Neuropathic Form Research Articles

Validation analysis of Polish version of Neuropathic Pain Questionnaire - Short Form (NPQ-SF-PL) and assessment of quality of life in patients with chronic neuropathic pain.

The aims of this study were to translate and culturally adapt the Polish version (PL) of the Neuropathic Pain Questionnaire-Short Form (NPQ-SF), as well as to compare this questionnaire to other diagnostic tools in terms of reliability and psychometric validity. Neuropathic pain (NP) affects up to 10% of the general population. Despite a large number of studies, almost 50% of patients have a poor therapeutic outcome. Diagnostic tools are intended to distinguish between NP and non-NP (NoP) and to guide the examiner to perform further diagnostics in accordance with the guidelines. A total of 140 patients with chronic pain (ChP), 90 with NP and 50 with NoP, were enrolled into this study. NPQ-SF-PL has been developed following the guidelines for translation and cultural adaptation. Reliability of the translated version was examined using internal consistency, predictive validity, and intraclass correlation coefficient (ICC). In the study, women predominated over men, and the average age was 53.22. Cronbach's α value for the entire scale was 0.76 and ICC for test-retest reliability was 0.631. Receiver-operating characteristic curve analysis gave a sensitivity of 90.0% and a specificity of 88.0%. Area under the curve was 0.94. NPQ-SF-PL was moderately associated with self-completed Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) and weakly associated with the Numerical Rating Scale (NRS). The NP group obtained statistically significantly lower scores than the NoP group in all domains of the 36-Item Short Form Health Survey (SF-36), thus indicating worse health status. Patients aged over 41 years presented a worse quality of life compared to younger ones. Also, more than half of the patients with NP of both genders experienced symptoms of mild or more severe depression. NPQ-SF-PL is a valid screening tool for assessing NP in Polish chronic pain patients. The obtained results showed very good psychometric properties and adequate internal consistency. The repeatability of the questionnaire indicated moderate reliability. Clinical implications/future directions. We believe this study will provide physicians with a new instrument for the evaluation of NP for clinical and research purposes.

Intracerebroventricular Enzyme Replacement Therapy in Patients with Neuropathic Form of Mucopolysaccharidosis Type II: to Help Practicing Physician

Mucopolysaccharidosis type II (Hunter syndrome, MPS II) is a rare hereditary disease from the group of hereditary metabolic diseases. There are neuropathic and non-neuropathic forms of this disease. The neuropathic form is most common and leads to severe cognitive impairment and progressive damage of central nervous system. Nowadays, early diagnosis and timely initiation of pathogenetic therapy in patients with orphan diseases is the crucial problem of modern pediatrics. Intracerebroventricular administration of idursulfase beta is one of the promising treatment options in patients with neuropathic form of MPS II as it prevents severe complications development. The study of new pathogenetic therapy methods for rare hereditary diseases will help doctors of pediatric specialties to route patient correctly in timely manner to receive all the necessary treatment.

Natural disease course of chronic visceral acid sphingomyelinase deficiency in adults: A first step toward treatment criteria.

Acid sphingomyelinase deficiency (ASMD) is an ultra-rare lysosomal storage disease with a broad spectrum of manifestations ranging from severe neuropathic forms to attenuated, chronic visceral forms. Manifestations of the chronic visceral subtype are variable and encompass different degrees of hepatosplenomegaly, pulmonary disease and dyslipidemia. The aim of this study was to provide insights into the natural course of adult patients with the chronic visceral subtype. Based on these insights, we proposed tentative criteria for initiation and follow-up of enzyme replacement therapy (ERT). The data of 23 adult patients were collected in a prospective study. Clinical, genetic and demographic data, plasma measurements, abdominal imaging, pulmonary imaging, pulmonary function tests and quality of life questionnaires were collected. Stability of disease based on several clinical, biochemical and radiological markers (i.e., spleen volume, platelet levels, liver volume, alanine aminotransferase [ALT] levels, diffusion capacity of the lungs for carbon monoxide [DLCO] chitotriosidase activity and lysosphingomyelin [LSM]) was assessed. Cardiovascular risk was estimated based on sex, age, smoking, systolic blood pressure and lipid profile. Quality of life was evaluated with the 36-Item Short Form Health Survey and the Health Assessment Questionnaire. Median follow-up was 6.1 years (range 1.3-19.5 years). The most common manifestations were splenomegaly (100%), decreased high-density lipoprotein cholesterol (HDL-C) plasma levels (83%), (signs of) steatosis measured with transient elastography (82%), thrombocytopenia (64%), hepatomegaly (52%) and decreased diffusion capacity (45%). The majority of markers remained stable during follow-up. Twelve patients showed progression of disease: four for spleen volume, two for liver volume, three for DLCO, seven for chitotriosidase activity and three for LSM. One patient showed progression of disease based on four markers, although this patient did not report any problems at the last visit. Cardiovascular risk was estimated and was increased in half of the patients older than 40 years. Patient-reported quality of life did not differ from the general population, but differences in median 36-Item Short Form Health Survey (SF-36) scores of patients with severe pulmonary involvement and those of patients without pulmonary involvement were observed. Tentative criteria for initiation and effect of therapy were proposed. In conclusion, the chronic visceral subtype of ASMD showed a predominantly stable disease course in this cohort. We propose that ERT should be initiated on an individual basis and only in case of progression or symptomatic disease. Collection and analysis of real world data are necessary to refine start, stop and follow-up criteria in the future.

