Intravenous methadone causes acute toxic and delayed inflammatory encephalopathy with persistent neurocognitive impairments.

BACKGROUND: The mu-opioid agonist methadone is administered orally and used in opioid detoxification and in the treatment of moderate-to-severe pain. Acute oral methadone-use and -abuse have been associated with inflammatory and toxic central nervous system (CNS) damage in some cases and cognitive deficits can develop in long-term methadone users. In contrast, reports of intravenous methadone adverse effects are rare. CASE PRESENTATION: Here, we report a patient who developed acute bilateral hearing loss, ataxia and paraparesis subsequently to intravenous methadone-abuse. While the patient gradually recovered from these deficits, widespread magnetic resonance imaging changes progressed and delayed-onset encephalopathy with signs of cortical dysfunction persisted. This was associated with changes in the composition of monocyte and natural killer cell subsets in the cerebrospinal fluid. CONCLUSION: This case suggests a potential bi-phasic primary toxic and secondary inflammatory CNS damage induced by intravenous methadone.

Acute paraparesis in HIV-infected patient after initiation of highly active antiretroviral therapy.

Neurological syndromes occur in around 40-70% of HIV-infected people. Direct central nervous system involvement by the virus usually manifests as HIV encephalitis, HIV leucoencephalopathy, vacuolar leucoencephalopathy or vacuolar myelopathy. Indirect involvement is usually associated with neurotropic opportunistic infections which include tuberculosis, toxoplasmosis, cryptococcosis and viral encephalitis such as herpes simplex, varicella-zoster, cytomegalovirus and Human polyomavirus 2. We report a case of transverse myelitis in a recently diagnosed HIV patient who was otherwise asymptomatic initially and developed paraparesis after 1 month of initiation of antiretroviral therapy. After ruling out opportunistic infections and other causes of compressive and non-compressive myelopathy, development of transverse myelitis was attributed to immune reconstitution inflammatory syndrome in view of baseline low CD4 count and their improvement after HAART initiation. Prompt treatment with corticosteroids successfully reversed the symptoms.

Complete clinical and functional recovery following low-dose methotrexate related paraparesis in a patient with compound c.1298A>C AND c.677C>T MTHFR polymorphism: A case report.

RATIONALE: The mechanisms of action of MTX (methotrexate) in the treatment of RA (rheumatoid arthritis) and PsA (psoriatic arthritis) is related to its antifolic activity, due to the high affinity for enzymes that require folate cofactors as dihydrofolate reductase and to the anti-inflammatory activity derivated from the inhibition of thymidylate synthetase that leads to the over-production of adenosine. PATIENT CONCERNS: Our patient was a 41-year-old female, affected by PsA in treatment since 2 years with low-dose methylprednisolone and low-dose subcutaneous MTX. The treatment was effective. The patient subacutely developed a severe paraparesis with impossibility of gait or standing without aid and was admitted to a Neurology Department where the cause of the paraparesis was not clear in spite of accurate radiological neurophysiologic and laboratory tests. Therefore, she was admitted in a rehabilitation unit. DIAGNOSIS AND INTERVENTIONS: Paraparesis in PsA patient in treatment with methotrexate. MTX toxicity was hypothesized; therefore the drug was discontinued while i.m. folic acid and cyanocobalamin were administered for 20 days. The diagnosis was clinical, based on neurological examination (paraparesis) and on the chronic use of MTX (hypothesis of toxicity). OUTCOMES: The patient obtained a complete resolution of paraparesis. Genetic analyses showed associated a compound heterozygosity for the c.1298A>C and c.677C>T variants of methylenetetrahydrofolate reductase (MTHFR) gene. LESSONS: Neurological side effects of MTX are uncommon. In literature no previous case of MTX induced paraparesis in patients treated with low-dose MTX for chronic arthritis has been described. The association between the gene polymorphisms of MTHFR (c.1298A>C and c.677C>T) and MTX toxicity in arthritis patients is confirmed. The case also confirms that folates are a precious antidote of MTX toxicity.

Acute transient spinal paralysis and cardiac symptoms following an accidental epidural potassium infusion - a case report.

