Effect of melatonin on peripheral nerve damage resulting from tibial defect in rats / Efecto de la melatonina sobre el daño de los nervios periféricos como resultado de un defecto tibial en ratas

SUMMARY: Peripheral nerve damage (PNI) can cause demyelination, axonal degeneration and loss of motor and sensory function. Melatonin with its antioxidative effect, has been reported to reduce scar formation in nerve injury, take a role in repair process by suppressing fibroblast proliferation in the damaged area. It was aimed to investigate the effect of melatonin in the repair of peripheral nerve damage and the relationship between S100 proteins and angiogenic regulation. Wistar albino rats were divided into 3 groups. In the Defect group, 6 mm tibial bone defect using a motorized drill was created and kept immobile for 28 days. In Defect + graft group, tibial bone defect with allograft treatment was applied and kept immobile for 28 days. In Defect + graft + Melatonin group, melatonin was administered to defect + allograft group. All rats were sacrified by decapitation, skin and tibia bone were removed then fixed with 10 % neutral buffered formalin and embedded in paraffin, sections were examined under light microscopy. In the Defect+Graft group, enlargement and occlusion of the vessels with degeneration of the epineural sheath, thickening of the endoneural sheath and mild hyperplasia of schwannocytus (Schwann cells) were remarkable. In the Defect+Graft+Melatonin group, the epineural sheath was tight and regular, the axonal structures were prominent in the endoneural area. Mild S100 expression was observed in Defect+Graft group in fibers of the endoneural region with a prominent expression in schwannocytus. In Defect+Graft+Melatonin group (10mg/kg), S100 expression was moderate in areas where schwannocytus proliferated and nerve-connective tissue sheaths were reconstructed. VEGF expression was moderate in endoneural, perineural and epineural connective tissue sheaths in the Defect+Graft+Melatonin group, with negative expression in blood vessel endothelial cells, but with a positive expression in schwannocytus. We conclude that with the application of melatonin; oxidative stress decreases, schwannocytus proliferation increases, having positive influence on nerve repair with the regulation of S100 signaling and angiogenetic structuring.

RESUMEN: El daño a los nervios periféricos puede causar desmielinización, degeneración axonal y pérdida de la función motora y sensorial. Se ha informado que la melatonina, con su efecto antioxidante, reduce la formación de cicatrices en lesiones nerviosas y desempeña un papel en el proceso de reparación al suprimir la proliferación de fibroblastos en el área dañada. El objetivo de este trabajo fue investigar el efecto de la melatonina en la reparación del daño de los nervios periféricos y la relación entre las proteínas S100 y la regulación angiogénica. Ratas albinas Wistar se dividieron en 3 grupos. En el grupo Defecto, se creó un defecto óseo tibial de 6 mm con un taladro motorizado y se mantuvo inmóvil durante 28 días. En el grupo Defecto + injerto, se aplicó tratamiento de defecto óseo tibial con aloinjerto y se mantuvo inmóvil durante 28 días. En el grupo Defecto + injerto + Melatonina, se administró melatonina al grupo defecto + aloinjerto. Todas las ratas fueron sacrificadas por decapitación, se extrajo la piel y el hueso de la tibia y luego se fijaron con formalina tamponada neutra al 10 % y se incluyeron en parafina, las secciones se examinaron bajo microscopía óptica. En el grupo Defecto+Injerto, fueron notables el agrandamiento y la oclusión de los vasos con degeneración de la vaina epineural, engrosamiento de la vaina endoneural e hiperplasia leve de los schwannocitos (neurolemnocitos). En el grupo Defecto+Injerto+Melatonina, la vaina epineural era estrecha y regular, las estructuras axonales eran prominentes en el área endoneural. Se observó expresión leve de S100 en el grupo Defecto+Injerto en fibras de la región endoneural con una expresión prominente en los schwannocitos. En el grupo Defecto+Injerto+Melatonina, la expresión de S100 fue moderada en áreas donde proliferaron los schwannocitos y se reconstruyeron las vainas de tejido conectivo nervioso. La expresión de VEGF fue moderada en vainas de tejido conectivo endoneural, perineural y epineural en el grupo Defecto+Injerto+Melatonina, con expresión negativa en células endoteliales de vasos sanguíneos, pero con expresión positiva en schwannocitos. Concluimos que con la aplicación de melatonina; disminuye el estrés oxidativo, aumenta la proliferación de schwannocitos, influyendo positivamente en la reparación nerviosa con la regulación de la señalización S100 y la estructuración angiogenética.

