Severe axonal neuropathy is a late manifestation of SPG11

Complex hereditary spastic paraplegia (HSP) is a clinically heterogeneous group of disorders usually inherited in an autosomal recessive manner. In the past, complex recessive spastic paraplegias have been frequently associated with SPG11 mutations but also with defects in SPG15, SPG7 and a handful of other rare genes. Pleiotropy exists in HSP genes, exemplified in the recent association of SPG11 mutations with CMT2. In this study, we performed whole exome sequence analysis and identified two siblings with novel compound heterozygous frameshift SPG11 mutations. The mutations segregated with disease were not present in control databases and analysis of skin fibroblast derived mRNA indicated that the SPG11 truncated mRNA species were not degraded significantly by non-sense mediated mRNA decay. These siblings had severe early-onset spastic paraplegia but later in their disease developed severe axonal neuropathy, neuropathic pain and blue/black foot discolouration likely caused by a combination of the severe neuropathy with autonomic dysfunction and peripheral oedema. We also identified a similar late-onset axonal neuropathy in a Cypriot SPG11 family. Although neuropathy is occasionally present in SPG11, in our SPG11 patients reported here it was particularly severe, highlighting the association of axonal neuropathy with SPG11 and the late manifestation of axonal peripheral nerve damage

The elements of pathology and physiology of microsurgical flaps

Clinica de Chirurgie Plastică și Microchirurgie Reconstructivă, USMF “Nicolae Testemițanu”, Chișinău, Republica Moldova, Al XII-lea Congres al Asociației Chirurgilor „Nicolae Anestiadi” din Republica Moldova cu participare internațională 23-25 septembrie 2015Introducere: Transferul microchirurgical la prima vedere, pe lîngă cursul de dezvoltare extrem de rapid al nanomedicinei, s-ar părea că rezolvă livrarea țesuturilor pentru plastia și reconstrucția zonelor afectate ale corpului uman. În realitate, direcția acestui vector nu este suficient elucidată și la moment rămîn a fi discutate semnele de întrebare, care apar pe marginea acestui subiect. Scopul: Interpretarea corectă a concepțiilor modificărilor care au loc în lambou, în baza cărora ulterior vom putea stabili un algoritm de supraveghere și de tratament bine elucidat și funcționabil. Material și metode: Au fost studiate 112 surse de specialitate care reflectă starea țesuturilor umane în anumite situații critice, inclusiv în lambouri. Rezultate: Chirurgia lambourilor este însoțită de trauma chirurgicală, iar transferul de țesuturi este urmat de leziuni ischemice de reperfuzie, ceea ce poate compromite tot rezultatul intervenției. Este acceptat faptul că leziunea de reperfuzie este un proces inflamator modulat de mecanisme complexe de semnalizare, care în cele din urmă duce la moartea celulară și afectarea lamboului. Restabilirea fluxului sanguin este esențială pentru supraviețuirea lamboului, cu toate acestea, paradoxul este că reperfuzia produce un prejudiciu ischemic prin numeroase căi inflamatorii. Concluzie: Blocajul acut al fluxului sanguin, fără depistarea de curînd și tratarea activă, poate urma cu acțiune sistemică sub forma insuficienței poliorganice și moarte.Introduction: The microsurgical transfer, besides the extremely rapid development of nanomedicine, seems that solves and offers solutions pertaining to the supply of tissues for the plasty and reconstruction of affected areas of the human body. In fact, the direction of this vector isn’t fully elucidated and at this moment remains to be discussed the questions which appear on this subject. Purpose: Correct interpretation of the concept of changes which take place in the flap, on the basis of which, later we’ll be able to establish a well understood and functional algorithm of monitoring and treatment. Material and methods: It has been studied 112 specialized literature sources that reflect the state of human tissues in some critical situations, including flaps. Results: Flap’s surgery is accompanied buy surgical trauma, and transfer of human tissues is followed by ischemic lesions of reperfusion, which can compromise the whole outcome of the interventions. It is recognized that the lesions of reperfusion is an inflammatory process, modulated by complex signaling mechanisms which eventually leads to cell death and flap’s damage. Restoring blood flow is essential for the flap’s survival; however, the paradox is that reperfusion produces an ischemic injury through numerous inflammatory pathways. Conclusions: Acute blockage of blood flow, without early detection and active treatment, soon is followed by systemic action in the form of polyorganic insufficiency and death

