Capecitabine-related neurotoxicity presenting with agraphia.

INTRODUCTION: Capecitabine is a pre-metabolite of 5-fluorouracil and is used as a chemotherapeutic agent. Among the common side effects of capecitabine, there are gastrointestinal side effects including nausea, vomiting, and diarrhea, and dermatological side effects including hand-foot syndrome and skin pigmentation change. However, neurological side effects of capecitabine are very rare. We describe herein a patient who developed neurological side effects in the form of agraphia and dysarthria on the 7th day of capecitabine treatment. CASE REPORT: A 34-year-old male patient, who was being followed up with the diagnosis of colon cancer, presented with speech and writing disorder that developed while under capecitabine treatment. Dysarthria and agraphia were detected in his neurological examination. Diffusion-weighted magnetic resonance imaging (MRI) revealed acute diffusion restriction in the splenium of the corpus callosum and at the level of the bilateral centrum semiovale. Brain MRI revealed symmetrical T2-weighted fluid-attenuated inversion recovery (T2-FLAIR) signal increases at the right temporoparietal medial, corpus callosum level, and bilateral white matter level. MANAGEMENT & OUTCOME: The capecitabine treatment was terminated, and methylprednisolone treatment was administered and plasmapheresis procedure was carried out. Subsequently, significant improvement was observed in the clinical findings and neuroimaging. DISCUSSION: Capecitabine is used as an oral agent; thus, it provides ease of use. Neurological side effects associated with the use of capecitabine reportedly occur very rarely. The findings of this case demonstrated that leukoencephalopathy can be seen during the use of capecitabine, imaging results are very important in the diagnosis of leukoencephalopathy, and improvement can be achieved with the termination of the capecitabine treatment.

Metronidazole-induced reversible cerebellar dysfunction.

A 73-year-old man who presented with fever and abdominal discomfort was diagnosed to have a liver abscess. He was treated with antimicrobials which included metronidazole. One month into treatment, he developed neurological symptoms and signs that were suggestive of cerebellar pathology. MRI of the brain showed T2/fluid attenuated inversion recovery hyperintensities involving bilateral dentate, fastigial and interpositus nuclei. After excluding common aetiologies, the possibility of metronidazole-induced neurotoxicity was considered. After stopping metronidazole, his symptoms and signs resolved. A subsequent MRI scan of the brain showed reversal of changes. Neurotoxicity caused by metronidazole is an uncommon adverse effect of a commonly used antimicrobial drug and should be considered in the appropriate clinical scenario.

Irinotecan-Associated Dysarthria in Patients with Pancreatic Cancer: A Single Site Experience.

BACKGROUND Irinotecan, a topoisomerase I inhibitor, is a cytotoxic chemotherapeutic agent used to treat multiple malignancies, including those of colorectal, pancreatic, cervical, esophageal, gastric, and lung origin. Dysarthria, a state of difficult or unclear articulation of speech, has been reported as a rare side effect of irinotecan through multiple case reports and case series, but with limited published data aimed at understanding the underlying mechanism and effective management strategies. CASE REPORT We describe herein 3 cases of patients with pancreatic malignancy who experienced dysarthria while being treated with a chemotherapy regimen containing irinotecan at an ambulatory outpatient satellite chemotherapy site. All patients described received first-line FOLFIRINOX for pancreatic cancer and experienced dysarthria during their first infusion of irinotecan. In all cases, dysarthria was observed as a transient adverse drug reaction within the first 10 to 70 min of irinotecan infusion, which resolved rapidly upon pausing infusion without any long-term sequalae. All patients remained conscious and alert; physical and neurological examinations at dysarthria onset revealed no abnormalities. Some patients experienced distal extremity paresthesia, a known manifestation of oxaliplatin-induced acute neurotoxicity, and diaphoresis and nausea. Increased infusion time effectively prevented dysarthria during subsequent infusions. CONCLUSIONS Oncologists, pharmacists, nurses, and other care team members should be aware that irinotecan-associated dysarthria is a rare, mild, and self-limiting phenomenon to avoid inadvertently altering or withholding therapy. We suggest extending irinotecan infusion time, as opposed to dose reduction or treatment discontinuation, as a practical clinical management strategy for patients who develop recurrent dysarthria secondary to irinotecan infusion.

Articulation lost in space. The effects of local orobuccal anesthesia on articulation and intelligibility of phonemes.

