Chronic inflammatory demyelinating polyradiculoneuropathy: can a diagnosis be made in patients not fulfilling electrodiagnostic criteria?

BACKGROUND AND PURPOSE: The aim was to identify the clinical and diagnostic investigations that may help to support a diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in patients not fulfilling the European Federation of Neurological Societies and Peripheral Nerve Society (EFNS/PNS) electrodiagnostic criteria. METHODS: The data from patients with a clinical diagnosis of CIDP included in a national database were retrospectively reviewed. RESULTS: In all, 535 patients with a diagnosis of CIDP were included. This diagnosis fulfilled the EFNS/PNS criteria in 468 patients (87.2%) (definite in 430, probable in 33, possible in three, while two had chronic immune sensory polyradiculopathy). Sixty-seven patients had a medical history and clinical signs compatible with CIDP but electrodiagnostic studies did not fulfill the EFNS/PNS criteria for CIDP. These patients had similar clinical features and frequency of abnormal supportive criteria for the diagnosis of CIDP compared to patients fulfilling EFNS/PNS criteria. Two or more abnormal supportive criteria were present in 40 (61.2%) patients rising to 54 (80.6%) if a history of a relapsing course as a possible supportive criterion was also included. Increased cerebrospinal fluid proteins and response to immune therapy most frequently helped in supporting the diagnosis of CIDP. Response to therapy was similarly frequent in patients fulfilling or not EFNS/PNS criteria (87.3% vs. 85.9%). CONCLUSIONS: Patients with a clinical diagnosis of CIDP had similar clinical findings, frequency of abnormal supportive criteria and response to therapy compared to patients fulfilling EFNS/PNS criteria. The presence of abnormal supportive criteria may help in supporting the diagnosis of CIDP in patients with a medical history and clinical signs compatible with this diagnosis but non-diagnostic nerve conduction studies.

Risk factors for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP): antecedent events, lifestyle and dietary habits. Data from the Italian CIDP Database.

BACKGROUND AND PURPOSE: The role of lifestyle and dietary habits and antecedent events has not been clearly identified in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: Information was collected about modifiable environmental factors and antecedent infections and vaccinations in patients with CIDP included in an Italian CIDP Database. Only patients who reported not having changed their diet or the lifestyle habits investigated in the study after the appearance of CIDP were included. The partners of patients with CIDP were chosen as controls. Gender-matched analysis was performed with randomly selected controls with a 1:1 ratio of patients and controls. RESULTS: Dietary and lifestyle data of 323 patients and 266 controls were available. A total of 195 cases and 195 sex-matched controls were used in the analysis. Patients eating rice at least three times per week or eating fish at least once per week appeared to be at decreased risk of acquiring CIDP. Data on antecedent events were collected in 411 patients. Antecedent events within 1-42 days before CIDP onset were reported by 15.5% of the patients, including infections in 12% and vaccinations in 1.5%. Patients with CIDP and antecedent infections more often had an acute onset of CIDP and cranial nerve involvement than those without these antecedent events. CONCLUSIONS: The results of this preliminary study seem to indicate that some dietary habits may influence the risk of CIDP and that antecedent infections may have an impact on the onset and clinical presentation of the disease.

Histological assessment of new bone formation with biomimetic scaffold in the presence of bone loss in trauma surgery.

Open reduction and internal fixation (ORIF) surgery may require the use of bone grafts (usually allogeneic). In the context of traumatology surgeries, the use of autologous grafts is almost never used and allogeneic grafts are not always available. In recent years, bone substitutes have been introduced in clinical practice to overcome these limitations. The purpose of this paper is to report two cases in which the use of a bone substitute was used to overcome the bone loss during surgeries of ORIF. Two patients, one with a tibial plateau fracture (Schatzker 6) and one with a proximal humerus fracture (Neer 4), underwent ORIF surgery. In both cases, due to a loss of bone stock, a synthetic bone substitute (OrthOss®) was used. One year after surgery, the complete osseointegration of the synthetic bone substitute was seen, both radiologically and histologically. This bone substitute may represent a safe and effective alternative to autologous bone grafts, avoiding adverse events related to donor-site morbidity.