Analysis of the prion protein gene in multiple system atrophy

Neurodegenerative diseases are a very diverse group of disorders but they share some common mechanisms such as abnormally misfolded proteins with prion-like propagation and aggregation. Creutzfeldt-Jakob disease (CJD) is the most prevalent prion disease in humans. In the sporadic form of CJD the only known risk factor is the codon 129 polymorphism. Recent reports suggested that α-synuclein in multiple system atrophy (MSA) has similar pathogenic mechanisms as the prion protein. Here we present 1 Italian family with MSA and prion disease. Also, cases of concurrent MSA and prion pathology in the same individual or family suggest the possibility of molecular interaction between prion protein and α-synuclein in the process of protein accumulation and neurodegeneration, warranting further investigations. We assessed the PRNP gene by whole-exome sequencing in 264 pathologically confirmed MSA cases and 462 healthy controls to determine whether the 2 diseases share similar risk factors. We then analyzed codon 129 polymorphism by Sanger sequencing and compared with previously published results in sporadic CJD. Homozygosity at codon 129 was present in 50% of pathologically confirmed MSA cases and in 58% of normal controls (odds ratio, 0.7 (95% confidence interval of 0.5-0.9)) compared with 88.2% in sporadic CJD. Our data show that the homozygous state of position 129 in the PRNP is not a risk factor for MSA. No other variants in the PRNP gene were associated with increased risk for MSA

Planning flaps in the calf according to availability physiology

Catedra de ortopedie și traumatologie, USMF „Nicolae Testemițanu”, Clinica de chirurgie plastică și microchirurgie reconstructivă a locomotorului, IMSP IMU, Chișinău, Republica Moldova, Conferința stiințifică „Nicolae Anestiadi – nume etern al chirurgiei basarabene” consacrată centenarului de la nașterea profesorului Nicolae Anestiadi 26 august 2016Introducere. Acest studiu a fost efectuat pentru a determina lățimea optima disponibila a zonei donatoare de lambou care nu va prejudicia închiderea primara a plăgii donore, fiind suturata primar plan cu plan.Scop. Evaluarea disponibilității tegumentare fiziologice a fiecărei regiuni donatoare de la nivelul gambei. Material și metode. Studiul a fost efectuat pe un lot de 30 de voluntari, pe membrele sănătoase. Limitele de vârsta in lot au fost de 20 - 60 de ani, divizate pe categorii a câte 10 ani, fiecare subcategorie incluzând minim 5 voluntari. Disponibilitatea fiziologica s-a calculat pentru lambourile: safen, sural, peronier superficial, suprameleolar, fibular, tibial posterior si tibial anterior. Tegumentul s-a plicaturat in centrul teritoriului donator (cetripet), pana când părtile plicaturate contactau formând duplicatura (Ld). Grosimea duplicaturii s-a măsurat, fiind trecuta pe linia milimetrica. Ulterior, plica cutanata era desfăcuta la parametrii normali ai tegumentului cu extensia acelorași puncte in exterior (centrifug), fixându-se lungimea in milimetri (Le). Disponibilitatea tegumentara fiziologica (Dt) s-a calculat după formula: Dt =Le – Ld. Rezultate. Cea mai mare disponibilitate fiziologica la nivelul gambei s-a determinat in regiunea lamboului safen (5.05±0.29 cm; n=30; p=0.033), urmata de regiunea lamboului sural (4.83±0.25 cm; n=30; p=0.028) si regiunea lamboului tibial anterior (4.28±0.20 cm; n=30; p=0.03). Cea mai mica disponibilitate fiziologica s-a determinat în regiunea lamboului supramaleolar (3.04±0.21 cm; n=30; p=0.018). Concluzii. În urma studiului efectuat am constatat ca ridicarea unui lambou cu lățimea disponibila fiziologica a regiunilor donatoare la gamba nu va produce probleme de închidere a plăgii donore, fiind suturata primar plan cu plan.Introduction. This study was conducted to determine the optimal, available width of the flap’s donor site that will not harm the primary closure of donor wound. Purpose. To assess the skin physiological availability of each donor region of the calf. Material and methods. The study was conducted on a group of 30 volunteers, assessing healthy limbs. Age limits in group were 20-60 years, divided into categories of 10 years, including at least 5 volunteers each category. Physiological availability was calculated for flaps: saphenous, sural, superficial peroneal, suprameleolar, fibular, posterior and anterior tibial. The skin was fold in the center of donor territory (centripetal) until the folded parts was contacting, forming a folding (Ld). Folding’s thickness was measured, being passed on millimeter line. Subsequently, skin fold was unfolded to normal skin with the extension of the same points outside (centrifugal), attaching the length in millimeters (Le). Skin physiological availability (Dt) was calculated using the formula: Dt = Le - Ld. Results. Highest physiological availability was determined in region of saphenous flap (5.05±0.29 cm; n = 30; p = 0.033), followed by the sural flap (4.83±0.25 cm; n=30; p= 0.028) and region of anterior tibial flap (4.28±0.20 cm, n=30; p=0.03). The smallest physiological availability was determined in the region of supramalleolar flap (3.04±0.21 cm, n = 30; p = 0.018). Conclusions. From this study we found that raising a flap with physiological available width of donor regions of calf will not cause problems in donor wound’s closure, this being sutured primary