Motor speech requires numerous neural computations including feedforward and feedback control mechanisms. A reduction of auditory or somatosensory feedback may be implicated in disorders of speech, as predicted by various models of speech control. In this paper the effects of reduced somatosensory feedback on articulation and intelligibility of individual phonemes was evaluated by using topical anesthesia of orobuccal structures in 24 healthy subjects. The evaluation was done using a combination of perceptual intelligibility estimation of consonants and vowels and acoustic analysis of motor speech. A significantly reduced intelligibility was found, with a major impact on consonant formation. Acoustic analysis demonstrated disturbed diadochokinesis. These results underscore the clinical importance of somatosensory feedback in speech control. The interpretation of these findings in the context of speech control models, neuro-anatomy and clinical neurology may have implications for subtyping of dysarthria.

Successful thrombolytic therapy with recombinant tissue plasminogen activator in ischemic stroke after idarucizumab administration for reversal of dabigatran: a case report.

BACKGROUND: Idarucizumab is a specific antidote for the anticoagulant dabigatran. Although its efficacy has been recently reported, the drug is still in postmarketing surveillance and requires case data in different emergency settings. A newer intravenous thrombolytic therapy with recombinant tissue plasminogen activator has been proposed after injection of idarucizumab in patients receiving dabigatran; however, the safety and efficacy of this therapy are equivocal because of the limited number of reported cases. We describe a case of a patient with acute lacunar stroke causing dysarthria and hemiparesis successfully treated with intravenous thrombolytic therapy with recombinant tissue plasminogen activator after reversal of dabigatran with idarucizumab. CASE PRESENTATION: A 67-year-old Asian woman was transferred to our emergency center 200 minutes after sudden onset of dysarthria and right-sided hemiparesis. She had been taking dabigatran for prevention of stroke recurrence caused by atrial fibrillation. Diffusion-weighted magnetic resonance imaging revealed a new lacunar infarction near old putamen infarctions. We treated her with intravenous thrombolytic therapy with recombinant tissue plasminogen activator after administering idarucizumab. The time to recombinant tissue plasminogen activator administration was 5 minutes from idarucizumab injection and 269 minutes from symptom onset. The patient's activated partial thromboplastin times were 68.0 and 43.2 seconds before and after the therapy, respectively. The patient's neurological symptoms improved significantly after the treatment, and she experienced no adverse events. CONCLUSIONS: Intravenous thrombolytic therapy with recombinant tissue plasminogen activator after reversal of dabigatran with idarucizumab may be safe and feasible in patients with acute ischemic stroke with lacunar infarct. Furthermore, intravenous thrombolytic therapy with recombinant tissue plasminogen activator could be used in patients in emergency settings until just before the end of the recommended time limit within which it needs to be administered because of the immediate effect of idarucizumab.

Irinotecan-associated dysarthria: A single institution case series with management implications in patients with gastrointestinal malignancies.

Irinotecan (Camptosar©, CPT-11), a topoisomerase I inhibitor, is a commonly used cytotoxic chemotherapeutic in the treatment of multiple malignancies, particularly of gastrointestinal origin. Dysarthria secondary to irinotecan has been described as a rare side effect in a few case reports with limited data to recommend appropriate management. We describe herein a large single institution experience of patients with gastrointestinal malignancies who experienced dysarthria while being treated with irinotecan-based chemotherapy regimens (FOLFIRINOX or FOLFIRI+/-bevacizumab). Eighteen patients developed neurological manifestations during irinotecan infusion with the majority ( n = 17) developing dysarthria. Patients also experienced other known side effects including cholinergic effects (abdominal bloating, diarrhea, facial flushing, diaphoresis, and rhinorrhea), nausea, fatigue, perioral paresthesia and musculoskeletal discomfort. The dysarthria occurred as early as with the first infusion of irinotecan ( n = 9), but several patients did not develop symptoms until subsequent infusions (range, 1-6). Dose alterations of irinotecan did not obviously impact the reccurrence or severity of dysarthria. Management strategies included close observation, atropine, slower irinotecan infusion rate, and reassurance. Dysarthria resolved without consequence in all patients within hours of completion of the infusion. Oncologists and pharmacists should be aware of irinotecan-associated dysarthria as a rare, self-limited phenomenon with no long-term sequelae, and appropriately counsel patients and infusion nurses to avoid inadvertently withholding potentially beneficial therapy for patients with gastrointestinal malignancies.

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.

[Encefalopathy as a side effect of metronidazole therapy ­ a case report]. / Metronidazol gav svår biverkning med neurologiska symtom - Möjligen finns ett mörkertal av odiagnostiserade patienter.

