"Ears of the Lynx" MRI Sign Is Associated with SPG11 and SPG15 Hereditary Spastic Paraplegia.

BACKGROUND AND PURPOSE: The "ears of the lynx" MR imaging sign has been described in case reports of hereditary spastic paraplegia with a thin corpus callosum, mostly associated with mutations in the spatacsin vesicle trafficking associated gene, causing Spastic Paraplegia type 11 (SPG11). This sign corresponds to long T1 and T2 values in the forceps minor of the corpus callosum, which appears hyperintense on FLAIR and hypointense on T1-weighted images. Our purpose was to determine the sensitivity and specificity of the ears of the lynx MR imaging sign for genetic cases compared with common potential mimics. MATERIALS AND METHODS: Four independent raters, blinded to the diagnosis, determined whether the ears of the lynx sign was present in each of a set of 204 single anonymized FLAIR and T1-weighted MR images from 34 patients with causal mutations associated with SPG11 or Spastic Paraplegia type 15 (SPG15). 34 healthy controls, and 34 patients with multiple sclerosis. RESULTS: The interrater reliability for FLAIR images was substantial (Cohen κ, 0.66-0.77). For these images, the sensitivity of the ears of the lynx sign across raters ranged from 78.8 to 97.0 and the specificity ranged from 90.9 to 100. The accuracy of the sign, measured by area under the receiver operating characteristic curve, ranged from very good (87.1) to excellent (93.9). CONCLUSIONS: The ears of the lynx sign on FLAIR MR imaging is highly specific for the most common genetic subtypes of hereditary spastic paraplegia with a thin corpus callosum. When this sign is present, there is a high likelihood of a genetic mutation, particularly associated with SPG11 or SPG15, even in the absence of a family history.

Intracranial arteries in individuals with the elastin gene hemideletion of Williams syndrome.

BACKGROUND AND PURPOSE: Williams syndrome, a rare genetic disorder with a striking neurobehavioral profile characterized by extreme sociability and impaired visuospatial construction abilities, is caused by a hemideletion that includes the elastin gene, resulting in frequent supravavular aortic stenosis and other stenotic arterial lesions. Strokes have been reported in Williams syndrome. Although the extracranial carotid artery has been studied in a sample of patients with Williams syndrome, proximal intracranial arteries have not. MATERIALS AND METHODS: Using MRA, we studied the intracranial vessels in 27 participants: 14 patients with Williams syndrome (age range, 18-44 years; mean age, 27.3 ± 9.1; 43% women) and 13 healthy control participants with similar age and sex distribution (age range, 22-52 years; mean age, 33.4 ± 7.6; 46% women). All participants with Williams syndrome had hemideletions of the elastin gene. Blinded to group allocation or to any other clinical data, a neuroradiologist determined the presence of intracranial vascular changes in the 2 groups. RESULTS: The Williams syndrome group and the healthy control group had similar patency of the proximal intracranial arteries, including the internal carotid and vertebral arteries; basilar artery; and stem and proximal branches of the anterior cerebral artery, MCA, and posterior cerebral arteries. The postcommunicating segment of the anterior cerebral artery was longer in the Williams syndrome group. CONCLUSIONS: Despite the elastin haploinsufficiency, the proximal intracranial arteries in Williams syndrome preserve normal patency.

EFNS guidelines on the use of neuroimaging in the management of motor neuron diseases.