EFFECTIVENESS OF AUTOLOGOUS PLATELET-RICH PLASMA FOR HEALING DIABETIC FOOT ULCERS

Autologous platelet-rich plasma (APRP) is widely used to accelerate the healing of chronic wounds. However, the advisability of its use in patients with diabetic foot ulcers (DFU), which develop in various forms of the disease and are associated with complex metabolic conditions, is still being discussed. This study consisted in a comparative analysis of the effectiveness of local use of autologous platelet-rich plasma in the treatment of DFU in patients with neuropathic and neuroischemic forms of the disease. A total of 106 patients with type 2 diabetes mellitus undergoing hospital treatment were divided into a study group (n=48) and a traditional wound therapy group (n=58), similar in ankle-brachial index values ​​and ulcer size. Systemic therapy in both groups of patients included measures to regulate metabolism and nutrition, and infection control. Treatment results were assessed by the area of foot wounds and duration of healing. The duration of therapy and the mean platelet concentration in autologous plasma did not differ between groups. The wound healing time in patients with the neuropathic form (60.4±23.77 days) and the neuroischemic form of the disease (64.8±29.6 days) during treatment with APRP was significantly shorter than in the subgroups of the comparison group with traditional treatment of DFU (85.11±40.7 and 90.40±47.12 days respectively) (p<0.01), but there was no significant difference between the subgroups receiving treatment with APRP. Although there was no significant difference in the average daily healing area among all subgroups (p>0.05), the rate of wound healing in the subgroups with APRP was higher (14.85±10.66 and 15.33±14.91 mm2/day, respectively) than in the subgroups of the comparison group (8.39±6.02 and 8.79±7.13 mm2/day, respectively), which confirms the effectiveness of local treatment with APRP in combination with traditional systemic therapy.

ROLE OF ADAPTATION TO CHRONIC HYPOXIA IN THE DEVELOPMENT OF DYSIMUNIC DISORDERS IN DIABETIC FOOT ULCER

The purpose of the study is to establish the relationship between the immune-mediated DFU in patients with T2DM and the degree of HIF-2-dependent adaptation to chronic hypoxia. Materials and Methods: We conducted a comparative analysis of patients’ clinical characteristics, laboratory markers of infection and individual parameters of adaptive immunity in patients of the main group with neuropathic and neuroischemic forms of T2DM (subgroup 1, n=51, ulcer area less than 6 cm2; subgroup 2, n=28, ulcer area more than 6 cm2), as well as in patients of the comparison group (n=44) with similar forms of T2DM. It was found that the nature of the response to hypoxia, mediated by HIF-2α, played an important role in regulating the activity of the adaptive immune response and the inflammatory-reparative process in patients with T2DM and destructed foot tissue. Results: The presence of foot wounds in patients with T2DM indicates a disruption of the HIF-2α-dependent adaptive response, which is accompanied by activation of inflammatory mediators and a decrease in IgG-dependent mechanisms. In patients with T2DM, increased HIF-2α expression in combination with increased production of immunoglobulins, is obviously a protective mechanism that prevents defects of foot tissue. Conclusion: The clinical and laboratory use of hypoxia biomarkers is promising for predicting the risk of infectious and destructive complications in patients with T2DM.

Incidence of Different Characters of Neuropathic Pain in Cancer Patients Coming to Tertiary Care Centre in North India Over A Period of 1 Year - An Observational Study.

Pain is classified as nociceptive, neuropathic, or nociplastic. Neuropathic pain presents as variable phenotypes (characters) based on specific aetiology and pathophysiology. This study aimed to find out among cancer patients the incidence of different phenotypes of neuropathic pain and form specific phenotypic clusters based on the underlying neurophysiology and association of sensory profile with various organ systems - A prospective observational study. The Institutional Ethical Committee clearance (IEC code: 2020-49-MD-EXP-15) https://ctri.nic.in/Clinicaltrials/showallp.php?mid1=44886&EncHid=88651.15716&userName=CTRI/2020/09/027964 approval was obtained. After written and informed consent, patients of age group 18-80 years, registering in the pain and palliative outpatient department or radiotherapy department with complaints of pain and not taking any anti-neuropathic pain medications, were enrolled. They were assessed using Leeds assessment of neuropathic symptoms and signs (LANSS) pain score, and a score of >12 was eligible for assessment of neuropathic pain phenotypes. Out of 210 cancer patients complaining of pain, a neuropathic component with LANSS >12 was found in 73 (34.76%). The most predominant phenotypes, allodynia> tingling> pricking = burning, were found in 72.60%, 56.16%, and 43.84% of patients, respectively. Phenotypes were clustered into Nodes 1 and 2 based on clinically significant separation of phenotypes. Node 1 had neuropathic pain of spontaneous origin found predominantly in gastrointestinal tract (GIT) and genitourinary tract (GUT) cancers. Node 2 had stimulus-evoked negative and positive characters which occurred in head and neck, thoracic, and spinal metastatic cancers. Careful patient assessment reveals the incidence of neuropathic pain in 34.76%; allodynia and tingling astable the most prominent phenotypes. Broadly, sensory characters were clustered into spontaneous and stimulus-evoked sensations with GIT and GUT cancers presenting with Node 1 symptoms.