BACKGROUND: To describe a case of an accidental epidural potassium infusion leading to an acute transient spinal paralysis and cardiac symptoms and review the literature on that topic. CASE PRESENTATION: We report the case of an accidental infusion of 900 mg potassium chloride 7.45% (KCl) into the epidural space, which occurred during epidural analgesia in a 74-year-old patient suffering from immobilization due to lumbar back pain as well as from a paralytic Ileus. The event was resulting in vegetative symptoms, such as tachycardia and hypertension accompanied by a motor complete tetraplegia (AIS B) sub C2 with respiratory depression. The endotracheal intubation was necessary. The patient was treated with 40 mg dexamethasone intravenously, as well an epidural lavage with sodium chloride solution 0.9% (NaCl) through the epidural catheter. The neurologic symptoms completely resolved within five days. An elevation of troponin-T values and a reduced left ventricular ejection fraction (LVEF) of 40% accompanied by transient pectanginous pain were documented. An exertional dyspnea remained. CONCLUSIONS: A symptom complex with elevated sympathetic nervous system activity up to a stress cardiomyopathy is possible following epidural potassium infusion. Additionally, generalized pain and muscle spasticity evolve and a progressive acute spinal cord injury syndrome can occur within minutes, accompanied by respiratory depression. Treatment consists of early intensive care and the symptomatic therapy of the associated symptoms, leading in most of the reported cases to a good clinical outcome.

Steroid-induced paraparesis: spinal epidural lipomatosis complicated by a wedge deformity of the middle thoracic vertebrae.

Steroid therapy is commonly prescribed, although a variety of complications have been reported. Among such complications, spinal epidural lipomatosis is rare and difficult to diagnose before paraparesis occurs. The purpose of this report is to present a rare but catastrophic complication of steroid therapy. A 64-year-old woman undergoing long-term steroid therapy suffered from an osteoporotic vertebral compression fracture and was unable to walk due to paraparesis. Magnetic resonance imaging (MRI) demonstrated a D7 compression fracture and stored epidural adipose tissue between D5 and D8. After surgery, the patient was able to walk with double canes. This case indicates that long-term steroid use has the potential to induce paraparesis.

Resolución espontánea de paraparesia por hematoma epidural dorsolumbar asociado a anestesia subaracnoidea y analgesia postoperatoria mediante catéter epidural / Spontaneous resolution of a paraparesis due to a dorsolumbar epidural haematoma associated with subarachnoid anaesthesia and postoperative analgesia using an epidural catheter

El hematoma epidural espinal secundario a anestesia neuroaxial es una complicación grave, aunque poco frecuente. La mayoría de los casos se asocia a tratamiento anticoagulante o circunstancias que favorezcan el sangrado. Por las graves secuelas secundarias a la compresión medular se considera una urgencia quirúrgica, siendo crucial en su pronóstico la precocidad en la descompresión medular. Presentamos un caso de hematoma epidural espinal dorsolumbar asociado a anestesia intradural y analgesia epidural en una paciente con tromboprofilaxis con heparina de bajo peso molecular, con recuperación espontánea con tratamiento conservador(AU)

Spinal epidural haematoma after neuroaxial anaesthesia is a rare but serious complication. Most cases are attributed to anticoagulant therapy or bleeding tendency. It presents as an acute spinal cord compression and usually requires emergency surgical decompression. The interval between the onset of clinical signs and surgical evacuation is very important, influencing the neurological prognosis. We report a case of a spinal epidural haematoma after epidural analgesia in a patient who was treated with low molecular weight heparin for thrombo-prophylaxis in the perioperative period. In some cases, such as the one reported here, good neurological recovery can be achieved with conservative management(AU)

Subacute steroid-induced paraparesis: surgical treatment of a devastating "invisible" side effect.

PURPOSE: To emphasize an underestimated side effect following long-term use of steroids. METHODS: We report on surgical treatment of two patients with serious neurologic deficits caused by epidural spinal lipoma following long-term intake of cortisone. RESULTS: Early decompression of the spinal cord by removal of epidural lipoma was the most effective treatment in these patients with progressive symptoms. CONCLUSION: Diagnostic work-up of such patients should include early spinal MRI resulting in surgical intervention, if indicated. Decompression of the spinal cord eventually combined with fusion is necessary.

A unique presentation of a spinal dural arteriovenous fistula exacerbated by steroids.