Treatment of infected nonunions of the tibia with tibial posterior cortico-periosteo-cutaneous perforator flaps

Clinica de Chirurgie Plastică și Microchirurgie reconstructivă, USMF “Nicolae Testemițanu”, Chișinău, Republica Moldova, Al XII-lea Congres al Asociației Chirurgilor „Nicolae Anestiadi” din Republica Moldova cu participare internațională 23-25 septembrie 2015Introducere: Tratamentul defectelor osoase la nivelul gambei rămîne a fi o problemă actuală, îndeosebi în cazurile unde se asociază infecția. Lambourile vascularizate axial posedă toleranță la agresiunea infecției și stimulează regenerarea țesuturilor. Scopul: Elaborarea unui nou management chirurgical al pseudoartrozei tibiale septice asociată cu defecte tisulare, care reprezintă o provocare atât pentru traumatolog, cât și pentru chirurgii plasticieni. În majoritatea cazurilor prezența infecției dictează o debridare agresivă, mărind defectul osos și tisular. În literatura de specialitate sunt o multitudine de studii ale metodelor de tratament al leziunilor tibiale septice prin transferul de os vascularizat, utilizând ca zone donatoare: fibula, creasta iliacă și, mai nou, condilul femural medial. Toate aceste metode necesită tehnici microchirurgicale meticuloase. Material și metode: Metoda se bazează pe colectarea unui lambou cortico-periosteocutan perforant tibial posterior, care include o grefă osoasă tibială. Acest lambou este alimentat de către perforanta tibială posterioară, determinată prin Doppler preoperator. În perioada anilor 2009-2014 au fost tratați cu succes 16 pacienți, utilizînd metoda dată (11 – pseudoartroze atrofice septice de tibie și 5 – pseudoartroze hipertrofice tibiale), în prezența infecţiei. Toți pacienţii aveau defect tisular, cu dimensiunile cuprinse între 2 x 1,5 cm și 5 x 2 cm. În toate cazurile stabilitatea osului s-a obţinut cu ajutorul fixatoarelor externe. Rezultate: Toate lambourile au supravieţuit. Timpul de la intervenția de reconstrucție pînă la înlăturarea fixatoarelor și reabilitarea mersului a fost între 95 și 176 zile. Concluzii: Lamboul cortico-periosteocutan perforant tibial posterior conduce spre o consolidare și regenerare a defectului tibial în termeni caracteristici fracturilor.Introduction: Treatment of leg’s bone defect continues to be an actual problem, especially in association of infection. An axial vascularized flap has tolerance to infection’s aggression, and stimulates tissues regeneration. Aim: To elaborate a new surgical management of septic tibial nonunion associated with soft tissue defects, which represent a challenge for traumatologist, as well as for reconstructive surgeons. Presence of infections dictates mostly of time necessity for an aggressive debridement which enlarges even more soft tissue and bone defects. In specialized literature there are a lot of studies of different methods for treating septic nonunion of tibia by vascularized bone transfer, using as donor sites fibula, ileac crest and more recent – medial femoral condyle. All these surgical approaches need meticulous microsurgical techniques. Material and methods: Our method is based on harvesting a cortico-periosteo-cutaneous tibial posterior perforator flap which involves a tibial bone graft. These flaps rely on tibial posterior perforator which is determined by preoperative Doppler examination. From 2009 till 2014 there were16 patients, successfully treated by this method (11 – with atrophic septic tibial nonunion and 5 – with hypertrophic tibial nonunion). All patients presented soft tissue defects with sizes varying from 2x1.5 cm till 5x2 cm. In all patients bone stability was obtained with external fixators. Results: All flaps survived. Time from reconstructive surgery to removal of external fixator and walk without crutches varied from 95 till 176 days. Conclusions: Cortico-periosteo-cutaneus tibial posterior perforator flap leads to regeneration and consolidation of septic tibial nonunion in terms characteristics for fractures