Hormonal and metabolic gender differences in a cohort of myotonic dystrophy type 1 subjects: a retrospective, case-control study.

PURPOSE: Myotonic dystrophy type 1 (DM1) is a genetic disorder caused by CTG expansion in the DMPK gene. The aim was to investigate the endocrine and metabolic aspects of DM1. PATIENTS AND METHODS: Retrospective, case-control study. We compared pituitary, thyroid, adrenal, gonadal and liver function and glycolipid metabolism of 63 DM1 patients against 100 control subjects. Given age-related differences, 2 further subgroups were created to investigate the pituitary-gonadal axis: < 41 (1a) and ≥ 41 (1b) years old for male subjects and < 46 (2a) and ≥ 46 (2b) years old for female subjects. Testicular and thyroid ultrasounds were also performed in the DM1 group. RESULTS: FT3 and FT4 were significantly lower in DM1 men than controls, while for both males and females, thyroglobulin, ACTH and cortisol were significantly higher in the DM1 group. Gonadotropin levels were significantly higher and inhibin B and DHEA-S levels significantly lower in DM1 patients than controls for both male subgroups. Testosterone and SHBG were significantly higher in controls than in patients for subgroup 1a. Prolactin was significantly higher in patients in subgroups 1b, while testosterone was lower in subgroup 2a than in age-matched female controls. A correlation between the number of CTG repeats and the percentage of male hypogonadal subjects was found. Finally, there was a worse glucose and lipid pattern and significantly higher transaminase and gamma-GT levels in both male and female patients. CONCLUSIONS: The high frequency of endocrine and metabolic abnormalities in DM1 highlights the importance of endocrine monitoring to enable the prompt initiation of a suitable therapy.

Effect of metabolic and antioxidant supplementation on sperm parameters in oligo-astheno-teratozoospermia, with and without varicocele: A double-blind placebo-controlled study.

Since sperm require high energy levels to perform their specialised function, it is vital that essential nutrients are available for spermatozoa when they develop, capacitate and acquire motility. However, they are vulnerable to a lack of energy and excess amounts of reactive oxygen species, which can impair sperm function, lead to immotility, acrosomal reaction impairment, DNA fragmentation and cell death. This monocentric, randomised, double-blind, placebo-controlled trial investigated the effect of 6 months of supplementation with l-carnitine, acetyl-l-carnitine and other micronutrients on sperm quality in 104 subjects with oligo- and/or astheno- and/or teratozoospermia with or without varicocele. In 94 patients who completed the study, sperm concentration was significantly increased in supplemented patients compared to the placebo (p = .0186). Total sperm count also increased significantly (p = .0117) in the supplemented group as compared to the placebo group. Both, progressive and total motility were higher in supplemented patients (p = .0088 and p = .0120, respectively). Although pregnancy rate was not an endpoint of the study, of the 12 pregnancies that occurred during the follow-up, 10 were reported in the supplementation group. In general, all these changes were more evident in varicocele patients. In conclusion, supplementation with metabolic and antioxidant compounds could be efficacious when included in strategies to improve fertility.

A novel gain-of-function mutation in ORAI1 causes late-onset tubular aggregate myopathy and congenital miosis.