Efficacy of Wen-Luo-Tong on Peripheral Neuropathy Induced by Chemotherapy or Target Therapy: A Randomized, Double-Blinded, Placebo-Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate the efficacy of Wen-Luo-Tong Granules (WLT) local administration in the treatment of patients with peripheral neuropathy (PN) induced by chemotherapy or target therapy.@*METHODS@#This study is a randomized, double-blinded, and placebo-controlled trial. Seventy-eight patients with PN induced by chemotherapy or target therapy were enrolled from China-Japan Friendship Hospital between July 2019 and January 2020. They were randomly assigned to WLT (39 cases) and control groups (39 cases) using a block randomization method. The WLT group received WLT (hand and foot bath) plus oral Mecobalamin for 1 week, while the control group received placebo plus oral Mecobalamin. The primary endpoint was PN grade evaluated by the National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE). The secondary endpoints included quantitative touch-detection threshold, neuropathy symptoms, Quality of Life Questionnaire-Chemotherapy Induced Peripheral Neuropathy (QLQ-CIPN20), and Quality of Life Questionnaire-Core30 (QLQ-C30).@*RESULTS@#After treatment, the PN grade in the WLT group was significantly lower than that in the control group (1.00 ± 0.29 vs. 1.75 ± 0.68, P<0.01). The total effective rate in the WLT group was significantly higher than that in the control group (82.05% vs. 51.28%, P<0.01). Compared with the control group, the touch-detection thresholds at fingertips, neuropathy symptom score, QLQ-CIPN 20 (sensory scale, motor scale, autonomic scale, and sum score), and QLQ-C30 (physical functioning, role functioning, emotional functioning, and global health) in the WLT group significantly improved after treatment (P<0.01 or P<0.05).@*CONCLUSION@#WLT local administration was significantly effective in the treatment of patients with PN induced by chemotherapy or target therapy. (Trial registration No. ChiCTR1900023862).

A case of malignant atrophic papulosis with cranial nerve and peripheral nerve impairment

Malignant atrophic papulosisis is a rare, multisystem obliterative vasculopathy of unknown etiology, occasionally involving the cranial nerve. We describe the first case of malignant atrophic papulosisis with cranial nerve and peripheral nerve involvement in China. A 47-year-old woman presented to our hospital with atrophic porcelain white papules over the trunk and extremities, numbness in the right calf, vision decrease and impaired movement of the right eye. She was diagnosed with malignant atrophic papulosisis, based on characteristic symptoms and histopathologic examination. The patient was treated with dipyridamole and aspirin for 9 months, but later died of gastrointestinal hemorrhage. We reviewed currently available case reports on cranial nerve involvement in malignant atrophic papulosisis and emphasized the importance of skin biopsy in diagnosing this disease.

Prospective evaluation of the effect of short-term oral vitamin D supplementation on peripheral neuropathy in type 2 diabetes mellitus

We aimed to assess the efficacy of short-term oral vitamin D supplementation on peripheral neuropathy in patients with type 2 diabetes. Materials and This prospective, placebo-controlled trial included 112 type 2 diabetic patients with diabetic peripheral neuropathy [DPN] and vitamin D [25[OH]D] deficiency. Patients were sequentially assigned to a treatment group [n = 57] and a placebo group [n = 55]. DPN was assessed using a neuropathy symptom score [NSS], a neuropathy disability score [NDS] and a nerve conduction study [NCS]. Vitamin D status was determined by measuring the serum total 25[OH]D concentration. Patients received either oral vitamin D[3] capsules or starch capsules once weekly for 8 weeks. The primary outcome was changes in NSS and NDS from baseline. The secondary outcome was changes in the NCS result. Serum 25[OH]D concentrations significantly improved after oral vitamin D supplementation in the treatment group when compared to the placebo group [32.8 +/- 23.7 vs. 1.1 +/- 3.6, p < 0.0001]. Similarly, the improvement in NSS values was significantly greater in the treatment group than in the placebo group [-1.49 +/- 1.37 vs. -0.20 +/- 0.59, p < 0.001]. No improvement was observed for NDS and NCS between the 2 groups after treatment. Short-term oral vitamin D[3] supplementation improved vitamin D status and the symptoms of neuropathy in patients with type 2 diabetes

Beyond ten cycles of cabazitaxel for castrate-resistant prostate cancer.

