Dose-response relationship between local anesthetic volume and hemidiaphragmatic paresis following ultrasound-guided supraclavicular brachial plexus blockade.

BACKGROUND: There is no consensus regarding what volume of local anesthetic should be used to achieve successful supraclavicular block while minimizing hemidiaphragmatic paresis (HDP). This study investigated the dose-response relationship between local anesthetic volume and HDP after ultrasound-guided supraclavicular brachial plexus block. METHODS: A dose escalation design was used to define the dose response curve for local anesthetic volume and incidence of HDP in subjects undergoing upper extremity surgery with supraclavicular block as the primary anesthetic. Dosing levels of 5, 10, 15, 20, 25, 30, 35 and 40 mL of local anesthetic were administered in cohorts of three subjects per dose. Diaphragm function was assessed with M-mode ultrasound before and after block. Secondary objectives included assessment of negative inspiratory force (NIF), oxygen saturation, subjective dyspnea and extent of sensory and motor blockade. RESULTS: Twenty-one subjects completed the study. HDP was present at all doses, with an incidence of 33% at 5 mL to 100% at 30-35 mL. There was a significant decrease in NIF (7.5 cmH2O, IQR (22,0); p=0.01) and oxygen saturation on room air (1%, IQR (2,0); p=0.01) 30 min postblock in subjects experiencing HDP but not in those without HDP. There was no increase in dyspnea in subjects with or without HDP. No subject required respiratory intervention. Motor and sensory block improved with increasing dose, and subjects with HDP exhibited denser blocks than those without (p<0.01). CONCLUSIONS: There is no clinically relevant volume of local anesthetic at which HDP can be avoided when performing a supraclavicular block. In our subject population free of respiratory disease, HDP was well tolerated. TRIAL REGISTRATION NUMBER: NCT03138577.

Methotrexate-Induced Subacute Neurotoxicity Surrounding an Ommaya Reservoir in a Patient with Lymphoma.

BACKGROUND Intraventricular administration of methotrexate (MTX) using an Ommaya reservoir is a useful therapeutic maneuver for malignant CNS involvement in patients with hematological malignancies. MTX-induced subacute neurotoxicity is a rare complication that typically progresses with involvement of the basal ganglia. Local toxicity due to misplaced catheters has been described, although the impact of normally positioned catheters on toxicity is not clear. CASE REPORT We report the case of a 21-year-old man diagnosed with stage IV diffuse large B-cell lymphoma who experienced a central nervous system relapse. While receiving intraventricular MTX using an Ommaya reservoir and systemic MTX, he experienced sudden left-side hemiparesis. All diagnostic tests were negative except for altered MRI findings with FLAIR hyperintensity in the basal ganglia and restricted diffusion in the same location that followed the track of the Ommaya catheter. The syndrome resolved after administration of high-dose steroids, and the patient received subsequent MTX courses without recurrence. CONCLUSIONS MTX-induced neurotoxicity is a rare adverse event related to systemic and intrathecal administration of the drug. Many cases of Ommaya-related CNS symptoms have been described, although most were related to misplaced or malfunctioning catheters. Here we present a case of subacute MTX toxicity affecting the area around a correctly positioned catheter, suggesting that the catheter track could be more susceptible to MTX-induced toxicity.

Subacute Methotrexate Encephalopathy Mimicking Ischemic Stroke With Dynamic Changes on Magnetic Resonance Imaging.

We report a 35-year-old woman who suddenly developed left hemiparesis and dysarthria at 13days after treatment with intrathecal and intravenous methotrexate for intravascular large B cell lymphoma with possible central nervous system infiltration. Seven hours after onset, she developed further right hemiparesis and aphasia. However, the majority of neurologic symptoms disappeared spontaneously and completely by 34hours. We also recorded the dynamic progression and regression of abnormal signals in the bilateral corona radiata on diffusion-weighted imaging, in parallel with neurologic symptoms. The rapid reversal of MR abnormalities and neurologic symptoms allowed us to diagnose methotrexate encephalopathy, and exclude intravascular large B cell lymphoma recurrence and regular brain infarction. The case provides new data on the dynamic changes of abnormal signals on magnetic resonance imaging in methotrexate encephalopathy over a short recovery time.

