Value of gradient-echo magnetic resonance imaging in the diagnosis of familial cerebral cavernous malformation

BACKGROUND: Cerebral cavernous malformations (CCMs) are congenital vascular anomalies that can cause seizures, intracranial hemorrhages, focal neurological deficits, and migrainelike headaches. Magnetic resonance (MR) imaging has substantially facilitated diagnosis of CCM. It is now widely accepted that familial clustering with an autosomal dominant inheritance pattern should be suspected in cases of multiple lesions. OBJECTIVE: To determine by MR imaging the penetrance of cavernous malformations in a 3-generation family that included 5 members with typical clinical signs and diagnostic findings. METHODS: All family members underwent routine MR T1-weighted and T2-weighted spin-echo sequences in addition to MR T2-weighted gradient-echo sequences. RESULTS: Four family members had been symptomatic with either brainstem bleeding, headaches, or focal neurological signs. The gradient-echo sequences yielded a dramatically higher sensitivity with regard to lesion number and distribution.As in previous reports of familial CCM, an increase in lesion number with increasing age, changes in lesion characteristics, de novo occurrence in serial MR imaging over time, and the phenomenon of anticipation could be confirmed in this family. CONCLUSION: Magnetic resonance gradient-echo sequences should be considered the method of choice for diagnosis of familial CCM.     

Familial cerebral cavernous malformation: report of a further Italian family

Cerebral cavernous malformations (CCMs) are vascular abnormalities that may cause seizures, headaches, intracerebral hemorrhages, and focal neurological deficits; they can also be clinically silent and may occur as a sporadic or an autosomal dominant condition. Three genes have been identified as causing familial CCM: KRIT1/CCM1, MGC4607/CCM2, and PDCD10/CCM3, mapping, respectively, on chromosomes 7q, 7p, and 3q. This is a report on an Italian family affected by CCM due to a KRIT1 gene mutation on exon 13. The mother suffered from a cerebellar hematoma and was severely disabled; one son had suffered from intractable seizures and underwent surgery for removal of a cavernous angioma, while another son was asymptomatic. Brain MRI showed CCMs in all patients. This report underlines that a familial form of CCM could be suspected when a patient presents with multiple CCMs; neurologists and neurosurgeons should be aware that genetic testing for these forms is available.     

Clinical and muscle magnetic resonance imaging study of an Italian family with autosomal dominant inclusion body myopathy not linked to known genetic loci

Abstract The objective was to report a clinical, pathological and muscle magnetic resonance (MR) study of an Italian family with an autosomal dominant inclusion body myopathy (AD-IBM). Eight subjects (age range 20–56 years; 5 females and 3 males) belonging to four generations were studied. Onset of disturbances (distal weakness at lower limbs) ranged from 20 to 28 years. CK levels were increased to five times. Only in an early stage oedema of involved muscles has been demonstrated by muscle MR. Quadriceps femoris was characteristically spared; in the last phases a mild involvement of the vasti became evident with persistent sparing of the rectus femori. Rimmed vacuoles and hyperphosphorylated tau filaments were evident at muscle biopsy. Linkage analysis excluded the association of the disease to chromosome loci 14q11, 17p13.1, 2p13, 19p13. The study suggests that quadriceps sparing is a characteristic feature also of AD-IBM. This finding could represent a muscle-image hallmark helpful in diagnosis of autosomal dominant muscular disorders.     

Clinical features and microsurgical treatment of pediatric patients with cerebral cavernous malformation

