[Show abstract][Hide abstract] ABSTRACT: Brain malformations are a common finding in patients with microcephaly, increasing the probability of an underlying genetic disorder. If combined with further findings such as developmental delay or a seizure disorder, cerebral MR imaging with neuroradiological evaluation should therefore be considered early during clinical workup. In particular, the observation of holoprosencephaly or cortical malformations may provide important clues for initiating phenotype-specific genetic testing. This article reviews more common forms of syndromic and non-syndromic forms of microcephaly, with associated neuroradiological findings such as periventricular nodular heterotopia, lissencephaly, double cortex, holoprosencephaly, pontocerebellar hypoplasia and agenesis of the corpus callosum, and suggest algorithms for diagnostic workup.
No preview · Article · Dec 2015 · Medizinische Genetik
[Show abstract][Hide abstract] ABSTRACT: Background
Heterozygous loss of function mutations within the Filamin A gene in Xq28 are the most frequent cause of bilateral neuronal periventricular nodular heterotopia (PVNH). Most affected females are reported to initially present with difficult to treat seizures at variable age of onset. Psychomotor development and cognition may be normal or mildly to moderately impaired. Distinct associated extracerebral findings have been observed and may help to establish the diagnosis including patent ductus arteriosus Botalli, progressive dystrophic cardiac valve disease and aortic dissection, chronic obstructive lung disease or chronic constipation. Genotype-phenotype correlations could not yet be established.
Sanger sequencing and MLPA was performed for a large cohort of 47 patients with Filamin A associated PVNH (age range 1 to 65 years). For 34 patients more detailed clinical information was available from a structured questionnaire and medical charts on family history, development, epileptologic findings, neurological examination, cognition and associated clinical findings. Available detailed cerebral MR imaging was assessed for 20 patients.
Thirty-nine different FLNA mutations were observed, they are mainly truncating (37/39) and distributed throughout the entire coding region. No obvious correlation between the number and extend of PVNH and the severity of the individual clinical manifestation was observed. 10 of the mutation carriers so far are without seizures at a median age of 19.7 years. 22 of 24 patients with available educational data were able to attend regular school and obtain professional education according to age.
We report the clinical and mutation spectrum as well as MR imaging for a large cohort of 47 patients with Filamin A associated PVNH including two adult males. Our data are reassuring in regard to psychomotor and cognitive development, which is within normal range for the majority of patients. However, a concerning median diagnostic latency of 17 to 20 years was noted between seizure onset and the genetic diagnosis, intensely delaying appropriate medical surveillance for potentially life threatening cardiovascular complications as well as genetic risk assessment and counseling prior to family planning for this X-linked dominant inherited disorder with high perinatal lethality in hemizygous males.
Preview · Article · Dec 2015 · Orphanet Journal of Rare Diseases
[Show abstract][Hide abstract] ABSTRACT: Background:
Patients with LIS1-associated classic lissencephaly typically present with severe psychomotor retardation and drug-resistant epilepsy within the first year.
To analyze the epileptogenic phenotype and response to antiepileptic therapy in LIS1-associated classic lissencephaly.
Retrospective evaluation of 22 patients (8months-24years) with genetically and radiologically confirmed LIS1-associated classic lissencephaly in 16 study centers.
All patients in our cohort developed drug-resistant epilepsy. In 82% onset of seizures was noted within the first six months of life, most frequently with infantile spasms. Later in infancy the epileptogentic phenotype became more variable and included different forms of focal seizures as well generalized as tonic-clonic seizures, with generalized tonic-clonic seizures being the predominant type. Lamotrigine and valproate were rated most successful with good or partial response rates in 88-100% of the patients. Both were evaluated significantly better than levetiracetam (p<0.05) and sulthiame (p<0.01) in the neuropediatric assessment and better than levetiracetam, sulthiame (p<0.05) and topiramate (p<0.01) in the family survey. Phenobarbital and vigabatrin achieved good or partial response in 62-83% of the patients.
Our findings suggest that patients with LIS1-associated lissencephaly might benefit most from lamotrigine, valproate, vigabatrin or phenobarbital.
