Effect of mitoxantrone on MRI in progressive MS: results of the MIMS trial.

OBJECTIVE: To evaluate the effects of mitoxantrone (Mx) in progressive multiple sclerosis (MS) on MRI. METHODS: A total of 194 patients with worsening relapsing-remitting or secondary progressive MS were treated with Mx 12 mg/m2 (n = 34), Mx 5 mg/m2 (n = 40), or placebo (n = 36) at 3-month intervals IV over a 2-year period. In preselected MRI centers unenhanced and Gd-enhanced MRI scans were performed at month (M) 0, 12, and 24 in a non-randomized subset of 110 patients and non-selected for MRI criteria. The primary MRI outcome measure was the total number of MRI scans with positive Gd enhancement per group. RESULTS: Twelve mg/m2 Mx failed to reach a significant difference from placebo as measured by the primary MRI outcome at month 12 (p = 0.431) and 24 (p = 0.065). Secondary MRI outcome measures: 5 mg/m2 Mx influenced favorably the number of Gd-enhancing lesions only at month 24 (p = 0.004), but not at month 12 (p = 0.095). Twelve mg/m2 Mx reduced the number of T2-weighted lesions at month 24 (p = 0.027) and showed a positive trend at month 12 (p = 0.069), but not 5 mg/m2 Mx. The number of active MR lesions showed a strong trend toward reduction in the 12 mg/m2 Mx group only at month 24 (p = 0.054). All comparisons are vs placebo, and unadjusted for baseline incidence. CONCLUSIONS: In the MIMS trial 12 mg/m2 Mx does not reduce the number of MRI scans with positive Gd enhancement at month 12 and 24 vs placebo. Results of secondary MRI outcome measures are suggestive of a positive impact of 12 and 5 mg/m2 Mx on some of the Gd enhanced and unenhanced MRI measures as expected from other Mx MRI studies in the past.

[Enhanced MR-angiography (CE-MRA) of the supraaortic arteries: dose reduction with a contrast agent of high relaxivity (Gd-BOPTA)]. / Kontrastmittelverstärkte MR-Angiographie (CE-MRA) der supraaortalen Arterien: Dosisreduktion bei einem Kontrastmittel hoher Relaxivität (Gd-BOPTA).

PURPOSE: Reducing the amount of contrast medium in contrast-enhanced MR-angiography (CE-MRA) of the cervical vessels could lead to considerable cost reduction. This study investigates whether the amount of contrast medium possessing high relaxivity can be reduced without loss of diagnostic information. MATERIALS AND METHODS: In a prospective study the supraaortic vessels of 40 patients were examined on a 1.5 T MR-system using 10 or 20 ml Gd-BOPTA (MultiHance). The examinations were evaluated by measurement of the signal increase in the common carotid arteries in 38 patients. Furthermore, CE-MRA was rated by two independent observers, who were blinded to the amount of contrast medium and degree of stenosis. Rating criteria were quality of arterial contrast and image impression. RESULTS: Signal increase in the carotid artery was identical for 10 and 20 ml Gd-BOPTA in 12 patients with optimal bolus timing (10 ml: 454 +/- 58; 20 ml: 458 +/- 63). Signal intensities were significantly lower for 10 ml when bolus timing was suboptimal (281 +/- 80 vs 353 +/- 65; p < 0.02). The quality of the CE-MRA using 10 and 20 ml Gd- BOPTA was rated as identical by the observers, and the amount of contrast medium used could not be deduced from the images. CONCLUSION: Image quality and signal values of the carotid arteries did not differ in CE-MRA performed with either 10 ml or 20 ml Gd-BOPTA (MultiHance) as long as the examination is adequate. Thus, cost reduction can be achieved with a reduced standard dose of 10 ml Gd-BOPTA without loss of diagnostic information.

Spontaneous occlusion of a cerebral arteriovenous malformation: angiography and MR imaging follow-up and review of the literature.

We present the angiographic and MR imaging course of a 62-year-old man with a right parietal high-flow arteriovenous malformation (AVM), which was diagnosed because of seizures. A spontaneous, complete, and asymptomatic occlusion of the AVM was confirmed by a second angiography 3 months later. The possible mechanisms leading to the occlusion are discussed, and a brief review of the literature is given.

[Bithalamic infarcts as the etiology of acute stupor. Early diagnosis with diffusion-weighted MRI]. / Bithalamische Infarkte als Ursache einer akuten Bewusstseinsstörung. Frühdiagnose mittels diffusionsgewichteter MRT.