Cross-leg technique in the treatment of tibial bone defects

Clinica de Chirurgie Plastică şi Microchirurgie Reconstructivă, USMF “Nicolae Testemițanu”, Chişinău, Republica Moldova, Al XII-lea Congres al Asociației Chirurgilor „Nicolae Anestiadi” din Republica Moldova cu participare internațională 23-25 septembrie 2015Introducere: În situații deosebite, unde vasele membrului traumatizat au suportat leziuni importante şi nu pot fi utilizate ca sursă receptoare, se foloseşte metoda de plastie a defectelor „împrumutînd” temporar surse donatoare de pe membrele alăturate. Scopul: Identificarea aspectelor esențiale în literatura de specialitate şi în baza studiului propriu, ceea ce vizează ulterior transferul de lambou fibular osteocutanat prin metoda “cross-leg”. Material și metode: Transferul de fibulă vascularizată prin metoda “cross-leg” a fost efectuată la 4 pacienți – bărbați, cu un defect osos tibial cuprins între 10 şi 24 cm. Metoda cuprinde 2 etape. Timpul I a presupus o incizie verticală pe partea anterolaterală a gambei şi două incizii transversal-paralele pînă la adîncul fasciei profunde. Lamboul fiind ridicat în plan subfascial, incizia a fost continuată pînă la fibulă cu secționarea ulterioară în proximal şi distal. Inciziile transversale sînt continuate în plan subfascial pînă la limita postero-medială a tibiei, păstrîndu-se septul crural posterior şi integritatea perforantelor. Ambele gambe sînt fixate în aparat extern pe un termen de aproximativ 21 de zile. Timpul II presupune disecția lamboului de la locul donator, iar defectul donator este grefat. Rezultate: Indicații pentru procedeul dat sunt leziunile grave vasculare la membrul afectat, care nu permit un transfer liber sau un procedeu microchirurgical. Concluzii: Lamboul fibular osteofasciocutanat este un lambou sigur pentru acoperirea defectelor osoase şi tisulare, doar în concordanță strictă cu stabilirea indicațiilor şi contraindicațiilor către acest procedeu.Introduction: In special situations, where vessels of injured limb suffered severe lesions and can’t be used as recipient source, it uses method of defect’s plasty ”borrowing” temporary donor sources from adjacent limbs. Purpose: Identification of essential theoretical and practical issues in literature and based on own experience, which aims further transfer of fibular osteo-cutaneous flap using cross-leg method. Material and methods: The vascularized fibula transfer using “cross leg” method in treatment of tibial bone defects was performed in 4 men, with tibial bone defect between 10 and 24 cm. The method consists in performing a 2 stage surgery. Initially, first stage assumed a vertical incision on the antero-lateral side of the lower leg and 2 transverse parallel incisions to depth of deep fascia. Raising flap in a subfascial plan, incision was continued until the fibula with its subsequent proximal and distal sectioning. Transverse incisions were continued in subfascial plan until the postero-medial limit of the tibia, preserving posterior crural septum and integrity of perforator vessels. Both legs were attached to an external device for a period of approximately 21 days. Later, the second stage assumed the flap’s dissection from the donor area, and the grafting of the defect. Results: Respecting the method’s principle is possible to treat bone defects when an usual microsurgical technique is not feasible due to severe concomitant ipsilateral vascular lesions. Conclusions: The fascio-osteo-cutaneous fibular flap is a safe flap for coverage of bone and tissues defects, only in accordance with strict preset of indications and contraindications of the procedure