Clinical Outcomes of Patients with Chronic Neuropathic Form of Gaucher Disease in the Spanish Real-World Setting: A Retrospective Study.

This was a retrospective, multicenter study that aimed to report the characteristics of type 3 Gaucher disease (GD3) patients in Spain, including the genotype, phenotype, therapeutic options, and treatment responses. A total of 19 patients with GD3 from 10 Spanish hospitals were enrolled in the study (14 men, 5 women). The median age at disease onset and diagnosis was 1 and 1.2 years, respectively, and the mean age at follow-up completion was 12.37 years (range: 1-25 years). Most patients exhibited splenomegaly (18/19) and hepatomegaly (17/19) at the time of diagnosis. The most frequent neurological abnormalities at onset were psychomotor retardation (14/19) and extrinsic muscle disorders (11/19), including oculomotor apraxia, supranuclear palsy, and strabismus. The L444P (c.1448T>C) allele was predominant, with the L444P (c.1448T>C) homozygous genotype mainly associated with visceral manifestations like hepatosplenomegaly, anemia, and thrombocytopenia. All patients received enzyme replacement therapy (ERT); other treatments included miglustat and the chaperone (ambroxol). Visceral manifestations, including hepatosplenomegaly and hematological and bone manifestations, were mostly controlled with ERT, except for kyphosis. The data from this study may help to increase the evidence base on this rare disease and contribute to improving the clinical management of GD3 patients.

Mutations in alpha-B-crystallin cause autosomal dominant axonal Charcot-Marie-Tooth disease with congenital cataracts.

Mutations in the alpha-B-crystallin (CRYAB) gene have initially been associated with myofibrillar myopathy, dilated cardiomyopathy and cataracts. For the first time, peripheral neuropathy is reported here as a novel phenotype associated with CRYAB. Whole-exome sequencing was performed in two unrelated families with genetically unsolved axonal Charcot-Marie-Tooth disease (CMT2), assessing clinical, neurophysiological and radiological features. The pathogenic CRYAB variant c.358A>G;p.Arg120Gly was segregated in all affected patients from two unrelated families. The disease presented as late onset CMT2 (onset over 40 years) with distal sensory and motor impairment and congenital cataracts. Muscle involvement was probably associated in cases showing mild axial and diaphragmatic weakness. In all cases, nerve conduction studies demonstrated the presence of an axonal sensorimotor neuropathy along with chronic neurogenic changes on needle examination. In cases with late onset autosomal dominant CMT2 and congenital cataracts, it is recommended that CRYAB is considered for genetic testing. The identification of CRYAB mutations causing CMT2 further supports a continuous spectrum of expressivity, from myopathic to neuropathic and mixed forms, of a growing number of genes involved in protein degradation and chaperone-assisted autophagy.

The results of neuropathic forms diabetic foot treatment with lipoic acid preparations

Проанализированы результаты лечения 123 больных с синдромом диабетической стопы. В соответствии с современными представлениями, ведущей причиной развития синдрома диабетической стопы и последующей ампутации является диабетическая полинейропатия нижних конечностей. Последняя и связанные с ней деформации стопы, а также потеря защитной болевой чувствительности приводят к возникновению спонтанных язвенных дефектов мягких тканей стопы с дальнейшим их инфицированием и развитием гнойно-некротического процесса. Изучались их дермографические данные, анамнез, клинические проявления и течение заболевания, состояние компенсации углеводного и липидного обменов. Определялись степень тяжести нейропатии, ее клинические проявления, наличие язвенно-некротических поражений, их происхождение, наличие сопутствующей макроангиопатии нижних конечностей, состояние костей стопы, наличие проявлений микроангиопатии. Было также проведено исследование эффективности и переносимости больными разных доз препаратов альфа-липоевой кислоты (600, 900 и 1200 мг в сутки), которую использовали для этиотропного лечения нейропатии. Исследовано влияние препарата альфа-липоевой кислоты на лечение диабетической нейропатии у пациентов, страдающих гнойно-некротическими формами синдрома диабетической стопы. Установлена высокая эффективность применения данной группы препаратов, как в стандартных, так и в увеличенных дозах. Исследование продемонстрировало, что парентеральное введение препаратов альфа-липоевой кислоты как в дозе 600 мг, так и 900 и 1200 мг в сутки одинаково хорошо переносится больными, не вызывает достоверно значимых побочных эффектов и позволяет рекомендовать применение данной группы препаратов внутривенно капельно с последующим применением 600 мг/сутки перорально при лечении больных с синдромом диабетической стопы, осложненным язвенно-некротическим процессом. The results of treatment of 123 patients with diabetic foot syndrome were analyzed. According to modern concepts, the leading cause of the development of diabetic foot syndrome and subsequent amputation is diabetic polyneuropathy of the lower extremities. The latter and associated foot deformities, as well as the loss of protective pain sensitivity, lead to spontaneous ulcerative defects in the soft tissues of the foot with their further infection and the development of a purulent-necrotic process. Their dermographic data, anamnesis, clinical manifestations and the course of the disease, the state of compensation of carbohydrate and lipid metabolism were studied. The severity of neuropathy, its clinical manifestations, the presence of ulcerative-necrotic lesions, their origin, the presence of concomitant macroangiopathy of the lower extremities, the condition of the bones of the foot, the presence of manifestations of microangiopathy were determined. A study was also conducted on the effectiveness and tolerability of patients with different doses of alpha-lipoic acid preparations (600, 900 and 1200 mg per day), which was used for the etiotropic treatment of neuropathy. The effect of alpha-lipoic acid on the treatment of diabetic neuropathy in patients suffering from purulent-necrotic forms of diabetic foot syndrome was studied. The high efficiency of the use of this group of drugs, both in standard and in increased doses, has been established. The study demonstrated that parenteral administration of alpha-lipoic acid preparations, both at a dose of 600 mg, and 900 and 1200 mg per day, is equally well tolerated by patients, does not cause significantly significant side effects and allows us to recommend the use of this group of drugs intravenously, followed by the use of 600 mg /day orally in the treatment of patients with diabetic foot syndrome complicated by ulcerative necrotic process.