Fast diagnostic evaluation of somnolent or unconscious patients is a demanding task for neurologists. Apart from postictal, metabolic, and toxic causes, vascular syndromes must be rapidly identified in order to initiate a specific fibrinolytic therapy. Given its high mortality if not treated in time, this dictum holds especially true for basilar artery occlusion. However, certain ischemic lesions in the vascular territory of the basilar artery without occlusion of the basilar artery itself can also result in somnolence, sopor, or even unconsciousness. Here we report early imaging signs of bithalamic infarctions as the cause of acute sopor using diffusion-weighted (DW)-MRI, which reliably identifies acute bithalamic infarctions as a possible cause of acute consciousness disturbance, even with noncooperative patients.

Ultrasonography and contrast-enhanced MRA in ICA-stenosis: is conventional angiography obsolete?

BACKGROUND: The standard techniques for the screening and staging of internal carotid artery (ICA) stenosis are Doppler (continuous wave) and Duplex sonography. For the imaging of ICA occlusive disease, magnetic resonance angiography (MRA) is replacing digital subtraction angiography (DSA). The purpose of this observational study was to assess whether contrast enhanced MRA (CE-MRA) combined with ultrasound provided sufficient information for the planning of surgical treatment. METHODS: CE-MRA was performed in 195 patients (mean age 67.5 years) with sonographic evidence of severe ICA stenosis. The MRA examination protocol contained a heavily T1-weighted contrast bolus enhanced 3D-gradient echo sequence. The degree of stenosis was estimated retrospectively by two experienced neuroradiologists who were blinded to the sonographic findings. RESULTS: The consistency of MRA and ultrasound was sufficient to plan thrombendarterectomy in 182/195 patients. The estimations of the degree of stenosis were congruent between MRA and ultrasound in 91% of 197 vessels with high-degree carotid artery stenosis. CE-MRA evaluation had a high interobserver agreement. In 3 cases ultrasound examination diagnosed a filiform ICA stenosis which was not visible with MRA. In all these cases, DSA and the intraoperative findings revealed very short (1-2 mm), high-grade, excentric stenosis. CE-MRA correctly detected patency in 5 patients with high-grade and low-flow carotid artery stenosis, which had been regarded as occluded by ultrasound. Conversely with, in CE-MRA two occluded vessels were falsely considered as open. CONCLUSION: The combination of sonography and CE-MRA is a powerful tool for the non-invasive presurgical evaluation of the carotid arteries. DSA should be reserved for selected cases.

[Contrast enhanced MR-angiography (CE-MRA): do contrast media with higher T1 relaxation improve imaging of carotid stenoses?]. / Kontrastangehobene MR-Angiographie (CE-MRA): Verbessern Kontrastmittel mit höherer T1-Relaxivität die Darstellung von Karotisstenosen?

PURPOSE: CE-MRA is a powerful tool for the non-invasive evaluation of carotid artery occlusive disease. However, due to certain drawbacks, it has not completely replaced DSA. The purpose of this study was to evaluate if Gd-BOPTA, a contrast agent with high T1 relaxivity, can increase the diagnostic accuracy of CE-MRA. MATERIAL AND METHODS: The CE-MRA examinations of 54 consecutive patients were evaluated by two experienced radiologists, independently. The examinations of 27 patients were contrasted either with 20 ml Gd-BOPTA or with 20 ml Gd-DTPA. The reviewers were blinded to the contrast agent chosen and to the ultrasound results. They rated the overall image quality and the degree of the ICA stenoses. RESULTS: For the estimation of the degree of the ICA stenoses there was a high interrater validity. In comparison to the ultrasound findings, 6 of 50 high-degree stenoses were underestimated as moderate stenoses. In one of seven sonographically occluded vessels, MRA revealed residual patency in the vessel lumen. It was not possible to identify the contrast agent that was taken for a study. Subjective estimation of the image quality (arterial contrast of the ICA, contrast of the other vessels, and general impression) did not significantly change with the contrast agent employed. CONCLUSION: The diagnostic accuracy of CE-MRA for the evaluation of internal carotid artery stenoses is not improved by Gd-BOPTA if identical volumina of contrast media are applied. The potential of this contrast agent can be the reduction of the amount of contrast without loss of diagnostic information. Further studies are necessary.

[Not Available]. / Medulloblastom des Kleinhirnwurms mit Liquorraumaussaat Ungewöhnliche klinische und MRT-Präsentation : Ungewöhnliche klinische und MRT-Präsentation.

Medulloblastoma, the most frequent pediatric brain tumor, has known propensity for subarachnoid dissemination. Spinal metastases indicate a poor prognosis. Intraventricular spread is much less common.We report a case of primary intraventricular dissemination with precocious puberty as the first clinical symptom due to a metastasis at the infundibulary stalk. This has not been reported so far as initial symptom of a medulloblastoma. Furthermore, we encountered an unusually mild contrast enhancement of the spinal and intraventricular metastases. Delayed scanning after contrast administration and FLAIR sequences proved to be particularly valuable in this case.

Subarachnoid hemorrhage due to septic embolic infarction in infective endocarditis.