Background: There are limited data regarding cabazitaxel use beyond 10 cycles. Patients and Methods: Retrospective analysis of prospectively collected data of patients with metastatic castrate-resistant prostate cancer who received over 10 cycles of cabazitaxel after docetaxel failure. Results: Four patients received between 14 and 27 cycles. Reasons for stopping cabazitaxel were toxicity (2), progression (1) and logistics (1). Two of the three patients with measurable disease attained a partial remission (PR). Three patients continued to have a PSA response after 10 cycles; PSA nadir occurred between 17 and 23 cycles. Other than peripheral neuropathy (PN), all the cabazitaxel-related toxicities occurred after the initial cycles and did not increase cumulatively. Clinically significant neuropathy occurred after 15-17 cycles. The cabazitaxel-induced PN was partially reversible, with improvement from grade 3 to grade 2 after a 3-5-month long drug holiday. Conclusion: Cautiously continuing cabazitaxel until progression or intolerable toxicity may maximize efficacy.

Restless legs syndrome in subjects with a knee prosthesis: evidence that symptoms are generated in the periphery

OBJECTIVE: There are no data adressing the prevalence of restless legs syndrome in subjects who have knee prosthesis. Therefore, we conducted a cross-sectional survey of subjects who underwent knee prosthesis surgery. METHOD: A total of 107 subjects (30 male, 77 female) were interviewed over the telephone regarding restless legs syndrome symptoms. If the patients exhibited symptoms of the syndrome, we conducted face-to-face interviews. Lastly, a therapeutic test with pramipexole was proposed for each subject. RESULTS: In our cohort, 7 males (23 percent) and 30 females (39 percent) had restless legs syndrome. Of these, 6 males and 23 females were submitted to face-to-face-interview. Of the males, 5 (83 percent) had restless legs after the knee surgeryexclusively in the operated leg- and reported no family restless legs history. One man had a prior case of bilateral restless legs syndrome, a positive family history and claimed exacerbation of symptoms in the operated leg. Among the females, 16 (69 percent) had restless legs prior to surgery. A total of 10 female patients reported bilateral symptoms, with fewer symptoms in the operated leg, while 6 displayed a worse outcome in the operated leg. The 7 females (31 percent) without restless legs prior to surgery and without a family history experienced symptoms only in the operated leg. All subjects responded favorably to the pramipexole therapeutic test. CONCLUSION: Our results suggest that secondary unilateral restless legs syndrome may ensue from knee prosthesis surgery and that the symptoms are generated in the peripheral nervous system.

Lead-induced peripheral neuropathy following ayurvedic medication.

Lead poisoning following intake of Ayurvedic medication is one of the recent areas of concern. We report a case of a 58-year-old type II diabetic man who was stable with diet control and 30 mg pioglitazone per day. He took Ayurvedic medication for generalized weakness and developed peripheral neuropathy following its intake. He was found to have high blood and urinary lead levels and was diagnosed to have subacute lead poisoning. He was treated with d-Penicillamine for 8 weeks, following which his lead levels became normal. The use of d-Penicillamine was proved highly effective in treating a case of lead poisoning.

Neuroplasticidad y dolor / Neuroplasticity and pain

Todas las formas de dolor incluyen el desarrollo de un estado de hiperalgesia que ilustra la naturaleza dinámica y plástica de la sensación de dolor. La hiperalgesia es la característica más importante del proceso doloroso y es la expresión de la hipersensibilidad de las vías del dolor inducida por la sensibilización de los receptores periféricos que registran eventos dolorosos y de las neuronas que transmiten y procesan esta información sensorial al SNC. Los nociceptores periféricos se sensibilizan adquiriendo una mayor y a veces nueva capacidad de respuesta a los estímulos periféricos. Por otra parte, un proceso de plasticidad sináptica, del cual se ha identificado una variedad de componentes moleculares, interviene en la amplificación central de las señales de las aferencias nociceptivas, lo cual evoca la hipersensibilidad de las neuronas centrales. El resultado final es un proceso sensorial que, a pesar de haber sido puesto en marcha inicialmente por una lesión, puede no mantener una relación estrecha con la lesión original y convertirse en un estado de dolor crónico sin tener una causa definida.

