Assessment of potential cardiotoxic side effects of mitoxantrone in patients with multiple sclerosis

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/m(2) 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. Copyright (C) 2005 S. Karger AG, Basel

A clinical and EEG scoring system that predicts early cortical response (N20) to somatosensory evoked potentials and outcome after cardiac arrest

<p>Abstract</p> <p>Background</p> <p>Anoxic coma following cardiac arrest is a common problem with ethical, social, and legal consequences. Except for unfavorable somatosensory-evoked potentials (SSEP) results, predictors of unfavorable outcome with a 100% specificity and a high sensitivity are lacking. The aim of the current research was to construct a clinical and EEG scoring system that predicts early cortical response (N20) to somatosensory evoked potentials and 6-months outcome in comatose patients after cardiac arrest.</p> <p>Methods</p> <p>We retrospectively reviewed the records of all consecutive patients who suffered cardiac arrest outside our hospital and were subsequently admitted to our facility from November 2002 to July 2006. We scored each case based on early clinical and EEG factors associated with unfavorable SSEPs, and we assessed the ability of this score to predict SSEP results and outcome.</p> <p>Results</p> <p>Sixty-six patients qualified for inclusion in the cohort. Among them, 34 (52%) had unfavorable SSEP results. At day three, factors independently associated with unfavorable SSEPs were: absence of corneal (14 points) and pupillary (21 points) reflexes, myoclonus (25 points), extensor or absent motor response to painful stimulation (28 points), and malignant EEG (11 points). A score >40 points had a sensitivity of 85%, a specificity of 84%, and a positive predictive value (PPV) of 85% to predict unfavorable SSEP results. A score >88 points had a PPV of 100%, but a sensitivity of 18%. Overall, this score had an area under ROC curves of 0.919. In addition, at day three, a score > 69 points had a PPV of 100% with a sensitivity of 32% to predict death or vegetative state.</p> <p>Conclusion</p> <p>A scoring system based on a combination of clinical and EEG findings can predict the absence of early cortical response to SSEPs. In settings without access to SSEPs, this score may help decision-making in a subset of comatose survivors after a cardiac arrest.</p

Motion Perception in Patients with Idiopathic Bilateral Vestibular Hypofunction

We measured vestibular perceptual thresholds in patients with idiopathic bilateral vestibulopathy to assess the distribution of peripheral vestibular damage in this disorder. Thresholds were measured with standard psychometric techniques in 4 patients and compared with thresholds in normal subjects and patients with completely absent peripheral vestibular function. Motion paradigms included yaw rotation (testing the lateral canals), interaural translation (testing the utricles), superior-inferior translation (testing the saccules), and roll tilt (testing the vertical semicircular canals and the otolith organs). We found that perceptual thresholds were abnormally elevated in the patients with idiopathic bilateral vestibulopathy for yaw rotation at all frequencies and for interaural translation at only the lower frequencies. Thresholds were normal for the other 2 motion paradigms. The results demonstrate that the distribution of vestibular dysfunction in this disorder is not uniform but, rather, can affect lateral canal and utricular thresholds while relatively sparing vertical canal and saccular function

Covert Anti-Compensatory Quick Eye Movements during Head Impulses

BACKGROUND: Catch-up saccades during passive head movements, which compensate for a deficient vestibulo-ocular reflex (VOR), are a well-known phenomenon. These quick eye movements are directed toward the target in the opposite direction of the head movement. Recently, quick eye movements in the direction of the head movement (covert anti-compensatory quick eye movements, CAQEM) were observed in older individuals. Here, we characterize these quick eye movements, their pathophysiology, and clinical relevance during head impulse testing (HIT). METHODS: Video head impulse test data from 266 patients of a tertiary vertigo center were retrospectively analyzed. Forty-three of these patients had been diagnosed with vestibular migraine, and 35 with Menière’s disease. RESULTS: CAQEM occurred in 38% of the patients. The mean CAQEM occurrence rate (per HIT trial) was 11±10% (mean±SD). Latency was 83±30 ms. CAQEM followed the saccade main sequence characteristics and were compensated by catch-up saccades in the opposite direction. Compensatory saccades did not lead to more false pathological clinical head impulse test assessments (specificity with CAQEM: 87%, and without: 85%). CAQEM on one side were associated with a lower VOR gain on the contralateral side (p<0.004) and helped distinguish Menière’s disease from vestibular migraine (p = 0.01). CONCLUSION: CAQEM are a common phenomenon, most likely caused by a saccadic/quick phase mechanism due to gain asymmetries. They could help differentiate two of the most common causes of recurrent vertigo: vestibular migraine and Menière’s disease