During antibiotic therapy, a 56-year-old man with a Streptococcus bovis endocarditis developed an infarction of the right middle cerebral artery (MCA). Thirty hours after stroke onset, cranial computed tomography controls demonstrated a secondary subarachnoid hemorrhage, marked in the cistern of the right MCA. The latent period, cerebrospinal fluid analysis, angiographic and pathologic findings favor the assumption of a pyogenic arterial wall necrosis of the MCA due to a septic embolus. This pathomechanism of intracranial hemorrhage in infective endocarditis should be distinguished from a rupture of a mycotic aneurysm.

Small rosarylike infarctions in the centrum ovale suggest hemodynamic failure.

BACKGROUND AND PURPOSE: Lesions in the centrum ovale may be classified as microangiopathic (lacunar) lesions and hemodynamic infarctions. To distinguish between them, a size of more than 2 cm has been postulated for hemodynamic infarctions. The reliability of this criterion was assessed with MR imaging. METHODS: In 16 patients with unilateral or bilateral occlusion or high-grade stenosis of the internal carotid artery (ICA), CO2 testing revealed an ipsilateral hemodynamic failure. Each hemisphere in these patients was assessed separately for the presence and size of centrum ovale lesions. RESULTS: Five of the 16 patients suffered from large cortical infarctions with a probable embolic pathogenesis. In the remaining 11 patients (22 hemispheres), a hemodynamic failure was found in 15 hemispheres, due to occlusion (13 hemispheres) or high-grade ICA stenosis (two hemispheres). MR imaging revealed centrum ovale infarctions with a size of more than 2 cm in three of the 15 hemispheres. In eight hemispheres, multiple small lesions (< 1.5 cm; three to 30 per hemisphere) could be found with a rosarylike or sickle-shaped distribution. In none of these eight cases did MR images show lacunar infarctions in the typical regions of the brain. CONCLUSION: Our results favor the assumption that the MR finding of multiple small (< 1.5 cm) rosarylike lesions in the centrum ovale seems to be typical in patients with hemodynamic failure due to severe ICA disease.

[The supratrochlear artery as an indicator of cerebral hemodynamics in carotid occlusion]. / Die Arteria supratrochlearis als Indikator für die zerebrale Hämodynamik bei Karotisverschlüssen.

AIM: In internal carotid artery (ICA) occlusions a reversal flow in the ophthalmic artery (OA) has been considered both an important collateral as well as a sign of inadequate intracranial cross-flow. The aim of the study was to evaluate the effect of OA collateral on the cerebral haemodynamics using ultrasound and CCT. METHODS: In 540 patients with a total of 577 ICA occlusions the presence of an OA collateral was investigated with periorbital continuous-wave Doppler sonography and the findings were correlated with the ipsilateral cerebrovascular reserve capacity (CVR), measured with the Transcranial Doppler (TCD) CO2 test. Moreover, in 128 of 577 ICA occlusions the presence of an OA collateral was compared with the type of infarction in CCT and the neurological deficit. RESULTS: In 577 ICA occlusions an OA collateral was found in 59.4% (n = 343), whereas there was no or anterograde OA flow in 40.6% (n = 234). A significant correlation could be demonstrated between the CO2 reactivity and an OA collateral, which was present in 51.3% ipsilateral to a normal CVR (n = 175), in 66.9% ipsilateral to a diminished CVR (n = 115) and in 82.8% ipsilateral to an exhausted CVR (n = 53). Patients with OA collateral had a 15.5% risk of developing an exhausted CO2 reactivity, while there was only a 4.7% risk in the remaining patients (p < 0.001). In the 23 patients with haemodynamic infarctions in CCT the highest percentage of an OA collateral (87%) was found; no correlation could be demonstrated in these cases between the degree of neurological impairment and OA collateral flow. CONCLUSION: Patients with ICA occlusions and an OA collateral are subject to a more than a threefold risk of suffering from an exhausted CO2 reactivity in comparison with those revealing no reversal OA flow. Nevertheless, in patients with ICA occlusions and an OA collateral, CO2 reactivity was found to be normal in 51%, implying that in individual cases ultrasonic investigation of the periorbital flow is in itself insufficient to estimate the haemodynamic stroke risk and therefore cannot replace the TCD CO2 testing.

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.

[The significance of quantitative computerized tomography in the long-term prognosis of ischemic stroke]. / Die Bedeutung der quantitativen Computertomographie für die Langzeitprognose von ischämischen Grosshirninsulten.

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.

Course of cerebrovascular reactivity in patients with carotid artery occlusions.