An update on advances in magnetic resonance imaging of multiple system atrophy

In this review, we describe how different neuroimaging tools have been used to identify novel MSA biomarkers, highlighting their advantages and limitations. First, we describe the main structural MRI changes frequently associated with MSA including the 'hot cross-bun' and 'putaminal rim' signs as well as putaminal, pontine, and middle cerebellar peduncle (MCP) atrophy. We discuss the sensitivity and specificity of different supra- and infratentorial changes in differentiating MSA from other disorders, highlighting those that can improve diagnostic accuracy, including the MCP width and MCP/superior cerebellar peduncle (SCP) ratio on T1-weighted imaging, raised putaminal diffusivity on diffusion-weighted imaging, and increased T2* signal in the putamen, striatum, and substantia nigra on susceptibility-weighted imaging. Second, we focus on recent advances in structural and functional MRI techniques including diffusion tensor imaging (DTI), resting-state functional MRI (fMRI), and arterial spin labelling (ASL) imaging. Finally, we discuss new approaches for MSA research such as multimodal neuroimaging strategies and how such markers may be applied in clinical trials to provide crucial data for accurately selecting patients and to act as secondary outcome measures

Automated Brainstem Segmentation Detects Differential Involvement in Atypical Parkinsonian Syndromes

OBJECTIVE: Brainstem segmentation has been useful in identifying potential imaging biomarkers for diagnosis and progression in atypical parkinsonian syndromes (APS). However, the majority of work has been performed using manual segmentation, which is time consuming for large cohorts. METHODS: We investigated brainstem involvement in APS using an automated method. We measured the volume of the medulla, pons, superior cerebellar peduncle (SCP) and midbrain from T1-weighted MRIs in 67 patients and 42 controls. Diagnoses were corticobasal syndrome (CBS, n = 14), multiple system atrophy (MSA, n = 16: 8 with parkinsonian syndrome, MSA-P; 8 with cerebellar syndrome, MSA-C), progressive supranuclear palsy with a Richardson’s syndrome (PSP-RS, n = 12), variant PSP (n = 18), and APS not otherwise specified (APS-NOS, n = 7). RESULTS: All brainstem regions were smaller in MSA-C (19–42% volume difference, p < 0.0005) and in both PSP groups (18–33%, p < 0.0005) than in controls. MSA-P showed lower volumes in all regions except the SCP (15–26%, p < 0.0005). The most affected region in MSA-C and MSA-P was the pons (42% and 26%, respectively), while the most affected regions in both the PSP-RS and variant PSP groups were the SCP (33% and 23%, respectively) and midbrain (26% and 24%, respectively). The brainstem was less affected in CBS, but nonetheless, the pons (14%, p < 0.0005), midbrain (14%, p < 0.0005) and medulla (10%, p = 0.001) were significantly smaller in CBS than in controls. The brainstem was unaffected in APS-NOS. CONCLUSION: Automated methods can accurately quantify the involvement of brainstem structures in APS. This will be important in future trials with large patient numbers where manual segmentation is unfeasible