All froms of pain include the development of a hyperalgesic state that illustrates the dynamic and plastic nature of pain sesation. Hyperalgesia is the most prominent feature of the pain process and is the expression of hypersensitivity of the pain pathway induced by the sensitization of the peripheral receptors that signal painful events and of the neurons that transmit and process this sensory information to the CNS. Peripheral nociceptors can be sensitized, acquiring enhanced, and sometimes novel, responsiveness to peripheral stimuli. On the other hand a process of synaptic plasticity, of which several molecular components have already been identified, mediates the central amplification of the afferent signals that leads to the hypersensitivity of central neurons. The final result is a sensory process that, although initially triggered by injury, may not keep a close relationship with the originating injury and develop into a chronic pain state in the absence of a defined cause.

Síndrome de dolor regional complejo tipo II: manejo interdisciplinario / Type II complex regional pain syndrome: multidisciplinary approach

El síndrome de dolor regional complejo tipo II o causalgia es un cuadro que se presenta con dolor intenso y síntomas autonómicos importantes, que alteran la calidad de vida de los pacientes. Sus mecanismos fisiopatológicos todavía están en discusión y la evidencia disponible para su manejo aún es escasa. Actualmente, la tendencia es hacia un manejo interdisciplinario que abarque terapias psicológicas, de rehabilitación, en conjunto con un correcto manejo del dolor.

Type II complex regional pain syndrome causes accute pain and autonomous symptoms that alter the patient's quality of life. Discussion with respect to the syndrome physiopathologic mechanisms is still open and available evidence is scarce. The present trend is the multidisciplinary approach with teams using psychological, rehabilitation and pain management therapies.

Neurotoxocarosis

Infection of humans with embryonated eggs of Toxocara canis (larva migrans) remains asymptomatic, or results in covert or common toxocarosis, visceral larva migrans syndrome, or ophthalmologic and neurologic impairment. Though neurological manifestations of Toxocara canis larvae are rare, toxocarosis remains an important differential diagnosis of various neurological disorders. Manifestations of the central nervous system are dementia, meningo-encephalitis, myelitis, cerebral vasculitis, epilepsy, or optic neuritis. Manifestations of the peripheral nervous system comprise radiculitis, affection of cranial nerves, or musculo-skeletal involvement. If toxocarosis is neglected, ignored, or refused as a differential of these abnormalities, it may be easily overlooked for years. Early recognition and treatment of the infection is, however, of paramount importance since it reduces morbidity and mortality and the risk of secondary superinfection. Like the visceral manifestations, neurological manifestations of toxocarosis are treated by benzimidazole components, most frequently albendazole, corticosteroids, or diethylcarbamazine. If detected and treated early, the prognosis of neurological manifestations of toxocarosis is favourable.

Infecção humana com ovos embrionados de Toxocara canis (larva migrans) pode permanecer assintomática ou resultar em toxocaríase acentuada ou comum, síndrome da larva migrans visceral ou manifestações neurológicas ou oftalmológicas. Embora manifestações neurológicas das larvas de Toxocara canis sejam raras, a toxocaríase permanece como importante diagnóstico diferencial de várias manifestações neurológicas. Manifestações do sistema nervoso central são demência, meningoencefalite, mielite, vasculite cerebral, epilepsia, ou neurite ótica. Manifestações do sistema nervoso periférico compreendem radiculite, agressão de nervos cranianos ou envolvimento músculo-esquelético. Se a toxocaríase é negligenciada, ignorada, ou recusada como diferencial destas anormalidades, ela pode ser facilmente desapercebida por anos. Reconhecimento precoce de tratamento da infecção é portanto de fundamental importância uma vez que reduz sua morbidade e mortalidade e o risco de superinfecção secundária. Da mesma maneira que as manifestações viscerais, as neurológicas são tratadas por benzimidazólicos, mais freqüentemente albendazole, corticosteróides ou dietilcarbamazine. Se detectado e tratado precocemente, o prognóstico das manifestações neurológicas da toxocaríase é favorável.

Clinical and laboratory features and response to treatment in patients presenting with vitamin B12 deficiency-related neurological syndromes.

