Through a Glass, Darkly

Tyler, Kenneth L.; McArthur, Justin C.

doi:10.1001/archneur.59.6.909

Cited by 30 publications

(10 citation statements)

References 46 publications

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“…The mean follow-up time in our study was comparable to a recent meta-analysis by Ghalie et al [33]. In their meta-analysis of 1,378 patients, the safety of mitoxantrone applied as a single-agent therapy for MS was evaluated from three clinical trials, two of them retrospective chart reviews (the MIMS-study by Hartung et al [1]; a French study by Edan et al [14], and a German study by Mauch et al [15, 16]).…”

Section: Discussionmentioning

confidence: 99%

Assessment of Potential Cardiotoxic Side Effects of Mitoxantrone in Patients with Multiple Sclerosis

Zingler

Näbauer²,

Jahn

et al. 2005

Eur Neurol

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Previous studies showed that mitoxantrone can reduce disability progression in patients with multiple sclerosis (MS). There is, however, concern that it may cause irreversible cardiomyopathy with reduced left ventricular (LV) ejection fraction (EF) and congestive heart failure. The aim of this prospective study was to investigate cardiac side effects of mitoxantrone by repetitive cardiac monitoring in MS patients. The treatment protocol called for ten courses of a combined mitoxantrone (10 mg/m² body surface) and methylprednisolone therapy. Before each course, a transthoracic echocardiogram was performed to determine the LV end-diastolic diameter, the end-systolic diameter and the fractional shortening; the LV-EF was calculated. Seventy-three patients participated (32 males; age 48 ± 12 years, range 20–75 years; 25 with primary progressive, 47 with secondary progressive and 1 with relapsing-remitting MS) who received at least four courses of mitoxantrone. Three of the 73 patients were excluded during the study (2 patients discontinued therapy; 1 patient with a previous history of ischemic heart disease developed atrial fibrillation after the second course of mitoxantrone). The mean cumulative dose of mitoxantrone was 114.0 ± 33.8 mg. The mean follow-up time was 23.4 months (range 10–57 months). So far, there has been no significant change in any of the determined parameters (end-diastolic diameter, end-systolic diameter, fractional shortening, EF) over time during all follow-up investigations. Mitoxantrone did not cause signs of congestive heart failure in any of the patients. Further cardiac monitoring is, however, needed to determine the safety of mitoxantrone after longer follow-up times and at higher cumulative doses.

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Section: Discussionmentioning

confidence: 99%

Assessment of Potential Cardiotoxic Side Effects of Mitoxantrone in Patients with Multiple Sclerosis

Zingler

Näbauer²,

Jahn

et al. 2005

Eur Neurol

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“…In clinical practice, determining the HIV viral load in the CSF is important for monitoring the therapeutic effects of ARV treatment, for identifying patients with CNS escape (compartmentalization), and for determining the differential diagnosis in psychiatric disorders 5 .…”

Section: Hiv Viral Load In the Csfmentioning

confidence: 99%

“…The incidence of infection is increasing in some vulnerable groups, mainly young men who have sex with men (MSM) and older people 1,2 . The nervous and the immune systems are HIV target organs 3,4,5 . The introduction of highly active antiretroviral therapy (HAART) has changed the clinical situation for patients with AIDS, decreased the incidence of opportunistic infections, and thus lowered mortality.…”

mentioning

confidence: 99%

“…The purpose of this review is to discuss the indications for cerebrospinal fluid (CSF) analysis in HIV infection in clinical practice. CSF analysis during HIV infection is indicated for the diagnosis of opportunistic infections and co-infections; the diagnosis of meningitis, acute or chronic, caused by HIV; the quantification of HIV viral load in CSF; and the analysis of HIV compartmentalization in the CNS 5 . Table 1 summarizes CNS complications in HIV infection.…”

mentioning

confidence: 99%

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Cerebrospinal fluid analysis in the HIV infection and compartmentalization of HIV in the central nervous system

Almeida

2015

Arq. Neuro-Psiquiatr.

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The nervous system plays an important role in HIV infection. The purpose of this review is to discuss the indications for cerebrospinal fluid (CSF) analysis in HIV infection in clinical practice. CSF analysis in HIV infection is indicated for the diagnosis of opportunistic infections and co-infections, diagnosis of meningitis caused by HIV, quantification of HIV viral load, and analysis of CNS HIV compartmentalization. Although several CSF biomarkers have been investigated, none are clinically applicable. The capacity of HIV to generate genetic diversity, in association with the constitutional characteristics of the CNS, facilitates the generation of HIV quasispecies in the CNS that are distinct from HIV in the systemic circulation. CSF analysis has a well-defined and valuable role in the diagnosis of CNS infections in HIV/AIDS patients. Further research is necessary to establish a clinically applicable biomarker for the diagnosis of HIV-associated neurocognitive disorders.

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“…Its long-term use is limited by severe, dose-related or unrelated side effects [1,2,3,4,5] such as cardiotoxicity and leukemia. Cardiotoxicity may occur at low cumulative MTX doses [6] but its frequency is significantly higher for cumulative doses superior to 140 mg/m 2 [1,2]. The estimated risk of cardiotoxicity is approximately 12% for decreased rate of left ventricular ejection fraction (LVEF) and 0.4% for congestive heart failure (CHF) [7].…”

Section: Introductionmentioning

confidence: 99%

Tolerability and Acceptance of Prolonged Low/Delayed Mitoxantrone Regimens in Patients with Worsening Multiple Sclerosis

Zecca¹,

Petrini²,

Limoni³

et al. 2010

Eur Neurol

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Background: Severe side effects such as cardiotoxicity and leukemia limit long-term use of mitoxantrone (MTX) despite its recommendation in patients with malignant forms of relapsing remitting (RR) and secondary progressive (SP) multiple sclerosis (MS). Methods: We analyzed data on tolerability, measured as compliance with the treatment, and patients’ acceptance of an alternative MTX treatment schedule in 12 patients with aggressive RRMS or SPMS treated for at least 3 years with low/delayed dose MTX. Results: Twelve patients received 9–17 cycles of MTX treatment, with individual median doses of 7.6–12.16 mg/m²/course during 36 to 114 (median 49.5) months resulting in cumulative doses of 101.9–143.0 mg/m² per patient. The overall follow-up period was 37–122 (median 69.5) months. Treatment was well tolerated and appreciated by patients according to the Treatment Satisfaction-Visual Analogue Scale. No significant safety findings were seen concerning cardiological, hematological and oncological follow-up. The patients showed a stabilization of disease progression and a reduced annual relapse rate. Conclusions: Delayed, and/or dose-reduced, long-term MTX regimens over several years might represent a feasible alternative treatment for MS patients without any other therapeutic options.

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Through a Glass, Darkly

Cited by 30 publications

References 46 publications

Assessment of Potential Cardiotoxic Side Effects of Mitoxantrone in Patients with Multiple Sclerosis

Assessment of Potential Cardiotoxic Side Effects of Mitoxantrone in Patients with Multiple Sclerosis

Cerebrospinal fluid analysis in the HIV infection and compartmentalization of HIV in the central nervous system

Tolerability and Acceptance of Prolonged Low/Delayed Mitoxantrone Regimens in Patients with Worsening Multiple Sclerosis

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