BACKGROUND AND PURPOSE: These European Federation of Neurological Societies guidelines on neuroimaging of motor neuron diseases (MNDs) are designed to provide practical help for the neurologists to make appropriate use of neuroimaging techniques in patients with MNDs, which ranges from diagnostic and monitoring aspects to the in vivo study of the pathobiology of such conditions. METHODS: Literature searches were performed before expert members of the Task Force wrote proposal. Then, consensus was reached by circulating drafts of the manuscript to the Task Force members and by discussion of the classification of evidence and recommendations. RESULTS AND CONCLUSIONS: The use of conventional MRI in patients suspected of having a MND is yet restricted to exclude other causes of signs and symptoms of MN pathology [class IV, level good clinical practice point (GCPP)]. Although the detection of corticospinal tract hyperintensities on conventional MRI and a T2-hypointense rim in the pre-central gyrus can support a pre-existing suspicion of MND, the specific search of these abnormalities for the purpose of making a firm diagnosis of MND is not recommended (class IV, level GCPP). At present, advanced neuroimaging techniques, including diffusion tensor imaging and proton magnetic resonance spectroscopic imaging, do not have a role in the diagnosis or routine monitoring of MNDs yet (class IV, level GCPP). However, it is strongly advisable to incorporate measures derived from these techniques into new clinical trials as exploratory outcomes to gain additional insights into disease pathophysiology and into the value of these techniques in the (longitudinal) assessment of MNDs (class IV, level GCPP).

Fatigue in multiple sclerosis is associated with the disruption of frontal and parietal pathways.

BACKGROUND: Fatigue is one of the most frequent and disturbing symptoms in multiple sclerosis (MS), directly affecting the patient's quality of life. However, many questions remain unclear regarding the anatomic brain correlate of MS-related fatigue. OBJECTIVE: To assess the relationship between fatigue and white matter lesion location and gray matter atrophy. METHODS: In this study, 60 patients with MS were evaluated with the Modified Fatigue Impact Scale and magnetic resonance imaging. Location of white matter lesion was analyzed using a voxel-by-voxel lesion probability mapping approach and gray matter atrophy degree and location using an optimized voxel-based morphometry method. RESULTS: We found a correlation between lesion load and fatigue score (T2 lesion load: r=0.415, P=0.001; T1 lesion load r=0.328, P=0.011). Moreover, fatigue correlated with lesions in the right parietotemporal (periatrial area, juxtaventricular white matter deep in the parietal lobe and callosal forceps) and left frontal (middle-anterior corpus callosum, anterior cingulum and centrum semiovale of the superior and middle frontal gyri) white matter regions (P<0.001 in all cases). Finally, fatigue score significantly correlated with gray matter atrophy in frontal regions, specifically, the left superior frontal gyrus and bilateral middle frontal gyri (P<0.001 in all cases). CONCLUSION: Our results suggest that the symptom of fatigue is associated with a disruption of brain networks involved in cognitive/attentional processes.

Forceps minor region signal abnormality "ears of the lynx": an early MRI finding in spastic paraparesis with thin corpus callosum and mutations in the spatacsin gene (SPG11) on chromosome 15.

BACKGROUND AND PURPOSE: A thin corpus callosum on magnetic resonance imaging (MRI) characterizes a type of autosomal recessive disorder with progressive spastic paraparesis and cognitive impairment. Known as Hereditary Spastic Paraparesis with Thin Corpus Callosum (HSP-TCC), it has been associated with mutations of the SPG11 gene. No other specific MRI findings have been reported. METHODS: We studied with MRI four patients from three families with HSP-TCC who had identified causal mutations in the SPG11 gene. RESULTS: In all individuals studied the region of the forceps minor of the corpus callosum, corresponding to the genu fibers, appeared bright on T2-weighted and dark on T1-weighted images. On axial sections, the frontal horn region bore a remarkable resemblance to the ears of a lynx, with the areas of abnormal signal reminiscent of the tufts of hair crowning the tips of the ears of this animal. Less specific findings included a box-shape appearance of the calloso-caudate angle and diffusely increased signal in the hemispheric white matter. CONCLUSION: Abnormal MRI signal in the region of the forceps minor of the corpus callosum is a characteristic early imaging finding of HSP-TCC with SPG11 mutations.

SPG11 compound mutations in spastic paraparesis with thin corpus callosum.