Evaluation and Management of Acute-Onset Hemiparesis in an Adolescent With Leukemia.

Emergency departments (EDs) are alert to the possibility of stroke and the need for early interventions to improve long-term clinical outcomes. However, new-onset hemiparesis in pediatric patients with leukemia may be due to a number of different etiologies, including most common side effects from chemotherapeutic agents. We present a case of a 15-year-old boy with pre-B acute lymphoblastic leukemia on chemotherapy, having recently received a high-dose methotrexate infusion in addition to intrathecal methotrexate therapy, who presented to our ED with acute right-sided hemiparesis. He was initially suspected as having a possible ischemic stroke. Magnetic resonance imaging (diffusion-weighted and fluid-attenuated inversion recovery sequence) demonstrated focal areas of diffusion restriction, an early sign of delayed-onset methotrexate neurotoxicity. Our patient received appropriate supportive care and leucovorin rescue with gradual clinical recovery, after a prolonged hospitalization and acute care rehabilitation over the course of several months. Our case illustrates the need for ED providers to consider methotrexate neurotoxicity in pediatric oncology patients presenting with acute neurologic changes.

Internal carotid artery occlusion and stroke as a complication of cisplatin-based chemotherapy for metastatic testicular germ cell tumour.

Testicular tumours are the most common tumours in young men. Germ cell tumours (GCTs) account for 95% of all testicular cancers, and the non-seminomatous type (NSGCT) accounts for 50% of all GCTs. Cisplatin-based chemotherapy is curative in up to 90% of patients, but it is not without its inherent risks. Ischaemic stroke is a very uncommon, but severe complication of cisplatin-based chemotherapy. Strokes in young patients cause a disproportionately large economic impact by leaving victims disabled during their most productive years and strains the healthcare system with expensive hospital stays. We present a case of a young male patient with past medical history of metastatic NSGCT with the sudden onset of dysarthria, left hemiplegia and ipsilateral hemisensory loss 3 days after receiving cisplatin-based chemotherapy. Subsequent studies revealed a stroke involving the right middle cerebral artery territory secondary to an acute right internal carotid occlusion.

[Consciousness Impairment and Left Hemiparesis due to Contrast Medium in the Coil Embolization of Unruptured Large Right Middle Cerebral Artery Aneurysm: A Case Report].

Neurological deficits following coil embolization of anterior circulation aneurysms due to the toxicity of contrast medium are rare. Here, we describe a patient with mild consciousness impairment and left hemiparesis following coil embolization of a large right middle cerebral artery aneurysm without evidence of ischemia or hemorrhage, who recovered completely with conservative treatment. The patient's clinical course and radiological findings led us to conclude that the neurological deficits were due to the toxic effect of contrast medium used during the coil embolization.

Generalized seizures and transient contralateral hemiparesis following retrobulbar anesthesia: a case report.

BACKGROUND: Retrobulbar block is a local anesthetic technique widely used for intraocular surgery. Although retrobulbar anesthesia is considered to be relatively safe, a number of serious adverse events have been reported. To our knowledge, immediate onset of generalized seizures with contralateral hemiparesis after retrobulbar anesthesia has not been reported. CASE PRESENTATION: A 62-year-old Caucasian healthy male with a right eye retinal detachment was admitted for pars plana vitrectomy. During retrobulbar anesthesia with ropivacaine and before needle withdrawal, the patient developed twitching of the face which rapidly progressed to generalized tonic-clonic seizures. Arterial oxygen saturation decreased to 75 %. Chin lift was performed and 100 % oxygen was administrated via face mask, which increased saturation to 99 %. Midazolam 2 mg was administrated intravenously to control seizures. After cessation of seizures, left-sided hemiparesis was evident. Brain computed tomography and electroencephalogram were normal 3 h later. The patient underwent pars plana vitrectomy under general anesthesia 4 days later. CONCLUSION: Serious complications of local anesthesia for ophthalmic surgery are uncommon. We present a case in which generalized tonic-clonic seizures developed during retrobulbar anesthesia, followed by transient contralateral hemiparesis. The early onset of seizures indicated intra-arterial injection of the anesthetic. Our case suggested the need for close monitoring during the performance of retrobulbar anesthesia and the presence of well-trained personnel for early recognition and immediate management of the complications.

