[Cannabinoids in multiple sclerosis -- therapeutically reasonable?].
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Cannabinoids↗
Biomedical subjects
E Mauch
Publications and source records attributed to E Mauch.
Cardiac adverse effects associated with mitoxantrone (Novantrone) therapy in patients with MS.
BACKGROUND: Mitoxantrone (MITO) is associated with dose-related cardiotoxicity when administered concomitantly with other cytotoxic agents with or without radiotherapy for leukemia and solid tumors. OBJECTIVE: To review observed cardiotoxicity of single-agent MITO therapy for MS. METHODS: Records of 1,378 patients from three clinical trials of MITO treatment for MS were reviewed for signs and symptoms of cardiac dysfunction and left ventricular ejection fraction (LVEF) results. Duration of follow-up was a median of 29 months (4,084 patient-years). RESULTS: No patients experienced congestive heart failure (CHF) before treatment. Cumulative MITO doses ranged from 2 to 183 mg/m(2) (mean 60.5 mg/m(2), median 62.5 mg/m(2)), and 141 patients received >100 mg/m(2). Two of 1,378 patients experienced CHF after initiating MITO therapy. Of 1,378 patients, 779 completed baseline and scheduled follow-up LVEF testing. Baseline LVEF was >50% in all 779 patients. Seventeen of 779 patients had asymptomatic LVEF of <50% (incidence proportion = 2.18%, 95% CI = 1.28 to 3.47%). Although the incidence of asymptomatic LVEF of <50% was not significantly related to monthly versus 3-monthly therapy, duration of therapy, age, or gender, asymptomatic LVEF of <50% trended higher with a cumulative dose of >/=100 mg/m(2) (5.0%) than with <100 mg/m(2) (1.8%) (p = 0.06). CONCLUSIONS: The observed incidence of CHF in patients with MS who received a mean cumulative dose of 60.5 mg/m(2) MITO was <0.20%. Continued monitoring of patients with MS who are receiving MITO is needed to determine whether the incidence of CHF increases with higher cumulative MITO doses and prolonged follow-up.
Adolescent↗
A study of therapy-related acute leukaemia after mitoxantrone therapy for multiple sclerosis.
To evaluate the incidence of therapy-related acute leukaemia (t-AL) after single-agent mitoxantrone (MITO) treatment, we reviewed medical records of patients in three studies of single-agent MITO therapy for multiple sclerosis (MS) and existing literature on MITO therapy in MS, leukaemia, and solid tumors. Of 1378 MITO recipients in the three MS studies (mean cumulative dose of 60 mg/m2 and mean follow-up of 36 months), one patient had t-AL, an observed incidence proportion of 0.07% [95% confidence interval (CI) = 0.00-0.40%]. There were no cases of t-AL in published reports of nine additional studies of single-agent MITO therapy for MS. There was one published case report of acute promyelocytic leukoemia detected five years after initiating MITO therapy for MS. The observed incidence proportion of t-AL is very low in patients who received MITO as single-agent therapy for MS. Although these observations provide preliminary reassurance, extended follow-up of these patients and those who receive higher cumulative doses of MITO is required to define the long-term risk of t-AL after MITO therapy for MS.
Acute Disease↗
Increased V/D-ratio in lumbosacral SEP's as a new electrophysiological measure of spasticity.
STUDY DESIGN: Open-label, prospective study. OBJECTIVE: To establish the amplitude-ratio of V-response and D-response (V/D-ratio) as a new measure of spasticity, comparing the motor effect of the H-reflex to the sensoric input. METHODS: In 13 legs of seven patients with spasticity and in four legs of patients without central nervous system disease, maximal M-response and maximal H-reflex were recorded. Lumbosacral SEP's were recorded with the same stimulus parameters as the maximal H-reflex. H/M-ratio and V/D-ratio were compared to the increased muscle tone. RESULTS: The H/M-ratio and the V/D-ratio in legs with spasticity differed significantly from the H/M-ratio and the V/D-ratio in normal legs. But only the V/D-ratio was higher in legs with moderately or highly increased muscle tone than in legs with slightly increased muscle tone. CONCLUSION: The V/D-ratio increases in spasticity and shows an even closer relationship to increased muscle tone than the H/M-ratio.