BACKGROUND: Autosomal recessive hereditary spastic paraparesis with thin corpus callosum (ARHSP-TCC) is being increasingly recognized as a variety of spastic paraplegia with mental retardation. SPG11 gene mutations have been reported to be associated with ARHSP-TCC. METHODS: As an independent group, we investigated SPG11 gene involvement in four individuals not previously described with either recessive or sporadic HSP-TCC presentation. RESULTS: Chromosome 15q13-15 segregating autosomal disease haplotypes were different across the kindreds and sequencing of SPG11 identified four novel frameshift/nonsense segregating mutations and the R2034X mutation, which were in heterozygous compound status. The affected examined had decreased thalamic and bilateral paracentral frontal lobe metabolism on (18)F-flurodeoxyglucose PET. CONCLUSIONS: Loss-of-function SPG11 mutations are the major cause of autosomal recessive hereditary spastic paraparesis with thin corpus callosum in Southern Europe, even in apparently sporadic cases. Decreased thalamic metabolism was consistently a phenotypical SPG11 mutation hallmark.

A patient with MV2 subtype of sporadic Creutzfeldt-Jakob disease and atypical clinical presentation.

We report the case of a 71-year-old woman with progressive dementia over the course of 4 years, characterized by prominent pyramidal signs and by the lack of ataxia and other cerebellar signs. Creutzfeldt-Jakob disease (CJD) was not suspected during the patient's life. Autopsy brain tissue showed severe spongiform encephalopathy with kuru-like, but not florid, plaques in neocortex and cerebellum. Massive synaptic diffuse and plaque-like PrP(Sc) deposition was found in the cerebral cortex, striatum, cerebellum and brainstem. Genetic analysis revealed no PRNP gene mutations and methionine/valine heterozygosity (MV) at codon 129. The pathogenic scrapie prion protein (PrP(Sc)) pattern detected by Western blot was Type 2. However, this pattern showed a single unglycosylated band in contrast to the doublet described for MV2 subtype of sCJD with kuru plaques. In summary, this is an autopsy case report of a particular presentation of MV2 subtype of sCJD.

Topography of cortical activation differs for fundamental and harmonic frequencies of the steady-state visual-evoked responses. An EEG and PET H215O study.

In humans, visual flicker stimuli of graded frequency (2-90 Hz) elicit an electroencephalographic (EEG) steady-state visual-evoked response (SSVER) with the same fundamental frequency as the stimulus and, in addition, a series of harmonic responses. The fundamental component of the SSVER is generated by increased synaptic activity in primary visual cortex (V1). We set out to determine the cortical origin of the harmonic responses in humans. For this purpose, we recorded the SSVERs at 5 different frequencies (5, 10, 15, 25, and 40 Hz) and measured regional cerebral blood flow (rCBF) with positron emission tomography-H(2)(15)O at rest and during visual stimulation at the same frequencies. The rCBF contrast weighted by the amplitude of the SSVERs first harmonics showed activation of a swath of cortex perpendicular to V1, including mostly the inferior half of the parieto-occipital sulcus. This area overlapped minimally with the primary visual cortex activated by the fundamental frequency. A different method, estimating EEG cortical source current density with low-resolution brain electromagnetic tomography, gave the same results. Our finding suggests that the inferior portion of the banks of the parieto-occipital sulci contains association visual cortex involved in the processing of stimuli that can be as simple as a flickering light source.

EFNS guideline on neuroimaging in acute stroke. Report of an EFNS task force.

Neuroimaging techniques are necessary for the evaluation of stroke, one of the leading causes of death and neurological impairment in developed countries. The multiplicity of techniques available has increased the complexity of decision making for physicians. We performed a comprehensive review of the literature in English for the period 1965-2005 and critically assessed the relevant publications. The members of the panel reviewed and corrected an initial draft, until a consensus was reached on recommendations stratified according to the European Federation of Neurological Societies (EFNS) criteria. Non-contrast computed tomography (CT) scan is the established imaging procedure for the initial evaluation of stroke patients. However, magnetic resonance imaging (MRI) has a higher sensitivity than CT for the demonstration of infarcted or ischemic areas and depicts well acute and chronic intracerebral hemorrhage. Perfusion and diffusion MRI together with MR angiography (MRA) are very helpful for the acute evaluation of patients with ischemic stroke. MRI and MRA are the recommended techniques for screening cerebral aneurysms and for the diagnosis of cerebral venous thrombosis and arterial dissection. For the non-invasive study of extracranial vessels, MRA is less portable and more expensive than ultrasonography but it has higher sensitivity and specificity for carotid stenosis. Transcranial Doppler is very useful for monitoring arterial reperfusion after thrombolysis, for the diagnosis of intracranial stenosis and of right-to-left shunts, and for monitoring vasospasm after subarachnoid hemorrhage. Currently, single photon emission computed tomography and positron emission tomography have a more limited role in the evaluation of the acute stroke patient.