[Hemiparesis and facial palsy caused by methotrexate]. / Hemiparesia y parálisis facial transitorias causadas por metotrexato.

Methotrexate used in the treatment of acute lymphocytic leukemia, can cause neurotoxicity, including a rare presentation with hemiparesis. We describe two teenagers, who during the implementation of the M phase of the protocol, suffered hemiparesis, facial paresis and dysarthria which quickly reversed. Leukemia involvement of the central nervous system and stroke, were ruled out. We briefly review the pathophysiology of methotrexate neurotoxicity, the characteristics of the focal paresis presentation and magnetic resonance image findings.

D-dimer elevation and paresis predict thromboembolic events during bevacizumab therapy for recurrent malignant glioma.

BACKGROUND: The major side-effects of bevacizumab in glioma treatment are venous thromboembolic events (VTE). We retrospectively evaluated factors potentially predictive of thromboembolic events. PATIENTS AND METHODS: Bevacizumab, alone or in combination with chemotherapy was used as salvage therapy for recurrence in malignant glioma every two weeks. None but one patient received anti-coagulants. Before each bevacizumab cycle differential blood cell count, kidney and liver parameters, D-dimers, neurological status, body-mass index, vital signs and signs of venous thrombosis were assessed. RESULTS: Thirty-eight patients received 428 cycles of bevacizumab. In five patients (13%), six VTE were observed. These complications were preceded four weeks before the onset of symptoms by D-dimer elevation above 0.865 mg/l [p<0.0001; sensitivity=89% (95% confidence interval=83-93%); specificity=89% (95% CI=52-100%)]. An existing hemiparesis constituted a 27-fold risk elevation for thrombotic complication (p<0.0001, χ(2)-test). CONCLUSION: D-Dimer elevation or hemiparesis predict VTE under bevacizumab and chemotherapy, four weeks before the event becomes clinically apparent. Future investigations should determine if prophylactic anti-coagulants for patients at risk may reduce the risk of VTE.

Repeated injection of contrast medium inducing dysfunction of the blood-brain barrier: case report.

An early 60s-year-old man suffered reversible dysfunction of the blood-brain barrier (BBB) induced by repeated injection of contrast medium during coil embolization of intracranial unruptured aneurysm. He presented with convulsion during coil embolization, and neurological symptoms of aphasia and right hemiparesis continued for 5 days, and then improved completely. All transient radiological abnormalities were limited to the territory of the left internal carotid artery, where contrast medium was injected repeatedly. Repeated computed tomography, magnetic resonance imaging, single-photon emission computed tomography, and cerebrospinal fluid test findings indicated that temporary dysfunction of the BBB might have occurred. Dysfunction of the BBB in the anterior circulation induced by contrast medium is rare. Tolerance to toxicity of contrast medium may depend on the individual patient, and repeated injection of contrast medium may cause dysfunction of the BBB, leading to toxic dysfunction directly in the brain.

Methotrexate-induced acute toxic leukoencephalopathy.

