Toxic Myelopathy Research Articles

Evaluation of the implementation of Diagnostic Criteria of Occupational Acute Neurotoxic Diseases Caused by Chemicals (GBZ 76-2002)

Objective: To investigate the implementation of Diagnostic Criteria of Occupational Acute Neurotoxic Diseases Caused by Chemicals (GBZ 76-2002) for accumulating basis of standard revision. Methods: In February 2020, 85 experts in occupational diseases and neurology from 39 medical and health institutions were selected as the respondents. The modified Delphi method was used to establish the standard evaluation index system and special group was organized for discussing the pre-survey and completing the questionnaire survey. Questionnaire survey was performed to investigate the grasp of the standards, application and modification suggestions of respondents. Results: The respondents' mastery of standard-related knowledge mainly came from work experience (84.7%, 72/85) , standard learning (81.2%, 69/85) and training (75.3%, 64/85) . Among the institutions in which the respondents worked, 98.8% (84/85) could carry out CT examinations, 96.5% (82/85) could carry out nerve conduction velocity and electromyography examinations, 89.4% (76/85) could carry out EEG examinations, 80% (68/85) could carry out evoked potential examinations and 72.9% (62/85) could carry out MRI examinations. Among the toxicants diagnosed as occupational acute toxic myelopathy, 10.6% (9/85) were organic phosphorus and 9.4% (8/85) were asphyxiating gas; Among the toxicants diagnosed as delayed peripheral neuropathy, pesticides accounted for 25.9% (22/85) and asphyxiating gases accounted for 12.9% (11/85) . 85.9% (73/85) of the respondents believed that the basis for the classification of acute toxic encephalopathy needed to supplement objective evidence; 80.0% (68/85) of the respondents thought that the diagnosis and classification of peripheral neuropathy should be refined according to the abnormal indexes of neuroelectromyography. Conclusion: The applicability of the criteria needs to be improved because the current criteria has a long application cycle without enough objective investigation bases in classification criteria index.

Metabolic and Toxic Myelopathies.

Metabolic and toxic causes of myelopathy form a heterogeneous group of disorders. In this review, we discuss the causes of metabolic and toxic myelopathies with respect to clinical presentation, pathophysiology, diagnostic testing, treatment, and prognosis. This review is organized by temporal course (hyperacute, acute, subacute, and chronic) and etiology (e.g., nutritional deficiency, toxic exposure). Broadly, the myelopathies associated with dietary toxins (neurolathyrism, konzo) and decompression sickness present suddenly (hyperacute). The myelopathies associated with heroin use and electrical injury present over hours to days (acutely). Most nutritional deficiencies (cobalamin, folate, copper) and toxic substances (nitrous oxide, zinc, organophosphates, clioquinol) cause a myelopathy of subacute onset. Vitamin E deficiency and hepatic myelopathy cause a chronic myelopathy. Radiation- and intrathecal chemotherapy-induced myelopathy can cause a transient and/or a progressive syndrome. For many metabolic and toxic causes of myelopathy, clinical deficits may stabilize or improve with rapid identification and treatment. Familiarity with these disorders is therefore essential.

Metabolic and Toxic Myelopathies.

This article describes the clinical presentation, relevant diagnostic investigations, and treatment of metabolic and toxic myelopathies. Metabolic myelopathies, including those due to deficiency of vitamin B12, folate, copper, or vitamin E, are preventable and typically respond to supplementation. In metabolic myelopathy, early recognition and treatment are important to reduce morbidity, particularly due to subacute combined degeneration of the spinal cord. Toxic myelopathies, including those due to medical interventions (eg, methotrexate, radiation), dietary toxins (eg, lathyrism, konzo), and drugs of abuse (eg, heroin), typically result in permanent neurologic deficits. Toxic myelopathy due to hepatic dysfunction may be reversible if patients receive early intervention, whereas nitrous oxide myelopathy responds to vitamin B12 replacement and cessation of exposure. In toxic myelopathy, it is best to avoid the provoking factor when possible or attempt to mitigate risk by identifying risk factors for developing myelopathy. Metabolic and toxic myelopathies are important causes of morbidity that require a high index of suspicion for diagnosis.