AIMS AND OBJECTIVES: To study the clinical and laboratory features of patients admitted with vitamin B12 deficiency-related (B12def) neurological syndromes. SETTINGS AND DESIGN: A hospital-based retrospective and prospective study conducted at a referral teaching hospital. MATERIALS AND METHODS: Consecutive patients admitted with vitamin B12 deficiency-related neurological disorders during a three-year period from June 2000 to May 2003 were included. Data regarding clinical and laboratory features were obtained. Follow-up was done at least six months following treatment with parenteral vitamin B12. Chi-square test was used for statistical analysis. RESULTS: A total of 63 patients (52 males) with a mean age of 46.2 years were studied. The mean duration of symptoms at presentation was 10.3 months. Myeloneuropathy (54%) was the commonest neurological manifestation, followed by myeloneuropathy with cognitive dysfunction (34%), and peripheral neuropathy (9%). Neuropsychiatric manifestations and dementia were observed in 38% and 19% of patients respectively. All the patients had megaloblastic changes in the bone marrow smear. Eleven (17.5%) patients had both hemoglobin and the mean corpuscular volume (MCV) within the normal range. Follow-up after at least six months of therapy with parenteral B12 showed improvement in 54% patients. CONCLUSIONS: A high index of suspicion of B12def is required in patients presenting with myelopathy, cognitive decline, or neuropathy. A normal hemoglobin or MCV does not exclude B12def; therefore, other tests such as bone marrow smear and serum vitamin B12 assay are essential, as the condition is often reversible with treatment.

Effects of ganglioside on paclitaxel (Taxol) induced neuropathy in rats.

The effects of ganglioside on paclitaxel induced neuropathy were studied in 15 female Wistar rats. The animals were equally divided into 3 groups based on the type of administrated drug. The first (C-group) received an intraperitoneal weekly injection of 1 ml of NSS for five weeks. The second (P-group) received 9 mg/kg of a paclitaxel intraperitoneal weekly injection for five weeks. The third (PG-group) received both ganglioside and paclitaxel. Sensory evaluation and electrophysiologic studies of the tail nerve were performed before the administration of the first dose and at the end of the experiment. Morphological evaluation of the sciatic nerve was also studied. The results revealed the mean reaction time of the tail flick test, latency, amplitude and nerve conduction velocity of the P-group in the first and seventh week were of significant difference. However, there was no significant difference detected in those of the C-group and the PG-group. There was significant difference in all parameters between the PG and P-groups but not between the PG and C-groups. Cross sections of the sciatic nerve in the P-group showed mild endoneurium edema and some degenerated axons. Small myelinated nerve fibers in the PG-group were prominent. The results of this study indicated that ganglioside treatment could produce some beneficial effects in an animal model of paclitaxel induced neuropathy.

Terapêutica intravenosa com metilprednisolona e ciclofosfamida na vasculite do sistema nervoso periférico: avaliaçäo de oito pacientes / Intravenous theraphy with methylprednisolone and cyclophosphamide in vasculitis of peripheral nervous system: evaluation of 8 patients

O comprometimento do sistema nervoso periférico é frequente nas vasculites sistêmicas e contribui decisivamente para o diagnóstico. Oito pacientes foram estudados: sete do sexo feminino e um do sexo masculino; cinco brancos, dois negros, um amarelo; média de idade de 55,9 anos; quatro com poliarterite nodosa, um com lúpus eritematoso sistêmico, um com artrite reumatóide, um com vasculite isolada do sistema nervoso periférico e um com vasculite livedóide. Todos foram submetidos a terapêutica intravenosa com pulsos mensais de metilprednisolona (1 g/dia/3dias) e ciclofosfamida (1 g/dia). Cinco pacientes melhoraram, dois permaneceram inalterados e um faleceu. A melhora neurológica objetiva ocorreu após o terceiro ou quarto pulso e nos pacientes com menor duraçao da doença.

Nonsystemic vasculitic neuropathy.

The clinical, electrophysiological and pathological features and prognosis of 9 patients with nonsystemic vasculitic neuropathy are described. Nonsystemic vasculitic neuropathy accounted for 3% of cases of biopsy proven cases of various neuropathies and formed 56% of vasculitic neuropathy. Both clinically and on electrophysiological testing, mononeuritis multiplex was the form of neuropathy in 5 patients and 3 had sensory neuropathy. All the patients had a necrotizing vasculitis on nerve biopsy. Axonal degeneration was seen in teased fibers in all the patients. Eight patients showed good functional recovery one was left with mild bilateral claw hands.