The aim of the present study was to describe the clinical features and to evaluate the surgical treatment outcomes of pediatric patients with cerebral cavernous malformations (CCM). We investigated 85 children (53 boys and 32 girls), aged from 6 months to 17.9 years with CCM. Seizures and symptomatic hemorrhages, which were the most frequent symptoms, occurred in 81 patients. Nine patients had a positive family history of CCM. Eighty patients underwent microsurgical treatment after strict operative indications were met. Neuronavigation, combined with intraoperative ultrasonography or functional MRI, was used for precise localization of the lesions. The principles of minimally invasive techniques were followed during surgery. A total of 89 lesions were removed in 80 patients, and there were no deaths. During their hospital stay, only nine patients suffered from postoperative seizures, which were controlled with medication. Postoperative neurological deficits improved in 27 patients, were unchanged in nine, and worsened in two. With the help of advanced neuroimaging, a satisfactory surgical outcome was achieved for 10 lesions located in eloquent brain areas and four lesions in the brain stem. A follow-up study of 66 patients showed that all of these patients remained seizure-free, and nine patients with postoperative neurological deficits gradually recovered. Microsurgical treatment should be performed early for pediatric patients with CCM. Accurate localization of the lesions and the use of minimally invasive techniques and functional MRI monitoring were the key features of the surgical procedures.     

Clinical, genetic, and cardiac magnetic resonance imaging findings in primary desminopathies

We report the clinical, genetic and cardiac magnetic resonance imaging (MRI) findings in 11 German patients with heterozygous E245D, D339Y, R350P and L377P desmin mutations and without cardiac symptoms. Clinical evaluation revealed a marked variability of skeletal muscle, respiratory and cardiac involvement even between patients with identical mutations, ranging from asymptomatic to severely affected. While echocardiography did not show any pathological findings in all 11 patients, cine MRI revealed focal left ventricular hypertrophy in 2 patients and MR delayed enhancement imaging displayed intramyocardial fibrosis in the left ventricle in 4 patients indicating early myocardial involvement. Our data argue against distinct genotype-phenotype correlations and suggest that comprehensive cardiac MRI is superior to conventional echocardiography for the detection of early and clinically asymptomatic stages of cardiomyopathy in desminopathy patients. Therefore, cardiac MRI may serve as a screening tool to identify patients at risk, which might benefit from early pharmacological and/or interventional (e.g. implantable cardioverter-defibrillator devices) therapy.     

Scalp cavernous angioma presenting as sinus pericranii: diagnostic value of cerebral angiography and magnetic resonance imaging

Objects: Sinus pericranii is only a symptom complex, and it can have a variety of etiologies. Therefore, it is important to differentiate these etiologies preoperatively by means of radiological examinations. A 5-year-old boy was admitted with a soft and fluctuant tumor in the right parietal region near the midline. The tumor appeared when the child was in a recumbent position, distending noticeably with the Valsalva maneuver and disappearing completely when the patient was in the sitting position. Methods: Magnetic resonance imaging showed the lesion with honeycomb-like heterogeneous iso- and low-intensity signals on the T1-weighted image and with heterogeneous high- and iso- intensity signal on the T2-weighted image. Dynamic study with an injection of gadolinium diethylene-triaminopentaacetic acid demonstrated and nodular peripheral enhancement at early phase and subsequent progressive enhancement towards the center of tumor. The internal carotid angiogram was normal. The external carotid angiogram, however, showed a tumor stain fed by the superficial temporal arteries. The stain was retained until the late phase and drained into the scalp veins and into the superior sagittal sinus. Following direct injection of contrast medium into the tumor there was prolonged retention of the medium in the tumor and leakage into scalp veins and the superior sagittal sinus. The mass under the periosteum was totally removed and proved to be a cavernous angioma. Conclusions: Scalp cavernous angioma is one of the etiologies of sinus pericranii and may be diagnosed preoperatively by cerebral angiography or magnetic resonance imaging. Serial dynamic magnetic resonance imaging will be particularly helpful for this diagnosis. Received: 25 September 1998 Revised: 20 July 1999     

Three-tesla magnetic resonance imaging study of cerebral microbleeds in patients with ischemic stroke

Abstract

Objectives: The aims of this study were to analyse the distribution of cerebral microbleeds (CMBs) in patients with ischemic stroke and study the relationship between CMBs and the severity of old lacunar infarcts and cerebral white matter changes.