[SPECT and PET in neurology]. / SPECT y PET en neurología.

Both single photon emission computed tomography (SPECT) and positron emission tomography (PET) are helpful in the practice of neurology. Ictal SPECT is useful to determine the origin of focal seizures in the pre-surgical evaluation. In some centers, it is used to predict the likelihood of massive cerebral swelling after stroke and of cerebral infarction after a subarachnoid hemorrhage. It has also been used to study dopaminergic function in parkinsonian syndromes and in the evaluation of dementia. Given its higher resolution and some other factors, PET is more useful in the evaluation of brain tumors, dementia and the parkinsonian syndromes. It is also useful in the presurgical evaluation of epilepsy.

[Neuroimaging in Alzheimer's disease: an overview]. / La neuroimagen en la enfermedad de Alzheimer: perspectiva actual.

INTRODUCTION: Clinically, computerized tomography scanning and magnetic resonance imaging (MRI) are the neuroimaging techniques most frequently used in the work up of progressive cognitive impairment, in order to rule out tumors or other treatable etiologies. However, as we move closer to having more effective treatments for Alzheimer's disease (AD), we experience a greater need to use markers of early brain injury. Among them is neuroimaging. In this review we give some examples of the role of MRI and of functional MRI (fMRI) as markers of early brain changes. DEVELOPMENT: Regional metabolism, studied with positron emission tomography (PET) can also be used advantageously to depict early cortical changes in mild cognitive impairment (MCI) and even presymptomatic AD. SPECT, less expensive than PET, has a lower sensitivity, but has been extensively studied and using quantification methods can help even in MCI. Newer PET markers allow for the evaluation of activated microglia in vivo, as well as for the study of amyloid deposition in the brain and the activity of enzymes such as acetyl-cholinesterase. CONCLUSION: Future refinements in the neuroimaging techniques seem likely to help in the early diagnosis, evaluation of potential treatments and clarification of pathogenetic mechanisms in AD.

Comparison of three different volumes of mepivacaine in axillary plexus block using multiple nerve stimulation.

BACKGROUND: The multiple injection technique for axillary block, in which the four distal nerves of the plexus are located by a nerve stimulator and separately injected, has been shown to provide a high success rate and a short onset time. This randomized double-blind study was conducted to compare the effectiveness of three different volumes of mepivacaine 10 mg x ml(-1) in patients undergoing elective distal upper limb surgery under axillary brachial plexus block with the four-nerve approach. The number of complete sensory blocks was the primary efficacy variable. METHODS: A total of 114 adult patients were randomly allocated to receive 36 (n=38), 28 (n=38), and 20 ml (n=38) of mepivacaine 10 mg x ml(-1). In each group, volumes were equally distributed in the four nerve territories. In all patients, performance time, latency time, block characteristics, need of supplementary blocks, tourniquet tolerance, duration of analgesia, and complications were recorded. RESULTS: Complete sensory block was obtained in 97% of patients receiving a volume of 36 ml, 97% of those receiving 28 ml, and 94% of those receiving 20 ml. One patient in the group of 28 ml and five patients in the group of 20 ml experienced pain on inflation of the tourniquet. Two months after surgery, no case of postoperative neurological dysfunction was observed. CONCLUSIONS: The three volumes (38, 28, and 20 ml) of mepivacaine 10 mg x ml(-1) ensured a similar and high percentage of complete sensory blocks in axillary brachial plexus anaesthesia with nerve stimulation involving the location of four motor responses.