062 Alcohol associated toxic myelopathy with normal hepatic function

IntroductionAlcohol related neurological dysfunction affects the central and peripheral nervous system. We present a rare consequence of excessive alcohol consumption. A 42-year-old female consuming 2 bottles of wine daily for the preceding 5 years presented with 12 months of progressive gait disturbance. Examination revealed a spastic paraparesis with prominent dorsal column signs. Extensive work up found no alternate cause for her presentation. The final diagnosis was direct alcohol mediated toxic myelopathy. We reviewed the current literature on this rare condition.MethodsWe searched PubMED/OVID databases with the terms ‘alcohol AND myelopathy’.ResultsThere is a paucity of research on this clinical entity. Sage et al.1 described 5 well-nourished alcoholics presenting with a progressive myelopathy. As with our patient, routine laboratory tests, including nutritional screen, were normal. CT Myelogram revealed no structural cause. CSF was normal. In contrast, a myelopathic syndrome can occur in alcoholic hepatic failure, attributed to portosystemic shunting of blood, with resultant hyper-ammonaemia and demyelination of corticospinal tracts.2–4ConclusionAlcohol associated toxic myelopathy is a rare entity, distinct from hepatic myelopathy. It is thought to result from direct toxic effects of ethanol on corticospinal and large myelinated sensory tracts. The sensory involvement is unique for this entity, which distinguishes it from hepatic myelopathy, where corticospinal involvement predominates. It is prudent to look for other potentially treatable secondary causes of myelopathy. Abstinence from alcohol results in modest improvement in symptoms. Minimal literature exists on this clinical entity and further research is required.ReferencesSage JI, et al. Alcoholic myelopathy without substantial liver disease. A syndrome of progressive dorsal and lateral column dysfunction. Arch Neurol. 1984 Sep;41(9):999–1001.Premkumar M, et al. Hepatic Myelopathy in a Patient with Decompensated Alcoholic Cirrhosis and Portal Colopathy. Volume 2012, Article ID 735906, 4 pages.Koo JE, et al. Hepatic myelopathy as a presenting neurological complication in patients with cirrhosis and spontaneous splenorenal shunt. Korean J Hepatol. 2008 Mar;14(1):89–96.Kori P, et al. Hepatic myelopathy: an unusual neurological complication of chronic liver disease presenting as quadriparesis. BMJ Case Rep. 2013; 2013: bcr2013009078.

Serious Erysipelas Revealing an Iatrogenic Hematotoxicity to Tamoxifen

Tamoxifen is an anti estrogen recommended in the treatment of estrogendé pendants cancers. Its side effects are rare and haematological toxicity is extremely rare. We relate an original case of severe erysipelas which revealed a toxic myelopathy to tamoxifen.

Metabolic and Toxic Myelopathies

Myelopathy may occur as a consequence of various metabolic and toxic conditions. This article provides an update on the clinical presentations, diagnostic evaluations, and management of metabolic and toxic myelopathies. Myelopathy and myeloneuropathy due to vitamin B12 deficiency is increasing in prevalence partly because of an aging population. Early recognition of the clinical symptoms and rapid initiation of treatment is essential. Copper deficiency is now also recognized as causing a similar clinical picture as vitamin B12 deficiency. Conditions leading to copper deficiency include bariatric surgery and excessive zinc intake. Unusual conditions such as lathyrism and konzo are relevant to all neurologists because of emigration from less well-developed countries. Myelopathy can also occur from substance abuse (eg, heroin and nitrous oxide), and early diagnosis could lead to improved patient outcomes. The spinal cord may also be injured in decompression illness that occurs in sport divers and individuals who work in pressurized atmospheres. Knowledge and recognition of the various metabolic and toxic causes of myelopathy is important for the practicing neurologist, as timely diagnosis and rapid initiation of therapy is essential to improve the chances for recovery.