Methods: The study population consisted of 247 consecutive inpatients with ischemic stroke. Magnetic resonance imaging findings of these inpatients were observed. CMBs were counted respectively according to their locations, including the corticosubcortical regions, basal ganglia, thalami, brainstem and cerebellum. The number of the old lacunes and the severity of the cerebral white matter changes were also recorded. Based on the occurrence of CMBs, the patients were divided into two groups (72 patients with CMBs; 175 patients without CMBs).

Results: The most common location of CMBs in patients with ischemic stroke was the basal ganglia, followed by the corticosubcortical region, the thalami, the brainstem and the cerebellum. The severity of CMBs was closely correlated with the severity of lacunar infarcts and cerebral white matter changes, respectively.

Discussion: CMBs are closely related with cerebral microangiopathy and may be a marker of advanced stage cerebral microangiopathy.     

Clinicopathological and genetic studies of two further Italian families with cerebral autosomal dominant arteriopathy

We report on two Italian families with an early-adult onset autosomal dominant disorder, characterized by leukoencephalopathy, migraine, psychiatric disturbances, stroke and dementia. These findings fulfill the diagnostic criteria for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) syndrome. Moreover, to confirm the CADASIL gene location to 19p12, we performed a linkage analysis with four microsatellite markers. The results of the genetic study gave positive but not significant lod scores, indicating only weak evidence of a linkage with 19p12. In one autopsy case, we found extensive ischemic changes due to the selective involvement of the small muscular arteries of the cerebral white matter. The lesions consisted of a thickening of the media with deposition of granular eosinophilic material. Ultrastructural examination of the arterial walls showed graded damage to smooth muscle cells, mostly of the longitudinal layer, and an abnormal proliferation of basal lamina components. Immunocytochemical analysis showed strong reactivity using antibodies to collagen IV and smooth myosin proteins. The results suggest a primary involvement of the smooth muscle cells of small cerebral arteries, with a secondary alteration of basal lamina components and elastic tissue. Received: 13 December 1995 / Revised, accepted: 14 February 1996     

Diffusion-weighted magnetic resonance imaging of cerebral ischemia

Functional magnetic resonance imaging is providing new insight into neurologic imaging that was not possible with conventional techniques. Diffusion magnetic resonance imaging is one aspect of functional imaging and it allows detection of acute cerebral ischemia that would not have been identified with standard T2-weighted sequences while also differentiating acute from chronic stroke. These unique characteristics suggest tremendous potential of diffusion imaging to help direct therapy of acute ischemic stroke. An understanding of the principles of diffusion imaging is necessary for optimal application of this technique.     

Linkage to the CCM2 locus and genetic heterogeneity in familial cerebral cavernous malformation

BACKGROUND: Cerebral cavernous malformation (CCM) is a form of intracranial vascular disease that may arise sporadically or be dominantly inherited. Linkage studies have revealed genetic heterogeneity among the dominantly inherited forms suggesting the existence of at least three loci called CCM1, CCM2 and CCM3. METHODS: In the present study, we screened five families with dominantly inherited CCM for CCM1 gene mutations with denaturing high performance liquid chromatography (DHPLC). Then, we performed linkage analysis and haplotyping on these five families using highly polymorphic markers at the candidate CCM loci. RESULTS: None of the five families tested with DHPLC were found to have mutations in the CCM1 gene. Based on haplotyping, we identified three families segregating alleles for CCM2, while two families segregated alleles for CCM3. Using linkage analysis, we could confirm that one family (IFCAS-1) had a positive Lod score of 2.03 (p<0.0001) at the CCM2 locus using marker D7S678. CONCLUSIONS: The present study is the first one to replicate linkage at the CCM2 locus and provides a fifth family identified as such. It also supports the concept of genetic heterogeneity in CCM, identifying four other families that showed no mutations in the CCM1 gene.     

Cardiovascular magnetic resonance imaging evaluation of two families with Becker muscular dystrophy

In this study we evaluated two families with Becker muscular dystrophy and although the patients were completely asymptomatic and with normal ECG and echocardiogram, their left ventricular function was abnormal and the presence of subepicardial scar tissue was identified in the majority of them. The latter was also documented in one of the mothers, who had normal systolic function and was free of symptoms. Cardiac evaluation with cardiovascular magnetic resonance is sensitive enough to detect abnormal findings in BMD patients, missed by conventional echocardiography. Due to its ability to perform tissue characterization non-invasively, cardiovascular magnetic resonance can detect silent myocardial lesions in patients with Becker muscular dystrophy.     