Spinal dural arteriovenous fistula (DAVF) is an acquired vascular malformation of the spinal cord that presents as a congestive myelopathy resulting from venous hypertension, edema, and ischemia within the cord. Acute clinical exacerbations have been demonstrated in a variety of clinical settings. We report a unique presentation of a 45-year-old male with progressive paraplegia that acutely worsened following three independent treatments with oral and intravenous steroid administration. Spinal angiogram revealed a spinal DAVF at L3 and the patient underwent successful surgical repair. This report highlights the clinical presentation of spinal DAVF and emphasizes the unique and important potential relationship between steroid administration and clinical deterioration.

Paraplegia and paraparesis from intrathecal methotrexate and cytarabine contaminated with trace amounts of vincristine in China during 2007.

PURPOSE: The production and administration of drugs used intrathecally requires special care to prevent contamination with neurotoxic agents. In 2007, we investigated a widespread outbreak of paraplegia and paraparesis among Chinese patients who received intrathecal drugs to identify the presumed contaminant and its source to prevent further cases. PATIENTS AND METHODS: We defined a case as onset from January 1 to October 31, 2007, of bilateral flaccid paraparesis or paraplegia or retention and incontinence of stool or urine, in a patient receiving intrathecal drugs. Using a retrospective cohort approach, we selected 12 hospitals from all hospitals that had reported cases. In these hospitals, we identified all 448 patients (including 107 cases) who received intrathecal chemotherapy or chemoprophylaxis in 2007. We calculated attack rates and Mantel-Haenszel adjusted risk ratios for intrathecal drug type and lot. RESULTS: All 12 hospitals used intrathecal methotrexate or cytarabine produced by one pharmaceutical plant. Only two lots of each drug were associated with cases. Lot-specific attack rates ranged from 42% to 100% (risk ratio, ∞; lower confidence bounds, 1.8 to 7.3). Vincristine production had immediately preceded production of the implicated lots on the same equipment. By using ultra performance liquid chromatography, we detected vincristine (0.28 to 18 µg) in unused vials from implicated lots of methotrexate and cytarabine. CONCLUSION: Trace amounts of vincristine that contaminated intrathecal drugs caused a large outbreak of severe neurologic damage. Vincristine and other neurotoxic drugs should not be produced on any equipment that is also used for producing drugs that are to be administered intrathecally.

Chronic inflammatory demyelinating polyneuropathy associated with tumor necrosis factor-alpha antagonists.

Biologic therapy with tumor necrosis factor (TNF)-alpha antagonists for rheumatoid arthritis has been well established. We describe two patients with rheumatoid arthritis who developed chronic inflammatory demyelinating polyneuropathy (CIDP) during their course of therapy with TNF-alpha antagonists. A 45-year-old woman and a 49-year-old man, both with a history of rheumatoid arthritis, were treated with etanercept and infliximab, respectively. Clinical signs of peripheral neuropathy developed 2 weeks and 12 months after the initiation of TNF-alpha antagonists. Electrodiagnostic studies at variable points during the disease course showed signs of acquired demyelination consistent with CIDP. Cerebrospinal fluid examination showed albuminocytologic dissociation (total protein concentration 118 mg/dl and 152 mg/dl, respectively). Both patients failed to improve after discontinuation of the offending agent, and they responded poorly to corticosteroids. However, there was clinical and electrophysiologic recovery after initiation of intravenous immunoglobulin (IVIg) therapy. CIDP may occur early or late during the treatment course with TNF-alpha antagonists. IVIg may reverse and stabilize the inflammatory process.

Hind-limb paraparesis in a rat model for neurolathyrism associated with apoptosis and an impaired vascular endothelial growth factor system in the spinal cord.

Neurolathyrism is a motor neuron disease characterized by lower limb paraparesis. It is associated with ingestion of a plant excitotoxin, beta-N-oxalyl-L-alphabeta-diaminopropionic acid (L-beta-ODAP), an agonist of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate-type glutamatergic receptors. Previously, a limited model of neurolathyrism was reported for the rat. To improve upon the model, we stressed rat pups by separation from their mothers, followed by the subcutaneous L-beta-ODAP treatment, resulting in a 4.6-fold higher incidence (14.0-15.6%) of the paraparesis compared with the prior study. The number and size of motor neurons in these rats were decreased only in the lumbar and sacral cord segments, at approximately 13-36 weeks after treatment. Only lumbar and sacral spinal cord tissue revealed pathological insults typical of physical and ischemic spinal cord injury in the surviving motor neurons. In addition, extensive but transient hemorrhage occurred in the ventral spinal cord parenchyma of the rat, and numerous TdT-mediated dUTP-biotin nick end-labeling (TUNEL)-positive cells were also observed. In parallel, vascular endothelial growth factor receptor (VEGFR)-2 (Flk-1) levels were significantly lowered in the lumbosacral spinal cord of the paraparetic rats compared with their controls, suggesting a failure of the VEGF system to protect neurons against L-beta-ODAP toxicity. We propose, based on these data, a novel pathological process of motor neuron death induced by peripheral L-beta-ODAP. For the first time, we present a model of the early molecular events that occur during chemically induced spinal cord injury, which can potentially be applied to other neurodegenerative disorders.