We present three members of an Italian family affected by tubular aggregate myopathy (TAM) and congenital miosis harboring a novel missense mutation in ORAI1. All patients had a mild, late onset TAM revealed by asymptomatic creatine kinase (CK) elevation and congenital miosis consistent with a Stormorken-like Syndrome, in the absence of thrombocytopathy. Muscle biopsies showed classical histological findings but ultrastructural analysis revealed atypical tubular aggregates (TAs). The whole body muscle magnetic resonance imaging (MRI) showed a similar pattern of muscle involvement that correlated with clinical severity. The lower limbs were more severely affected than the scapular girdle, and thighs were more affected than legs. Molecular analysis revealed a novel c.290C>G (p.S97C) mutation in ORAI1 in all affected patients. Functional assays in both human embryonic kidney (HEK) cells and myotubes showed an increased rate of Ca2+ entry due to a constitutive activation of the CRAC channel, consistent with a 'gain-of-function' mutation. In conclusion, we describe an Italian family harboring a novel heterozygous c.290C>G (p.S97C) mutation in ORAI1 causing a mild- and late-onset TAM and congenital miosis via constitutive activation of the CRAC channel. Our findings extend the clinical and genetic spectrum of the ORAI1-related TAM.

LOPED study: looking for an early diagnosis in a late-onset Pompe disease high-risk population.

OBJECTIVE: A multicentre observational study was aimed to assess the prevalence of late-onset Pompe disease (LOPD) in a large high-risk population, using the dried blood spot (DBS) as a main screening tool. DESIGN/METHODS: 17 Italian neuromuscular centres were involved in the late-onset Pompe early diagnosis (LOPED) study. Inclusion criteria were: (1) age ≥5 years, (2) persistent hyperCKaemia and (3) muscle weakness at upper and/or lower limbs (limb-girdle muscle weakness, LGMW). Acid α-glucosidase (GAA) activity was measured separately on DBS by fluorometric as well as tandem mass spectrometry methods. A DBS retest was performed in patients resulted positive at first assay. For the final diagnosis, GAA deficiency was confirmed by a biochemical assay in skeletal muscle, whereas genotype was assessed by GAA molecular analysis. RESULTS: In a 14-month period, we studied 1051 cases: 30 positive samples (2.9%) were detected by first DBS screening, whereas, after retesting, 21 samples were still positive. Biochemical and molecular genetic studies finally confirmed LOPD diagnosis in 17 cases (1.6%). The median time from the onset of symptoms/signs to diagnosis was 5 years. Among those patients, 35% showed presymptomatic hyperCKaemia and 59% showed hyperCKaemia+LGMW, whereas 6% manifested with LGMW. CONCLUSIONS: LOPED study suggests that GAA activity should be accurately screened by DBS in all patients referring for isolated hyperCKaemia and/or LGMW. A timely diagnosis was performed in five patients with presymptomatic hyperCKaemia, but two had already manifested with relevant changes on muscle morphology and MRI. Consequently, enzyme replacement therapy was started in 14/17 patients, including the 2 patients still clinically presymptomatic but with a laboratory evidence of disease progression.

ACP1 genetic polymorphism and spermatic parameters in men with varicocele.

Platelet-derived growth factor (PDGF) and its receptors (PDGFRs) play a key role in the regulation of the embryonic and postnatal development of male gonads. PDGF deficiency is associated with severe spermatogenic impairment. ACP1 is a phosphoprotein tyrosine phosphatase that is able to dephosphorylate PDGFR, decreasing its activity as growth factor. The enzyme is polymorphic and shows strong differences in enzymatic activity among genotypes. At the Outpatient Department for Infertility, University of Rome La Sapienza, we investigated the effect of high-activity ACP1 genotype on spermatic parameters in 105 subjects referred to for varicocele. ACP1 genotype was determined by DNA analysis. In ACP1 *B/*C genotype, which shows the highest enzymatic activity, spermatic concentration is significantly lower and atypical spermatozoa are significantly more frequent as compared to other ACP1 genotypes. It is concluded that subjects carrying *B/*C genotype who represent about 10% of the population have a severe impairment of spermatic parameters in the presence of varicocele.

Early orthodontic treatment: a new index to assess the risk of malocclusion in primary dentition.