INTERLEUKINS AND EICOSANOIDS: PATHOGENETIC PATTERNS OF DIABETIC FOOT ULCER

We examined 40 patients with neuropathic (group 1, n=20) and neuroischemic (group 2, n=20) diabetic foot. Before surgical treatment, we studied the content of cytokines (TNF-α, IFN-γ, IL-1β, IL-6 and IL-10) and eicosanoids (LTB4 and PGE2) in the exudate of the ulcer discharge. Pathogenetic mechanisms of inflammation disorders in patients with neuropathic and neuroischemic forms of diabetic foot are different. The neuropathic form is characterized by an increase in the level of TNF-α and IL-6 in the wound exudate, inhibition of the IL-1β and IL-10 secretion, and the predominance of LTB4 in contrast to inhibition of PGE2 synthesis. At the same time, the formation of CD8+ is inhibited as well as the switching of the neutrophilic phase to the macrophage phase by maintaining the conditions for the differentiation of M1 macrophages. In the neuroischemic form, we revealed hyperproduction of IL-1β, IL-10, IFN-γ, CD4+ with inhibition of IL-6 secretion and eicosanoids imbalance (PGE2 prevail over LTB4). This disrupts the differentiation of M2 macrophages. All identified disorders may be due to the persistence of various neutrophil phenotypes in the wound.

Neuropathic pain: Mechanisms and therapeutic strategies.

The physiopathology and neurotransmission of pain are of an owe inspiring complexity. Our ability to satisfactorily suppress neuropathic or other forms of chronic pain is limited. The number of pharmacodynamically distinct and clinically available medications is low and the successes achieved modest. Pain Medicine practitioners are confronted with the ethical dichotomy imposed by Hippocrates: On one hand the mandate of primum non nocere, on the other hand, the promise of heavenly joys if successful divinum est opus sedare dolorem. We briefly summarize the concepts associated with nociceptive pain from nociceptive input (afferents from periphery), modulatory output [descending noradrenergic (NE) and serotoninergic (5-HT) fibers] to local control. The local control is comprised of the "inflammatory soup" at the site of pain origin and synaptic relay stations, with an ATP-rich environment promoting inflammation and nociception while an adenosine-rich environment having the opposite effect. Subsequently, we address the transition from nociceptor pain to neuropathic pain (independent of nociceptor activation) and the process of sensitization and pain chronification (transient pain progressing into persistent pain). Having sketched a model of pain perception and processing we attempt to identify the sites and modes of action of clinically available drugs used in chronic pain treatment, focusing on adjuvant (co-analgesic) medication.