Electric Stimulation↗
GH, IGF-I, IGFBP-3 and IGFBP-2 in cerebrospinal fluid of infants, during puberty and in adults.
During diagnostic lumbar punctions cerbrospinal fluid (CSF) was collected for the determination of GH, IGF-I, IGFBP-3 and IGFBP-2. The patients were 0.3 to 68 years od and suffered from viral infections, leukemias, M. Hodgkin or multiple sclerosis. Only CSF samples without any pathological alterations were analysed. In infants and adults CSF GH concentrations significantly declined with age, while IGF-I and the two binding proteins were unrelated to age. GH was not correlated to IGF-I, IGFBP-3 or IGFBP-2. However, IGF-I was strongly related to IGFBP-3 (r = 0.529; < 0.001) and IGFBP-2 (r = 0.796; < 0.001) as was IGFBP-3 to IGFBP-2 (r = 0.685; < 0.001), suggesting dependence of the three variables. With IGFBP-3 or IGFBP-2 as control variables (partial correlation) IGF-I was no longer related to the binding proteins, while the relation of IGFBP-3 to IGFBP-2 remained unchanged with IGF-I as the control variable (r = 0.687; < 0.001). The results suggest that the age-related decrease of CSF GH may contribute to the age-dependent decline of GH receptors in brain, which are up-regulated by GH. Furthermore, in CSF IGF-I concentrations were determined by the two binding proteins. It may be speculated that the transfer of IGF-I through the blood CSF barrier or its production in brain may be closely related to the IGF-binding proteins.
Adolescent↗
The effects of therapy on spasticity utilizing a motorized exercise-cycle.
UNLABELLED: F-wave amplitudes have been used to demonstrate changes of motor neuron excitability in patients receiving pharmacological antispastic therapy as well as in those having physiotherapy. In this study it is shown that F-wave amplitudes can also be used to document changes of motor neuron excitability as an effect of the therapy with a motorized exercise-cycle, which moves the legs of paraplegic patients in a way similar to cycling. Ten F-waves were recorded immediately before and after the therapy with a motorized exercise-cycle in 70 legs of 35 patients with spastic paraparesis. Mean F-wave amplitude, mean F-wave/M-response ratio and maximum F-wave/M-response ratio were significantly lower after therapy than before. CONCLUSION: The antispastic effect of the therapy with a motorized exercise-cycle may be documented by a decrease of F-wave-amplitude parameters.
Adult↗
Intrathecal baclofen therapy for stiff-man syndrome and progressive encephalomyelopathy with rigidity and myoclonus.
We report on eight patients with stiff-man syndrome (SMS) or its "plus" variant, progressive encephalomyelopathy with rigidity and myoclonus (PERM) receiving intrathecal baclofen via pump. In six of the patients, follow-ups continued for approximately 2.5 to 6.5 years after pump implantation. Intrathecal baclofen was an effective last-resort alternative for patients who responded poorly to or did not tolerate oral antispasticity medications. General mobility increased, and spasms and rigidity were reduced; however, no complete remissions were observed either before or after pump implantation. PERM patients showed more severe and rapid progression of symptoms and more attacks of autonomic dysregulation than SMS patients. They also required higher doses and more rapid dosage increases. Complications of intrathecal baclofen therapy included spasm-induced rupture of the catheter, catheter dislocation causing radicular symptoms, and pump malfunction resulting in inaccurate dosage administration. Patients suffered fewer side effects with intrathecal baclofen than with oral medication, but overdose resulted in a transient, comalike state in one patient and sudden dosage reduction due to pump failure was fatal in another.
Adult↗
Effects of physiotherapy on F-wave-amplitudes in spasticity.