AIM: A new index targeted on the risk of malocclusions in primary dentition, called Baby-ROMA (Risk Of Malocclusion Assessment) index, was set up to assess risks/benefits in early orthodontic therapies. The Baby-ROMA index was designed from the observation that some of the malocclusion signs, observed in primary dentition, can worsen with growth, others remain the same over time and others can even improve. Therefore it would be important to classify the malocclusions observed at an early stage on a risk- based scale. MATERIALS AND METHODS: The reliability of the index was tested on 200 children, referred by their paediatricians to two different Orthodontic Departments, aged 4-6 years and in full primary dentition. The children were evaluated by two operators, both trained and calibrated on the use of the Baby-ROMA index. RESULTS: The K test showed a high reproducibility of the index. It is shown that 50% of patients presented malocclusion and crossbite had the highest prevalence, followed by tooth decay and early loss of deciduous teeth and negative overjet. CONCLUSION: The Baby-ROMA index was helpful to assess the severity of malocclusion and the timing for orthodontic treatment in very young patients (primary teeth).

Case report of patients treated with an orthodontic and myofunctional protocol.

BACKGROUND: Occlusion alterations can be associated to bad habits (such as thumb sucking, oral breathing, atypical swallowing and labial interposition) which can lead to functional anomalies. CASE REPORT: Three cases are reported with the good results of myofunctional and orthodontic therapy. CONCLUSION: When there are bad habits, orthodontics should be combined with a myofunctional therapy.

Distal Tibia Fractures: is the Tibia First Technique a Rational Approach?

Introduction: In this retrospective case-series study we discuss the clinical and radiographic outcomes obtained following the "tibia-first concept" in the treatment of distal tibia fractures, both in patients with fibular comminution and in cases with a simple fibula fracture. Materials and methods: We analysed a consecutive series of 64 patients who presented at our emergency department with a distal articular tibial and fibular fracture from January 2015 to September 2020. A total of 22 patients met the inclusion and exclusion criteria and were included in the study. Clinical and radiographic examination were performed at each follow-up. To quantify pain and functional disability, the Foot and Ankle Outcome Score (FAOS) and the American Orthopaedic Foot and Ankle Society's ankle-hindfoot scale (AOFAS) were applied. Results: The overall mean age was 52.8 years, and the mean follow-up was 13.18 months. Multiple scales data from the FAOS were as follows: pain score 80.70; symptoms score 81.69; activities of daily living score 87.22; quality of life 76.05. The mean AOFAS ankle-hindfoot score was 74.36. Conclusions: Even though the principles of Rüedi and Allgöwer are still valid, in specific circumstances, the tibia-first concept could be considered as a valid option for the treatment of these demanding fractures. If a good reduction is obtained intra-operatively by ligamentotaxis, we recommend fixing the tibia first, avoiding surgical stress on tissues derived from a previous fibular fixation.

A two-window mini-open approach for suprapectoral tenodesis for traumatic ruptures of the long head of the biceps tendon.

Abstract: Traumatic rupture of the long head of biceps tendon (LHBT) in the young is rare and it is often related to sports. We describe a technical note of a mini open supra-pectoral tenodesis fixed by the "ToggleLoc™" (Zimmer Biomet, Warsaw, IN, USA) and performed by a two-window approach. The proposed technique guarantees an optimal visualization with low risk of complications and without arthroscopic assistance.

Primary metastatic neuroendocrine small cell bladder cancer: a case report and literature review.

Small cell carcinoma of the urinary bladder (SCCUB) is a rare variant of neuroendocrine nonepithelial tumor. Clinically, SCCUB appears like a flat or ulcerated lesion and microscopically can cause microvascular invasion and necrosis. Small cell cancer, rarely found in the urogenital tract in a primitive form, usually coexists with urothelial bladder cancers. It has an incidence of 0.35-0.7% of all bladder neoplasms and survival at 5 years is estimated to be around 8%. A 60-year-old man who was a smoker was referred to our department with episodes of gross hematuria and pain in the lumbar region. After an extensive transurethral resection of the bladder, including of the muscular layer, the diagnosis of small cell carcinoma of the bladder was made. The neoplastic cells were positive with immunohistochemical staining for chromogranin A, paranuclear reactivity to cytokeratin and neuron-specific enolase. A total-body CT scan revealed lymph node involvement and hepatic, adrenal and lung metastases. Because of the advanced stage it was decided to avoid radical cystectomy and perform chemotherapy. The patient underwent two different cycles of cisplatin chemotherapy following international recommendations, but unfortunately without any response. After palliative therapy, the patient died in January 2010.