ODP186 Difficulties in diagnosing MODY: clinical case

Abstract Background MODY is one of the monogenic forms of diabetes mellitus, which includes 14 subtypes with different course and clinical picture. Final clinical diagnosis involves a molecular genetic study and is a key factor in successful treatment. Clinical case. Patient P., 33 years old, complained of aggravation of the condition after and during the dialysis procedure: general weakness, blood pressure rose to 220 mmHg, after the procedure a drop to 110-120 mmHg, lack of effect from hypertensive drugs, headaches. In 2004, type 1 diabetes mellitus was diagnosed based on complaints of polydipsia, polyuria, and fasting glycemia up to 9 mmol/l. Basic bolus insulin therapy was prescribed. Patient noted a frequent development of hypoglycemic conditions and independently canceled insulin therapy. For a long time the patient went without hypoglycemic therapy. In 2016, baseline insulin therapy was prescribed again, which resulted with frequent episodes of hypoglycemia resuming. In 2019, a diagnosis of MODY type 3 was made without medical and genetic counseling. Due to the high level of C-peptide 3057.1 pmol /L (160-1100), Repaglinide 0.5 mg was prescribed to be taken 3 times a day. Against the background of this treatment, compensation and stabilization of the condition has been observed. Family history: the mother has diabetes mellitus since the age of 22, manifested during pregnancy; receives Glibenclamide with a positive effect. Since 2011, diabetic distal sensorimotor polyneuropathy of the upper and lower extremities, diabetic foot syndrome, neuropathic form have been identified. Ulcerative defect of the I degree. Long-term non-healing trophic ulcer of the right foot for 6 years. In 2016, chronic kidney disease C5 A3 was detected. At the moment, the patient is on program dialysis. Complications of nephropathy were verified – secondary hyperparathyroidism, osteoporosis, moderate nephrogenic anemia, symptomatic nephrogenic arterial hypertension of grade 3, risk 4. In 2018, proliferative diabetic retinopathy of both eyes was detected. Total recurrent hemophthalmos of the right eye, subtotal hemophthalmos of the left eye. In 2021, autonomic neuropathy, gastrointestinal form and autonomic cardiovascular form were verified. The patient underwent a molecular genetic study for the identification of pathogenic mutations in the HNF1A gene, however, according to the study, mutations in the HNF1A gene were not detected. Thus, the diagnosis of MODY type 3 has not been confirmed. It is necessary to conduct a further diagnostic search for the type of MODY in order to make a final diagnosis. Conclusion This clinical case demonstrates the importance of a personalized approach to each patient, as well as conducting a molecular genetic study to make a final clinical diagnosis and prescribe timely pathogenetic therapy. Presentation: No date and time listed

STIMULATION OF THE WOUND PROCESS IN LONG-TERM UNHEALED WOUNDS IN PATIENTS WITH DIABETIC FOOT SYNDROME

The purpose of the work. Compare the effectiveness of PRP and general accepted methods of local therapy for long-term unhealed wounds in patients with diabetic foot syndrome.
 Materials and methods. A study was performed in 33 long-term patients unhealed wounds on the foot and leg in the neuropathic form of diabetic foot syndrome. Patients were divided into two groups depending on the nature of the received therapies - PRP and local therapy according to generally accepted principles. The effectiveness of therapy was assessed by the nature of changes in the microflora and c wound cell composition, as well as wound surface area on the 1st day, 8th and 22nd after starting treatment.
 Results. The use of PRP allowed to observe on the 8th day regenerative-inflammatory type of cytogram, have manifestations of vascularization and epithelialization, reduce the number of patients with infected wounds by 2.7 times and reducing the wound surface area by 1.7 cm, which is 3.4 times more than in the second group (0.5 cm). The introduction of the second dose of PRP is even more stimulating reparative changes in the wound, manifested by the regenerative type of cytogram, reducing the number of infected wounds by 8 times, and reducing the area wound surface 2 times from the first measurement, while in the second group only on the 22nd day there were positive changes that were characteristic of the first group on the 8th day.
 Conclusion. Thus, the use of PRP in therapy is long unhealed wounds in diabetic foot syndrome, is a promising area of ​​regenerative therapy. PRP is a way to obtain a natural concentration of internal factors of growth with minimal invasiveness and low costs. Proposed method of biological therapy in such patients is simple and affordable for both patient and for the doctor.

Recurrent foot ulcers in patients with diabetes mellitus in out-patient care

OBJECTIVE. Relapses of diabetic foot ulcers are an urgent problem of outpatient surgery, however, risk factors for relapse, as well as the definition of relapse itself remain a subject of discussion. The presented study investigates the frequency of relapses of ulcerative foot defects in diabetes mellitus, the risk factors for their development and treatment outcomes, based on the definition of relapse as the development of a repeated defect in the same place as the healed defect.METHODS AND MATERIALS. The data of 1714 patients with foot ulcers (2213 ulcerative defects) from 01.2012 to 01.2017 were studied. Patients were divided into two groups: with relapses (n=239, 13.9%) and without them (n=1475). Risk factors for relapse, characteristics of patients and ulcerative defects, and treatment outcomes were evaluated.RESULTS. Relative risk for relapse: type 1 diabetes mellitus (1.36); Charcot foot (1.65); history of amputation of the great toe (1.35); severe polyneuropathy (1.25); neuropathic foot (1.37). Relapses/single ulcer (%): superficial lesion 72.8/63.3 (р<0.01); primary healing: 61.1/52.7 (p=0.025); healing after surgery (amputations excluded): 4.2/4.5 (ns); amputations: 7.1/6.6 (ns) of which major 5.9/20.6 (p=0.01); non-healing (%): 11.7/5.5 (р=0.001); loss of follow-up (%): 15.9/30.7 (р=0.0001). Median duration of the treatment (days) of relapses/single ulcer: conservative 147/114; healing after surgery (amputations excluded) 241/170; after amputation 286/182. Revascularization in relapses – 7 (100%), with single ulcers – 66 (59.5% of patients with critical ischemia).CONCLUSION. 5-years relapse rate was 13.9 %. Patients with Charcot foot, postoperative deformities and with neuropathic form of diabetic foot syndrome are more prone for foot reulceration. Recurrent ulcers are characterized with longer duration of the treatment however their primary healing rate is higher compared with single ulcer group. The results of the study were significantly influenced by the high frequency of loss of follow-up in both groups.