Toxic myelopathy secondary to recreational nitrous oxide abuse

Toxic myelopathy secondary to recreational nitrous oxide abuse

Myelopathy mimicking subacute combined degeneration in a Down syndrome patient with methotrexate treatment for B lymphoblastic leukemia: Report of an autopsy case

We report clinicopathological features of a 23-year-old woman with Down syndrome (DS) presenting with subacute myelopathy treated with chemotherapy, including intravenous and intrathecal administration of methotrexate (MTX), and with allogenic bone-marrow transplantation for B lymphoblastic leukemia. Autopsy revealed severe demyelinating vacuolar myelopathy in the posterior and lateral columns of the spinal cord, associated with macrophage infiltration, marked axonal loss and some swollen axons. Pathological changes of posterior and lateral columns were observed from the medulla oblongata to lumbar cord. Proximal anterior and posterior roots were preserved. Cerebral white matter was relatively well preserved. There were no vascular lesions or meningeal dissemination of leukemia. Longitudinal extension of cord lesions was extensive, unlike typical cases of subacute combined degeneration (SACD), but distribution of lesions and histological findings were similar to that of SACD. DS patients show heightened sensitivity to MTX because of their genetic background. Risk factors for toxic myelopathy of DS are discussed, including delayed clearance of MTX despite normal renal function, alterations in MTX polyglutamation and enhanced folic acid depletion due to gene dosage effects of chromosome 21. Alteration of folate metabolism and/or vitamin B12 levels through intravenous or intrathecal administration of MTX might exist, although vitamin B12 and other essential nutrients were managed using intravenous hyperalimentation. To the best of our knowledge, this is the first report of an autopsy case that shows myelopathy mimicking SACD in a DS patient accompanied by B lymphoblastic leukemia. The case suggests a pathophysiological mechanism of MTX-related myelopathy in DS patients with B lymphoblastic leukemia mimicking SACD.

Metabolic and Toxic Myelopathies

The myelopathies discussed in this article have an underlying metabolic or toxic etiology. They have many clinical, electrophysiologic, and neuropathologic similarities. Preferential involvement of the dorsal columns and/or corticospinal tracts is commonly seen. Variable degrees of peripheral nerve and/or optic nerve involvement may be present. In the presence of clinical or electrophysiologic evidence of peripheral nerve involvement, the term myeloneuropathy is commonly used. The metabolic and toxic myelopathies discussed here are divided into three categories: disorders due to an identified nutrient deficiency such as the subacute combined degeneration of cobalamin/vitamin B12 or copper deficiency, disorders that have a geographical predilection and are due to a suspected toxin such as lathyrism, and disorders due to a possible toxin but without a geographical predilection such as hepatic myelopathy (Table 1).

Neurolathyrism: two Ethiopian case reports and review of the literature

Neurolathyrism is a toxic myelopathy caused by ingestion of the Lathyrus sativus grasspea. An irreversible acute to subacute spastic paraparesis or quadriparesis ensues. Despite public education, new cases of this preventable disease still occur. Two Ethiopian cases of neurolathyrism are reported to illustrate the disease, followed by a literature review. Two teenage male farmers from the same village developed irreversible spastic myelopathy following L. sativus ingestion. There was no sensory, sphincter or bulbar dysfunction. Likely causative factors identified were increased consumption of L. sativus prior to and following disease onset, heavy physical exertion and male gender, similar to those reported in the literature. Neurolathyrism is an entirely preventable neurotoxic myelopathy with permanent disability accrued. Treatment is symptomatic. Because of personal disability and subsequent socioeconomic effects, this disease warrants further public health measures to prevent occurrence. Education, avoidance of the grasspea and measures to reduce toxin burden are possible methods.

METABOLIC AND TOXIC MYELOPATHIES

The myelopathies discussed in this article have an underlying metabolic or toxic etiology. They have many clinical, electrophysiologic, and neuropathologic similarities. Preferential involvement of the dorsal columns and/or corticospinal tracts is commonly seen. Variable degrees of peripheral nerve and/or optic nerve involvement may be present. In the presence of clinical or electrophysiologic evidence of peripheral nerve involvement, the term myeloneuropathy is commonly used. The metabolic and toxic myelopathies discussed here are divided into three categories: disorders due to an identified nutrient deficiency such as the subacute combined degeneration of cobalamin/vitamin B12 or copper deficiency, disorders that have a geographical predilection and are due to a suspected toxin such as lathyrism, and disorders due to a possible toxin but without a geographical predilection such as hepatic myelopathy (Table 1).