No preview · Article · Oct 2015 · Brain & development
[Show abstract][Hide abstract] ABSTRACT: Background:
Severe cerebral vasospasm is a major cause of death and disability in patients with aneurysmal subarachnoid hemorrhage. No causative treatment is yet available and hypertensive hypervolemic therapy (HHT) is often insufficient to avoid delayed cerebral ischemia and neurological deficits. We compared patients receiving continuous intra-arterial infusion of the calcium-antagonist nimodipine with a historical group treated with HHT and oral nimodipine alone.
Between 0.5 and 1.2 mg/h of nimodipine were continuously administered by intra-arterial infusion via microcatheters either into the internal carotid or vertebral artery or both, depending on the areas of vasospasm. The effect was controlled via multimodal neuromonitoring and transcranial Doppler sonography. Outcome was determined by means of the Glasgow Outcome Scale at discharge and 6 months after the hemorrhage and compared to a historical control group.
Twenty-one patients received 28 intra-arterial nimodipine infusions. Six months after discharge, the occurrence of cerebral infarctions was significantly lower (42.6 %) in the nimodipine group than in the control group (75.0 %). This result was reflected by a significantly higher proportion (76.0 %) of patients with good outcome in the nimodipine-treated group, when compared to 10.0 % good outcome in the control group. Median GOS was 4 in the nimodipine group and 2 in the control group (p = 0.001).
Continuous intra-arterial nimodipine infusion is an effective treatment for patients with severe cerebral vasospasm who fail to respond to HHT and oral nimodipine alone. Key to the effective administration of continuous intra-arterial nimodipine is multimodal neuromonitoring and the individual adaptation of dosage and time of infusion for each patient.
No preview · Article · Jun 2015 · Acta Neurochirurgica
[Show abstract][Hide abstract] ABSTRACT: Intracranial hemorrhages are associated with high rates of disability and mortality. Telemedicine in general provides clinical healthcare at a distance by using videotelephony and teleradiology and is used particularly in acute stroke care medicine (TeleStroke). TeleStroke considerably improves quality of stroke care (for instance, by increasing thrombolysis) and may be valuable for the management of intracranial hemorrhages in rural hospitals and hospitals lacking neurosurgical departments, given that surgical/interventional therapy is only recommended for a subgroup of patients. The aim of this study was to analyze the frequency, anatomical locations of intracranial hemorrhage, risk factors, and the proportion of patients transferred to specialized hospitals. We evaluated teleconsultations conducted between 2008 and 2010 in a large cohort of patients consecutively enrolled in the Telemedical Project for Integrated Stroke Care (TEMPiS) network. In cases in which intracranial hemorrhage was detected, all images were re-examined and analyzed with a focus on frequency, location, risk factors, and further management. Overall, 6187 patients presented with stroke-like symptoms. Intracranial hemorrhages were identified in 631 patients (10.2%). Of these, intracerebral hemorrhages were found in 423 cases (67.0%), including 174 (41.1%) in atypical locations and 227 (53.7%) in typical sites among other locations. After 14 days of hospitalization in community facilities, the mortality rate in patients with intracranial hemorrhages was 15.1% (95/631). Two hundred and twenty-three patients (35.3%) were transferred to neurological/neurosurgical hospitals for diagnostic workup or additional treatment. Community hospitals are confronted with patients with intracranial hemorrhage, whose management requires specific neurosurgical and hematological expertise with respect to hemorrhage subtype and clinical presentation. TeleStroke networks help select patients who need advanced neurological and/or neurosurgical care. The relatively low proportion of interhospital transfers shown in this study reflects a differentiated decision process on the basis of both guidelines and standard operating procedures.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
The BLADE (PROPELLER) technique reduces artefacts in imaging of the cervical spine in sagittal orientation, but till now failed to do so in axial orientation, because here it increased through plane CSF-flow artefacts, which spoiled the benefit of BLADE artefact reduction "in plane". The aim of this study was to compare a BLADE sequence with optimised measurement parameters in axial orientation to T2-TSE.
