. She showed an axonal sensory-motor polyneuropathy like Charcot-Marie-Tooth disease (CMT), myopathy, rigid spine and respiratory dysfunction; however, she did not show any cardiomyopathy, which is a common symptom in BAG3 mutation. Lower limb MRI and whole spine MRI showed bilateral symmetric fatty atrophy of muscles at the lower limb and paraspinal muscles. When we track traceable MRI 1 year later, the muscle damage progressed slowly. As far as our knowledge, this is the first Korean patient with BAG3 mutation. We described a BAG3 mutation patient with atypical phenotype of CMT and myopathy, and those are expected to broaden the clinical spectrum of the disease and help to diagnose it.

SCO2 mutations cause early-onset axonal Charcot-Marie-Tooth disease associated with cellular copper deficiency.

Recessive mutations in the mitochondrial copper-binding protein SCO2, cytochrome c oxidase (COX) assembly protein, have been reported in several cases with fatal infantile cardioencephalomyopathy with COX deficiency. Significantly expanding the known phenotypic spectrum, we identified compound heterozygous variants in SCO2 in two unrelated patients with axonal polyneuropathy, also known as Charcot-Marie-Tooth disease type 4. Different from previously described cases, our patients developed predominantly motor neuropathy, they survived infancy, and they have not yet developed the cardiomyopathy that causes death in early infancy in reported patients. Both of our patients harbour missense mutations near the conserved copper-binding motif (CXXXC), including the common pathogenic variant E140K and a novel change D135G. In addition, each patient carries a second mutation located at the same loop region, resulting in compound heterozygote changes E140K/P169T and D135G/R171Q. Patient fibroblasts showed reduced levels of SCO2, decreased copper levels and COX deficiency. Given that another Charcot-Marie-Tooth disease gene, ATP7A, is a known copper transporter, our findings further underline the relevance of copper metabolism in Charcot-Marie-Tooth disease.

Rigid spine syndrome associated with sensory-motor axonal neuropathy resembling Charcot-Marie-Tooth disease is characteristic of Bcl-2-associated athanogene-3 gene mutations even without cardiac involvement.

INTRODUCTION: Bcl-2-associated athanogene-3 (BAG3) mutations have been described in rare cases of rapidly progressive myofibrillar myopathies. Symptoms begin in the first decade with axial involvement and contractures and are associated with cardiac and respiratory impairment in the second decade. Axonal neuropathy has been documented but usually not as a key clinical feature. METHODS: We report a 24-year-old woman with severe rigid spine syndrome and sensory-motor neuropathy resembling Charcot-Marie-Tooth disease (CMT). RESULTS: Muscle MRI showed severe fat infiltration without any specific pattern. Deltoid muscle biopsy showed neurogenic changes and discrete myofibrillar abnormalities. Electrocardiogram and transthoracic echocardiography results were normal. Genetic analysis of a panel of 45 CMT genes showed no mutation. BAG3 gene screening identified the previously reported c.626C>T, pPro209Leu, mutation. DISCUSSION: This case indicates that rigid spine syndrome and sensory-motor axonal neuropathy are key clinical features of BAG3 mutations that should be considered even without cardiac involvement. Muscle Nerve, 57: 330-334, 2018.

[Corrective procedures and indications for cavovarus foot deformities in children and adolescents]. / Korrekturen und Indikationen einer Pes-cavovarus-Deformität bei Kindern und Jugendlichen.