Hematologic aspects of myeloablative therapy and bone marrow transplantation

The transplantation of bone marrow cells or isolated hematopoietic stem cells from the bone marrow or peripheral blood is a widely utilized form of therapy for patients with incurable diseases of the hematopoietic and immune systems. Successful engraftment of the transplanted stem cells in an adequately prepared recipient normally leads to bone marrow reconstitution over a period of several weeks, accompanied by more gradual reconstitution of the immune system. Since the recipient is profoundly ill during the initial treatment period, laboratory data is critical for monitoring engraftment, detecting residual/recurrent disease, and identifying problems that may delay bone marrow reconstitution or lead to other medical complications. Accurate blood cell counts are imperative, and most bone marrow transplantation patients undergo periodic monitoring with bone marrow aspirates and biopsies with cytogenetic, molecular, and multiparametric flow cytometric studies. The potential complications of bone marrow transplantation include engraftment failure and delayed engraftment, infection, residual bone marrow disease, acute and chronic graft versus host disease, myelofibrosis, therapy-related acute leukemia, post-transplant lympho-proliferative disorders, and toxic myelopathy.

Acute panmyelosis with myelofibrosis: a clinicopathological study on 46 patients including histochemistry of bone marrow biopsies and follow-up.

Controversy continues whether acute panmyelosis with myelofibrosis (APMF) exists as a well-defined clinicopathological entity. Following exclusion of overt acute myeloid leukemia (AML), especially the megakaryoblastic subtype, a retrospective study was performed on 46 patients with clinical and morphological features suggesting the diagnosis of APMF. All patients had a bone marrow (BM) biopsy performed at onset, and 13 had follow-up examinations. Enzyme histochemical and immunohistochemical techniques were applied and BM features evaluated by a semiquantitative scoring system. Clinical findings consisted of pancytopenia associated with a left-shifted differential count of the peripheral blood (less than 5% blasts) and no or minor splenomegaly. During follow-up (median survival 9 months) 35 patients developed severe BM insufficiency and 10 transformed into overt AML. Although myelofibrosis was a characteristic finding, other BM features proved to be heterogeneous. Cellularity was reduced in 13 and increased in 25 specimens. Most prominent was a left-shifted, often macrocytic erythropoiesis and a maturation defect of the neutrophil series. In 15 patients an increase (less than 20%) in CD34+ progenitors, immature myelomonocytic cells, and megakaryoblasts was noted. Abnormalities of megakaryocytes (atypical microforms, clustering, dysplasia) were regularly present. The stroma showed an inflammatory reaction (perivascular plasmacytosis, lymphoid nodules, many macrophages, iron deposits) in about 50% of the samples. Sequential BM biopsies revealed an accumulation of lysozyme-expressing myelomonocytic and CD34+ progenitor cells suggesting an increase in blasts. In conclusion, APMF may not be a distinct entity, but includes hyperfibrotic myelodysplastic syndromes (MDS) either primary or secondary, a rare form of initial AML with fibrosis, and even cases of toxic myelopathy.

Acute Panmyelosis with Myelofibrosis

Acute panmyelosis with myelofibrosis (APMF) is an ill-defined disorder that may either evolve as a clonal hematopoietic condition or as a sequel of toxic exposure to the bone marrow (BM). Therefore, controversy and discussion continues as to whether APMF may be considered as a hyperfibrotic (de novo) myelodysplastic syndrome (MDS), as acute myeloid leukemia (AML) or as a severe toxic myelopathy with accompanying myelofibrosis. In this context scant knowledge exists about BM findings, but especially evolution of this disorder according to sequential examinations. Clinically patients present with pancytopenia, a very few blasts in the peripheral blood and no or little splenomegaly. Initially BM histopathology is characterized by different degrees of reticulin-collagen fibrosis and wide ranges of cellularity with a prominent left-shifted and often macrocytic erythropoiesis associated with a reduction and maturation defects of the neutrophil series. Most conspicuous are abnormalities of the megakaryocytes including loose clustering, dislocation towards the endosteal border and appearance of atypical microforms with compact nuclei. Moreover, besides myelofibrosis in a number of patients the interstitial compartment displays a remarkable inflammatory reaction with lymphoid nodules, abundant iron-laden macrophages, perivascular plasmacytosis and increase in microvessels. Repeatedly performed BM biopsies reveal an accumulation of dispersed or clustered CD34+ and lysozyme-expressing blasts in keeping with the insidious transformation into acute leukemia. Prognosis is unfavorable with a median survival of less than 1 year. In conclusion, APMF has to be regarded as a condition that shows considerable overlappings with primary hyperfibrotic MDS, AML and toxic myelopathy (secondary MDS) with accompanying myelofibrosis and therefore can not be considered as a definite clinical entity.