Нейропатичні форми лізосомних хвороб накопичення в Україні

Актуальність. На сьогодні виявлені кілька тисяч спадкових захворювань, що характеризуються ураженням нервової системи. До них належать лізосомні хвороби накопичення. Група цих захворювань включає майже 60 різних нозологічних форм спадкових моногенних порушень обміну речовин. Клінічна картина лізосомних хвороб характеризується прогредієнтним перебігом, мультисистемними порушеннями (ураження кісток скелета, м’язів, серцево-судинної, дихальної систем тощо). За тяжкого перебігу цих захворювань відзначають ураження нервової системи. Нейродегенеративні захворювання у дітей зазвичай спричинені лізосомними хворобами накопичення (ЛХН). Діагностика лізосомних хвороб в Україні розпочата у 1995 р. в НДСЛ «Охматдит». Уперше в Україні проаналізовані всі випадки лізосомних хвороб накопичення, діагностовані в період 1995–2016 рр., а також їх поширеність в українській популяції. Останніми роками спектр лабораторної діагностики ЛХН суттєво розширився, накопичено унікальний досвід клінічної ідентифікації різних форм цих рідкісних захворювань, що позначається на частоті їх виявлення, дає можливість аналізувати епідеміологічні показники, розробляти ефективні заходи щодо оптимізації ранньої діагностики. Мета. Вивчення поширеності та спектра нейропатичних форм лізосомних хвороб накопичення в Україні, порівняння отриманих результатів з даними епідеміологічних досліджень, проведених в інших країнах. Матеріали та методи. Проаналізовано клінічні та лабораторні дані пацієнтів, у яких діагностовано різні форми лізосомних хвороб, у тому числі і нейропатичні, за період спостереження 1995–2016 рр. НДСЛ «Охматдит» — єдиний лікувальний заклад в Україні, де здійснюється клініко-лабораторна діагностика цих захворювань. Поширеність лізосомних хвороб розраховували як відношення загальної кількості пацієнтів із діагнозом певної ЛХН до загальної кількості дітей, народжених живими у той самий період часу, що і хворі, в яких у подальшому діагностовано лізосомні хвороби (з розрахунку на 100 000 осіб, які народилися живими). Результати. Діагноз лізосомної хвороби встановлено у 343 хворих серед 324 родин з усіх регіонів України. Найбільш численними в структурі лізосомних хвороб виявилися сфінголіпідози (52 % спостережень) і мукополісахаридози (30 %). Нейропатичний варіант перебігу діагностований у 84 (47 %) серед 179 хворих із групи сфінголіпідозів. Хворобу Гоше діагностовано у 19,4 % хворих серед усіх лізосомних хвороб. ІІ тип хвороби Гоше (гостра нейропатична форма) відзначений у 3 (5 %) пацієнтів, ІІІ тип — у 5 (8 %). Проте, за даними дослідників з інших країн, у різних популяціях частка нейропатичної форми хвороби Гоше різниться, що, ймовірно, зумовлене особливостями певної популяції. GM1- і GM2-гангліозидози діагностовано нами у 8 % спостережень, метахроматична лейкодистрофія — у 7 %. Друге місце в структурі лізосомних хвороб посідає велика гетерогенна група мукополісахаридозів — 30 % спостережень. Синдром Хантера діагностований у 34 % спостережень у структурі мукополісахаридозів, синдром Санфіліппо (найчастіше типу А) — у 24,4 %. Нейрональний цероїдліпофусциноз ІІ типу діагностований нами у 22 хворих серед 22 родин, нейрональний цероїдліпофусциноз І типу не виявлений в жодного пацієнта. Вік 85 % (n = 291) пацієнтів, у яких було встановлено діагноз лізосомного захворювання, був молодше 18 років. Вікові інтервали селективної вибірки пацієнтів для подальшої лабораторної діагностики мають неабияке значення. Певною проблемою для України є несвоєчасне виявлення лізосомних захворювань у регіонах. Висновки. Структура лізосомних хвороб накопичення, виявлених в Україні, цілком відповідає такій в інших країнах, де ці хвороби ефективно діагностують упродовж тривалого часу. Нейропатичні форми становлять 57 % у структурі лізосомних хвороб накопичення. Ця гетерогенна група захворювань, що вимагає складної поетапної клініко-лабораторної діагностики, і є однією з основних причин виникнення нейродегенеративних захворювань у дитячому віці. Дані нашого дослідження щодо поширеності нейропатичних форм ЛХН в Україні є попередніми і потребують подальшого вивчення.