Functional magnetic resonance imaging of brain plasticity in patients with stroke and arteriovenous malformation

After stroke, the degree of recovery varies from patient to patient. Functional magnetic resonance imaging of motor, sensory, and language systems has been used to evaluate brain plasticity in patients recovering from a stroke. Patients with arteriovenous malformations also have been tested with functional magnetic resonance imaging to investigate plasticity of brain function. Arteriovenous malformations may cause the developing brain to develop such that unexpected areas are responsible for functions typically performed by the regions of the brain with the arteriovenous malformations.     

Tuberous sclerosis with cardiogenic cerebral embolism: magnetic resonance imaging

A girl with tuberous sclerosis and intracardiac masses had at least two episodes of cardiogenic cerebral embolization, the attacks characterized by acute onset of prolonged neurologic dysfunction arising from different vascular distributions in both cerebral hemispheres. Renal embolization was suggested by hematuria. Magnetic resonance imaging (MRI) demonstrated ischemic lesions in cerebral locations predicted by the clinical signs. MRI also demonstrated extensive areas compatible with the dysmyelination of tuberous sclerosis.     

Clinical and radiological correlates of reduced cerebral blood flow measured using magnetic resonance imaging

BACKGROUND: Methods for determining cerebral blood flow (CBF) using bolus-tracking magnetic resonance imaging (MRI) have recently become available. Reduced apparent diffusion coefficient (ADC) values of brain tissue are associated with reductions in regional CBF in animal stroke models. OBJECTIVES: To determine the clinical and radiological features of patients with severe reductions in CBF on MRI and to analyze the relationship between reduced CBF and ADCs in acute ischemic stroke. DESIGN: Case series. SETTING: Referral center. METHODS: We studied 17 patients with nonlacunar acute ischemic stroke in whom perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) were performed within 7 hours of symptom onset. A PWI-DWI mismatch of more than 20% was required. We compared patients with ischemic lesions that had CBF of less than 50% relative to the contralateral hemisphere with patients with lesions that had relative CBF greater than 50%. Characteristics analyzed included age, time to MRI, baseline National Institutes of Health Stroke Scale score, mean ADC, DWI and PWI lesion volumes, and 1-month Barthel Index score. RESULTS: Patients with low CBF (n = 5) had lower ADC values (median, 430 x 10 (-6) mm(2)/s vs. 506 x 10 (-6) mm(2)/s; P =.04), larger DWI volumes (median, 41.8 cm(3) vs. 14.5 cm(3); P =.001) and larger PWI lesions as defined by the mean transit time volume (median, 194.6 cm(3) vs. 69.3 cm(3); P =.01), and more severe baseline National Institutes of Health Stroke Scale scores (median, 15 vs. 9; P =.02). CONCLUSION: Ischemic lesions with severe CBF reductions, measured using bolus-tracking MRI, are associated with lower mean ADCs, larger DWI and PWI volumes, and higher National Institutes of Health Stroke Scale scores.     

Leber's hereditary optic neuropathy: genetic, biochemical, and phosphorus magnetic resonance spectroscopy study in an Italian family

Three siblings of a family affected with Leber's hereditary optic neuropathy (LHON) showed a mitochondrial DNA mutation at position 11778. The lactate response to a standardized effort was increased in only one case. Muscle biopsies and biochemistry of muscle and platelet mitochondrial enzymes were normal. All patients showed an altered energy metabolism during exercise and during recovery after exercise on phosphorus 31-magnetic resonance spectroscopy (31P-MRS) of muscle. Brain 31P-MRS showed a decreased energy reserve (decreased PCr/Pi ratio) in all patients. 31P-MRS noninvasively demonstrated an altered mitochondrial energy metabolism in muscle and, for the first time, in the brains of LHON patients.