Materials and methods:
Both sequences were compared in 58 patients with 31 discal, 16 bony and 11 spinal cord lesions. Image sharpness, reliability of spinal cord depiction, CSF flow artefacts and lesion detection were evaluated by 3 independent observers. Additionally the observers were asked which sequence they would prefer for diagnostic workup. Statistical evaluations were performed using sign and χ2 test.
BLADE was significantly superior concerning image sharpness, spinal cord depiction and overall lesion detection. BLADE was rated better for most pathologies, for bony lesions the differences compared with TSE were statistically significant. Regarding CSF-flow artefacts both sequences showed no difference. All readers preferred BLADE in side by side reading.
An optimised axial T2 BLADE sequence decreases the problems of increased through plane CSF-flow artefacts in this orientation. By reducing various other artefacts it yields better image quality and has the potential to reduce the number of non-diagnostic examinations especially in uncooperative patients.
No preview · Article · Sep 2014 · RöFo - Fortschritte auf dem Gebiet der R
[Show abstract][Hide abstract] ABSTRACT: Patient: Female, 78 Final Diagnosis: Cerebral hyperperfusion syndrome Symptoms: - Medication: - Clinical Procedure: Endovascular embolectomy Specialty: Neurology.
Cerebral hyperperfusion syndrome (cHS) is a well known but rare complication after carotid endarterectomy, carotid angioplasty with stenting, and stenting of intracranial arterial stenosis. The clinical presentation may vary from acute onset of focal oedema (stroke-like presentation) and intracerbral hemorrhage to delayed (>24h hours after the procedure) presentation with seizures, focal motor weakness, or late intracerebral hemorrhage. The incidence of cHS after carotid endarterectomy ranges from 0-3% and defined as an increase of the ipsilateral cerebral blood flow up to 40% over baseline in ultrasound.
We present a case of a 78-year-old woman with an acute ischemic stroke due to left side middle cerebral artery territory with right sided hemiparesis and aphasia (NIHSS 16). After systemic thrombolysis embolectomy using a retractable stent (Solitaire(®) device) was performed and resulted in complete and successful recanalization of MCA including its branches about 210 minutes after symptom onset but, partial dislocation of thrombotic material into the anterior cerebral artery (ACA).
Cerebral hyperperfusion syndrome should be considered in patients with clinical deterioration after successful recanalisation and the early diagnosis and treatment may be important for neurological outcome after endovascular embolectomy.
Preview · Article · Nov 2013 · American Journal of Case Reports
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Using the BLADE (PROPELLER) technique for T2-weighted MR imaging of the cervical spine has proven to be a reliable tool for reducing artifacts typically for this region. The aim of this study was to evaluate whether the application of BLADE sequences has an impact on the detection of small or low contrast spinal cord and epidural lesions.
Materials and methods:
A standard TSE and a BLADE sequence were compared in 33 patients with 46 spinal cord and epidural lesions for T2-weighted sagittal imaging of the cervical spine. Image sharpness, visualization of the dura, reliability of spinal cord depiction as well as lesion contrast were evaluated by two independent readers. Additionally two experienced neuroradiologists selected in consensus the sequence they would prefer for diagnostic purposes. Statistical evaluations were performed using the sign and the χ2 test.
BLADE was significantly superior to TSE regarding image sharpness, visualization of the dura and reliability of spinal cord depiction. Regarding lesion contrast there was a positive trend towards the BLADE sequence. In 17 of 46 lesions, BLADE was judged superior to TSE, while TSE was favored in 10 lesions. In consensus reading both neuroradiologists preferred BLADE for overall image quality in 27 of 33 patients and for lesion contrast in 10 and TSE in 14 of the 33 patients, but 3 TSE sequences were rated as non-diagnostic regarding this criterion.
For the detection of even small and low-contrast spinal cord lesions, BLADE is at least equivalent to TSE, yielding better overall image quality and fewer non-diagnostic images.