Cavovarus deformities in children and adolescents require sound considerations concerning the timing for corrective surgery. Progression can be recognized best by repeated pedographic examination with evaluation of the typical features of cavovarus deformity. Surgical correction consists of a combination of soft tissue release, bony realignment, and restoration of muscle balance. In most cases plantar or medioplantar soft tissue release should be considered, whereas calf muscle lengthening is rarely indicated. Typical joint-sparing bone procedures are elevating osteotomies at the medial tarsometatarsal ray and realigning calcaneal osteotomies. Advanced cases require navicular-cuneiforme arthrodesis for correction of severe cavus component, hindfoot fusion at the Chopart line, or Lambrinudi triple fusion. Supramalleolar rotational osteotomy should be considered in severe cases. Peroneal dysfunction is addressed by peroneus longus to brevis transfer, posterior tibial tendon transfer compensates for severe extensor weakness to a certain degree, claw toes can be rebalanced by flexor or extensor tendon transfer, often in combination with proximal interphalangeal joint fusion. Surgical treatment should take into account the components of deformity, muscular function, progression and the underlying disease of the individual case. Further deterioration can be prevented by adequate surgery in the young patient. However, repeated surgical interventions may be necessary later in this patient group.

Utility of PET/CT with fluorine-18-fluorodeoxyglucose-labeled autologous leukocytes for diagnosing diabetic foot osteomyelitis in patients with Charcot's neuroarthropathy.

OBJECTIVE: Diabetic foot osteomyelitis (DFO) is difficult to diagnose in the presence of Charcot's neuroarthropathy (CN) and bone biopsy is not always possible. We aimed to assess the efficacy of PET/computed tomography using F-fluoride (F-fluoride PET/CT) and fluorine-18-fluorodeoxyglucose-labeled autologous leukocytes (F-FDG-LL PET/CT) in comparison with contrast-enhanced MRI (CEMRI) for the detection of DFO. PATIENTS AND METHODS: Thirty-two patients with chronic CN and foot ulcer suspected of having DFO were prospectively evaluated. All patients underwent radiography, CEMRI, F-fluoride PET/CT, and F-FDG-LL PET/CT of the feet. Bone biopsy and microbiological culture from the suspected site of osteomyelitis was considered the gold standard. RESULTS: Twenty-three patients fulfilled the inclusion criteria. Bone culture was suggestive of DFO in 12 patients. CEMRI identified 10 of the 12 cases of osteomyelitis. F-fluoride PET/CT and F-FDG-LL PET/CT showed increased tracer uptake (SUVmax=22.7±18.1 and 8.4±4.7, respectively) at the clinically involved site in 10 of the 12 patients (TP). Among 11 biopsy-negative patients, CEMRI reported DFO in four (false positive); there were no false positives with F-FDG-LL PET/CT. The sensitivity and specificity of F-FDG-LL PET/CT was 83.3 and 100% compared with 83.3 and 63.6% for CEMRI, respectively, for the diagnosis of DFO in the background of CN. CONCLUSION: F-FDG-LL PET/CT has high specificity for the diagnosis of DFO in complicated diabetic foot. The F-fluoride PET/CT helps in the characterization the extent of underlying CN. An early and accurate diagnosis with F-FDG-LL PET/CT aids the rational initiation of antibiotics for DFO.

Utilization of PET imaging in differential diagnostics between a tumefactive multiple sclerosis lesion and low-grade glioma.

We present a case where a 30-year-old man with a history of combined MS and Charcot-Marie-Tooth (CMT I) disease was additionally diagnosed and treated for grade II glioma (astrocytoma). Tumefactive MS and gliomas are sometimes difficult to distinguish from one another based on conventional magnetic resonance imaging (MRI). In our case, positron emission tomography (PET) scans with(11)C-methionine ((11)C-MET) and (11)C-PK11195 radioligands were performed to aid in differential diagnostics. The diagnosis was confirmed finally by brain biopsy. The usefulness of PET imaging in differential diagnostics between tumefactive MS and glioma is discussed.

Multiple bilateral spinal nerve root calcifications in Charcot-Marie-Tooth disease.

We present a patient with Charcot-Marie-Tooth disease with multiple bilateral symmetrical cervical nerve root calcifications. To our knowledge, such a finding has not been described in the literature in association with this disease. We propose that multiple bilateral symmetrical spinal nerve root calcifications may be an additional imaging feature, possibly diagnostic, in this hereditary motor and spinal neuropathy.