[Immunosuppression - too strong or too weak?]. / Immunsuppression - zu stark oder zu schwach?

A 52 year old patient with immunosuppressive therapy for ANCA-negative vasculitis presented with fever and paraparesis of the legs, laboratory findings displayed high inflammatory markers. The differential diagnosis comprised acute infection, an exacerbation of vasculitis or a drug reaction. Despite meticulous diagnostics, including FDG-PET, no definitive cause for the symptoms could be uncovered. Empirical antibiotic treatment in combination with high doses of glucocorticosteroids lead to prompt resolution of fever and inflammatory laboratory markers.

Paraparesis or incomplete paraplegia? How should we call it?

INTRODUCTION: The neurological examination terminologies and definitions of the status of spinal cord injured (SCI) patients are of great importance to establish scales and provide standard nomenclatures. There is a disagreement between the classical neurological terminology and the definitions of complete and incomplete paraplegia that have been proposed in traumatic spinal cord injured patients. OBJECTIVE: To discuss the adequacy and the impact of the terms incomplete paraplegia and paraparesis in current literature. MATERIALS AND METHODS: A review of the origin of the terms, definitions and nomenclatures applied by the most widespread assessment scales in traumatic SCI published in peer review papers was performed, searching the scales cited on the references of the latest American Spinal Injury Association classification (2002; available in http://www.asia-spinalinjury.org/ ) up to the first classification, described by Frankel et al. [14]. RESULTS: The term "incomplete paraplegia" has been used to define clinical situations classically described as "paraparesis". CONCLUSION: The terms "complete" and "incomplete" are adequately used to characterize the completeness of spinal cord lesion but inadequately used when associated to the term "plegia" as a qualifier. Therefore, patients with any preservation of motor strength below the injury level should be described as paraparetic and not as incomplete paraplegic.

Simultaneous posterior ischemic optic neuropathy, cerebral border zone infarction, and spinal cord infarction after correction of malignant hypertension.

A 31-year-old woman developed bilateral posterior ischemic optic neuropathy and infarctions of the cerebral arterial border zones and spinal cord after correction of malignant hypertension. Although a few reports have described patients with neurologic abnormalities after treatment of malignant hypertension, full clinical and neuroimaging documentation of this combination of findings has not occurred. This case report suggests that the relative hypotension of autoregulatory failure induced by treatment of malignant hypertension may give rise to these neurologic complications.

Anterior lumbosacral polyradiculopathy after intrathecal administration of methotrexate.

Transient paraparesis has been reported with intrathecal chemotherapy agents and the most common cause is an incomplete inflammatory myelopathy. We report a case of a 30-year-old man diagnosed with acute lymphoblastic leukaemia who developed subacute anterior lumbosacral polyradiculopathy following intrathecal methotrexate, an unusual complication of intrathecal chemotherapy in adults. Spinal magnetic resonance discarded myelopathy. Cerebrospinal fluid exam showed elevation of protein, mononuclear pleocytosis and immunoglobulin synthesis. Electrodiagnostic study showed alterations of sensory and motor conductions only in lower limbs, consistent with multilevel radiculopathy. Differential diagnosis included toxic and neoplastic polyradiculopathy, and axonal variant of acute inflammatory demyelinating polyradiculoneuropathy. The authors review possible pathogenic mechanisms and propose several therapeutic and preventive options.

Vincristine-induced acute neurotoxicity versus Guillain-Barré syndrome: a diagnostic dilemma.

We report the case of a patient with acute lymphoblastic leukaemia who, after the initiation of treatment with vincristine (VCR), developed a fulminant motor polyradiculoneuropathy resembling an axonal variant of Guillain-Barré syndrome (GBS). This report shows that differentiating between axonal GBS and VCR-induced acute neurotoxicity may be a challenge for clinicians.