Polirradiculoneuropatia desmielinizante inflamatória crônica. Estudo de 18 pacientes / Chronic inflammatory demyelinating polyradiculoneuropathy. Study of 18 cases

Neste estudo prospectivo analisamos as características clínicas, evoluçäo e resposta terapêutica de 18 pacientes com a forma idiopática de polirradiculoneuropatia desmielinizante inflamatória crônica, que foram acompanhados por período que variou de 4 a 127 meses. O sexo masculino predominou sobre o feminino (1,25:1) e a idade de início dos sintomas variou de 6 a 85 anos. Observamos a preponderância da forma de evoluçäo progressiva (61,1 por cento) sobre a forma recidivante (38,9 por cento), bem como a baixa ocorrência de fatores predisponentes (16,7 por cento). Todos os pacientes apresentavam comprometimento sensitivo e motor, associado a hipo ou arreflexia, enquanto apenas três (16,7 por cento) apresentavam comprometimento de nervos cranianos. No exame do líquor, as taxas de proteínas estavam elevadas em 88,9 por cento dos pacientes, com média de 203,4 mg/dl. A eletroneuromiografia mostrou alteraçöes desmielinizantes em todos os pacientes, associadas a alteraçöes axonais em 94,4 por cento deles. Em todos os sete pacientes submetidos a biopsia de nervo sural encontramos alteraçöes compatíveis com desmielinizaçäo/remielinizaçäo. A análise com imunofluorescência, realizada em três pacientes foi normal em um e evidenciou depósito de anticorpos anti-CD3 em dois e anti-HLA-Dr em um. Optamos pela prednisona como tratamento inicial em todos os pacientes, sendo mantida posteriormente em doses reduzidas e em dias alternados em 72,2 por cento deles. Dois pacientes (11,1 por cento) estäo assintomáticos mesmo após retirada total da medicaçäo e introduzimos azatioprina, associada ou näo ao corticóide, nos quatro pacientes com má resposta à prednisona. Até a última avaliaçäo, 16 pacientes (88,9 por cento) evoluíram com melhora funcional.

Neuropatia idiopática do plexo lombossacro em criança: relato de caso / Idiopathic lumbosacral plexus neuropathy in child: case report

Os autores relatam um caso de plexopatia lombossacra em criança e em que a extensa investigaçao, incluindo ressonância nuclear magnética normal, biópsia muscular compatível com desinervaçao inicial e eletromiografia normal, afastou condiçoes associadas. O paciente apresentava dor intensa, fraqueza e atrofia do membro inferior esquerdo, reflexo aquileu ausente e reflexo patelar diminuído à esquerda. Parestesia no membro envolvido acompanhava o quadro. O tratamento realizado foi dexametasona por um mês e morfina intratecal durante três meses. A evoluçao foi favorável, apresentando, após um ano, atrofia discreta do membro acometido e leve paresia do músculo iliopsoas esquerdo.

La ozonoterapia en la neuropatía epidémica forma óptica ¿Beneficio y riesgo? / Ozone therapy in the management of the optic neuritis epidemic. Benefits od risks?

Se realizó un ensayo clínico terapéutico multicéntrico en Ciudad de La Habana, en 576 pacientes afectados de neuropatía epidémica forma óptica, en el período comprendido entre abril de 1993 y febrero de 1994. Se emplearon 11 esquemas de tratamiento, distribuidos aleatoriamente entre los hospitales participantes. Los grupos de tratamiento incluidos fueron : dexametasona, metilprednisolona, hidroxicobalamina+metionina+tiosulfato de sodio, vitaminas, magnetoterapia, ozonoterapia, oxigenación hiperbárica, electroforesis endonasal con vitamina B1, factor de trasnferencia, interferón (INF) alfa natural e interferón alfa 2b recombinante. A todos los pacientes del estudio se les administró vitaminas de base y se consideró a aquéllos tratados con vitaminas sólo como grupo control. La evaluación de los casos se realizó a los 21 días (alta hospitalaria), al mes, 3 y 6 meses, respectivamente. El tratamiento con ozono reflejó diferencias estadísticamente significativas (p<0,05) (en cada uno de los cortes evaluativos efectuados) en cuanto a mejoría y recuperación de los casos tratados con ese proceder. En el resto de los esquemas terapéuticos empleados no se encuentran diferencias significativas. Se evidenció la utilización de las vitaminas