F-wave amplitudes have been used to demonstrate changes of motor neuron excitability in spasticity and pharmacological antispastic therapy. In this study it is shown that F-wave amplitudes can also be used to document changes of motor neuron excitability as an effect of physiotherapy. Ten F-waves were recorded immediately before and after physiotherapy in 42 legs of 21 patients with spastic paraparesis due to multiple sclerosis. Mean F-wave amplitude, maximum F-wave amplitude, mean F-wave/M-response ratio and maximum F-wave/M-response ratio were significantly lower after physiotherapy than before. Therefore the antispastic effect of physiotherapy is documented by a decrease of F-wave-amplitude parameters.
Adult↗
[The exencephaly-anencephaly sequence. Ultrasound diagnosis in early pregnancy].
AIM: In animal studies exencephaly is well described as a precursor of anencephaly. We have evidence that also in the human fetus the transition from exencephaly to anencephaly is possible. METHOD: We diagnosed either exencephaly or anencephaly by high-frequency vaginal ultrasound in 14 human fetuses at gestational ages varying between 9 + 4 and 22 + 3 weeks. RESULTS: In the first trimester exencephaly was the predominant finding, while in the second trimester the classic appearance of anencephaly was seen more often. In one fetus with exencephaly diagnosed at a gestational age of 12 + 2 weeks, where the parents decided not to intervene, the transition to anencephaly was documented by serial ultrasound examinations. CONCLUSIONS: Our findings support an exencephaly-anencephaly sequence also in humans. The cephalic changes resulting in the classic anencephalic appearance are of importance for the first trimester diagnosis with high resolution vaginal probe ultrasound.
Anencephaly↗
Serial gadolinium-enhanced magnetic resonance imaging in patients with multiple sclerosis treated with mitoxantrone.
Serial gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) was used to monitor the effect of mitoxantrone in ten patients with rapidly deteriorating multiple sclerosis (MS). MRI was performed as a baseline and thereafter at 1, 3, 6, 9, 12 and 24 months. The total number of Gd-enhancing lesions diminished from 169 at baseline to 10 after 1 year and to 5 after 2 years. This reduction and the percentage of follow-up MRI studies showing no Gd enhancement were more pronounced than in other MRI studies of the natural course of MS. Measured with quantitative neurological scales, only one patient showed deterioration after 2 years; nevertheless, the changes in MRI were much more marked than those observed clinically. Serial Gd-MRI therefore, seems necessary for documenting efficacy in future therapeutic trials.
Adult↗
Early cognitive impairment in multiple sclerosis detected by a screening with a vocabulary-test.
Vocabulary deficits in multiple sclerosis patients do not fit to the concept of subcortical dementia usually applied to describe cognitive impairment in multiple sclerosis. In a screening of young patients with a vocabulary test a significant correlation was found between the age at the onset of symptoms and the score in this test. This may lead to an explanation of vocabulary deficits recently described as results of a slowed language acquisition caused by subcortical lesions in early multiple sclerosis.
Adult↗
[The significance of quantitative computerized tomography in the long-term prognosis of ischemic stroke].
The courses of 118 patients who had suffered a supratentorial ischaemic infarction were observed over a mean follow-up period of 4 years. One goal of this study was to assess the prognostic value of quantitative cranial computerized tomography (CT). The infarct volume was determined using CT and expressed quantitatively as a percentage of the total brain volume. The infarct volume correlated negatively with the global outcome as estimated by the Barthel Index. It correlated positively with the occurrence of psychiatric alterations, disturbances of consciousness or alterations in the EEG. Nicotine, alcohol consumption and hyperuricaemia were the most frequent risk factors identified for men, while for women, especially those over 60, cardiac diseases were the most relevant risk factors. In looking only at the older patients, age, psychiatric alterations and cardiac disease at the time of the stroke were unfavourable prognostic factors. CT lesions in the basal ganglia were also unfavourable prognostic factors. Infarcts in the posterior cerebral artery region were seen as prognostically favourable. During the 4-year follow-up period, the reinfarction rate was 26%. Nearly 50% of the total patient population died. This group was significantly older, had more psychiatric alterations as well as multiple infarct areas in CT.
Adolescent↗
Neurological and neuropsychiatric dysfunction in primary Sjögren's syndrome.