Possibilities of rehabilitation in atherosclerosis of arteries of the lower limbs in combination with diabetes

BACKGROUND: According to the World Health Organization, more than 17 million people die from cardiovascular diseases every year in the world. Coronary heart disease is the leading cause of death in industrialized countries.
 AIMS: To evaluate the immediate result of treatment by revascularization of the limb and organ-preserving surgical interventions for purulent-necrotic lesions of the feet, neuropathic form of diabetic foot with osteoarthropathy in chronic arterial insufficiency of the IV degree.
 MATERIAL AND METHODS: In the paper, the authors investigated possible treatments with different limb lesions in patients diagnosed with diabetes mellitus. Since in this disease there are complications on the cardiovascular system, most people are diagnosed with obliterating atherosclerosis, which leads to slow necrosis of the limbs. This causes diabetes patients, not only severe pain and an aesthetically unsightly state of the body, but also noticeably worsens the quality of life.
 RESULTS: With a consolidated approach to this problem, endocrinologists and cardiovascular surgeons developed and tested the method of endascular surgery. Patients diagnosed with obliterating lower extremity vascular atherosclerosis against the background of diabetes mellitus with trophic and necrotic lesions of the peripheral lower extremities underwent enduscular surgery to revascularize the limb, which showed not just positive immediate treatment results, but gave opportunities to preserve patients limbs.
 CONCLUSION: Timely recognition and treatment of purulent-necrotic lesions of the feet, the neuropathic form of diabetic foot with osteoarthropathy requires an interdisciplinary approach and close cooperation of doctors of different specialties - endocrinologists, surgeons, podiatrists, orthopedists, general practitioners, etc. Only if these conditions are met, it is possible to achieve significant success and minimize the number of irreversible deformities and amputations of the feet, the weighting of disability groups.

Brain Volume Alterations Using 3tesla Magnetic Resonance and Neuropsychological Findings in Gaucher Disease Patients

▪Gaucher Disease (GD) is a metabolic inherited disorder, that classically includes three clinical phenotypes. Type I GD (GD1) is considered as a non-neuronopathic variant and can mimic a hematologic disease; type II (GD2) is classified as an acute neuropathic form and type III (GD3) is characterized by a slower and progressive neurological involvement. A protective role of N370S mutation against neurological impairment had been previously hypothesized in GD1, however, increasing data and our experience show that patients with GD1 may present clinical signs of parkinsonism, frequently combined with cognitive impairment and behavioral alterations. Structural brain changes associated with cognitive impairments in GD patients, especially type I, has not yet been reported.The prospective study, called SENOPRO_GAUCHER, has investigated in depth, the neurological status in GD patients using a multidisciplinary approach, including 3Tesla magnetic resonance (3T MR). This study was approved by our Ethics Committee. Baseline data on neurological, psychological, psychiatric, somatosensory, and motor evaluations, and electroencephalography (EEG) surprisingly revealed two, or more, clinical and/or instrumental, neurological signs in all GD1 patients, and a wide spectrum of neurological abnormalities in all GD3 patients.We, hereby, report the results of investigations on brain structure of GD patients, compared to that of healthy subjects, using 3T MR, in order to evaluate whether brain alterations can predict neurocognitive impairment in GD patients, especially GD1. Out of 22 GD patients, assessed for neuropsychological and psychiatric functions, 19 (17 GD1, 2 GD3, median age = 44, range 17 - 68 years) underwent 3T MR examination. Regarding genotyping, all but one of the 17 GD1 patients was N370S mutation heterozygous.A Voxel-based Morphometry (VBM) analysis was performed to investigate brain structure in the 19 GD patients and in 19 healthy subjects with no neurological or neuropsychiatric disease. The healthy subjects, matched to patients by age, sex, and education, in addition to 3T MR, underwent neuropsychological assessment using Mini-Mental State Exam and Mental Deterioration Battery, to evaluate cognitive functions and mental deterioration, respectively. Qualitative MR examinations revealed unspecific abnormalities in 7/17 GD1 patients. In particular, cortical and/or subcortical areas of gliosis (4 patients), vascular ectasia extended from the left frontal surface of the brain to the lateral ventricle (1 patient), dilation of perivascular spaces in the sub-cortical and nucleus-basal area (1 patient), diffuse suffering of the brain white matter due to a chronic ischemic vascular damage (1 patient) were found. Concurrently, results of the VBM analysis revealed that a set of regions, mostly located in the prefrontal and parieto-occipital cortex, were significantly reduced in GD patients, compared to healthy subjects. The most affected regions included the frontal eye fields, the dorso-lateral prefrontal cortex, the posterior cingulate cortex, and the V3B area. Psychological and psychiatric evaluations underlined anxiety, depression, and somatic concerns in 10/17 GD1 patients, combined with cognitive impairments in two of them. Moreover, 1/2 GD3 and 5/17 GD1 patients showed cognitive impairments in attention, language, short-term memory, and executive cognitive functions. The local brain volume reductions, detected in GD1 patients, were in line with the cognitive impairments resulted in the neuropsychological assessment. Cortical reductions of fronto-parietal regions, responsible for the planning and execution of movements, are compatible with impairments in executive functions (digit-span) and visuo-spatial memory, found in GD1 patients. Moreover, impairments in short-term memory observed in GD1 patients are compatible with cortical reductions in the frontal cortex found by the VBM analysis.In conclusion, focal brain differences found between GD1 patients and healthy subjects may predict and clarify the cognitive impairments and behavioural alterations observed in GD patients. The brain structural analyses, associated with neuropsychological assessment, suggest that a multidisciplinary approach is necessary in evaluating GD1 patients. DisclosuresGiona: Sanofi Genzyme: Consultancy, Research Funding, Speakers Bureau; Takeda: Speakers Bureau; Novartis: Consultancy.