Causal relationship between malocclusion and oral muscles dysfunction: a model of approach.

AIM: Bad habits result in altered functions which with time can cause anomalies of the orofacial morphology. To solve these problems, orthodontic treatment can be supported by myofunctional therapy in order to recover the normal functionality of the oral muscles. The aim of this study is to assess the need to treat patients with neuromuscular disorders, from both the occlusion and the muscles condition approach in order to obtain the balance needed for the stability of treatment. MATERIALS AND METHODS: A sample of 23 patients with atypical swallowing was included in this study, some of them presented thumb sucking and oral breathing. After case history collection, in order to make a correct orthodontic and functional diagnosis, correction of anomalies was carried out since they could compromise the success of the therapy (maxillary contraction, oral breathing, and short lingual fraenum). Then a different therapeutic approach was applied on the basis of the specific dental features. RESULTS: Both from the diagnostic and therapeutic point of view, important results were achieved especially through muscle analysis with dynamometer and surface electromyography. CONCLUSION: Orthodontic therapy, in the presence of bad habits, is not enough to solve orthodontic issues, it must be combined with a myofunctional treatment. The success of the therapy is granted only when patients and their family comply with the treatment and all factors which can prevent success of the therapy are removed.

Patients treated with orthodontic-myofunctional therapeutic protocol.

AIM: The aim of this study is to report three cases that needed myofunctional and orthodontic treatment and the good results achieved after the therapy. Orthodontic treatment alone, in presence of bad habits, is not enough to solve the orthodontic issues, so it needs to be combined with myofunctional treatment.

Diagnosis and management of a superior gluteal artery lesion following intramedullary fixation of a diaphyseal femoral fracture: a case report.

Introduction: Femur fractures represent a major public health issue and are commonly treated by intramedullary nailing. Among the possible complications of this technique, the injury of the superior gluteal artery (SGA) is quite rare, but it must be promptly recognized and treated. Case report: A 35-year-old male was admitted with a right femur diaphyseal fracture. After an early damage control surgery, he under-went a close reduction and long intramedullary nail fixation. During the post-operative rehabilitation, a sudden hip pain and hemoglobin drop occurred. A CT-scan showed an extensive hematoma; angiography confirmed a superior gluteal artery bleeding which was subsequently treated with selective embolization. Discussion and Conclusion: Whenever a patient presents with postoperative suspect of active bleeding, it is important to consider even the rarest complications. Sharing our experience in the management of a SGA lesion case, we want to stress the importance of its early diagnosis and correction, since it can represent a life-threatening condition.

Demonstration of ignition radiation temperatures in indirect-drive inertial confinement fusion hohlraums.

We demonstrate the hohlraum radiation temperature and symmetry required for ignition-scale inertial confinement fusion capsule implosions. Cryogenic gas-filled hohlraums with 2.2 mm-diameter capsules are heated with unprecedented laser energies of 1.2 MJ delivered by 192 ultraviolet laser beams on the National Ignition Facility. Laser backscatter measurements show that these hohlraums absorb 87% to 91% of the incident laser power resulting in peak radiation temperatures of T(RAD)=300 eV and a symmetric implosion to a 100 µm diameter hot core.

Immunosuppressive treatment in refractory chronic inflammatory demyelinating polyradiculoneuropathy. A nationwide retrospective analysis.

