Basilar Artery Changes in Fabry Disease.

BACKGROUND AND PURPOSE: Dolichoectasia of the basilar artery is a characteristic finding of Fabry disease. However, its prevalence, severity, and course have been poorly studied. This study quantitatively evaluated, by MRA, a panel of basilar artery parameters in a large cohort of patients with Fabry disease. MATERIALS AND METHODS: Basilar artery mean diameter, curved length, "origin-to-end" linear distance (linear length), and tortuosity index ([curved length ÷ linear length] - 1) were retrospectively measured on 1.5T MRA studies of 110 patients with Fabry disease (mean age, 39.4 ± 18.6 years; 40 males) and 108 control patients (mean age, 42.0 ± 18.2 years; 40 males). RESULTS: Patients with Fabry disease had increased basilar artery mean diameter (P < .001) and basilar artery linear length (P = .02) compared with control patients. Basilar artery curved length and tortuosity index correlated with age in both groups (P < .001), whereas basilar artery linear length correlated with age only in patients with Fabry disease (P = .002). Patients with Fabry disease showed a basilar artery curved length mean increase of 4.2% (9.7% in male patients with Fabry disease versus male control patients), whereas the basilar artery mean diameter had a mean increase of 12.4% (14.3% in male patients with Fabry disease versus male control patients). Male patients with Fabry disease had increased basilar artery mean diameter, curved length, and tortuosity index compared with female patients with Fabry disease (P = .04, P = .02, and P < .001, respectively) and male control patients (P < .001, P = .01, and P = .006, respectively). Female patients with Fabry disease demonstrated an age-dependent increase of basilar artery mean diameter that became significant (P < .001) compared with female control patients above the age of 45 years. CONCLUSIONS: The basilar artery of patients with FD is subjected to major remodeling that differs according to age and sex, thus providing interesting clues about the pathophysiology of cerebral vessels in Fabry disease.

Cell Therapy for Parkinson's Disease: A Translational Approach to Assess the Role of Local and Systemic Immunosuppression.

Neural transplantation is a promising therapeutic approach for neurodegenerative diseases; however, many patients receiving intracerebral fetal allografts exhibit signs of immunization to donor antigens that could compromise the graft. In this context, we intracerebrally transplanted mesencephalic pig xenografts into primates to identify a suitable strategy to enable long-term cell survival, maturation, and differentiation. Parkinsonian primates received WT or CTLA4-Ig transgenic porcine xenografts and different durations of peripheral immunosuppression to test whether systemic plus graft-mediated local immunosuppression might avoid rejection. A striking recovery of spontaneous locomotion was observed in primates receiving systemic plus local immunosuppression for 6 mo. Recovery was associated with restoration of dopaminergic activity detected both by positron emission tomography imaging and histological examination. Local infiltration by T cells and CD80/86+ microglial cells expressing indoleamine 2,3-dioxigenase were observed only in CTLA4-Ig recipients. Results suggest that in this primate neurotransplantation model, peripheral immunosuppression is indispensable to achieve the long-term survival of porcine neuronal xenografts that is required to study the beneficial immunomodulatory effect of local blockade of T cell costimulation.

Brain anatomical substrates of mirror movements in Kallmann syndrome.

Among male patients affected by Kallmann syndrome, a genetically determined disease due to defective neural migration leading to hypogonadropic hypogonadism and hypo/anosmia, about 40% present the peculiar phenomenon of mirror movements, i.e. involuntary movements mirroring contralateral voluntary hand movements. Several pathogenic hypotheses have been proposed, but the ultimate neurological mechanisms are still elusive. The aim of the present study was to investigate brain anatomical substrates of mirror movements in Kallmann syndrome by means of a panel of quantitative MRI analyses. Forty-nine male Kallmann syndrome patients underwent brain MRI. The study protocol included 3D-T1-weighted gradient echo, fluid attenuated inversion recovery and diffusion tensor imaging. Voxel-based morphometry, sulcation, curvature and cortical thickness analyses and tract based spatial statistics were performed using SPM8, Freesurfer and FSL. All patients underwent a complete physical and neurological examination including the evaluation of mirror movements (according to the Woods and Teuber criteria). Kallmann syndrome patients presenting with mirror movements (16/49, 32%) displayed the following brain changes: 1) increased gray matter density in the depth of the left precentral sulcus behind the middle frontal gyrus; 2) decreased cortical thickness in the precentral gyrus bilaterally, in the depth of right precentral sulcus and in the posterior portion of the right superior frontal gyrus; and 3) decreased fractional anisotropy in the left hemisphere involving the temporal lobe and peritrigonal white matter. No differences were shown by cortical curvature and sulcation analyses. The composite array of brain changes observed in Kallmann syndrome patients with mirror movements likely represents the anatomical-structural underpinnings leading to the peculiar derangement of the complex circuitry committed to unilateral hand voluntary movements.

Degeneration and plasticity of the optic pathway in Alström syndrome.