No preview · Article · Sep 2013 · RöFo - Fortschritte auf dem Gebiet der R
[Show abstract][Hide abstract] ABSTRACT: To evaluate if the use of BLADE sequences might overcome some limitations of magnetic resonance imaging (MRI) in the extracranial head and neck, which is a diagnostically challenging area with a variety of artifacts and a broad spectrum of potential lesions.
After informed consent and Institutional Review Board approval, two different BLADE sequences with (BLADE IR) and without inversion pulse (BLADE) were compared to turbo-spin echo (TSE) with fat saturation for coronal T1-weighted postcontrast imaging of the extracranial head and neck region in 40 individuals of a routine patient collective. Visual evaluation of image sharpness, motion artifacts, vessel pulsation, contrast of anatomic structures, contrast of pathologies to surrounding tissue as well as BLADE-specific artifacts was performed by two experienced, independent readers. Statistical evaluation was done by using the Wilcoxon test.
Both BLADE and BLADE IR were significantly superior to TSE regarding pulsation artifacts and delineation of thoracic structures. TSE provided better results concerning contrast muscle/fat tissue and contrast lymph nodes/fat. More important, it showed significantly better contrast of several lesions, facilitating the detection of patient pathology.
T1-weighted coronal imaging of the extracranial head and neck region is demanding. T1-weighted BLADE sequences still have drawbacks in anatomical contrast and lesion detection but offer possibilities to achieve reasonable image quality in difficult cases with a variety of artifacts. J. Magn. Reson. Imaging 2013;37:660—668.
No preview · Article · Mar 2013 · Journal of Magnetic Resonance Imaging
[Show abstract][Hide abstract] ABSTRACT: We describe retrospectively the course of 17 AIDS patients with progressive multifocal leukoencephalopathy (PML) and give a review of their clinical symptoms and survival times. The relative frequency of PML in our cohort of AIDS patients was 2.6%. The mean of CD4-positive cells was 80.5±82.5/μl. CD4-positive cells were >200/μl only in one patient and increased significantly under a combination of three antiretroviral drugs whereas, with the other patients, CD4-positive cells did not increase with a maximum of two antiretroviral drugs. The mean survival time was 6.6 (1.5–20) months and correlated positively with the number of CD4-positive cells. The diagnosis of PML can be regarded as confirmed when JC-virus DNA is detectable in cerebrospinal fluid, typical changes can be seen in MRI and typical clinical symptoms occur.
No effective therapy is known to date. Single case reports on therapy with cidofovir, as in one of the cases described here, showed positive results.
[Show abstract][Hide abstract] ABSTRACT: Cerebral amyloid angiopathy (CAA) is a degenerative disorder characterized by amyloid-β (Aβ) deposition in the blood-brain barrier (BBB). CAA contributes to injuries of the neurovasculature including lobar hemorrhages, cortical microbleeds, ischemia, and superficial hemosiderosis. We postulate that CAA pathology is partially due to Aβ compromising the BBB.
We characterized 19 patients with acute stroke with "probable CAA" for neurovascular pathology based on MRI and clinical findings. Also, we studied the effect of Aβ on the expression of tight junction proteins and matrix metalloproteases (MMPs) in isolated rat brain microvessels.
Two of 19 patients with CAA had asymptomatic BBB leakage and posterior reversible encephalopathic syndrome indicating increased BBB permeability. In addition to white matter changes, diffusion abnormality suggesting lacunar ischemia was found in 4 of 19 patients with CAA; superficial hemosiderosis was observed in 7 of 9 patients. Aβ(40) decreased expression of the tight junction proteins claudin-1 and claudin-5 and increased expression of MMP-2 and MMP-9. Analysis of brain microvessels from transgenic mice overexpressing human amyloid precursor protein revealed the same expression pattern for tight junction and MMP proteins. Consistent with reduced tight junction and increased MMP expression and activity, permeability was increased in brain microvessels from human amyloid precursor protein mice compared with microvessels from wild-type controls.
Our findings indicate that Aβ contributes to changes in brain microvessel tight junction and MMP expression, which compromises BBB integrity. We conclude that Aβ causes BBB leakage and that assessing BBB permeability could potentially help characterize CAA progression and be a surrogate marker for treatment response.