Acute lymphoblastic leukemia (ALL) is one of the most common malignancies of childhood, which is treated with high doses of methotrexate (MTX), as it crosses the blood-brain barrier and can be administered intravenously and via intrathecal route to eradicate leukemic cells from central nervous system (CNS). Additionally, high doses of MTX not only prevent CNS recurrence but also hematologic relapses. Although, standard treatment protocol for ALL includes multimodality therapy, MTX is usually associated with neurotoxicity and affects periventricular deep white matter region. Methotrexate-induced 'acute toxic leukoencephalopathy' has varying clinical manifestations ranging from acute neurological deficit to seizures or encephalopathy. Diffusion weighted magnetic resonance imaging (DW-MRI) is widely available and routinely used in clinical practice to identify acute stroke and also to distinguish acute stroke from non-stroke like conditions. We report a local teenage Chinese girl who developed 2 discrete episodes of left upper and lower limb weakness with left facial nerve paresis after receiving the 2 nd and 3 rd cycle of high dose of intravenous and intrathecal methotrexate, without having cranial irradiation. After each episode of her neurological deficit, the DW-MRI scan showed focal restricted diffusion in right centrum semiovale. Her left sided focal neurological deficit and facial nerve paresis almost completely subsided on both these occasions within 3 days of symptom onset. Follow-up DW-MRI, after her neurological recovery, revealed almost complete resolution of previously noted restricted diffusion in right centrum semiovale, while the lesion was not evident on concurrent T2W (T2-weighted) and FLAIR (Fluid-Attenuated Inversion recovery) sequences, nor showed any post contrast enhancement on post gadolinium enhanced T1W (T1-weighted) sequences. No residual neurological deficit or intellectual impairment was identified on clinical follow up over a 2 year period.

Diplopia após injeção de toxina botulínica tipo A para rejuvenescimento facial / Diplopia after injection of botulinic toxin type A for facial rejuvenation

Relato de 4 casos de pacientes encaminhadas ao serviço de Ortóptica deste Hospital, que apresentaram diplopia após a injeção de toxina botulínica tipo A para rejuvenescimento facial. Nas medidas de ângulo do estrabismo em posições diagnósticas todas apresentaram microestrabismo paralítico, sendo duas por déficit da função do músculo oblíquo inferior e duas por déficit de função de músculo reto lateral. Baseados nos casos descritos, aconselha-se aos profissionais que fazem uso desta toxina para fins de rejuvenescimento facial que estejam atentos para a diplopia como efeito colateral.

Report of 4 patients referred to the Orthoptics Service of this Hospital, who presented diplopia after the injection of botulinic toxin type A for facial rejuvenation.When measuring the angle of the strabismus in the diagnostic positions, all of the patients presented paralitical micro strabismus, two of them due to inferior oblique paresisand the other two due to lateral rectus paresis. Based on the cases described, we advise the professionals that make use of BTA for facial rejuvenation to be aware of diplopia as a complication.

Fatal PML associated with efalizumab therapy: insights into integrin αLß2 in JC virus control.

OBJECTIVES: Progressive multifocal leukoencephalopathy (PML) has become much more common with monoclonal antibody treatment for multiple sclerosis and other immune-mediated disorders. METHODS: We report 2 patients with severe psoriasis and fatal PML treated for ≥3 years with efalizumab, a neutralizing antibody to αLß2-leukointegrin (LFA-1). In one patient, we conducted serial studies of peripheral blood and CSF including analyses of leukocyte phenotypes, migration ex vivo, and CDR3 spectratypes with controls coming from HIV-infected patients with PML. Extensive pathologic and histologic analysis was done on autopsy CNS tissue of both patients. RESULTS: Both patients developed progressive cognitive and motor deficits, and JC virus was identified in CSF. Despite treatment including plasma exchange (PE) and signs of immune reconstitution, both died of PML 2 and 6 months after disease onset. Neuropathologic examination confirmed PML. Efalizumab treatment was associated with reduced transendothelial migration by peripheral T cells in vitro. As expression levels of LFA-1 on peripheral T cells gradually rose after PE, in vitro migration increased. Peripheral and CSF T-cell spectratyping showed CD8+ T-cell clonal expansion but blunted activation, which was restored after PE. CONCLUSIONS: From these data we propose that inhibition of peripheral and intrathecal T-cell activation and suppression of CNS effector-phase migration both characterize efalizumab-associated PML. LFA-1 may be a crucial factor in homeostatic JC virus control.