BACKGROUND AND PURPOSE: Alström syndrome is a rare inherited ciliopathy in which early progressive cone-rod dystrophy leads to childhood blindness. We investigated functional and structural changes of the optic pathway in Alström syndrome by using MR imaging to provide insight into the underlying pathogenic mechanisms. MATERIALS AND METHODS: Eleven patients with genetically proved Alström syndrome (mean age, 23 years; range, 6-45 years; 5 females) and 19 age- and sex-matched controls underwent brain MR imaging. The study protocol included conventional sequences, resting-state functional MR imaging, and diffusion tensor imaging. RESULTS: In patients with Alström syndrome, the evaluation of the occipital regions showed the following: 1) diffuse white matter volume decrease while gray matter volume decrease spared the occipital poles (voxel-based morphometry), 2) diffuse fractional anisotropy decrease and radial diffusivity increase while mean and axial diffusivities were normal (tract-based spatial statistics), and 3) reduced connectivity in the medial visual network strikingly sparing the occipital poles (independent component analysis). After we placed seeds in both occipital poles, the seed-based analysis revealed significantly increased connectivity in patients with Alström syndrome toward the left frontal operculum, inferior and middle frontal gyri, and the medial portion of both thalami (left seed) and toward the anterior portion of the left insula (right and left seeds). CONCLUSIONS: The protean occipital brain changes in patients with Alström syndrome likely reflect the coexistence of diffuse primary myelin derangement, anterograde trans-synaptic degeneration, and complex cortical reorganization affecting the anterior and posterior visual cortex to different degrees.

Brain changes in Kallmann syndrome.

BACKGROUND AND PURPOSE: Kallmann syndrome is a rare inherited disorder due to defective intrauterine migration of olfactory axons and gonadotropin-releasing hormone neurons, leading to rhinencephalon hypoplasia and hypogonadotropic hypogonadism. Concomitant brain developmental abnormalities have been described. Our aim was to investigate Kallmann syndrome-related brain changes with conventional and novel quantitative MR imaging analyses. MATERIALS AND METHODS: Forty-five male patients with Kallmann syndrome (mean age, 30.7 years; range, 9-55 years) and 23 age-matched male controls underwent brain MR imaging. The MR imaging study protocol included 3D-T1, FLAIR, and diffusion tensor imaging (32 noncollinear gradient-encoding directions; b-value=800 s/mm2). Voxel-based morphometry, sulcation, curvature, and cortical thickness analyses and tract-based spatial statistics were performed by using Statistical Parametric Mapping 8, FreeSurfer, and the fMRI of the Brain Software Library. RESULTS: Corpus callosum partial agenesis, multiple sclerosis-like white matter abnormalities, and acoustic schwannoma were found in 1 patient each. The total amount of gray and white matter volume and tract-based spatial statistics measures (fractional anisotropy and mean, radial, and axial diffusivity) did not differ between patients with Kallmann syndrome and controls. By specific analyses, patients with Kallmann syndrome presented with symmetric clusters of gray matter volume increase and decrease and white matter volume decrease close to the olfactory sulci; reduced sulcal depth of the olfactory sulci and deeper medial orbital-frontal sulci; lesser curvature of the olfactory sulcus and sharper curvature close to the medial orbital-frontal sulcus; and increased cortical thickness within the olfactory sulcus. CONCLUSIONS: This large MR imaging study on male patients with Kallmann syndrome featured significant morphologic and structural brain changes, likely driven by olfactory bulb hypo-/aplasia, selectively involving the basal forebrain cortex.

Wernicke-like encephalopathy during classic maple syrup urine disease decompensation.

We describe a new neuroradiologic picture observed during metabolic decompensation in two maple syrup urine disease (MSUD) patients that resembles Wernicke encephalopathy (WE). Clinical observations and the review of the literature regarding WE and MSUD pathophysiology prompted us to hypothesize a pathogenic link between these two disorders. Based on these findings, clinicians and neuroradiologists should be aware of MSUD as a possible predisposing factor of WE in children.

Spinal subtraction MRI for diagnosis of epidural leakage in SIH.

OBJECTIVE: To explore the efficacy of spinal MRI study with subtraction analysis as a rapid, reliable, and noninvasive procedure to detect epidural CSF collection in spontaneous intracranial hypotension (SIH) syndrome. METHODS: Seventeen patients (mean age 42 years, age range 17-65 years; 11 female) with SIH diagnosed using the International Classification of Headache Disorders criteria and 13 age-matched control subjects underwent standard sagittal spinal MRI. Postprocessing image analysis with subtraction of T1-weighted from T2-weighted MRI scans was performed and tested for the detection of the CSF leak. RESULTS: The CSF epidural collection was visible in all patients with SIH and was detected at the dorsal (16 of 17), cervical (13 of 17), lumbar (13 of 17), and sacral (12 of 17) levels. None of the control subjects showed a CSF leak. Diverticula were present in 23% of patients, whereas the actual site of the CSF leak was recognized in only one patient. Eight patients were treated conservatively, whereas 9 patients required an epidural blood patch, performed at a fixed L2-L3 or L3-L4 spinal level, with complete recovery. CONCLUSIONS: Spinal MRI with dedicated subtraction analysis could represent the first-line diagnostic tool in the management of patients with SIH, thus leaving invasive investigation for selected patients, such those requiring dural surgery.

Hypophyseal triplication: case report and embryologic considerations.

SUMMARY: Hypophyseal triplication is malformation that has not been described previously. We present a child with midline abnormalities who underwent epignathus excision at birth. Brain MR imaging revealed 2 paired lateral pituitary glands and an oval midline gland, each with an independent stalk, connected to a thickened third ventricle floor. Because malformations represent a failure in embryogenesis, this case may provide interesting clues on the normal development of the hypophysis.