Encefalopathy as a side effect of metronidazole therapy - a case report  Neurological symptoms as side effects of pharmacological treatment generally tend to remain underdiagnosed. In this report, we present a case of a 79 year old patient that developed encephalopathy whilst undergoing prophylactic treatment with Metronidazole. The initial presentation of disseminated neurological symptoms lead to the suspicion of a cerebrovascular lesion. However, exacerbation of symptomatology with gait disturbance, ataxia and dysarthria challenged the preliminary diagnosis. Brain magnetic resonance imaging (MRI) demonstrated T2 hyper-intensity over bilateral dentate nuclei. A drug history revealed that the patient had been treated with Metronidazole daily for several weeks due to a surgical condition. Cessation of the drug provided reversal of symptoms and radiological findings upon follow up MRI. This case report aims at increasing awareness regarding side effects of Metronidazole as well as early detection in patients who present with neurological symptoms.

Irinotecan-induced dysarthria: A case report and review of the literature.

Irinotecan-induced dysarthria has been reported in the literature, but the underlying mechanism of this neurotoxicity remains unclear. Here, we present a 35-year-old female with metastatic colon cancer who experienced dysarthria during irinotecan infusion. Her symptoms were decreased and eventually eliminated with subsequent increases in infusion time. When the patient returned to original 90 min infusion time, symptoms were significantly reduced in both severity and duration as compared to the first infusion. We suggest infusion time as a potential intervention for patients experiencing dysarthria, and we review the existing literature, explore treatment options, and discuss proposed mechanisms surrounding this unusual adverse drug reaction.

Metronidazole-Induced Encephalopathy in Alcoholic Liver Disease: A Diagnostic and Therapeutic Challenge.

BACKGROUND: Acute encephalopathy in a patient with alcoholic liver disease (ALD) is a commonly encountered emergency situation occurring most frequently due to liver failure precipitated by varying etiologies. Acute reversible cerebellar ataxia with confusion secondary to prolonged metronidazole use has been reported rarely as a cause of encephalopathy in patients with ALD. CASE REPORT: We describe a decompensated ALD patient with recurrent pyogenic cholangitis associated with hepatolithiasis who presented to the emergency department with sudden-onset cerebellar ataxia with dysarthria and mental confusion after prolonged use of metronidazole. Magnetic resonance imaging (MRI) of the brain was suggestive of bilateral dentate nuclei hyper intensities on T2 and fluid-attenuated inversion recovery sections seen classically in metronidazole-induced encephalopathy (MIE). Decompensated liver cirrhosis resulted in decreased hepatic clearance and increased cerebrospinal fluid concentration of metronidazole leading to toxicity at a relatively low total cumulative dose of 22 g. Both the clinical symptoms and MRI brain changes were reversed at 7 days and 6 weeks, respectively, after discontinuation of metronidazole. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: A patient with ALD presenting with encephalopathy creates a diagnostic dilemma for the emergency physician regarding whether to continue metronidazole and treat for hepatic encephalopathy or to suspect for MIE and withhold the drug. Failure to timely discontinue metronidazole may worsen the associated hepatic encephalopathy in these patients. Liver cirrhosis patients have higher mean concentration of metronidazole and its metabolite in the blood, making it necessary to keep the cumulative dose of metronidazole to < 20 g in them.

Analysis of a distinct speech disorder seen in chronic manganese toxicity following Ephedrone abuse.

INTRODUCTION: In the last fifteen years a new cause of chronic manganese toxicity has been recognized. It follows recreational intravenous injections of Ephedrone, synthesized from a cold remedies contained pseudoephedrine. Potassium permanganate is used as an oxidant. It presents with severe parkinsonism-dystonia and a characteristic dysarthria. OBJECTIVES: We performed a focus perceptual study of dysarthria in Ephedrone induced parkinsonism and compared the findings with the speech disorders seen in Parkinson's disease (PD) and Progressive Supranuclear Palsy (PSP). METHODS: A digital voice recording, perceptual speech analysis (Darley, 1975) [18], serial neurological assessment and Brain Magnetic Resonance (MR) imaging were performed at the Lviv regional Clinical Hospital. The results were analysed at the Institute of Neurology in London. RESULTS: Dysarthria developed after 8.5±3.2months of daily intravenous Ephedrone abuse and was an initial symptom in a third of cases. It was characterised by a robotic-flat prosody, whispering or continuous phonation, an inability to regulate pitch and volume, frozen lip articulation, a variable degree of dystonic tightness, difficulties in speech initiation and palladia, There was no nasality and swallowing was normal. In some patients speech deteriorated even after the discontinuation of Ephedrone. MR imaging, performed soon after drug cessation showed T1 signal hyperintesity in striatum and pallidum, especially in the Globus Pallidum interna. CONCLUSION: Ephedrone induced chronic manganese toxicity can lead to a mixed hypokinetic-dystonic dysarthria with a distinct dystonic pattern. Perceptual speech analysis can be a helpful ancillary investigation in the differential diagnosis of parkinsonism, and may permit the recognition of chronic manganese toxicity.