BACKGROUND AND PURPOSE: There are other options open to patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) who are non-responders to conventional treatment, including immunosuppressive and immunomodulatory agents (IA). The aim of this study was to assess whether the use of IA is able to increase the number of responders. METHODS: Clinical and electrophysiological data of patients with refractory CIDP, followed at 10 Italian centres, were collected, and the clinical outcome (Rankin Scale) and drug side effects (SE) for the different therapies were analysed. RESULTS: A total of 110 patients were included. These patients underwent 158 different therapeutic procedures with IA. Seventy-seven patients were treated with azathioprine, 18 rituximab, 13 cyclophosphamide, 12 mycophenolate mofetil, 12 cyclosporine, 12 methotrexate, 11 interferon-alpha and three interferon beta-1a. The percentage of patients who responded to azathioprine (27%) was comparable to the percentage of responders to other therapies, after the exclusion of interferon beta-1a that was not effective in any of the three patients treated. The percentage of SE ranges from 8% (methotrexate) to 50% (cyclosporine). CONCLUSIONS: One-fourth of patients, refractory to conventional treatment, showed an improvement in their disability with IA. Methotrexate had the lowest SE; cyclosporine was associated with severe SE and often led to drug discontinuation.

Short-term clinical outcome of not-fixed posterolateral fragment for tibial plateau fractures.

BACKGROUND: Tibial plateau fractures pose multiple challenges to the surgeon given their frequent intra-articular involvement and the tendency to displace under axial load. The aim of this study is to de-scribe the clinical outcomes of a retrospective case series in which tibial plateau fractures were not treated with PL fragment osteosynthesis. METHODS: In the present retrospective study, we included patients treated for tibial plateau fracture with PL fragment in our department from January 2016 to January 2020. All patients were seen at the outpa-tient clinic 2 and 5 weeks after surgery, and at 3, 6 and 12 months, and thereafter at regular intervals, depending on the overall clinical status. Every patient included in this study was then contacted by phone to assess self-reported clinical outcomes. The Oxford Knee Score (OKS) questionnaire was used to assess functional outcomes. Patients were divided in six groups depending on the three-column classification by Lou (groups A1-A6). Patients were also divided in four groups based on the whole area of the PL column and on the depression of the PL fragment (group B1-B4). One-way ANOVA was used to compare groups of patients. RESULTS: OKS scores, extension and step-off of the PL fragment were analyzed in groups A1 - A6. No significant differences between OKS scores and step-off were found, while statistical difference was found between surfaces of PL fragment. No significant difference was found between OKS scores in groups B1-B4. CONCLUSION: Our findings suggest that the treatment outcome is influenced not only by the superficial involvement or collapse of PL fragments, but also by other variables, including BMI, pre-injury physi-cal health, and age.

A combined paratricipital and triceps-splitting approach for distal humeral metaphyseal-diaphyseal fractures in adults.

BACKGROUND: Distal metaphyseal-diaphyseal fractures of the hume-rus can be challenging. The success lies in achieving a stable fixation that could allow early functional recovery. Our aim is to combine dif-ferent approaches already reported, to obtain an ideal surgical strategy for treating these fracture patterns. METHODS: In this retrospective study, we present the clinical outco-me of a 12-patient cohort in which we used a combined paratricipital and triceps-splitting approach to the distal humerus. The mean age of the group was 50 years (range 17 - 88). Clinical and radiographic evaluation was performed at 1, 3, 6, and 12 months after surgery and thereafter, depending on the necessity of a further control. Patients' range of motion (ROM) of the elbow was reported, and functional outcome was assessed using the Mayo Elbow Performance Index (MEPI).The minimum follow-up was fixed at 12 months. RESULTS: Union was achieved in all fractures. After a median follow-up of 15.7 months (range 12-21), none of the patients complained of any limitation in daily activities. The ROM at the last follow-up was complete in eight patients. Instead, three patients had ROM limitations, but none of them mentioned limitations in the activities of daily living. We observed a single iatrogenic radial nerve palsy undergoing a full functional recovery at the final follow-up. No further complications occurred. CONCLUSION: We believe that the here presented modified approach could represent a solution that meets the modern demands for both ro-bust fixation and early mobilization, with minimal soft tissues damage around distal humeral fractures.