In a prospective clinical investigation of 20 patients with primary Sjögren's syndrome (SS), neurological complications, not attributable to other diseases were detected in 14 patients (= 70%). Dysfunction of the peripheral nervous system (PNS) was nearly twice as frequent as central nervous system (CNS) complications. PNS involvement was dominated by symmetric sensory neuropathies, carpal tunnel syndromes, cranial nerve palsies (above all trigeminal sensory neuropathy) and pupillary dysfunction. CNS impairment was represented by cortical atrophy (n = 4), hemiparesis (n = 1) and aseptic meningitis (n = 1). Though CNS complications were rare, psychometric testing revealed diminished cognitive capacity in 14 patients. In addition to the characteristic sicca syndrome patients suffered from musculoskeletal pain and recurring abnormal sensation which frequently lead to the misdiagnosis of functional disorders. Additionally the frequent occurrence of psychiatric symptoms such as nervosity and depression support the impression of a psychosomatic pattern with no organic basis.
Adult↗
[Immunosuppressive therapy of multiple sclerosis with mitoxantrone].
Preliminary clinical results indicate that the cytostatic agent mitoxantrone is an effective and very tolerable substance for treating multiple sclerosis (ms). Our own experience, added to the findings of other pilot studies, seems to indicate that disease progression can be slowed in a majority of patients with rapidly progressive ms. Mitoxantrone is mainly excreted by the hepato-biliary pathways and therefore it can be used in patients with renal insufficiency or chronic cystopyelitis, a frequently occurring condition in ms. The side effects observed in our therapeutic scheme which could be attributed to mitoxantrone were tolerable. Mild gastrointestinal complaints were occasionally reported and vomiting was very rare. A carcinogenic effect from mitoxantrone has not been reported. A decrease in the leucocyte count is to be expected 6-15 days following treatment administration. Potential cardiotoxicity represents the primary long term adverse reaction and thus patients with cardiovascular risk factors should not be treated with mitoxantrone. Once a cumulative dosage of 140 mg/m2 is reached cardiac function tests, including echocardiography with measurement of the left ventricular ejection fraction, should be routinely carried out preceding each treatment administration in all patients. Mitoxantrone is currently not licensed for use in patients with ms and therefore should be restricted to patients with rapid disease progression where other generally accepted treatment modalities have failed.
Adult↗
Monitoring of intracapillary HbO2 in foetal scalp during delivery.
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Capillaries↗
Treatment of multiple sclerosis with mitoxantrone.
Ten multiple sclerosis patients, all with a rapid deteriorating disease profile, were treated with 12 mg/m2 of the cytostatic agent mitoxantrone, administered every 3 months. This dosage is only 25% of what a patient with a solid tumour would normally receive during the same time period. In all treated patients the deterioration was stopped following the initial dosage; in four out of ten patients there was even an immediate improvement of the neurological status. Eight out of nine patients showed an improvement after 1 year as compared with their enrollment status; the other one remained stabile. In correlation with the clinical improvement, the mean P100 latencies of visual evoked potentials showed a reduction after 1 year. However, the changes identified through magnetic resonance imaging were even clearer than those seen clinically. At admission, this group of patients presented with a total of 169 gadolinium (Gd)-enhancing lesions. Only 10 lesions were enhancing in nine patients 12 months after the initiation of treatment. It appears that mitoxantrone accelerates the disappearance of Gd-enhancing lesions and prevents the development of new ones. Minimal side effects such as mild nausea and a slight faintness were evident in six patients and then for only 1-2 days.
Adult↗
[Simultaneous occurrence of sarcoidosis and MS or sarcoidosis within the clinical picture of multiple sclerosis?].
Twelve years following the diagnosis of a histologically proved Sarcoidosis, a patient developed a central paresis of one lower limb. Two years later, tetraparesis, bladder dysfunction, ataxia and an internuclear bilateral ophthalmoplegia occurred. In CSF oligoclonal IgG without dysfunction of the blood brain barrier was found. On the basis of these data multiple sclerosis was diagnosed.
Adult↗
[The clinical value of Doppler sonography].
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Blood Flow Velocity↗