Decreasing the local anesthetic volume from 20 to 10 mL for ultrasound-guided interscalene block at the cricoid level does not reduce the incidence of hemidiaphragmatic paresis.

BACKGROUND AND OBJECTIVES: This prospective, randomized, double blind study was designed to determine whether reduction in volume from 20 to 10 mL of ropivacaine 0.5% for ultrasound-guided interscalene block might decrease the incidence of diaphragmatic paresis and preserve pulmonary function. METHOD: Thirty patients scheduled for arthroscopic shoulder surgery were randomized to receive either 10 or 20 mL of ropivacaine 0.5% for interscalene block at the level of the cricoid cartilage. General anesthesia was administered for surgery, and the surgeon infiltrated lidocaine at the port sites. Hemidiaphragmatic excursion and pulmonary function tests were measured before block, 15 mins after block, and at the time of discharge from recovery room. Onset and duration of sensory dermatomal spread, motor block, pain scores, and analgesic consumption were recorded. RESULTS: Hemidiaphragmatic paresis occurred 15 mins after block performance in 14 of 15 patients in each group. At postanesthesia care unit discharge, 13 of 15 patients in each group continued to demonstrate hemidiaphragmatic paresis. Significant reduction of spirometric values(forced vital capacity, forced expiratory volume at 1 sec, and peak expiratory flow) occurred to a similar degree in both groups after block.Sensory dermatomal spread, motor block, pain scores, and analgesic consumption were not significantly different between groups. CONCLUSIONS: Decreasing the volume for interscalene block from 20 to 10 mL did not reduce the incidence of hemidiaphragmatic paresis or impairment in pulmonary function, which persisted at discharge from recovery room. No significant differences in quality or duration of analgesia were observed.

The effect of muscle paralysis using Botox on the healing of tendon to bone in a rat model.

HYPOTHESIS: Despite good clinical results after rotator cuff repair, follow-up studies show significant rates of failed healing. This may be because of excessive tension on the repaired tendon due to shoulder motion. We hypothesized that botulinum toxin A injections would result in improved attachment strength and collagen organization at the tendon-bone interface at early time points but may result in decreased mechanical properties at later time points because of the negative effects of stress deprivation. MATERIALS AND METHODS: We performed division and repair of the supraspinatus tendon in 132 rats: 66 underwent repair alone and 66 received injections of botulinum toxin into the muscle before repair. Rats were killed at 4, 8, and 24 weeks and were evaluated by use of histologic, biomechanical, and micro-computed tomography analyses. RESULTS: At 4 and 24 weeks, there was no significant difference in load to failure between groups. At 8 weeks, the botulinum group had a significantly lower load to failure compared with controls (27.7 N vs 46.7 N, P < .01). The weight of the supraspinatus muscle was significantly decreased at 4 and 8 weeks in the botulinum group, but it recovered by 24 weeks. Micro-computed tomography analysis showed the botulinum group to have significantly less bone volume, total mineral content, and total mineral density at 8 weeks. Histologic analysis showed formation of a more normal tidemark and increased collagen fiber organization in the botulinum specimens at 4 weeks. DISCUSSION: Botulinum toxin A-treated specimens had increased collagen fiber organization at 4 weeks and decreased mechanical properties at later time points. The rapid healing of the rat rotator cuff likely makes it difficult to realize benefits from reduction in strain.

[Hemiparesis in acute lymphoblastic leukemia]. / Hemiparese bei akuter lymphoblastischer Leukämie.

The case of an adolescent female patient with acute lymphoblastic leukemia and stroke-like hemiparesis demonstrates a typical manifestation of methotrexate-induced acute encephalopathy. This rare entity occurs both in children and adults and can result from intrathecal as well as high dose intravenous administration of methotrexate. Diagnosis can confidently be made using cerebral MRI including diffusion-weighted imaging (DWI), so that patients can be informed about the favorable prognosis.