Multimodal Spinal Cord Mapping during Spinal Cord Stimulator Placement: Technical Note

ABSTRACT Spinal cord stimulation is used to treat patients with severe neuropathic pain and other forms of debilitating back pain. Spinal cord stimulators (SCS) can either be placed under sedation or general anesthesia (GA). This study evaluated the utility of neurogenic evoked potentials in enabling multimodal spinal cord mapping (MSCM) for the placement of SCSs under GA. The goal of our MSCM paradigm, which integrated recordings from multiple antidromic and orthodromic generators, was to enable the use of precise neuromonitoring techniques, typically used for localizing the midline of the dorsal spinal cord in intramedullary tumor cases, for the safe placement of SCSs. Two distinct modalities were incorporated - orthodromic responses from the somatosensory cortex (Cp3-Cp4 cancellation) and antidromic stimulation via the SCS which resulted in compound nerve action potentials of the extremities. In addition, two incidental findings were made. First, our results suggest that previous investigations may have incorrectly identified compound muscle action potentials as compound nerve action potentials. Additionally, anti D-wave responses, that are theorized to be the equivalent of a D-wave, were observed. This manuscript describes the first use of MSCM, which will ultimately provide neurophysiologists more information during SCS implantation, enabling them to confirm midline placement more confidently. MSCM also allows the application of techniques typically used in spinal cord tumors, allowing the neurophysiologist to maintain proficiency with these techniques on more common procedures. The parallel collection of several sources of data will allow for future studies that better define which mapping methods are the most accurate.

Psychometric and accuracy comparison of three commonly used questionnaires for the diagnosis of neuropathic pain.

Objectives:Diagnosis of neuropathic pain is challenging. Recently, scientists developed multiple questionnaires to expedite this diagnosis including the Self-completed Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS), Douleur Neuropathique 4 questionnaire (DN4), and Neuropathic Pain Questionnaire–Short Form (NPQ-SF).Materials and Methods:We conducted a prospective cohort study to compare the psychometric characteristics and accuracy of the three questionnaires. We assessed reliability with the Cronbach's α reliability coefficient and inter-item correlations, and validity with receiver operating characteristic (ROC) and correlation analyses. We assessed agreement between the diagnosis of the questionnaires and the reference clinical diagnosis using Cohen's kappa coefficient.Results:188 patients were analyzed: 141 (75%) had “definite neuropathic” and 47 (25%) had “nonneuropathic” pain. The NPQ-SF and S-LANSS questionnaires demonstrated acceptable reliability with Cronbach's α coefficient values of 0.54 (95% CI: 0.41–0.64) and 0.65, (95%CI: 0.57–0.72), respectively. The DN4 questionnaire demonstrated high reliability with Cronbach's α coefficient of 0.74 (95%CI: 0.68–0.79). The NPQ-SF, DN4, and S-LANSS questionnaires demonstrated “excellent” diagnostic ability with an area under the ROC curve of 0.82 (95% CI: 0.75–0.89), 0.89 (95% CI: 0.83–0.95), and 0.83 (95% CI: 0.75–0.90), respectively. Based on their optimal cutoff values, the DN4 had the highest sensitivity and lowest specificity in discriminating between neuropathic and nonneuropathic patients, while the S-LANSS had the lowest sensitivity and highest specificity.Conclusion:Both NPQ-SF and S-LANSS demonstrated acceptable reliability, while DN4 demonstrated high reliability. All three demonstrated excellent diagnostic validities; however, it is important to consider the sensitivity and specificity of each.

Bubbling Treatment Option in the Complex Therapy of Diabetic Foot Syndrome

Diabetes mellitus (DM) is the most common and socially significant endocrine disease that leads to early disability and is the most common cause of mortality in patients after cancer and cardiovascular pathology. The cost of managing patients with diabetes can reach 30% of the country's health budget, 90% of which is spent on the treatment of its complications. Diabetic foot syndrome (DFS) is developed in 20-80% of patients and is one of the most dangerous late complications. In clinical practice, various approaches to its treatment are used, but the number of high amputation and mortality rate in this group of patients remains significant. The aim of the study was to improve the results of treatment of patients with diabetic foot syndrome (DFS) by including the bubbling treatment method in the program of therapeutic measures. Forty-eight patients with neuropathic and neuroischemic forms of DFS were treated. The control group consisted of 23 patients receiving conventional treatment, the main group included 26 patients, who were applied bubbling treatment option locally. The analysis of groups of patients showed no significant differences by gender, age, stages of diabetic foot syndrome, depth of necrotic defect, complications and concomitant diseases. The use of the bubbling treatment method in the complex treatment of patients with DFS allowed more effectively arresting symptoms of local (edema, hyperemia, wound exudate, necrolysis) and general inflammation, anemia and intoxication syndromes, contributed to the activation of regeneration processes in soft tissues, which, combined with complex FDS treatment, together, reduced the number of amputations by 18.7%.