Differentiation of granulomatous lesions in the bone marrow

Granulomas are an infrequent finding in bone marrow biopsies and may be associated with a broad spectrum of infectious and non-infectious disorders. In this context sarcoidosis generally reveals the highest incidence of such bone marrow lesions. Other granulomas may be encountered in drug-induced secondary changes (toxic myelopathy) and in particular also in HIV myelopathy. In these cases the granulomas are small, ill-defined and difficult to recognize. Special staining methods are required to detect microorganisms. Fibrin ring granulomas (doughnut granulomas) are typical for Q-fever, but may also be seen in reactive conditions, after drug therapy and in the course of other infectious disorders, such as Lyme disease. Therefore a broad serological testing should be performed. In conclusion, in most cases the morphological findings in the bone marrow are not specific so that a synoptical approach regarding histological, clinical and serological data is warranted to reach the correct diagnosis.

Focal lymphoid aggregates (nodules) in bone marrow biopsies: differentiation between benign hyperplasia and malignant lymphoma--a practical guideline.

AIMS: To provide practical guidelines for the differentiation between benign and malignant focal lymphoid aggregates (lymphoid nodules) in routinely referred bone marrow trephine biopsies, using a synoptic approach including clinical...

Histopathology of the bone marrow in toxic myelopathy. A study of drug induced lesions in 57 patients.

Following the introduction of numerous highly effective drugs in recent decades, haematologists are confronted with a panmyelopathy or "toxic myelopathy" originating from the exhibition of certain therapeutic regimens. Among 16,711 trephines referred to us in the last 5 1/2 years, 57 cases or 0.34 percent were found to have clear evidence of lesions caused by the ingestion of potentially toxic agents. The evaluation of the histopathology shows two groups of alterations which concern the haematopoietic parenchyma as well as the mesenchyme of the bone marrow. Different degrees of cellularity ranging from aplasia to regenerative hyperplasia and a pronounced mesenchymal reaction with proteinaceous oedema, perivascular plasmacytosis and frequent necrobiosis of neutrophilic granulocytes or cellular debris are the most conspicuous features. However, the histopathology of the bone marrow described gives no indication of the specific drug responsible and no specific suggestion of any group of drugs. Generally the histopathology allows the recognition of lesions which are induced by the toxicity of these agents. Therefore a bone marrow biopsy should be included in the diagnostic procedures whenever a toxic lesion is suspected of causing haematological disorders, particularly in all cases of uncertain pancytopenia.

MYELITIC AND MYELOPATHIC LESIONS (A CLINICOPATHOLOGIC STUDY)

By far the largest number of cases of diffuse nonsystemic disease of the cord, excluding multiple sclerosis, are the so-called myelopathies or myeloses. In these, the histopathologic changes, although essentially similar, may show some variations, largely owing to differences in the causative agents and the duration of the disease. Myelopathic processes in diffuse nonsystemic disease of the cord, excluding multiple sclerosis, may be produced by (1) toxins or (2) circulatory interference. Toxins may produce myelopathy by affecting the ectodermal or the mesodermal elements of the cord, or both. Our cases belonged to the ectodermal group, and the pathologic process resembled that produced experimentally by introducing various toxins into the circulation or into the subarachnoid space. In the absence of other demonstrable etiologic factors we designate these cases as toxic myelopathies. When the mesodermal elements (blood vessels) alone are involved, the pathologic process is one of secondary softening due to circulatory