BACKGROUND AND PURPOSE: Patients with internal carotid artery occlusions and highly impaired cerebrovascular reactivity have been identified as having an increased risk of stroke. It is still unclear, however, whether cerebral hemodynamics may be restored in the course of time by the development of collaterals. METHODS: During a 5-year period we assessed cerebrovascular reactivity in 452 carotid occlusions by transcranial Doppler CO2 testing. Ninety-eight patients could be reinvestigated at least once after 2 to 58 months (mean follow-up time, 26 months). RESULTS: On admission, patients with recent transient ischemic attack or stroke (< or = 3 months) as well as patients with contralateral carotid stenoses of 80% diameter reduction or greater and occlusions revealed a significantly higher incidence of impaired CO2 reactivity (P < .0001 and P < .01, respectively). During follow-up, 64% of the patients with no or minor contralateral carotid stenoses, but only 22% of the patients with bilateral carotid occlusions, showed a spontaneous improvement in cerebrovascular reactivity (P < .001), mainly during the first few months. In six of eight patients cerebral hemodynamics on the occluded side improved after endarterectomy of a contralateral high-grade carotid stenosis. Five of the patients who did not undergo surgery developed a stroke during follow-up, with three of them occurring in patients with permanently exhausted cerebrovascular reactivity. CONCLUSIONS: In the majority of patients with carotid occlusions an initially impaired cerebrovascular reactivity improves spontaneously with time. This could influence therapeutic decisions: During the first few months antihypertensive treatment may be avoided in such cases until a reestablished reactivity can be demonstrated. If cerebral hemodynamics remain depleted, extracranial-intracranial bypass surgery or endarterectomy of an asymptomatic contralateral high-grade carotid stenosis could be helpful.

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.

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.

Carbon dioxide reactivity and patterns of cerebral infarction in patients with carotid artery occlusion.

A total of 106 patients with 112 internal carotid artery occlusions were investigated by cranial computed tomography and transcranial Doppler ultrasonography (CO2 test), giving a measure of the cerebrovascular reserve capacity. The morphological patterns of the ischaemic lesions were classified into three categories: lacunar, thromboembolic and haemodynamic infarctions. Of 29 patients with an exhausted CO2 reactivity, 19 showed a haemodynamic type of infarction, whereas of 45 cases with a normal CO2 reactivity only 2, and of 38 patients with a diminished CO2 reactivity only 3 had haemodynamically caused infarctions (P less than 0.001). The correlation between an exhausted CO2 reactivity and the presence of haemodynamic infarctions could be of value for therapy in patients with carotid artery occlusions.

Effective treatment of chronically progressive multiple sclerosis with low-dose cyclophosphamide with minor side-effects.

Twenty-one multiple sclerosis (MS) patients with a chronically progressive course were treated with a low dose of cyclophosphamide (CY). The control group consisted of 21 MS patients with a chronically progressive course who received the standard treatment (ACTH or cortisone). The control group consisted of patients who preferred the standard therapy because of its beneficial effects. In contrast, the patients of the CY group wanted to try a new therapy because the standard therapy was not effective. Thus before starting the study the progression of the disease was faster in the CY group than in the standard therapy group. As regards age, sex and degree of disability, the two groups were comparable. For 20 of the 21 patients in the CY group the degree of disability (Kurtzke scale) remained stable over 1 year; for 2 of the 20 stable patients there was even an improvement. In the standard therapy group, 7 out of 21 patients were stable over 1 year, while 14 showed progressive disability. A quantitative neurological score at the beginning and 1 year after the therapy showed a nearly identical difference between the CY group and the control group. The changes of the patients' abilities in daily-life activities (which were observed and recorded by the nurses) were similar to the Kurtzke scale data obtained by the physicians. The beneficial effect of CY in chronically progressive MS was thus highly significant (P less than 0.001). The side-effects of low-dose CY were fewer than those of ACTH.

[Headache of unknown origin: brain tumor? Indications for computer tomography]. / Kopfschmerz unklarer Genese: Hirntumor?

Headache is the most frequent initial as well as the principle symptom of brain tumours. In 25 patients with brain tumours, in whom the initial symptom was headache, a further symptom of cerebral origin did not appear until after an interval of 40 months on average (median 11.5 months, 95% confidence limits of the median 4 and 60 months). Whereas tumours associated with short case-histories of headache are mostly glioblastomas, previously unrecognised tumours associated with long-standing headache are predominantly slow-growing, in the main easily operable, brain tumours. Pure headache-tumours occur predominantly in "silent" regions: in the subdominant (right) hemisphere and also in the frontal lobes as well as mid-basal in the sella area. In comparison with electroencephalography, X-ray of the skull, scintigraphy and sonography, computerised tomography is the superior non-invasive diagnostic procedure. A tumour-excluding headache does not exist. A typical migraine attack, when appearing for the first time in middle-age, can be the first indication of a brain tumour. Any reservations on the use of computerised tomography in regard to headache, when this has not been present since childhood as intermittent migraine, are, even from the point of view of cost, no longer tenable.